bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications
Authors: Balancin Marcelo Luiz , Baldavira Camila Machado , Prieto Tabatha Gutierrez , Machado-Rugolo Juliana , Farhat Cecília , Assato Aline Kawassaki , Velosa Ana Paula Pereira , Teodoro Walcy Rosolia , Ab'Saber Alexandre Muxfeldt , Takagaki Teresa Yae , Capelozzi Vera Luiza 
Published: April 2022

BackgroundMalignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression.MethodsIn a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome.ResultsEpithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm2) for epithelioid MM.ConclusionDifferential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.
A Novel Gene Signature Associated With “E2F Target” Pathway for Predicting the Prognosis of Prostate Cancer
Authors: Xia Haoran , Wang Miaomiao , Su Xiaonan , Lv Zhengtong , Yan Qiuxia , Guo Xiaoxiao , Liu Ming 
Published: April 2022

Background: The effect of the adenoviral early region 2 binding factors (E2Fs) target pathway on prostate cancer is not clear. It is necessary to establish an E2F target-related gene signature to predict prognosis and facilitate clinical decision-making.Methods: An E2F target-related gene signature was established by univariate and LASSO Cox regression analyses, and its predictive ability was verified in multiple cohorts. Moreover, the enrichment pathway, immune microenvironment, and drug sensitivity of the activated E2F target pathway were also explored.Results: The E2F target-related gene signature consisted of MXD3, PLK1, EPHA10, and KIF4A. The patients with high-risk scores showed poor prognosis, therapeutic resistance, and immunosuppression, along with abnormal growth characteristics of cells. Tinib drugs showed high sensitivity to the expression of MXD3 and EPHA10 genes.Conclusion: Our research established an E2F target-related signature for predicting the prognosis of prostate cancer. This study provides insights into formulating individualized detection and treatment as well as provides a theoretical basis for future research.
Beneficial Effects of Nut Consumption on Cognitive Function Among Elderly: Findings From a 6-Year Cohort Study
Authors: Li Fudong , Jiang Weiping , Wang Junbiao , Zhang Tao , Gu Xue , Zhai Yujia , Wu Mengna , Xu Le , Lin Junfen 
Published: April 2022

ObjectiveTo evaluate the longitudinal association of nut consumption with cognitive function in Chinese elderly.MethodsWe analyzed the data from Zhejiang Ageing and Health Cohort Study including 9,028 participants. Nut consumption was evaluated in baseline questionnaire beginning at 2014. Cognitive function was assessed repeatedly through the Mini-Mental State Examination (MMSE) at baseline and three waves of follow-up (2015, 2016, and 2019–2020). Cognitive impairment was defined using education-specific cut-off points. Log-binomial regression models with the generalized estimating equations, controlled for an extensive range of potential confounders, were utilized to evaluate the association and estimate relative risk (RR).ResultsAfter 6 years of follow-up, 3,266 (36.18%) participants were indicated as cognitive impairment by MMSE at least once. Compared with non-consumers or less-than-weekly consumers, participants consuming ≥70 g/week of nuts had 17% lower risks of cognitive impairment (RR = 0.83, 95% CI 0.75–0.91), whereas no association was found in those consuming &lt;70 g/week of nuts. Moreover, relatively infrequent higher-amount consuming (≥70 g within one consuming day each week) was not associated with better cognitive performance. Furthermore, we did not observe significant effect modification caused by frequency of other food intake.ConclusionHigher nut consumption was prospectively related to a lower risk of cognitive impairment in Chinese elderly.
Effects of Acute Partial Sleep Deprivation and High-Intensity Interval Exercise on Postprandial Network Interactions
Authors: Papadakis Zacharias , Garcia-Retortillo Sergi , Koutakis Panagiotis 
Published: April 2022

