bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applications of implementation science frameworks, models and theories in disparities-focused cancer screening interventions: a scoping review protocol
Authors: Xiong Serena , Klesges Lisa , Doering Michelle , Pratt Rebekah J 
Published: December 2023

BackgroundImplementation science (IS) frameworks, models and theories (FMTs) have gained popularity in guiding the implementation and evaluation of evidence-based interventions (EBIs) for cancer screening. However, there are significant research gaps in understanding their applications in cancer health disparities contexts. This paper outlines a scoping review protocol designed to explore the utilisation of IS FMTs in cancer screening EBIs to inform intervention designs and adaptations.Methods and analysisThis scoping review protocol adheres to Arksey and O’Malley’s five-step methodological framework for conducting scoping studies. Search strategies were conducted in five bibliographic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science and EMBASE. The search was run on 22 June 2023 with an English language filter and a date limit of 2001-current. Two reviewers will independently screen studies for inclusion and exclusion criteria. A third reviewer will be consulted, where appropriate at any of the review stages, to achieve consensus or resolve conflicts. Data will be collected, managed and analysed using Covidence. A narrative synthesis, based on Popayet al’s methodology, will guide reporting and summarisation of results. The review will adhere to the PRISMA Extension for Scoping Reviews guidelines.Ethics and disseminationThis scoping review is a novel approach for examining a growing corpus of research literature on IS FMT applications used in cancer screening EBIs. As a secondary analysis, this scoping review does not require approval from an institutional review board. We anticipate the review will produce insightful information (eg, challenges, key areas for future directions) on the applications of IS TMFs in designing, deploying and testing EBIs for populations experiencing cancer screening disparities. We will disseminate the results through journals and conferences targeting IS and cancer prevention researchers and practitioners.
Protocol for a systematic review of reviews on training primary care providers in dermoscopy to detect skin cancers
Authors: McCaffrey Nikki , Bucholc Jessica , Ng Leo , Chai Kevin , Livingstone Ann , Murphy April , Gordon Louisa G 
Published: December 2023

IntroductionGlobally, incidence, prevalence and mortality rates of skin cancers are escalating. Earlier detection by well-trained primary care providers in techniques such as dermoscopy could reduce unnecessary referrals and improve longer term outcomes. A review of reviews is planned to compare and contrast the conduct, quality, findings and conclusions of multiple systematic and scoping reviews addressing the effectiveness of training primary care providers in dermoscopy, which will provide a critique and synthesis of the current body of review evidence.Methods and analysisFour databases (Cochrane, CINAHL, EMBASE and MEDLINE Complete) will be comprehensively searched from database inception to identify published, peer-reviewed English-language articles describing scoping and systematic reviews of the effectiveness of training primary care providers in the use of dermoscopy to detect skin cancers. Two researchers will independently conduct the searches and screen the results for potentially eligible studies using ‘Research Screener’ (a semi-automated machine learning tool). Backwards and forwards citation tracing will be conducted to supplement the search. A narrative summary of included reviews will be conducted. Study characteristics, for example, population; type of educational programme, including content, delivery method, duration and assessment; and outcomes for dermoscopy will be extracted into a standardised table. Data extraction will be checked by the second reviewer. Methodological quality will be evaluated by two reviewers independently using the Critical Appraisal Tool for Health Promotion and Prevention Reviews. Results of the assessments will be considered by the two reviewers and any discrepancies will be resolved by team consensus.Ethics and disseminationEthics approval is not required to conduct the planned systematic review of peer-reviewed, published articles because the research does not involve human participants. Findings will be published in a peer-reviewed journal, presented at leading public health, cancer and primary care conferences, and disseminated via website postings and social media channels.PROSPERO registration numberCRD42023396276.
How did New Zealand’s regional District Health Board groupings work to improve service integration and health outcomes: a realist evaluation
Authors: Penno Erin , Atmore Carol , Maclennan Brett , Richard Lauralie , Wyeth Emma , Richards Rosalina , Doolan-Noble Fiona , Gray Andrew R , Sullivan Trudy , Gauld Robin , Stokes Tim 
Published: December 2023

