bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using structural equation modelling to characterise multilevel socioecological predictors and mediators of condom use among transgender women and cisgender men who have sex with men in the Philippines
Authors: Restar Arjee , Ogunbajo Adedotun , Adia Alexander , Nazareno Jennifer , Hernandez Laufred , Sandfort Theo , Lurie Mark , Cu-Uvin Susan , Operario Don 
Published: July 2020

BackgroundRisks for condomless sex among transgender women and cisgender men who have sex with men (trans-WSM and cis-MSM, respectively) in the Philippines, where HIV recently became a national public health crisis, are shaped and exacerbated by various risk factors across multiple levels.MethodsBetween June 2018 and August 2019, we conducted a cross-sectional online study with 318 trans-WSM and cis-MSM respondents from Manila and Cebu cities. Structural equational modelling procedures were performed to determine direct, indirect and overall effects between condom use and latent variables across multiple socioecological levels: personal (ie, condom self-efficacy), social (ie, social capital), environmental (ie, barriers to condom and HIV services) and structural (ie, structural violence, antidiscrimination policies).ResultsAdjusted for gender, age, location and income, our model showed that: (1) all latent variables at the structural and environmental levels were significantly positively associated with each other (all ps<0.05); (2) barriers to condom and HIV services were significantly negatively associated with social capital (p<0.001) as well as condom self-efficacy (p<0.001); and (3) there were significantly positive associations between social capital and condom self-efficacy (p<0.001), and between condom self-efficacy and condom use (p<0.001). Moreover, social capital and condom self-efficacy fully mediated and buffered the negative effects between environmental and structural barriers and condom use.ConclusionThis is the first known study pointing to multiple relationships and pathways across multiple socioecological levels that can potentially be leveraged for future interventions aimed at improving condom use among Filipinx trans-WSM and cis-MSM. Such interventions should be multicomponent and build and/or strengthen social capital and condom self-efficacy, as well as intentionally target prominent structural and environmental barriers to condom use.
Ultrasound-guided tendon debridement improves pain, function and structure in persistent patellar tendinopathy: short term follow-up of a case series
Authors: Masci Lorenzo , Alfredson Hakan , Neal Brad , Wynter Bee William 
Published: July 2020

There is a need for effective therapeutic options for resistant patellar tendinopathy. Ultrasound (US)-guided arthroscopic debridement has demonstrated promising clinical results.ObjectivesTo prospectively evaluate pain, function, tendon structure and adverse events after US and colour Doppler (CD)-guided arthroscopic debridement for persistent painful patellar tendinopathy.Materials and methodsTwenty-three consecutive patients (19 males and 4 females, mean age 28 years (±8), symptom duration 25 months (±21)), who had failed conservative management including progressive loading, were included. US+CD and ultrasound tissue characterisation (UTC) examination verified the clinical diagnosis and quantified baseline tendon structure. Patients were treated with US+CD-guided arthroscopic debridement followed by a specific rehabilitation protocol. Outcomes were VISA-P score for pain and function and UTC for tendon structure. Adverse events were specifically elicited.ResultsAt 6-month follow-up, mean VISA-P score increased from 40 (±21.0) to 82 (±15) (mean deviation (MD)=42.0, 95% CI 32 to 53,d=2.4), while organised echo pixels (combined UTC type I+II) increased from 55.0% (±17.0) to 69.0% (±15.0) (MD=14.0,d=0.7, 95% CI 2 to 21). Both outcomes exceeded minimum detectable change values. Twenty-one participants returned to their prediagnosis activity levels, and there were no significant adverse events.ConclusionsUS-guided patellar tendon debridement for persistent patellar tendinopathy improved symptoms and tendon structure without complications at 6-month follow-up. A majority (21/23) of the patients returned to their preinjury activity level. Further studies with longer follow-ups, preferably randomised and controlled, are needed.
Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer
Authors: Sasaki Akinori , Kawazoe Akihito , Eto Testuya , Okunaka Mashiro , Mishima Saori , Sawada Kentaro , Nakamura Yoshiaki , Kotani Daisuke , Kuboki Yasutoshi , Taniguchi Hiroya , Kojima Takashi , Doi Toshihiko , Yoshino Takayuki , Akimoto Tetsuo , Shitara Kohei 
Published: July 2020

