bluuebunny/crossref_metadata_2025_split huggingface dataset:
GranularNF
Authors: Wu Ziyan , Cui Tianming , Narayanan Arvind , Zhang Yang , Lu Kangjie , Zhai Antonia , Zhang Zhi-Li 
Published: August 2022

In this paper, we consider the challenges that arise from the need to scale virtualized network functions (VNFs) at 100 Gbps line speed and beyond. Traditional VNF designs are monolithic in state management and scheduling: internally maintaining all states and operations associated with them. Without proper design considerations, it suffers from limitations when scaling at 100 Gbps link speed and beyond: the inability of efficient utilization of the cache because of the contention due to the frequent control plane activities, computational/memory-intensive tasks taking up CPU times, shares states causing the synchronization among the cores.
We address these limitations by arguing for the need to granularly decompose a VNF into data/control components that are co-located within a server but can be independently scaled among the cores. To realize the approach, we design a "serverless" programming framework with novel abstraction to optimize the data components that must process packets at the line speed, reduce the contention of the data states and enable run-time scheduling of different components for improved resource utilization. The abstractions, combined with the runtime system that we design, help NFV developers focus on the logic and correctness of VNF programming without worrying about how VNFs may be scaled in or out. We evaluate our platform by comparing it with monolithic approaches using different workloads and by analyzing its advantages of separation on scalability, performance determinism, and feature velocity.
Prognostic Value of GPNMB, EGFR, p-PI3K, and Ki-67 in Patients with Esophageal Squamous Cell Carcinoma
Authors: Wang Bo , Li Mengyan , Su Anna , Gao Yongmei , Shi Yan , Li Chao , Liu Wenying , Su Liping , Li Wan , Ma Yuqing 
Published: August 2022

Background. GPNMB is a newly discovered tumour-promoting factor that may promote tumour cell progression by activating the PI3K/AKT pathway by EGFR. However, there are insufficient studies about GPNMB in ESCC. This study investigated the relationship between GPNMB and EGFR/PI3K pathway genes in ESCC. Methods. The expression levels of GPNMB, EGFR, p-PI3K, and Ki-67 were examined using immunohistochemistry. Statistical analysis was done by SPSS 22.0 and R. Results. GPNMB mRNA expression is higher in ESCC compared with paracancerous tissues. The expression of EGFR, PIK3CA, PIK3CB, and AKT1 was increased in GPNMB upregulated samples. GPNMB expression was positively correlated with EGFR, p-PI3K, and Ki-67 expression. GPNMB was expressed higher in the AJCC III stage, lymph node metastasis, and moderately poorly differentiated patients. EGFR was higher expressed in patients with vascular invasion; p-PI3K expression in Kazak was higher than that in Han; Ki-67 expression was higher in

tumour

size
≥
3

cm

. Patients with high expression of GPNMB, p-PI3K, and Ki-67 had worse OS. p-PI3K, Ki-67, nerve invasion, and lymphatic metastasis were independent risk factors, and postoperative adjuvant therapy was a protective factor in ESCC. Conclusion. As a tumour-promoting factor, GPNMB is expected to be a potential target for ESCC.
Phase Ia/b, Open-Label, Multicenter Study of AZD4635 (an Adenosine A2A Receptor Antagonist) as Monotherapy or Combined with Durvalumab, in Patients with Solid Tumors
Authors: Lim Emerson A. , Bendell Johanna C. , Falchook Gerald S. , Bauer Todd M. , Drake Charles G. , Choe Jennifer H. , George Daniel J. , Karlix Janet L. , Ulahannan Susanna , Sachsenmeier Kris F. , Russell Deanna L. , Moorthy Ganesh , Sidders Ben S. , Pilling Elizabeth A. , Chen Huifang , Hattersley Maureen M. , Das Mayukh , Kumar Rakesh , Pouliot Gayle P. , Patel Manish R. 
Published: August 2022

