bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons learnt from the implementation of new models of care delivery through alliance governance in the Southern health region of New Zealand: a qualitative study
Authors: Gurung Gagan , Jaye Chrystal , Gauld Robin , Stokes Tim 
Published: October 2022

ObjectivesTo explore the process of implementation of the primary and community care strategy (new models of care delivery) through alliance governance in the Southern health region of New Zealand (NZ).DesignQualitative semistructured interviews were undertaken. A framework-guided rapid analysis was conducted, informed by implementation science theory—the Consolidated Framework for Implementation Research.SettingSouthern health region of NZ (Otago and Southland).ParticipantsEleven key informants (Alliance Leadership Team members and senior health professionals) who were involved in the development and/or implementation of the strategy.ResultsThe large number of strategy action plans and interdependencies of activities made implementation of the strategy complex. In the inner setting, communication and relationships between individuals and organisations were identified as an important factor for joint and integrated working. Key elements of a positive implementation climate were not adequately addressed to better align the interests of health providers, and there were multiple competing priorities for the project leaders. A perceived low level of commitment from the leadership of both organisations to joint working and resourcing indicated poor organisational readiness. Gaps in the implementation process included no detailed implementation plan (reflected in poor execution), ambitious targets, the lack of a clear performance measurement framework and an inadequate feedback mechanism.ConclusionsThis study identified factors for the successful implementation of the PCSS using an alliancing approach in Southern NZ. A key enabler is the presence of a stable and committed senior leadership team working through high trust relationships and open communication across all partner organisations. With alliances, partnerships and networks increasingly held up as models for integration, this evaluation identifies important lessons for policy makers, managers and services providers both in NZ and internationally.
First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors
Authors: Davis Elizabeth J , Martin-Liberal Juan , Kristeleit Rebecca , Cho Daniel C , Blagden Sarah P , Berthold Dominik , Cardin Dana B , Vieito Maria , Miller Rowan E , Hari Dass Prashanth , Orcurto Angela , Spencer Kristen , Janik John E , Clark Jason , Condamine Thomas , Pulini Jennifer , Chen Xuejun , Mehnert Janice M 
Published: October 2022

BackgroundOX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.MethodsPhase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.ResultsEighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1–9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs.ConclusionNo safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors.Trial registration numberNCT02923349.
Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study
Authors: Buonsenso Danilo , Noguera-Julian Antoni , Moroni Rossana , Hernández-Bartolomé Angel , Fritschi Nora , Lancella Laura , Cursi Laura , Soler-Garcia Aleix , Krüger Renate , Feiterna-Sperling Cornelia , Sali Michela , Lo Vecchio Andrea , Scarano Sara , Hernanz Lobo Alicia , Espiau Maria , Soriano-Arandes Antonio , Cetin Benhur Sirvan , Brinkmann Folke , Ozere Iveta , Baquero-Artigao Fernando , Tsolia Maria , Milheiro Silva Tiago , Bustillo-Alonso Matilde , Martín Nalda Andrea , Mancini Margherita , Starshinova Anna , Ritz Nicole , Velizarova Svetlana , Ferreras-Antolín Laura , Götzinger Florian , Bilogortseva Olga , Chechenyeva Vira , Tebruegge Marc , Santiago-García Begoña 
Published: October 2022

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.
Effects of injection parameters on CRDI-equipped stationary diesel engine fuelled with neat biodiesel mix derived from waste feedstocks
Authors: Anto Alosius M. , Thomai Pushparaj , Sharma Vikas , Chandrasekaran Bharathi 
Published: October 2022