BackgroundThe efficacy and safety of chemotherapy (CTx) after anti-PD-1 therapy in patients with advanced gastric cancer (AGC) remains unclear.MethodsMedical records of consecutive patients with AGC treated with both CTx (taxanes plus ramucirumab, taxanes monotherapy or irinotecan) and anti-PD-1 therapy from June 2015 to April 2019 were retrospectively analysed. Patients were divided into two groups based on prior exposure to anti-PD-1 therapy: anti-PD-1-exposed and anti-PD-1-naïve groups. CTx-related outcomes were compared between two groups in the overall population and each CTx population.ResultsIn total, 233 patients (67 anti-PD-1-exposed, 166 anti-PD-1-naïve) were included. In the overall population, the objective response rate (ORR) to CTX was 44.6% in the anti-PD-1-exposed group and 19.6% in the anti-PD-1-naïve group (p=0.001); the median progression-free survivals (PFS) were 3.7 months and 3.3 months (HR=0.82, p=0.20), respectively. Among patients receiving taxanes plus ramucirumab (n=149), ORR (60.6% vs 20.0%, p<0.001) and median PFS (4.8 vs 3.4 months, p=0.004, HR=0.56) were significantly better in the anti-PD-1-exposed group (n=39) compared with the anti-PD-1-naïve group (n=110). These differences were not observed in patients receiving taxane monotherapy (n=34) or irinotecan (n=50). CTx after anti-PD-1 therapy showed no severe or unexpected adverse events.ConclusionsPrior anti-PD-1 therapy might increase tumour response to taxanes plus ramucirumab without unexpected adverse events, which warrants further investigations in a large cohort.
Optimal local anesthetic regimen for saddle block in ambulatory anorectal surgery: an evidence-based systematic review
Authors: Yung Eric M , Abdallah Faraj W , Todaro Carla , Spence Emily , Grant Andrew , Brull Richard 
Published: July 2020

BackgroundAmbulatory anorectal surgery requires an anesthetic of short duration but profound depth. Saddle block anesthesia (SBA) can provide dense sacral anesthesia with minimal motor blockade, but the ideal local anesthetic agent remains undefined. This systematic review aims to identify the optimal SBA regimen for ambulatory anorectal surgery.MethodsWe sought randomized trials examining SBA for ambulatory anorectal surgery and stratified patients into four subgroups according to local anesthetic type and dose: (1) longer acting, higher dose; (2) longer acting, lower dose; (3) shorter acting, higher dose; and (4) shorter acting, lower dose. Longer acting agents included bupivacaine and levobupivacaine; shorter acting agents included chloroprocaine, mepivacaine, and prilocaine. Lower dose was defined as ≤5 mg and ≤20 mg for longer and shorter acting local anesthetics, respectively. The primary outcome was time to discharge; secondary outcomes included times to sensory and motor block regression, urine voiding, and ambulation, as well as block success.ResultsA total of 11 trials (1063 patients) were included. Overall study quality and reporting consistency was poor. Doses ranged from 1.5–7.5 mg to 3–30 mg of longer and shorter acting local anesthetics, respectively. Hyperbaric local anesthetics were used in eight trials (953 patients, 86%). The median time to discharge appeared similar across all subgroups with an overall time of 182 (IQR 102) min. The use of long-acting, lower dose regimens was associated with a faster median time to motor block regression. Block success approached 99% among all trials.ConclusionsThere is presently insufficient qualitative and quantitative evidence to identify an optimal SBA regimen for ambulatory anorectal surgery. Nonetheless, we found that doses as low as 1.5 and 3 mg of longer and shorter acting hyperbaric local anesthetics, respectively, can achieve effective and reliable SBA with timely hospital discharge. Despite similar discharge times, longer acting, lower dose local anesthetics may produce faster motor block regression following SBA for ambulatory anorectal surgery.
Pyrvinium Pamoate Induces Death of Triple-Negative Breast Cancer Stem–Like Cells and Reduces Metastases through Effects on Lipid Anabolism
Authors: Dattilo Rosanna , Mottini Carla , Camera Emanuela , Lamolinara Alessia , Auslander Noam , Doglioni Ginevra , Muscolini Michela , Tang Wei , Planque Melanie , Ercolani Cristiana , Buglioni Simonetta , Manni Isabella , Trisciuoglio Daniela , Boe Alessandra , Grande Sveva , Luciani Anna Maria , Iezzi Manuela , Ciliberto Gennaro , Ambs Stefan , De Maria Ruggero , Fendt Sarah-Maria , Ruppin Eytan , Cardone Luca 
Published: July 2020

