bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining associations between remote work and anxiety and depression: a longitudinal survey study in Israel
Authors: Moran Mika Ruchama , Heller Oren , Chun Yung , Shlomo Yaniv , Grinstein-Weiss Michal 
Published: September 2023

IntroductionAccumulating evidence points at increases in mental health problems during the COVID-19 pandemic, which has been attributed, among other things, to social distancing policies, such as the shift to remote work from home (henceforth: remote work). The current study examines whether changes during the COVID-19 pandemic in working environments from on-site to remote work (or vice versa) are associated with changes in anxiety and depressive symptoms among Israeli employees with different demographic characteristics.MethodsWe administered three consecutive online surveys between January and November 2021 among 2389 Israelis who work. We conducted panel regression models with individual fixed effects using anxiety and depressive symptoms as outcomes and remote work as exposure, while accounting for sociodemographic variables. We repeated this analysis among subgroups defined by demographic characteristics.ResultsSymptoms of anxiety (Generalized Anxiety Disorder-7) and depression (Patient Health Questionnaire-9) decreased from 4.27 and 5.98 in January to 3.35 and 4.57 in November 2021, respectively. Increased risk for anxiety and depressive symptoms were significantly associated with remote work. These associations were significant among non-partnered adults and among adults with no children, but not among partnered adults and those with children. Remote work was significantly associated with anxiety among men and with depression among women.ConclusionsRemote work is associated with anxiety and depression and these associations vary across different sociodemographic groups.
Reflux conditions induce E-cadherin cleavage and EMT via APE1 redox function in oesophageal adenocarcinoma
Authors: Lu Heng , Cao Long Long , Ballout Farah , Belkhiri Abbes , Peng DunFa , Chen Lei , Chen Zheng , Soutto Mohammed , Wang Timothy C , Que Jianwen , Giordano Silvia , Washington Mary Kay , Chen Steven , McDonald Oliver Gene , Zaika Alexander , El-Rifai Wael 
Published: September 2023

ObjectiveChronic gastro-oesophageal reflux disease, where acidic bile salts (ABS) reflux into the oesophagus, is the leading risk factor for oesophageal adenocarcinoma (EAC). We investigated the role of ABS in promoting epithelial-mesenchymal transition (EMT) in EAC.DesignRNA sequencing data and public databases were analysed for the EMT pathway enrichment and patients’ relapse-free survival. Cell models, pL2-IL1β transgenic mice, deidentified EAC patients’ derived xenografts (PDXs) and tissues were used to investigate EMT in EAC.ResultsAnalysis of public databases and RNA-sequencing data demonstrated significant enrichment and activation of EMT signalling in EAC. ABS induced multiple characteristics of the EMT process, such as downregulation of E-cadherin, upregulation of vimentin and activation of ß-catenin signalling and EMT-transcription factors. These were associated with morphological changes and enhancement of cell migration and invasion capabilities. Mechanistically, ABS induced E-cadherin cleavage via an MMP14-dependent proteolytic cascade. Apurinic/apyrimidinic endonuclease (APE1), also known as redox factor 1, is an essential multifunctional protein. APE1 silencing, or its redox-specific inhibitor (E3330), downregulated MMP14 and abrogated the ABS-induced EMT. APE1 and MMP14 coexpression levels were inversely correlated with E-cadherin expression in human EAC tissues and the squamocolumnar junctions of the L2-IL1ß transgenic mouse model of EAC. EAC patients with APE1highand EMThighsignatures had worse relapse-free survival than those with low levels. In addition, treatment of PDXs with E3330 restrained EMT characteristics and suppressed tumour invasion.ConclusionReflux conditions promote EMT via APE1 redox-dependent E-cadherin cleavage. APE1-redox function inhibitors can have a therapeutic role in EAC.
Bispecific antibody CD73xEGFR more selectively inhibits the CD73/adenosine immune checkpoint on cancer cells and concurrently counteracts pro-oncogenic activities of CD73 and EGFR
Authors: Ploeg Emily Maria , Samplonius Douwe Freerk , Xiong Xiao , Ke Xiurong , Hendriks Mark Alexander Johannes Martinus , Britsch Isabel , van Wijngaarden Anne Paulien , Zhang Hao , Helfrich Wijnand 
Published: September 2023

