bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vertebroplasty and kyphoplasty in the USA from 2004 to 2017: national inpatient trends, regional variations, associated diagnoses, and outcomes
Authors: Hafezi-Nejad Nima , Bailey Christopher R , Solomon Alex J , Abou Areda Moustafa , Carrino John A , Khan Majid , Weiss Clifford R 
Published: December 2020

BackgroundTo explore the national inpatient trends, regional variations, associated diagnoses, and outcomes of vertebral augmentation (vertebroplasty and kyphoplasty) in the USA from 2004 to 2017.MethodsData from the National Inpatient Sample were used to study hospitalization records for percutaneous vertebroplasty and kyphoplasty. Longitudinal projections of trends and outcomes, including mortality, post-procedural complications, length of stay, disposition, and total hospital charges were analyzed.ResultsFollowing a period of decreased utilization from 2008 to 2012, hospitalizations for vertebroplasty and kyphoplasty plateaued after 2013. Total hospital charges and overall financial burden of hospitalizations for vertebroplasty and kyphoplasty increased to a peak of $1.9 billion (range $1.7–$2.2 billion) in 2017. Overall, 8% of procedures were performed in patients with a history of malignancy. In multivariable modeling, lung cancer (adjusted OR (aOR) 2.6 (range 1.4–5.1)) and prostate cancer (aOR 3.4 (range 1.2–9.4)) were associated with a higher risk of mortality. The New England region had the lowest frequency of routine disposition (14.1±1.1%) and the lowest average hospital charges ($47 885±$1351). In contrast, 34.0±0.8% had routine disposition in the West Central South region, and average hospital charges were as high as $99 836±$2259 in the Pacific region. The Mountain region had the lowest number of procedures (5365±272) and the highest mortality rate (1.2±0.3%).ConclusionNational inpatient trends of vertebroplasty and kyphoplasty utilization remained stable after a period of decline from 2008 to 2012, while the financial burden of hospitalizations increased. Despite recent improvements in outcomes, significant regional variations persisted across the USA.
Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective
Authors: Zaidat Osama O , Ribo Marc , Mattle Heinrich Paul , Saver Jeffrey L , Bozorgchami Hormozd , Yoo Albert J , Ehm Alexandra , Kottenmeier Emilie , Cameron Heather L , Qadeer Rana A , Andersson Tommy 
Published: December 2020

BackgroundFirst-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed.ObjectiveTo assess the economic impact of achieving complete or near complete reperfusion after the first pass.MethodsPost hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c–3 was achieved, stratified into two groups: (1) mTICI 2c–3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK).ResultsAmong patients who achieved mTICI 2c–3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0–2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24–33% reduction) and annual care (11–27% reduction) costs across all countries.ConclusionsFPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.
DNA methylation is associated with airflow obstruction in patients living with HIV
Authors: Hernandez Cordero Ana I , Yang Chen Xi , Obeidat Maen , Yang Julia , MacIsaac Julie , McEwen Lisa , Lin David , Kobor Michael , Novak Richard , Hudson Fleur , Klinker Hartwig , Dharan Nila , Man SF Paul , Sin Don D , Kunisaki Ken , Leung Janice 
Published: December 2020

Introduction
People living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.

Methods

Using blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV
1
, FEV
1
/FVC ratio and FEV
1
decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.

Results

Airflow obstruction as defined by a FEV
1
/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV
1
/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV
1
and FEV
1
/FVC, respectively. No positions were associated with FEV
1
decline.

Conclusion
A large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.
Impact of distance on postoperative follow-up in patients of pediatric surgery: a retrospective review
Authors: Wiebe Meagan E , Shawyer Anna C 
Published: December 2020

