bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung Adenocarcinoma Cells Promote Self-Migration and Self-Invasion by Activating Neutrophils to Upregulate Notch3 Expression of Cancer Cells
Authors: Peng Weidong , Sheng Youjing , Xiao Han , Ye Yuanzi , Kwantwi Louis Boafo , Cheng Lanqing , Wang Yuanchong , Xu Jiegou , Wu Qiang 
Published: January 2022

Background: Invasion and migration of cancer cells play a key role in lung cancer progression and metastasis. Tumor-associated neutrophils (TANs) are related to poor prognosis in many types of cancer. However, the role of TANs in lung cancer is controversial. In this study, we investigated the effect of TANs on the invasion and migration of lung adenocarcinoma.Methods: Immunohistochemistry was performed to detect the density of infiltrating TANs and the expression of Notch3 in 100 lung adenocarcinoma tissues. Flow cytometry was used to observe the viability of neutrophils, which were isolated from healthy peripheral blood and then exposed to the supernatant of cultured lung adenocarcinoma cell lines. After treating with tumor-associated neutrophils culture supernatant, NeuCS (supernatant of cultured neutrophils), tumor cells culture supernatant, Medium (serum-free medium), respectively, the migration and invasion of the lung cancer cells before and after transfected by si-Notch3 were detected by transwell assay and wound healing assay. Kaplan-Meier plotter (http://kmplot.com/analysis/index.php?p) was used to analyze the prognostic role of the density of TANs on lung adenocarcinoma and TIMER ((http://cistrome.dfci.harvard.edu/TIMER/) was used to detect the expression of Notch3 on lung adenocarcinoma.Results: The infiltration of TANs was observed in the parenchyma and stroma of the lung adenocarcinoma, the density of TANs was positively related to the TNM stage and negatively related to the differentiation and prognosis. Notch3 expression of cancer cells was negatively related to the tumor differentiation and prognosis. Compared to quiescent neutrophils, the viability of TCCS-activated neutrophils was enhanced. Both migration and invasion of A549 and PC9 cells were significantly promoted by TANs, while after knocking down Notch3, the migration and invasion of the cancer cells were not affected by TANs. Bioinformatics analysis showed that the density of TANs and the expression of Notch3 were related to the poor prognosis.Conclusion: The results indicated that lung adenocarcinoma cells promote self-invasion and self-migration by activating neutrophils to upregulate the Notch3 expression of cancer cells. The density of infiltrating TANs may be a novel marker for the poor prognosis of lung adenocarcinoma. Targeting TANs might be a potential therapeutic strategy for lung cancer treatment.
Which Exercise Interventions Can Most Effectively Improve Reactive Balance in Older Adults? A Systematic Review and Network Meta-Analysis
Authors: Kim Youngwook , Vakula Michael N. , Bolton David A. E. , Dakin Christopher J. , Thompson Brennan J. , Slocum Timothy A. , Teramoto Masaru , Bressel Eadric 
Published: January 2022

BackgroundReactive balance is the last line of defense to prevent a fall when the body loses stability, and beneficial effects of various exercise-based interventions on reactive balance in older adults have been reported. However, their pooled evidence on the relative effects has yet to be described.ObjectiveTo review and evaluate the comparative effectiveness of various exercise-based interventions on reactive balance in older adults.MethodsNine electronic databases and reference lists were searched from inception to August 2021. Eligibility criteria according to PICOS criteria were as follows: (1) population: older adults with the mean age of 65 years or above; (2) intervention and comparison: at least two distinct exercise interventions or one exercise intervention with a no-exercise controlled intervention (NE) compared in each trial; (3) outcome: at least one measure of reactive balance; (4) study: randomized controlled trial. The main network meta-analysis was performed on data from the entire older adult population, involving all clinical conditions as well as healthy older adults. Subgroup analyses stratified by characteristics of participants (healthy only) and reactive balance outcomes (simulated slip or trip while walking, simulated forward falls, being pushed or pulled, and movable platform) were also conducted.ResultsThirty-nine RCTs (n = 1388) investigating 17 different types of exercise interventions were included in the network meta-analysis. Reactive balance training as a single intervention presented the highest probability (surface under the cumulative ranking (SUCRA) score) of being the best intervention for improving reactive balance and the greatest relative effects vs. NE in the entire sample involving all clinical conditions [SUCRA = 0.9; mean difference (95% Credible Interval): 2.7 (1.0 to 4.3)]. The results were not affected by characteristics of participants (i.e., healthy older adults only) or reactive balance outcomes.Summary/ConclusionThe findings from the NMA suggest that a task-specific reactive balance exercise could be the optimal intervention for improving reactive balance in older adults, and power training can be considered as a secondary training exercise.
Overtraining Syndrome as a Complex Systems Phenomenon
Authors: Armstrong Lawrence E. , Bergeron Michael F. , Lee Elaine C. , Mershon James E. , Armstrong Elizabeth M. 
Published: January 2022