Introduction: High-intensity interval exercise (HIIE) is deemed effective for cardiovascular and autonomic nervous system (ANS) health-related benefits, while ANS disturbance increases the risk for cardiovascular disease (CVD). Postprandial lipemia and acute-partial sleep deprivation (APSD) are considered as CVD risk factors due to their respective changes in ANS. Exercising in the morning hours after APSD and have a high-fat breakfast afterwards may alter the interactions of the cardiovascular, autonomic regulation, and postprandial lipemic systems threatening individuals’ health. This study examined postprandial network interactions between autonomic regulation through heart rate variability (HRV) and lipemia via low-density lipoprotein (LDL) cholesterol in response to APSD and HIIE.Methods: Fifteen apparently healthy and habitually good sleepers (age 31 ± 5.2 SD yrs) completed an acute bout of an isocaloric HIIE (in form of 3:2 work-to-rest ratio at 90 and 40% of VO2 reserve) after both a reference sleep (RSX) and 3–3.5 h of acute-partial sleep deprivation (SSX) conditions. HRV time and frequency domains and LDL were evaluated in six and seven time points surrounding sleep and exercise, respectively. To identify postprandial network interactions, we constructed one correlation analysis and one physiological network for each experimental condition. To quantify the interactions within the physiological networks, we also computed the number of links (i.e., number of significant correlations).Results: We observed an irruption of negative links (i.e., negative correlations) between HRV and LDL in the SSX physiological network compared to RSX. Discussion: We recognize that a correlation analysis does not constitute a true network analysis due to the absence of analysis of a time series of the original examined physiological variables. Nonetheless, the presence of negative links in SSX reflected the impact of sleep deprivation on the autonomic regulation and lipemia and, thus, revealed the inability of HIIE to remain cardioprotective under APSD. These findings underlie the need to further investigate the effects of APSD and HIIE on the interactions among physiological systems.
Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?
Authors: Ding Jiangwei , Wang Lei , Li Wenchao , Wang Yangyang , Jiang Shucai , Xiao Lifei , Zhu Changliang , Hao Xiaoyan , Zhao Jiali , Kong Xuerui , Wang Ziqin , Lu Guangyuan , Wang Feng , Sun Tao 
Published: April 2022

BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.
Long-Term Health Outcomes of Infantile Spasms Following Prednisolone vs. Adrenocorticotropic Hormone Treatment Characterized Using Phenome-Wide Association Study
Authors: Baker Monika , Mason Clint C. , Wilkes Jacob , Sant David , Sweney Matthew , Bonkowsky Joshua L. 
Published: April 2022

ObjectiveTo determine differences in long-term health and neurological outcomes following infantile spasms (IS) in patients treated with adrenocorticotropic hormone (ACTH) vs. prednisolone/prednisone (PRED).MethodsA retrospective, case-control study of patients with an International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9) diagnosis of IS, identified over a 10-year period from a national administrative database, was conducted. IS patients treated with ACTH or PRED were determined and cohorts established by propensity score matching. Outcomes, defined by hospital discharge ICD codes, were followed for each patient for 5 years. Related ICD codes were analyzed jointly as phenotype codes (phecodes). Analysis of phecodes between cohorts was performed including phenome-wide association analysis.ResultsA total of 5,955 IS patients were identified, and analyses were subsequently performed for 493 propensity score matched patients, each in the ACTH and PRED cohorts. Following Bonferroni correction, no phecode was more common in either cohort (p &lt; 0.001). However, assuming an a priori difference, one phecode, abnormal findings on study of brain or nervous system (a category of abnormal neurodiagnostic tests), was more common in the PRED cohort (p &lt;0.05), and was robust to sensitivity analysis. Variability in outcomes was noted between hospitals.SignificanceWe found that long-term outcomes for IS patients following ACTH or PRED treatment were very similar, including for both neurological and non-neurological outcomes. In the PRED-treated cohort there was a higher incidence of abnormal neurodiagnostic tests, assuming an a priori statistical model. Future studies can evaluate whether variability in outcomes between hospitals may be affected by post-treatment differences in care models.
The Last Decade Publications on Diabetic Peripheral Neuropathic Pain: A Bibliometric Analysis
Authors: Du Shu-Hao , Zheng Yi-Li , Zhang Yong-Hui , Wang Ming-Wen , Wang Xue-Qiang 
Published: April 2022

