bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Hydrus and iStent microinvasive glaucoma surgery implants in combination with phacoemulsification for treatment of open-angle glaucoma: systematic review and network meta-analysis
Authors: Hu Rongrong , Guo Dongyu , Hong Nan , Xuan Xiuyuan , Wang Xiaoyu 
Published: June 2022

ObjectivesTo compare the efficacy and safety of two Schlemm’s canal-based microinvasive glaucoma surgery (MIGS) devices, the Hydrus Microstent and the iStent Trabecular Bypass combined with phacoemulsification for treatment of open-angle glaucoma.DesignSystematic review and network meta-analysis.MethodsLiterature searches were conducted on PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov to identify randomised controlled trials (RCTs) assessing the Hydrus or the iStent implantation combined with phacoemulsification for treatment of open-angle glaucoma until September 2020. Risk of bias was assessed using a six-item modified Jadad scale. Effects were estimated using the intraocular pressure (IOP) reduction (IOPR), the percentage of IOPR and the proportion of medication-free patients at follow-up end. Safety was estimated using the proportions of adverse events. The network meta-analysis was conducted within a Bayesian framework using the Markov Chain Monte Carlo method in ADDIS software.ResultsSix prospective RCTs comprising 1397 patients were identified. Regarding the absolute value and the percentage of IOPR, the Hydrus and 2-iStent implantation combined with phacoemulsification were significantly more effective than phacoemulsification alone. Rank probability analysis revealed the Hydrus might be the best choice to lower IOP. There was no significant difference in the proportion of medication-free patients among groups. The Hydrus and 2-iStent implantation had a higher probability to achieve the medication-free status versus the 1-iStent implantation and phacoemulsification alone. Overall safety profiles were good for each device with the focal peripheral anterior synechiae more frequently reported in Hydrus eyes.ConclusionsThe Hydrus implantation may have a slight advantage over the 1-iStent or 2-iStent implantation in combination with phacoemulsification to treat open-angle glaucoma. Our findings might be of some uncertainty due to the limited included data. Further studies are needed to investigate whether our findings are robust, including high-quality RCTs to directly compare these MIGS devices.
Comparison of different severe obesity definitions in predicting future cardiometabolic risk in a longitudinal cohort of children
Authors: Kakinami Lisa , Smyrnova Anna , Paradis Gilles , Tremblay Angelo , Henderson Melanie 
Published: June 2022

ObjectivesSevere obesity (SO) prevalence varies between reference curve-based definitions (WHO: ≥99th percentile, Centers for Disease Control and Prevention (CDC): >1.2×95th percentile). Whether SO definitions differentially predict cardiometabolic disease risk is critical for proper clinical care and management but is unknown.DesignProspective cohort studySettingSO definitions were applied at baseline (2005–2008, Mage=9.6 years, n=548), and outcomes (fasting lipids, glucose, homoeostatic model assessment (HOMA-IR) and blood pressure) were assessed at first follow-up (F1: 2008–2011, Mage=11.6 years) and second follow-up (2015–2017, Mage=16.8 years) of the Quebec Adipose and Lifestyle Investigation in Youth cohort in Montreal, Quebec.ParticipantsRespondents were youth who had at least one biological parent with obesity.Primary outcome measuresUnfavourable cardiometabolic levels of fasting blood glucose (≥6.1 mmol/L), insulin resistance (HOMA-IR index ≥2.0), high-density lipoprotein <1.03 mmol/L, low-density lipoprotein ≥2.6 mmol/L and triglycerides >1.24 mmol/L. Unfavourable blood pressure was defined as ≥90th percentile for age-adjusted, sex-adjusted and height-adjusted systolic or diastolic blood pressure.AnalysisArea under the receiver operating characteristic curve (AUC) and McFadden psuedo R2 for predicting F1 or F2 unfavourable cardiometabolic levels from baseline SO definitions were calculated. Agreement was assessed with kappas.ResultsBaseline SO prevalence differed (WHO: 18%, CDC: 6.7%). AUCs ranged from 0.52 to 0.77, with fair agreement (kappa=37%–55%). WHO-SO AUCs for detecting unfavourable HOMA-IR (AUC>0.67) and high-density lipoprotein (AUC>0.59) at F1 were statistically superior than CDC-SO (AUC>0.59 and 0.53, respectively; p<0.05). Only HOMA-IR and the presence of more than three risk factors had acceptable model fit. WHO-SO was not more predictive than WHO-obesity, but CDC-SO was statistically inferior to CDC-obesity.ConclusionWHO-SO is statistically superior at predicting cardiometabolic risk than CDC-SO. However, as most AUCs were generally uninformative, and obesity definitions were the same if not better than SO, the improvement may not be clinically meaningful.
Use of 18F-NaF PET in the staging of skeletal metastases of newly diagnosed, high-risk prostate cancer patients: a nationwide cohort study
Authors: Mogensen Anna Winther , Petersen Lars J , Torp-Pedersen Christian , Nørgaard Mette , Pank Marie T , Zacho Helle D 
Published: June 2022

