bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of Radiological and Clinical Baseline Data for Outcome Prediction of Patients With an Acute Ischemic Stroke
Authors: Ramos Lucas A. , Os Hendrikus van , Hilbert Adam , Olabarriaga Silvia D. , Lugt Aad van der , Roos Yvo B. W. E. M. , Zwam Wim H. van , Walderveen Marianne A. A. van , Ernst Marielle , Zwinderman Aeiko H. , Strijkers Gustav J. , Majoie Charles B. L. M. , Wermer Marieke J. H. , Marquering Henk A. 
Published: April 2022

BackgroundAccurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for stroke focused mostly on clinical characteristics and radiological scores available at baseline. Radiological images are composed of millions of voxels, and a lot of information can be lost when representing this information by a single value. Therefore, in this study we aimed at developing prediction models that take into account the whole imaging data combined with clinical data available at baseline.MethodsWe included 3,279 patients from the MR CLEAN Registry; a prospective, observational, multicenter registry of patients with ischemic stroke treated with EVT. We developed two approaches to combine the imaging data with the clinical data. The first approach was based on radiomics features, extracted from 70 atlas regions combined with the clinical data to train machine learning models. For the second approach, we trained 3D deep learning models using the whole images and the clinical data. Models trained with the clinical data only were compared with models trained with the combination of clinical and image data. Finally, we explored feature importance plots for the best models and identified many known variables and image features/brain regions that were relevant in the model decision process.ResultsFrom 3,279 patients included, 1,241 (37%) patients had a good functional outcome [modified Rankin Scale (mRS) ≤ 2] and 1,954 (60%) patients had good reperfusion [modified Thrombolysis in Cerebral Infarction (eTICI) ≥ 2b]. There was no significant improvement by combining the image data to the clinical data for mRS prediction [mean area under the receiver operating characteristic (ROC) curve (AUC) of 0.81 vs. 0.80] above using the clinical data only, regardless of the approach used. Regarding predicting reperfusion, there was a significant improvement when image and clinical features were combined (mean AUC of 0.54 vs. 0.61), with the highest AUC obtained by the deep learning approach.ConclusionsThe combination of radiomics and deep learning image features with clinical data significantly improved the prediction of good reperfusion. The visualization of prediction feature importance showed both known and novel clinical and imaging features with predictive values.
Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients
Authors: Li Yuanyuan , Dong Bingbin , Wu Wei , Wang Jiawei , Jin Hao , Chen Kangmei , Huang Kangling , Huang Songyin , Yao Yandan 
Published: April 2022

BackgroundGrowing evidence supports the modulatory role of human gut microbiome on neoadjuvant chemotherapy (NAC) efficacy. However, the relationships among the gut microbiome, tumor-infiltrating lymphocytes (TILs), and NAC response for breast cancer (BC) patients remain unclear. We thus proposed this preliminary study to investigate the relationship between gut microbiome and BC patients’ responses to NAC treatment as well as underlying mechanisms.MethodsPrior to receiving NAC, the fecal metagenome collected from 23 patients with invasive BC was analyzed. Patients were subsequently assigned to the NAC non-effectual group and the NAC effectual group based on their response to NAC. The peripheral T lymphocyte subset counts were examined by flow cytometry methods. CellMinor analysis was employed to explore the relationship between CD4 mRNA expression and the reaction of tumor cells to NAC drugs.ResultsThe gut microbiomes of the NAC non-effectual group showed characteristics of low diversity with low abundances, distinct metagenomic composition with decreased butyrate-producing and indolepropionic acid-producing bacteria, and increased potential pathobionts compared with the NAC effectual group. The combination of Coprococcus, Dorea, and uncultured Ruminococcus sp. serves as signature bacteria for distinguishing NAC non-effectual group patients from the NAC effectual group. The absolute numbers of CD4+ and CD8+ TIL infiltration in tumors in the NAC non-effectual group were significantly lower than those in the effectual group. Similar findings were reported for the CD4+ T lymphocytes in the peripheral blood (p’s &lt; 0.05). NAC effectual-related signature bacteria were proportional to these patients’ CD4+ T lymphocyte counts in peripheral blood and tumors (p’s &lt; 0.05). CellMinor analysis showed that the CD4 mRNA expression level dramatically climbed with increased sensitivity of tumor cells to NAC drugs such as cyclophosphamide, cisplatin, and carboplatin (p’s &lt; 0.05).ConclusionsThe composition of the gut microbial community differs between BC patients for whom NAC is effective to those that are treatment resistant. The modulation of the gut microbiota on host CD4+ T lymphocytes may be one critical mechanism underlying chemosensitivity and NAC pathologic response. Taken together, gut microbiota may serve as a potential biomarker for NAC response, which sheds light on novel intervention targets in the treatment of NAC non-effectual BC patients.
Microbiome Analysis and Pharmacovigilance After Inhaled Glucocorticoid: Oral Dysbiosis With the Isolation of Three Rothia Species and Subsequent Sjögren’s Syndrome
Authors: Zdziarski Przemysław , Paściak Mariola , Gamian Andrzej 
Published: April 2022