BackgroundDiabetic peripheral neuropathic pain (DPNP) is a usual complication of diabetes with a high incidence and mortality. Many diabetes-related studies have been published in various journals. However, bibliometrics and visual analyses in the domain of DPNP research are still lacking. The study aimed to offer a visual method to observe the systematic overview of global research in this field from 2011 to 2021.MethodsThe publications from the Science Citation Index Expanded in Web of Science (WOS) in the past 11 years (from 2011 to 2021) were collected and sorted out, and those related to DPNP were extracted and analyzed. The article language was limited in English. Then, CiteSpace V was used for the bibliometric analysis of the extracted literature.ResultsA total of 1,422 articles met the inclusion criteria. A continuous but unstable growth in the amounts of papers published on DPNP was observed over the last 11 years. The subject sort of the 1,422 papers mainly concentrates on Endocrinology Metabolism, Clinical neurology and Neurosciences from the WOS. According to the research contribution in the field of DPNP, the United States occupies a leading position, with the highest amounts of publications, citations, open access, and the H- index.ConclusionThis study provides a visual analysis method for the trend of DPNP, and offers some hidden serviceable information that may define new directions for future research.
Early Postoperative Exposure to High-Fat Diet Does Not Increase Long-Term Weight Loss or Fat Avoidance After Roux-en-Y Gastric Bypass in Rats
Authors: Ismaeil Aiman , Gero Daniel , Boyle Christina N. , Alceste Daniela , Taha Osama , Spector Alan C. , Lutz Thomas A. , Bueter Marco 
Published: April 2022

BackgroundBariatric surgery alters food preferences in rats and reportedly decreases desire to consume high-fat high-sugar food in humans. The aim of this study was to investigate whether early post-operative exposure to high-fat food could increase body weight loss after Roux-en-Y gastric bypass (RYGB) by triggering fat avoidance.MethodsMale Wistar rats underwent either RYGB (n = 15) or sham-operations (n = 16). Preoperatively a standardized 4-choice cafeteria diet [dietary options: low-fat/low-sugar (LFLS), low-fat/high-sugar (LFHS), high-fat/low-sugar (HFLS), high-fat/high-sugar (HFHS)] was offered. First, each option was available for 4 days, thereafter rats were offered the 4 options simultaneously for 3 days preoperatively. Post-surgery, 8 rats in the RYGB- and 8 in the sham-group were exposed to a high-fat content diet (Oatmeal + 30% lard, OM+L) for 10 days, while 7 RYGB rats and 8 sham-rats received OM alone. From the 11th postoperative day, the 4-choice cafeteria diet was reintroduced for 55-days. The intake of all available food items, macronutrients and body weight changes were monitored over 8 weeks. Main outcomes were long-term body-weight and daily change in relative caloric intake during the postoperative cafeteria period compared to the preoperative cafeteria.ResultsDuring the first 12 days of postoperative cafeteria access, RYGB-rats exposed to OM+L had a higher mean caloric intake per day than RYGB rats exposed to OM alone (Δ10 kCal, Padj = 0.004), but this difference between the RYGB groups disappeared thereafter. Consequently, in the last 33 days of the postoperative cafeteria diet, the mean body weight of the RYGB+OM+L group was higher compared to RYGB+OM (Δ51 g, Padj &lt; 0.001). RYGB rats, independently from the nutritional intervention, presented a progressive decrease in daily consumption of calories from fat and increased their daily energy intake mainly from non-sugar carbohydrates. No such differences were detected in sham-operated controls exposed to low- or high fat postoperative interventions.ConclusionA progressive decrease in daily fat intake over time was observed after RYGB, independently from the nutritional intervention. This finding confirms that macronutrient preferences undergo progressive changes over time after RYGB and supports the role of ingestive adaptation and learning. Early postoperative exposure to high-fat food failed to accentuate fat avoidance and did not lead to superior weight loss in the long-term.
Survival Analysis in Male Breast Cancer With Bone Metastasis Based on the SEER Database
Authors: Zhou Xingjuan , Zhang Junwei , Wang Yunqing , Cao Zhenguo 
Published: April 2022

PurposeBreast cancer (BC) has been extensively and deeply studied as the number one malignant tumor in women, but its status in male patients, especially in male metastatic patients, is rarely reported. Thus, this study aimed to explore the prognosis and risk factors of male BC with bone metastasis.Patients and MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients diagnosed with male BC with bone metastasis from 2010 to 2016. Risk factors of overall survival (OS) and cancer-specific survival (CSS) were analyzed by univariable and multivariable Cox analyses. We also drew Kaplan–Meier plots to show the correlation between independent risk factors and survival.ResultsA total of 207 male BC patients with bone metastasis were included for analysis. Approximately one-third of patients also had lung metastasis. Luminal A subtype comprised 58.5% of the overall patient population. These patients had a poor prognosis, with 3-year OS and CSS rates, 36.7% and 39.5%, respectively. Further analysis revealed that age ≤60 years old, luminal A or B, and surgery were independent predictors of prolonged OS and CSS. On Cox multivariable analysis, brain metastasis was associated with OS and not CSS.ConclusionWe identified four independent factors associated with prognosis in male BC patients with bone metastasis, namely age, tumor subtype, surgery, and brain metastasis. Knowing these risk factors will help clinicians make more appropriate treatment plans.
1.5T MR-Guided Daily Adaptive Stereotactic Body Radiotherapy for Prostate Re-Irradiation: A Preliminary Report of Toxicity and Clinical Outcomes
Authors: Cuccia Francesco , Rigo Michele , Figlia Vanessa , Giaj-Levra Niccolò , Mazzola Rosario , Nicosia Luca , Ricchetti Francesco , Trapani Giovanna , De Simone Antonio , Gurrera Davide , Naccarato Stefania , Sicignano Gianluisa , Ruggieri Ruggero , Alongi Filippo 
Published: April 2022