AbstractPurpose:To evaluate AZD4635, an adenosine A2A receptor antagonist, as monotherapy or in combination with durvalumab in patients with advanced solid tumors.Patients and Methods:In phase Ia (dose escalation), patients had relapsed/refractory solid tumors; in phase Ib (dose expansion), patients had checkpoint inhibitor–naïve metastatic castration-resistant prostate cancer (mCRPC) or colorectal carcinoma, non–small cell lung cancer with prior anti–PD-1/PD-L1 exposure, or other solid tumors (checkpoint-naïve or prior anti–PD-1/PD-L1 exposure). Patients received AZD4635 monotherapy (75–200 mg once daily or 125 mg twice daily) or in combination with durvalumab (AZD4635 75 or 100 mg once daily). The primary objective was safety; secondary objectives included antitumor activity and pharmacokinetics; exploratory objectives included evaluation of an adenosine gene signature in patients with mCRPC.Results:As of September 8, 2020, 250 patients were treated (AZD4635, n = 161; AZD4635+durvalumab, n = 89). In phase Ia, DLTs were observed with monotherapy (125 mg twice daily; n = 2) and with combination treatment (75 mg; n = 1) in patients receiving nanosuspension. The most common treatment-related adverse events included nausea, fatigue, vomiting, decreased appetite, dizziness, and diarrhea. The RP2D of the AZD4635 capsule formulation was 75 mg once daily, as monotherapy or in combination with durvalumab. The pharmacokinetic profile was dose-proportional, and exposure was adequate to cover target with 100 mg nanosuspension or 75 mg capsule once daily. In patients with mCRPC receiving monotherapy or combination treatment, tumor responses (2/39 and 6/37, respectively) and prostate-specific antigen responses (3/60 and 10/45, respectively) were observed. High versus low blood-based adenosine signature was associated with median progression-free survival of 21 weeks versus 8.7 weeks.Conclusions:AZD4635 monotherapy or combination therapy was well tolerated. Objective responses support additional phase II combination studies in patients with mCRPC.
Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer
Authors: Constantinidou Anastasia , Marcou Yiola , Toss Michael S. , Simmons Timothy , Bernhisel Ryan , Hughes Elisha , Probst Braden , Meek Stephanie , Kakouri Eleni , Georgiou Georgios , Zouvani Ioanna , Savvidou Gabriella , Kuhl Vanessa , Doedt Jennifer , Wagner Susanne , Gutin Alexander , Slavin Thomas P. , Lanchbury Jerry S. , Kronenwett Ralf , Ellis Ian O. , Rakha Emad A. 
Published: August 2022

Abstract

Purpose:
The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor–positive (ER+), HER2− breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women.

Experimental Design:
Tumor samples from 385 pre-menopausal women with ER+, HER2− primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence–free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan–Meier analysis.

Results:
After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18–1.50; P = 7.2 × 10–6; HR, 3.58; 95% CI, 2.26–5.66; P = 9.8 × 10–8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40–15.17; P = 4.2 × 10–3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%–99%) and 76% (95% CI, 67%–82%), respectively.

Conclusions:
The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.
High-Dimensional and Spatial Analysis Reveals Immune Landscape–Dependent Progression in Cutaneous Squamous Cell Carcinoma
Authors: Ferguson Angela L. , Sharman Ashleigh R. , Allen Ruth O. , Ye Thomas , Lee Jenny H. , Low Tsu-Hui H. , Ch'ng Sydney , Palme Carsten E. , Ashford Bruce , Ranson Marie , Clark Jonathan R. , Patrick Ellis , Gupta Ruta , Palendira Umaimainthan 
Published: August 2022

AbstractPurpose:The tumor immune microenvironment impacts the biological behavior of the tumor, but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown.Experimental Design:We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasized using multiparameter imaging mass cytometry. The cohort included both immunosuppressed patients (IS) and patients with an absence of clinical immune-suppression (ACIS). Spatial analyses were used to identify cellular interactions that were associated with tumor behavior.Results:Nonprogressing primary HNcSCC were characterized by higher CD8+ and CD4+ T-cell responses, including numerically increased regulatory T cells. In contrast, primary lesions from HNcSCC patients who progressed were largely devoid of T cells with lower numbers of innate immune cells and increased expression of checkpoint receptors and in the metastatic lesions were characterized by an accumulation of B cells. Spatial analysis reveals multiple cellular interactions associated with nonprogressing primary tumors that were distinct in primary tumors of disease-progressing patients. Cellular regional analysis of the tumor microenvironment also shows squamous cell–enriched tumor regions associated with primary nonprogressing tumors.Conclusions:Effective responses from both CD8+ and CD4+ T cells in the tumor microenvironment are essential for immune control of primary HNcSCC. Our findings indicate that the early events that shape the immune responses in primary tumors dictate progression and disease outcomes in HNcSCC.
Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study
Authors: Mao Lili , Fang Meiyu , Chen Yu , Wei Xiaoting , Cao Jun , Lin Jing , Zhang Peng , Chen Ling , Cao Xiao , Chen Yujun , Guo Jun , Si Lu 
Published: August 2022

Abstract

Purpose:
Anti–programmed cell death-1 monotherapy is part of standard therapy for cutaneous melanoma but has low efficacy in mucosal melanoma. We evaluated the efficacy and safety of atezolizumab plus bevacizumab as first-line therapy for advanced mucosal melanoma.

Patients and Methods:
This multicenter, open-label, single-arm, phase II study used a Simon's two-stage design. Atezolizumab (fixed-dose, 1,200 mg) and bevacizumab (7.5 mg/kg) were administered by intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR), determined per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety, with adverse events (AE) summarized using NCI-CTCAE v5.0.