Background: Treatment of respiratory tract diseases with inhaled glucocorticoids is a form of therapy that has been used for many years. It shows lower potency of side effects; nevertheless, microbiome change, sinopulmonary dysbiosis, secondary immunodeficiency, and immunomodulatory effects are underestimated. The latest guideline recommendations introduce the use of empirical antibiotic and/or multiplying inhaled glucocorticoids in therapeutic intervention of asthma and chronic pulmonary obstructive disease.Aims and objectives: The aim of the study was to describe a simple, universal, and cost-effective method of microbiome analysis for clinical trials. Such a general method for monitoring pharmacovigilance should be widely available and reliable.Methods: The study material included two kinds of swabs, taken from the same mouth ulcerations of patients with asthma treated with a temporary quadruple dose of fluticasone. The microbiological investigation was performed, and identification of the isolates was carried out using the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS) Biotyper.Results: The analysis of dry swab demonstrated the presence of typical oral bacteria (Neisseria spp. and Streptococcus spp.), alongside with the potentially pathogenic Actinomyces spp. and three different Rothia species, identified simultaneously: R. aeria, R. dentocariosa, and R. mucilaginosa. Although quadrupled dose of corticoids was discontinued and ulcer healing was observed, the patients required topical therapy for maintained xerostomia. Progressive systemic autoimmunity (seronegative Sjögren’s syndrome with major organ involvement) was observed later.Conclusion: Topical steroids (especially in quadruple dose) require attention to safety, immunomodulation, and microbiological outcome. They showed systemic side effects: microbiome alteration, humoral (IgG) immunodeficiency, and systemic autoimmunity. Isolation of three species of Rothia from a patient with mouth ulcers after steroid therapy suggests their participation in infectious and inflammatory processes. The proposed a methodology using MALDI-TOF-MS may be a prototype approach for microbial diagnostics in clinical trials of immunomodulatory drugs.
Acute Administration of Metformin Protects Against Neuronal Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury via Regulation of the AMPK/CREB/BDNF Pathway
Authors: Liu Ke , Li Lulu , Liu Zhijun , Li Gang , Wu Yanqing , Jiang Xingjun , Wang Mengdie , Chang Yanmin , Jiang Tingting , Luo Jianheng , Zhu Jiahui , Li Hongge , Wang Yong 
Published: April 2022

Metformin is a first-line anti-diabetic agent with a powerful hypoglycemic effect. Several studies have reported that metformin can improve the prognosis of stroke patients and that this effect is independent of its hypoglycemic effect; however, the specific mechanism remains unclear. In this research, we explored the effect and specific mechanism of metformin in cerebral ischemia-reperfusion (I/R) injury by constructing a transient middle cerebral artery occlusion model in vivo and a glucose and oxygen deprivation/reoxygenation (OGD/R) model in vitro. The results of the in vivo experiments showed that acute treatment with low-dose metformin (10 mg/kg) ameliorated cerebral edema, reduced the cerebral infarction volume, improved the neurological deficit score, and ameliorated neuronal apoptosis in the ischemic penumbra. Moreover, metformin up-regulated the brain-derived neurotrophic factor (BDNF) expression and increased phosphorylation levels of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB) in the ischemia penumbra. Nevertheless, the above-mentioned effects of metformin were reversed by Compound C. The results of the in vitro experiments showed that low metformin concentrations (20 μM) could reduce apoptosis of human umbilical vein endothelial cells (HUVECs) under OGD/R conditions and promote cell proliferation. Moreover, metformin could further promote BDNF expression and release in HUVECs under OGD/R conditions via the AMPK/CREB pathway. The Transwell chamber assay showed that HUVECs treated with metformin could reduce apoptosis of SH-SY5Y cells under OGD/R conditions and this effect could be partially reversed by transfection of BDNF siRNA in HUVECs. In summary, our results suggest that metformin upregulates the level of BDNF in the cerebral ischemic penumbra via the AMPK/CREB pathway, thereby playing a protective effect in cerebral I/R injury.
Chinese Herbal Medicine (Yiqi-Yangyin-Jiedu Decoction) Combined With Osimertinib as First-Line Treatment in EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer (CATLA-2): A Study Protocol for a Double-Blind Randomized Controlled Trial
Authors: Yao Jialin , Lu Yan , Jiao Lijing , Bi Ling , Yang Wenxiao , Su Lingzi , Shi Jun , Wang Zhe , Gong Yabin , Xu Ling 
Published: April 2022

