bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a harmonized bronchopulmonary dysplasia definition: a study protocol for an international Delphi procedure
Authors: Katz Trixie A , Bancalari Eduardo , Gordijn Sanne J , Higgins Rosemary D , Isayama Tetsuya , Jensen Erik A , Offringa Martin , Pillow J Jane , Shah Prakesh S , Soll Roger F , Stoecklin Benjamin , Mugie Suzanne M , van Kaam Anton H , Onland Wes 
Published: October 2023

IntroductionBronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth with lifelong consequences. Multiple BPD definitions are currently used in daily practice. Uniformity in defining BPD is important for clinical care, research and benchmarking. The aim of this Delphi procedure is to determine what clinicians and researchers consider the key features for defining BPD. With the results of this study, we hope to advance the process of reaching consensus on the diagnosis of BPD.Methods and analysisA Delphi procedure will be used to establish why, when and how clinicians propose BPD should be diagnosed. This semi-anonymous iterative technique ensures an objective approach towards gaining these insights. An international multidisciplinary panel of clinicians and researchers working with preterm infants and/or patients diagnosed with BPD will participate. Steering committee members will recruit potential participants in their own region or network following eligibility guidelines to complete a first round survey online. This round will collect demographic information and opinions on key features of BPD definitions. Subsequent rounds will provide participants with the results from the previous round, for final acceptance or rejection of key features. Statements will be rated using a 5-point Likert scale. After completing the Delphi procedure, an (online) consensus meeting will be organised to discuss the results.Ethics and disseminationFor this study, ethical approval a waiver has been provided. However, all participants will be asked to provide consent for the use of personal data. After the Delphi procedure is completed, it will be published in a peer-reviewed journal and disseminated at international conferences.
Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation
Authors: Galloo Xavier , Fortuni Federico , Meucci Maria Chiara , Butcher Steele C , Dietz Marlieke F , Prihadi Edgard A , Cosyns Bernard , Delgado Victoria , Bax Jeroen J , Ajmone Marsan Nina 
Published: October 2023

ObjectiveSevere secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function, as assessed by RA-reservoir-strain (RASr), show lower long-term prognosis.MethodsConsecutive patients, from a single centre, with first diagnosis of severe STR and RASr measure available, were included. Extensive echocardiographic analysis comprised measures of cardiac chamber size and function, assessed also by two-dimensional speckle-tracking strain analysis. Primary outcome was all-cause mortality, analysed from inclusion until death or last follow-up. The association of RASr with the outcome was evaluated by Cox regression analysis and Akaike information criterion.ResultsA total of 586 patients with severe STR (age 68±13 years; 52% male) were included. Patients presented with mild right ventricular (RV) dilatation (end-diastolic area 13.8±6.5 cm2/m2) and dysfunction (free-wall strain 16.2±7.2%), and with moderate-to-severe RA dilatation (max area 15.0±5.3 cm2/m2); the median value of RASr was 13%. In the overall population, 10-year overall survival was low (40%, 349 deaths), and was significantly lower in patients with lower RASr (defined by the median value): 36% (195 deaths) for RASr ≤13% compared with 45% (154 deaths) for RASr >13% (log-rank p=0.016). With a median follow-up of 6.6 years, RASr was independently associated with all-cause mortality (HR per 5% RASr increase:0.928; 95% CI 0.864 to 0.996; p=0.038), providing additional value over relevant clinical and echocardiographic covariates (including RA size and RV function/size).ConclusionsPatients with severe STR presented with significant RA remodelling, and lower RA function, as measured by RASr, was independently associated with all-cause mortality, potentially improving risk stratification in these patients.
Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine
Authors: Faria Carla , Gava Fabien , Gravelle Pauline , Valero Juan Garcia , Dobaño-López Celia , Van Acker Nathalie , Quelen Cathy , Jalowicki Gael , Morin Renaud , Rossi Cédric , Lagarde Jean-Michel , Fournié Jean-Jacques , Ysebaert Loïc , Laurent Camille , Pérez-Galán Patricia , Bezombes Christine 
Published: October 2023