ObjectiveTo determine whether preoperative staging of high-risk prostate cancer with 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases.DesignNationwide, population-based cohort study using real-world data.SettingThe study used national health registries, including all sites in Denmark from 2011 to 2018.ParticipantsNewly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either 18F-NaF PET or bone scintigraphy.Main outcome measuresThe risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival.ResultsBetween 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent 18F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the 18F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving 18F-NaF PET and bone scintigraphy, respectively.ConclusionPatients with high-risk prostate cancer undergoing preoperative staging with 18F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups.
Availability, accessibility and activation of mental health services among university students in Africa: a protocol of a mixed-methods systematic review with meta-analysis and meta-synthesis
Authors: Wao Hesborn , Wao Melvin A , Muriithi Ian , Seraii Paul , Syonguvi Jackline 
Published: June 2022

IntroductionIn Africa, the prevalence of mental health problems is higher among university students than in the general population. A number of systematic reviews and recent prevalence studies have focused on prevalence of mental health issues among college. This mixed-methods systematic review, including meta-analysis and meta-synthesis, will explore: what mental health services are available to university students; the extent to which students access available services and factors associated with service access; and the degree to which students activate (use) accessible services and factors associated with service activation.Methods and analysisWe will conduct electronic literature search of the following databases: PubMed, Cochrane Library, Semantic Scholar, ERIC, Trip Database, Medline and PsycINFO. Disagreement, if any, will be resolved by a third reviewer. Two reviewers will independently assess the methodological quality of included studies using relevant tools. For cross-sectional studies, we will use the Joanna Briggs Institute Checklist for Analytical Cross Sectional Studies whereas qualitative or mixed-methods studies will be assessed using the Critical Appraisal Skills Programme. OR, risk ratio or mean difference with 95% CI will be considered as the effect size. We will assess heterogeneity between studies by appropriate subgroup analyses. Publication bias will be detected using funnel plots.Ethics and disseminationEthical clearance is not required as we are not collecting primary data. Findings will be disseminated via relevant scientific conferences and peer-reviewed publications.PROSPERO registration numberCRD42022296870.
Characteristics of knowledge translation platforms and methods for evaluating them: a scoping review protocol
Authors: Schmidt Bey-Marrie , Cooper Sara , Young Taryn , Jessani Nasreen S 
Published: June 2022

IntroductionKnowledge translation platforms (KTPs) are intermediary organisations, initiatives or networks whose intent is to bridge the evidence into action divide. Strategies and tools include collaborative knowledge production, capacity building, information exchange and dialogue to facilitate relevant and timely engagement between researchers and decision-makers and other relevant stakeholders. With the wide range of definitions and descriptions of KTPs, there is a need to (1) provide a nuanced understanding of characteristics of KTPs and (2) assess and consolidate research methods used in mapping and evaluating KTPs to inform standardised process and impact evaluation.Methods and analysisThis scoping review will follow the recommended and accepted methods for scoping reviews and reporting guidelines. Eligibility for inclusion is any conceptual or empirical health-related qualitative, quantitative and/or mixed method studies including (1) definitions, descriptions and models or frameworks of KTPs (including those that do not self-identify as KTPs, eg, university research centres) and (2) research methods for mapping and/or evaluating KTPs. Searches will be carried out in PubMed, Scopus, CINAHL, Embase, Global Health and Web of Science using a predetermined search strategy, without any date, language or geographical restrictions. Two reviewers will independently screen titles and abstracts. One reviewer will complete data extraction for all included studies, and another will check a sample of 50% of the included studies. The analysis and synthesis will provide (1) an understanding of the various characteristics of KTPs; (2) insight into characteristics or factors that make them resilient and/or adaptive to facilitate impact (ie, influence policy and practice); and (3) an overview of the various methods for mapping and evaluating KTPs. We will explore enhancing an existing framework for classifying KTPs, or perhaps even developing a new framework for identifying and monitoring KTPs if necessary and relevant.Ethics and disseminationThis scoping review does not require ethics approval, as we will only include information from previously conducted studies and we will not involve human participants. The results will be submitted to a peer-reviewed scientific journal for publication and as conference presentations.
The 2HDM doppelganger
Authors: Coleppa Baradhwaj , Sarkar Agnivo 
Published: June 2022

AbstractWe discuss the structure of a model with an extended gauge symmetry group $$SU(2)\times SU(2)\times U(1)$$

