bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between PIRCHE‐II scores and de novo allosensitization after reduction of immunosuppression during SARS‐CoV‐2 infection in kidney transplant recipients
Authors: Castrezana‐Lopez Kai , Malchow Ronja , Nilsson Jakob , Kokkonen Sanna M. , Rho Elena , von Moos Seraina , Mueller Thomas F. , Schachtner Thomas 
Published: March 2023

AbstractBackgroundBefore the availability of mRNA vaccines, many transplant centers chose to significantly reduce maintenance immunosuppression in kidney transplant recipients (KTRs) with SARS‐CoV‐2 infection. The extent to which this increases the risk of allosensitization is unclear.MethodsIn this observational cohort study, we analyzed 47 KTRs from March 2020 to February 2021 who underwent substantial reduction of maintenance immunosuppression during SARS‐CoV‐2 infection. KTRs were followed at 6 and 18 months concerning the development of de novo donor‐specific anti‐HLA (human leukocyte antigen) antibodies (DSA). The HLA‐derived epitope mismatches were calculated using the predicted indirectly recognizable HLA‐epitopes (PIRCHE‐II) algorithm.ResultsIn total, 14 of 47 KTRs (30%) developed de novo HLA antibodies after the reduction of maintenance immunosuppression. KTRs with higher total PIRCHE‐II scores and higher PIRCHE‐II scores for the HLA‐DR locus were more likely to develop de novo HLA antibodies (p = .023, p = .009). Furthermore, 4 of the 47 KTRs (9%) developed de novo DSA after reduction of maintenance immunosuppression, which were exclusively directed against HLA‐class II antigens and also showed higher PIRCHE‐II scores for HLA‐class II. The cumulative mean fluorescence intensity of 40 KTRs with preexisting anti‐HLA antibodies and 13 KTRs with preexisting DSA at the time of SARS‐CoV‐2 infection remained stable after the reduction of maintenance immunosuppression (p = .141; p = .529).ConclusionsOur data show that the HLA‐derived epitope mismatch load between donor and recipient influences the risk of de novo DSA development when immunosuppression is temporarily reduced. Our data further suggest that reduction in immunosuppression should be made more cautiously in KTRs with high PIRCHE‐II scores for HLA‐class II antigens.
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Coupling of Volumetric Flowfield and Surface Effectiveness Measurements for Flat-Plate Film Cooling With Cylindrical Holes Using Tomographic Particle Image Velocimetry and Pressure-Sensitive Paint
Authors: Wang Hanlin , Wright Lesley M. 
Published: March 2023

AbstractIn this study, a series of time-averaged tomographic particle image velocimetry (TPIV) measurements are completed for simple angle, cylindrical film cooling holes on a flat plate with an inclination angle of 30 deg and a diameter of 4 mm. The flat plate is installed in a low-speed wind tunnel with a mainstream turbulence intensity of Tu=8% and an average velocity of 21.6 m/s. The blowing ratios of the jet range from M = 0.3 to M = 1.5, and the density ratio of the jet is fixed at DR = 1. The Reynolds number of the cooling jet varies from 1700 to 8400. The repeatability and accuracy of the tomographic particle imaging velocimetry (TPIV) measurements are compared against the results obtained by other flowfield measurement techniques. The results of the TPIV measurements are presented in velocity and vorticity iso-surface distributions in 3D, as well as 2D planar slices of velocity, vorticity, turbulence intensity, and Reynolds Stress distributions within the measurement volume. The characteristics of the flowfield are coupled with the detailed film cooling effectiveness distribution obtained using the pressure-sensitive paint (PSP) technique. An inverse relation among volumetric turbulence accumulation (TA) and surface film effectiveness, η, can be correlated.
Gait, physical activity and tibiofemoral cartilage damage: a longitudinal machine learning analysis in the Multicenter Osteoarthritis Study
Authors: Costello Kerry E , Felson David T , Jafarzadeh S Reza , Guermazi Ali , Roemer Frank W , Segal Neil A , Lewis Cora E , Nevitt Michael C , Lewis Cara L , Kolachalama Vijaya B , Kumar Deepak 
Published: March 2023