Abstract

Cancer stem-like cells (CSC) induce aggressive tumor phenotypes such as metastasis formation, which is associated with poor prognosis in triple-negative breast cancer (TNBC). Repurposing of FDA-approved drugs that can eradicate the CSC subcompartment in primary tumors may prevent metastatic disease, thus representing an effective strategy to improve the prognosis of TNBC. Here, we investigated spheroid-forming cells in a metastatic TNBC model. This strategy enabled us to specifically study a population of long-lived tumor cells enriched in CSCs, which show stem-like characteristics and induce metastases. To repurpose FDA-approved drugs potentially toxic for CSCs, we focused on pyrvinium pamoate (PP), an anthelmintic drug with documented anticancer activity in preclinical models. PP induced cytotoxic effects in CSCs and prevented metastasis formation. Mechanistically, the cell killing effects of PP were a result of inhibition of lipid anabolism and, more specifically, the impairment of anabolic flux from glucose to cholesterol and fatty acids. CSCs were strongly dependent upon activation of lipid biosynthetic pathways; activation of these pathways exhibited an unfavorable prognostic value in a cohort of breast cancer patients, where it predicted high probability of metastatic dissemination and tumor relapse. Overall, this work describes a new approach to target aggressive CSCs that may substantially improve clinical outcomes for patients with TNBC, who currently lack effective targeted therapeutic options.

Significance:
These findings provide preclinical evidence that a drug repurposing approach to prevent metastatic disease in TNBC exploits lipid anabolism as a metabolic vulnerability against CSCs in primary tumors.
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance
Authors: Pettitt Stephen J. , Frankum Jessica R. , Punta Marco , Lise Stefano , Alexander John , Chen Yi , Yap Timothy A. , Haider Syed , Tutt Andrew N.J. , Lord Christopher J. 
Published: July 2020

Abstract

Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This identified reversion “hotspots” and “deserts” in regions encoding the N and C terminus, respectively, of BRCA2, suggesting that pathogenic mutations in these regions may be at higher or lower risk of reversion. Missense and splice-site pathogenic mutations in BRCA1/2 also appeared less likely to revert than truncating mutations. Most reversions were &lt;100 bp deletions. Although many deletions exhibited microhomology, this was not universal, suggesting that multiple DNA-repair processes cause reversion. Finally, we found that many reversions were predicted to encode immunogenic neopeptides, suggesting a route to the treatment of reverted disease. As well as providing a freely available database for the collation of future reversion cases, these observations have implications for how drug resistance might be managed in BRCA-mutant cancers.

Significance:
Reversion mutations in BRCA genes are a major cause of clinical platinum and PARP inhibitor resistance. This analysis of all reported clinical reversions suggests that the position of BRCA2 mutations affects the risk of reversion. Many reversions are also predicted to encode tumor neoantigens, providing a potential route to targeting resistance.
This article is highlighted in the In This Issue feature, p. 1426
Single-Cell Transcriptomic Profiling of Vascular Smooth Muscle Cell Phenotype Modulation in Marfan Syndrome Aortic Aneurysm
Authors: Pedroza Albert J. , Tashima Yasushi , Shad Rohan , Cheng Paul , Wirka Robert , Churovich Samantha , Nakamura Ken , Yokoyama Nobu , Cui Jason Z. , Iosef Cristiana , Hiesinger William , Quertermous Thomas , Fischbein Michael P. 
Published: July 2020

Objective:
To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS).

