bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Efficacy and Safety of Anterograde vs. Retrograde Iodine Staining During Esophageal Chromoendoscopy: A Single-Center, Prospective, Parallel-Group, Randomized, Controlled, Single-Blind Trial
Authors: Tian Xu , Yang Wei , Chen Wei-Qing 
Published: November 2021

Background and Aim: Chromoendoscopy with iodine staining is an important diagnostic method for esophageal carcinomas or precancerous lesions. Unfortunately, iodine staining can be associated with numerous adverse events (AEs). We found that the starting position of spraying iodine solution is likely the main reason of causing AEs. We conducted this work to determine whether clinical outcomes from anterograde iodine staining were superior to those achieved after retrograde iodine staining.Methods: A total of 134 subjects with a health risk appraisal flushing (HRA-F) score of &gt;6 for esophageal cancer were randomly assigned to receive anterograde or retrograde iodine staining in the esophagus. The primary endpoints were the pain and the amount of iodine solution consumption. The secondary endpoints were iodine-staining effect, detection yield, and response to starch indicator.Results: Nine patients suffered from pain and six patients revealed positive response to starch indicator in retrograde iodine-staining group; however, no patient reported pain (0/67) and all patients revealed a negative response to starch indicator in anterograde iodine-staining group. The amount of iodine solution consumption in anterograde iodine-staining group (4.97 mL) was significantly lower than that (6.23 mL) in retrograde iodine-staining group; however, the iodine-staining effect and detection yield were comparable between the two groups.Conclusions: Anterograde iodine staining during Lugol chromoendoscopy appears to be as effective, but significantly safer than retrograde iodine staining.
Androgen Receptor Pathway Activity Assay for Sepsis Diagnosis and Prediction of Favorable Prognosis
Authors: Bouwman Wilbert , Verhaegh Wim , Stolpe Anja van de 
Published: November 2021

Introduction: Sepsis is a life-threatening complication of a bacterial infection. It is hard to predict which patients with a bacterial infection will develop sepsis, and accurate and timely diagnosis as well as assessment of prognosis is difficult. Aside from antibiotics-based treatment of the causative infection and supportive measures, treatment options have remained limited. Better understanding of the immuno-pathophysiology of sepsis is expected to lead to improved diagnostic and therapeutic solutions.Functional activity of the innate (inflammatory) and adaptive immune response is controlled by a dedicated set of cellular signal transduction pathways, that are active in the various immune cell types. To develop an immune response-based diagnostic assay for sepsis and provide novel therapeutic targets, signal transduction pathway activities have been analyzed in whole blood samples from patients with sepsis.Methods: A validated and previously published set of signal transduction pathway (STP) assays, enabling determination of immune cell function, was used to analyze public Affymetrix expression microarray data from clinical studies containing data from pediatric and adult patients with sepsis. STP assays enable quantitative measurement of STP activity on individual patient sample data, and were used to calculate activity of androgen receptor (AR), estrogen receptor (ER), JAK-STAT1/2, JAK-STAT3, Notch, Hedgehog, TGFβ, FOXO-PI3K, MAPK-AP1, and NFκB signal transduction pathways.Results: Activity of AR and TGFβ pathways was increased in children and adults with sepsis. Using the mean plus two standard deviations of normal pathway activity (in healthy individuals) as threshold for abnormal STP activity, diagnostic assay parameters were determined. For diagnosis of pediatric sepsis, the AR pathway assay showed high sensitivity (77%) and specificity (97%), with a positive prediction value (PPV) of 99% and negative prediction value (NPV) of 50%. For prediction of favorable prognosis (survival), PPV was 95%, NPV was 21%. The TGFβ pathway activity assay performed slightly less for diagnosing sepsis, with a sensitivity of 64% and specificity of 98% (PPV 99%, NPV 39%).Conclusion: The AR and TGFβ pathways have an immunosuppressive role, suggesting a causal relation between increased pathway activity and sepsis immunopathology. STP assays have been converted to qPCR assays for further evaluation of clinical utility for sepsis diagnosis and prediction of prognosis, as well as for prediction of risk at developing sepsis in patients with a bacterial infection. STPs may present novel therapeutic targets in sepsis.
Clinical Significance of Diffusely Increased Uptake of 68Ga-FAPI in Thyroid Gland
Authors: Liu Huipan , Yang Xiao , Liu Lin , Lei Lei , Wang Li , Chen Yue 
Published: November 2021

