bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Self-Assembling and Disassembling (SADA) Bispecific Antibody (BsAb) Platform for Curative Two-step Pretargeted Radioimmunotherapy
Authors: Santich Brian H. , Cheal Sarah M. , Ahmed Mahiuddin , McDevitt Michael R. , Ouerfelli Ouathek , Yang Guangbin , Veach Darren R. , Fung Edward K. , Patel Mitesh , Burnes Vargas Daniela , Malik Aiza A. , Guo Hong-Fen , Zanzonico Pat B. , Monette Sebastien , Michel Adam O. , Rudin Charles M. , Larson Steven M. , Cheung Nai K. 
Published: September 2020

Abstract

Purpose:
Many cancer treatments suffer from dose-limiting toxicities to vital organs due to poor therapeutic indices. To overcome these challenges we developed a novel multimerization platform that rapidly removes tumor-targeting proteins from the blood to substantially improve therapeutic index.

Experimental Design:
The platform was designed as a fusion of a self-assembling and disassembling (SADA) domain to a tandem single-chain bispecific antibody (BsAb, anti-ganglioside GD2 × anti-DOTA). SADA–BsAbs were assessed with multiple in vivo tumor models using two-step pretargeted radioimmunotherapy (PRIT) to evaluate tumor uptake, dosimetry, and antitumor responses.

Results:
SADA–BsAbs self-assembled into stable tetramers (220 kDa), but could also disassemble into dimers or monomers (55 kDa) that rapidly cleared via renal filtration and substantially reduced immunogenicity in mice. When used with rapidly clearing DOTA-caged PET isotopes, SADA–BsAbs demonstrated accurate tumor localization, dosimetry, and improved imaging contrast by PET/CT. When combined with therapeutic isotopes, two-step SADA-PRIT safely delivered massive doses of alpha-emitting (225Ac, 1.48 MBq/kg) or beta-emitting (177Lu, 6,660 MBq/kg) S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) payloads to tumors, ablating them without any short-term or long-term toxicities to the bone marrow, kidneys, or liver.

Conclusions:
The SADA–BsAb platform safely delivered large doses of radioisotopes to tumors and demonstrated no toxicities to the bone marrow, kidneys, or liver. Because of its modularity, SADA–BsAbs can be easily adapted to most tumor antigens, tumor types, or drug delivery approaches to improve therapeutic index and maximize the delivered dose.
See related commentary by Capala and Kunos, p. 377
Response to Anti-PD-1 in Microsatellite-Stable Colorectal Cancer: A STAT Need
Authors: Nusrat Maliha 
Published: September 2020

Abstract
Most colorectal cancers are microsatellite-stable with no response to anti-PD-1 therapy, necessitating the development of new immunomodulatory treatment strategies. Coinhibition of anti-PD-1 and STAT3 can elicit an effective antitumor response in a small subset of patients with microsatellite-stable colorectal cancer, and biomarkers predictive of response are under investigation.
See related article by Kawazoe et al., p. 5887
Proof of Concept of a Personalized Genetic Risk Tool to Promote Smoking Cessation: High Acceptability and Reduced Cigarette Smoking
Authors: Ramsey Alex T. , Bourdon Jessica L. , Bray Michael , Dorsey Amelia , Zalik Maia , Pietka Amanda , Salyer Patricia , Chen Li-Shiun , Baker Timothy B. , Munafò Marcus R. , Bierut Laura J. 
Published: September 2020