ObjectiveTo (1) develop and evaluate a machine learning model incorporating gait and physical activity to predict medial tibiofemoral cartilage worsening over 2 years in individuals without advanced knee osteoarthritis and (2) identify influential predictors in the model and quantify their effect on cartilage worsening.DesignAn ensemble machine learning model was developed to predict worsened cartilage MRI Osteoarthritis Knee Score at follow-up from gait, physical activity, clinical and demographic data from the Multicenter Osteoarthritis Study. Model performance was evaluated in repeated cross-validations. The top 10 predictors of the outcome across 100 held-out test sets were identified by a variable importance measure. Their effect on the outcome was quantified by g-computation.ResultsOf 947 legs in the analysis, 14% experienced medial cartilage worsening at follow-up. The median (2.5–97.5th percentile) area under the receiver operating characteristic curve across the 100 held-out test sets was 0.73 (0.65–0.79). Baseline cartilage damage, higher Kellgren-Lawrence grade, greater pain during walking, higher lateral ground reaction force impulse, greater time spent lying and lower vertical ground reaction force unloading rate were associated with greater risk of cartilage worsening. Similar results were found for the subset of knees with baseline cartilage damage.ConclusionsA machine learning approach incorporating gait, physical activity and clinical/demographic features showed good performance for predicting cartilage worsening over 2 years. While identifying potential intervention targets from the model is challenging, lateral ground reaction force impulse, time spent lying and vertical ground reaction force unloading rate should be investigated further as potential early intervention targets to reduce medial tibiofemoral cartilage worsening.
When ACL reconstruction does not help: risk factors associated with not achieving the minimal important change for the KOOS Sport/Rec and QoL
Authors: Kaarre Janina , Simonson Rebecca , Ris Viktor , Snaebjörnsson Thorkell , Irrgang James J , Musahl Volker , Samuelsson Kristian , Hamrin Senorski Eric 
Published: March 2023

ObjectivesTo determine factors associated with not achieving a minimal important change (MIC) in the Knee injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation (Sport/Rec), and Knee-Related Quality of Life (QoL) subscales 1 year after anterior cruciate ligament reconstruction (ACL-R).MethodsThis study used data from the Swedish National Knee Ligament Registry. Multivariable logistic regression models were used to identify factors associated with not achieving a MIC. The change in the preoperative and postoperative KOOS Sport/Rec and QoL subscale scores were dichotomised based on not achieving MIC for both subscales versus achieving MIC for either one or both subscales. The MICs for the Sport/Rec and QoL subscales were 12.1 and 18.3, respectively, and were used to combine both subscales into a single variable (Sport & QoL).ResultsOf 16 131 included patients, 44% did not achieve the MIC for the combined Sport/Rec and QoL subscales 1 year after ACL-R. From the multivariable stepwise logistic regression, older patients (OR 0.91, 95% CI 0.88 to 0.94; p<0.0001), males (OR 0.93, 95% CI 0.87 to 0.99; p=0.034) and patients receiving hamstring tendon autograft ACL-R (OR 0.70, 95% CI 0.60 to 0.81; p<0.0001) had lower odds of not achieving the MIC 1 year after ACL-R compared with younger patients, females and patients receiving patellar tendon autograft. Furthermore, patients with cartilage injuries (OR 1.17, 95% CI 1.09 to 1.27; p<0.0001) and higher pre-operative KOOS Sport/Rec and QoL scores (OR 1.34, 95% CI 1.31 to 1.36; p<0.0001) had higher odds of not achieving the MIC.ConclusionYounger patients, females and patients with cartilage injuries and higher pre-operative Sport/Rec and QoL KOOS scores are less likely to benefit from ACL-R and subsequently, have a lower probability for improved Sport/Rec and QoL scores after ACL-R. Furthermore, graft choice may also affect the risk of not achieving the MIC.Level of evidenceRetrospective cohort study, level III.
Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study
Authors: O’Brien Kelly K , Brown Darren A , McDuff Kiera , St. Clair-Sullivan Natalie , Solomon Patricia , Chan Carusone Soo , McCorkell Lisa , Wei Hannah , Goulding Susie , O'Hara Margaret , Thomson Catherine , Roche Niamh , Stokes Ruth , Vera Jaime H , Erlandson Kristine M , Bergin Colm , Robinson Larry , Cheung Angela M , Torres Brittany , Avery Lisa , Bannan Ciaran , Harding Richard 
Published: March 2023

