bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum lipidome unravels a diagnostic potential in bile acid diarrhoea
Authors: Lewinska Monika , Kårhus Martin Lund , Ellegaard Anne-Marie Gade , Romero-Gómez Manuel , Macias Rocio I R , Andersen Jesper B , Knop Filip Krag 
Published: April 2023

ObjectiveBile acid diarrhoea (BAD) is debilitating yet treatable, but it remains underdiagnosed due to challenging diagnostics. We developed a blood test-based method to guide BAD diagnosis.DesignWe included serum from 50 treatment-naive patients with BAD diagnosed by gold standard75selenium homotaurocholic acid test, 56 feature-matched controls and 37 patients with non-alcoholic fatty liver disease (NAFLD). Metabolomes were generated using mass spectrometry covering 1295 metabolites and compared between groups. Machine learning was used to develop a BAD Diagnostic Score (BDS).ResultsMetabolomes of patients with BAD significantly differed from controls and NAFLD. We detected 70 metabolites with a discriminatory performance in the discovery set with an area under receiver-operating curve metric above 0.80. Logistic regression modelling using concentrations of decanoylcarnitine, cholesterol ester (22:5), eicosatrienoic acid, L-alpha-lysophosphatidylinositol (18:0) and phosphatidylethanolamine (O-16:0/18:1) distinguished BAD from controls with a sensitivity of 0.78 (95% CI 0.64 to 0.89) and a specificity of 0.93 (95% CI 0.83 to 0.98). The model was independent of covariates (age, sex, body mass index) and distinguished BAD from NAFLD irrespective of fibrosis stage. BDS outperformed other blood test-based tests (7-alpha-hydroxy-4-cholesten-3-one and fibroblast growth factor 19) currently under development.ConclusionsBDS derived from serum metabolites in a single-blood sample showed robust identification of patients with BAD with superior specificity and sensitivity compared with current blood test-based diagnostics.
In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study
Authors: Pepe Francesco , Guerini-Rocco Elena , Fassan Matteo , Fusco Nicola , Vacirca Davide , Ranghiero Alberto , Venetis Konstantinos , Rappa Alessandra , Taormina Sergio Vincenzo , Russo Gianluca , Rebellato Elena , Munari Giada , Moreno-Manuel Andrea , De Angelis Carmine , Zamagni Claudio , Valabrega Giorgio , Malapelle Umberto , Troncone Giancarlo , Barberis Massimo , Iaccarino Antonino 
Published: April 2023

AimsPoly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays.MethodsA total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen’s (dual) and Fleiss (triple) κ coefficients.ResultsIn-houseBRCA1/2molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%.ConclusionsIn-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.
Comparison of design characteristics and toxicant emissions from Vuse Solo and Alto electronic nicotine delivery systems
Authors: Talih Soha , Karaoghlanian Nareg , Salman Rola , Fallah Sacha , Helal Alissa , El-Hage Rachel , Saliba Najat , Breland Alison , Eissenberg Thomas , Shihadeh Alan 
Published: April 2023

Introduction
Vuse Solo is the first electronic nicotine delivery system (ENDS) authorised by the US Food and Drug Administration for marketing in the USA. Salient features of the Vuse Solo product such as nicotine form, draw resistance, power regulation and electrical characteristics have not been reported previously, and few studies have examined the nicotine and other toxicant emissions of this product. We investigated the design characteristics and toxicant emissions of the Solo as well as Alto, another Vuse product with a greater market share than Solo.

Methods
Total/freebase nicotine, propylene glycol to vegetable glycerin ratio, carbonyl compounds (CC) and reactive oxygen species (ROS) were quantified by gas chromatography, high-performance liquid chromatography and fluorescence from aerosol emissions generated in 15 puffs of 4 s duration. The electric power control system was also analysed.

Results
The average power delivered was 2.1 W and 3.9 W for Solo and Alto; neither system was temperature-controlled. Vuse Solo and Alto, respectively, emitted nicotine at a rate of 38 µg/s and 115 µg/s, predominantly in the protonated form (>90%). Alto’s ROS yield was similar to a combustible cigarette and one order of magnitude greater than that of Solo. Total carbonyls from both products were two orders of magnitude lower than combustible cigarettes.