BackgroundCD73 is an ecto-enzyme that is involved in the conversion of pro-inflammatory extracellular ATP (eATP) excreted by cancer cells under stress to anti-inflammatory adenosine (ADO). A broad variety of solid cancer types was shown to exploit CD73 overexpression as a suppressive immune checkpoint. Consequently, CD73-antagonistic antibodies, most notably oleclumab, are currently evaluated in several multicenter trials for clinical applicability. However, the efficacy of conventional monospecific CD73-inhibiting antibodies may be limited due to on-target/off-tumor binding to CD73 on normal cells. Therefore, a novel approach that more selectively directs CD73 immune checkpoint inhibition towards cancer cells is warranted.MethodsTo address this issue, we constructed a novel tetravalent bispecific antibody (bsAb), designated bsAb CD73xEGFR. Subsequently, the anticancer activities of bsAb CD73xEGFR were evaluated using in vitro and in vivo tumor models.ResultsIn vitro treatment of various carcinoma cell types with bsAb CD73xEGFR potently inhibited the enzyme activity of CD73 (~71%) in an EGFR-directed manner. In this process, bsAb CD73xEGFR induced rapid internalization of antigen/antibody complexes, which resulted in a prolonged concurrent displacement of both CD73 and EGFR from the cancer cell surface. In addition, bsAb CD73xEGFR sensitized cancer to the cytotoxic activity of various chemotherapeutic agents and potently inhibited the proliferative/migratory capacity (~40%) of cancer cells. Unexpectedly, we uncovered that treatment of carcinoma cells with oleclumab appeared to enhance several pro-oncogenic features, including upregulation and phosphorylation of EGFR, tumor cell proliferation (~20%), and resistance towards cytotoxic agents and ionizing radiation (~39%). Importantly, in a tumor model using immunocompetent BALB/c mice inoculated with syngeneic CD73pos/EGFRposCT26 cancer cells, treatment with bsAb CD73xEGFR outperformed oleclumab (65% vs 31% tumor volume reduction). Compared with oleclumab, treatment with bsAb CD73xEGFR enhanced the intratumoral presence of CD8posT cells and M1 macrophages.ConclusionsBsAb CD73xEGFR outperforms oleclumab as it inhibits the CD73/ADO immune checkpoint in an EGFR-directed manner and concurrently counteracts several oncogenic activities of EGFR and CD73. Therefore, bsAb CD73xEGFR may be of significant clinical potential for various forms of difficult-to-treat solid cancer types.
Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice
Authors: Nguyen Khoa A , DePledge Lisa N , Bian Li , Ke Yao , Samedi Von , Berning Amber A , Owens Philip , Wang Xiao-Jing , Young Christian D 
Published: September 2023

BackgroundOral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC.MethodsOur study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation.ResultsIn our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner.ConclusionsOverall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.
Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada’s population
Authors: Yusuf Fardowsa L A , Asaf Ayesha , Marrie Ruth Ann , Li Ping , McKay Kyla , Zhao Yinshan , Zhu Feng , Maxwell Colleen , Tremlett Helen 
Published: September 2023

BackgroundPopulation-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce.MethodsWe accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date (‘MS onset’) was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups.ResultsFrom 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces.ConclusionsCanada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.
Autoantibody status according to multiparametric assay accurately estimates connective tissue disease classification and identifies clinically relevant disease clusters
Authors: Cafaro Giacomo , Bartoloni Elena , Baldini Chiara , Franceschini Franco , Riccieri Valeria , Fioravanti Antonella , Fornaro Marco , Ghirardello Anna , Palterer Boaz , Infantino Maria , Rigon Amelia , Del Rosso Stefania , Gerli Roberto , Villalta Danilo , Bizzaro Nicola 
Published: September 2023