S
U
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2
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U
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2
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×
U
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with a correspondingly rich Electroweak Symmetry Breaking structure. In spite of the additional scalar degrees of freedom in the model, the presence of the extra gauge group SU(2) and its associated heavy vector bosons ensures that the scalar spectrum of the model after symmetry breaking is identical to that of the Two Higgs Doublet Models. We construct the model and discuss its implications, specifically the phenomenology associated with this class of models in contrast to the 2HDM.
Abstract 101: JAK-independent STAT5 signaling as a node of therapeutic vulnerability in glioblastoma
Authors: Blomquist Mylan , Tuncali Serdar , Sereduk Christopher , Kloss Jean , Loftus Joseph , Tran Nhan 
Published: June 2022

Abstract
Glioblastoma (GBM), the most common primary brain tumor in adults, comprises all WHO Grade IV gliomas of astrocytic origin. Despite extensive characterization of the molecular and genetic features of GBM, there remains a paucity of viable treatment options, and this disease confers a dismal 5% 5-year survival rate. Genomic amplification of epidermal growth factor receptor (EGFR) occurs in 40-60% of primary GBM. Half of all EGFR-amplified cases of GBM also harbor EGFRvIII, a constitutively active, truncated variant of EGFR. EGFR and EGFRvIII transduce oncogenic signals via cytoplasmic mediators, including the JAK/STAT signal transduction pathway. The oncogenic role of STAT3 has been well-studied in CNS malignancies; STAT3 has been found to induce the expression of target genes involved in the proliferative and invasive phenotypes of GBM. However, little is known about the mechanism and role of STAT5 activation in GBM progression. Microenvironmental cues and EGFRvIII signaling, lost in adherent cell culture, are required for STAT5 activation, making STAT5 difficult to study by conventional cell culture methods. Our recent data from patient-derived xenograft (PDX) cultures demonstrates that activation of STAT5 is important in GBM cell invasion and survival. Further, STAT5 activation is present predominantly at the invasive periphery of the tumor. In this study, we seek to characterize the mechanism and role of STAT5 activation downstream of EGFRvIII in GBM. RNA sequencing of PDX tumors expressing stable shRNA knockdown of STAT3 or STAT5 indicate both redundant and distinct transcriptional changes induced by STAT3 and STAT5 in GBM. We also find that while STAT3 activation is dependent upon JAK1/2, STAT5 activation is JAK-independent downstream of EGFRvIII in GBM. Depletion of JAK1/2 expression by siRNA oligonucleotides and pharmacologic inhibition of JAK1/2 suppressed STAT3 activation but not STAT5. In fact, targeting JAK2 with kinase inhibitor WP1066 suppressed STAT3 activation, but increased activation of STAT5 in GBM cells expressing EGFR/EGFRvIII. Inhibition of Src family kinases (SFK), a family of upstream signaling effectors of the JAK/STAT pathway, attenuates both STAT3 and STAT5 activation. These results suggest that activation of STAT5 may provide a therapeutic escape mechanism to JAK-STAT3 inhibition in GBM, necessitating dual STAT3 and STAT5 inhibition to successfully inhibit the distinct oncogenic signals transmitted by STAT3 and STAT5 to promote GBM cell survival and resistance.
Citation Format: Mylan Blomquist, Serdar Tuncali, Christopher Sereduk, Jean Kloss, Joseph Loftus, Nhan Tran. JAK-independent STAT5 signaling as a node of therapeutic vulnerability in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 101.
Abstract 1014: A framework for research scientists to include patient advocates in cancer research
Authors: Stires Hillary , Bado Igor , Brown Thelma , Carlson Martha , Chan Isaac S. , Echeverria Gloria V. , Ewald Andrew J. , Lloyd Carla , Maues Julia , Oesterreich Steffi , Riter Robert N. , Shanahan Kelly , Welm Alana L. , Newby Josh 
Published: June 2022

Abstract
The inclusion of patient advocates in basic cancer research has emerged as a valuable practice to ensure research is intentional, to support effective communication with broader audiences, and to directly connect researchers with those whom they are striving to help. Despite this value, many researchers do not work with patient advocates. To understand why and build a roadmap for more engagement in the future, we hosted a workshop with patient advocates and research scientists then presented findings and discussed further at an international conference. We acknowledged four main barriers: 1) It is not clear to everyone why patient advocates should be included in research, 2) Researchers are worried about saying the wrong thing, 3) Researchers do not know where to meet patient advocates, and 4) Researchers do not know how to include patient advocates in research. We identified best practices from various organizations and opportunities to overcome these barriers in the short- and long-term. This is the first time a multi-stakeholder group has come together to provide ways to support research scientists with overcoming barriers to regularly working with patient advocates. Ultimately, these relationships will improve cancer research and more quickly accomplish our collective goal of improving lives of those who have been diagnosed with cancer.
Citation Format: Hillary Stires, Igor Bado, Thelma Brown, Martha Carlson, Isaac S. Chan, Gloria V. Echeverria, Andrew J. Ewald, Carla Lloyd, Julia Maues, Steffi Oesterreich, Robert N. Riter, Kelly Shanahan, Alana L. Welm, Josh Newby. A framework for research scientists to include patient advocates in cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1014.
Abstract 1024: The challenge of standardizing the measurement of an imprecise biomarker like HRD
Authors: Konigshofer Yves , Butler Matthew G. , Nahlik Krystyna , Lowe Dana Ruminski , Huang Catherine , Clement Omoshile , Garlick Russell K. 
Published: June 2022