This present work deals with the effects of injection parameters such as pilot-main injection mass ratio and dwell time on combustion, performance, and emission characteristics of a diesel engine. A single cylinder diesel engine is used in this research work with the flexibilities to modify different variables via open electronic control unit. Biodiesel mix (BDM) used in the present work is derived from waste feedstocks of used cooking oil and chicken fat. Throughout the experiment, engine load and speed were maintained constantly at 4.51 brake mean effective pressure and 1500 rpm, respectively. Different pilot mass ratios (10%, 20%, and 30%) and dwell times (20° crank angle (CA), 30° CA, and 40° CA) were tested and results were compared with conventional mode combustion. The results indicated that the pilot injections helped to reduce the ignition lag period and also shortened the combustion duration. The highest brake thermal efficiency of 34.78% was identified with the lowest pilot mass of 10%. According to the results, increased dwell time decreased the oxides of nitrogen emissions but increased the hydrocarbon emissions. The experiment revealed that BDM made of waste feedstocks could be an effective alternative for engine applications with optimized engine operating conditions.
Emerging Technologies in K–12 Education: A Future HCI Research Agenda
Authors: Van Mechelen Maarten , Smith Rachel Charlotte , Schaper Marie-Monique , Tamashiro Mariana , Bilstrup Karl-Emil , Lunding Mille , Graves Petersen Marianne , Sejer Iversen Ole 
Published: October 2022

This systematic mapping review sheds light on how emerging technologies have been introduced and taught in various K–12 learning settings, particularly with regard to artificial intelligence (AI), machine learning (ML), the internet of things (IoT), augmented reality (AR), and virtual reality (VR). These technologies are rapidly being integrated into children's everyday lives, but their functions and implications are rarely understood due to their complex and distributed nature. The review provides a rigorous overview of the state of the art based on 107 records published across the fields of human-computer interaction, learning sciences, computing education, and child–computer interaction between 2010 and 2020. The findings show the urgent need on a global scale for inter- and transdisciplinary research that can integrate these dispersed contributions into a more coherent field of research and practice. The article presents nine discussion points for developing a shared agenda to mature the field. Based on the HCI community's expertise in human-centred approaches to technology and aspects of learning, we argue that the community is ideally positioned to take a leading role in the realisation of this future research agenda.
Comparing New York Heart Association Class and Patient-Reported Outcomes Among Patients Hospitalized for Heart Failure
Authors: Cosiano Michael F. , Vista Andrew , Sun Jie-Lena , Alhanti Brooke , Harrington Josephine , Butler Javed , Starling Randall C. , Mentz Robert J. , Greene Stephen J. 
Published: October 2022

Background:
Alignment between clinician-reported New York Heart Association (NYHA) class compared and patient-reported outcomes among patients hospitalized for heart failure is unclear.

Methods:
ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was a global randomized trial comparing nesiritide versus placebo among patients hospitalized for heart failure, irrespective of ejection fraction. Among patients with complete baseline data for NYHA class and the patient-reported EuroQOL-5 dimensions ([EQ-5D], both utility index and visual analog scale), levels of each scale were mapped across 4 prespecified categories “best” to “worst.” Minor and moderate-severe discordance were defined as NYHA class and EQ-5D differing by 1 level and ≥2 levels, respectively. Multivariable models assessed factors independently associated with moderate-severe discordance, and associations between discordance and clinical outcomes.

Results:

Among 5741 patients, concordance, minor discordance, and moderate-severe discordance between NYHA class and EQ-5D utility index occurred in 22%, 40%, and 38% of patients, respectively. For NYHA class and EQ-5D visual analog scale, this categorization occurred in 29%, 48%, and 23%. Discordance was more often due to disproportionately higher EQ-5D score (78% of discordance cases with utility index, and 70% with visual analog scale). NYHA class IV, higher EQ-5D scores, race, and geographic region were among patient factors independently associated with moderate-severe discordance. Magnitude of discordance was not associated with clinical outcomes; however, EQ-5D utility index disproportionately worse than NYHA class was associated with increased 180-day mortality (adjusted hazard ratio 1.27 [95% CI, 1.01–1.60];
P
=0.04).

Conclusions:
In a global trial cohort of patients hospitalized for heart failure, the majority of patients exhibited discordance between clinician-reported NYHA class and patient-reported health status. Multiple patient factors were independently associated with moderate-severe discordance, and patients who perceived their health status as worse than the clinician’s perception had higher mortality.