ObjectiveAssessment of circulating autoantibodies represents one of the earliest diagnostic procedures in patients with suspected connective tissue disease (CTD), providing important information for disease diagnosis, identification and prediction of potential clinical manifestations. The purpose of this study was to evaluate the ability of multiparametric assay to correctly classify patients with multiple CTDs and healthy controls (HC), independent of clinical features, and to evaluate whether serological status could identify clusters of patients with similar clinical features.MethodsPatients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SjS), undifferentiated connective tissue disease (UCTD), idiopathic inflammatory myopathies (IIM) and HC were enrolled. Serum was tested for 29 autoantibodies. An XGBoost model, exclusively based on autoantibody titres was built and classification accuracy was evaluated. A hierarchical clustering model was subsequently developed and clinical/laboratory features compared among clusters.Results908 subjects were enrolled. The classification model showed a mean accuracy of 60.84±4.05% and a mean area under the receiver operator characteristic curve of 88.99±2.50%, with significant discrepancies among groups. Cluster analysis identified four clusters (CL). CL1 included patients with typical features of SLE. CL2 included most patients with SjS, along with some SLE and UCTD patients with SjS-like features. CL4 included anti-Jo1 patients only. CL3 was the largest and most heterogeneous, including all the remaining subjects, overall characterised by low titre or lower-prevalence autoantibodies.ConclusionExtended multiparametric autoantibody assay allowed an accurate classification of CTD patients, independently of clinical features. Clustering according to autoantibody titres is able to identify clusters of CTD subjects with similar clinical features, independently of their final diagnosis.
Automatic analysis of bronchus-artery dimensions to diagnose and monitor airways disease in cystic fibrosis
Authors: Lv Qianting , Gallardo-Estrella Leticia , Andrinopoulou Eleni-Rosalina , Chen Yuxin , Charbonnier Jean-Paul , Sandvik Rikke Mulvad , Caudri Daan , Nielsen Kim Gjerum , de Bruijne Marleen , Ciet Pierluigi , Tiddens Harm 
Published: September 2023

BackgroundCystic fibrosis (CF) lung disease is characterised by progressive airway wall thickening and widening. We aimed to validate an artificial intelligence-based algorithm to assess dimensions of all visible bronchus-artery (BA) pairs on chest CT scans from patients with CF.MethodsThe algorithm fully automatically segments the bronchial tree; identifies bronchial generations; matches bronchi with the adjacent arteries; measures for each BA-pair bronchial outer diameter (Bout), bronchial lumen diameter (Bin), bronchial wall thickness (Bwt) and adjacent artery diameter (A); and computes Bout/A, Bin/A and Bwt/A for each BA pair from the segmental bronchi to the last visible generation. Three datasets were used to validate the automatic BA analysis. First BA analysis was executed on 23 manually annotated CT scans (11 CF, 12 control subjects) to compare automatic with manual BA-analysis outcomes. Furthermore, the BA analysis was executed on two longitudinal datasets (Copenhagen 111 CTs, ataluren 347 CTs) to assess longitudinal BA changes and compare them with manual scoring results.ResultsThe automatic and manual BA analysis showed no significant differences in quantifying bronchi. For the longitudinal datasets the automatic BA analysis detected 247 and 347 BA pairs/CT in the Copenhagen and ataluren dataset, respectively. A significant increase of 0.02 of Bout/A and Bin/A was detected for Copenhagen dataset over an interval of 2 years, and 0.03 of Bout/A and 0.02 of Bin/A for ataluren dataset over an interval of 48 weeks (all p<0.001). The progression of 0.01 of Bwt/A was detected only in the ataluren dataset (p<0.001). BA-analysis outcomes showed weak to strong correlations (correlation coefficient from 0.29 to 0.84) with manual scoring results for airway disease.ConclusionThe BA analysis can fully automatically analyse a large number of BA pairs on chest CTs to detect and monitor progression of bronchial wall thickening and bronchial widening in patients with CF.
Nariai-like black holes in light of scale-dependent gravity
Authors: Rincón Ángel , Bargueño Pedro 
Published: September 2023

