bluuebunny/crossref_metadata_2025_split huggingface dataset:
CT airway remodelling and chronic cough
Authors: Abozid Hazim , Kirby Miranda , Nasir Neha , Hartl Sylvia , Breyer-Kohansal Robab , Breyer Marie-Kathrin , Burghuber Otto C , Bourbeau Jean , Wouters Emiel F M , Tan Wan 
Published: May 2023

RationaleStructural airway changes related to chronic cough (CC) are described in the literature, but so far reported data are rare and non-conclusive. Furthermore, they derive mainly from cohorts with small sample sizes. Advanced CT imaging not only allows airway abnormalities to be quantified, but also to count the number of visible airways. The current study evaluates these airway abnormalities in CC and assesses the contribution of CC in addition to CT findings on the progression of airflow limitation, defined as a decline in forced expiratory volume in 1 s (FEV1) over time.MethodsA total of 1183 males and females aged ≥40 years with thoracic CT scans and valid spirometry from Canadian Obstructive Lung Disease, a Canadian multicentre, population-based study has been included in this analysis. Participants were stratified into 286 never-smokers, 297 ever-smokers with normal lung function and 600 with chronic obstructive pulmonary disease (COPD) of different severity grades. Imaging parameters analyses included total airway count (TAC), airway wall thickness, emphysema as well as parameters for functional small airway disease quantification.ResultsIrrespective of COPD presence, CC was not related to specific airway and lung structure features. Independent of TAC and emphysema score, CC was highly associated with FEV1 decline over time in the entire study population, particularly in ever-smokers (p<0.0001).ConclusionThe absence of specific structural CT features independently from COPD presence indicate that other underlying mechanisms are contributing to the symptomatology of CC. On top of derived CT parameters, CC seems to be independently associated with FEV1 decline.Trial registration numberNCT00920348.
Comparison of intravenous paracetamol (acetaminophen) to intravenously or intramuscularly administered non-steroidal anti-inflammatory drugs (NSAIDs) or opioids for patients presenting with moderate to severe acute pain conditions to the ED: systematic review and meta-analysis
Authors: Qureshi Isma , Abdulrashid Khadiga , Thomas Stephen H , Abdel-Rahman Manar E , Pathan Sameer A , Harris Tim 
Published: May 2023

ObjectiveParacetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to provide analgesia for patients with moderate to severe pain. This systematic review and meta-analysis evaluated the level of analgesia provided by intravenous paracetamol (IVP) alone compared with NSAIDs (intravenous or intramuscular), or opioids (intravenous) alone in adults attending the ED with acute pain.MethodsTwo authors independently searched PubMed (MEDLINE), Web of Science, Embase (OVID), Cochrane Library, SCOPUS and Google Scholar (3 March 2021–20 May 2022) for randomised trials without any language or date restriction. Clinical trials were evaluated using the Risk of Bias V.2 tool. The primary outcome was mean difference (MD) for pain reduction at 30 min (T30) post analgesia delivery. The secondary outcomes were MD in pain reduction at 60, 90 and 120 min; the need for rescue analgesia; and the occurrence of adverse events (AEs).ResultsTwenty-seven trials (5427 patients) were included in the systematic review and 25 trials (5006 patients) in the meta-analysis. There was no significant difference in pain reduction at T30 between the IVP group and opioids (MD −0.13, 95% CI −1.49 to 1.22) or IVP and NSAIDs (MD −0.27, 95% CI −1.0 to 1.54. There was also no difference at 60 min, IVP group versus opioid group (MD −0.09, 95% CI −2.69 to 2.52) or IVP versus NSAIDs (MD 0.51, 95% CI 0.11 to 0.91). The quality of the evidence using Grading of Recommendations, Assessments, Development and Evaluations methodology was low for MD in pain scores.The need for rescue analgesia at T30 was significantly higher in the IVP group compared with the NSAID group (risk ratio (RR): 1.50, 95% CI 1.23 to 1.83), with no difference found between the IVP group and the opioid group (RR: 1.07, 95% CI 0.67 to 1.70). AEs were 50% lower in the IVP group compared with the opioid group (RR: 0.50, 95% CI 0.40 to 0.62), whereas no difference was observed in the IVP group compared with the NSAID group (RR: 1.30, 95% CI 0.78 to 2.15).ConclusionIn patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable alternative.PROSPERO registration numberCRD42021240099.
Answering calls for rigorous health equity research: a cross-sectional study leveraging electronic health records for data disaggregation in Latinos
Authors: Heintzman John , Dinh Dang , Lucas Jennifer A , Byhoff Elena , Crookes Danielle M , April-Sanders Ayana , Kaufmann Jorge , Boston Dave , Hsu Audree , Giebultowicz Sophia , Marino Miguel 
Published: May 2023

