bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of assessment of programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer biopsies and surgical specimens
Authors: Noske Aurelia , Steiger Katja , Ballke Simone , Kiechle Marion , Oettler Dirk , Roth Wilfried , Weichert Wilko 
Published: January 2023

AimsProgrammed death-ligand 1 (PD-L1) status in triple-negative breast cancer (TNBC) is important for immune checkpoint inhibitor therapies but may vary between different immunohistochemical assays, scorings and the type of specimen used for analysis.MethodsWe compared the analytical concordance of three clinically relevant PD-L1 assays (VENTANA SP142, VENTANA SP263 and DAKO 22C3 pharmDx) assessing immune cell score (IC), tumour proportion score and combined positive score (CPS) in preoperative biopsies and resection specimens of primary TNBC. PD-L1 expression was scored on virtual whole slide images and compared with expression data from corresponding surgical specimens.ResultsThe mean PD-L1 positivity in TNBC biopsies defined as IC ≥1% and CPS ≥1 ranged between 11% and 61% with the lowest positivity for SP142 and highest for SP263. The corresponding surgical specimens showed overall higher positivity rates (53%–75%). When comparing biopsies with surgical specimens, the agreement for PD-L1 positivity with SP263 and 22C3 at IC score ≥1% and CPS ≥1 was fair (kappa 0.47–0.52) and poor for SP142 (kappa 0.15–0.19). Using CPS ≥10 cut-off, the agreement for SP263 was excellent (kappa 0.751) but poor for 22C3 (kappa 0.261). Spearman correlation coefficients ranged between 0.489 and 0.75 indicating a generally moderate to strong correlation between biopsies and surgical specimens for all assays and scores.ConclusionsWe demonstrate high accordance between biopsies and surgical specimens for SP263 and 22C3 scoring but less for SP142. Generally, biopsies are suitable for PD-L1 testing in TNBC but the appropriate assay, scoring and cut-off must be considered.
Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020
Authors: Albrecht Katinka , Strangfeld Anja , Marschall Ursula , Callhoff Johanna 
Published: January 2023

ObjectiveTo investigate prevalence, incidence and medication of interstitial lung disease (ILD) among German individuals with rheumatoid arthritis (RA).MethodsNationwide BARMER claims data from 2007 to 2020 were used. RA-ILD was identified by diagnosis codes, prescription of disease-modifying antirheumatic drugs (DMARDs) and lung diagnostics. ILD was assigned as incident or prevalent relative to the year of the first diagnosis. We identified prescriptions of glucocorticoids, conventional synthetic (cs), biological (b) and targeted synthetic (ts)DMARDs, antifibrotics and rheumatology and/or pulmonology care.ResultsAmong all persons with RA (40 686 in 2007 to 85 175 in 2020), 1.7%–2.2%/year had ILD with a slight decline since 2013. Incident ILD was 0.13%–0.21% per year and remained stable over time. ILD was more common in seropositive RA, in men and in the elderly (mean age 72 years in 2020). Glucocorticoids (84% to 68%), csDMARD (83% to 55%) and non-steroidal anti-inflammatory drug use (62% to 38%) declined, while bDMARDs (16% to 24%) rose. In 2020, 7% received tsDMARDs, 3% antifibrotics, 44% analgesics and 30% opioids. DMARD therapy was more common if a rheumatologist was involved and antifibrotics if a pulmonologist was involved. Opioid use was highest if no specialist was involved (39%) but also common in rheumatology care (32%) and less frequent in pulmonology care (21%).ConclusionsRA-ILD is rare and mainly affects elderly persons. No trend in incidence was observed but treatment strategies have enlarged. Specialist care is necessary to provide disease-specific therapies. The continuing high analgesic and opioid demand shows unmet needs in these patients.
Delays in care for hydrocephalus and spina bifida at a tertiary hospital in Somaliland
Authors: Dahir Shukri , Cotache-Condor Cesia , Grimm Andie , Mohamed Mubarak , Rice Henry , Smith Emily , Ismail Edna Adan 
Published: January 2023