Conclusion
Vuse Solo is an above-Ohm ENDS that emits approximately one-third the nicotine flux of a Marlboro Red cigarette (129 µg/s) and considerably lower CC and ROS yields than a combustible cigarette. With its higher power, the nicotine flux and ROS yield from Alto are similar to Marlboro Red levels; Alto may thus present greater abuse liability than the lower sales-volume Solo.
Long-term axial performance of continuous-flight pile in frozen soil
Authors: Gao Shuai , Sego David , Deng Lijun 
Published: April 2023

A number of buildings in the Canadian Arctic communities have failed or showed signs of failure of pile foundations caused by climate-change-induced excessive settlements. Effects of climate change warrant alternative pile types and new installation methods. Installing a pile into frozen soils by the torque method is rare in current practice of the Canadian Arctic. The continuous-flight pile is a new foundation type that is installed by torque. This study is aimed at investigating the axial load transfer of continuous-flight piles in frozen soils under long-term loads. A primary objective is to examine the effects of soil temperature, water content, and soil salinity on the resistance and the failure mode of continuous-flight piles in frozen soils. A series of axial load tests of model continuous-flight piles with a shaft diameter of 89 mm were carried out in the lab. Results show that primary and secondary creeps were observed during the constant load tests. The cylindrical shear mode and individual bearing mode were observed and inferred from the measured data. The adfreeze shear resistance and the individual plate bearing resistance under constant loads were estimated and verified using data from the literature. The adfreeze resistance increased with the applied load, and the plate bearing resistance increased as the normalized pile displacement rate increased. The mobilized adfreeze and plate bearing resistances suggest a potential increased load capacity of the continuous-flight pile compared to conventional smooth piles of similar diameter.
Proton, deuteron and triton flow measurements in Au+Au collisions at $$\sqrt{s_{_{{\text {NN}}}}}= 2.4$$ GeV
Authors: Adamczewski-Musch J. , Arnold O. , Behnke C. , Belounnas A. , Berger-Chen J. C. , Blanco A. , Blume C. , Böhmer M. , Bordalo P. , Chlad L. , Ciepal I. , Deveaux C. , Dreyer J. , Epple E. , Fabbietti L. , Filip P. , Fonte P. , Franco C. , Friese J. , Fröhlich I. , Galatyuk T. , Garzón J. A. , Gernhäuser R. , Greifenhagen R. , Gumberidze M. , Harabasz S. , Heinz T. , Hennino T. , Hlavac S. , Höhne C. , Holzmann R. , Kämpfer B. , Kardan B. , Koenig I. , Koenig W. , Kohls M. , Kolb B. W. , Korcyl G. , Kornakov G. , Kornas F. , Kotte R. , Kugler A. , Kunz T. , Lalik R. , Lapidus K. , Lopes L. , Lorenz M. , Mahmoud T. , Maier L. , Malige A. , Mangiarotti A. , Markert J. , Matulewicz T. , Maurus S. , Metag V. , Michel J. , Mihaylov D. M. , Müntz C. , Münzer R. , Naumann L. , Nowakowski K. , Parpottas Y. , Pechenov V. , Pechenova O. , Piasecki K. , Pietraszko J. , Przygoda W. , Pysz K. , Ramos S. , Ramstein B. , Rathod N. , Rodriguez-Ramos P. , Rosier P. , Rost A. , Rustamov A. , Salabura P. , Scheib T. , Schuldes H. , Schwab E. , Scozzi F. , Seck F. , Sellheim P. , Selyuzhenkov I. , Siebenson J. , Silva L. , Singh U. , Smyrski J. , Sobolev Yu. G. , Spataro S. , Spies S. , Ströbele H. , Stroth J. , Sturm C. , Svoboda O. , Szala M. , Tlusty P. , Traxler M. , Tsertos H. , Wagner V. , Wendisch C. , Wiebusch M. G. , Wirth J. , Wójcik D. , Zumbruch P. ,   HADES collaboration
Published: April 2023

