bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Ankle-Brachial Index Is Associated With Stroke Recurrence in Ischemic Stroke Patients With Atrial Fibrillation
Authors: Han Minho , Baik Minyoul , Kim Young Dae , Choi Junghye , Seo Kangsik , Park Eunjeong , Heo Ji Hoe , Nam Hyo Suk 
Published: October 2021

Introduction: Cardioembolic stroke (CE) has poor outcomes and high recurrence rates. A low ankle-brachial index (ABI &lt;0.9) is associated with atrial fibrillation (AF) and poor stroke outcomes. We investigated whether a low ABI is associated with stroke recurrence, major adverse cardiovascular events (MACE), and mortality in patients with CE and whether this association is affected by AF.Methods: We enrolled patients with CE who underwent ABI measurements during hospitalization. Recurrent stroke was defined based on newly developed neurologic symptoms with relevant lesions 7 days after the index stroke. MACE comprised stroke recurrence, myocardial infarction, or death.Results: Of 775 patients, 427 (55.1%) were AF patients and 348 (44.9%) were non-AF patients. Patients were followed up for a median of 33.6 (IQR, 18.0–51.6) months. In total, 194 (25.0%) patients experienced MACE, including 77 (9.9%) patients with stroke recurrence and 101 (13.0%) patients with mortality, during the study period. Multivariable Cox regression analysis showed that an ABI &lt;0.9 was independently associated with MACE (AF patients: hazard ratio [HR] = 2.327, 95% confidence interval [CI] = 1.371–3.949, non-AF patients: HR = 3.116, 95% CI = 1.465–6.629) and mortality (AF patients: HR = 2.659, 95% CI = 1.483–4.767, non-AF patients: HR = 3.645, 95% CI = 1.623–8.187). Stroke recurrence was independently associated with an ABI &lt;0.9 in AF patients (HR = 3.559, 95% CI = 1.570–8.066), but not in non-AF patients (HR = 1.186, 95% CI = 0.156–8.989).Conclusions: We found that a low ABI is associated with stroke recurrence, MACE, and mortality in patients with CE. In particular, the association between ABI and recurrent stroke is only present in AF patients. A low ABI may be a useful prognostic marker in patients with CE, especially in AF patients.
Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)—Data From a Local Norwegian Cohort
Authors: Jaklin Andreas K. , Benjaminsen Espen , Alstadhaug Karl B. 
Published: October 2021

Objective: We aimed to determine the effectiveness of natalizumab (NTZ) by assessing overall No Evidence of Disease Activity 3 (NEDA-3) in a local Norwegian cohort.Background: NTZ is an immunomodulating drug used in the treatment of multiple sclerosis (MS). It has typically been used as a second-line treatment, but certain patients with high disease activity have started directly with NTZ.Methods: This retrospective cohort study includes all patients who received NTZ for relapsing–remitting MS at Nordland Hospital in the period 2008–2018. In June 2019, status for every patient was assessed, and a survival curve was used to show the cumulative probability of achieving NEDA-3 over time.Results: The cohort consisted of 66 patients, 49 women and 17 men with a mean age of 40.0 ± 10.8 years. Each patient received on average 45.8 ± 36.4 NTZ infusions. Mean age and Expanded Disability Status Scale (EDSS) at first infusion was 34.8 ± 10.5 and 3.2 ± 1.9, respectively. Prior to NTZ treatment, 83% had used other disease modulating drugs and 65% were anti-JC virus (JCV) seronegative. During the study period, seven patients converted to seropositive. In 2019, 40 patients had switched or stopped treatment: 19 due to positive JCV serostatus, 9 due to disease activity, 7 due to adverse effects or complications (1 progressive multifocal leukoencephalopathy), 2 due to pregnancy, and 3 due to autologous hematopoietic cell transplantation abroad. Three patients experienced rebound in the wake of discontinuation (7.5%). Of the patients receiving NTZ for more than 3 years (n = 33), 50% had achieved NEDA-3 after 3 years. Compared to those with evidence of disease activity (EDA), these NEDA-3 patients had significant lower EDSS score before first NTZ treatment (p = 0.04). They were also slightly, but not significantly, younger at debut of their MS, at the diagnosis and at first NTZ treatment. Of all the patients who ever started on NTZ, 23% had achieved NEDA-3 5 years later. The mean EDSS in 2019 was 3.6 ± 2.5.Conclusion: Despite the high rate of treatment switch, mainly due to the risk of PML, almost one in four who started on NTZ achieved NEDA-3 after 5 years, and the overall disease progression was low in the total cohort. Treating less advanced disease seems to predict better long-term stability.
Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis
Authors: Wehmeyer Laura , Schüller Thomas , Kiess Jana , Heiden Petra , Visser-Vandewalle Veerle , Baldermann Juan Carlos , Andrade Pablo 
Published: October 2021

Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus–nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus–parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically.Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences.Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis.Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses.Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.
Identification of Prognostic Model Based on Immune-Related LncRNAs in Stage I-III Non-Small Cell Lung Cancer
Authors: Li Qiaxuan , Yao Lintong , Lin Zenan , Li Fasheng , Xie Daipeng , Li Congsen , Zhan Weijie , Lin Weihuan , Huang Luyu , Wu Shaowei , Zhou Haiyu 
Published: October 2021

BackgroundLong non-coding RNAs (lncRNAs) participate in the regulation of immune response and carcinogenesis, shaping tumor immune microenvironment, which could be utilized in the construction of prognostic signatures for non-small cell lung cancer (NSCLC) as supplements.MethodsData of patients with stage I-III NSCLC was downloaded from online databases. The least absolute shrinkage and selection operator was used to construct a lncRNA-based prognostic model. Differences in tumor immune microenvironments and pathways were explored for high-risk and low-risk groups, stratified by the model. We explored the potential association between the model and immunotherapy by the tumor immune dysfunction and exclusion algorithm.ResultsOur study extracted 15 immune-related lncRNAs to construct a prognostic model. Survival analysis suggested better survival probability in low-risk group in training and validation cohorts. The combination of tumor, node, and metastasis staging systems with immune-related lncRNA signatures presented higher prognostic efficacy than tumor, node, and metastasis staging systems. Single sample gene set enrichment analysis showed higher infiltration abundance in the low-risk group, including B cells (p&lt;0.001), activated CD8+ T cells (p&lt;0.01), CD4+ T cells (p&lt;0.001), activated dendritic cells (p&lt;0.01), and CD56+ Natural killer cells (p&lt;0.01). Low-risk patients had significantly higher immune scores and estimated scores from the ESTIMATE algorithm. The predicted proportion of responders to immunotherapy was higher in the low-risk group. Critical pathways in the model were enriched in immune response and cytoskeleton.ConclusionsOur immune-related lncRNA model could describe the immune contexture of tumor microenvironments and facilitate clinical therapeutic strategies by improving the prognostic efficacy of traditional tumor staging systems.
Aesthetical and Accuracy Outcomes of Reconstruction of Maxillary Defect by 3D Virtual Surgical Planning
Authors: Wang Yang , Qu Xingzhou , Jiang Junjian , Sun Jian , Zhang Chenping , He Yue 
Published: October 2021

BackgroundReconstruction of maxillary defect resulting from trauma or oncology surgery is of great importance for patients with physical and psychological complications. The virtual surgical planning (VSP) and 3D printing technics had been used in recent years which simplified the surgical procedure and promoted success and accuracy. To assess the accuracy and outcome of VSP surgery, here we report our experience in maxillary reconstruction retrospectively.MethodPatients who received maxillary defect reconstruction from 2013 to 2020 were analyzed retrospectively. These patients were divided into two groups. Group 1 received VSP and 3D printed guiding plates in the surgery, while group 2 underwent free-hand surgery (FHS). Patients with different vertical and horizontal defects were classified according to Brown and Shaw classification. Clinical information and postoperative complications of all patients were collected. For patients with unilateral maxillary defect, orbit volume, orbit height, and the contour of the reconstructed side were compared with the normal side.ResultThirty-four patients who achieved the criteria were analyzed, of which 20 patients underwent VSP surgery. There were primary and secondary reconstruction cases in both two groups. Vascularized iliac crest flap was used in three cases, and fibula flap was performed in the other cases. One flap collapse occurred in FHS group. Seven patients in VSP group received dental implants, while the number in FHS group was 0. In vertical class III cases, the differences in orbit height (ΔD) and orbit volume (ΔV) between normal side and reconstructed side were measured and compared in the two groups. The mean ΔD is 1.78 ± 1.33 mm in VSP group and 4.25 ± 0.95 mm in FHS group, while the mean ΔV is 2.04 ± 0.85 cm3 in VSP group and 3.25 ± 0.17 cm3 in FHS group. The alterations of orbit height and volume in VSP group were much smaller than that in FHS group with statistical significance. From the perspective of aesthetics, the color-gradient map indicates a more symmetric and smoother curve of post-operation appearance in VSP group.ConclusionCompared with traditional free-hand surgical technics, VSP and 3D printing guiding plates can allow for a more accurate maxillary reconstruction with improved aesthetics.
Survival of Neoadjuvant and Adjuvant Therapy Compared With Surgery Alone for Resectable Esophageal Squamous Cell Carcinoma: A Systemic Review and Network Meta-Analysis
Authors: Ma Zeliang , Yuan Meng , Bao Yongxing , Wang Yang , Men Yu , Hui Zhouguang 
Published: October 2021