AbstractIn this work, we investigate for the first time Nariai-like black hole solutions in four dimensional space time with spherical symmetry in the context of scale-dependent gravity. In particular, we construct self-consistent solutions in such a way that the classical one that coming from Einstein theory) is also contained into our new results. We start by considering a truncated effective Einstein–Hilbert action with cosmological constant in which both the gravitational and the cosmological couplings are elevated to scale-dependent functions (instead of being coupling constants), taking advantage of the scale-dependent scenario, which is a concrete and simple approach strongly inspired by asymptotically safe gravity. We briefly discuss black hole thermodynamics and and compare it with its classical counterpart. The impact of non-Einsteinian features is encoded by the scale-dependent parameter, $$\epsilon $$
ϵ
. A few comments regarding the topology of the solution and their impact are also mentioned.
Photon region and shadow of a rotating 5D black string
Authors: Tang Zi-Yu , Kuang Xiao-Mei , Wang Bin , Qian Wei-Liang 
Published: September 2023

AbstractTo explore the possible clues for the extra dimension from the Event Horizon Telescope (EHT) observations, we study the shadow of the rotating 5D black string in General Relativity (GR). Instead of investigating the shadow in the effective 4D theory, we concern the motion of photons along the extra dimension z with a conserved momentum $$P_z$$

P
z

, which appears as an effective mass in the geodesic equations of photons. The existence of $$P_z$$

P
z

enlarges the photon regions and the shadow of the rotating 5D black string while it has slight impact on the distortion. The EHT observations of M87* and SgrA* can rule out the black string model with an infinite length along the extra dimension, and support the hypothesis that the extra dimension is compact to avoid the Gregory-Laflamme (GL) instability, where the length of the black string/the compact extra dimension can be constrained as $$2.03125~\textrm{mm} \lesssim \ell \lesssim 2.6~\textrm{mm}$$

2.03125

mm
≲
ℓ
≲
2.6

mm

and $$2.28070~\textrm{mm} \lesssim \ell \lesssim 2.6~\textrm{mm}$$

2.28070

mm
≲
ℓ
≲
2.6

mm

respectively.
Iterated Ore polynomial maps
Authors: Leroy André , Nasernejad Mehrdad 
Published: September 2023

We study a natural notion of polynomial maps attached to elements of an iterated Ore extension [Formula: see text]. We develop some tools to analyze these maps such as good points, multilinear transformations and P-independence. We also present polynomial maps arising in the Multivariate extensions [Formula: see text], introduced by Martínez-Peñas and Kschischang [Evaluation and interpolation over multivariate skew polynomial rings, J. Algebra 525 (2019) 111–139], through the use of Multilinear polynomial maps.
Estimating the Location of Acoustic Sources with Oceanic Internal Gravity Waves via Frequency-Difference Source Localization
Authors: Spiesberger John L. , Geroski David J. , Dowling David R. 
Published: September 2023