AbstractHigh-precision measurements of flow coefficients $$v_{n}$$

v
n

($$n = 1 - 4$$

n
=
1
-
4

) for protons, deuterons and tritons relative to the first-order spectator plane have been performed in Au+Au collisions at $$\sqrt{s_{_{{\text {NN}}}}}= 2.4$$

s

NN

=
2.4

GeV with the High-Acceptance Di-Electron Spectrometer (HADES) at the SIS18/GSI. Flow coefficients are studied as a function of transverse momentum $$p_{{\text {t}}}$$

p
t

and rapidity $$y_{{\text {cm}}}$$

y
cm

over a large region of phase-space and for several classes of collision centrality. A clear mass hierarchy, as expected by relativistic hydrodynamics, is found for the slope of $$v_{1}$$

v
1

, $$d v_{1}/d y^{\prime }|_{y^{\prime } = 0}$$

d

v
1

/
d

y
′

|

y
′

=
0

where $$y^{\prime }$$

y
′

is the scaled rapidity, and for $$v_{2}$$

v
2

at mid-rapidity. Scaling with the number of nucleons is observed for the $$p_{{\text {t}}}$$

p
t

dependence of $$v_{2}$$

v
2

and $$v_{4}$$

v
4

at mid-rapidity, which is indicative for nuclear coalescence as the main process responsible for light nuclei formation. $$v_{2}$$

v
2

is found to scale with the initial eccentricity $$\langle \epsilon _{2} \rangle $$

⟨

ϵ
2

⟩

, while $$v_{4}$$

v
4

scales with $$\langle \epsilon _{2} \rangle ^{2}$$

⟨

ϵ
2

⟩

2

and $$\langle \epsilon _{4} \rangle $$

⟨

ϵ
4

⟩

. The multi-differential high-precision data on $$v_{1}$$

v
1

, $$v_{2}$$

v
2

, $$v_{3}$$

v
3

, and $$v_{4}$$

v
4

provides important constraints on the equation-of-state of compressed baryonic matter.
Evaluation of Inflammatory Infiltration in the Retroperitoneal Space of Acute Pancreatitis Using Computer Tomography and Its Correlation with Clinical Severity
Authors: Xu YuLong , Ye ChunJuan , Tan Bing 
Published: April 2023

This paper investigates the correlation between the degree and severity of CT inflammatory infiltration in the retroperitoneal space of acute pancreatitis (AP). A total of 113 patients were included based on diagnostic criteria. The general data of the patients and the relationship between the computed tomography severity index (CTSI) and pleural effusion (PE), involvement, degree of inflammatory infiltration of retroperitoneal space (RPS), number of peripancreatic effusion sites, and degree of pancreatic necrosis on contrast-enhanced CT at different times were studied. The results showed that the mean age of onset in females was later than that in males; 62 cases involved RPS to varying degrees, with a positive rate of 54.9% (62/113), and the total involvement rates of only the anterior pararenal space (APS); both APS and perirenal space (PS); and APS, PS, and posterior pararenal space (PPS) were 46.9% (53/113), 53.1% (60/113), and 17.7% (20/113), respectively. The degree of inflammatory infiltration in the RPS worsened with the increase in CTSI score; the incidence of PE was higher in the group greater than 48 hours than in the group less than 48 hours; necrosis >50% grade was predominant (43.2%) 5 to 6 days after onset, with a higher detection rate than other time periods (

P

< 0.05). Thus, when the PPS was involved, the patient’s condition can be treated as severe acute pancreatitis (SAP); the higher the degree of inflammatory infiltration in the retroperitoneum, the higher the severity of AP. Enhanced CT examination 5 to 6 days after onset in patients with AP revealed the greatest extent of pancreatic necrosis.
Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort: Results from the Randomized SweBCG91RT Trial
Authors: Stenmark Tullberg Axel , Sjöström Martin , Niméus Emma , Killander Fredrika , Chang S. Laura , Feng Felix Y. , Speers Corey W. , Pierce Lori J. , Kovács Anikó , Lundstedt Dan , Holmberg Erik , Karlsson Per 
Published: April 2023

Abstract

Purpose:
The local immune infiltrate's influence on tumor progression may be closely linked to tumor-intrinsic factors. The study aimed to investigate whether integrating immunologic and tumor-intrinsic factors can identify patients from a low-risk cohort who may be candidates for radiotherapy (RT) de-escalation.