Abstract
Here we present data on the characterization and implementation of a set of reference materials for the standardization of homologous recombination deficiency (HRD) assessment. The safety and effectiveness profile of a drug can be improved by using it in patients where that drug is most likely to be effective. While PARP inhibitors are indicated for use in some patients with ovarian, breast, pancreatic, and prostate cancer, patients with other cancers that are deficient in homologous recombination repair (HRR) might also benefit from their use. However, determining whether a cancer is HRD-positive is neither trivial nor precise. While clinical trials have shown that patients with deleterious mutations in BRCA2 and BRCA1 are most likely to benefit from PARP inhibitors, determining that a given BRCA mutation (or set of such mutations) is in fact deleterious is frequently not straightforward. Therefore, assays are now looking for signs of HRD, such as genomic instability consistent with non-homologous end joining (NHEJ) being used for the repair of double-stranded breaks in DNA as opposed to HRR. For example, some assays look at the combination of loss of heterozygosity (LOH) and large-scale state transitions (LST) across chromosomes as well as telomeric allelic imbalance (TAI) when determining whether a cancer is HRD-positive, while other assays use alternative approaches. How those characteristics are measured, integrated, and distilled into a final determination of whether HRD is present or absent varies, which can create uncertainty around treatment options and enrollment into clinical trials. This also makes the path of follow-on companion diagnostics challenging because perfect agreement between imprecise measurements is unlikely. In order to enable more standardized reporting of HRD and to enable the assessment of HRD assays, we created a set of characterized reference materials composed of HRD negative, borderline, and positive tumor/normal matched cell lines that were analyzed using both array-based and next generation sequencing-based assays in order to characterize chromosomal changes across their genomes and obtain HRD scores. Because of differences in the results, assay imprecision should be taken into account in clinical trials that implement cutoffs in order to establish safety data for patients who are biomarker-negative but may be biomarker-positive in a future assay, which is similar to what is done for complementary diagnostics.
Citation Format: Yves Konigshofer, Matthew G. Butler, Krystyna Nahlik, Dana Ruminski Lowe, Catherine Huang, Omoshile Clement, Russell K. Garlick. The challenge of standardizing the measurement of an imprecise biomarker like HRD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1024.
Abstract 1029: The anti-androgen seviteronel sensitizes triple-negative breast cancer to chemotherapy
Authors: Juan Beatriz P. San , Hediyah-Zadeh Soroor , Rangel Laura , Rodriguez Vanina , Milioli Heloisa H. , Kohane Felix , Purcell Carley A. , Hickey Therese E. , Goldstein Leonard D. , Lock John G. , Davis Melissa J. , Chaffer Christine L. 
Published: June 2022

Abstract
Therapeutic strategies that improve survival outcomes for advanced-stage breast cancers have proven a major clinical challenge. Here, we define an androgen receptor (AR) signalling network that governs the maintenance and de novo formation of cancer stem cells in triple-negative breast cancer. In response to chemotherapy, AR activation switches cells into a cancer stem cell state, while AR antagonism suppresses cancer stem cell formation and function. In vivo, we validate that the AR antagonist, seviteronel, significantly improves chemotherapy-mediated inhibition of primary and metastatic tumour growth. Analysing three independent triple-negative breast cancer patient cohorts we identify that cytoplasmic AR expression prognosticates poor survival in treatment-naïve patients and predicts poor response to chemotherapy. Additionally, Phase II clinical trial data demonstrates that seviteronel treatment followed by chemotherapy improved survival outcomes in triple-negative breast cancer patients expressing high cytoplasmic AR levels. Seviteronel combined with chemotherapy represents a promising therapeutic strategy for triple-negative breast cancer patients.
Citation Format: Beatriz P. San Juan, Soroor Hediyah-Zadeh, Laura Rangel, Vanina Rodriguez, Heloisa H. Milioli, Felix Kohane, Carley A. Purcell, Therese E. Hickey, Leonard D. Goldstein, John G. Lock, Melissa J. Davis, Christine L. Chaffer. The anti-androgen seviteronel sensitizes triple-negative breast cancer to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1029.