Approach and Results:

We performed single-cell RNA sequencing to study aortic root/ascending aneurysm tissue from
Fbn1

C1041G/
+

(MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult
Fbn1

C1041G/
+

mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE
−/−
mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 (
Serpine1
) and Kruppel-like factor 4 (
Klf4
). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of
Fbn1

C1041G/
+

SMC/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young
Fbn1

C1041G/
+

mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, suggesting activation of phenotype modulation. modSMCs were not found in nondilated adult
Fbn1

C1041G/
+

descending thoracic aortas. Single-cell RNA sequencing from human MFS aortic root aneurysm tissue confirmed analogous SMC modulation in clinical disease. Enhanced expression of TGF-β (transforming growth factor beta)-responsive genes correlated with SMC modulation in mouse and human data sets.

Conclusions:

Dynamic SMC phenotype modulation promotes extracellular matrix substrate modulation and aortic aneurysm progression in MFS. We characterize the disease-specific signature of modSMCs and provide temporal, transcriptomic context to the current understanding of the role TGF-β plays in MFS aortopathy. Collectively, single-cell RNA sequencing implicates TGF-β signaling and
Klf4
overexpression as potential upstream drivers of SMC modulation.
Para- and Proto-Sports Diplomacy of Contested Territories: CONIFA as a Platform for Football Diplomacy
Authors: Ganohariti Ramesh , Dijxhoorn Ernst 
Published: July 2020

Summary
International relations and sport have become increasingly intertwined, with sport and sports events being used for various diplomatic and political goals. Yet, membership of FIFA and the IOC is largely organised along lines of sovereign statehood. Like other fora of diplomacy, this excludes contested territories that wish to engage in diplomacy for various political, economic, and cultural reasons. Yet, these entities can engage in international sports (diplomacy) through membership of the Confederation of Independent Football Associations (CONIFA). This paper finds that while the participating entities often make a political statement, there is little evidence that participation in CONIFA has positively impacted their foreign policy goals. Furthermore, beyond CONIFA, contested territories have been unable to advance their sporting sovereignty or engage in diplomatic relations with recognised states. However, CONIFA aids in nation branding through hosting rights and media attention, and contributes to strengthening the ‘national’ identity of the participants.
Senses as Capacities
Authors: O’Callaghan Casey 
Published: July 2020

Abstract
This paper presents an account of the senses and what differentiates them that is compatible with richly multisensory perception and consciousness. According to this proposal, senses are ways of perceiving. Each sense is a subfaculty that comprises a collection of perceptual capacities. What each sense shares and what differentiates one sense from another is the manner in which those capacities are exercised. Each way of perceiving involves a distinct type of information gathering, individuated by the information it functions to extract and the medium from which it does so. This approach distinguishes the project of characterizing and differentiating senses from that of attributing experiences to sensory modalities. Perceptual experiences are episodes in which perceptual capacities are exercised. Conscious perceptual episodes may be ascribed to distinct sensory modalities, according to the manners in which perceptual capacities are deployed on an occasion. According to this account, senses are not exclusive. First, their capacities may overlap. Second, perceptual episodes, including conscious experiences, may belong to multiple senses. Indeed, some episodes require the joint use of several senses. In this account, subjects have only limited first-person knowledge of the senses they employ.
An Interactive Online Course in Climate and Climate Change: Advancing Climate Literacy for Non–Atmospheric Science Majors
Authors: Dzambo Andrew M. , Mooney Margaret , Handlos Zachary J. , Lindstrom Scott , Hang Yun , Ackerman Steve A. 
Published: July 2020