ObjectiveThe optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. Surgery is the primary treatment but with poor results. Attempts to improve patient survival have been made by introducing chemotherapy, radiotherapy, or both. However, randomized comparisons for all these strategies are not always available. This network meta-analysis compared the overall survival of neoadjuvant and adjuvant therapy with surgery alone to identify the most effective approach.MethodsWe systematically searched electronic databases (PubMed, Embase, and Cochrane Library) for relevant studies published before April 2021. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, neoadjuvant chemotherapy (NCT), radiotherapy (NRT) or chemoradiotherapy (NCRT), adjuvant chemotherapy (ACT), radiotherapy (ART), or chemoradiotherapy (ACRT). The hazard ratios (HR) and 95% confidence intervals (CIs) of overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework, and the relative effects of all possible comparisons were made. The ranking analysis was performed to support the decision in clinical practice.ResultsA total of 19 relevant trials with 3,749 patients were identified. Compared with surgery alone, NCRT (HR 0.76, 95% CI 0.65–0.89) and NCT (HR 0.81, 95% CI 0.70–0.94) significantly improved OS, while other treatments, including NRT (HR 0.86, 95% CI 0.66–1.08), ACRT (HR 0.73, 95% CI 0.49–1.08), ACT (HR 0.96, 95% CI 0.75–1.21), and ART (HR 0.86, 95% CI 0.66–1.14), provided no significant survival advantage. None of the neoadjuvant and adjuvant treatments showed a statistically significant difference in OS to each other when compared in pairs.ConclusionFor resectable esophageal squamous cell carcinoma, this network meta-analysis showed that NCRT may be the optimal strategy, NCT may be the second choice, while other multimodality treatments could not improve OS compared with surgery alone. It remains unclear whether ESCC will benefit from adding radiotherapy into the neoadjuvant treatment.Systematic Review RegistrationWe registered this meta-analysis protocol at the prospective register of systematic reviews, PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=172745 (Identification code: CRD42020172745).
CDCA7 Facilitates Tumor Progression by Directly Regulating CCNA2 Expression in Esophageal Squamous Cell Carcinoma
Authors: Li Hongyi , Weng Yongjia , Wang Shaojie , Wang Fang , Wang Yanqiang , Kong Pengzhou , Zhang Ling , Cheng Caixia , Cui Heyang , Xu Enwei , Wei Shuqing , Guo Dinghe , Chen Fei , Bi Yanghui , Meng Yongsheng , Cheng Xiaolong , Cui Yongping 
Published: October 2021