ObjectivesIn Aotearoa New Zealand (NZ), integration across the healthcare continuum has been a key approach to strengthening the health system and improving health outcomes. A key example has been four regional District Health Board (DHB) groupings, which, from 2011 to 2022, required the country’s 20 DHBs to work together regionally. This research explores how this initiative functioned, examining how, for whom and in what circumstances regional DHB groupings worked to deliver improvements in system integration and health outcomes and equity.DesignWe used a realist-informed evaluation study design. We used documentary analysis to develop programme logic models to describe the context, structure, capabilities, implementation activities and impact of each of the four regional groupings and then conducted interviews with stakeholders. We developed a generalised context-mechanisms-outcomes model, identifying key commonalities explaining how regional work ‘worked’ across NZ while noting important regional differences.SettingNZ’s four regional DHB groupings.ParticipantsForty-nine stakeholders from across the four regional groupings. These included regional DHB governance groups and coordinating regional agencies, DHB senior leadership, Māori and Pasifika leadership and lead clinicians for regional work streams.ResultsRegional DHB working was layered on top of an already complex DHB environment. Organisational heterogeneity and tensions between local and regional priorities were key contextual factors. In response, regional DHB groupings leveraged a combination of ‘hard’ policy and planning processes, as well as ‘soft’, relationship-based mechanisms, aiming to improve system integration, population health outcomes and health equity.ConclusionThe complexity of DHB regional working meant that success hinged on building relationships, leadership and trust, alongside robust planning and process mechanisms. As NZ reorients its health system towards a more centralised model underpinned by collaborations between local providers, our findings point to a need to align policy expectations and foster environments that support connection and collegiality across the health system.
Cross-sectional study assessing health outcome priorities of older adults with multimorbidity at a primary care setting in Singapore
Authors: Ng Xin Rong , Tey Yu Xuan Sheryl , Lew Kaiwei Jeremy , Lee Poay Sian Sabrina , Lee Eng Sing , Sim Sai Zhen 
Published: December 2023

ObjectivesManaging older adults with multimorbidity may be challenging due to the conflicting benefits and harms of multiple treatments. Thus, it is important to identify patients’ health outcome priorities to align treatment goals with their health preferences. This study aimed to use the Outcome Prioritisation Tool (OPT) to describe the health outcome priorities of older adults with multimorbidity and determine the factors associated with these priorities. Additionally, it aimed to assess the ease of completing the OPT in Singapore’s primary care population.DesignCross-sectional study conducted from January to March 2022.SettingA public primary care centre in Singapore.Participants65 years and older with multimorbidity.Outcome measuresPrimary outcome measure was the most important health outcome priorities on the OPT. Secondary outcome measures were factors affecting these priorities and ease of completing the OPT.ResultsWe enrolled 180 participants (mean age: 73.2±6.1 years). Slightly more than half (54.4%) prioritised ‘staying alive’, while the remainder (45.6%) prioritised ‘maintaining independence’ (25.6%), ‘relieving pain’ (10.6%) and ‘relieving other symptoms’ (9.4%). Participants with six or more chronic conditions were three times (OR 3.03 (95% CI1.09 to 8.42)) more likely to prioritise ‘staying alive’ compared with participants with three conditions. Most participants (69.4%) agreed that the OPT was easy to complete, and the mean time taken to complete the OPT was 3.8±1.6 minutes.Conclusion‘Staying alive’ was the most important health outcome priority, especially for older adults with six or more chronic conditions. The OPT was easily completed among older adults with multimorbidity in primary care. Further qualitative studies can be conducted to understand the factors influencing patients’ priorities and explore the relevance of the OPT in guiding treatment decisions.
Feebly-interacting particles: FIPs 2022 Workshop Report
Authors: Antel C. , Battaglieri M. , Beacham J. , Boehm C. , Buchmüller O. , Calore F. , Carenza P. , Chauhan B. , Cladè P. , Coloma P. , Crivelli P. , Dandoy V. , Darmé L. , Dey B. , Deppisch F. F. , De Roeck A. , Drewes M. , Echenard B. , Flambaum V. V. , Foldenauer P. , Gatti C. , Giannotti M. , Golutvin A. , Gonzalez-Garcia M. C. , Gori S. , Goudzovski E. , Granelli A. , Grote H. , Guellati-Khelifa S. , Hajer J. , Harris P. , Hearty C. , Heuchel D. , Hostert M. , Junius S. , Kahlhoefer F. , Klaric J. , Kling F. , Klose P. , Knolle J. , Kopp J. , Kwon O. , Lantwin O. , Lanfranchi G. , Li L. , Lindner A. , Lopez-Pavon J. , Marocco J. , Martin J. W. , Middleton S. , Milstead S. , Oceano I. , O’Hare C. A. J. , Paoloni A. , Pascoli S. , Petcov S. T. , Pospelov M. , Pöttgen R. , Raggi M. , Ripellino G. , Samsonov I. B. , Sandner S. , Söldner-Rembold S. , Shelton J. , Song N. , Sun C. , Stadnik Y. V. , Tastet J.-L. , Toro N. , Tran N. , Trevisani N. , Ulmer S. , Urrea S. , Velghe B. , Wallisch B. , Wong Y. Y. Y. , Zorbilmez C. , Zurek K. 
Published: December 2023

