bluuebunny/crossref_metadata_2025_split huggingface dataset:
A realist synthesis of educational outreach visiting and integrated academic detailing to influence prescribing in ambulatory care: why relationships and dialogue matter
Authors: Luetsch Karen , Wong Geoff , Rowett Debra 
Published: May 2023

BackgroundMany quality improvement initiatives in healthcare employ educational outreach visits, integrating academic detailing to bridge evidence-practice gaps and accelerate knowledge translation. Replicability of their outcomes in different contexts varies, and what makes some visiting programmes more successful than others is unclear.ObjectiveWe conducted a realist synthesis to develop theories of what makes educational outreach visiting integrating academic detailing work, for whom, under which circumstances and why, focusing on the clinician-visitor interaction when influencing prescribing of medicines in ambulatory care settings.MethodsThe realist review was performed in accordance with RAMESES standards. An initial programme theory was generated, academic databases and grey literature were screened for documents with detail on contexts, intervention and outcomes. Using realist logic of analysis, data from 43 documents were synthesised in the generation of a refined programme theory, supported by additional theoretical frameworks of learning and communication.ResultsTwenty-seven interdependent context-mechanism-outcome configurations explain how clinicians engage with educational outreach visits integrating academic detailing through programme design, what matters in programme design and the educational visitor-clinician interaction and how influence extends beyond the visit. They suggest that in addition to relevance, credibility and trustworthiness of a visit’s contents, communication and clinical skills of educational visitors, the relationship between the educational visitor and clinician, built on a dialogue of learning from and sense-making with each other, creates conditions of critical thinking which are conducive to facilitating prescribing practice change when necessary.ConclusionThis realist synthesis elucidates that the quality of clinician-educational visitor interactions is pivotal to educational outreach visiting programmes. Building and sustaining relationships, and establishing an open dialogue are important; neglecting these undermines the impact of visits. Educational visitors can facilitate clinicians’ reflection on practice and influence their prescribing. Clinicians value the discussion of individualised, tailored information and advice they can translate into their practice.PROSPERO registration numberCRD42021258199.
Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial
Authors: Chesney Jason A , Puzanov Igor , Collichio Frances A , Singh Parminder , Milhem Mohammed M , Glaspy John , Hamid Omid , Ross Merrick , Friedlander Philip , Garbe Claus , Logan Theodore , Hauschild Axel , Lebbé Celeste , Joshi Harshada , Snyder Wendy , Mehnert Janice M 
Published: May 2023

Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.Eligible patients with unresectable stage IIIB‒IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone. T-VEC was administered intralesionally at 106plaque-forming units (PFU)/mL in week 1, followed by 108PFU/mL in week 4 and every 2 weeks thereafter. Ipilimumab (3 mg/kg every 3 weeks; ≤4 doses) was administered intravenously starting at week 1 in the ipilimumab arm and week 6 in the combination arm. The primary end point was investigator-assessed objective response rate (ORR) per immune-related response criteria; key secondary end points included durable response rate (DRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.Overall, 198 patients were randomized to receive the combination (n=98) or ipilimumab (n=100). The combination improved the ORR versus ipilimumab (35.7% vs 16.0%; OR 2.9; 95% CI 1.5 to 5.7; p=0.003). DRR was 33.7% and 13.0% (unadjusted OR 3.4; 95% CI 1.7 to 7.0; descriptive p=0.001), respectively. Among the objective responders, the median DOR was 69.2 months (95% CI 38.5 to not estimable) with the combination and was not reached with ipilimumab. Median PFS was 13.5 months with the combination and 6.4 months with ipilimumab (HR 0.78; 95% CI 0.55 to 1.09; descriptive p=0.14). Estimated 5-year OS was 54.7% (95% CI 43.9 to 64.2) in the combination arm and 48.4% (95% CI 37.9 to 58.1) in the ipilimumab arm. Forty-seven (48.0%) and 65 (65.0%) patients in the combination and ipilimumab arms, respectively, received subsequent therapies. No new safety signals were reported.At the 5-year follow-up, the improved response rates observed with T-VEC plus ipilimumab were durable. This is the first randomized controlled study of the combination of an oncolytic virus and a checkpoint inhibitor that meets its primary end point.Trial registration number:NCT01740297.
CD73 and PD-L1 dual blockade amplifies antitumor efficacy of SBRT in murine PDAC models
Authors: Ye Jian , Gavras Nicholas W , Keeley David C , Hughson Angela L , Hannon Gary , Vrooman Tara G , Lesch Maggie L , Johnston Carl J , Lord Edith M , Belt Brian A , Linehan David C , Eyles Jim , Gerber Scott A 
Published: May 2023

