bluuebunny/crossref_metadata_2025_split huggingface dataset:
Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH)
Authors: Gordon Victoria Mary , Adhikary Ratul , Aithal Guruprasad P , Appleby Victoria , Das Debasish , Day James , Delahooke Toby , Dixon Selena , Elphick David , Hardie Claire , Heneghan Michael , Hoeroldt Barbara , Hooper Patricia , Hutchinson John , Jones Rebecca L , Khan Faisal , Metcalf Jane , Nkhoma Alick , Pelitari Stavroula , Prince Martin , Prosser Annell , Saksena Sushma , Sathyanarayana Vinay , Vani Deven , Yeoman Andrew , Gleeson Dermot 
Published: May 2021

BackgroundAutoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals.MethodsCentres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool.ResultsHospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3–23) gastroenterologists; including 3 (0–10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18–100) of all consultants managing AIH: in DGH’s 92% (20–100) vs 46% (17–100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital.ConclusionManagement of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.
Machine learning model for predicting out-of-hospital cardiac arrests using meteorological and chronological data
Authors: Nakashima Takahiro , Ogata Soshiro , Noguchi Teruo , Tahara Yoshio , Onozuka Daisuke , Kato Satoshi , Yamagata Yoshiki , Kojima Sunao , Iwami Taku , Sakamoto Tetsuya , Nagao Ken , Nonogi Hiroshi , Yasuda Satoshi , Iihara Koji , Neumar Robert , Nishimura Kunihiro 
Published: May 2021

ObjectivesTo evaluate a predictive model for robust estimation of daily out-of-hospital cardiac arrest (OHCA) incidence using a suite of machine learning (ML) approaches and high-resolution meteorological and chronological data.MethodsIn this population-based study, we combined an OHCA nationwide registry and high-resolution meteorological and chronological datasets from Japan. We developed a model to predict daily OHCA incidence with a training dataset for 2005–2013 using the eXtreme Gradient Boosting algorithm. A dataset for 2014–2015 was used to test the predictive model. The main outcome was the accuracy of the predictive model for the number of daily OHCA events, based on mean absolute error (MAE) and mean absolute percentage error (MAPE). In general, a model with MAPE less than 10% is considered highly accurate.ResultsAmong the 1 299 784 OHCA cases, 661 052 OHCA cases of cardiac origin (525 374 cases in the training dataset on which fourfold cross-validation was performed and 135 678 cases in the testing dataset) were included in the analysis. Compared with the ML models using meteorological or chronological variables alone, the ML model with combined meteorological and chronological variables had the highest predictive accuracy in the training (MAE 1.314 and MAPE 7.007%) and testing datasets (MAE 1.547 and MAPE 7.788%). Sunday, Monday, holiday, winter, low ambient temperature and large interday or intraday temperature difference were more strongly associated with OHCA incidence than other the meteorological and chronological variables.ConclusionsA ML predictive model using comprehensive daily meteorological and chronological data allows for highly precise estimates of OHCA incidence.
Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection
Authors: Kotecha Deevia , Garcia-Guimaraes Marcos , Premawardhana Diluka , Pellegrini Dario , Oliver-Williams Clare , Bountziouka Vasiliki , Wood Alice , Natarajan Nalin , Jackson Robert , Chan Nathan , Ziaullah Jan , Rakhit Roby D , Hoole Stephen P , Johnson Tom W , Kadziela Jacek , Ludman Peter , Samani Nilesh J , Maas Angela H E M , van Geuns Robert-Jan , Alfonso Fernando , Adlam David 
Published: May 2021

ObjectiveTo investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.MethodsSCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).ResultsSCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06–3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38–3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12–7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29–61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.ConclusionWhile a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.
NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy
Authors: Miyazaki Takahiro , Maiti Mekhala , Hennessy Marlene , Chang Thomas , Kuo Peiwen , Addepalli Murali , Obalapur Palakshi , Sheibani Sara , Wilczek Joanna , Pena Rhoneil , Quach Phi , Cetz Janet , Moffett Andrew , Tang Yinyan , Kirk Peter , Huang Jicai , Sheng Dawei , Zhang Ping , Rubas Werner , Madakamutil Loui , Kivimäe Saul , Zalevsky Jonathan 
Published: May 2021