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the prognosis of non-small cell lung cancer (NSCLC) with EGFR mutation-positive. Although third-generation EGFR-TKI osimertinib is demonstrated with superior efficacy compared with first-generation EGFR-TKIs, acquired resistance to EGFR-TKIs remains the bottleneck. The Chinese herbal medicine (CHM) Yiqi-Yangyin-Jiedu decoction (YYJD) has been shown to delay acquired resistance to first-generation EGFR-TKIs in the CATLA study, but there is no high-level evidence for its effect when combined with osimertinib. This trial aims to evaluate the efficacy and safety of YYJD combined with osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC.Methods: This is a double-blind, multi-center, randomized controlled trial conducted in eight hospitals in China. A total of 314 participants will be randomly assigned to the osimertinib plus YYJD group (O+YYJD) or the osimertinib plus placebo group (O+placebo). Treatment will last until disease progression or death. Patients diagnosed with advanced NSCLC harboring EGFR Ex19del or L858R will be enrolled if they are ready to take osimertinib as first-line treatment, aged 18–74 years old, and provide signed informed consent. The primary outcome is progression-free survival (PFS). The secondary outcomes include a comparison of overall survival (OS), objective response rate (ORR), disease control rate (DCR), and quality of life (QoL). The analysis will be based on intention-to-treat and per-protocol subject analysis principles.Discussion: The goal of this trial is to evaluate the efficacy and safety of YYJD when added to osimertinib as first-line treatment in EGFR mutation-positive advanced NSCLC.
Hydralazine Associated With Reduced Therapeutic Phlebotomy Frequency in a Nationwide Cohort Study: Real-World Effectiveness for Drug Repurposing
Authors: Lin Wei-Zhi , Chung Chi-Hsiang , Shaiu Chia-Yang , Yang Bing-Heng , Chien Wu-Chien 
Published: April 2022

Background: Therapeutic phlebotomy, known as scheduled bloodletting, has been the main method for managing erythrocytosis symptoms and thrombocytosis-associated complications in various blood disorders. One of the major indications for phlebotomy is polycythemia vera (PV). The main goal of current treatment strategies for patients who require phlebotomy is to prevent thrombohemorrhagic complications rather than to prolong survival or lessen the risk of myelofibrotic or leukemic progression. Additional cytoreductive therapy is recommended for high-risk PV, for which the common first-line drug is hydroxyurea. However, recent evidence suggests that phlebotomy may not reduce the risk of thrombosis in patients with PV. Further evidence suggests that patients with PV treated with hydroxyurea who require three or more phlebotomy procedures per year have a higher risk of thrombotic complications.Methods: We hypothesized that a drug-repurposing strategy of utilizing antineoplastic drugs for patients who require phlebotomy would result in greater benefits than would phlebotomy. The antihypertensive hydralazine and the anticonvulsant valproate, which have both been reported to have antineoplastic activity that mimics cytoreductive agents, were selected as candidates for the drug-repositioning strategy in a retrospective cohort study. We measured the hazard ratios (HR) and the frequencies of phlebotomy in patients with prescriptions for hydralazine or valproate or the two drugs in combination by using data from Taiwan’s National Health Insurance Research Database from 2000 to 2015 (n = 1,936,512).Results: The HRs of undergoing phlebotomy in groups with hydralazine, valproate, and combination hydralazine–valproate prescriptions were reduced to 0.729 (p = 0.047), 0.887 (p = 0.196), and 0.621 (p = 0.022), respectively. The frequency of undergoing phlebotomy decreased from 2.27 to 1.99, 2.01, and 1.86 per person-year (p = 0.015), respectively. However, no significant differences were observed for the hydralazine group or the hydralazine–valproate combination group.Conclusion: Whether a repurposed drug can serve as a cytoreductive agent for patients who require phlebotomy depends on its risk–benefit balance. We suggest that hydralazine, instead of the hydralazine–valproate combination, is a reasonable alternative for patients who require regular phlebotomy.
Exposure to Olfactory Alcohol Cues During Non-rapid Eye Movement Sleep Did Not Decrease Craving in Patients With Alcohol Dependence
Authors: Zhu Ran , Ni Zhaojun , Tao Ran , Cheng Jun , Pang Liangjun , Zhang Shun , Zhang Yang , Xue Yanxue , Ma Yundong , Sun Wei , Lu Lin , Deng Jiahui , Sun Hongqiang 
Published: April 2022