IntroductionCountry of birth/nativity information may be crucial to understanding health equity in Latino populations and is routinely called for in health services literature assessing cardiovascular disease and risk, but is not thought to co-occur with longitudinal, objective health information such as that found in electronic health records (EHRs).MethodsWe used a multistate network of community health centres to describe the extent to which country of birth is recorded in EHRs in Latinos, and to describe demographic features and cardiovascular risk profiles by country of birth. We compared geographical/demographic/clinical characteristics, from 2012 to 2020 (9 years of data), of 914 495 Latinos recorded as US-born, non-US-born and without a country of birth recorded. We also described the state in which these data were collected.ResultsCountry of birth was collected for 127 138 Latinos in 782 clinics in 22 states. Compared with those with a country of birth recorded, Latinos without this record were more often uninsured and less often preferred Spanish. While covariate adjusted prevalence of heart disease and risk factors were similar between the three groups, when results were disaggregated to five specific Latin countries (Mexico, Guatemala, Dominican Republic, Cuba, El Salvador), significant variation was observed, especially in diabetes, hypertension and hyperlipidaemia.ConclusionsIn a multistate network, thousands of non-US-born, US-born and patients without a country of birth recorded had differing demographic characteristics, but clinical variation was not observed until data was disaggregated into specific country of origin. State policies that enhance the safety of immigrant populations may enhance the collection of health equity related data. Rigorous and effective health equity research using Latino country of birth information paired with longitudinal healthcare information found in EHRs might have significant potential for aiding clinical and public health practice, but it depends on increased, widespread and accurate availability of this information, co-occurring with other robust demographic and clinical data nativity.
Screening of normal endoscopic large bowel biopsies with interpretable graph learning: a retrospective study
Authors: Graham Simon , Minhas Fayyaz , Bilal Mohsin , Ali Mahmoud , Tsang Yee Wah , Eastwood Mark , Wahab Noorul , Jahanifar Mostafa , Hero Emily , Dodd Katherine , Sahota Harvir , Wu Shaobin , Lu Wenqi , Azam Ayesha , Benes Ksenija , Nimir Mohammed , Hewitt Katherine , Bhalerao Abhir , Robinson Andrew , Eldaly Hesham , Raza Shan E Ahmed , Gopalakrishnan Kishore , Snead David , Rajpoot Nasir 
Published: May 2023

ObjectiveTo develop an interpretable artificial intelligence algorithm to rule out normal large bowel endoscopic biopsies, saving pathologist resources and helping with early diagnosis.DesignA graph neural network was developed incorporating pathologist domain knowledge to classify 6591 whole-slides images (WSIs) of endoscopic large bowel biopsies from 3291 patients (approximately 54% female, 46% male) as normal or abnormal (non-neoplastic and neoplastic) using clinically driven interpretable features. One UK National Health Service (NHS) site was used for model training and internal validation. External validation was conducted on data from two other NHS sites and one Portuguese site.ResultsModel training and internal validation were performed on 5054 WSIs of 2080 patients resulting in an area under the curve-receiver operating characteristic (AUC-ROC) of 0.98 (SD=0.004) and AUC-precision-recall (PR) of 0.98 (SD=0.003). The performance of the model, named Interpretable Gland-Graphs using a Neural Aggregator (IGUANA), was consistent in testing over 1537 WSIs of 1211 patients from three independent external datasets with mean AUC-ROC=0.97 (SD=0.007) and AUC-PR=0.97 (SD=0.005). At a high sensitivity threshold of 99%, the proposed model can reduce the number of normal slides to be reviewed by a pathologist by approximately 55%. IGUANA also provides an explainable output highlighting potential abnormalities in a WSI in the form of a heatmap as well as numerical values associating the model prediction with various histological features.ConclusionThe model achieved consistently high accuracy showing its potential in optimising increasingly scarce pathologist resources. Explainable predictions can guide pathologists in their diagnostic decision-making and help boost their confidence in the algorithm, paving the way for its future clinical adoption.
Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis
Authors: Strijbis Eva M , Coerver Eline , Mostert Jop , van Kempen Zoé L E , Killestein Joep , Comtois Jacynthe , Repovic Pavle , Bowen James D , Cutter Gary , Koch Marcus 
Published: May 2023