IntroductionOur aim was to describe episodic nature of disability among adults living with Long COVID.MethodsWe conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We recruited participants via collaborator community organisations in Canada, Ireland, UK and USA.We recruited adults who self-identified as living with Long COVID with diversity in age, gender, race/ethnicity, sexual orientation and duration since initial COVID infection between December 2021 and May 2022. We used a semistructured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis.ResultsAmong the 40 participants, the median age was 39 years (IQR: 32–49); majority were women (63%), white (73%), heterosexual (75%) and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterised by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with ‘ups and downs’, ‘flare-ups’ and ‘peaks’ followed by ‘crashes’, ‘troughs’ and ‘valleys’, likened to a ‘yo-yo’, ‘rolling hills’ and ‘rollercoaster ride’ with ‘relapsing/remitting’, ‘waxing/waning’, ‘fluctuations’ in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterised as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health.ConclusionAmong this sample of adults living with Long COVID, experiences of disability were described as episodic, characterised by fluctuating health challenges, which may be unpredictable in nature. Results can help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.
Risk factors for structural and functional progression of primary open-angle glaucoma in an African ancestry cohort
Authors: Salowe Rebecca J , Chen Yineng , Zenebe-Gete Selam , Lee Roy , Gudiseva Harini V , Di Rosa Isabel , Ross Ahmara G , Cui Qi N , Miller-Ellis Eydie , Addis Victoria , Sankar Prithvi S , Daniel Ebenezer , Ying Gui-shuang , O'Brien Joan M 
Published: March 2023

Background/aimsTo investigate the rates of structural and functional progression of primary open-angle glaucoma in an African ancestry cohort and identify risk factors for progression.MethodsThis retrospective study included 1424 eyes from glaucoma cases in the Primary Open-Angle African American Glaucoma Genetics cohort, with ≥2 visits for retinal nerve fibre layer (RNFL) thickness and mean deviation (MD) measurements over ≥6-month follow-up. The rates of structural progression (change in RNFL thickness/year) and functional progression (change in MD/year) were calculated from linear mixed effects models, accounting for intereye correlation and longitudinal correlation. Eyes were categorised as slow, moderate or fast progressors. Risk factors for progression rates were assessed using univariable and multivariable regression models.ResultsThe median (interquartile) rates of progression were −1.60 (−2.05 to –1.15) µm/year for RNFL thickness and −0.40 (−0.44 to –0.34) decibels/year for MD. Eyes were categorised as slow (structural: 19%, functional: 88%), moderate (structural: 54%, functional: 11%) and fast (structural: 27%, functional: 1%) progressors. In multivariable analysis, faster RNFL progression was independently associated with thicker baseline RNFL (p<0.0001), lower baseline MD (p=0.003) and beta peripapillary atrophy (p=0.03). Faster MD progression was independently associated with higher baseline MD (p<0.0001), larger cup-to-disc ratios (p=0.02) and lower body mass index (p=0.0004).ConclusionThe median rates of structural and functional progression in this African ancestry cohort were faster than the rates reported from previously published studies in other ethnic groups. Higher baseline RNFL thickness and MD values were associated with faster progression rates. Results highlight the importance of monitoring structural and functional glaucoma progression to provide timely treatment in early disease.
Efficacy and toxicity of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy
Authors: Bhave Prachi , Hong Angela , Lo Serigne N , Johnson Rebecca , Mangana Johanna , Johnson Douglas B , Dulgar Ozgecan , Eroglu Zeynep , Yeoh Hui-Ling , Haydon Andrew , Lodde Georg C , Livingstone Elisabeth , Khattak Adnan , Kähler Katharina , Hausschild Axel , McArthur Grant A , Menzies Alexander Maxwell , Long Georgina , Wang Wei , Carlino Matteo S 
Published: March 2023