BackgroundProstate re-irradiation is an attractive treatment option in the case of local relapse after previous radiotherapy, either in the definitive or in the post-operative setting. In this scenario, the introduction of MR-linacs may represent a helpful tool to improve the accuracy and precision of the treatment.MethodsThis study reports the preliminary data of a cohort of 22 patients treated with 1.5T MR-Linacs for prostate or prostate bed re-irradiation. Toxicity was prospectively assessed and collected according to CTCAE v5.0. Survival endpoints were measured using Kaplan-Meier method.ResultsFrom October 2019 to October 2021, 22 patients received 1.5T MR-guided stereotactic body radiotherapy for prostate or prostate-bed re-irradiation. In 12 cases SBRT was delivered to the prostate, in 10 to the prostate bed. The median time to re-RT was 72 months (range, 12-1460). SBRT was delivered concurrently with ADT in 4 cases. Acute toxicity was: for GU G1 in 11/22 and G2 in 4/22; for GI G1 in 7/22, G2 in 4/22. With a median follow-up of 8 months (3-21), late G1 and G2 GU events were respectively 11/22 and 4/22. Regarding GI toxicity, G1 were 6/22, while G2 3/22. No acute/late G≥3 GI/GU events occurred. All patients are alive. The median PSA-nadir was 0.49 ng/ml (0.08-5.26 ng/ml), for 1-year BRFS and DPFS rates of 85.9%. Twenty patients remained free from ADT with 1-year ADT-free survival rates of 91.3%.ConclusionsOur experience supports the use of MR-linacs for prostate or prostate bed re-irradiation as a feasible and safe treatment option with minimal toxicity and encouraging results in terms of clinical outcomes.
Effects of Posaconazole on Tacrolimus Population Pharmacokinetics and Initial Dose in Children With Crohn’s Disease Undergoing Hematopoietic Stem Cell Transplantation
Authors: Chen Xiao , Wang Dongdong , Zheng Feng , Zhu Lin , Huang Yidie , Zhu Yiqing , Huang Ying , Xu Hong , Li Zhiping 
Published: April 2022

The present study explored the effects of posaconazole on tacrolimus population pharmacokinetics (PPK) in children with Crohn’s disease (CD) undergoing hematopoietic stem cell transplantation (HSCT). Tacrolimus concentrations, physiological and biochemical factors, and concomitant medications from 51 CD children undergoing HSCT were used to establish a PPK model based on a nonlinear mixed-effect model. Steady-state concentrations of tacrolimus for children weighing less than 20 kg treated with different dose regimens were simulated by the Monte Carlo method. Weight and concomitant medications were included as covariates. At the same weight, the relative tacrolimus clearance was 1:0.43 in children without or with posaconazole. Compared to children not receiving posaconazole, the simulated tacrolimus steady-state concentrations at different doses for different body weights were all higher in children receiving posaconazole (p &lt; 0.01). Furthermore, in children not receiving posaconazole, the dosage regimen with the best probability of achieving the target concentration was 0.6 mg/kg/day for children weighing 5–8.2 kg and 0.5 mg/kg/day for children weighing 8.2–20 kg, while for children receiving posaconazole, the best probability of reaching the target concentration of tacrolimus was a dosage regimen of 0.5 mg/kg/day for children weighing 5–20 kg. In conclusion, the PPK for tacrolimus was determined in children with CD undergoing HSCT for the first time. Co-treatment with posaconazole significantly increased tacrolimus concentrations, and we recommend a specific initial dose regimen for tacrolimus.