bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease
Authors: Trebicka Jonel , Gu Wenyi , de Ledinghen Victor , Aubé Christophe , Krag Aleksander , Praktiknjo Michael , Castera Laurent , Dumortier Jerome , Bauer David Josef Maria , Friedrich-Rust Mireen , Pol Stanislas , Grgurevic Ivica , Zheng Rongqin , Francque Sven , Gottfriedovà Halima , Mustapic Sanda , Sporea Ioan , Berzigotti Annalisa , Uschner Frank Erhard , Simbrunner Benedikt , Ronot Maxime , Cassinotto Christophe , Kjaergaard Maria , Andrade Filipe , Schulz Martin , Semmler Georg , Drinkovic Ida Tjesic , Chang Johannes , Brol Maximilian Joseph , Rautou Pierre Emmanuel , Vanwolleghem Thomas , Strassburg Christian P , Boursier Jerome , Ferstl Philip Georg , Rasmussen Ditlev Nytoft , Reiberger Thomas , Vilgrain Valerie , Guibal Aymeric , Guillaud Olivier , Zeuzem Stefan , Vassord Camille , Lu Xue , Vonghia Luisa , Senkerikova Renata , Popescu Alina , Margini Cristina , Wang Wenping , Thiele Maja , Jansen Chrisitan 
Published: January 2021

ObjectiveLiver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.DesignThis international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.ResultsAfter screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.ConclusionThe M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
Large granular lymphocyte leukaemia study at the University Hospital of Donostia
Authors: Uranga Alasne , González Carmen , Furundarena J R , Robado Naiara , Rey Mercedes , Aragon Larraitz , Urreta Iratxe , Aranbarri Ane , De Juan Maria Dolores , Araiz Maria 
Published: January 2021

IntroductionLarge granular lymphocyte (LGL) leukaemia is considered a mature T-cell or natural killer (NK) cell neoplasm, characterised by a clonal proliferation of LGL.AimsTo analyse the characteristics and to establish (if possible) the prognostic parameters of these patients diagnosed in a single centre: University Hospital of Donostia.MethodsWe retrospectively studied data about 308 patients with LGL leukaemia diagnosed in our centre.ResultsThe frequency of T-LGL leukaemia and chronic lymphoproliferative disorder of NK cells was 89% and 6.8% respectively, and no aggressive NK-LGL leukaemia was seen in our population. The median age at diagnosis was 65.7 years and male-to-female ratio was 1.08. 59% of our patients were asymptomatic at the time of diagnosis. Most patients presented lymphocytosis and 63.6% more than 20% LGLs in the peripheral blood count, but it has to be taken into account that these results may be influenced by the selection bias of our study, as we recognised these patients as ‘alarms of the laboratory analysers’. Neutropenia was the most common cytopenia, and autoimmune disorders were described in 16.5% of the patients. Only 12 patients (3.9%) required treatment, a much lower percentage that the one reported in the literature, and this is consistent with the fact that patients were less symptomatic than in other series, as we expected. The 5-year and 15-year overall survival was 92% and 87%, respectively.ConclusionsOur patients may represent the even more benign end of the spectrum of clonal T LGL and NK proliferations.
Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund’s adjuvant, cyclophosphamide, and polyICLC (Mel63)
Authors: Slingluff, Jr. Craig L , Petroni Gina R , Chianese-Bullock Kimberly A , Wages Nolan A , Olson Walter C , Smith Kelly T , Haden Kathleen , Dengel Lynn T , Dickinson Anna , Reed Caroline , Gaughan Elizabeth M , Grosh William W , Kaur Varinder , Varhegyi Nikole , Smolkin Mark , Galeassi Nadejda V , Deacon Donna , Hall Emily H 
Published: January 2021