BackgroundStereotactic body radiotherapy (SBRT) induces immunogenic cell death, leading to subsequent antitumor immune response that is in part counterbalanced by activation of immune evasive processes, for example, upregulation of programmed cell death-ligand 1 (PD-L1) and adenosine generating enzyme, CD73. CD73 is upregulated in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue and high expression of CD73 in PDACs is associated with increased tumor size, advanced stage, lymph node involvement, metastasis, PD-L1 expression and poor prognosis. Therefore, we hypothesized that blockade of both CD73 and PD-L1 in combination with SBRT might improve antitumor efficacy in an orthotopic murine PDAC model.MethodsWe assessed the combination of systemic blockade of CD73/PD-L1 and local SBRT on tumor growth in primary pancreatic tumors, and investigated systemic antitumor immunity using a metastatic murine model bearing both orthotopic primary pancreatic tumor and distal hepatic metastases. Immune response was quantified by flow cytometric and Luminex analyses.ResultsWe demonstrated that blockade of both CD73 and PD-L1 significantly amplified the antitumor effect of SBRT, leading to superior survival. The triple therapy (SBRT+anti-CD73+anti-PD-L1) modulated tumor-infiltrating immune cells with increases of interferon-γ+CD8+T cells. Additionally, triple therapy reprogramed the profile of cytokines/chemokines in the tumor microenvironment toward a more immunostimulatory phenotype. The beneficial effects of triple therapy are completely abrogated by depletion of CD8+T cells, and partially reversed by depletion of CD4+T cells. Triple therapy promoted systemic antitumor responses illustrated by: (1) potent long-term antitumor memory and (2) enhanced both primaryandliver metastases control along with prolonged survival.
Examining the differences between physician and administrative leaders at Cleveland Clinic and the implications for leadership development programming
Authors: Thoebes Gina Phelps , Rife Gary Logan , Porter Tracy Hopkins 
Published: May 2023

BackgroundThe healthcare industry is currently facing unprecedented challenges, and the need for effective leadership has never been higher. One way organisations might address the need for healthcare leadership is through tailored leadership development programmes, which are designed to maximise impact. This research sought to examine potential differences between physician and administrative leaders’ unique needs and to use this information to inform the design of future leadership development programmes.MethodsSurvey data from a sample of international leaders who participated in cohort-based leadership development programmes at the Mandel Global Leadership and Learning Institute at Cleveland Clinic were examined to explore potential differences between physician and administrative leaders in order to cultivate future training outcomes.ResultsFindings demonstrate that there are significant differences in personality, motivation to lead and leadership self-efficacy between the two populations at Cleveland Clinic.ConclusionsThese results indicate how understanding specific traits, motivations and developmental needs of the target audience may guide the development of more effective leadership development programming. Future directions for addressing leadership development in the healthcare industry are also discussed.
Primary care doctors’ perceived needs for physician leadership development in rural and remote settings of Aceh province, Indonesia
Authors: Maulina Fury , Hasanbasri Mubasysyir , Busari Jamiu O , Scheele Fedde 
Published: May 2023

BackgroundGlobally, rural/remote health systems fall short of optimal performance. Lack of infrastructure, resources, health professionals and cultural barriers affect the leadership in these settings. Given those challenges, doctors serving disadvantaged communities must develop their leadership skills. While high-income countries already had learning programmes for rural/remote areas, low-income and middle-income countries (LMICs), such as Indonesia, are lagging behind. Through the lens of the LEADS framework, we examined the skills doctors perceived as most essential to support their performance in rural/remote areas.MethodsWe conducted a quantitative study, including descriptive statistics. Participants were 255 rural/remote primary care doctors.ResultsWe discovered that communicating effectively, building trust, facilitating collaboration, making connections and creating coalitions among diverse groups were most essential in rural/remote communities. When rural/remote primary care doctors serve in such cultures, may need to prioritise harmony within the community and social order values.ConclusionsWe noted that there is a need for culture-based leadership training in rural or remote settings of Indonesia as LMIC. In our view, if future doctors receive proper leadership training that focuses on being competent rural physicians, they will be better prepared and equipped with the skills that rural practice in a specific culture requires.
Chemotherapy-induced peripheral neurotoxicity: single-centre prospective study
Authors: Ben Kridis Wala , Toumi Nabil , Khanfir Afef 
Published: May 2023