The phenomenon of reduced athletic performance following sustained, intense training (Overtraining Syndrome, and OTS) was first recognized more than 90 years ago. Although hundreds of scientific publications have focused on OTS, a definitive diagnosis, reliable biomarkers, and effective treatments remain unknown. The present review considers existing models of OTS, acknowledges the individualized and sport-specific nature of signs/symptoms, describes potential interacting predisposing factors, and proposes that OTS will be most effectively characterized and evaluated via the underlying complex biological systems. Complex systems in nature are not aptly characterized or successfully analyzed using the classic scientific method (i.e., simplifying complex problems into single variables in a search for cause-and-effect) because they result from myriad (often non-linear) concomitant interactions of multiple determinants. Thus, this review 1) proposes that OTS be viewed from the perspectives of complex systems and network physiology, 2) advocates for and recommends that techniques such as trans-omic analyses and machine learning be widely employed, and 3) proposes evidence-based areas for future OTS investigations, including concomitant multi-domain analyses incorporating brain neural networks, dysfunction of hypothalamic-pituitary-adrenal responses to training stress, the intestinal microbiota, immune factors, and low energy availability. Such an inclusive and modern approach will measurably help in prevention and management of OTS.
Characteristics of Brain White Matter Microstructure in HIV Male Patients With Primary Syphilis Co-Infection
Authors: Qi Yu , Li Rui-Li , Wang Yuan-Yuan , Wang Wei , Liu Xu-Ze , Liu Jing , Li Xing , Zhang Xiao-Dong , Yu Wen , Liu Jiao-Jiao , Guo Yi-Fan , Rao Bo , Li Hong-Jun 
Published: January 2022

Purpose: To investigate the effect of syphilis infection on the microstructure of white matter (WM) in HIV-infected male patients using diffusion tensor imaging (DTI).Methods: Twenty-seven HIV-infected male patients with current syphilis or a history of syphilis (HIV +/syphilis +), twenty-nine HIV-infected male patients without syphilis co-infection (HIV +/syphilis–), and twenty-nine healthy controls (HC) were enrolled. All participants received DTI, and all patients received comprehensive neuropsychological assessment. Tract-based spatial statistics (TBSS) was adopted to analyze the DTI measures: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Correlation analysis was conducted to investigate the relationships between DTI measures and cognitive performance.Results: There were no significant differences in DTI measures between HIV+/syphilis– and HC. Compared with HC, lower FA was found in body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), the bilateral anterior corona radiata (ACR), superior corona radiata (SCR), posterior corona radiata (PCR), and posterior thalamic radiation (PTR) in HIV+/syphilis+ (p &lt; 0.05). Higher RD was found in BCC and SCC (p &lt; 0.05). Compared with HIV+/syphilis–, lower scores were found in complex motor skills (CMS) in HIV+/syphilis+, lower FA was found in BCC, SCC, GCC, the bilateral ACR, SCR, PCR, PTR, cingulate gyrus (CGC), the right inferior fronto-occipital fasciculus (IFO), the retrolenticular part of internal capsule (RLIC), sagittal stratum (SS), external capsule (EC) in HIV+/syphilis+ (p &lt; 0.01). Correlation analysis uncorrected for multiple comparisons showed there was a positive correlation between FA in GCC and CMS, FA in BCC, and CMS in HIV+/syphilis+.Conclusions: Syphilis co-infection can have an additive or synergistic effect on the brain WM in HIV-infected subjects. HIV-infected patients without syphilis should be actively treated to avoid syphilis infection.
Efficacy of Anti-seizure Medications, Quinidine, and Ketogenic Diet Therapy for KCNT1-Related Epilepsy and Genotype-Efficacy Correlation Analysis
Authors: Lin Zehong , Sang Tian , Yang Ying , Wu Yuan , Dong Yan , Ji Taoyun , Zhang Yuehua , Wu Ye , Gao Kai , Jiang Yuwu 
Published: January 2022