AbstractParticle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.
Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory
Authors: Alvero Ayesha B. , Fox Alexandra , Madina Bhaskara Reddy , Krady Marie M. , Gogoi Radhika , Chehade Hussein , Nakaar Valerian , Almassian Bijan , Yarovinsky Timur O. , Rutherford Thomas , Mor Gil 
Published: December 2023

Abstract
Current immunotherapies have proven effective in strengthening antitumor immune responses, but constant opposing signals from tumor cells and the surrounding microenvironment eventually lead to immune escape. We hypothesized that in situ release of antigens and regulation of both the innate and adaptive arms of the immune system would provide a robust and long-term antitumor effect by creating immunologic memory against tumors. To achieve this, we developed CARG-2020, a genetically modified virus-like vesicle (VLV) that is a self-amplifying RNA with oncolytic capacity and encodes immune regulatory genes. CARG-2020 carries three immune modulators: (i) the pleiotropic antitumor cytokine IL12, in which the subunits (p35 and p40) are tethered together; (ii) the extracellular domain (ECD) of the protumor IL17RA, which serves as a dominant-negative antagonist; and (iii) a shRNA targeting PD-L1. Using a mouse model of ovarian cancer, we demonstrated the oncolytic effect and immune-modulatory capacities of CARG-2020. By enhancing IL12 and blocking IL17 and PD-L1, CARG-2020 successfully reactivated immune surveillance by promoting M1, instead of M2, macrophage differentiation, inhibiting MDSC expansion and establishing a potent CD8+ T cell–mediated antitumoral response. Furthermore, we demonstrated that this therapeutic approach provided tumor-specific and long-term protection against the establishment of new tumors. Our results provide a rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients to enhance antitumor responses and prevent a recurrence.
Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination
Authors: Simmons Kristen , Thomas Jane V. , Ludford Kaysia , Willis Jason A. , Higbie Victoria S. , Raghav Kanwal P.S. , Johnson Benny , Dasari Arvind , Kee Bryan K. , Parseghian Christine M. , Lee Michael S. , Le Phat H. , Morelli Maria P. , Shen John Paul , Bent Alisha , Vilar Eduardo , Wolff Robert A. , Kopetz Scott , Overman Michael J. , Morris Van Karlyle 
Published: December 2023

Abstract

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas – MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3–51.9). After a median follow-up of 22.6 months (range, 0.3–71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control.

Significance:
Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.
Evaluating the Performance of the North Pacific Victoria Mode as an ENSO Predictor Based on Multimodel Ensemble Hindcasts
Authors: Ren Zhengyi , Ding Ruiqiang , Mao Jiangyu , Ji Kai , Li Zongrong 
Published: December 2023

Abstract
The Victoria mode (VM), similar to the Pacific meridional mode (PMM), is forced by North Pacific Oscillation atmospheric variability. Both the boreal spring VM and PMM can trigger the onset of El Niño–Southern Oscillation (ENSO) events in the following winter. Previous studies have examined the precursor relationship between the PMM and ENSO based on a subset of models drawn from the North American Multimodel Ensemble (NMME) system. They suggested that the PMM can act as a precursor to El Niño events, whereas it fails to predict La Niña events. Utilizing the hindcasts of these models from NMME, this study further investigates the role of the VM as an ENSO predictor to examine the real usefulness of the VM for ENSO prediction. When compared with the PMM, the VM can predict both El Niño and La Niña events with some skill, showing that the VM seems to be a more reliable predictor of ENSO. We found that the unique role of the VM in ENSO prediction originates from the symmetric impact of the VM on ENSO events. The VM, as a basin-scale sea surface temperature (SST) pattern, combines the role of the SST over the subtropical northeastern Pacific that is similar to the PMM in initializing El Niño events with that of the SST over the western North Pacific that is different from PMM in initializing La Niña events, resulting in the symmetric effect of the VM on ENSO prediction. Thus, it is useful to consider VM variability as a reference for ENSO prediction.