ObjectiveChemotherapy-induced peripheral neurotoxicity (CIPN) ranges from simple paresthesia to paralysis, which may be transient or irreversible. The aim of our study was to detect CINP in our patients undergoing chemotherapy and to study the cumulative neurotoxic doses for the different drugs.MethodsThis is a cross-sectional prospective study carried out in the medical oncology department of the Habib Bourguiba University Hospital in Sfax. A survey was conducted to detect and explore possible chemo-induced peripheral neuropathy in patients undergoing known potentially neurotoxic anti-cancer treatments.ResultsSeventy-three patients were included in the study. The average age was 51.8 years (13–80 years). The prevalence of CIPN was 52.1%. CIPN was classified as grade I in 24 (63.2%) cases and grade II in 14 (36.8%) cases. No grade III or IV peripheral neuropathy was detected in our patients. Paclitaxel was the drug with the highest incidence of CIPN (76.9%). The chemotherapy (CT) protocols most prone to chemotherapy-induced peripheral neurotoxicity (CIPN) were based on taxanes (47.3%) and oxaliplatin (59%). Paclitaxel was the drug most likely to cause CIPN (76.9%) (p=0.031). Paclitaxel single dose per cycle of 175 mg/m2(66.67%) was more associated with the occurrence of CIPN than 80 mg/m2(40%), but without significant difference (p=0.437). The average cumulative dose was estimated at 315 mg/m2for docetaxel, 474 mg/m2for oxaliplatin and 579 mg/m2for paclitaxel (p=0.16).ConclusionThe prevalence of NPCI was 51.1% in our series. Oxaliplatin and taxanes were the main contributors to this complication with cumulative dose over than 300 mg/m2.
R-matrix atomic data for application in astrophysics and fusion
Authors: Ramsbottom C. A. , Ballance C. P. , McCann M. 
Published: May 2023

Abstract
A selection of electron-impact excitation R-matrix calculations completed by the collision group at Queens University Belfast are discussed. The atomic data calculated are the foundation of applications in a variety of fields, a sample of which are presented here. They include an analysis of Fe ii emission in active galactic nuclei, the possible presence of Pt and Au in the spectra of binary neutron star mergers and the viability of W ions as a diagnostic tool in magnetically confined tokamak plasmas. The radiative atomic data were computed using the most recent version of the fully relativistic structure code grasp0 and the collision cross sections were evaluated using the recently developed pdarcR-matrix package.

Graphic abstract
Chelating agents for the removal of calcareous deposits from archaeological ceramic materials. Compositional evaluation after immersion and physical gel application methods
Authors: Sáenz-Martínez Águeda , Pérez-Estébanez Marta , Alvarez de Buergo Mónica , San Andrés Margarita 
Published: May 2023

AbstractThe removal of calcareous deposits from archaeological ceramics is a very normal conservation-restoration treatment. Among the products used, chelating agents are quite common, including ethylenediaminetetraacetic acid salts (EDTA) (Berducou in La Conservation en archéologie: méthodes et pratique de la conservation-restauration des vestiges archéologiques, Masson, Paris, 1990; Buys and Oakley The conservation and restoration of ceramics, Butterworth-Heinemann, Oxford, 1993; Crisci et al. in Appl Phys A Mater Sci Process, 2010. https://doi.org/10.1155/2009/893528). Nevertheless, some studies have proved that they can cause damages on the ceramic pieces, regarding changes in their composition, such as dissolution of calcareous components and metallic oxides leaching (Gibson in Stud Conserv, 1971. https://doi.org/10.1155/2009/893528; Fernández and Seva Sautuola in Rev del Inst Prehist y Arqueol 9:471–982, 2003). As a consequence, their artistic values might also change. In spite of that, these products are nowadays still in use, meaning that the treatments might be changing the information that archaeological ceramics carry. However, from the 80 s onwards a more secure alternative to direct application methods based on thickening agents was developed. With the aim of analysing the degradation mechanisms that may take place after the cleaning treatments’ application, ceramic specimens with artificial calcareous deposits (Sáenz-Martínez et al. in Eur Phys J Plus 136:798, 2021) were treated with a low-concentrated solution of EDTA tetrasodium salt applied by immersion and thickened with xanthan gum powder (Vanzan® NF-C). Finally, the products from the cleaning treatments were neutralised, respectively, by immersion and by rinsing with deionized water. The composition of the ceramic samples was established before the growth of calcareous deposits and after the treatments, in order to determine their effectiveness and safety. According to the results, EDTA salt treatments, both by immersion and thickened, were effective regarding the removal of the calcareous deposits and did not modify the elemental and mineralogical original composition of the specimens (XRF, XRPD, TG-DSC). In addition, no gel residues were detected by FTIR-ATR.
Circumferential buckling of a hydrogel tube emptying upon dehydration
Authors: Curatolo M. , Lisi F. , Napoli G. , Nardinocchi P. 
Published: May 2023