Experimental Design:
The SweBCG91RT trial included 1,178 patients with stage I to IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median of 15.2 years. We trained two models designed to capture immunologic activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could further stratify tumors, allowing for identifying a subgroup where RT de-escalation is feasible, despite clinical indicators of a high risk of ipsilateral breast tumor recurrence (IBTR).

Results:
The prognostic effect of the immunologic model could be predicted by the tumor-intrinsic model (Pinteraction = 0.01). By integrating measurements of the immunologic- and tumor-intrinsic models, patients who benefited from an active immune infiltrate could be identified. These patients benefited from standard RT (HR, 0.28; 95% CI, 0.09–0.85; P = 0.025) and had a 5.4% 10-year incidence of IBTR after irradiation despite high-risk genomic indicators and a low frequency of systemic therapy. In contrast, high-risk tumors without an immune infiltrate had a high 10-year incidence of IBTR despite RT treatment (19.5%; 95% CI, 12.2–30.3).

Conclusions:
Integrating tumor-intrinsic and immunologic factors may identify immunogenic tumors in early-stage breast cancer populations dominated by ER-positive tumors. Patients who benefit from an activated immune infiltrate may be candidates for RT de-escalation.
Targeting RET Solvent-Front Mutants with Alkynyl Nicotinamide-Based Inhibitors
Authors: Khatri Ujjwol , Dayal Neetu , Hu Xueqing , Larocque Elizabeth , Naganna Nimishetti , Shen Tao , Liu Xuan , Holtsberg Frederick W. , Aman M. Javad , Sintim Herman O. , Wu Jie 
Published: April 2023

Abstract
Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation RET TKIs. While acquired RET G810C/R/S/V mutations were reported in selpercatinib-treated patients, it was unclear whether all of these and other potential G810 mutants are resistant to selpercatinib and pralsetinib. Here, we profiled selpercatinib and pralsetinib on all six possible G810 mutants derived from single nucleotide substitution and developed novel alkynyl nicotinamide-based RET TKIs to inhibit selpercatinib/pralsetinib-resistant RET G810 mutants. Surprisingly, the G810V mutant found in a clinical study was not resistant to selpercatinib or pralsetinib. Besides G810C/R/S, G810D also conferred selpercatinib/pralsetinib resistance. Alkynyl nicotinamide compounds such as HSN608, HSL476, and HSL468 have better drug-like properties than alkynyl benzamides. Six of these compounds inhibited all six G810 solvent-front mutants and the V804M gatekeeper mutant with IC50 &lt; 50 nmol/L in cell culture. Oral administration of HSN608 at a well-tolerated dose (30 mg/kg) gave plasma level &gt; 30x the IC50s of inhibiting all G810 mutants in cell culture. In cell-derived xenograft tumors driven by KIF5B-RET (G810C) that contains the most frequently observed solvent-front mutant in selpercatinib-treated patients, HSN608, HSL476, and HSL468 significantly suppressed and caused regression of the selpercatinib-resistant tumors. This study clarifies the sensitivities of different RET solvent-front mutants to selpercatinib and pralsetinib and identifies novel alkylnyl nicotinamide-based RET TKIs for inhibiting selpercatinib/pralsetinib-resistant G810 mutants.
N-of-1 Trials in Cancer Drug Development
Authors: Gouda Mohamed A. , Buschhorn Lars , Schneeweiss Andreas , Wahida Adam , Subbiah Vivek 
Published: April 2023

Summary:
The current approaches for cancer drug development lag behind an accelerated need in the field for a fast and efficient method for evaluating drugs in the personalized medicine era. In that regard, N-of-1 studies emerge as a potential addition to the drug development arsenal, although there are several considerations before its broad application becomes feasible. In essence, N-of-1 trials are a departure from the traditional “drug-centric” model to a “patient-centric” model. Herein, we review the concept of N-of-1 trials and provide real-world examples of their use in the developmental therapeutics field. N-of-1 trials offer an exceptional opportunity for fast-tracking of cancer drug development in the precision oncology era.
Manifestation of the Yezidi Identity
Authors: Açıkyıldız Birgül 
Published: April 2023

