bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participant-Level Analysis of the Effects of Interventions on Patient-Reported Outcomes in Patients With Chronic Ankle Instability
Authors: Powden Cameron J. , Koldenhoven Rachel M. , Simon Janet E. , Fraser John J. , Rosen Adam B. , Jaffri Abbis , Mitchell Andrew B. , Burcal Christopher J. 
Published: September 2022

Context: Intervention studies for chronic ankle instability (CAI) often focus on improving physical impairments of the ankle complex. However, using an impairments-focused approach may miss psychological factors that may mediate function and recovery. Patient-reported outcome (PRO) measures can be used to assess several dimensions of the health-related quality of life (HRQoL) and deliver enhanced patient-centered care. Therefore, the purpose of this investigation was to evaluate group-level improvements in HRQoL and treatment response rates following various interventions in patients with CAI. Design: Cross-sectional. Methods: Data from 7 previous studies were pooled by the chronic ankle instability outcomes network for participant-level analysis, resulting in 136 patients with CAI. Several interventions were assessed including balance training, gait biofeedback, joint mobilizations, stretching, and strengthening, with treatment volume ranging from 1 to 4 weeks. Outcome measures were PROs that assessed ankle-specific function (Foot and Ankle Ability Measure), injury-related fear (Tampa Scale of Kinesiophobia and Fear Avoidance Belief Questionnaire), and global well-being (Disablement in the Physically Active); the PROs assessed varied between studies. Preintervention to postintervention changes were evaluated using separate Wilcoxon signed-rank tests and effect sizes, and a responder analysis was conducted for each PRO. Results: Significant, moderate to large improvements were observed in PROs that assessed ankle-specific function, injury-related fear, and global well-being following intervention (P < .001). Responder rates ranged from 39.0% to 53.3%, 12.8% to 51.4%, and 37.8% for ankle specific function, injury-related fear, and global well-being, respectively. Conclusions: Various interventions can lead to positive improvements in HRQoL in patients with CAI. Treatment response rates at improving HRQoL are similar to response rates at improving impairments such as balance, further reinforcing the need for individualized treatment approaches when treating a patient with CAI.
Safety, Tolerability, and Pharmacokinetics of the Novel Antiviral Agent Ensitrelvir Fumaric Acid, a SARS-CoV-2 3CL Protease Inhibitor, in Healthy Adults
Authors: Shimizu Ryosuke , Sonoyama Takuhiro , Fukuhara Takahiro , Kuwata Aya , Matsuo Yumiko , Kubota Ryuji 
Published: September 2022

Ensitrelvir is a novel selective inhibitor of the 3C-like protease of SARS-CoV-2, which is essential for viral replication. This phase 1 study of ensitrelvir assessed its safety, tolerability, and pharmacokinetics of single (part 1,
n
= 50) and multiple (part 2,
n
= 33) ascending oral doses.
Geographically weighted regression in mineral exploration: A new application to investigate mineralization
Authors: Wang Wenlei , Zhao Jie , Cheng Qiuming 
Published: September 2022

ABSTRACT
Geographically weighted regression (GWR) is an effective model for the investigation of spatially nonstationary relations among variables in the geographical and social sciences. GWR was introduced to the field of mineral exploration to further understanding of the location, controlling factors, and coupling mechanisms related to the triggering of mineralization—in other words, the where, what, and how. Previous studies reported that Cu and Au in a porphyry system present a paragenetic relation at different stages of mineralization, which can be an informative indicator in mineral exploration. As a successor, the current study further applies the GWR model to characterize the paragenetic relation between the ore-forming elements Cu and Au in the Duolong mineral district of Tibet, China, in a spatial scenario. Unlike the spatially varied ore-forming mechanism quantified by the regression coefficients of GWR, the coefficient of determination (R2) is discussed to verify the existence and to evaluate the strength of the paragenetic relation between Cu and Au, because regression coefficients can only inform the mutual influence between one and the other. Furthermore, the fractal and multifractal-based spectrum–area method is adopted to separate the GWR results into anomaly and background. Areas with GWR results that indicate the existence and intensity of a paragenetic relation are mapped as target areas for mineral exploration. The current quantitative recognition of mineralization represents a meaningful and useful extension to the application and interpretation of the GWR model.
A Method for Investigating Nanosecond Processes in Micropinch Discharge Plasma
Authors: Dolgov A. N. , Klyachin N. A. , Prokhorovich D. E. 
Published: September 2022