AbstractA cylindrical hydrogel tube, completely submerged in water, hydrates by swelling and filling its internal cavity. When it comes back into contact with air, it dehydrates: the tube thus expels the solvent through the walls, shrinking. This dehydration process causes a depression in the tube cavity, which can lead to circumferential buckling. Here we study the occurrence of such buckling using a continuous model that combines nonlinear elasticity with Flory–Rehner theory, to take into account both the large deformations and the active behaviour of the hydrogel. In quasi-static approximation, we use the incremental deformation formalism, extended to the chemo-mechanical equations, to determine the threshold value of the enclosed volume at which buckling is triggered. This critical value is found to depend on the shell thickness, chemical potential and constitutive features. The results obtained are in good agreement with the results of the finite element simulations of the complete dynamic problem.
Miniaturized Ultrawideband Microstrip Antenna for IoT-Based Wireless Body Area Network Applications
Authors: Pandey Utkarsh , Singh Parulpreet , Singh Raghvendra , Gupta Narbada Prasad , Arora Sandeep Kumar , Nizeyimana Eric 
Published: May 2023

In this paper, we present an extremely compact ultrawideband (UWB) monopole microstrip patch antenna for a wireless body area network (WBAN). The proposed antenna is fabricated on a flexible Rogers RT-5880 dielectric substrate of thickness 0.5 mm and has an overall size of

20
×
15
×
0.5

m

m

3

. The proposed antenna achieves a wideband characteristic with the help of a modified ground plane with a monopole pair. The monopole antenna is fed through a microstrip line and has a good impedance matching over a frequency band of 3.2 to 15 GHz (and beyond), with an axial ratio below 3 dB and a high efficiency of 77–95%. This antenna is designed to cover almost the complete UWB range; bandwidth for antenna is 11.52 GHz (3.48-15 GHz). The antenna has a realized gain of 2.3–7.2 dBi throughout the frequency band and has been tested for conformality. Measured results are found to be in good correlation with the simulated results. The antenna has also been tested for specific absorption rate (SAR) values within the simulation to compare with Federal Communications Commission (FCC) limits and verify their suitability for the Internet of Things- (IoT-) based wearable body area network.
Incidence and Mortality Rates for Childhood Acute Lymphoblastic Leukemia in Puerto Rican Hispanics, 2012–2016
Authors: Montes-Rodríguez Ingrid M. , Soto-Salgado Marievelisse , Torres-Cintrón Carlos R. , Tomassini-Fernandini Jonnalie C. , Suárez Erick , Clavell Luis A. , Cadilla Carmen L. 
Published: May 2023

Abstract

Background:
Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI).

Methods:
Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period.

Results:
PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups.

Conclusions:
PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed.

Impact:
This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US.
See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999
MDM2-PROTAC versus MDM2 Inhibitors: Beyond p53 Reactivation
Authors: Peuget Sylvain , Selivanova Galina 
Published: May 2023

Summary:In this issue of Cancer Discovery, Adams and colleagues present the discovery of a potent PROTAC, MDM2 degrader, which activates wild-type p53 leading to cancer cell death. Importantly, in a number of in vitro and in vivo experiments, the authors show that the depletion of MDM2 by PROTAC kills p53-mutant or p53-null cancer cells.See related article by Adams et al., p. 1210 (5).
Breast Cancer Stem Cell–Derived Tumors Escape from γδ T-cell Immunosurveillance In Vivo by Modulating γδ T-cell Ligands
Authors: Raute Katrin , Strietz Juliane , Parigiani Maria Alejandra , Andrieux Geoffroy , Thomas Oliver S. , Kistner Klaus M. , Zintchenko Marina , Aichele Peter , Hofmann Maike , Zhou Houjiang , Weber Wilfried , Boerries Melanie , Swamy Mahima , Maurer Jochen , Minguet Susana 
Published: May 2023

Abstract

There are no targeted therapies for patients with triple-negative breast cancer (TNBC). TNBC is enriched in breast cancer stem cells (BCSC), which play a key role in metastasis, chemoresistance, relapse, and mortality. γδ T cells hold great potential in immunotherapy against cancer and might provide an approach to therapeutically target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor-sensing mechanisms, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. Herein, we show that patient-derived triple-negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T-cell immunotherapy. We unraveled concerted differentiation and immune escape mechanisms: xenografted BCSCs lost stemness, expression of γδ T-cell ligands, adhesion molecules, and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither promigratory engineered γδ T cells, nor anti–PD-1 checkpoint blockade, significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells and could be pharmacologically reverted by zoledronate or IFNα treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.