Purpose: To determine the clinical significance of diffuse uptake of 68Ga-FAPI in the thyroid.Methods: From January 2020 to September 2021, all subjects with diffuse thyroid uptake in 68Ga-FAPI PET/CT were investigated in our hospital, and compared with the age and sex matched control group. The 68Ga-FAPI uptake in the thyroid gland was analyzed semi-quantitatively using the maximum standardized uptake value (SUVmax), and regression analysis was used to analyze the correlation between available serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb).Results: Among 815 subjects, 39 subjects were found diffuse FAPI uptake in thyroid gland; 11 subjects refused further examination; a total of 28 subjects were included in the analysis, and 27 subjects were diagnosed with chronic thyroiditis (including 20 subjects with Hashimoto's thyroiditis), 3 subjects with Grave's disease, 3 subjects with only serum TSH elevated, and 1 subject with malignant of thyroid and thyroiditis. The SUVmax of 27 subjects with thyroiditis was 5.75 ± 5.45. No significant correlation was found between the SUVmax and the level of serum TSH (P = 0.389) or TPOAb (P = 0.426).Conclusion: The incidentally discovered diffusely increased 68Ga-FAPI uptake in the thyroid gland is mostly related to chronic lymphocytic (Hashimoto's) thyroiditis. 68Ga-FAPI uptake level correlated neither with the degree of hypothyroidism nor with the titer of TPOAb. In addition, immune-related thyroiditis with immune checkpoint inhibitors may be accidentally found on 68Ga-FAPI, which may be helpful in facilitate timely intervention.
Mapping Knowledge Structure and Themes Trends of Osteoporosis in Rheumatoid Arthritis: A Bibliometric Analysis
Authors: Wu Haiyang , Cheng Kunming , Guo Qiang , Yang Weiguang , Tong Linjian , Wang Yulin , Sun Zhiming 
Published: November 2021

Background: Rheumatoid arthritis is a chronic disabling disease characterized by chronic inflammation, articular cartilage destruction, and reduced bone mass. Multiple studies have revealed that the development of osteoporosis in rheumatoid arthritis (RA; ORA) patients could be led to a reduced quality of life and increased healthcare costs. Nevertheless, no attempt has been made to analyze the field of ORA research with the bibliometric method. This study aimed to provide a comprehensive overview of the knowledge structure and theme trends in the field of ORA research from a bibliometric perspective.Methods: Articles and reviews regarding ORA from 1998 to 2021 were identified from the Web of Science database. An online bibliometric platform, CiteSpace, and VOSviewer software were used to generate visualization knowledge maps including co-authorship, co-citation, and co-occurrence analysis. SPSS, R, and Microsoft Excel software were used to conduct curve fitting and correlation analysis, and to analyze quantitative indicators, such as publication and citation counts, h-index, and journal citation reports.Results: A total of 1,081 papers with 28,473 citations were identified. Publications were mainly concentrated in North America, Western Europe, and Eastern Asia. Economic strength is an important factor affecting scientific output. The United States contributed the most publications (213) with the highest h-index value (46) as of September 14, 2021. Diakonhjemmet Hospital and professor Haugeberg G were the most prolific institution and influential authors, respectively. Journal of Rheumatology was the most productive journal concerning ORA research. According to the burst references, “anti-citrullinated protein antibodies” and “preventing joint destruction” have been recognized as the hot research issues in the domain. The keywords co-occurrence analysis identified “teriparatide,” “interleukin-6,” “Wnt,” and “vertebral fractures” as the important future research directions.Conclusion: This was the first bibliometric study comprehensively summarizing the trends and development of ORA research. Our findings could offer practical sources for scholars to understand the key information in this field, and identify the potential research frontiers and hot directions in the near future.
Epidemiologic Features, Survival, and Prognostic Factors Among Patients With Different Histologic Variants of Glioblastoma: Analysis of a Nationwide Database
Authors: Shieh Li-Tsun , Ho Chung-Han , Guo How-Ran , Huang Chien-Cheng , Ho Yi-Chia , Ho Sheng-Yow 
Published: November 2021