BackgroundChildhood neurosurgical conditions such as hydrocephalus and spina bifida represent a significant burden of death and disability worldwide, particularly in low and middle-income countries. However, there are limited data on the disease prevalence and delays in care for pediatric neurosurgical conditions in very low-resource settings. This study aims to characterize the delays in access to care for pediatric neurosurgical conditions in Somaliland.MethodsWe performed a retrospective review of all children with congenital hydrocephalus and spina bifida admitted to the Edna University Hospital (EAUH) in Somaliland between 2011 and 2018. Patient demographics were analyzed with descriptive statistics and χ2test statistics. We defined delays in care for each condition based on standard care in high-income settings. Univariate and multivariate logistic regression were performed to evaluate predictors of delay in care. Statistical significance was set at p<0.05.ResultsA total of 344 children were admitted to EAUH with neurosurgical conditions from 2011 to 2018. The most common condition was congenital hydrocephalus (62%). Delays in care were found for 90% of patients and were associated with the type of diagnosis and region. The longest delay among children with spina bifida was 60 months, while the longest delay for children with congenital hydrocephalus was 36 months. Children with congenital hydrocephalus or spina bifida traveling from foreign countries had the highest waiting time to receive care, with a median delay of 8 months (IQR: 5–11 months) and 4 months (IQR: 3–7 months), respectively.ConclusionWe found significant delays in care for children with neurosurgical conditions in Somaliland. This country has an urgent need to scale up its surgical infrastructure, workforce, and referral pathways to address the needs of children with hydrocephalus and spina bifida.
Quasi-local studies of the particle surfaces and their stability in general spacetimes
Authors: Song Yong , Zhang Chuanyu 
Published: January 2023

AbstractIn this paper, enlightened by the definition of the photon surface given by Claudel, Virbhadra and Ellis, we give a quasi-local definition of the particle surface. From this definition, one can study the evolution of the circular orbits in general spacetime. Especially, we pointed out that this definition can be used to get the spherical circular orbits in stationary spacetimes which cannot be got by the definition of Claudel, Virbhadra and Ellis. Further, we give a condition to exclude the particle surface in spacetime without gravity. Simultaneously, we give a quasi-local definition of the stability of the particle surface in general spacetime. From this definition, one can get the evolution equation of the innermost stable circular orbit (ISCO) in general spacetime. To verify the correctness of these definitions, we studied the circular orbits in some special cases and the results are all consistent with the previous results.
Analysis of heat flow in the post-quasi-static approximation for gravitational collapse in five dimension
Authors: Zahra A. , Mardan S. A. , Noureen I. 
Published: January 2023

AbstractIn this work, a generalized framework of the post-quasistatic approximation in higher dimensional non-comoving coordinates is presented. We study the evolution of adiabatically radiating and dissipative fluid configuration in higher dimensional post-quasi-static approximation. An iterative method for describing self-gravitating spheres is developed for this purpose. Dissipation is described by free-streaming radiation and heat flux. We match the higher dimensional interior solution, in non-comoving coordinates, with the corresponding Vaidya exterior solution. The generalized form of post-quasistatic approximation leads to a system of higher dimensional surface equations. The surface equations are of significant importance in the understanding of the physical phenomenon like luminosity, Doppler shift and red-shift at the boundary surface of gravitating sources.
Gauge field localization in branes: coupling to a scalar function and coupling to torsion in teleparallel gravity scenario
Authors: Moreira A. R. P. , Belchior F. M. , Maluf R. V. , Almeida C. A. S. 
Published: January 2023

