bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community partnerships in emerging immigrant communities: Lessons learned addressing Latino childhood weight disparities
Authors: DeCamp Lisa Ross , Acosta Jennifer , Bou Delgado Laura , Guerrero Vazquez Monica , Polk Sarah 
Published: February 2021

AbstractLatino children have disproportionately high childhood obesity rates, and U.S.‐born Latino children of immigrant parents experience higher overweight/obesity rates than other Latino children. Community‐based participatory research (CBPR) to engage Latino immigrant families and Latino‐serving community organizations is one mechanism to address the lack of effective and practical interventions addressing childhood obesity disparities among Latino children. We present lessons learned from applying CBPR methods to a partnership focused on developing a child obesity treatment program for Latino immigrant families in an emerging Latino immigrant destination to inform the use of CBPR methods in other partnerships in emerging immigrant communities. We encountered challenges working within the partnership related to entrenched sociopolitical hierarchies that were not inclusive of immigrant community leaders, capacity building for partners with limited literacy and administrative experience, and how best to use complementary methods and frameworks to support a community‐engaged research process. This work is one way to promote shared learning among the community of researchers using CBPR and other engagement methods to partner with emerging immigrant communities. Together with our community partners, we can identify strategies to more effectively partner to promote health equity and work toward social justice for all members of our communities.
Lessons from implementing community‐based group classes for severe hypertension
Authors: Bulgin Dominique , Whitney Colette A. , Bakovic Melanie , Kang Yunah , Granger Bradi B. , Biola Holly R. 
Published: February 2021

AbstractDue to the impact of persistent structural racism, Black men have low rates of hypertension treatment and control despite having high rates of hypertension‐related mortality. Peer‐based education can improve blood pressure monitoring and lower blood pressure in Black men with hypertension. To address this disparity, we implemented weekly community‐based group classes for severe hypertension at a Federally Qualified Health Center. After 9 months, 28 classes were held and 96 individuals were served. Fifty‐six percent of the person‐hours of attendance have been by Black men. Seven individuals were interviewed about their perspectives and preferences for the classes. They reported that the peer‐based model of the group classes was advantageous, and they would recommend the classes to a friend. Successes of implementation included (a) ability to facilitate medication adjustments for participants with blood pressure readings that were over target goal, (b) capacity to give participants take‐home blood pressure monitors, (c) and the community‐centered approach. Challenges included variability in attendance by participants and retention of individuals with uncontrolled hypertension in primary care. These findings have implications for other Federally Qualified Health Centers seeking to design similar health promotion programs and policy makers evaluating the funding and reimbursement models for community‐based disease management programs.
Targeted Reduction of p-Boxes in Risk Assessments With Mixed Aleatory and Epistemic Uncertainties
Authors: Rohmer Jeremy 
Published: February 2021

Abstract
The treatment of uncertainty using extra-probabilistic approaches, like intervals or p-boxes, allows for a clear separation between epistemic uncertainty and randomness in the results of risk assessments. This can take the form of an interval of failure probabilities; the interval width W being an indicator of “what is unknown.” In some situations, W is too large to be informative. To overcome this problem, we propose to reverse the usual chain of treatment by starting with the targeted value of W that is acceptable to support the decision-making, and to quantify the necessary reduction in the input p-boxes that allows achieving it. In this view, we assess the feasibility of this procedure using two case studies (risk of dike failure, and risk of rupture of a frame structure subjected to lateral loads). By making the link with the estimation of excursion sets (i.e., the set of points where a function takes values below some prescribed threshold), we propose to alleviate the computational burden of the procedure by relying on the combination of Gaussian process (GP) metamodels and sequential design of computer experiments. The considered test cases show that the estimates can be achieved with only a few tens of calls to the computationally intensive algorithm for mixed aleatory/epistemic uncertainty propagation.
Possibilistic Uncertainty Quantification in One-Dimensional Consolidation Problems
Authors: Boumezerane Djamalddine 
Published: February 2021

Abstract
In this study, we use possibility distribution as a basis for parameter uncertainty quantification in one-dimensional (1D) consolidation problems. A possibility distribution is the one-point coverage function of a random set and is viewed as containing both partial ignorance and uncertainty. Vagueness and scarcity of information needed for characterizing the coefficient of consolidation in clay can be handled using possibility distributions. Possibility distributions can be constructed from existing data, or based on the transformation of probability distributions. An attempt is made to set a systematic approach for estimating uncertainty propagation during the consolidation process. The measure of uncertainty is based on Klir's definition (1995). We make comparisons with results obtained from other approaches (probabilistic…) and discuss the importance of using possibility distributions in this type of problem.
Computer-Aided Design/Tolerancing Integration: A Novel Tolerance Analysis Model of Assemblies With Composite Positional Defects and Deformations of Nonrigid Parts
Authors: Korbi A. , Tlija M. , Louhichi B. 
Published: February 2021