BackgroundNKTR-255 is a novel polyethylene glycol-conjugate of recombinant human interleukin-15 (rhIL-15), which was designed to retain all known receptor binding interactions of the IL-15 molecule. We explored the biologic and pharmacologic differences between endogenous IL-15 receptor α (IL-15Rα)-dependent (NKTR-255 and rhIL-15) and IL-15Rα-independent (precomplexed rhIL-15/IL-15Rα) cytokines.MethodsIn vitro pharmacological properties of rhIL-15, NKTR-255 and precomplex cytokines (rhIL-15/IL-15Rα and rhIL-15 N72D/IL-15Rα Fc) were investigated in receptor binding, signaling and cell function. In vivo pharmacokinetic (PK) and pharmacodynamic profile of the cytokines were evaluated in normal mice. Finally, immunomodulatory effect and antitumor activity were assessed in a Daudi lymphoma model.ResultsNKTR-255 and rhIL-15 exhibited similar in vitro properties in receptor affinity, signaling and leukocyte degranulation, which collectively differed from precomplexed cytokines. Notably, NKTR-255 and rhIL-15 stimulated greater granzyme B secretion in human peripheral blood mononuclear cells versus precomplexed cytokines. In vivo, NKTR-255 exhibited a PK profile with reduced clearance and a longer half-life relative to rhIL-15 and demonstrated prolonged IL-15R engagement in lymphocytes compared with only transient engagement observed for rhIL-15 and precomplexed rhIL-15 N72D/IL-15Rα Fc. As a consequent, NKTR-255 provided a durable and sustained proliferation and activation of natural killer (NK) and CD8+T cells. Importantly, NKTR-255 is more effective than the precomplexed cytokine at inducing functionally competent, cytotoxic NK cells in the tumor microenvironment and the properties of NKTR-255 translated into superior antitumor activity in a B-cell lymphoma model versus the precomplexed cytokine.ConclusionsOur results show that the novel immunotherapeutic, NKTR-255, retains the full spectrum of IL-15 biology, but with improved PK properties, over rhIL-15. These findings support the ongoing phase 1 first-in-human trial (NCT04136756) of NKTR-255 in participants with relapsed or refractory hematologic malignancies, potentially advancing rhIL-15-based immunotherapies for the treatment of cancer.
FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I–III
Authors: Jiang Minlin , Wu Chunyan , Zhang Liping , Sun Chenglong , Wang Hao , Xu Yi , Sun Hui , Zhu Jun , Zhao Wencheng , Fang Qiyu , Yu Jia , Chen Peixin , Wu Shengyu , Zheng Zixuan , He Yayi , Zhou Caicun 
Published: May 2021