BackgroundFollicular lymphoma (FL), the most common indolent non-Hodgkin’s Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses.MethodsTo capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability.ResultsFL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+cells positive for PD-1 and TIM-3.ConclusionsIn summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.
Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models
Authors: Sandker Gerwin Gerhard Wemke , Middelburg Jim , Wilbrink Evienne , Molkenboer-Kuenen Janneke , Aarntzen Erik , van Hall Thorbald , Heskamp Sandra 
Published: October 2023

BackgroundCD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and CD3 for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the tumor uptake and the extracellular dose. To optimize their currently limited efficacy in solid tumors, increased understanding of their pharmacokinetics and in vivo internalization is needed.MethodsHere, were studied the pharmacokinetics and in vivo internalization of CD3xTRP1, a fully murine Fc-inert bsAb, in endogenous TRP1-expressing immunocompetent male C57BL/6J mice bearing TRP1-positive and negative tumors over time. Matching bsAbs lacking TRP1-binding or CD3-binding capacity served as controls. BsAbs were radiolabeled with111In to investigate their pharmacokinetics, target binding, and biodistribution through SPECT/CT imaging and ex vivo biodistribution analyses. Co-injection of111In- and125I-labeled bsAb was performed to investigate the in vivo internalization by comparing tissue concentrations of cellular residing111In versus effluxing125I. Antitumor therapy effects were evaluated by monitoring tumor growth and immunohistochemistry.ResultsSPECT/CT and biodistribution analyses showed that CD3xTRP1 specifically targeted TRP1-positive tumors and CD3-rich lymphoid organ and uptake peaked 24 hours pi (KPC3-TRP1: 37.7%ID/g±5.3%ID/g, spleen: 29.0%ID/g±3.9%ID/g). Studies with control bsAbs demonstrated that uptake of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues was primarily receptor-mediated. Together with CD3xTRP1 in the circulation being mainly unattached, this indicates that CD3+T cells are generally not traffickers of CD3-bsAbs to the tumor. Additionally, target-mediated clearance by TRP1-expressing melanocytes was not observed. We further demonstrated rapid internalization of CD3xTRP1 in KPC3-TRP1 tumors (24 hours pi: 54.9%±2.3% internalized) and CD3-rich tissues (spleen, 24 hours pi: 79.7%±0.9% internalized). Therapeutic effects by CD3xTRP1 were observed for TRP1-positive tumors and consisted of high tumor influx of CD8+T cells and neutrophils, which corresponded with increased necrosis and growth delay.ConclusionsWe show that CD3xTRP1 efficiently targets TRP1-positive tumors and CD3-rich tissues primarily through receptor-mediated targeting. We further demonstrate rapid receptor-mediated internalization of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues. Even though this significantly decreases the therapeutical available dose, CD3xTRP1 still induced effective antitumor T-cell responses and inhibited tumor growth. Together, our data on the pharmacokinetics and mechanism of action of CD3xTRP1 pave the way for further optimization of CD3-bsAb therapies.
Facilitators and barriers to hypertension management in urban Nepal: findings from a qualitative study
Authors: Bhattarai Sanju , Bajracharya Swornim , Shrestha Archana , Skovlund Eva , Åsvold Bjørn Olav , Mjolstad Bente Prytz , Sen Abhijit 
Published: October 2023