BackgroundFocal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity.MethodsWe used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS,NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS,NCT00030966) RCTs. We determined the proportion of participants developing new T2 lesions, contrast-enhancing lesions (CELs) and relapses over 2 years of follow-up as a function of age, and investigated the association of age with time to first relapse using time-to-event analyses.ResultsAt baseline, there were no differences between age groups in T2 lesion volume and number of relapses in the year before inclusion. In SENTINEL, older participants had a significantly lower number of CELs. During both trials, the number of new CELs and the proportion of participants developing new CELs were significantly lower in older age groups. The number of new T2 lesions and the proportion of participants with any radiological disease activity during follow-up were also lower in older age groups, especially in the control arms.ConclusionsOlder age is associated with a lower prevalence and degree of focal inflammatory disease activity in treated and untreated RRMS. Our findings inform the design of RCTs, and suggest that patient age should be taken into consideration when deciding on immunomodulatory treatment in RRMS.
Efficient simulation of multielectron dynamics in molecules under intense laser pulses: implementation of the multiconfiguration time-dependent Hartree–Fock method based on the adaptive finite element method
Authors: Orimo Yuki , Sato Takeshi , Ishikawa Kenichi L. 
Published: May 2023

We present an implementation of the multiconfiguration time-dependent Hartree–Fock method based on the adaptive finite element method for molecules under intense laser pulses. For efficient simulations, orbital functions are propagated by a stable propagator using the short iterative Arnoldi scheme and our implementation is parallelized for distributed memory computing. This is demonstrated by simulating high-harmonic generation from a water molecule and achieves a simulation of multielectron dynamics with overwhelmingly less computational time, compared to our previous work [Sawada, R. et al. Phys. Rev. A, 2016, 93, 023434].
The Environment Agency Chalk groundwater level monitoring network in England
Authors: Farrell Rolf Peter , Whiteman Mark 
Published: May 2023

Abstract
This paper reviews the Environment Agency chalk groundwater level monitoring network. The network has evolved over many years to enable management of the resource and to assess the impact of abstractions on the environment. The paper considers the strengths and weaknesses of the network, the use and accessibility of the data and how the network supports, and works with, the Environment Agency's regional groundwater models. It concludes with the suggestion that the network is suffering from a degree of lack of maintenance and that there is a disparity between the ambitions of the modelling programme with its Modflow6-driven shift to multi-layer conceptualization and a largely open-hole, single-layer monitoring installation.
Geological and chronostratigraphic overview of the Upper Triassic and Jurassic successions of the Junggar Basin, NW China
Authors: Sha Jingeng , Fang Yanan , Cheng Jinhui , Wang Yaqiong , Li Sha , Yang Xiaoju , Li Jiahao , Zhang Haichun 
Published: May 2023