BackgroundImmunotherapies may prolong the survival of patients with small-cell lung cancer (SCLC) to some extent. The role of forkhead box protein P3 (FOXP3) in tumor microenvironment (TME) remains controversial. We aimed to examine FOXP3-related expression characteristics and prognostic values and to develop a clinically relevant predictive system for SCLC.MethodsWe enrolled 102 patients with histologically confirmed SCLC at stages I–III. Through immunohistochemistry, we determined the expression pattern of FOXP3 and its association with other immune biomarkers. By machine learning and statistical analysis, we constructed effective immune risk score models. Furthermore, we examined FOXP3-related enrichment pathways and TME traits in distinct cohorts.ResultsIn SCLC, FOXP3 level was significantly associated with status of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), CD4, CD8, and CD3 (p=0.002, p=0.001, p=0.002, p=0.030, and p<0.001). High FOXP3 expression showed longer relapse-free survival (RFS) than the low-level group (41.200 months, 95% CI 26.937 to 55.463, vs 14.000 months, 95% CI 8.133 to 19.867; p=0.008). For tumor-infiltrating lymphocytes (TILs), subgroup analysis demonstrated FOXP3 and PD-1, PD-L1, lymphocyte activation gene-3, CD3, CD4, or CD8 double positive were significantly correlated with longer RFS. We further performed importance evaluation for immune biomarkers, constructed an immune risk score incorporating the top three important biomarkers, FOXP3, TIL PD-L1, and CD8, and found their independently prognostic role to predict SCLC relapse. Better predictive performance was achieved in this immune risk model compared with single-indicator-based or two-indicator-based prediction systems (area under the curve 0.715 vs 0.312–0.711). Then, relapse prediction system integrating clinical staging and immune risk score was established, which performed well in different cohorts. High FOXP3-related genes were enriched in several immune-related pathways, and the close relationships of interleukin-2,CD28, basic excision repair genesMUTYH,POLD1,POLD2, and oxidative phosphorylation related gene cytochrome c oxidase subunit 8A with FOXP3 expression were revealed. Moreover, we found low-immune risk score group had statistically higher activated CD4+memory T cells (p=0.014) and plasma cells (p=0.049) than the high-risk group. The heterogeneity of tumor-infiltrating immune cells might represent a promising feature for risk prediction in SCLC.ConclusionFOXP3 interacts closely with immune biomarkers on tumor-infiltrating cells in TME. This study highlighted the crucial prognostic value and promising clinical applications of FOXP3 in SCLC.
Leveraging physician leadership in healthtech startups in India
Authors: Raj Ankit 
Published: May 2021

BackgroundIndia has seen a rapid surge in health tech startups that have disrupted many aspects of the healthcare industry. While positive trends have emerged in online pharmacy, telemedicine, and medical education; we are still to see these health tech startups create similar dividends in other aspects of healthcare especially in direct care and treatment. While startups have grown leaps and bounds in multiple industries, health tech startups have not grown to the same extent. There are many existing factors for this supposedly lackluster performance. The author discusses one of these factors contributing to the slow growth of health tech startups in India.ConclusionThe author highlights the lack of intent from the top leadership and executive bodies of these startups to involve physicians at all levels of decision making. A lack of insights from professionals directly involved with the functioning of healthcare and lack of inexperience from outsiders managing these startups may have contributed to this slow growth of health tech startups in India. The author further discusses possible solutions and key factors that can help contribute to better engagement of physicians in decision-making tables of the health tech startups.
Right atrium and cryptogenic ischaemic stroke in the young: a case–control study
Authors: Pöyhönen Pauli , Kuusisto Jouni , Pirinen Jani , Räty Heli , Lehmonen Lauri , Paakkanen Riitta , Martinez-Majander Nicolas , Gerdts Eva , Putaala Jukka , Sinisalo Juha , Järvinen Vesa 
Published: May 2021