AimTo evaluate the efficacy of anti-seizure medications (ASMs), quinidine, and ketogenic diet therapy (KDT) for KCNT1-related epilepsy and to explore genotype-efficacy correlations.MethodsWe collected the data for KCNT1-related epilepsy cases from our hospital's medical records and the literature. In total, 50 patients received quinidine, 23 received classical KDT, and 15 received ASMs; all ASM data were from our hospital owing to the lack of detailed ASM data in the literature. The efficacy rates (ERs) of the treatments were compared; an ER that reduced the number of seizures by ≥50% was considered positive. Efficacy according to genotype was also assessed.ResultsThe ERs for the 30 patients at our hospital were 40, 26.7, 30, and 44.4% for all treatments, ASMs, quinidine, and KDT, respectively. For all patients (ours and those in previous reports), the overall ERs for quinidine and KDT were 26.0 and 43.5%, respectively (P = 0.135). The ERs for quinidine and KDT in functional domain variant-related epilepsy differed significantly (20.6 vs. 53.8%; P = 0.037).InterpretationKDT may be better at treating KCNT1-related epilepsy than quinidine; ASMs were the least effective. KDT is a viable treatment option for functional domain variant-related epilepsy.
Effects of High-Temperature, High-Pressure, and Ultrasonic Treatment on the Physicochemical Properties and Structure of Soluble Dietary Fibers of Millet Bran
Authors: Wei Chunhong , Ge Yunfei , Liu Dezhi , Zhao Shuting , Wei Mingzhi , Jiliu Junchen , Hu Xin , Quan Zhigang , Wu Yunjiao , Su Youtao , Wang Yifei , Cao Longkui 
Published: January 2022

ObjectivesThe effects of high-temperature, high-pressure, and ultrasonic treatment on the physicochemical properties and structure of soluble dietary fibers in millet bran were studied to provide a comprehensive reference for the utilization of millet bran.MethodsDifferent physical methods were used to treat millet bran dietary fibers, and their microstructures and Fourier-transform infrared spectra before and after modification were compared. The physicochemical properties (water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, cation exchange capacity), total antioxidant capacity, and thermal characteristics were also analyzed.ResultsThere were no significant changes in the chemical groups of millet bran's soluble dietary fibers after modification, but cracks appeared on the surface of the fibers and the structure became loose and porous. Fiber agglomeration was observed, as well as improved thermal stability. After modification, the water-holding capacity, swelling capacity, oil-holding capacity, fat-binding capacity, and cation exchange capacity of millet bran were improved. When compared to the original soluble dietary fibers, ultrasound-treated fibers showed the most substantial improvement in all four capabilities, with increases of 140, 50, 78.1, 65.7, and 37.8%, respectively, compared with the original soluble dietary fibers (P &lt; 0.05). The total antioxidant capacity of the ultrasound-treated fibers was found to be higher than those of the fibers that underwent the other three treatments (P &lt; 0.05).ConclusionsThe physicochemical qualities and structural characteristics of the soluble dietary fibers in millet bran are affected by all three physical modification methods; however, the physicochemical properties of the ultrasound-treated fibers are most significantly improved.
Combined Association of Tumoral PD-L1 Expression and Pretreatment Presence of Epstein-Barr Virus DNA With Risk Stratification and Prognosis of Patients With Nasopharyngeal Carcinoma
Authors: Li Xiaoyu , Peng Xingchen , Zhao Sha , Zhang Hong , Jiang Yong , Liu Fei , Ai Ping 
Published: January 2022

BackgroundLittle is known about whether the combination of tumor programmed death-ligand 1 (PD-L1) expression and pretreatment EBV DNA status can help stratify nasopharyngeal carcinoma (NPC) patients by risk of metastasis or predict prognosis.MethodsPD-L1 expression was assessed using immunohistochemical staining of 78 non-keratinizing NPC patients with clinical data. Survival outcomes and independent prognostic factors were identified.ResultsSeventy-eight patients were included, high PD-L1 expression was observed in 25 of 43 patients (58%) with metastasis, while it was observed only in 7 of 35 patients (20%) without metastasis. Multivariate analyses showed that progression-free survival (PFS) was independently predicted by tumoral PD-L1 expression and pretreatment EBV DNA status. When combining, 93.75% patients with high PD-L1 and EBV infection developed distant metastasis, and those patients were associated with worse PFS.ConclusionsBoth PD-L1 expression and pretreatment EBV DNA are closely related to metastasis and prognosis of NPC patients. Their combination can facilitate risk stratification and prognosis prediction, which may improve disease treatment and management.
Prognostic Value of the Geriatric Nutritional Risk Index in Non-Small Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Wang Haoyu , Li Cui , Yang Ruiyuan , Jin Jing , Liu Dan , Li Weimin 
Published: January 2022

BackgroundNovel evidence showed that the Geriatric Nutritional Risk Index (GNRI) may lead to poor prognosis of human cancers. Therefore, we conducted a meta-analysis to explore the impact of GNRI in lung cancer and its prognostic value.MethodsWe searched the databases of PubMed, Web of Science, Embase, Scopus, and Cochrane Library up to July 2021 for relevant research and merged the hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association between GNRI and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with lung cancer. ResultsEight studies involving 2,399 patients were included in our primary meta-analysis. The results indicated that lower level of GNRI was associated with poorer OS, RFS, and CSS of lung cancer patients (OS: HR = 1.99, 95% CI: 1.68–2.35, p &lt; 0.0001; RFS: HR = 2.34, 95% CI: 1.11–4.95, p = 0.0258; CSS: HR = 2.45, 95% CI: 1.43–4.18, p = 0.0011). The association was robust after subgroup analysis and sensitivity analysis.ConclusionsGNRI may be a prognostic factor of lung cancer, which can lead to poorer survival. However, more prospective studies are necessary to confirm the results.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42021269574.
Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine
Authors: Ailani Jessica , Rabany Liron , Tamir Shira , Ironi Alon , Starling Amaal 
Published: January 2022