Abstract

The vast, widely exposed terrestrial (lacustrine to fluvial) Upper Triassic–Jurassic (except Tithonian) successions of the Junggar Basin not only record most of the stratigraphic boundaries of the Upper Triassic and Jurassic, including the Triassic–Jurassic boundary and the Hettangian–Sinemurian, Sinemurian–Pliensbachian, Pliensbachian–Toarcian, Lower–Middle Jurassic, Middle–Upper Jurassic and Oxfordian–Kimmeridgian boundaries, but also record a range of geological, organic, palaeogeographic and palaeoclimatic events known to have happened globally in the Late Triassic and Jurassic. The Triassic–Jurassic boundary is placed in the stratigraphic interval of the first occurrence of
Retitriletes austroclavatidites
and
Callialasporites dampieri
and the last occurrence of
Lunatisporites rhaeticus
. The end-Triassic mass extinction is characterized by the disappearance of most of the sporomorph and macro-plant taxa. The end-Triassic mass extinction occurred before the first occurrence of the sporomorph
Cerebropollenites thiergartii
, and ended after its appearance when life began to revive. The Junggar Basin was situated at a high latitude during the Late Triassic–Early Jurassic Pliensbachian ‘hothouse’ and ‘greenhouse’ periods. The Late Triassic–Mid Jurassic Bajocian was humid and warm, and rich in coal swamps, except the Toarcian, which yields little coal because it was relatively warmer and drier. It became arid from the early Late Jurassic Oxfordian.
Late Devonian shear-zone reactivation in the Canadian Appalachian orogen
Authors: Piette-Lauzière Nicolas , Larson Kyle P. , Kellett Dawn A. , Rogers Neil , Powell Jeremy 
Published: May 2023

Abstract

Oblique accretion zones often display transpressive, strike-slip and transtensive structures of different orientations with respect to the convergence axis. The Late Devonian oblique collision of Meguma within the Canadian Appalachian orogen is often characterized as transpressive. However, the simultaneous opening of the Maritimes Basin indicates that the orogenesis also partitioned into an extensional component. In this context, few of the shear zones reactivated during this time period have been characterized while accounting for the possibility of strain partitioning. To do so, we characterize the kinematics and timing of deformation of the Eastern Highlands Shear Zone (EHSZ) and the Coinneach Brook Shear Zone (CBSZ) on Cape Breton Island, Nova Scotia, using a combination of U–Pb geochronology (zircon, monazite, xenotime and apatite) and
40
Ar/
39
Ar geochronology
in situ
and step-heating experiments (amphibole, muscovite and biotite). Results show that the Silurian EHSZ was reactivated at
c.
385–367 Ma and the CBSZ was formed at
c.
395–369 Ma, both yielding oblique kinematics. Together, these structures accommodated the rapid exhumation of the Cape Breton Highlands during the docking of the Meguma terrane. This study thus highlights the heterogeneous distribution of transtensive and transpressive deformation during the Neoacadian Orogeny.
ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis
Authors: Perez-Oquendo Mabel , Manshouri Roxsan , Tian Yanhua , Fradette Jared J. , Rodriguez B. Leticia , Kundu Samrat T. , Gibbons Don L. 
Published: May 2023

Abstract

Epithelial-to-mesenchymal transition results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. The transcription repressor zinc finger E-box-binding homeobox 1 (ZEB1) binds to E-boxes of gene promoter regions to suppress the expression of epithelial genes. ZEB1 has inconsistent molecular weights, which have been attributed to posttranslational modifications (PTM). We performed mass spectrometry and identified K811 acetylation as a novel PTM in ZEB1. To define the role of ZEB1 acetylation in regulating function, we generated ZEB1 acetyl-mimetic (K811Q) and acetyl-deficient (K811R) mutant-expressing non–small cell lung cancer cell lines (NSCLC). We demonstrate that the K811R ZEB1 (125 kDa) has a shorter protein half-life than wild-type (WT) ZEB1 and K811Q ZEB1 (∼225 kDa), suggesting that lack of ZEB1 acetylation in the lower molecular weight form affects protein stability. Further, the acetylated form of ZEB1 recruits the nucleosome remodeling and deacetylase (NuRD) complex to bind the promoter of its target genes mir200c-141 and SEMA3F. RNA-sequencing revealed that WT ZEB1 and K811Q ZEB1 downregulate the expression of epithelial genes to promote lung adenocarcinoma invasion and metastasis, whereas the K811R ZEB1 does not. Our findings establish that the K811 acetylation promotes ZEB1 protein stability, interaction with other protein complexes, and subsequent invasion/metastasis of lung adenocarcinoma via epithelial-to-mesenchymal transition.