BackgroundRecent studies suggest left atrial (LA) dysfunction in cryptogenic stroke. We studied the dynamics of right atrium (RA) and right atrial appendage (RAA) in young adults with cryptogenic stroke. We hypothesised that bi-atrial dysfunction and blood stagnation might contribute to thrombosis formation in patients with patent foramen ovale (PFO), as deep venous thrombosis is detected only in the minority of patients.MethodsThirty patients (aged 18–49) with a first-ever cryptogenic stroke and 30 age-matched and sex-matched stroke-free controls underwent cardiac magnetic resonance (CMR) imaging. An approach to estimate the RAA volume was developed, using crista terminalis and pectinate muscles as anatomical landmarks. Atrial expansion indices were calculated as (maximal volume – minimal volume) ×100%/minimal volume. Total pulmonary to systemic blood flow ratio (Qp/Qs) was based on phase contrast CMR. Right-to-left shunt (RLS) was evaluated with transoesophageal echocardiography in 29 patients and transcranial Doppler in 30 controls, moderate-to-severe RLS considered as clinically significant.ResultsWe found that RA and RAA volumes were similar between patients and controls. Also, RA expansion index was similar, but RAA (95.6%±21.6% vs 108.7%±25.8%, p=0.026) and LA (126.2%±28% vs 144.9%±36.3%, p=0.023) expansion indices were lower in patients compared with controls. Seven (24%) of 29 patients had an RLS compared with 1 (3%) of 30 controls (p=0.012). Among 59 study subjects, RLS was associated with lower RA (81.9%±15.9% vs 98.5%±29.5%, p=0.030), RAA (84.7%±18% vs 105.6%±24.1%, p=0.022), LA (109.8%±18.6% vs 140.1%±33.7%, p=0.017) and LAA (median 102.9% (IQR 65.6%–121.7%) vs 229.1% (151.8%–337.5%], p=0.002) expansion indices and lower Qp/Qs ratio (0.91±0.06 vs 0.98±0.07, p=0.027).ConclusionsThis study suggests bi-atrial dysfunction in young adults with cryptogenic stroke, associated with moderate-to-severe RLS. Dysfunction of the atria and atrial appendages may be an additional mechanism for PFO-related stroke.Trial registration numberNCT01934725.
Soil-water retention behaviour of fine/coarse soil mixture with varying coarse grain contents and fine soil dry densities
Authors: Su Yu , Cui Yu-Jun , Dupla Jean-Claude , Canou Jean 
Published: May 2021

The interlayer soil identified in conventional French rail track corresponds to a mixture of fine soil and coarse grains. To investigate the role of fines in the soil-water retention property of such a mixture, different coarse grain contents fv and dry densities of fine soil ρd–f were considered. The filter paper method was applied to measure matric suction. Mercury intrusion porosimetry tests were performed to observe the microstructure of the fine soil. In terms of the gravimetric water content of fine soil wf with matric suction ψ, the soil-water retention curve (SWRC) was significantly affected by ρd–f for ψ < 715 kPa, while independent of ρd–f for ψ > 715 kPa. Interestingly, this threshold ψ corresponded to a delimiting pore diameter of the bi-modal microstructure of fine soil, which separated micropores from macropores. In terms of degree of saturation Sr with ψ, the SWRC was significantly affected by ρd–f in the full suction range, while it was independent of fv. These findings help to better understand the results for samples where dry density of mixture ρd is kept constant: an increase in fv resulted in a decrease in ρd–f and the suction changed accordingly. In this case, both fv and ψ affected the mechanical behavior.
Preliminary observations on the flower visitors ofNasa colanii(Loasaceae), a poorly known species endemic to northern Peru
Authors: Wong Sato Akira A. , Villanueva-Espinoza Rosa , Revilla Italo , Fernandez-Hilario Robin 
Published: May 2021

Nasa is the most diverse genus among the family Loasaceae and it is mainly distributed in Peru. Most species of this genus are microendemics, with distributions restricted to very specific locations; such is the case of Nasa colanii Dostert & Weigend. This species — previously only known from the type collected in 1978 from the Amazonas region of Peru — lacks information about its biology and ecology. To improve our understanding of the reproductive biology and pollination ecology of N. colanii, we observed flower development and insect floral visits in a cloud forest in the Amazonas region. The flowers of N. colanii are nectariferous and protandrous. The typical stamen movement to the flower center of the subfamily Loasoideae appears to be autonomous. Only well-developed (elongated) pistils showed positive stigmatic receptivity to 3% hydrogen peroxide. Syrphid flies (Baccha sp.) and small beetles (Baridinae spp. and Alticini sp.) were the only observed flower visitors. The syrphid flies visited the flower and foraged for pollen, whereas the small beetles were found already in the flowers and seemingly used it as a shelter. Results suggest that N. colanii might be adapted to fly pollination.
On nuclear coalescence in small interacting systems
Authors: Kachelrieß M. , Ostapchenko S. , Tjemsland J. 
Published: May 2021

