bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral Blood Flow Is Not a Direct Surrogate of Behavior: Performance Models Suggest a Role for Functional Meta-Networks
Authors: Sidtis John J. 
Published: February 2022

BackgroundFunctional brain imaging has become the dominant approach to the study of brain-behavior relationships. Unfortunately, the behavior half of the equation has been relegated to second-class status when it is not ignored completely. Different approaches to connectivity, based on temporally correlated physiological events across the brain, have ascended in place of behavior. A performance-based analysis has been developed as a simple, basic approach to incorporating specific performance measures obtained during imaging into the analysis of the imaging data identifying clinically relevant regions.MethodsThis paper contrasts performance-based lateralized regional cerebral blood flow (CBF) predictors of speech rate during Positron Emission Tomography with the values of these regions and their opposite hemisphere homologs in which a performance-based model was not applied. Five studies were examined: two that utilized normal speakers, one that utilized ataxic speakers, and two that examined Parkinsonian speakers.ResultsIn each study, the predictors were lateralized but the blood flow values that contributed to the performance-based analysis were bilateral. The speech-rate predictor regions were consistent with clinical studies on the effects of focal brain damage.ConclusionsThis approach has identified a basic, reproducible blood flow network that has predicted speech rate in multiple normal and neurologic groups. While the predictors are lateralized consistent with lesion data, the blood flow values of these regions are neither lateralized nor distinguished from their opposite hemisphere homologs in their magnitudes. The consistent differences between regional blood flow values and their corresponding regression coefficients in predicting performance suggests the presence of functional meta-networks that orchestrate the contributions of specific brain regions in support of mental and behavioral functions.
Inhibiting Sphingosine 1-Phosphate Receptor Subtype 3 Attenuates Brain Damage During Ischemia-Reperfusion Injury by Regulating nNOS/NO and Oxidative Stress
Authors: Fan Xuehui , Chen Hongping , Xu Chen , Wang Yingju , Yin Pengqi , Li Meng , Tang Zhanbin , Jiang Fangchao , Wei Wan , Song Jihe , Li Guozhong , Zhong Di 
Published: February 2022

BackgroundIschemic stroke (IS) is a common disease endangering human life and health. Cerebral ischemia triggers a series of complex harmful events, including excitotoxicity, inflammation and cell death, as well as increased nitric oxide production through the activation of nitric oxide synthase (NOS). Oxidative stress plays a major role in cerebral ischemia and reperfusion. Sphingosine 1-phosphate receptor subtype 3 (S1PR3), a member of S1P’s G protein-coupled receptors S1PR1-S1PR5, is involved in a variety of biological effects in the body, and its role in regulating oxidative stress during cerebral ischemia and reperfusion is still unclear.MethodsTransient middle cerebral artery occlusion (tMCAO) mice were selected as the brain ischemia–reperfusion (I/R) injury model. Male C57/BL6 mice were treated with or without a selective S1PR3 inhibition after tMCAO, and changes in infarct volume, Nissl staining, hematoxylin-eosin (H&amp;E) staining and NOS protein, nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) content after tMCAO were observed.ResultsIn the cerebral ischemia–reperfusion model, inhibition of S1PR3 improved the infarct volume and neuronal damage in mice after tMCAO. Similarly, inhibition of S1PR3 can reduce the expression of NO synthase subtype neuronal NOS (nNOS) and reduce the production of NO after cerebral ischemia. After cerebral ischemia and reperfusion, the oxidative stress response was enhanced, and after the administration of the S1PR3 inhibitor, the SOD content increased and the MDA content decreased, indicating that S1PR3 plays an important role in regulating oxidative stress response.ConclusionInhibiting S1PR3 attenuates brain damage during I/R injury by regulating nNOS/NO and oxidative stress, which provides a potential new therapeutic target and mechanism for the clinical treatment of IS.
Artificial Intelligence-Aided Diagnosis Software to Identify Highly Suspicious Pulmonary Nodules
Authors: Lv Jun , Li Jianhui , Liu Yanzhen , Zhang Hong , Luo Xiangfeng , Ren Min , Gao Yufan , Ma Yanhe , Liang Shuo , Yang Yapeng , Song Zhenchun , Gao Guangming , Gao Guozheng , Jiang Yusheng , Li Ximing 
Published: February 2022