AbstractSince 2013, the Department of Atmospheric and Oceanic Sciences at the University of Wisconsin–Madison has offered an online course titled “Climate and Climate Change.” Students enrolled in this course learn the physical principles governing Earth’s climate and climate change within the broader context of societal impacts and global political considerations. Students interact weekly with each other about these topics, and frequent instructor interaction stimulates further learning related to the course goals. The course was delivered through a balanced mix of forum discussions, weekly worksheets, quizzes, and a final project. For this study, student climate literacy was assessed through voluntary pre- and post-course surveys containing student self-assessment questions and a variety of questions directly based on course content. Post-course survey results indicate 99% of students taking this course feel “fairly well informed” or “very well informed” about their physical understanding of Earth’s climate and the numerous processes governing climate change. The 2019 cohort observed a statistically significant increase in the percentage of students adopting the viewpoint that climate change is caused primarily by human activities. We present a template for implementation in other Earth science or atmospheric science curricula, which includes discussion forum, quiz, and worksheet examples from this course.
Effectiveness of a 12-Month Emergency Radiology Curriculum for Improving Self-Confidence and Competence of Postgraduate Year 1 Radiology Residents—A Canadian Study
Authors: Strong Hilary , Bissell Mary Beth , Collins Jennifer , Hartery Angus 
Published: July 2020

Purpose: Limited radiology curriculum during postgraduate year 1 of radiology residency combined with increasing workloads during emergency radiology call have contributed to heightened anxiety and responsibilities for junior residents. This study aimed to evaluate the effectiveness of a 12-month emergency radiology curriculum on self-rated confidence and general competence of Canadian postgraduate year 1 radiology residents. Methods: A cohort of Canadian postgraduate year 1 Diagnostic Radiology residents voluntarily enrolled in a 12-month self-directed online emergency radiology curriculum (9 modules). Participants completed pretest and posttest surveys and examinations to gauge their self-rated competence on module material and knowledge acquisition, respectively. Average pretest and posttest scores were compared using Student 2-tailed unpaired t test, and Likert data from self-reported confidence were compared using a Mann Whitney U test. Statistical significance was defined as P < .05. Results: Sixty-six trainees completed at least 1 module, and 15 trainees completed all 9 modules. Both self-rated confidence and posttest scores were statistically higher after module completion ( P < .001) for all 9 learning modules. The greatest improvement in test scores was seen in the female genitourinary module (28.12 ± 3.018; difference between pretest and posttest means ± SEM). Conclusions: Our study demonstrates learning benefits for junior radiology trainees who participated in a self-directed online emergency radiology curriculum during postgraduate year 1. In the face of ever-increasing demands for imaging in on-call settings across Canada, inclusion of a self-directed online curriculum may become more important for upcoming competency-based medical education as it encourages a learner-driven and non-time-based method of education.
External validation of STONE, modified STONE, and CHOKAI scores for the diagnosis of ureteral stones in the Turkish population
Authors: Acar Yahya Ayhan , Uysal Emin 
Published: July 2020

Background: Scoring systems seem to be effective in the management of patients with uncomplicated ureteral stones. However, their efficiency may differ by population. Objectives: We aimed to validate STONE, modified STONE, and CHOKAI scores for the diagnosis of ureteral stones in the Turkish population. Methods: We conducted a retrospective chart review between 01 February 2018 and 30 November 2018, in an academic emergency department. Demographics, laboratory findings, and radiologic tests of patients with flank pain were obtained. Computed tomography was used as the gold standard for the diagnosis of ureteral stones. STONE, modified STONE, and CHOKAI scores were calculated for each patient. The performance of the scoring systems was compared in terms of their specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, negative predictive value, and positive predictive value. Results: A total of 157 patients were included in the study. The mean age was 38.47 ± 14.87 years, and 103 (65.6%) of the patients were males. The prevalence of ureteral stones was 84.0%, 88.9%, and 85.0% in the high-risk patients and 12%, 9.4%, and 22.7% in the low-risk patients for the STONE, modified STONE, and CHOKAI scores, respectively. Area under the curve values for the STONE, modified STONE, and CHOKAI scores were 0.776 (p = 0.001; 0.692–0.860 95% confidence interval), 0.825 (p < 0.001; 0.749–0.901 95% confidence interval), and 0.869 (p < 0.001; 0.806–0.932 95% confidence interval), respectively. The specificity and sensitivity values of STONE, modified STONE, and CHOKAI scores for the diagnosis of ureteral stones were 64.71, 71.70; 70.59, 87.74; and 66.67, 90.57, respectively. Conclusion: The CHOKAI score displayed the best performance compared to STONE and modified STONE in diagnosing ureteral stones in the Turkish population.