Registration:
URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT00475852.
Efficacy and Safety of an Investigational Single-Course CRISPR Base-Editing Therapy Targeting
PCSK9
in Nonhuman Primate and Mouse Models
Authors: Lee Richard G. , Mazzola Anne Marie , Braun Maurine C. , Platt Colin , Vafai Scott B. , Kathiresan Sekar , Rohde Ellen , Bellinger Andrew M. , Khera Amit V. 
Published: October 2022

Background:

VERVE-101 is an investigational in vivo CRISPR base-editing medicine designed to alter a single DNA base in the
PCSK9
gene, permanently turn off hepatic protein production, and thereby durably lower low-density lipoprotein cholesterol. We test the efficacy, durability, tolerability, and potential for germline editing of VERVE-101 in studies of nonhuman primates and a murine F1 progeny study.

Methods:
Cynomolgus monkeys were given a single intravenous infusion of a vehicle control (n=10) or VERVE-101 at a dose of 0.75 mg/kg (n=4) or 1.5 mg/kg (n=22) with subsequent follow-up up to 476 days. Two studies assessed the potential for germline editing, including sequencing sperm samples from sexually mature male nonhuman primates treated with VERVE-101 and genotyping offspring from female mice treated with the murine surrogate of VERVE-101 (VERVE-101mu).

Results:

Liver biopsies 14 days after dosing noted mean
PCSK9
editing of 46% and 70% in monkeys treated with VERVE-101 at 0.75 and 1.5 mg/kg, respectively. This translated into mean reductions in blood PCSK9 (proprotein convertase subtilisin/kexin type 9) of 67% and 83% and reductions of low-density lipoprotein cholesterol of 49% and 69% at the 0.75 and 1.5 mg/kg doses, respectively, assessed as time-weighted average change from baseline between day 28 and up to 476 days after dosing. Liver safety monitoring noted a transient rise in alanine aminotransferase and aspartate aminotransferase concentrations after infusion that fully resolved by day 14 with no accompanying change in total bilirubin. In a subset of monkeys necropsied 1 year after dosing, no findings related to VERVE-101 were identified on macroscopic and histopathologic assessment of the liver and other organs. In the study to assess potential germline editing of male nonhuman primates, sperm samples collected after VERVE-101 dosing showed no evidence of
PCSK9
editing. Among 436 offspring of female mice treated with a saturating dose of VERVE-101mu, the
PCSK9
edit was transmitted in 0 of 436 animals.

Conclusions:
VERVE-101 was well tolerated in nonhuman primates and led to 83% lower blood PCSK9 protein and 69% lower low-density lipoprotein cholesterol with durable effects up to 476 days after dosing. These results have supported the initiation of a first-in-human clinical trial in patients with heterozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease.
Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study
Authors: Durda Peter , Raffield Laura M. , Lange Ethan M. , Olson Nels C. , Jenny Nancy Swords , Cushman Mary , Deichgraeber Pia , Grarup Niels , Jonsson Anna , Hansen Torben , Mychaleckyj Josyf C. , Psaty Bruce M. , Reiner Alex P. , Tracy Russell P. , Lange Leslie A. 
Published: October 2022

Background
Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome‐wide association study to identify sCD163‐associated variants.

Methods and Results

We measured plasma sCD163 in 5214 adults (aged ≥65 years, 58.7% women, 16.2% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow‐up was 26 years. Genome‐wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all‐cause mortality (hazard ratio [HR], 1.08 [95% CI, 1.04–1.12] per SD increase), cardiovascular disease mortality (HR, 1.15 [95% CI, 1.09–1.21]), incident coronary heart disease (HR, 1.10 [95% CI, 1.04–1.16]), and incident heart failure (HR, 1.18 [95% CI, 1.12–1.25]). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome‐wide association studies identified 38 variants on chromosome 2 near
MGAT5
(top result rs62165726,
P
=3.3×10
−18
),19 variants near chromosome 17 gene
ASGR1
(rs55714927,
P
=1.5×10
−14
), and 18 variants near chromosome 11 gene
ST3GAL4
. These regions replicated in the European ancestry ADDITION‐PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo‐Danish‐Dutch study of Intensive Treatment Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781
P
=7.1×10
−9
) in the
HLA
region, and 3 variants (rs115391969
P
=4.3×10
−8
) near the chromosome 16 gene
MYLK3
.