Abstract
Nowadays, the tolerancing integration in computer-aided design (CAD) tools remains among the major goals of mechanical manufacturers. In the virtual product development, ideal and rigid models are used in the digital mockup (DMU). Hence, research works developed integrated CAD models for tolerance analysis, while considering manufacturing defects. However, the tolerance analysis in the case of composite positional tolerance for feature patterns, commonly used in the industry, becomes a difficult activity with the consideration of parts deformations. Thus, this paper presents a novel CAD model for the tolerance analysis considering composite positional defect of features set and nonrigid component deformations due to external mechanical loads. The modeling of rigid components with dimensional defects is established based on the numerical perturbation method. Indeed, the relationships between driving and driven dimensions are determined to obtain the configurations in maximum and least material of the CAD model. Thereafter, the geometrical deviations are modeled by face displacements. The modeling of composite positional errors is performed while respecting the feature relating position tolerance zone framework and the pattern-location tolerance zone framework constraints, as well as the maximum or least material condition. The deviations caused by nonrigid part deformations are considered by the integration of finite element results into the CAD model. The realistic configurations of the assembly are obtained after the updating of mating constraints between rigid and nonrigid parts with defects. The composite positional tolerance is analyzed with the simulation of relative motion between parts. A case study is proposed to evaluate the developed tolerancing method.
Machine-Specific Estimation of Milling Energy Consumption in Detailed Design
Authors: Boettjer Till , Thoft Krogshave Johan , Ramanujan Devarajan 
Published: February 2021

AbstractManufacturing is a significant contributor to global greenhouse gas emissions and there is an urgent need to reduce the energy consumption of production processes. An important step towards this goal is proactively estimating process energy consumption at the detailed design stage. This is a challenging task as variabilities in factors such as process specifications, machine tool architecture, and workpiece geometry can significantly reduce the accuracy of the estimated energy consumption. This paper discusses a methodology for machine-specific energy estimation in milling processes at the detailed design stage based on the unit process life cycle inventory (UPLCI) model. We develop an adjusted UPLCI model that includes adjustment factors for uncertainties in machine tool specifications and the specific cutting energy of a workpiece material. These adjustment factors are calculated through experimental measurement of energy consumption for a reference test part on a specific machine tool. To validate the adjusted UPLCI model, we conducted a case study that measured the energy consumption for machining three parts made of Aluminum 6082 on two separate three-axis vertical milling machines, a Chevalier QP2040-L and a Leadwell MCV-OP. Results show that the UPLCI model consistently overestimated the total energy consumption for machining the three validation parts across both machine tools. We also found that the adjusted UPLCI model significantly reduced the estimation errors for the same tests for both machine tools.
Coping and support-seeking in out-of-home care: a qualitative study of the views of young people in care in England
Authors: Hiller Rachel M , Halligan Sarah L , Meiser-Stedman Richard , Elliott Elizabeth , Rutter-Eley Emily , Hutt Tilly 
Published: February 2021

ObjectivesYoung people who have been removed from their family home and placed in out-of-home care have commonly experienced abuse, neglect and/or other forms of early adversity. High rates of mental health difficulties have been well documented in this group. The aim of this research was to explore the experiences of these young people within the care system, particularly in relation to support-seeking and coping with emotional needs, to better understand feasible and acceptable ways to improve outcomes for these young people.Design and study settingThis study used 1:1 semistructured qualitative interviews with young people in out-of-home care in England, to provide an in-depth understanding of their views of coping and support for their emotional needs, both in terms of support networks and experiences with mental health services. Participants were 25 young people aged 10–16 years old (56% female), and included young people living with non-biological foster carers, kinship carers and in residential group homes.ResultsParticipants described positive (eg, feeling safe) and negative (eg, feeling judged) aspects to being in care. Carers were identified as the primary source of support, with a supportive adult central to coping. Views on support and coping differed for young people who were experiencing more significant mental health difficulties, with this group largely reporting feeling unsupported and many engaging in self-harm. The minority of participants had accessed formal mental health support, and opinions on usefulness were mixed.ConclusionsResults provide insight, from the perspective of care-experienced young people, about both barriers and facilitators to help-seeking, as well as avenues for improving support.
Reaching the summit of discharge summaries: a quality improvement project
Authors: Richmond Richard Thomas , McFadzean Isobel Joy , Vallabhaneni Pramodh 
Published: February 2021