Abstract
The technique is described and the results of studies of the spatial structure and dynamics of X-ray sources in the plasma of a micropinch discharge are presented. The applied technique made it possible to temporarily link the process of electron acceleration in a quasi-static electric field of a resistive nature to the process of forming a microstretch in a Z-pinch in a medium of heavy elements with a nanosecond time resolution.
Dilution Microcryostat–Insert for Microwave Spectroscopy and Magnetic Resonance
Authors: Smirnov A. I. , Soldatov T. A. , Edelman V. S. 
Published: September 2022

Abstract
An autonomous dilution microrefrigerator manufactured as an insert into a helium cryostat with a superconducting magnet is described. In this refrigerator, the 3He circulation in the circuit filled with a 3He–4He mixture (mixer–heat exchanger–still–condenser–heat exchanger–mixer) is achieved due to the condensation of mixture vapors on the walls of the condenser, which is cooled by the 3He bath pumped out by a sorption pump, as well as entry of the condensate into the mixer under the action of gravity. An 8-mm-range resonator that contains a sample is connected to the mixer via a heat conductor; the sample is located at the center of a superconducting solenoid with a field of up to 80 kOe. Radiation passes from the generator through a waveguide to the resonator, and the signal that passed through the resonator arrives at the detector. The generator and detector are at room temperature. The device is designed for microwave spectroscopy of magnetic materials at temperatures in the range of ~0.09–3 K. The time within which the temperature is maintained at a level of ~0.1 K is 4–6 h. The results of a test experiment on the antiferromagnetic resonance in a MnCO3 single crystal are presented.
Feeding of Fish at the Seamounts of the Whale Ridge (South-Eastern Atlantic Ocean). 2. Splendid alfonsino Beryx splendens (Berycidae)
Authors: Gushchin A. V. 
Published: September 2022

Abstract
The feeding characteristics of splendid alfonsino Beryx splendens from the seamounts of the Whale Ridge have been studied. A wide range of food organisms in feeding of splendid alfonsino has been confirmed, comprising meso- and macroplankton of the sound-scattering layers of the mesopelagial. Benthic organisms have not been found in the food spectra of splendid alfonsino. The food spectra of splendid alfonsino differ in populations inhabiting distant groups of the seamounts of the Whale Ridge due to the difference in the composition of the available food items and environmental conditions, fish body size, season, and sampling period. Splendid alfonsino has a pronounced diurnal feeding dynamics: the fish feed most intensively in the evening and at the beginning of the night, when the organisms of the sound-scattering layers migrate to the upper water layers. At this time, maximum feeding and minimum digestion of food are noted. Splendid alfonsino selects organisms of 0.9–130.0 mm (on average, 36.1 mm) in size for feeding. As the body length increases, splendid alfonsino switches to feeding on larger prey, while the ratio of the size of the prey to the size of splendid alfonsino changes little (9.7–11.5%).
Targeting two distinct epitopes on human CD73 with a bispecific antibody improves anticancer activity
Authors: Gammelgaard Odd L , Terp Mikkel G , Renn Christian , Labrijn Aran F , Hamaker Oliver , Nielsen Aaraby Y , Vever Henriette , Hansen Soren WK , Gjerstorff Morten F , Müller Christa E , Parren Paul WHI , Ditzel Henrik J 
Published: September 2022

BackgroundImmunosuppressive extracellular adenosine is generated by the enzymatic activity of CD73. In preclinical models, antibodies (Abs) targeting different epitopes on CD73 exert anticancer activity through distinct mechanisms such as inhibition of enzymatic activity, engagement of Fc receptors, and spatial redistribution of CD73.MethodsUsing controlled Fab arm exchange, we generated biparatopic bispecific antibodies (bsAbs) from parental anti-CD73 Abs with distinct anticancer activities. The resulting anticancer activity was evaluated using in vitro and in vivo models.ResultsWe demonstrate that different anticancer activities can be combined in a biparatopic bsAb. Remarkably, the bsAb significantly improved the enzyme inhibitory activity compared with the parental Abs, which led to neutralization of adenosine-mediated T-cell suppression as demonstrated by proliferation and interferon gamma (IFN-γ) production and prolonged survival of tumor-bearing mice. Additionally, the bsAb caused more efficient internalization of cell surface CD73 and stimulated potent Fc-mediated engagement of human immune effector cells in vitro and in vivo.ConclusionsOur data collectively demonstrate that complementary anticancer mechanisms of action of distinct anti-CD73 Abs can be combined and enhanced in a biparatopic bsAb. The multiple mechanisms of action and superior activity compared with the monospecific parental Abs make the bsAb a promising candidate for therapeutic targeting of CD73 in cancer. This concept may greatly improve future Ab design.
Selective targeting of GARP-LTGFβ axis in the tumor microenvironment augments PD-1 blockade via enhancing CD8+T cell antitumor immunity
Authors: Li Anqi , Chang Yuzhou , Song No-Joon , Wu Xingjun , Chung Dongjun , Riesenberg Brian P , Velegraki Maria , Giuliani Giuseppe D , Das Komal , Okimoto Tamio , Kwon Hyunwoo , Chakravarthy Karthik B , Bolyard Chelsea , Wang Yi , He Kai , Gatti-Mays Margaret , Das Jayajit , Yang Yiping , Gewirth Daniel T , Ma Qin , Carbone David , Li Zihai 
Published: September 2022