Results:
Overall, 43 patients were enrolled, including 20 (46.5%) with unresectable and 23 (53.5%) with metastatic mucosal melanoma. Median follow-up was 13.4 months at data cutoff (July 30, 2021). Forty patients were evaluable for response: ORR was 45.0% [95% confidence interval (CI), 29.3%–61.5%; one complete response, 17 partial responses]. Median PFS was 8.2 months (95% CI, 2.7–9.6); 6- and 12-month PFS rates were 53.4% (95% CI, 36.6%–67.6%) and 28.1% (95% CI, 14.2%–43.9%), respectively. Median OS was not reached (NR; 95% CI, 14.4–NR). Six- and 12-month OS rates were 92.5% (95% CI, 78.5%–97.5%) and 76.0% (95% CI, 57.1%–87.5%), respectively. Median DOR was 12.5 months (95% CI, 5.5–NR). Overall, 90.7% (39/43) of patients experienced treatment-related AEs; 25.6% (11/43) experienced grade ≥3 events.

Conclusions:
Atezolizumab in combination with bevacizumab showed promising efficacy and manageable safety in patients with advanced mucosal melanoma.
Raptinal Induces Gasdermin E–Dependent Pyroptosis in Naïve and Therapy-Resistant Melanoma
Authors: Vernon Megane , Wilski Nicole A. , Kotas Daniel , Cai Weijia , Pomante Danielle , Tiago Manoela , Alnemri Emad S. , Aplin Andrew E. 
Published: August 2022

Abstract

Lack of response and acquired resistance continue to be limitations of targeted and immune-based therapies. Pyroptosis is an inflammatory form of cell death characterized by the release of inflammatory damage-associated molecular patterns (DAMP) and cytokines via gasdermin (GSDM) protein pores in the plasma membrane. Induction of pyroptosis has implications for treatment strategies in both therapy-responsive, as well as resistance forms of melanoma. We show that the caspase-3 activator, raptinal, induces pyroptosis in both human and mouse melanoma cell line models and delays tumor growth in vivo. Release of DAMPs and inflammatory cytokines was dependent on caspase activity and GSDME expression. Furthermore, raptinal stimulated pyroptosis in melanoma models that have acquired resistance to BRAF and MEK inhibitor therapy. These findings add support to efforts to induce pyroptosis in both the treatment-naïve and resistant settings.

Implications:
Raptinal can rapidly induce pyroptosis in naïve and BRAFi plus MEKi-resistant melanoma, which may be beneficial for patients who have developed acquired resistance to targeted therapies.
Management of Infective Endocarditis in People Who Inject Drugs: A Scientific Statement From the American Heart Association
Authors: Baddour Larry M. , Weimer Melissa B. , Wurcel Alysse G. , McElhinney Doff B. , Marks Laura R. , Fanucchi Laura C. , Esquer Garrigos Zerelda , Pettersson Gosta B. , DeSimone Daniel C. ,   on behalf of the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Peripheral Vascular Disease
Published: August 2022

Background:
The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis–related documents.

Methods:
A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates.

Conclusions:
Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.
Terminology for a FAIR Framework for the Virus Outbreak Data Network-Africa
Authors: Plug Ruduan , Liang Yan , Aktau Aliya , Basajja Mariam , Oladipo Francisca , van Reisen Mirjam 
Published: August 2022

Abstract
The field of health data management poses unique challenges in relation to data ownership, the privacy of data subjects, and the reusability of data. The FAIR Guidelines have been developed to address these challenges. The Virus Outbreak Data Network (VODAN) architecture builds on these principles, using the European Union's General Data Protection Regulation (GDPR) framework to ensure compliance with local data regulations, while using information knowledge management concepts to further improve data provenance and interoperability. In this article we provide an overview of the terminology used in the field of FAIR data management, with a specific focus on FAIR compliant health information management, as implemented in the VODAN architecture.
Possibility of Enhancing Digital Health Interoperability in Uganda through FAIR Data
Authors: Basajja Mariam , Nambobi Mutwalibi , Wolstencroft Katy 
Published: August 2022

Abstract
The digital health landscape in Uganda is plagued by problems with interoperability and sustainability, due to fragmentation and a lack of integrated digital health solutions. This can be partly attributed to the absence of policies on the interoperability of data, as well as the fact that there is no common goal to make digital data and data infrastructure interoperable across the data ecosystem. The promulgation of the FAIR Guidelines in 2016 brought together various data stewards and stakeholders to adopt a common vision on data management and enable greater interoperability. This article explores the potential of enhancing digital health interoperability through FAIR by analysing the digital solutions piloted in Uganda and their sustainability. It looks at the factors that are currently hindering interoperability by examining existing digital health solutions in Uganda, such as the Digital Health Atlas Uganda (DHA-U) and Uganda Digital Health Dashboard (UDHD). The level of FAIRness of the two dashboards was determined using the FAIR Evaluation Services tool. Analysis was also carried out to discover the level of FAIRness of the digital health solutions within the dashboards and the most frequently used software applications and data standards by the different digital health interventions in Uganda.
Qatar: Constitutional Challenges
Authors: Al-Sayed Hassan Abdulrahim 
Published: August 2022