BackgroundIn patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurrence within local nodal basins without improving overall survival or quality of life. However, the study was conducted prior to the current era of adjuvant systemic therapies and when CLND was the standard approach for microscopic nodal disease. As such, there is currently no data on the role of adjuvant RT in patients with melanoma who recur during or after adjuvant immunotherapy, including those that may or may not have undergone prior CLND. In this study, we aimed to answer this question.MethodsPatients with resected stage III melanoma who received adjuvant anti-programmed cell death protein-1 (PD-1) (±ipilimumab) immunotherapy with a subsequent locoregional (lymph node and/or in-transit metastases) recurrence were retrospectively identified. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was rate of subsequent locoregional recurrence; secondary outcomes were locoregional recurrence-free survival (lr-RFS2) and overall RFS (RFS2) to second recurrence.ResultsIn total, 71 patients were identified: 42 (59%) men, 30 (42%) BRAF V600E mutant, 43 (61%) stage IIIC at diagnosis. Median time to first recurrence was 7 months (1–44), 24 (34%) received adjuvant RT and 47 (66%) did not. Thirty-three patients (46%) developed a second recurrence at a median of 5 months (1–22). The rate of locoregional relapse at second recurrence was lower in those who received adjuvant RT (8%, 2/24) compared with those who did not (36%, 17/47, p=0.01). Adjuvant RT at first recurrence was associated with an improved lr-RFS2 (HR 0.16, p=0.015), with a trend towards an improved RFS2 (HR 0.54, p=0.072) and no effect on risk of distant recurrence or overall survival.ConclusionThis is the first study to investigate the role of adjuvant RT in patients with melanoma with locoregional disease recurrence during or after adjuvant anti-PD-1-based immunotherapy. Adjuvant RT was associated with improved lr-RFS2, but not risk of distant recurrence, demonstrating a likely benefit in locoregional disease control in the modern era. Further prospective studies are required to validate these results.
The role of Zn ions in the interaction between SARS-CoV-2 orf7a protein and BST2/tetherin
Authors: Botticelli S. , Chiaraluce R. , Consalvi V. , La Penna G. , Pasquo A. , Petrosino M. , Proux O. , Rossi G. C. , Stellato F. , Morante S. 
Published: March 2023

AbstractIn this paper, we provide evidence that Zn$$^{2+}$$

2
+

ions play a role in the SARS-CoV-2 virus strategy to escape the immune response mediated by the BST2-tetherin host protein. This conclusion is based on sequence analysis and molecular dynamics simulations as well as X-ray absorption experiments [1].
Non-invasive evidence of mercury soaps in painted miniatures on ivory
Authors: Garrappa Silvia , Bezdička Petr , Švarcová Silvie , Hradilová Janka , Pech Michal , Hradil David 
Published: March 2023

AbstractThis work focuses on a non-invasive study of two selected painted miniature portraits on ivory to describe the degradation processes resulting from the interaction between mercury-based and lead-based pigments with oils. In the studied miniatures, containing both lead white and cinnabar, the formation of metal soaps has been clearly detected. However, until now they have been identified exclusively as lead soaps. In this study, the formation of mercury soaps has been evidenced in painted artworks for the first time, together with the well-known lead soaps. The fully non-invasive analytical approach involved the use of large-area X-ray fluorescence scanning, X-ray powder diffraction and Fourier transform infrared spectroscopy accompanied by Raman spectroscopy. It enabled complex description of the miniatures, leading to both the identification and the deduction of approximate composition of mercury soaps. In addition, approximate calculations of the amount of pigments consumed by saponification unveiled the complex processes taking place in the oil-based paint containing both cinnabar and lead white, which were further studied within long-term model experiments monitored by both Fourier transform infrared spectroscopy and X-ray powder diffraction.
Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib plus Osimertinib in an EGFR Mutation–Positive, MET-Amplified Non–Small Cell Lung Cancer Model
Authors: Jones Rhys D.O. , Petersson Klas , Tabatabai Areya , Bao Larry , Tomkinson Helen , Schuller Alwin G. 
Published: March 2023