AbstractThe formation of light nuclei can be described as the coalescence of clusters of nucleons into nuclei. In the case of small interacting systems, such as dark matter and $$e^+e^-$$

e
+

e
-

annihilations or pp collisions, the coalescence condition is often imposed only in momentum space and hence the size of the interaction region is neglected. On the other hand, in most coalescence models used for heavy ion collisions, the coalescence probability is controlled mainly by the size of the interaction region, while two-nucleon momentum correlations are either neglected or treated as collective flow. Recent experimental data from pp collisions at LHC have been interpreted as evidence for such collective behaviour, even in small interacting systems. We argue that these data are naturally explained in the framework of conventional QCD inspired event generators when both two-nucleon momentum correlations and the size of the hadronic emission volume are taken into account. To include both effects, we employ a per-event coalescence model based on the Wigner function representation of the produced nuclei states. This model reproduces well the source size for baryon emission and the coalescence factor $$B_2$$

B
2

measured recently by the ALICE collaboration in pp collisions.
No-go theorem for inflation in Ricci-inverse gravity
Authors: Do Tuan Q. 
Published: May 2021

AbstractIn this paper, we study the so-called Ricci-inverse gravity, which is a very novel type of fourth-order gravity proposed recently. In particular, we are able to figure out both isotropically and anisotropically inflating universes to this model. More interestingly, these solutions are shown to be free from a singularity problem. However, stability analysis based on the dynamical system method shows that both isotropic and anisotropic inflation of this model turn out to be unstable against field perturbations. This result implies a no-go theorem for both isotropic and anisotropic inflation in the Ricci-inverse gravity.
No light at the end of the tunnel
Authors: Reiss H. R. 
Published: May 2021

Abstract
The tunneling model for laser-induced processes implies the replacement of the propagating field of a laser by an oscillatory electric field. The view of the electric field as the primary influence in charged particle interactions fails for laser processes where the propagation property is important. Electric fields lack several quintessential laser-field properties that become dominant at high intensities and/or low frequencies. Quantum tunneling is not a concept generally suited to laser light. Conversely, laser criteria do not apply to electric-field phenomena like Sauter–Schwinger pair production in the vacuum, contrary to a widespread assumption.

Graphic abstract
Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine Expression
Authors: Parajuli Gyanu , Tekguc Murat , Wing James B. , Hashimoto Ari , Okuzaki Daisuke , Hirata Takeshi , Sasaki Atsushi , Itokazu Takahide , Handa Haruka , Sugino Hirokazu , Nishikawa Yoshihiro , Metwally Hozaifa , Kodama Yuzo , Tanaka Shinya , Sabe Hisataka , Yamashita Toshihide , Sakaguchi Shimon , Kishimoto Tadamitsu , Hashimoto Shigeru 
Published: May 2021

AbstractThe acquisition of mesenchymal traits leads to immune evasion in various cancers, but the underlying molecular mechanisms remain unclear. In this study, we found that the expression levels of AT-rich interaction domain-containing protein 5a (Arid5a), an RNA-binding protein, were substantially increased in mesenchymal tumor subtypes. The deletion of Arid5a in tumor cell lines enhanced antitumor immunity in immunocompetent mice, but not in immunodeficient mice, suggesting a role for Arid5a in immune evasion. Furthermore, an Arid5a-deficient tumor microenvironment was shown to have robust antitumor immunity, as manifested by suppressed infiltration of granulocytic myeloid-derived suppressor cells and regulatory T cells. In addition, infiltrated T cells were more cytotoxic and less exhausted. Mechanistically, Arid5a stabilized Ido1 and Ccl2 mRNAs and augmented their expression, resulting in enhanced tryptophan catabolism and an immunosuppressive tumor microenvironment. Thus, our findings demonstrate the role of Arid5a beyond inflammatory diseases and suggest Arid5a as a promising target for the treatment of immunotolerant malignant tumors.See related Spotlight by Van den Eynde, p. 854.