Frequency-difference source localization (FDSL) is a relatively new method for locating sources emitting acoustic or electromagnetic waves from recorded data. Estimates of location are produced by matching a nonlinear function of the received data with the same nonlinear function of modeled data. This so-called matched-field approach depends on the accuracy of the modeled field. FDSL exhibits less sensitivity to model errors in some cases of interest. Fluctuations of the speed of sound in the ocean are affected by a wide variety of phenomena and internal gravity waves is one where their spectrum is usually well known. There is no analytical theory for predicting how these fluctuations of sound speed affect the accuracy of FDSL, leaving a numerical evaluation as the alternative for the focus of this paper. Experimental application of FDSL was previously made for an acoustic source of 100 Hz bandwidth surrounding 250 Hz for a 129 km section in the Philippine Sea with data recorded on a long vertical array [Geroski and Dowling, Long-range frequency-difference source localization in the Philippine Sea, J. Acoust. Soc. Am. 146 (2019) 4727–4739.]. The role of internal waves is quantified with a realistic FDSL simulation using models based on the parabolic and ray approximations of the linear acoustic wave equation. The modeled vertical variation of FDSL error is similar to observed while the modeled horizontal error is too small. The complicated software model is automatic but is computationally intensive, with our version needing about 1.5 mo to compute on a PC with 16 cpu cores.
Empowering Storage Systems Research with NVMeVirt: A Comprehensive NVMe Device Emulator
Authors: Kim Sang-Hoon , Shim Jaehoon , Lee Euidong , Jeong Seongyeop , Kang Ilkueon , Kim Jin-Soo 
Published: September 2023

There have been drastic changes in the storage device landscape recently. At the center of the diverse storage landscape lies the NVMe interface, which allows high-performance and flexible communication models required by these next-generation device types. However, its hardware-oriented definition and specification are bottlenecking the development and evaluation cycle for new revolutionary storage devices. Furthermore, existing emulators lack the capability to support the advanced storage configurations that are currently in the spotlight.
In this article, we present NVMeVirt, a novel approach to facilitate software-defined NVMe devices. A user can define any NVMe device type with custom features, and NVMeVirt allows it to bridge the gap between the host I/O stack and the virtual NVMe device in software. We demonstrate the advantages and features of NVMeVirt by realizing various storage types and configurations, such as conventional SSDs, low-latency high-bandwidth NVM SSDs, zoned namespace SSDs, and key-value SSDs with the support of PCI peer-to-peer DMA and NVMe-oF target offloading. We also make cases for storage research with NVMeVirt, such as studying the performance characteristics of database engines and extending the NVMe specification for the improved key-value SSD performance.
Standardized Protocol for Chest Tube Management for Trauma Patients Significantly Decreases Complications
Authors: Dai Christopher A. , Fang Christopher J. , Schwartz David , Enderson Jessica , McMann Ashley , Hyde Russel , Smith Nathan , Serfin Jennifer 
Published: September 2023

Background. As health care shifts to a value-based model with a focus on patient outcomes per dollar spent, it is important to develop and evaluate standardized protocols that ultimately lead to improved patient outcomes and decreased hospital complications. Prior to our chest tube protocol, chest tube management at our Trauma Center was nonuniform and surgeon-specific. The aim of this study was to (1) develop an institutional standardized protocol for chest tube management at our Level II Trauma Center and (2) compare patient outcomes before and after the implementation of our protocol. Methods. An institutional, standardized protocol was initiated at our Level II-Certified Trauma Center teaching hospital in 2014. An IRB-approved, single-institution retrospective chart review was performed between January 2011 and May 2017, in order to capture the 3 years prior and 3 years after protocol implementation. All patients with a diagnosis of hemothorax or pneumothorax (H/PTX) from blunt or penetrating trauma that resulted in a >24 French chest tube placement were included in the study. Patients were excluded if interventional radiology (IR) placed the chest tube, the mechanism was nontraumatic, or the patient expired at index hospitalization. Univariate analyses were performed to evaluate significant differences in patient outcomes before and after the implementation of the protocol. Results. A total of 143 patients were analyzed for this study, with 43 preprotocol patients and 100 postprotocol patients. Hospital length of stay (LOS), persistent H/PTX, and the need for further surgical intervention all improved after the implementation of the standardized protocol (

p

< 0.04). Conclusions. Our standardized protocol for chest tube management at our Level II Trauma Center significantly improved patient outcomes and can serve as a model for similar institutions.