BackgroundImmune checkpoint blockade (ICB) has revolutionized cancer immunotherapy. However, most patients with cancer fail to respond clinically. One potential reason is the accumulation of immunosuppressive transforming growth factor β (TGFβ) in the tumor microenvironment (TME). TGFβ drives cancer immune evasion in part by inducing regulatory T cells (Tregs) and limiting CD8+T cell function. Glycoprotein-A repetitions predominant (GARP) is a cell surface docking receptor for activating latent TGFβ1, TGFβ2 and TGFβ3, with its expression restricted predominantly to effector Tregs, cancer cells, and platelets.MethodsWe investigated the role of GARP in human patients with cancer by analyzing existing large databases. In addition, we generated and humanized an anti-GARP monoclonal antibody and evaluated its antitumor efficacy and underlying mechanisms of action in murine models of cancer.ResultsWe demonstrate that GARP overexpression in human cancers correlates with a tolerogenic TME and poor clinical response to ICB, suggesting GARP blockade may improve cancer immunotherapy. We report on a unique anti-human GARP antibody (named PIIO-1) that specifically binds the ligand-interacting domain of all latent TGFβ isoforms. PIIO-1 lacks recognition of GARP-TGFβ complex on platelets. Using humanLRRC32(encoding GARP) knock-in mice, we find that PIIO-1 does not cause thrombocytopenia; is preferentially distributed in the TME; and exhibits therapeutic efficacy against GARP+and GARP-cancers, alone or in combination with anti-PD-1 antibody. Mechanistically, PIIO-1 treatment reduces canonical TGFβ signaling in tumor-infiltrating immune cells, prevents T cell exhaustion, and enhances CD8+T cell migration into the TME in a C-X-C motif chemokine receptor 3 (CXCR3)-dependent manner.ConclusionGARP contributes to multiple aspects of immune resistance in cancer. Anti-human GARP antibody PIIO-1 is an efficacious and safe strategy to block GARP-mediated LTGFβ activation, enhance CD8+T cell trafficking and functionality in the tumor, and overcome primary resistance to anti-PD-1 ICB. PIIO-1 therefore warrants clinical development as a novel cancer immunotherapeutic.
Velocity map imaging and cross sections of Fe(CO)5 for FEBIP applications
Authors: Pintea Maria , Mason Nigel , Tudorovskaya Maria 
Published: September 2022

AbstractThe present paper intends to be a new study of a widely used precursor in nanostructure deposition and FEBID processes with focus on its fragmentation at collisions with low energy electrons. Newer developments in nanotechnology with applications to focused electron beam-induced deposition (FEBID) and extreme ultraviolet lithography (EUVL) based on irradiation-induced chemistry come with advances in the size of the nanostructures at the surface and their flexibility in creating highly complex 3D structures. The deformation in the main structures of the FEBID process characterized by elongation, reduction in diameter of the main structure and the deposition of additional thin layers around the structure, on the substrate, are results of the secondary electrons effect, colliding with energies lower than 20 eV. Fe(CO)5 is one of the most used compounds in FEBID processes as it has a high vaporization pressure and has been shown to provide high-purity deposits (over 90%). This paper combines experiment and simulations to study electron scattering from Fe(CO)5, using Quantemol-N simulations with mass spectroscopy techniques to present the fragmentation pathways and channel distributions for each of the resulting negative ions at low electron energies, while experimental data on dissociative electron attachment make use of the velocity-sliced map imaging (VMI) technique to determine the anions at the incident electron energies. The Quantemol-N simulation package as a standalone is used to study collision processes of low-energy electrons with Fe(CO)5 molecules including elastic, electronic excitation, and dissociative electron attachment (DEA) cross sections for a wide range of process in nuclear industry, medical research and quantum chemistry.
Graphical abstract
Effect of Interconnector Rib on Optimization of SOFC Structural Parameters
Authors: Wang Chen , Li Zheng , He Qijiao , Zhu Meng , Ni Meng 
Published: September 2022