Background: Glioblastoma (GBM) is the most common primary intracranial malignancy. Previous studies found incidence of GBM varies substantially by age, sex, race and ethnicity, and survival also varies by country, ethnicity, and treatment. Gliosarcoma (GSM) and giant cell glioblastoma (GC-GBM) are different histologic variants of GBM with distinct clinico-pathologic entities. We conducted a study to compare epidemiology, survival, and prognostic factors among the three.Methods: We identified GBM patients diagnosed between 2000 and 2016 using the Taiwan Cancer Registry and followed them using the death registry. Survival was compared among conventional GBM and two histologic variants. The potential confounding factors evaluated in this study included registered year, age, sex, and treatment modality (resection, radiotherapy, and chemotherapy).Results: We enrolled 3,895 patients, including 3,732 (95.8%) with conventional GBM, 102 (2.6%) with GSM, and 61 (1.6%) with GC-GBM. GC-GBM patients had younger mean age at diagnosis (49.5 years) than conventional GBM patients (58.7 years) and GSM patients (61.3 years) (p &lt; 0.01). The three groups had similar sex distributions (p = 0.29). GC-GBM had a longer median survival [18.5, 95% confidence interval (CI): 15.8–25.3 months] than conventional GBM (12.5, 95%CI: 12.0–13.0 months) and GSM (12.8, 95%CI: 9.2–16.2 months), and the differences in overall survival did not attain statistical significance (p = 0.08, log-rank test). In univariate analysis, GC-GBM had better survival than conventional GBM, but the hazard ratio (0.91) did not reach statistical significance (95%CI: 0.69–1.20) in the multivariate analysis. Young ages (≤ 40 years), female sex, resection, radiotherapy, and chemotherapy were factors associated with better survival in overall GBMs. In subtype analyses, these factors remained statistically significant for conventional GBM, as well as radiotherapy for GSM.Conclusion: Our analysis found conventional GBM and its variants shared similar poor survival. Factors with age ≤ 40 years, female sex, resection, radiotherapy, and chemotherapy were associated with better prognosis in conventional GBM patients.
Trauma Immediately Preceding REM-Behavior Disorder: A Valuable Prognostic Marker?
Authors: Williams Stevie R. , Henzler Nelly , Peřinová Pavla , Morrison Ian A. , Ellis Jason G. , Riha Renata L. 
Published: November 2021