Abstract
This article aims to examine the relationship between cemeteries and Yezidi identity by focusing on the Goristana Hesen Begê (Hesen Beg Cemetery), which belongs to the villages of Geliyê Sora (Güneli), Mezre (Çilesiz), Xanik/Berhokê (Mağaracık), and Efşe (Kaleli), and is located in Nusaybin in southeastern Turkey. It will analyse the tombstones’ architectural features and symbols and question how the Yezidi identity reconstructs and transforms itself in modern monumental funerary architecture in southeastern Turkey. Ritual practices in the Goristana Hesen Begê indicate that death rituals can be employed to strengthen and integrate the social boundaries of the community. Thus, it will discuss the meaning of places of memory and mortuary practices for the exiled Yezidis and their roles as identity markers in the reproduction of social relations within the Yezidi community.
Credible Commitment or Sham Devotion to the International Criminal Court: Whither Nigeria, Kenya and Uganda?
Authors: Anya Sylvester , Osuagwu Adrian , Onyeabor Emmanuel , Okubuiro Joycelin , Nwankwo Matthew , Onyeonagu Daniel , Enemo Ifeoma 
Published: April 2023

Abstract
There is a pattern of inconsistent behaviour among some African states towards the International Criminal Court (ICC) showing credible commitment and sham devotion. This study poses a question: what will be of the status of Nigeria, Kenya and Uganda (the Triad) vis-à-vis the ICC by the end of 2023, considering the pattern of behaviour of these states so far, evidence from data and the spate of domestication and exit procedures in homogeneous African states in contemporary times? The objectives of the study are to predict the status of the Triad by 2023 and reflect on the implication of the predictions for the on-going viability, sustainability and credibility challenges facing the ICC in Africa. The study finds that: the pattern of Nigeria’s behaviour shows sham devotion and predicts that she will not domesticate the Rome Statute come 2023; the pattern of Kenya’s behaviour straddles credible commitment and sham devotion and she may maintain her membership of the ICC by 2023; the pattern of Uganda’s behaviour shows fairly credible commitment mixed with sham devotion and she will maintain her membership of the Statute come 2023. These predictions have implications on the ongoing viability, sustainability and credibility challenges facing the ICC in Africa.
Philosophical Tools for Educational Culture: Reconstructing Data and Assessment Practices
Authors: Tschaepe Mark 
Published: April 2023

Abstract
Assessment practices have come to dominate much of formalized education, especially within the United States. Currently, learning analytics (la) and educational data mining (edm) are purported by many educational companies and institutions to successfully improve learning through what are often considered as objective collection, classification, and analysis of educational data. Enthusiasm about big data in education has contributed to the naturalization of datafication within the field. Educational data is regarded as a natural resource that exists ‘out there’ to be mined by edm and refined by la. Once refined, it is thought to bear the truth of educational assessment that leads to successful learning outcomes.
Bibliometrics and Qualitative Assessment: a Pragmatist Approach
Authors: Waks Leonard , Kramer Eli Orner 
Published: April 2023

Abstract
In this essay we explore whether and how we should use bibliometrics in hiring, promoting, and granting in the academy. We suggest a Deweyan-Hickmanian pragmatist approach to reflecting on the technology of bibliometrics as a resource for inherently qualitative judgements in these deliberations. We begin with a literature review of current work evaluating the role and use of bibliometrics in the academy, from advocating for them to questioning their construct validity and assessing their limitations and/or dangerous consequences. In the next section, we take a step back and provide a Deweyan philosophical analysis of the validity and practical use of qualitative assessment. In our conclusion we reflect on what pragmatism can teach about recent algorithmic tools used for faculty evaluation.
Hickman and Dewey: Naturalism’s Hope?
Authors: Saatkamp Herman J. 
Published: April 2023

Abstract
Larry Hickman has fostered his own analysis, explication and application of Dewey’s philosophy as well as overseen the critical edition of John Dewey’s works at the Center for Dewey Studies. In America our democracy is struggling, making Hickman’s scholarly work even more important. I attempt to explain some of Hickman’s use of Dewey’s philosophy to address current issues that include the roles of religion and education in American democracy. Much of Hickman’s pragmatic naturalism provides hope for democracy as a way of life and as a governmental organization. But will that hope meet contemporary challenges in our society? I suggest some possible limitations to Dewey’s and Hickman’s views but highlight the central role both play in American philosophy.