Interconnector (IC) is a key component for current collection in solid oxide fuel cell (SOFC) stacks, but leads to uneven distribution of gas (especially O2) and significantly reduces the power density. In this paper, a 3D numerical model is developed to study the effect of interconnector on the optimization of cathode structures of a planar SOFC. After model validation, parametric analyses are conducted to investigate the effects of cathode structural properties on the SOFC performance and temperature distribution, considering the interconnect dimensions and parameter variations along the flow channel. It is found that the interconnector causes more non-uniform distribution of oxygen in the downstream cathode than in the upstream. Increasing porosity or cathode thickness can improve the oxygen uniformity and the cell electrochemical performance especially in the downstream. However, too high porosity (ε > 0.4) or too thick cathode (t
c > 250 μm) can cause significant ohmic or concentration losses, respectively. Besides, gradient porosity can increase the oxygen uniformity (up to 6.5%) and reduce the concentration loss (up to 10.6%) especially under the rib. In addition, a higher temperature region is observed in the cathode area under the channel, while increasing the porosity, the cathode thickness or using gradient porosity all cause a more uniform temperature distribution.
Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity
Authors: Sánchez-Paulete Alfonso R. , Mateus-Tique Jaime , Mollaoglu Gurkan , Nielsen Sebastian R. , Marks Adam , Lakshmi Ashwitha , Khan Jalal A. , Wilk C. Matthias , Pia Luisanna , Baccarini Alessia , Merad Miriam , Brown Brian D. 
Published: September 2022

Abstract

Tumor-associated macrophages (TAM) are one of the most abundant cell types in many solid tumors and typically exert protumor effects. This has led to an interest in macrophage-depleting agents for cancer therapy, but approaches developed to date have had limited success in clinical trials. Here, we report the development of a strategy for TAM depletion in mouse solid tumor models using chimeric antigen receptor (CAR) T cells targeting the macrophage marker F4/80 (F4.CAR-T). F4.CAR-T cells effectively killed macrophages in vitro and in vivo without toxicity. When injected into mice bearing orthotopic lung tumors, F4.CAR-T cells infiltrated tumor lesions and delayed tumor growth comparably with PD-1 blockade, and significantly extended mouse survival. Antitumor effects were mediated by F4.CAR-T–produced IFNγ, which promoted upregulation of MHC molecules on cancer cells and tumor-infiltrating myeloid cells. Notably, F4.CAR-T promoted expansion of endogenous CD8 T cells specific for tumor-associated antigen and led to immune editing of highly antigenic tumor cell clones. Antitumor impact was also observed in mouse models of ovarian and pancreatic cancer. These studies provide proof of principle to support CAR T-cell targeting of TAMs as a means to enhance antitumor immunity.
Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis
Authors: Kane Laura E. , Mellotte Gregory S. , Mylod Eimear , O'Brien Rebecca M. , O'Connell Fiona , Buckley Croí E. , Arlow Jennifer , Nguyen Khanh , Mockler David , Meade Aidan D. , Ryan Barbara M. , Maher Stephen G. 
Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88–0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78–0.83; P &lt; 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P &lt; 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P &lt; 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis.Significance:In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.
Early Rhythm Control in Patients With Atrial Fibrillation and High Comorbidity Burden
Authors: Rillig Andreas , Borof Katrin , Breithardt Günter , Camm A. John , Crijns Harry J.G.M. , Goette Andreas , Kuck Karl-Heinz , Metzner Andreas , Vardas Panos , Vettorazzi Eik , Wegscheider Karl , Zapf Antonia , Kirchhof Paulus 
Published: September 2022

Background:
The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known.

Methods:

These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA
2
DS
2
-VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA
2
DS
2
-VA score).

Results:

EAST-AFNET4 randomized 1093 patients with CHA
2
DS
2
-VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA
2
DS
2
-VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA
2
DS
2
-VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51–0.81];
P
< 0.001) but not in patients with CHA
2
DS
2
-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73–1.19];
P
=0.56,
P
interaction
=0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA
2
DS
2
-VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08];
P
=0.175), but occurred more often in patients with CHA
2
DS
2
-VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05–1.82];
P
=0.019,
P
interaction
=0.008). Life-threatening events or death were not different between groups (CHA
2
DS
2
-VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA
2
DS
2
-VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA
2
DS
2
-VA score), the
P
interaction
was not significant for the primary efficacy outcome (
P
=0.25), but remained significant (
P
=0.044) for the primary safety outcome.

Conclusions:

Patients with recently diagnosed atrial fibrillation and CHA
2
DS
2
-VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01288352. URL:
https://www.clinicaltrialsregister.eu
; Unique identifier: 2010-021258-20. URL:
https://www.isrctn.com/
; Unique identifier: ISRCTN04708680.