BackgroundPeptide vaccines designed to stimulate melanoma-reactive CD4+ T cells can induce T cell and antibody (Ab) responses, associated with enhanced overall survival. We hypothesized that adding toll-like receptor 3 agonist polyICLC to an incomplete Freund’s adjuvant (IFA) would be safe and would support strong, durable CD4+ T cell and Ab responses. We also hypothesized that oral low-dose metronomic cyclophosphamide (mCy) would be safe, would reduce circulating regulatory T cells (T-regs) and would further enhance immunogenicity.Participants and methodsAn adaptive design based on toxicity and durable CD4+ T cell immune response (dRsp) was used to assign participants with resected stage IIA-IV melanoma to one of four study regimens. The regimens included a vaccine comprising six melanoma peptides restricted by Class II MHC (6MHP) in an emulsion with IFA alone (Arm A), with IFA plus systemic mCy (Arm B), with IFA+ local polyICLC (Arm C), or with IFA+ polyICLC+ mCy (Arm D). Toxicities were recorded (CTCAE V.4.03). T cell responses were measured by interferon γ ELIspot assay ex vivo. Serum Ab responses to 6MHP were measured by ELISA. Circulating T-regs were assessed by flow cytometry.ResultsForty-eight eligible participants were enrolled and treated. Early data on safety and dRsp favored enrollment on arm D. Total enrollment on Arms A-D were 3, 7, 6, and 32, respectively. Treatment-related dose-limiting toxicities (DLTs) were observed in 1/7 (14%) participants on arm B and 2/32 (6%) on arm D. None exceeded the 25% DLT threshold for early closure to enrollment for any arm. Strong durable T cell responses to 6MHP were detected ex vivo in 0%, 29%, 67%, and 47% of participants on arms A-D, respectively. IgG Ab responses were greatest for arms C and D. Circulating T-regs frequencies were not altered by mCy.Conclusions6MHP vaccines administered with IFA, polyICLC, and mCy were well tolerated. The dRsp rate for arm D of 47% (90% CI 32 to 63) exceeded the 18% (90% CI 11 to 26) rate previously observed with 6MHP in IFA alone. Vaccination with IFA+ polyICLC (arm C) also showed promise for enhancing T cell and Ab responses.
CD8+CD103+ tissue-resident memory T cells convey reduced protective immunity in cutaneous squamous cell carcinoma
Authors: Lai Chester , Coltart George , Shapanis Andrew , Healy Conor , Alabdulkareem Ahmad , Selvendran Sara , Theaker Jeffrey , Sommerlad Matthew , Rose-Zerilli Matthew , Al-Shamkhani Aymen , Healy Eugene 
Published: January 2021

BackgroundTumor infiltrating lymphocytes play a key role in antitumor responses; however, while several memory T-cell subtypes have been reported in inflammatory and neoplastic conditions, the proportional representation of the different subsets of memory T cells and their functional significance in cancer is unclear. Keratinocyte skin cancer is one of the most common cancers globally, with cutaneous squamous cell cancer (cSCC) among the most frequent malignancies capable of metastasis.MethodsMemory T-cell subsets were delineated in human cSCCs and, for comparison, in non-lesional skin and blood using flow cytometry. Immunohistochemistry was conducted to quantify CD103+ cells in primary human cSCCs which had metastasized (P-M) and primary cSCCs which had not metastasized (P-NM). TIMER2.0 (timer.cistrome.org) was used to analyze TCGA cancer survival data based onITGAEexpression. Immunofluorescence microscopy was performed to determine frequencies of CD8+CD103+ cells in P-M and P-NM cSCCs.ResultsDespite intertumoral heterogeneity, most cSCC T cells were CCR7−/CD45RA− effector/resident memory (TRM) lymphocytes, with naive, CD45RA+/CCR7− effector memory re-expressing CD45RA, CCR7+/L-selectin+ central memory and CCR7+/L-selectin− migratory memory lymphocytes accounting for smaller T-cell subsets. The cSCC CD8+ T-cell population contained a higher proportion of CD69+/CD103+ TRMs than that in non-lesional skin and blood. These cSCC CD69+/CD103+ TRMs exhibited increased IL-10 production, and higher CD39, CTLA-4 and PD-1 expression compared with CD103− TRMs in the tumor. CD103+ cells were more frequent in P-M than P-NM cSCCs. Analysis of TCGA data demonstrated that high expression ofITGAE(encoding CD103) was associated with reduced survival in primary cutaneous melanoma, breast carcinoma, renal cell carcinoma, kidney chromophobe cancer, adrenocortical carcinoma and lower grade glioma. Immunofluorescence microscopy showed that the majority of CD103 was present on CD8+ T cells and that CD8+CD103+ cells were significantly more frequent in P-M than P-NM cSCCs.ConclusionThese results highlight CD8+CD103+ TRMs as an important functional T-cell subset associated with poorer clinical outcome in this cancer.
Monitored anesthesia care during mechanical thrombectomy for stroke: need for data-driven and individualized decisions
Authors: Nogueira Raul G , Mohammaden Mahmoud H , Moran Timothy P , Whalin Matthew K , Gershon Raphael Y , Al-Bayati Alhamza R R , Ratcliff Jonathan , Pisani Leonardo , Liberato Bernardo , Bhatt Nirav , Frankel Michael R , Haussen Diogo C 
Published: January 2021