AbstractThis paper is aimed at investigating the behavior of gauge vector and tensor fields on thick brane in f(T) gravity. This thick brane is not capable of providing a normalizable zero mode for both gauge and Kalb Ramond fields. To overcome this problem, we propose two distinct types of gauge-invariant couplings. In the first coupling, the fields are minimally coupled to the scalar field responsible for generating the thick brane. In the second coupling, we use the geometric coupling in which the fields are non-minimally coupled to torsion. Another issue that we investigate is resonant modes, which allow us to understand the massive spectrum of fields. Indeed we note that an internal structure appears for the Kalb–Ramond massive solutions and both couplings show resonant modes of the massive spectrum.
K-Theory of the maximal and reduced Roe algebras of metric spaces with A-by-CE coarse fibrations
Authors: Guo Liang , Luo Zheng , Wang Qin , Zhang Yazhou 
Published: January 2023

Let [Formula: see text] be a discrete metric space with bounded geometry. In this paper, we show that if [Formula: see text] admits an “A-by-CE” coarse fibration, then the canonical quotient map [Formula: see text] from the maximal Roe algebra to the Roe algebra of [Formula: see text], and the canonical quotient map [Formula: see text] from the maximal uniform Roe algebra to the uniform Roe algebra of [Formula: see text], induce isomorphisms on [Formula: see text]-theory. A typical example of such a space arises from a sequence of group extensions [Formula: see text] such that the sequence [Formula: see text] has Yu’s property A, and the sequence [Formula: see text] admits a coarse embedding into Hilbert space. This extends an early result of Špakula and Willett [Maximal and reduced Roe algebras of coarsely embeddable spaces, J. Reine Angew. Math. 678 (2013) 35–68] to the case of metric spaces which may not admit a coarse embedding into Hilbert space. Moreover, it implies that the maximal coarse Baum–Connes conjecture holds for a large class of metric spaces which may not admit a fibered coarse embedding into Hilbert space.
Epigenetic–Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer
Authors: Das Chandrima , Adhikari Swagata , Bhattacharya Apoorva , Chakraborty Sanjukta , Mondal Payel , Yadav Shalini S. , Adhikary Santanu , Hunt Clayton R. , Yadav Kamlesh K. , Pandita Shruti , Roy Siddhartha , Tainer John A. , Ahmed Zamal , Pandita Tej K. 
Published: January 2023

AbstractTherapy resistance is imposing a daunting challenge on effective clinical management of breast cancer. Although the development of resistance to drugs is multifaceted, reprogramming of energy metabolism pathways is emerging as a central but heterogenous regulator of this therapeutic challenge. Metabolic heterogeneity in cancer cells is intricately associated with alterations of different signaling networks and activation of DNA damage response pathways. Here we consider how the dynamic metabolic milieu of cancer cells regulates their DNA damage repair ability to ultimately contribute to development of therapy resistance. Diverse epigenetic regulators are crucial in remodeling the metabolic landscape of cancer. This epigenetic–metabolic interplay profoundly affects genomic stability of the cancer cells as well as their resistance to genotoxic therapies. These observations identify defining mechanisms of cancer epigenetics–metabolism–DNA repair axis that can be critical for devising novel, targeted therapeutic approaches that could sensitize cancer cells to conventional treatment strategies.
National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH)
Authors: Meric-Bernstam Funda , Ford James M. , O'Dwyer Peter J. , Shapiro Geoffrey I. , McShane Lisa M. , Freidlin Boris , O'Cearbhaill Roisin E. , George Suzanne , Glade-Bender Julia , Lyman Gary H. , Tricoli James V. , Patton David , Hamilton Stanley R. , Gray Robert J. , Hawkins Douglas S. , Ramineni Bhanumati , Flaherty Keith T. , Grivas Petros , Yap Timothy A. , Berlin Jordan , Doroshow James H. , Harris Lyndsay N. , Moscow Jeffrey A. 
Published: January 2023