BackgroundCDCA7 is a copy number amplified gene identified not only in esophageal squamous cell carcinoma (ESCC) but also in various cancer types. Its clinical relevance and underlying mechanisms in ESCC have remained unknown.MethodsTissue microarray data was used to analyze its expression in 179 ESCC samples. The effects of CDCA7 on proliferation, colony formation, and cell cycle were tested in ESCC cells. Real-time PCR and Western blot were used to detect the expression of its target genes. Correlation of CDCA7 with its target genes in ESCC and various SCC types was analyzed using GSE53625 and TCGA data. The mechanism of CDCA7 was studied by chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay.ResultsThe overexpression of CDCA7 promoted proliferation, colony formation, and cell cycle in ESCC cells. CDCA7 affected the expression of cyclins in different cell phases. GSE53625 and TCGA data showed CCNA2 expression was positively correlated with CDCA7. The knockdown of CCNA2 reversed the malignant phenotype induced by CDCA7 overexpression. Furthermore, CDCA7 was found to directly bind to CCNA2, thus promoting its expression.ConclusionsOur results reveal a novel mechanism of CDCA7 that it may act as an oncogene by directly upregulating CCNA2 to facilitate tumor progression in ESCC.
Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients
Authors: Xu Yihang , Cyriac Jonathan , De Ornelas Mariluz , Bossart Elizabeth , Padgett Kyle , Butkus Michael , Diwanji Tejan , Samuels Stuart , Samuels Michael A. , Dogan Nesrin 
Published: October 2021

PurposeTo assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients.MethodsSeventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis.ResultsAll the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (−5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (−5.74 ± 5.72 Gy), lower cochlea Dmean (left, −6.05 ± 4.33 Gy; right, −4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, −6.45% ± 5.32%; right, −6.92% ± 3.45%), and a lower integral dose (−0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans.ConclusionIMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.
Improving Quality Indicator of Melanoma Management – Change of Melanoma Mortality-to-Incidence Rate Ratio Based on a Hungarian Nationwide Retrospective Study
Authors: Várnai Máté , Kiss Zoltán , Gyulai Rolland , Oláh Judit , Holló Péter , Emri Gabriella , Csejtei András , Kenessey István , Benedek Angéla , Polányi Zoltán , Nagy-Erdei Zsófia , Dániel Andrea , Knollmajer Kata , Rokszin György , Fábián Ibolya , Barcza Zsófia , Polgár Csaba , Nagy Balázs , Liszkay Gabriella , Vokó Zoltán 
Published: October 2021

IntroductionThe incidence of melanoma has been increasing in the last decades. A retrospective Hungarian epidemiological study provided real-world data on incidence and mortality rates. There have been changing trends in incidence in Hungary in the last decade and mortality decreased, shifting mortality-to-incidence rate ratios (MIR). MIR is an indicator of cancer management quality.ObjectivesOur aim is to show the changes of melanoma MIR in Hungary between 2011 and 2018 and to compare the real-world evidence-based results of our Hungarian nationwide retrospective study with other European countries.MethodsMIR is calculated from the age-specific standardized incidence and mortality rates from our study. Annual MIR values are presented for the total population and for both sexes between 2011 and 2018, along with 95% confidence intervals. Comparison with European countries are shown for 2012 and 2018 based on the GLOBOCAN database and Eurostat health care expenditure per capita data.ResultsMIR decreased by 0.035 during the study years. The decrease was same in both sexes (0.031). Male had higher MIRs in all study years. In both 2012 and 2018, Hungarian MIR in both sexes was lower than the European Union average (males: 0.192 vs. 0.212 and 0.148 vs. 0.174 respectively, women: 0.107 vs. 0.129 and 0.083 vs. 0.107 respectively).DiscussionHungarian mortality-to-incidence ratio is the lowest in Central and Eastern Europe and is close to the level of Western and Northern European countries. The results are driven by the high number of new diagnosed melanoma cases.
Influence of Sex in the Molecular Characteristics and Outcomes of Malignant Tumors
Authors: Araujo Jhajaira M. , Rosas Gina , Belmar-López Carolina , Raez Luis E. , Rolfo Christian D. , Schwarz Luis J. , Infante-Huaytalla Ulises , Paez Kevin J. , García Luis R. , Alvarado Hober , Ramos Fany P. , Delgado-Espinoza Sheyla S. , Cardenas-Farfan Jhon B. , Cornejo Melanie , Zanabria Daniel , Colonio-Cossio Christian , Rojas-Jefferson Mario , Pinto Joseph A. 
Published: October 2021

BackgroundSex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer.MethodsA cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC).ResultsOverall, women had a decreased risk of death (HR = 0.73, CI95: 8%–42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men.ConclusionsThe study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.