Background: The definition of rapid eye movement (REM) sleep behavior disorder (RBD) has varied over the years. Rapid eye movement sleep behavior disorder can be considered isolated or idiopathic or can occur in the context of other disorders, including trauma-associated sleep disorder (TSD) and overlap parasomnia. However, whether trauma in RBD carries any prognostic specificity is currently unknown.Study Objectives: To test the hypothesis that RBD secondary to trauma is less likely to result in the development of neurodegeneration compared to idiopathic RBD (iRBD) without trauma in the general population.Methods: A retrospective cohort study of 122 consecutive RBD patients (103 males) at two tertiary sleep clinics in Europe between 2005 and 2020 was studied. Patients were diagnosed as having iRBD by video polysomnography (vPSG) and had a semi-structured interview at presentation, including specifically eliciting any history of trauma. Patients with secondary RBD to recognized causes were excluded from the study. Patients with iRBD were categorized into three groups according to reported trauma history: (1) No history of trauma, (2) traumatic experience at least 12 months prior to RBD symptom onset, and (3) traumatic experience within 12 months of RBD symptom onset. Idiopathic RBD duration was defined as the interval between estimated onset of RBD symptoms and last hospital visit or death. Follow-up duration was defined as the interval between iRBD diagnosis and last hospital visit or death.Results: In a follow-up period of up to 18 years, no patient who experienced trauma within 12 months preceding their iRBD diagnosis received a diagnosis of a neurodegenerative disorder (n = 35), whereas 38% of patients without trauma within the 12 months of symptom onset developed a neurodegenerative illness. These patients were also significantly more likely to have a family history of α-synucleinopathy or tauopathy.Conclusions: The development of RBD within 12 months of experiencing a traumatic life event, indistinguishable clinically from iRBD, did not lead to phenoconversion to a neurodegenerative disorder even after 18 years (mean follow up 6 years). We suggest that a sub-type of RBD be established and classified as secondary RBD due to trauma. Additionally, we advocate that a thorough psychological and trauma history be undertaken in all patients presenting with dream enactment behaviors (DEB).
Autonomic Modulation in Duchenne Muscular Dystrophy During a Computer Task: A Prospective Transversal Controlled Trial Assessment by Non-linear Techniques
Authors: Alvarez Mayra Priscila Boscolo , Monteiro Carlos Bandeira de Mello , Silva Talita Dias da , Valenti Vitor E. , Ferreira-Filho Celso , Sterr Annette , Vanderlei Luiz Carlos Marques , Ferreira Celso , Garner David M. 
Published: November 2021

Introduction: Due to functional and autonomic difficulties faced by individuals with Duchenne Muscular Dystrophy (DMD), the use of assistive technology is critical to provide or facilitate functional abilities. The key objective was to investigate acute cardiac autonomic responses, by application of Heart Rate Variability (HRV), during computer tasks in subjects with DMD via techniques based on non-linear dynamics.Method: HRV was attained via a Polar RS800CX. Then, was evaluated by Chaotic Global Techniques (CGT). Forty-five male subjects were included in the DMD group and age-matched with 45 in the healthy Typical Development (TD) control group. They were assessed for 20 min at rest sitting, and then 5 min whilst performing the maze task on a computer.Results: Both TD and DMD subjects exhibited a significantly reduced HRV measured by chaotic global combinations when undertaking the computer maze paradigm tests. DMD subjects presented decreased HRV during rest and computer task than TD subjects.Conclusion: While there is an impaired HRV in subjects with DMD, there remains an adaptation of the ANS during the computer tasks. The identification of autonomic impairment is critical, considering that the computer tasks in the DMD community may elevate their level of social inclusion, participation and independence.
A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma
Authors: Gao Xiaolei , Zhao Na , Dong Liying , Zheng Xuan , Zhang Yixin , Ding Chong , Zhao Shuyan , Ma Zeyun , Wang Yixiang 
Published: November 2021