BackgroundThe optimal anesthesia management for patients with stroke undergoing mechanical thrombectomy (MT) during the COVID-19 pandemic has become a matter of controversy. Some recent guidelines have favored general anesthesia (GA) in patients perceived as high risk for intraprocedural conversion from sedation to GA, including those with dominant hemispheric occlusions/aphasia or baseline National Institutes of Health Stroke Scale (NIHSS) score >15. We aim to identify the rate and predictors of conversion to GA during MT in a high-volume center where monitored anesthesia care (MAC) is the default modality.MethodsA retrospective review of a prospectively maintained MT database from January 2013 to July 2020 was undertaken. Analyses were conducted to identify the predictors of intraprocedural conversion to GA. In addition, we analyzed the GA conversion rates in subgroups of interest.ResultsAmong 1919 MT patients, 1681 (87.6%) started treatment under MAC (median age 65 years (IQR 55–76); baseline NIHSS 16 (IQR 11–21); 48.4% women). Of the 1677 eligible patients, 26 (1.6%) converted to GA including 1.4% (22/1615) with anterior and 6.5% (4/62) with posterior circulation strokes. The only predictor of GA conversion was posterior circulation stroke (OR 4.99, 95% CI 1.67 to 14.96, P=0.004). The conversion rates were numerically higher in right than in left hemispheric occlusions (1.6% vs 1.2%; OR 1.37, 95% CI 0.59 to 3.19, P=0.47) and in milder than in more severe strokes (NIHSS ≤15 vs >15: 2% vs 1.2%; OR 0.62, 95% CI 0.28 to 1.36, P=0.23).ConclusionsOur study showed that the overall rate of conversion from MAC to GA during MT was low (1.6%) and, while higher in posterior circulation strokes, it was not predicted by either hemispheric dominance or stroke severity. Caution should be given before changing clinical practice during moments of crisis.
Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments
Authors: Garcia-Aymerich Judith , Puhan Milo A , Corriol-Rohou Solange , de Jong Corina , Demeyer Heleen , Dobbels Fabienne , Erzen Damijan , Frei Anja , Gimeno-Santos Elena , Hopkinson Nicholas S , Ivanoff Nathalie , Karlsson Niklas , Louvaris Zafeiris , Polkey Michael I , Rabinovich Roberto A , Scuri Mario , Tabberer Maggie , Vogiatzis Ioannis , Troosters Thierry 
Published: January 2021

BackgroundThe Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients’ experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.ObjectiveTo test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.MethodsWe used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.ResultsWe included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score.ConclusionsThe D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.
Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers
Authors: Zhang Yingze , Tedrow John , Nouraie Mehdi , Li Xiaoyun , Chandra Divay , Bon Jessica , Kass Daniel J , Fuhrman Carl R , Leader Joseph K , Duncan Steven R , Kaminski Naftali , Sciurba Frank C 
Published: January 2021

BackgroundPentraxin 3 (PTX3) influences innate immunity and inflammation, host defence, the complement cascade and angiogenesis. PTX3 expression in lung and blood of subjects with tobacco exposure, and its potential relationship with disease pattern and clinical outcome are poorly understood.MethodsUsing independent platforms and cohorts, we identified associations of PTX3 gene expression in lung tissue and plasma from current and former tobacco smokers (with and without chronic obstructive pulmonary disease, COPD) to disease phenotypes including quantitative CT determined emphysema, lung function, symptoms and survival. Two putative regulatory variants of the PTX3 gene were examined for association with COPD manifestations. The relationship between plasma PTX3 and hyaluronic acid levels was further examined.ResultsPTX3 gene expression in lung tissue was directly correlated with emphysema severity (p<0.0001). Circulating levels of PTX3 were inversely correlated with FEV1 (p=0.006), and positively associated with emphysema severity (p=0.004) and mortality (p=0.008). Two PTX3 gene regulatory variants were associated with a lower risk for emphysema and expiratory airflow obstruction, and plasma levels of PTX3 and hyaluronic acid were related.ConclusionsThese data show strong and overlapping associations of lung and blood PTX3 levels, and PTX3 regulatory gene variants, with the severity of airflow obstruction, emphysema and mortality among smokers. These findings have potential implications regarding the pathogenesis of smoking-related lung diseases and warrant further exploration for the use of PTX3 as a predictive biomarker.
An enhanced care package to improve asthma management in Malawian children: a randomised controlled trial
Authors: Rylance Sarah , Chinoko Beatrice , Mnesa Bright , Jewell Chris , Grigg Jonathan , Mortimer Kevin 
Published: January 2021

Background
Shortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles.

Methods
We conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6–15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence.