Significance Statement
We aim to investigate whether the robust relationship between the boreal spring Victoria mode (VM) and the following winter ENSO in observations and climate models has any real predictive use, thus bridging the gap between theory and practical application. Our analyses based mainly on model hindcast datasets examine the forecasting skill of the VM for El Niño and La Niña events. We also reveal the symmetric impact of VM on ENSO through the analysis of observations, which explains the VM’s skill in predicting both El Niño and La Niña events. This study deepens our understanding of the effect of North Pacific SST variability on ENSO.
Exploration of mechanical and structural properties of bitumen modified with polyethylene glycol and ZnO-nano particles
Authors: Karim Inam , Iqbal Faisal , Ahmad Niaz , Shakoor Abdul , Naeem Junaid 
Published: December 2023

Bitumen is a petroleum residue that is extensively used as a pavement material. Rutting at high temperatures is one of the limitations of bitumen in warmer regions. The aim of this study is to improve the performance and increase the temperature susceptibility of neat bitumen. In this study, polyethylene glycol (PEG) and nano ZnO have been used to modify the properties of neat bitumen. Four samples were prepared by incorporating PEG and nano-ZnO with a standard laboratory mixer. Polyethylene glycol with 2%, 4%, 6%, and 8% by weight were mixed initially with neat bitumen along with nano ZnO (1.5% and 3%). To check its applicability in the road construction industry, the blends were subjected to mechanical properties tests such as ductility, flash point, fire point, softening point, and penetration test. It was investigated that decrease in ductility ranges from a maximum of 143 (neat bitumen) to a minimum of 83 (8 wt%). Softening point increased from 54°C to a maximum of 59°C (8 wt%). Flash and fire point increase first and then decrease; the optimum content was found to be 6%. The structural properties of blends were investigated using X-ray diffraction. The spectra show there is a shift of peaks in polymer-modified bitumen (PMB) as compared to neat bitumen, which leads to homogeneous mixing. The shift of peaks is because of an increase in interlayer spacing of neat bitumen and a decrease in Bragg’s angle. FT-IR analysis shows the presence of peaks in the range of 3000–2800 cm−1 which confirms the presence of additives in modified bitumen. SEM analysis was conducted to check the quality of dispersion and to investigate the microstructure. ZnO nano particles affect the mechanical properties of samples. The physical properties of polymer-modified bitumen (PMB), PEG, and nano ZnO blends enhance the stiffness of samples at high temperatures.
Polypharmacy and drug-drug interactions in metastatic breast cancer patients receiving cyclin-dependent kinase (CDK) 4/6 inhibitors
Authors: Kapagan Tanju , Bulut Nilufer , Erdem Gokmen Umut 
Published: December 2023

Introduction Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly changed the treatment strategy for patients with locally advanced or metastatic hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2) breast cancer. The purpose of the study was to determine the prevalence of drug-drug interactions (DDI) in breast cancer patients using CDK 4/6 inhibitors and the extent of DDI reflected in the clinic and to increase clinical awareness among physicians. Method The data of 115 metastatic breast cancer patients using CDK 4/6 inhibitors who were admitted to the Medical Oncology outpatient clinic between July 2021 and July 2023 were retrospectively reviewed. The Drugs.com® Drug Interaction Checker application was used for the interaction between the CDK 4/6 inhibitor and other drugs. Results Among patients included in the study, 97.3% had at least one additional drug use. We have identified a total of 170 potential DDI risks in 63.5 % of patients. Among these, 50.5% had a major potential DDI. In our study, there was a potential risk of QT prolongation in 45.2% of 170 DDI, an increase in the potential toxicity of the additional drug in 44.1%, an increase in the potential toxicity of the CDK 4/6 inhibitor in 5.3%, a decrease in the potential efficacy of the CDK 4/6 inhibitor in 2.9%, a decrease in the potential efficacy of the additional drug in 1.1%, and a serious potential infection risk in 1.1%. Most of the drug interactions were QT prolongation and increased toxicity of the additional drug. In terms of cardiovascular events, grade-2 and grade-3 QTc prolongation was found in 4.3% and 1.7% of these interactions, respectively. When evaluated in terms of CDK 4/6 inhibitor subtype, there was a potential risk of DDI at major level with Ribocilib and at moderate level with Palbociclib. Conclusion If CDK 4/6 inhibitors interact with concomitant drugs, they may cause an increase in the incidence of cardiac side effects and a decrease in the effect of the CDK 4/6 inhibitor or additional drug or an increase in toxicity. Increasing awareness of this issue will help to reduce the rates of side effects or toxicity and provide effective antitumour therapy.