Abstract
Relatively little is known about the possible effects of personalized genetic risk information on smoking, the leading preventable cause of morbidity and mortality. We examined the acceptability and potential behavior change associated with a personalized genetically informed risk tool (RiskProfile) among current smokers. Current smokers (n = 108) were enrolled in a pre-post study with three visits. At visit 1, participants completed a baseline assessment and genetic testing via 23andMe. Participants’ raw genetic data (CHRNA5 variants) and smoking heaviness were used to create a tailored RiskProfile tool that communicated personalized risks of smoking-related diseases and evidence-based recommendations to promote cessation. Participants received their personalized RiskProfile intervention at visit 2, approximately 6 weeks later. Visit 3 involved a telephone-based follow-up assessment 30 days after intervention. Of enrolled participants, 83% were retained across the three visits. Immediately following intervention, acceptability of RiskProfile was high (M = 4.4; SD = 0.6 on scale of 1 to 5); at 30-day follow-up, 89% of participants demonstrated accurate recall of key intervention messages. In the full analysis set of this single-arm trial, cigarettes smoked per day decreased from intervention to 30-day follow-up [11.3 vs. 9.8; difference = 1.5; 95% confidence interval (0.6–2.4); P = 0.001]. A personalized genetically informed risk tool was found to be highly acceptable and associated with a reduction in smoking, although the absence of a control group must be addressed in future research. This study demonstrates proof of concept for translating key basic science findings into a genetically informed risk tool that was used to promote progress toward smoking cessation.
Prevention Relevance: This study demonstrates that personal genetic information can be incorporated into a risk feedback tool that was highly acceptable to current smokers and associated with reductions in smoking. These findings may pave the way for effectiveness and implementation research on genetically-informed behavior change interventions to enhance cancer prevention efforts.
Outcome by Sex in Patients With Long QT Syndrome With an Implantable Cardioverter Defibrillator
Authors: Younis Arwa , Aktas Mehmet K. , Rosero Spencer , Kutyifa Valentina , Polonsky Bronislava , McNitt Scott , Sotoodehnia Nona , Kudenchuk Peter , Rea Thomas D. , Arking Dan E. , Goldenberg Ilan , Zareba Wojciech 
Published: September 2020

Background
Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time‐dependent life‐threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD).

Methods and Results

A total of 60 patients with long QT syndrome received an ICD for primary or secondary prevention indications. Life‐threatening events were evaluated from the date of ICD implant and included ICD shocks for ventricular tachycardia, ventricular fibrillation, or death. ICDs were implanted in 219 women (mean age 38±13 years), 46 girls (12±5 years), 55 men (43±17 years), and 40 boys (11±4 years). Mean follow‐up post‐ICD implantation was 14±6 years for females and 12±6 years for males. At 15 years of follow‐up, the cumulative probability of life‐threatening events was 27% in females and 34% in males (log‐rank
P
=0.26 for the overall difference). In the multivariable Cox model, sex was not associated with significant differences in risk first appropriate ICD shock (hazard ratio, 0.83 female versus male; 95% CI, 0.52–1.34;
P
=0.47). Results were similar when stratified by age and by genotype: long QT syndrome type 1 (LQT1), long QT syndrome type 2 (LQT2), and long QT syndrome type 3 (LQT3). Incidence of inappropriate ICD shocks was higher in males versus females (4.2 versus 2.7 episodes per 100 patient‐years;
P
=0.018), predominantly attributed to atrial fibrillation. The first shock did not terminate ventricular tachycardia/ventricular fibrillation in 48% of females and 62% of males (
P
=0.25).

Conclusions
In patients with long QT syndrome with an ICD, the risk and rate of life‐threatening events did not significantly differ between males and females regardless of ICD indications or genotype. In a substantial proportion of patients with long QT syndrome, first shock did not terminate ventricular tachycardia/ventricular fibrillation.
Modeling and detection of the prepared tool edge radius
Authors: Xuefeng Zhao , Hui Li , Lin He , Meng Tao 
Published: September 2020