Findings
Between September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, p<0.001). Fewer intervention children attended emergency healthcare (7.3% vs 25.4%, p=0.02) and missed school (20.0% vs 62.7%, p<0.001) compared with standard care children.

Interpretation
The intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings.

Trial registration number
PACTR201807211617031.
Long-term changes in body condition and gillnet selectivity in Lake Constance pelagic spawning whitefish (Coregonus wartmanni)
Authors: DeWeber J. Tyrell , Rösch Roland , Baer Jan , Brinker Alexander 
Published: January 2021

The body condition of Lake Constance pelagic spawning whitefish (Coregonus wartmanni) has changed substantially during the past century and altered the length-based selectivity of gillnets. Linked hierarchical models using Bayesian inference and error propagation were used to estimate the monthly body condition of whitefish from 1932 to 2018 and condition-dependent gillnet selectivity from 1964 to 2018. As expected, body condition followed past trends in nutrient dynamics and was highest in summer months. Body condition was clearly linked to gillnet selectivity, with a weight increase of a 300 mm whitefish from 205 to 260 g predicted to reduce the mean (from 374 to 330 mm) and standard deviation (from 30.8 to 25.1 mm) of lengths selected by a 38 mm mesh gillnet. Simulations demonstrate that such changes can reduce the mean age in harvest by over 1 year and greatly bias population age distribution estimates if selectivity changes are ignored. Similar variation in gillnet selectivity is expected where trophic conditions or other factors cause body condition differences, and accounting for these changes could reduce biases to inform fishery management.
A unified quark-nuclear matter equation of state from the cluster virial expansion within the generalized Beth–Uhlenbeck approach
Authors: Bastian Niels-Uwe Friedrich , Blaschke David Bernhard 
Published: January 2021

AbstractWe consider a cluster expansion for strongly correlated quark matter where the clusters are baryons with spectral properties that are described within the generalized Beth–Uhlenbeck approach by a medium dependent phase shift. We employ a simple ansatz for the phase shift which describes an on-shell bound state with an effective mass and models the continuum by an anti-bound state located at the mass of the three-quark continuum threshold, so that the Levinson theorem is fulfilled by construction. The quark and baryon interactions are accounted for by the coupling to scalar and vector meson mean fields modelled by density functionals. At increasing density and temperature, due to the different medium-dependence of quark and baryon masses, the Mott dissociation of baryons occurs and its contributions to the thermodynamics vanish. It is demonstrated on this simple example that this unified approach to quark-hadron matter is capable of describing crossover as well as first order phase transition behaviour in the phase diagram with a critical endpoint. Changing the meson mean field, the case of a “crossover all over” in the phase diagram is also obtained.
Mean-field BCS theory of the Meissner effect in bulk revisited
Authors: Bányai Ladislaus Alexander 
Published: January 2021

Abstract
We show that the implementation of the $$1/ c^2 $$

1
/

c
2

transverse current–current interaction between electrons resulting from the non-relativistic QED into the standard self-consistent electron BCS model in bulk under thermal equilibrium in the stable superconductive phase ensures the full compensation of a constant external magnetic field by the internal magnetic field created by the electrons, i.e. one has an ideal diamagnet.

GraphicAbstract
Non-linear plane gravitational waves as space-time defects
Authors: Carneiro F. L. , Ulhoa S. C. , Maluf J. W. , da Rocha-Neto J. F. 
Published: January 2021

AbstractWe consider non-linear plane gravitational waves as propagating space-time defects, and construct the Burgers vector of the waves. In the context of classical continuum systems, the Burgers vector is a measure of the deformation of the medium, and at a microscopic (atomic) scale, it is a naturally quantized object. One purpose of the present article is ultimately to probe an alternative way on how to quantize plane gravitational waves.
Induced THz transitions in Rydberg caesium atoms for application in antihydrogen experiments
Authors: Vieille-Grosjean M. , Dimova E. , Mazzotta Z. , Comparat D. , Wolz T. , Malbrunot C. 
Published: January 2021

Abstract
Antihydrogen atoms are produced at CERN in highly excited Rydberg states. However, precision measurements require anti-atoms in ground state. Whereas experiments currently rely on spontaneous emission only, simulations have shown that THz light can be used to stimulate the decay towards ground state and thus increase the number of anti-atoms available for measurements. We review different possibilities at hand to generate light in the THz range required for the purpose of stimulated deexcitation. We demonstrate the effect of a blackbody type light source, which however presents drawbacks for this application including strong photoionization. Further, we report on the first THz transitions in a beam of Rydberg caesium atoms induced by photomixers and conclude with the implications of the results for the antihydrogen case.

Graphic abstract