BackgroundDischarge summaries need to be completed in a timely manner, to improve communication between primary and secondary care, and evidence suggests that delays in discharge summary completion can lead to patient harm.Following a hospital health and safety review due to the sheer backlog of notes in the doctor’s room and wards, urgent action had to be undertaken to improve the discharge summary completion process at our hospital’s paediatric assessment unit. It was felt that the process would best be carried out within a quality improvement (QI) project.MethodsKotter’s ‘eight-step model for change’ was implemented in this QI project with the aim to clear the existing backlog of pending discharge summaries and improve the timeliness of discharge summary completion from the hospital’s paediatric assessment unit. A minimum target of 10% improvement in the completion rate of discharge summaries was set as the primary goal of the project.ResultsFollowing the implementation of the QI processes, we were able to clear the backlog of discharge summaries within 9 months. We improved completion within 24 hours, from <10% to 84%, within 2 months. The success of our project lies in the sustainability of the change process; to date we have consistently achieved the target completion rates since the inception of the project. As a result of the project, we were able to modify the junior doctor rota to remove discharge summary duty slots and bolster workforce on the shop floor. This is still evident in November 2020, with consistently improved discharge summary rates.ConclusionQI projects when conducted successfully can be used to improve patient care, as well as reduce administrative burden on junior doctors. Our QI project is an example of how Kotter’s eight-step model for change can be applied to clinical practice.
αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib
Authors: Fang Juemin , Ding Na , Guo Xianling , Sun Yan , Zhang Zhiwei , Xie Bailu , Li Zhong , Wang Hui , Mao Wei , Lin Zhicai , Qin Fei , Yuan Min , Chu Wenqi , Qin Huanlong , Qian Qijun , Xu Qing 
Published: February 2021

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in China. In particular, advanced/refractory ovarian cancer lacks effective targeted therapies due to the immunosuppressive and proangiogenic tumor microenvironment. Mesothelin (MSLN) has been found to be highly expressive in most EOC. Targeting MSLN by antibodies or chimeric antigen receptor-modified T (CAR-T) cells and immune checkpoint blockades as well as apatinib, an anti-angiogenic drug, have been used in patients with refractory ovarian cancer. Apatinib was reported to promote the infiltration of CD8+T cells in lung cancer. However, the combination therapy of CAR-T secreting anti-PD-1 antibody with apatinib in EOC has not been reported.Case presentationHere we report a case of refractory EOC in a patient who had relapsed after multiline chemotherapy. The patient received autologous T cells that contained sequences encoding single-chain variable fragments specific for MSLN and full-length antibody for PD-1 (αPD-1). The modified T cells were called αPD-1-mesoCAR-T cells. After infusion, the copy number and PD-1 antibody secretion of the CAR-T cells were increased in the blood. By application of multimodality tumor tracking, MRI of the liver showed shrinkage of metastatic nodules from average diameter of 71.3–39.1 mm at month 2. The patient achieved partial response and survived more than 17 months. IL-6 levels in the patient fluctuated from the baseline to 2–4-folds after treatment, but side effects were mild with only grade 1 hypertension and fatigue.ConclusionαPD-1-mesoCAR-T cell therapy combined with apatinib demonstrates a potential therapeutic effect on advanced refractory ovarian cancer.Trial registration numberNCT03615313.
'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies
Authors: Sinha Debottam , Srihari Sriganesh , Beckett Kirrliee , Le Texier Laetitia , Solomon Matthew , Panikkar Archana , Ambalathingal George R , Lekieffre Lea , Crooks Pauline , Rehan Sweera , Neller Michelle A. , Smith Corey , Khanna Rajiv 
Published: February 2021

BackgroundEpstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.MethodsTaking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.ResultsThese allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.ConclusionThese findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response.
Therapeutic depletion of CCR8+tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy
Authors: Van Damme Helena , Dombrecht Bruno , Kiss Máté , Roose Heleen , Allen Elizabeth , Van Overmeire Eva , Kancheva Daliya , Martens Liesbet , Murgaski Aleksandar , Bardet Pauline Madeleine Rachel , Blancke Gillian , Jans Maude , Bolli Evangelia , Martins Maria Solange , Elkrim Yvon , Dooley James , Boon Louis , Schwarze Julia Katharina , Tacke Frank , Movahedi Kiavash , Vandamme Niels , Neyns Bart , Ocak Sebahat , Scheyltjens Isabelle , Vereecke Lars , Nana Frank Aboubakar , Merchiers Pascal , Laoui Damya , Van Ginderachter Jo Agnes 
Published: February 2021

BackgroundModulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of selectivity for the tumor-infiltrating (ti-)Treg population, indicating the need for a ti-Treg specific biomarker.MethodsWe employed single-cell RNA-sequencing in a mouse model of non-small cell lung carcinoma (NSCLC) to obtain a comprehensive overview of the tumor-infiltrating T-cell compartment, with a focus on ti-Treg subpopulations. These findings were validated by flow cytometric analysis of both mouse (LLC-OVA, MC38 and B16-OVA) and human (NSCLC and melanoma) tumor samples. We generated two CCR8-specific nanobodies (Nbs) that recognize distinct epitopes on the CCR8 extracellular domain. These Nbs were formulated as tetravalent Nb-Fc fusion proteins for optimal CCR8 binding and blocking, containing either an antibody-dependent cell-mediated cytotoxicity (ADCC)-deficient or an ADCC-prone Fc region. The therapeutic use of these Nb-Fc fusion proteins was evaluated, either as monotherapy or as combination therapy with anti-programmed cell death protein-1 (anti-PD-1), in both the LLC-OVA and MC38 mouse models.ResultsWe were able to discern two ti-Treg populations, one of which is characterized by the unique expression ofCcr8in conjunction with Treg activation markers.Ccr8is also expressed by dysfunctional CD4+and CD8+T cells, but the CCR8 protein was only prominent on the highly activated and strongly T-cell suppressive ti-Treg subpopulation of mouse and human tumors, with no major CCR8-positivity found on peripheral Tregs. CCR8 expression resulted from TCR-mediated Treg triggering in an NF-κB-dependent fashion, but was not essential for the recruitment, activation nor suppressive capacity of these cells. While treatment of tumor-bearing mice with a blocking ADCC-deficient Nb-Fc did not influence tumor growth, ADCC-prone Nb-Fc elicited antitumor immunity and reduced tumor growth in synergy with anti-PD-1 therapy. Importantly, ADCC-prone Nb-Fc specifically depleted ti-Tregs in a natural killer (NK) cell-dependent fashion without affecting peripheral Tregs.ConclusionsCollectively, our findings highlight the efficacy and safety of targeting CCR8 for the depletion of tumor-promoting ti-Tregs in combination with anti-PD-1 therapy.
Value of systematic genetic screening of patients with amyotrophic lateral sclerosis
Authors: Shepheard Stephanie R , Parker Matthew D , Cooper-Knock Johnathan , Verber Nick S , Tuddenham Lee , Heath Paul , Beauchamp Nick , Place Elsie , Sollars Elizabeth S A , Turner Martin R , Malaspina Andrea , Fratta Pietro , Hewamadduma Channa , Jenkins Thomas M , McDermott Christopher J , Wang Dennis , Kirby Janine , Shaw Pamela J 
Published: February 2021

ObjectiveThe clinical utility of routine genetic sequencing in amyotrophic lateral sclerosis (ALS) is uncertain. Our aim was to determine whether routine targeted sequencing of 44 ALS-relevant genes would have a significant impact on disease subclassification and clinical care.MethodsWe performed targeted sequencing of a 44-gene panel in a prospective case series of 100 patients with ALS recruited consecutively from the Sheffield Motor Neuron Disorders Clinic, UK. All participants were diagnosed with ALS by a specialist Consultant Neurologist. 7/100 patients had familial ALS, but the majority were apparently sporadic cases.Results21% of patients with ALS carried a confirmed pathogenic or likely pathogenic mutation, of whom 93% had no family history of ALS. 15% met the inclusion criteria for a current ALS genetic-therapy trial. 5/21 patients with a pathogenic mutation had an additional variant of uncertain significance (VUS). An additional 21% of patients with ALS carried a VUS in an ALS-associated gene. Overall, 13% of patients carried more than one genetic variant (pathogenic or VUS). Patients with ALS carrying two variants developed disease at a significantly earlier age compared with patients with a single variant (median age of onset=56 vs 60 years, p=0.0074).ConclusionsRoutine screening for ALS-associated pathogenic mutations in a specialised ALS referral clinic will impact clinical care in 21% of cases. An additional 21% of patients have variants in the ALS gene panel currently of unconfirmed significance after removing non-specific or predicted benign variants. Overall, variants within known ALS-linked genes are of potential clinical importance in 42% of patients.