Implications:
The molecular mechanisms by which ZEB1 is regulated by K811 acetylation to promote protein stability, NuRD complex and promoter interactions, and function are relevant to the development of treatment strategies to prevent and treat metastasis in patients with NSCLC.
A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua 
Published: May 2023

Abstract

Lineage plasticity has long been documented in both small cell lung cancer (SCLC) and neuroblastoma, two clinically distinct neuroendocrine (NE) cancers. In this study, we quantified the NE features of cancer as NE scores and performed a systematic comparison of SCLC and neuroblastoma. We found neuroblastoma and SCLC cell lines have highly similar molecular profiles and shared therapeutic sensitivity. In addition, NE heterogeneity was observed at both the inter- and intra-cell line levels. Surprisingly, we did not find a significant association between NE scores and overall survival in SCLC or neuroblastoma. We described many shared and unique NE score–associated features between SCLC and neuroblastoma, including dysregulation of Myc oncogenes, alterations in protein expression, metabolism, drug resistance, and selective gene dependencies.

Implications:
Our work establishes a reference for molecular changes and vulnerabilities associated with NE to non-NE transdifferentiation through mutual validation of SCLC and neuroblastoma samples.
Left Ventricular Mechano-Energetic Efficiency Identifies an Early Impairment of Myocardial Blood Flow in Arterial Hypertension
Authors: Lembo Maria , Acampa Wanda , Rao Maria Assunta Elena , Manzi Maria Virginia , Morisco Carmine , Esposito Giovanni , Assante Roberta , Zampella Emilia , Nappi Carmela , Gaudieri Valeria , Mannarino Teresa , Mancusi Costantino , de Simone Giovanni , Izzo Raffaele , Cuocolo Alberto , Trimarco Bruno 
Published: May 2023

Background:
Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated possible relationships between positron emission tomography/computed tomography–derived myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi).

Methods:
Seventy-eight hypertensive patients without flow-limiting epicardial coronary artery disease underwent echocardiography, including MEEi computation, and cardiac positron emission tomography/computed tomography with assessment of MBF/mass ratio at rest and after stress and myocardial flow reserve. The lowest MEEi tertile (MEEi<0.031 mL/s/g) was compared to the merged second and third tertiles (MEEi≥0.031).

Results:

Patients in the lowest MEEi tertile were older, had higher systolic blood pressure and body mass index. They also had higher prevalence of LV hypertrophy, whereas lower resting and stress MBF/mass ratio. MEEi was significantly correlated with both resting (r=0.51;
P
<0.0001) and hyperemic (r=0.54;
P
<0.0001) MBF/mass ratios, whereas it was not related to myocardial flow reserve. Delta of MBF/mass ratio was lower in the lowest MEEi tertile than in the highest (
P
<0.0001). In separate multiple linear regression models, after adjusting for sex, systolic blood pressure, body mass index, prevalence of LV hypertrophy, left atrial volume index, and diuretic therapy, the association between LV MEEi and both hyperemic (beta coefficient=0.44;
P
=0.003) and resting (beta coefficient=0.35;
P
=0.008) MBF/mass ratio remained significant.

Conclusions:
In hypertensive patients without flow-limiting epicardial coronary artery disease, low values of MEEi could detect an early LV dysfunction involving an impairment of both resting and hyperemic MBF/mass ratios. MEEi has the advantage of simpler detection, cheaper costs than positron emission tomography/computed tomography, and a lack of radiation exposure.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02211365.
How the Soul Uses Its Tools: Flexible Agency in Aristotle’s Account of Animal Generation
Authors: Kress Emily 
Published: May 2023

Abstract
Aristotle claims that just as a builder uses ‘tools’ to build a house, so too the soul ‘use[s] heat and coldness as tools’ to build an animal (Generation of Animals 740b25–34). I consider two questions about this claim: (1) what sorts of things does the soul use, and what is it for things like them to be organized? and (2) what philosophical work does this sort of organization do in Aristotle’s account of animal generation? I argue that the soul needs flexible intermediate agents, that it organizes them in a way that exploits their flexibility, and that this is due to the demands of a complex, multi-stage process directed at a single end.