IntroductionTo evaluate the value of artificial intelligence (AI)-assisted software in the diagnosis of lung nodules using a combination of low-dose computed tomography (LDCT) and high-resolution computed tomography (HRCT).MethodA total of 113 patients with pulmonary nodules were screened using LDCT. For nodules with the largest diameters, an HRCT local-target scanning program (combined scanning scheme) and a conventional-dose CT scanning scheme were also performed. Lung nodules were subjectively assessed for image signs and compared by size and malignancy rate measured by AI-assisted software. The nodules were divided into improved visibility and identical visibility groups based on differences in the number of signs identified through the two schemes.ResultsThe nodule volume and malignancy probability for subsolid nodules significantly differed between the improved and identical visibility groups. For the combined scanning protocol, we observed significant between-group differences in subsolid nodule malignancy rates.ConclusionUnder the operation and decision of AI, the combined scanning scheme may be beneficial for screening high-risk populations.
125I Seed Brachytherapy for Refractory Loco-Regional Recurrence of Non-Anaplastic Thyroid Cancer
Authors: Yu Huimin , Zhang Hongtao , Gao Zhen , Liu Xiaoli , Zhang Lijuan , Di Xuemin , Wang Zeyang , Liu Zezhou , Sui Aixia , Wang Juan , Shi Gaofeng 
Published: February 2022

PurposeThe purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy as salvage treatment for recurrence from non-anaplastic thyroid cancer refractory to other modalities.MethodsBetween June 2006 and September 2019, fifteen patients with recurrent non-anaplastic thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or ultrasound images with the median prescription dose of 120 Gy (range, 100-140 Gy). The median seed number was 80 (range 10-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors.FindingsFifteen patients were selected, eleven of whom had papillary carcinoma, two suffered from follicular carcinoma, and two were diagnosed with medullary carcinoma. These patients had twenty-four nodes in total. After they received salvage surgery and/or radioactive iodine (RAI) therapy, local recurrence was detected in all of them. No less than one node was observed in everyone’s cervical or supraclavicular areas, and four patients had lung metastatic. The median follow-up period lasted 48 months (range, 5-93 months). All patients did not develop locoregional recurrence after experiencing 125I seed brachytherapy. Only three of them formed new metastases in nontarget regional nodes after brachytherapy, and additional brachytherapy can solve all regional failure problems. No significant adverse events were observed in any patient.ImplicationsFor the chosen patients, 125I seed brachytherapy is feasible for treating refractory local recurrence from non-anaplastic thyroid cancer. Further studies are required to determine the role of 125I seed brachytherapy in the treatment of thyroid cancer.
TikTok as an Information Hodgepodge: Evaluation of the Quality and Reliability of Genitourinary Cancers Related Content
Authors: Xue Xiaoqiang , Yang Xinyi , Xu Weifeng , Liu Guanghua , Xie Yi , Ji Zhigang 
Published: February 2022