AbstractOver the past decade, multiple trials, including the precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of the cancer histology. Although many therapies are now approved for the treatment of cancers harboring specific genomic alterations, most patients do not respond to therapies targeting a single alteration. Further, when antitumor responses do occur, they are often not durable due to the development of drug resistance. Therefore, there is a great need to identify rational combination therapies that may be more effective. To address this need, the NCI and National Clinical Trials Network have developed NCI-ComboMATCH, the successor to NCI-MATCH. Like the original trial, NCI-ComboMATCH is a signal-seeking study. The goal of ComboMATCH is to overcome drug resistance to single-agent therapy and/or utilize novel synergies to increase efficacy by developing genomically-directed combination therapies, supported by strong preclinical in vivo evidence. Although NCI-MATCH was mainly comprised of multiple single-arm studies, NCI-ComboMATCH tests combination therapy, evaluating both combination of targeted agents as well as combinations of targeted therapy with chemotherapy. Although NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. Although NCI-MATCH consisted of single-arm studies, ComboMATCH utilizes single-arm as well as randomized designs. NCI-MATCH had a separate, parallel Pediatric MATCH trial, whereas ComboMATCH will include children within the same trial. We present rationale, scientific principles, study design, and logistics supporting the ComboMATCH study.
The WAVE2/miR-29/Integrin-β1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer
Authors: Rana Priyanka S. , Wang Wei , Markovic Vesna , Szpendyk Justin , Chan Ernest Ricky , Sossey-Alaoui Khalid 
Published: January 2023

Breast cancer is the most frequently diagnosed malignancy in women and the major cause of death because of its invasion, metastasis, and resistance to therapies capabilities. The most aggressive subtype of breast cancer is triple-negative breast cancer (TNBC) due to invasive and metastatic properties along with early age of diagnosis and poor prognosis. TNBC tumors do not express estrogen, progesterone, and HER2 receptors, which limits their treatment with targeted therapies. Cancer invasiveness and metastasis are known to be promoted by increased cell motility and upregulation of the WAVE proteins. While the contribution of WAVE2 to cancer progression is well documented, the WAVE2-mediated regulation of TNBC oncogenic properties is still under investigated, as does the molecular mechanisms by which WAVE2 regulates such oncogenic pathways. In this study, we show that WAVE2 plays a significant role in TNBC development, progression, and metastasis, through the regulation of miR-29 expression, which in turn targets Integrin-β1 (ITGB1) and its downstream oncogenic activities. Conversely, we found WAVE2 expression to be regulated by miR-29 in a negative regulatory feedback loop. Reexpression of exogenous WAVE2 in the WAVE2-deficient TNBC cells resulted in reactivation of ITGB1 expression and activity, further confirming the specificity of WAVE2 in regulating Integrin-β1. Together, our data identify a novel WAVE2/miR-29/ITGB1 signaling axis, which is essential for the regulation of the invasion-metastasis cascade in TNBC. Our findings offer new therapeutic strategies for the treatment of TNBC by targeting WAVE2 and/or its downstream effectors.Significance:Identification of a novel WAVE2/miR-29/ITGB1 signaling axis may provide new insights on how WAVE2 regulates the invasion-metastasis cascade of TNBC tumors through the modulation of ITGB1 and miR-29.
Sampling-Dependent Transition Paths of Iceland–Scotland Overflow Water
Authors: Beron-Vera F. J. , Olascoaga M. J. , Helfmann L. , Miron P. 
Published: January 2023

Abstract
In this note, we apply transition path theory (TPT) from Markov chains to shed light on the problem of Iceland–Scotland Overflow Water (ISOW) equatorward export. A recent analysis of observed trajectories of submerged floats demanded revision of the traditional abyssal circulation theory, which postulates that ISOW should steadily flow along a deep boundary current (DBC) around the subpolar North Atlantic prior to exiting it. The TPT analyses carried out here allow attention to be focused on the portions of flow from the origin of ISOW to the region where ISOW exits the subpolar North Atlantic and suggest that insufficient sampling may be biasing the aforementioned demand. The analyses, appropriately adapted to represent a continuous input of ISOW, are carried out on three time-homogeneous Markov chains modeling the ISOW flow. One is constructed using a high number of simulated trajectories homogeneously covering the flow domain. The other two use much fewer trajectories which heterogeneously cover the domain. The trajectories in the latter two chains are observed trajectories or simulated trajectories subsampled at the observed frequency. While the densely sampled chain supports a well-defined DBC, whether this is a peculiarity of the simulation considered or not, the more heterogeneously sampled chains do not, irrespective of the nature of the trajectories used, i.e., observed or simulated. Studying the sampling sensitivity of the Markov chains, we can give recommendations for enlarging the existing float dataset to improve the significance of conclusions about long-time-asymptotic aspects of the ISOW circulation.
Meta-governance, uncertainty and self-organization in corporatist social service sectors: The case of Hong Kong
Authors: Wang Xiao Lu 
Published: January 2023