IntroductionIn Nepal, one-fourth of the adult population has hypertension. Despite provision of comprehensive hypertension services through the primary healthcare system, huge gaps in treatment and control of hypertension exist. Our study explored the individual, interpersonal, health system and community-level barriers and facilitators affecting hypertension management in urban Nepal.MethodsWe used a qualitative methodology informed by Kaufman’s socioecological model, conducting focus group discussions with hypertension patients and their family members. In-depth interviews with hypertension patients, healthcare providers and municipal officials were also conducted.ResultsWe found that inadequate knowledge about hypertension and harmful cultural beliefs hindered effective treatment of hypertension. Interrupted medical supply and distrust in primary healthcare providers affected the poor’s access to hypertension services. Poor communication between family members and gender norms affected adaptation of treatment measures. This study emphasised the role of family members in supporting patients in adhering to treatment measures and rebuilding community trust in primary healthcare providers for better access to hypertension services. The findings guided the development of a manual to be used by community health workers during home visits to support patients to control high blood pressure.ConclusionThe study highlights the importance of integrating various aspects of care to overcome the multiple barriers to hypertension management in urban settings in low-resource countries. Participatory home visits have the potential to empower individuals and families to develop and implement feasible and acceptable actions for home management of hypertension through improved adherence to antihypertensive medication, and behaviour change.
Serum calprotectin and renal function decline in ANCA-associated vasculitides: a post hoc analysis of MAINRITSAN trial
Authors: Romand Xavier , Paclet Marie Hélène , Chuong Minh Vu , Gaudin Philippe , Pagnoux Christian , Guillevin Loïc , Terrier Benjamin , Baillet Athan 
Published: October 2023

ObjectiveSerum calprotectin appears to be an interesting biomarker associated with renal vascular disease activity in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The aim of this study was to assess whether serum calprotectin levels can predict decline in renal function in AAV patients receiving maintenance therapy.MethodsSerum calprotectin levels were assessed at inclusion and month 6 in AAV patients, in complete remission after induction therapy, randomly assigned to rituximab or azathioprine. Renal function decline was defined as a 25% decrease in estimated glomerular filtration rate (eGFR) and a change in the eGFR category, or a decrease of 15 mL/min/1.73 m2. Relapse was defined as a Birmingham Vasculitis Activity Score >0 attributable to active vasculitis.ResultsSeventy-six AAV were included. Serum calprotectin increased from baseline to month 6 in patients with renal function decline (7940 (−226.0, 28 691) ng/ml vs −4800 (−18 777, 3708) ng/ml; p<0.001). An increase of calprotectin level was associated with a higher risk of subsequent renal function decline even after adjustment (OR 6.50 (95% CI 1.7 to 24.9) p=0.006). A significantly higher risk of relapse was observed in proteinase 3- AAV patients with an increase of serum calprotectin levels (OR 5.6 (95% CI 1.0 to 31.2), p=0.03).ConclusionAn increase in serum calprotectin by month 6 compared with inclusion during remission-maintenance therapy in AAV was associated with a higher risk of renal function decline in the following 12 months.Trial registration numberNCT00748644.
Cosmological solutions of chameleon scalar field model
Authors: Zaregonbadi Raziyeh , Saba Nasim , Farhoudi Mehrdad 
Published: October 2023

AbstractWe investigate cosmological solutions of the chameleon model with a non-minimal coupling between the matter and the scalar field through a conformal factor with gravitational strength. By considering the spatially flat FLRW metric and the matter density as a non-relativistic perfect fluid, we focus on the matter-dominated phase and the late-time accelerated-phase of the universe. In this regard, we manipulate and scrutinize the related field equations for the density parameters of the matter and the scalar fields with respect to the e-folding. Since the scalar field fluctuations depend on the background and the field equations become highly non-linear, we probe and derive the governing equations in the context of various cases of the relation between the kinetic and potential energies of the chameleon scalar field, or indeed, for some specific cases of the scalar field equation of state parameter. Thereupon, we schematically plot those density parameters for two different values of the chameleon non-minimal coupling parameter, and discuss the results. In the both considered phases, we specify that, when the kinetic energy of the chameleon scalar field is much less than its potential energy (i.e., when the scalar field equation of state parameter is $$\simeq - 1 $$