BackgroundTikTok is the world’s fastest-growing video application, with 1.6 billion users in 2021. More and more patients are searching for information on genitourinary cancers via TikTok. We aim to evaluate the functional quality and reliability of genitourinary cancer-related videos on it and share our thoughts based on the results for better public health promotion.Materials and MethodsWe retrieved 167 videos on bladder, prostate, and kidney cancer from TikTok. Only 61 videos (36.53%) met the inclusion criteria and were eventually regarded as sample videos. Each video’s length and descriptions, hashtags, number of views/likes/comments, forms of expression, and the uploader’s profile were included. Three validated assessment instruments: the Hexagonal Radar Schema, the Health on the Net Code scale, and the DISCERN instrument, were used for evaluating the quality and reliability of the information. All misinformation was counted and categorized. Univariate analysis of variance was performed for analyzing the results. The Post-Hoc least significant difference test was conducted to explore further explanation.ResultsAmongst 61 sample videos, healthcare practitioners contributed the most content (n = 29, 47.54%). However, 22 posts (36.07%) were misinformative, and the most common type was using outdated data. More than half of the videos could provide good (&gt; 1 point) content on the diseases’ symptoms and examinations. However, the definition and outcomes were less addressed (tied at 21%). The HONcode scale and the DISCERN instrument revealed a consistent conclusion that most videos (n = 59, 96.72%) on TikTok were of poor to mediocre quality. Videos published by media agencies were statistically better in terms of reliability and overall score (P = 0.003 and 0.008, respectively). Fifty-three videos (86.89%) had at least two unexplained medical terms. Healthcare professionals tend to use professional terms most (mean = 5.28 words).ConclusionsMost videos on genitourinary cancers on TikTok are of poor to medium quality and reliability. However, videos posted by media agencies enjoyed great public attention and interaction. Medical practitioners could improve the video quality by cooperating with media agencies and avoiding unexplained terminologies.
Predictive and Prognostic Role of Peripheral Blood T-Cell Subsets in Triple-Negative Breast Cancer
Authors: Li Meng , Xu Junnan , Jiang Cui , Zhang Jingyan , Sun Tao 
Published: February 2022

BackgroundTriple-negative breast cancer (TNBC), as a highly aggressive and metastatic tumor, can still not contain the medical needs. It has become an urgent problem to develop prognostic markers further and realize precision medicine. The predictive and prognostic significance of peripheral blood lymphocytes, as well as the clinicopathological factors affecting them, were explored in the present study.MethodsThe clinicopathological data of 278 patients with TNBC were collected and analyzed retrospectively. Peripheral blood lymphocytes (pBL) and blood routine indexes before treatment were quantified by flow cytometry analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier curve and Cox hazard proportion regression model. The associations between hematologic parameters and treatment response and clinicopathological characteristics were estimated by the Mann-Whitney test and Spearman test.ResultsCompared with all blood routine indexes, only a significant correlation between better treatment efficacy and higher peripheral CD4 +/CD8 + ratio of TNBC patients was observed (P=0.059), particularly those treated with chemotherapy combined with immune checkpoint inhibitors (P=0.048). Among the pBL subsets, CD4 + T lymphocyte was the only independent factor that could predict the prognosis of metastatic TNBC. Patients presenting higher values of peripheral CD4 + T lymphocytes showed longer PFS (median PFS 9 months vs. 5 months; HR =0.65, 95%CI: 0.440-0.973, P = 0.032) and OS (median OS 31 months vs. 16 months; HR=0 .63, 95%CI: 0.417-0.940, P&lt; 0.01). Especially CD4+ was found predictive for prognosis in TNBC patients who received chemotherapy (P&lt;0.05). Finally, the older age, higher clinical stage, and more advanced treatment lines were related to the lower level of CD4 +. The older age and having received neoadjuvant therapy were related to the lower CD4 +/CD8 + ratio (P&lt;0.05).ConclusionThe baseline CD4+/CD8+ cell ratio in peripheral blood is associated with therapeutic response, especially for chemotherapy combined with immunotherapy. Peripheral CD4+ cells can steadily predict all clinical outcomes for patients with mTNBC, and this clinical prognosis prediction is significantly related to chemotherapy. Peripheral CD4+ and CD4+/CD8+ are both closely associated with clinicopathological parameters.
Sex Differences in the Patterns of Systemic Agent use Among Patients With Psoriasis: A Retrospective Cohort Study in Quebec, Canada
Authors: Milan Raymond , LeLorier Jacques , Brouillette Marie-Josée , Holbrook Anne , Litvinov Ivan V. , Rahme Elham 
Published: February 2022

Background: Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined.Objectives: To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation.Methods: We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002–2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients.Results: We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20–10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28–7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56–4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46–0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57–0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30–2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51–0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59–0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57–0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011.Conclusion: Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients’ characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.
Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis
Authors: Xu Congcong , Zhuo Yating , Liu Yunyao , Chen Hao 
Published: February 2022