This article explores the relationship between meta-governance, uncertainty and governance network responses. A social network analysis was conducted on the interlocking directorate network among nonprofits before and after a market-oriented collibration triggered by a new public management reform to the corporatist social service provision system in Hong Kong. By unpacking and showing the distinct processes of network formation in response to substantive and strategic uncertainty arising from the market-oriented collibration, the study shows that although more nonprofit actors were directly included in the formalized policy venues after the reform, the network density and clustering coefficient dropped after the reform, potentially reducing the self-coordinating capacity of the governance network. However, for some nonprofit actors, node betweenness centrality increased and node degree centrality decreased, creating an enabling condition for adaption. Points for practitioners The uncertainties in meta-governance may bring about network processes at variance with the original intentions of public meta-governors that actors with complementary resources and competences combine their efforts in the provision of services and service innovation. To manage substantive and strategic uncertainties, public meta-governors need to find ways to increase the shared understandings of social problems, enhance the clarity of policy goals, and find a balance when collaborating between collaborative and market modes of governance.
Investigation of the spring-back phenomenon in two-dimensional bending of continuous glass fiber-reinforced polyamide composite sheets
Authors: Onur OZDEMIR A. 
Published: January 2023

Thermoplastic composite sheets have great potential for use in industrial applications owing to their fast-forming properties in the mold. One of the important matters of forming is the tendency of the part to recover elastically after it comes out of the mold. This behavior affects the dimensional accuracy of the final part. In this study, V-bending experiments were carried out to understand the spring-back phenomenon of continuous glass fiber-reinforced polyamide-6 composite sheets. Unidirectional and cross-ply composite sheets were used in the experiments and bending angle, die radius, pressure, and dwell-time were investigated systematically. After bending, the spring-back angles of the parts were measured and the effects of the inspected parameters were compared. Also, variations in part thickness caused by spring-back were evaluated. Finally, the deformations in the specimens resulting from the residual stress were visualized with a scanning electron microscope. When the results were compared, it was determined that the bending conditions where the spring-back defect could be minimized were 6 mm radius, 90° angle, 120 s dwell-time, and 3 MPa pressure. Under these situations and in sheets bent 90°, the amount of spring-back was determined as 22° for unidirectional composites and 15° for cross-ply composites.
Artificial intelligence in medicine – is too much transparency a good thing?
Authors: Nolan Paul 
Published: January 2023

Some encouraging uses for AI in medicine will lead to potentially novel legal liability issues. Complex algorithms involve an opacity that creates problems for the medical and legal professions alike. As iatrogenic injury is common in medical malpractice, the medical profession is understandably concerned when AI is introduced in diagnostic and therapeutic devices and events and outcome cannot be fully explained due to the “black box” effect. A concern about machine learning algorithms is the black box issue and understanding how conclusions or outcomes are reached. The deployment of AI devices in healthcare will require an increase in a clinician’s understanding of AI to increase the transparency of their use. An important aspect of medical treatment is the notion of “therapeutic privilege”. This will only arise in limited circumstances and requires the clinician to make a judgment, based on reasonable grounds, that the patient’s physical or mental health might be seriously harmed by providing the information. Given the complexity of AI and the black box effect, could too much AI transparency possibly overwhelm a patient, such that it may dissuade them from giving consent in circumstances where treatment is necessary and essential? In other words, too much AI transparency and information may inadvertently hinder treatment and progress.