Conclusions
Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular‐specific mortality and incident heart failure.
Antarctic Warming during Heinrich Stadial 1 in a Transient Isotope-Enabled Deglacial Simulation
Authors: Zhu Chenyu , Zhang Jiaxu , Liu Zhengyu , Otto-Bliesner Bette L. , He Chengfei , Brady Esther C. , Tomas Robert , Wen Qin , Li Qing , Zhu Chenguang , Zhang Shaoqing , Wu Lixin 
Published: October 2022

Abstract
Heinrich Stadial 1 (HS1) was the major climate event at the onset of the last deglaciation associated with rapid cooling in Greenland and lagged, slow warming in Antarctica. Although it is widely believed that temperature signals were triggered in the Northern Hemisphere and propagated southward associated with the Atlantic meridional overturning circulation (AMOC), understanding how these signals were able to cross the Antarctic Circumpolar Current (ACC) barrier and further warm up Antarctica has proven particularly challenging. In this study, we explore the physical processes that lead to the Antarctic warming during HS1 in a transient isotope-enabled deglacial simulation iTRACE, in which the interpolar phasing has been faithfully reproduced. We show that the increased meridional heat transport alone, first through the ocean and then through the atmosphere, can explain the Antarctic warming during the early stage of HS1 without notable changes in the strength and position of the Southern Hemisphere midlatitude westerlies. In particular, when a reduction of the AMOC causes ocean warming to the north of the ACC, increased southward ocean heat transport by mesoscale eddies is triggered by steeper isopycnals to warm up the ocean beyond the ACC, which further decreases the sea ice concentration and leads to more absorption of insolation. The increased atmospheric heat then releases to the Antarctic primarily by a strengthening zonal wavenumber-3 (ZW3) pattern. Sensitivity experiments further suggest that a ∼4°C warming caused by this mechanism superimposed on a comparable warming driven by the background atmospheric CO2 rise is able to explain the total simulated ∼8°C warming in the West Antarctica during HS1.
Surgical outcomes and optimal approach to treatment of aortic valve endocarditis with aortic root abscess – systematic review and meta-analysis
Authors: Harris William M , Sinha Shubhra , Caputo Massimo , Angelini Gianni D , Vohra Hunaid A 
Published: October 2022

Background Data on the postoperative outcomes for patients with infective endocarditis complicated by an aortic root abscess is sparse due to the condition’s low incidence and high mortality rates. This systematic review and meta-analysis aims to evaluate existing data on the impact of aortic root abscesses on the postoperative outcomes and to inform optimal surgical approach. Methods The online databases MEDLINE, EMBASE and Cochrane library were searched from 1990 to 2022 for studies comparing cohorts of surgically managed infective endocarditis patients with and without an aortic root abscess. Data was extracted by two independent investigators and aggregated in a random-effects model. Risk of bias was assessed using an adapted version of the Newcastle-Ottawa scale. Results Six clinical studies were included in the meta-analysis ( n 1982). The abscess group was associated with increased in-hospital mortality (OR 1.74 95%: CI 1.18–2.56) and late mortality (HR 1.27 95% CI:1.03–1.58). The reoperation meta-analysis was complicated by high rates of heterogeneity (I2 = 59%) and found no significant differences in reoperation between abscess and no abscess groups (HR=1.48: 95% CI:0.92–2.40). Post-hoc scatter graph showed a strong linear relationship (r 0.998), suggesting hospitals with higher rates of aortic root replacement achieve lower rates of reoperation for aortic root abscess patients compared with patch reconstruction. Conclusions The presence of an aortic root abscess in aortic valve endocarditis is associated with elevated early and late mortality despite modern standards of care. Additionally, aortic root replacement should be considered to have a favourable postoperative profile for use in this context.