Background and ObjectivesCue exposure therapy (CET) has been used to reduce alcohol use, but the effect of CET during sleep on alcohol dependence (AD) is unclear. The present study examined the effect of repeated exposure to an olfactory stimulus during non-rapid eye movement (NREM) sleep on cue reactivity and craving in patients with AD.MethodsThirty-five patients with AD were enrolled according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). All the subjects were randomly assigned to the experimental or control group. The experimental group was exposed to alcohol odor for 10 min during NREM sleep. The other group (controls) was exposed to water [control stimulus (CtrS)] for 10 min during NREM sleep. Demographic, alcohol-related, and clinical characteristics were collected at baseline. A cue-reactivity test was conducted before and after exposure to evaluate the effect of memory manipulation on acute response to an alcohol stimulus.ResultsThere were no significant time × group interactions according to the visual analog scale (VAS) score of craving intensity, skin conductance response (SCR), systolic blood pressure (SBP), and diastolic blood pressure (DBP; all p &gt; 0.05). Two-way ANOVA showed significant main effects of time on SCR [F(1,33) = 4.453, p = 0.043], SBP [F(1,33) = 14.532, p = 0.001], DBP [F(1,33) = 8.327, p = 0.007], Craving-VAS [F(1,33) = 1.997, p = 0.167] in two groups.ConclusionExposure to olfactory alcohol cues during NREM sleep had no significant effect on alcohol craving in subjects with AD during hospitalization.
Comparing Multi-Arm Robotics for In-Space Assembly
Authors: McBryan Katherine 
Published: April 2022

Robotic In-space assembly (ISA) is the next step to building larger and more permanent structures in orbit. Determining the best robot for ISA is difficult as it will not only depend on the structure being assembled but on how it is assembled. This analysis shows how changing some key design parameters can influence different robotic systems for ISA. This study focuses on the construction of a 20 m linear truss structure but also expands to a 10 and 50 m truss. Two categories of robots are included in this study: a stationary robot and a mobile robot which crawls along the structure. Both the stationary and crawling robotic systems utilize two planar dexterous manipulators to assemble individual truss pieces into a linear truss. In the case of the stationary robotic system a single long positioning leg is used to move the two dexterous arms into position. The crawling robotic system uses two planar manipulators to crawl along the truss. A systems level analysis is presented which details how the forces from the robotic systems drive the mass of the truss and also how the size of the truss segments drive the requirements of the robotic system. This analysis shows how changing some key design parameters can influence each of the different robotic systems and the truss design itself. The estimated masses of the robotic systems and the truss and the assembly time are presented. There are trade-offs to every robot design and understanding those trade-offs is essential to building a system that is not only efficient but also cost-effective.
Case Report: Congenital Intracranial Kaposiform Hemangioendothelioma Treated With Surgical Resection
Authors: Cai Yingjie , Li Jiayi , Yang Wei , Zhang Nan , Sun Hailang , Zhang Weiping , Ge Ming 
Published: April 2022