Abstract
Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor (TKI) recommended as first-line treatment for patients with locally advanced/metastatic EGFR mutation–positive (EGFRm) non–small cell lung cancer (NSCLC). However, MET amplification/overexpression is a common acquired osimertinib resistance mechanism. Savolitinib is an oral, potent, and highly selective MET-TKI; preliminary data suggest that combining osimertinib with savolitinib may overcome MET-driven resistance.
A patient-derived xenograft (PDX) mouse model with EGFRm, MET-amplified NSCLC was tested with a fixed osimertinib dose [10 mg/kg for exposures equivalent to (≈)80 mg], combined with doses of savolitinib (0–15 mg/kg, ≈0–600 mg once daily), both with 1-aminobenzotriazole (to better match clinical half-life). After 20 days of oral dosing, samples were taken at various time points to follow the time course of drug exposure in addition to phosphorylated MET and EGFR (pMET and pEGFR) change. Population pharmacokinetics, savolitinib concentration versus percentage inhibition from baseline in pMET, and the relationship between pMET and tumor growth inhibition (TGI) were also modeled.
As single agents, savolitinib (15 mg/kg) showed significant antitumor activity, reaching ∼84% TGI, and osimertinib (10 mg/kg) showed no significant antitumor activity (34% TGI, P &gt; 0.05 vs. vehicle). Upon combination, at a fixed dose of osimertinib, significant savolitinib dose-related antitumor activity was shown, ranging from 81% TGI (0.3 mg/kg) to 84% tumor regression (15 mg/kg). Pharmacokinetic–pharmacodynamic modeling showed that the maximum inhibition of both pEGFR and pMET increased with increasing savolitinib doses.
Savolitinib demonstrated exposure-related combination antitumor activity when combined with osimertinib in the EGFRm MET-amplified NSCLC PDX model.
Acute Influenza Infection Promotes Lung Tumor Growth by Reprogramming the Tumor Microenvironment
Authors: Garmendia Irati , Varthaman Aditi , Marmier Solenne , Angrini Mahmud , Matchoua Ingrid , Darbois-Delahousse Aurelie , Josseaume Nathalie , Foy Pierre-Emmanuel , Roumenina Lubka T. , Naouar Naïra , Meylan Maxime , Sibéril Sophie , Russick Jules , Joubert Pierre-Emmanuel , Leroy Karen , Damotte Diane , Mansuet-Lupo Audrey , Wislez Marie , Alifano Marco , Menger Laurie , Garcia-Verdugo Ignacio , Sallenave Jean-Michel , Lantz Olivier , Petitprez Florent , Cremer Isabelle 
Published: March 2023

AbstractOne billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on the composition of the tumor microenvironment (TME) and the clinical outcome of patients with NSCLC is largely unknown. We set out to understand how IAV load impacts cancer growth and modifies cellular and molecular players in the TME. Herein, we report that IAV can infect both tumor and immune cells, resulting in a long-term protumoral effect in tumor-bearing mice. Mechanistically, IAV impaired tumor-specific T-cell responses, led to the exhaustion of memory CD8+ T cells and induced PD-L1 expression on tumor cells. IAV infection modulated the transcriptomic profile of the TME, fine-tuning it toward immunosuppression, carcinogenesis, and lipid and drug metabolism. Consistent with these data, the transcriptional module induced by IAV infection in tumor cells in tumor-bearing mice was also found in human patients with lung adenocarcinoma and correlated with poor overall survival. In conclusion, we found that IAV infection worsened lung tumor progression by reprogramming the TME toward a more aggressive state.
Sepsis biomarkers: a review of the diagnostic value of presepsin
Authors: Ferreira Thalissa , Candido Marcelo Arruda , Soriano Francisco Garcia 
Published: March 2023

Sepsis is a prevalent syndrome with high morbimortality, so an efficient early diagnostic method is needed. Recent studies suggest that presepsin could be a potential biomarker to sepsis diagnosis and has a better performance than other more consolidated biomarkers, such as procalcitonin and CRP. This systematic review aims to develop assess the accuracy to sepsis diagnosis of the presepsin and compare with procalcitonin and C-reactive protein. A comprehensive systematic research was conducted in the PubMed and Virtual Health Library to collect studies published in the last two years that focused on presepsin diagnostic accuracy for sepsis. Eight studies were selected. All of them suggested that presepsin has some diagnostic value for sepsis. In four studies presepsin had a better performance than procalcitonin and in two studies presepsin performed better than CRP. Two studies did not show significant differences between presepsin and the other biomarkers. This review indicates that presepsin may have significant value for the early diagnosis of sepsis, corroborating to increase the efficiency of existing tools, such as CRP and procalcitonin. However, more studies are needed to confirm its efficiency as a single diagnosis’s marker.