Introduction: High-speed and high-efficient machining is the inevitable development direction of machining technology. The tool edge preparation can improve the life, cutting performance, and surface quality of a tool and help to achieve high-speed and efficient machining. Therefore, precise modeling and detection of the micron-level contour of a tool edge are crucial for edge preparation. The aim of this study is to provide the model and detect method of the prepared tool edge radius. Methods: The mathematical model of the milling tool trajectory is established through the Matlab. The material removal model by single abrasive particle is established based on the energy conservation principle and energy absorption theory. The material removal model by multiple abrasive grains on the cutting tool edge is constructed using the statistical methods. The mathematical model of the edge radius is established through the geometrical relationship. The milling edge preparation contour detection system is setup based on the machine vision principle through LabVIEW software. Finally, the edge radius at different process parameters is determined by the mathematical model and detection system, and the results are compared with the results of the scanning electron microscopic measurement (SEM). Results: Through the Comparison and analysis of the edge radius measured by the SEM and calculated by the proposed model. The maximum error between the analytical results and SEM measurements is 11.18 μm, while the minimum error is 0.07 μm. Through the comparison and analysis of the edge radius measured by the SEM and the edge detection system. The maximum difference between the two methods is 2.71 μm, and the minimum difference is 0.31 μm. The maximum difference in percentage is 9.2%, and the minimum difference in percentage is 1.2%. Discussions: The edge preparation mechanisms of a single particle and multiple particles on the tool edge are explained. A mathematical model of the edge radius is established, which provides a basis for a deeper understanding of the edge preparation effect. Based on the machine vision principle, the prepared tool micron-level edge detection method is proposed. The histogram specification method, median filtering, multi-threshold segmentation method, and Canny edge detection operator are adopted to obtain the edge contour. The comparison result shows that the mathematical model of the edge radius is accurate, and the proposed tool edge detection method is feasible, which lays the foundation for edge preparation and realization of high-speed and high-efficient machining.
Rapid formation of a radiolucent pancreatic stone: a case report (with video)
Authors: Wang Dan , Bi Ya-Wei , Xu Hao , Wang Teng , Li Zhao-Shen , Xu Zheng-Lei , Hu Liang-Hao 
Published: September 2020

Background Over 90% of pancreatic stones are radiopaque and can be treated with endoscopy or surgery. However, radiolucent stones are different than radiopaque stones in nature and formation, and therefore, treatment varies. Case presentation: A 25-year-old woman was admitted because of recurrent acute pancreatitis. Imaging examinations confirmed the diagnosis of chronic pancreatitis (CP), and which revealed the existence of radiolucent stones. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant protein-like radiolucent stones were extracted. Three 10F, 7-cm plastic stents were placed. However, the stents were completely occluded by radiolucent stones 1 month later. A nasopancreatic tube was then inserted and flushed regularly, but protein-like stones formed continuously. After multidisciplinary consultation, the following conservative treatment strategy was applied: 1) no more endotherapy; 2) a diet with 40% to 50% of calories from fat was recommended; 3) no pancreatic enzyme replacement therapy; and 4) regular exercise. The above advice aimed to stimulate the secretion of pancreatic fluid to achieve auto-flushing of the pancreatic duct and prevent protein-like stones from depositing. No acute pancreatitis recurred during the 5-year follow-up. Conclusions This strategy was effective for auto-flushing the pancreatic duct in patients with radiolucent pancreatic stones after the main pancreatic duct stricture was resolved.
Establishment of a quality control circle to reduce biofilm formation in flexible endoscopes by improvement of qualified cleaning rate
Authors: Luo Yingxia , Yang Qixuan , Li Bingkun , Yao Yao 
Published: September 2020

Objective In recent years, the Emergency Care Research Institute has advised that endoscope cleaning is of considerable importance. In the present study, a quality control circle (QCC) was used to reduce the formation of biofilms in flexible endoscopes within one hospital in Guangdong Province, China. Methods During reprocessing of 235 flexible endoscopes in the urology surgical suite, adenosine triphosphate (ATP) detection was used to monitor the efficacy of biofilm removal. The internal and external parts of flexible endoscopes were used as sampling sites by means of the flushing and smudge methods, respectively. When the two results reached the standard of less than 500 relative light units/piece at the same time, endoscopic biofilm clearance was considered to be qualified. A QCC was established to implement a 10-step plan-do-check-act model. Results The baseline qualified rate (i.e., ATP monitoring pass rate) during reprocessing of 235 flexible endoscopes was 50%. During the study, the qualified rate increased to 85.29% after establishment of the QCC. During reprocessing of 150 flexible endoscopes in the following 6 months, the qualified rate remained at 90%. Conclusion Establishment of the QCC improved the removal of biofilm from flexible endoscopes in the urology surgical suite.
Headache and rhinosinusitis: A review
Authors: Ceriani Claire EJ , Silberstein Stephen D 
Published: September 2020