≃
-
1

), the behavior of the chameleon model is similar to the $$\Lambda CDM$$

Λ
C
D
M

model. Such compatibility suggests that the chameleon model is phenomenologically viable and can be tested with the observational data.
Generalized teleparallel de Sitter geometries
Authors: Coley A. A. , Landry A. , van den Hoogen R. J. , McNutt D. D. 
Published: October 2023

AbstractTheories of gravity based on teleparallel geometries are characterized by the torsion, which is a function of the coframe, derivatives of the coframe, and a zero curvature and metric compatible spin-connection. The appropriate notion of a symmetry in a teleparallel geometry is that of an affine symmetry. Due to the importance of the de Sitter geometry and Einstein spaces within General Relativity, we shall describe teleparallel de Sitter geometries and discuss their possible generalizations. In particular, we shall analyse a class of Einstein teleparallel geometries which have a 4-dimensional Lie algebra of affine symmetries, and display two one-parameter families of explicit exact solutions.
Total 2-Rainbow Domination in Graphs: Complexity and Algorithms
Authors: Kumar Manjay , Reddy P. Venkata Subba 
Published: October 2023

For a simple, undirected graph [Formula: see text] without isolated vertices, a function [Formula: see text] which satisfies the following two conditions is called a total 2-rainbow dominating function (T2RDF) of [Formula: see text]. (i) For all [Formula: see text], if [Formula: see text] then [Formula: see text] and (ii) Every [Formula: see text] with [Formula: see text] is adjacent to a vertex [Formula: see text] with [Formula: see text]. The weight of a T2RDF [Formula: see text] of [Formula: see text] is the value [Formula: see text]. The total 2-rainbow domination number is the minimum weight of a T2RDF on [Formula: see text] and is denoted by [Formula: see text]. The minimum total 2-rainbow domination problem (MT2RDP) is to find a T2RDF of minimum weight in the input graph. In this article, we show that the problem of deciding if [Formula: see text] has a T2RDF of weight at most [Formula: see text] for star convex bipartite graphs, comb convex bipartite graphs, split graphs and planar graphs is NP-complete. On the positive side, we show that MT2RDP is linear time solvable for threshold graphs, chain graphs and bounded tree-width graphs. On the approximation point of view, we show that MT2RDP cannot be approximated within [Formula: see text] for any [Formula: see text] unless [Formula: see text] and also propose [Formula: see text]-approximation algorithm for it. Further, we show that MT2RDP is APX-complete for graphs with maximum degree 4. Next, it is shown that domination problem and the total 2-rainbow domination problems are not equivalent in computational complexity aspects. Finally, an integer linear programming formulation for MT2RDP is presented.
Mazon Creek fossils brought to you by coal, concretions and collectors
Authors: Burke Patricia J. Coorough , Mayer Paul S. , McCoy Victoria E. 
Published: October 2023

Abstract
The late Carboniferous (Middle Pennsylvanian, ∼307 Ma ago) Mazon Creek Lagerstätte found in northern Illinois, USA, is unique for its exceptional biotic diversity as well as the human endeavours, both professional and avocational, that brought vast numbers of fossils and new species to science. In 1997, the Mazon Creek Fossil Beds, exposed along the Mazon River near Benson Road, Morris, IL, became a National Historic Landmark.

The fossils are preserved in siderite (iron carbonate, FeCO
3
) concretions within the lower 3–8 m of the Francis Creek Shale Member of the Carbondale Formation, and often retain outlines of original soft tissues. The Mazon Creek biota includes over 465 animal and 350 plant species representing more than 100 orders, which is attributed to the preservation of organisms from multiple habitats and the large number of specimens collected. That phenomenon was made possible by coal extraction bringing concretions to the surface and highly motivated amateur collectors pursuing them. Some of the formerly mined areas continue to draw collectors and are preserved as part of the Mazonia-Braidwood State Fish and Wildlife Area. The fossils, fossil collectors and collection sites are a significant part of the cultural and scientific geoheritage.
Novel Approach to Accelerate Lung Cancer Research: Lung-MAP and the Potential of Public-Private Partnerships
Authors: Herbst Roy S. , Blanke Charles D. , Sigal Ellen V. 
Published: October 2023