BackgroundKaposiform hemangioendothelioma (KHE) is a locally aggressive but non-metastatic vascular neoplasm. Most studies have been restricted to small case series of limited generalizability. Intracranial KHE is extremely rare with only three cases reported in the literature. Here, we report a case of congenital intracranial KHE who underwent surgical resection, and no lesion recurrence was seen during the follow-up period of 13 months.Case DescriptionA 2-month-old boy initially presented with a left temporal mass following birth. Antenatal ultrasound at 36 weeks of gestation demonstrated a hyperechoic signal present in the left frontal lobe, with clear borders and irregular morphology. There were neither cutaneous abnormalities nor other neurologic examination abnormalities. No laboratory abnormality was identified. Computed tomography (CT) scans suggested that a massive hematoma was noted under the left frontal skull plate, with a little subdural hemorrhage in the adjacent temporal area. The adjacent meninges enhanced and thickened on contrasted T1 magnetic resonance (MR). After the multidisciplinary diagnostic assessment, the surgery was performed by the left frontotemporal craniotomy approach. The operation was extremely difficult. We completely removed the tumor, and the involved dura and brain tissue were resected with the lesion in a piecemeal fashion. On postoperative-day (POD) 3 and POD 14, the head CT re-examination revealed that cerebral perfusion improved gradually. The MRI of 6- and 12-month after operation showed no local recurrence or metastasis.ConclusionsIntracranial KHE is difficult to diagnose early and the prognosis has been uniformly poor. We supposed that meticulous intraoperative hemostasis is the key for a successful operation, and the radical resection of the tumor and involved structures are essential to reduce recurrence.
Describing Lettuce Growth Using Morphological Features Combined with Nonlinear Models
Authors: Li Qinglin , Gao Hongyan , Zhang Xiaodong , Ni Jiheng , Mao Hanping 
Published: April 2022

The aim of this study was to describe the sigmoidal growth behaviour of a lettuce canopy using three nonlinear models. Gompertz, Logistic and grey Verhulst growth models were established for the top projected canopy area (TPCA), top projected canopy perimeter (TPCP) and plant height (PH), which were measured by two machine vision views and 3D point clouds data. Satisfactory growth curve fitting was obtained using two evaluation criteria: the coefficient of determination (R2) and the mean absolute percentage error (MAPE). The grey Verhulst models produced a better fit for the growth of TPCA and TPCP, with higher R2 (RTPCA2=0.9097, RTPCP2=0.8536) and lower MAPE (MAPETPCA=0.0284, MAPETPCP=0.0794) values, whereas the Logistic model produced a better fit for changes in PH (RPH2=0.8991, MAPEPH=0.0344). The maximum growth rate point and the beginning and end points of the rapid growth stage were determined by calculating the second and third derivatives of the models, permitting a more detailed description of their sigmoidal behaviour. The initial growth stage was 1–5.5 days, and the rapid growth stage lasted from 5.6 to 26.2 days. After 26.3 days, lettuce entered the senescent stage. These inflections and critical points can be used to gain a better understanding of the growth behaviour of lettuce, thereby helping researchers or agricultural extension agents to promote growth, determine the optimal harvest period and plan commercial production.
Neutralización con KOH del aceite de pescado para la obtención de un efluente fertilizante
Authors: Cherrepano Manrique Reynaldo Francisco , Vélez Chang Yasmin Jesús , Legua Cárdenas José Antonio 
Published: April 2022

La presente propuesta es convertir un efluente en un recurso económico, para tal propósito se realizó pruebas experimentales a nivel laboratorio, donde se ensayó la neutralización en la refinación del aceite de pescado, el hidróxido de potasio como agente neutralizante que se propone sustituir al hidróxido de sodio, que actualmente la industria aceitera utiliza, para neutralizar la acidez libre del aceite crudo de pescado. Al realizarse la neutralización con hidróxido de potasio para reducir la acidez libre de los aceites, y realizar los lavados del aceite y neutralizar la acidez de estas aguas con hidróxido de amonio, se obtiene una solución mezcla con propiedades fertilizantes. Para mostrar las propiedades fertilizantes de esta mezcla obtenida se utilizaron como fertilizante foliar aplicado al cultivo rabanito, para ello se realizó la experimentación en campo, se hizo la instalación utilizando el Diseño de Bloques Completamente Aleatorio, con cinco tratamientos.