Purpose of review To explain our current understanding of headache attributed to rhinosinusitis, an often inappropriately diagnosed secondary headache. Recent findings Recent studies have shown that headache attributed to rhinosinusitis is often over-diagnosed in patients who actually have primary headache disorders, most commonly migraine. Failure to recognize and treat rhinosinusitis, however, can have devastating consequences. Abnormalities of the sinuses may also be treatable by surgical means, which may provide headache relief in appropriately selected patients. Summary It is important for the practicing physician to understand how rhinosinusitis fits into the differential diagnosis of headache, both to avoid overdiagnosis in patients with primary headache, and to avoid underdiagnosis in patients with serious sinus disease.
Efficacy of an orally administered combination of Lactobacillus paracasei LC11, cranberry and D-mannose for the prevention of uncomplicated, recurrent urinary tract infections in women
Authors: Murina Filippo , Vicariotto Franco , Lubrano Chiara 
Published: September 2020

Background: Most women experience a urinary tract infection (UTI) at least once in their lifetime. The present study determined the efficacy and safety of a combination of Lactobacillus paracasei LC11, cranberry and D-mannose (Lactoflorene Cist®) in the prophylaxis of recurrent uncomplicated UTIs in premenopausal women. Methods: This single-centre study enrolled premenopausal women aged 18–50 years with an acute UTI and a history of recurrent uncomplicated UTIs. Patients were first treated with fosfomycin (3 g once a day for 2 days) to eliminate any underlying infection, followed by treatment with Lactoflorene Cist® once a day for 10 days/month for 90 days (Group 1), Lactoflorene Cist® once daily for 90 days (Group 2) or no treatment (Group 3; control). The main study endpoint was the rate of UTI recurrence during the study period. Any adverse events with treatment were also recorded. Results: A total of 55 women (mean age 39.3 years; range: 20–46) were enrolled in the study. A significantly higher proportion of patients in the control group experienced UTIs during the study period compared with the two treatment groups (52.9% vs 16.0% in Group 1 and 15.5% in group 2; p < 0.01). Similarly, a higher proportion of patients in Group 1 (65.8%) and Group 2 (68.7%) remained UTI-free during the study versus the control group. No adverse events were reported in the treated patients. Conclusion: Prophylactic treatment with Lactoflorene Cist® was effective and safe in the management of recurrent uncomplicated UTIs in premenopausal women.
Prognostic Significance of ALDH1, Bmi1, and OCT4 Expression in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma
Authors: Rao Roopa S. , Raju K Lizbeth , Augustine Dominic , Patil Shankargouda 
Published: September 2020

Background: Increasing evidence suggests the involvement of cancer stem cells (CSCs) in both oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Among the various CSC markers, aldehyde dehydrogenase (ALDH) 1, B cell-specific Moloney murine leukaemia virus integration site 1 (Bmi1), and octamer-binding protein 4 (OCT4) have been noted to increase in OSCC. The aim of the study was to analyze ALDH1, Bmi1, and OCT4 expression in OED and OSCC with clinicopathologic correlation and survival analysis. Methods: A total of 40 cases each of OED and OSCC were retrieved from departmental archives. Expression of ALDH1, Bmi1, and OCT4 was analyzed using immunohistochemistry and was correlated with clinicopathological parameters. A follow-up ranging from 6 to 52 months was considered for Kaplan-Meier survival analysis. The log-rank test was performed to analyze significant difference in survival rates. Results: The expression levels of ALDH1, Bmi1, and OCT4 increased significantly from OED through OSCC ( P < .05). The expression of ALDH1 and OCT4 showed a significant correlation with lymph node metastasis. Positive cases of ALDH1 showed a significantly reduced survival rate compared to cases showing negative expression. Kaplan-Meier survival analysis showed a significant reduction of survival rate ( P = .00) in patients showing a positive expression for all the 3 markers. Conclusion: ALDH1 and OCT4 could be used as individual prognostic markers for assessing prognosis. ALDH1, Bmi1, and OCT4 could be used as a collective panel of markers to enable surgeons in predicting the prognosis of patients and thereby carry out prompt follow-up for such cases.
Gene Signatures and Prognostic Values of m6A RNA Methylation Regulators in Ovarian Cancer
Authors: Han Xiao , Liu Jie , Cheng Guomei , Cui Shihong 
Published: September 2020