Abstract
The National Cancer Institute recently found that death rates for non–small cell lung cancer (NSCLC) have been reduced by over 6% overall in recent years. This reduction in mortality has been accompanied by an average increase in overall survival and largely credited to the therapeutic advancements for the effective treatment of NSCLC. Numerous molecular alterations have been identified in NSCLC that have enabled the development of new drugs capable of targeting these changes and efficiently kill cancerous cells. New treatments to modulate patients' immune systems have been shown to be effective in stimulating natural immune cells to have an improved anti-cancer effect. While these types of approaches to treat cancer are providing new options for patients, leadership from the Food and Drug Administration (FDA) recognized that the expansion of targeted therapy in NSCLC presented significant promise, but evaluation of the safety and efficacy of these new drugs would be slowed if new models for conducting clinical studies were not identified. Specifically, the FDA recommended that a comprehensive approach be implemented to identify the patients that are the best candidates for these, and other new treatments based upon the molecular characteristics of their tumors, and more efficiently conduct the clinical studies necessary to evaluate the safety and efficacy of new drugs. To address this growing challenge, leading lung cancer experts and stakeholders across academia, government, industry, and patient advocacy came together to design a clinical research approach that could serve as a sustainable infrastructure for new lung cancer treatments called the Lung Cancer Master Protocol.
Adoptive T Cell Therapy in Solid Tumors: State-of-the Art, Current Challenges, and Upcoming Improvements
Authors: Dougé Aurore , El Ghazzi Nathan , Lemal Richard , Rouzaire Paul 
Published: October 2023

Abstract
In solid tumors, three main complementary approaches of adoptive T-cell therapies were successively developed: tumor-infiltrating lymphocytes, chimeric antigen receptor engineered T cells, and high-affinity T-cell receptor engineered T cells. In this review, we summarized rational and main results of these three adoptive T-cell therapies in solid tumors field and gave an overview of encouraging data and their limits. Then, we listed the major remaining challenges (including tumor antigen loss, on-target/off-tumor effect, tumor access difficulties and general/local immunosubversion) and their lines of research. Finally, we gave insight into the ongoing trials in solid tumor.
T cell–Dependent Bispecific Therapy Enhances Innate Immune Activation and Antibody-Mediated Killing
Authors: Besla Rickvinder , Penuel Elicia , Del Rosario Geoff , Cosino Ely , Myrta Szymon , Dillon Mike , Lazar Greg A. , Nickles Dorothee , Spiess Christoph , Yu Shang-Fan , Polson Andrew G. 
Published: October 2023

Abstract
T cell–retargeting therapies have transformed the therapeutic landscape for hematologic diseases. T cell–dependent bispecific antibodies (TDB) function as conditional agonists that induce a polyclonal T-cell response, resulting in target cell destruction and cytokine release. The relationship between this response and its effects on surrounding innate immune populations has not been fully explored. Here we show that treatment with mosunetuzumab in patients results in natural killer (NK) cell activation in the peripheral blood. We modeled this phenomenon in vitro and found that TDB-mediated killing activated NK cells, increasing NK function and antibody-dependent cellular cytotoxicity (ADCC), and enhanced the capability of macrophages to perform antibody-dependent cellular phagocytosis (ADCP). This enhancement was triggered by cytokines released through TDB treatment, with IL2 and IFNγ being major drivers for increased ADCC and ADCP, respectively. Surprisingly, cytolytic ability could be further augmented through neutralization of IL10 for NK cells and TNFα for macrophages. Finally, we showed that TDB treatment enhanced the efficacy of Fc-driven killing to an orthogonal solid tumor target in vivo. These results provide rationale for novel antibody therapy combinations that take advantage of both adaptive and innate immune responses.