This chapter examines the development of Qatar’s constitutional system. It is divided into two main sections. The first is historic: it describes Qatar’s political and constitutional system under British authority, under the Provisional Basic Law of 1970 (‘the Provisional Basic Law’), and under the amended Provisional Basic Law of 1972 (‘the Amended Provisional Basic Law’). The second section examines the events leading up to the passage of a permanent Constitution in 2004 (the ‘2004 Constitution’, or the ‘Permanent Constitution’), and in this section we learn about the scope of the democratic system and the principle of separation of powers stipulated in the Constitution. This section analyzes the main provisions of this text. It shows that while the 2004 Constitution provides for the transformation of Qatar’s fully appointed Advisory Council (the ‘Council’ or ‘Shura Council’) into a partially elected legislative body, these provisions were not enforced until the Shura Council elections of October 2021.
The chapter details how the 2004 Constitution created important changes by permitting – for the first time – the judiciary to exercise competence over administrative and constitutional matters. As a result, Qatar has established specialized administrative districts in the Court of First Instance and the Court of Appeal that exercise oversight over some government agencies. Yet even in this area, progress has been uneven. Although courts are empowered to exercise judicial review, specific areas of redress are deemed non-justiciable. In addition, provisions related to the development of a constitutional court remain un-activated. The chapter will also examine the Shura Council elections that took place in October 2021, and related events.
How to be Great (Britain)? Discourses of Greatness in the United Kingdom’s Referendums on Europe
Authors: Rogstad Adrian , Martill Benjamin 
Published: August 2022

Abstract
This article analyses the discursive constitution and contestation of British ‘greatness’ during the campaigns for the 1975 referendum on UK membership of the European Communities and the 2016 referendum on membership of the European Union. It finds that ideas about British greatness formed a central part of the discourse on Britain’s role in the world on both sides in each campaign, joining recent literature on Brexit challenging the view that greatness has been primarily a right-wing preoccupation. By demonstrating the existence of distinct yet overlapping discourses of greatness, the article also adds nuance to accounts of the centrality of greatness to British foreign policy identity. The article employs a discourse-theoretical approach to uncover the central discursive ‘nodal points’ and the ‘floating signifiers’ of greatness claimed by each side. Empirically, it draws on a collection of campaign materials from both referendums.
Globalisation, Divided Societies and Nation-Centred Economic Policies in America and Britain
Authors: Schirm Stefan A. 
Published: August 2022

Abstract
A stronger emphasis on domestic politics and national sovereignty has recently shaped international economic relations, for instance, in the United Kingdom and the United States. This trend weakened the liberal international economic order (lio) with its promotion of globalisation and multilateralism. Why have the UK and the US, which formerly spearheaded the liberal order, embraced nation-centred foreign economic policies (ncp) under the Trump and Johnson governments? I argue that domestic forces predominantly drove this shift, since a political de facto alignment of value-based societal ideas and material interests increasingly favoured national self-determination and the privileging of domestic groups. The negative consequences of the lio such as rising income inequality, job losses and a perceived heteronomy had strengthened societal ideas and interests that converged in support of ncp. I examine these arguments by applying the societal approach to governmental preference formation in case studies on Johnson’s Brexit policy and Trump’s trade policy towards China.
On a Path towards Forgiveness: Garden-Practices and Aesthetics of Engagement in Tan Twan Eng’s
Authors: Pradittatsanee Darin 
Published: August 2022

Abstract
This paper examines the human-nature relationship in the art of Japanese gardening in Tan Twan Eng’s The Garden of Evening Mists (2012). Drawing upon the aesthetics of Japanese gardening and theories of garden art, it argues that the novel advocates the complementarity of nature and human artifice in gardening. Japanese gardening which is related to the Taoist concept of yinyang and the Buddhist notion of impermanence, together with its principle of shakkei (borrowed landscape), suggests a combination of anthropocentric and ecocentric relationships with nature. Moreover, since Japanese aesthetics is interwoven with ways of living, the paper examines how the female protagonist’s apprenticeship to a Japanese gardener in the Cameron Highlands of Malaya gradually alters her mind and opens up ways of coping with her traumatic experience, during the Occupation, in a Japanese internment camp. It argues that gardening art, what art philosopher Arnold Berleant calls the “aesthetics of engagement,” and changing gardenscape induce the protagonist to comprehend impermanence, moral ambiguity and the complementary co-existence of memory and forgetting, all of which enable her to forgive the Japanese transgressors and to make peace with the past.