Simple SummaryClinically, aberrant lipid metabolism is responsible for overweight and/or obesity. Overweight is considered as an independent factor of cancer risk in 2019. Therefore, lipid metabolic reprogramming is an emerging hallmark of malignancy. It is an urgent need to comprehensively understand the relationship among lipid metabolism and HNSCC and identify a valuable biomarker for predicting prognosis of HNSCC patients. Three new findings were found in this study. Firstly, we identified the lipid-related differentially expressed genes (DEGs) by using the GEO microarrays and TCGA dataset. A novel lipid-related mRNA prognostic signature (LRPS, consisting of ADCY2, LIPE and OLR1) was developed, which could predict the survival and prognosis of HNSCC patients as an independent effective prognostic factor. Secondly, we found that the LRPS could indicate the type of infiltrated immune cells in HNSCC tumor microenvironment. Thirdly, we verified that the LPPS score could interpret the TP53 status of HNSCC. Our new findings indicated that LRPS has a potential to be a promising indicator of overall survival, TP53 status, and immune characteristics in HNSCC, and perhaps can monitor and guide the treatment efficacy and prognosis of HNSCC in the future.BackgroundHead and neck squamous cell carcinoma (HNSCC) is characterized by a high frequency of lymph node metastasis and a high mortality. Lipid metabolic reprogramming is an emerging carcinogen as its role in fulfilling cancer growth and spread. However, little is known about the correlation between lipid metabolism and HNSCC.Materials and MethodsExpressions of lipid-related genes were obtained from the Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases for differential and functional analyses. A total number of 498 patients from TCGA with complete information were included to identify a lipid-related prognostic signature (LRPS), based on ADCY2, LIPE, and OLR1, by using univariate and multivariate Cox regression analyses. LRPS-high and LRPS-low groups were accordingly divided to pathway and cell enrichment analyses.ResultsLRS-low patients had a better overall survival and relapse - free survival than LRS-high ones in HNSCC. The LRPS-high group was significantly related to perineural invasion of cancer, cancer-related pathways, high TP53 mutation rate, high proportion of natural killer T cells (NKT), dendritic cells, monocytes, Treg, and M1 and M2 macrophage infiltration in HNSCC tumor tissues. Conversely, the LRPS-low group correlated with DNA damage-related and T-cell-regulated pathways, low frequency of mutated TP53, and high infiltration of B cells and CD4+ effector cells including Th1 and Th2.ConclusionLRPS has a potential to be a promising indicator of overall survival, prognosis, TP53 status, and immune characteristics in HNSCC.
Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study
Authors: Zhang Qiyi , Liu Xingyu , Wei Shumei , Zhang Lufei , Tian Yang , Gao Zhenzhen , Jin Ming , Yan Sheng 
Published: November 2021

ObjectiveWe investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC).MethodsIn this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; &lt;60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers.ResultsAmong 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6–11.4) and the median OS was 17.7 months (95% CI: not estimable).ConclusionsLenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated.Clinical Trial Registrationwww.chictr.org.cn, ChiCTR2100044476.
Bothersome Hematospermia Following Stereotactic Body Radiation Therapy for Prostate Cancer
Authors: Shah Sarthak , Sholklapper Tamir , Creswell Michael , Pepin Abigail , Cantalino Jonathan , Hankins Ryan Andrew , Suy Simeng , Collins Sean P. 
Published: November 2021

BackgroundHematospermia following prostate radiation therapy is a benign and often self-limiting side effect. However, it may be bothersome to some men and their partners with a negative impact on sexual quality of life (QOL). This study sought to evaluate the incidence, duration, and resolution of hematospermia in patients following stereotactic body radiation therapy (SBRT) for prostate cancer.Methods227 patients treated with SBRT from 2013 to 2019 at Georgetown University Hospital for localized prostate carcinoma with a minimum follow up of two years were included in this retrospective review of data that was prospectively collected. Patients who were greater than 70 years old and/or received hormonal therapy were excluded. Hematospermia was defined as bright red blood in the ejaculate. Time points for data collection included initial consultation, pre-treatment, 1-, 3-, 6-, 9-, 12-, 18-, 24-month. All patients were treated with the CyberKnife Radiosurgical System (Accuray). Data on hematospermia including duration, resolution and recurrence was collected. Utilization of 5-alpha reductase inhibitors was documented at each visit.Results227 patients (45 low-, 177 intermediate-, and 5 high-risk according to the D’Amico classification) at a median age of 65 years (range 47-70) received SBRT for their localized prostate cancer. The 2-year cumulative incidence of hematospermia was 5.6%(14 patients). For these patients, all but one patient (93%) saw resolution of their hematospermia by two years post-SBRT. The median time for hematospermia was 9 months post-treatment. Of the 14 patients who reported hematospermia, 70% were managed with 5-alpha reductase inhibitors. Hematospermia was transient in most patients with 70% of the men reporting resolution by the next follow-up visit.ConclusionThe incidence of bothersome hematospermia following SBRT was low. Hematospermia, as noted by other studies, often self-resolves. 5-alpha reductase inhibitors may lead to quicker resolution of bothersome hematospermia.