Introduction: Migraine is a chronic neurological disease that is the primary cause of years lived with disability in people under the age of 50. Remote electrical neuromodulation (REN) is a novel drug-free acute treatment of migraine, that is FDA cleared for episodic and chronic migraine. As a prescribed digital therapeutic, REN enables large-scale post-marketing research, thus providing real-world information on the use of the intervention in a wide range of populations, environments, and situations.Methods: The REN device (®Nerivio) includes a secured, personal migraine diary, which patients can use to record their symptoms before treatment and 2 h post-treatment. Real-world data on REN treatments were collected via the app from patients across the United States who used Nerivio between October 1st, 2019, and May 24th, 2021. Data analysis focused on four metrics: 1. Per-treatment patterns of REN use as a standalone treatment vs. in combination with medications. 2. Per-user intra-individual efficacy across multiple treatments. 3. Distribution of treatment intensity among users (the electroceutical equivalent to treatment dose). 4. Prevalence and severity of adverse events.Results: 1. Out of 23,151 treatments, in 66.5% of treatments REN was used as a standalone treatment, in 12.9% it was followed by over-the-counter medications, and in 20.6% followed by prescription medications. 2. Out of 2,514 patients, response in at least 50% of treatments was achieved in 66.5% of cases for pain relief, and in 22.6% for pain freedom. 3. Out of 117,583 treatments, in 80% of cases intensity levels were between 18 and 55% of the stimulator's range. The mean intensity was 34.3% of the stimulator's output (±16.6%). 4. Out of 12,368 users (121,947 treatments), there were 59 users (0.48%) who reported device related adverse events, 56 (0.45%) of which were mild, three (0.03%) were moderate, and none were severe.Conclusions: The current analysis of real-world clinical data indicates that REN provides an efficacious, stable, and safe treatment option for acute treatment of migraine in real-world settings, both as a standalone replacement of pharmaceuticals, as well as an adjunct to medications.
Intravenous Immunoglobulin Combined With Corticosteroids for the Treatment of Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis: A Propensity-Matched Retrospective Study in China
Authors: Yang Lu , Shou Yan-Hong , Li Feng , Zhu Xiao-Hua , Yang Yong-Sheng , Xu Jin-Hua 
Published: January 2022

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe adverse drug reactions. The use of corticosteroids and intravenous immunoglobulin (IVIg) in SJS/TEN remains controversial.Methods: In this single-center, observational, propensity-matched, retrospective study, we collected a total of 224 patients with SJS/TEN who were hospitalized in our department from 2008 to 2019; according to treatment with IVIg combined with corticosteroids or with corticosteroids alone, patients were divided into combination therapeutic group (163 patients) and monotherapeutic group (61 patients). Patients from the two groups were matched by their propensity score in blocks of 2:1. Comparisons of the clinical characteristics and prognoses between propensity-matched SJS/TEN patients treated with IVIg combined with corticosteroids and corticosteroids alone were made.Results: After our propensity matching, a total of 145 patients were yielded, including 93 patients treated with IVIg and 52 patients not treated with IVIg. All of the 23 variables reflected good matching between patients treated with/without IVIg, and no significant difference was observed. Although there was no significant difference between the totally predicted and actual mortality in both of our groups, the actual mortality was lower than it was predicted in patients treated with IVIg [p &gt; 0.250, the standardized mortality ratio (SMR) was 0.38, 95% CI 0.00–0.91] and patients treated without IVIg (p = 1.000, the SMR was 0.75, 95% CI 0.00–1.76). IVIg tended toward reducing the time to arrest of progression by 1.56 days (p = 0.000) and the length of hospital stay by 3.37 days (p = 0.000). The mortality rate was 45% lower for patients treated with IVIg combined with corticosteroids than those only treated with corticosteroid therapy, although it was not statistically significant (p = 0.555). The incidence of skin infections was significantly lower in the combined therapy group (p &lt; 0.025), and the total infection rate of patients treated with combination therapy tended to decrease by 67% compared to patients treated with corticosteroids alone (p = 0.047).Conclusion: The actual mortality rate of patients treated with corticosteroids alone or IVIg combined with corticosteroids tended to be lower than those predicted by TEN-specific severity-of-illness score (SCORTEN), although there was no significance. Compared with those treated by corticosteroids alone, combination therapy was prone to bring a better prognosis for SJS/TEN patients.