Background: Cutaneous squamous cell carcinoma (cSCC) is a common cutaneous cancer with increasing incidence. Itraconazole has been identified as a potential anticancer drug candidate. However, the role of itraconazole in cSCC was still unclear. Our objective is exploring the therapeutic potential of itraconazole in cSCC and investigate its molecular mechanism.Methods: The anti-proliferation effect of itraconazole was tested with CCK-8 assay and clone formation assay. Cell cycle distribution and apoptosis rate were detected using flow cytometry and TUNEL assay, respectively. Transcriptomic and proteomic analyses were used to explore the underlying anti-cancer mechanism. Luciferase reporter assay was used for promoter activity. Reactive oxygen species (ROS), lipid peroxidation and iron accumulation were examined. The in vivo efficacy of itraconazole was assessed in a xenograft model.Results: Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of cSCC cells. An integrated analysis of transcriptomic and proteomic analyses identified that 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. HMGCS1 silencing reversed the antiproliferative activity of itraconazole in A431 cells. Dual-luciferase assay showed that itraconazole could promote HMGCS1 transcription. HMGCS1 silencing abated the expression of ACSL4 in A431 cells. The level of ROS, lipid peroxidation, as well as iron accumulation were increased by itraconazole. Moreover, treatment with itraconazole impeded tumor growth in A431-bearing mice.Conclusion: We proved itraconazole inhibits the growth of cSCC by regulating HMGCS1/ACSL4 axis.
Phenotyping Cardiopulmonary Exercise Limitations in Chronic Obstructive Pulmonary Disease
Authors: Gelinas Jinelle , Harper Megan , Sasso John , Wright Stephen , Melzer Bernie , Agar Gloria , Guenette Jordan , duManoir Gregory , Roman Michael , Rolf J. Douglass , Eves Neil 
Published: February 2022

BackgroundExercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes.MethodsPatients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) &lt; 90%pred], cardiovascular (VEpeak/MVC &lt; 85% or MVC-VEpeak &gt; 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred).ResultsFEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p &lt; 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p &lt; 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p &lt; 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype.ConclusionDistinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.
Quality of Life in Mothers With Perinatal Depression: A Systematic Review and Meta-Analysis
Authors: Li Jiaying , Yin Juan , Waqas Ahmed , Huang Zeyu , Zhang Hongji , Chen Manqing , Guo Yufei , Rahman Atif , Yang Lei , Li Xiaomei 
Published: February 2022

BackgroundThe prevalence of perinatal depression is high and its adverse effects on mothers and infants are extensive. Several studies have explored the relationship between perinatal depression and health-related quality of life (HRQoL), but little is known about the nature and magnitude of this effect. The objectives of this study were to evaluate the HRQoL of mothers with perinatal depression and compare the HRQoL of depressed mothers with that of non-depressed mothers.MethodsA systematic review was performed according to the PRISMA guidelines. PubMed, EMBASE, Scopus, PsycINFO, Web of Science, Cochrane Central Register, the China National Knowledge Infrastructure, the VIP Database, and the Wan Fang Database were searched. The retrieval time was from the establishment of the database to July 2020. A series of meta-analyses were run for each outcome pertaining to HRQoL sub-measures. Subgroup analyses were conducted based on country income category and time period.ResultsOf 7,945 studies identified, 12 articles were included in the meta-analysis, providing HRQoL data for 4,392 mothers. Compared with non-depressed mothers, mothers with perinatal depression reported significantly poor scores across all the quality-of-life domains. Mixed-effects analysis showed that there was no difference in the HRQoL scores of mothers with antepartum and postpartum depression. Mothers with perinatal depression in higher-income countries reported higher disability on role-physical (p = 0.02) and social functioning domains (p = 0.001) than those from lower-income countries.LimitationsDue to insufficient data, no regression analysis was performed. The inability to accurately determine the difference in HRQoL between antepartum and postpartum depression was because of the restriction of the included studies. Moreover, most of the included studies were conducted in middle-income countries and may have an impact on the applicability of the results. Subgroup analyses are observational and not based on random comparisons. The results of subgroup analyses should be interpreted with caution.ConclusionHRQoL is compromised in mothers with perinatal depression. Continuous efforts are required to improve the HRQoL of perinatal depressed mothers.Systematic Review Registration: CRD42020199488.