Background: N6-methyladenosine (m6A) is the most common form of mRNA modification under the field of “RNA epigenetics.” However, its role in ovarian cancer (OC) development is poorly understood. In the current study, we aimed to identify gene signatures and prognostic values of m6A RNA methylation regulators. Method: Specifically, we downloaded Mutations and Copy number variant (CNV) data from the TCGA database for 579 OC patients, then analyzed gene expression and prognosis value using integrative bioinformatics. Thereafter, we verified the related biological processes of Wilms’ tumor 1-associating protein (WTAP) gene using Gene set enrichment analysis (GSEA). Results: Results showed that almost all ovarian cancer patients (99.31%) have CNVs with at least 1 m6A regulatory gene, whereas 83.76% of cases exhibited concurrence of CNVs in more than 4 m6A regulatory genes. Additionally, alteration of m6A regulators was associated with historical grade, whereas integrative bioinformatics and Cox multivariate model analysis revealed a significant correlation between high WTAP expression and worse ovarian cancer outcomes. Moreover, GSEA revealed that high WTAP expression was associated with cell cycle regulation and MYC targets. Conclusion: Overall, our findings demonstrate the significance of high-frequency genetic alterations of m6A RNA methylation regulators and WTAP’s poor prognosis value in OC. These findings provide valuable insights into the role of m6A methylation in OC, and will be vital in guiding development of novel treatment therapies.
Hypertension and QT interval prolongation associated with targeted systemic cancer therapies
Authors: Fahey Olivia G , Piccolo Jennifer K , Bergsbaken Jason J , N Dow-Hillgartner Elizabeth 
Published: September 2020

Objective To summarize the proposed mechanisms behind hypertension and QT interval prolongation associated with use of targeted systemic cancer therapies and provide recommendations for monitoring or managing these toxicities. Summary The cardiotoxic effects of targeted systemic cancer therapies represents a new paradigm of cancer treatment associated cardiovascular adverse events. National guidelines regarding optimal monitoring and management strategies for hypertension and QT interval prolongation associated with use of these therapies are lacking. While the pathophysiological drivers of hypertension due to targeted systemic cancer therapies differ by class of targeted therapy, general management strategies do not. Routine blood pressure monitoring throughout the duration of therapy is recommended for all agents. Patients who experience hypertension often can be treated with the addition or modification of antihypertensive therapies. Uncontrolled hypertension despite optimal medical management may require dose modifications or discontinuation of the targeted systemic cancer therapy. Electrocardiogram monitoring is recommended for patients who receive targeted therapies that may prolong the QT interval. Minimizing or managing drug interactions with other QT prolonging medications is recommended in addition to ensuring adequate electrolyte supplementation. Dose modifications or discontinuation of the targeted systemic therapy may be necessary for patients who experience QT interval prolongation. Conclusions Appropriate cardiovascular monitoring and timely management of treatment-emergent toxicities can optimize therapy for patients receiving targeted systemic cancer therapies associated with a risk of drug-induced hypertension or QT interval prolongation.
Australian Press, Radio and Television Historiography: An Update
Authors: Griffen-Foley Bridget 
Published: September 2020

The thirtieth anniversary issue of MIA in May 2006 (no. 119) featured ‘Australian Press, Radio and Television Historiography: An Update’. In it, Bridget Griffen-Foley produced a bibliography of books, theses and special journal issues concerning the history of the Australian media completed or commenced since the publication of two well-known bibliographical essays by Henry Mayer and John Henningham in 1987–88. Bridget has now expanded and updated her bibliography. The websites of MIA and the new Centre for Media History at Macquarie University, to be headed by Bridget, aim to publish periodic updates of the ‘Update’. Readers of MIA might also be interested to learn that an email discussion list for those interested in Australian media history has recently been established. For information on the listserv, or to subscribe, go to: http://listserv.mq.edu.au/mailman/listinfo/amhlist