ObjectiveCentralization of medical services in Canada has resulted in patients travelling long distances for healthcare, which may compromise their health. We hypothesized that children living farther from a children’s hospital were offered and attended fewer follow-up appointments.MethodsWe reviewed children less than 17 years of age referred to the general surgery clinic at a tertiary children’s hospital during a 2-year period who underwent surgery. Descriptive statistics were performed.ResultsWe identified 723 patients. The majority were male (61%) with a median age of 7 years (range 18 days to16 years) and were from the major urban center (MUC) (56.3%). The median distance travelled to hospital for MUC patients was 8.9 km (range 0.9–22 km) vs 119.5 km (range 20.3–1950 km) for non-MUC patients. MUC children were offered more follow-up appointments (72.7% vs 60.8%, p<0.05). No significant differences existed in follow-up attendance rates (MUC 88.5% vs non-MUC 89.1%, p=0.84) or postoperative complications (9.8% vs 9.2%, p=0.78). There were no deaths.ConclusionsPatients living farther from a hospital were offered fewer follow-up appointments, but attended an equivalent rate of follow-ups when offered one. Telemedicine and remote follow-up are underused approaches that can permit follow-up appointments while reducing associated travel time and expenses.
Electroweak stability and discovery luminosities for new physics
Authors: Cankoçak Kerem , Demir Durmuş , Karahan Canan , Şen Sercan 
Published: December 2020

AbstractWhat is the luminosity needed for discovering new physics if the electroweak scale is to remain stable? In this work we study this question, with the pertinent example of a real singlet scalar which couples to the Higgs field at the renormalizable level. Observing that the electroweak scale remains stable if the two scalars couple in a see-sawic fashion through a mass-degeneracy-driven unification linkup among quartic couplings at a given scale, we show by detailed simulation studies of the $$pp\rightarrow (\mathrm{singlet\ scalar}) \rightarrow Z Z \rightarrow 4\ell $$

p
p
→
(

singlet

scalar

)
→
Z
Z
→
4
ℓ

channel that the HL-LHC, which is expected to deliver an integrated luminosity of $$3~\mathrm{ab^{-1}}$$

3

ab

-
1

, has no significant excess of signal over the background in the 800–2000 GeV mass range. The FCC-hh, on the other hand, can discover scalars up to a mass of 870 GeV with an integrated luminosity $$20~\mathrm{ab^{-1}}$$

20

ab

-
1

. Observation at $$3\sigma $$

3
σ

(discovery at $$5\sigma $$

5
σ

) of a new scalar with a minimum mass 800 GeV requires at least $$2~\mathrm{ab^{-1}}$$

2

ab

-
1

($$5.2~\mathrm{ab^{-1}}$$

5.2

ab

-
1

) integrated luminosity, showing that the new physics that does not destabilize the electroweak scale is accessible only at very high luminosities, and can be tested already in the early stages of the FCC-hh operation period.
The ATLAS Level-1 topological processor: Experience and upgrade plans
Authors: Martínez Carlos Moreno 
Published: December 2020

During Run 2 (2015–2018) the Large Hadron Collider has provided, at the World’s highest energy frontier, proton–proton collisions to the ATLAS experiment with high instantaneous luminosity (up to [Formula: see text]), placing stringent operational and physics requirements on the ATLAS trigger system in order to reduce the 40 MHz collision rate to a manageable event storage rate of 1 kHz, while not rejecting interesting collisions. The Level-1 trigger is the first rate-reducing step in the ATLAS trigger system with an output rate of up to 100 kHz and decision latency of less than 2.5 [Formula: see text]s. In Run 2, an important role was played by the Level-1 Topological Processor (L1Topo). This innovative system consists of two blades designed in AdvancedTCA form factor, mounting four individual state-of-the-art processors, and providing high input bandwidth and low latency data processing. Up to 128 topological trigger algorithms can be implemented to select interesting events by applying kinematic and angular requirements on electromagnetic clusters, hadronic jets, muons and total energy reconstructed in the ATLAS apparatus. This resulted in a significantly improved background rejection and enhanced acceptance of physics signal events, despite the increasing luminosity. The L1Topo system has become more and more important for physics analyses making use of low energy objects, commonly present in the Heavy Flavor or Higgs physics events, for example. An overview of the L1Topo architecture, simulation and performance results during Run 2 is presented alongside with upgrade plans for the L1Topo system to be installed for the future Run 3 data taking period.
Coprophilous fungal spores: non-pollen palynomorphs for the study of past megaherbivores
Authors: van Asperen Eline N. , Perrotti Angelina , Baker Ambroise 
Published: December 2020

Abstract
Spores from coprophilous fungi are some of the most widely used non-pollen palynomorphs. Over the last decades, these spores have become increasingly important as a proxy to study the Pleistocene and Holocene megafauna. Although the number of types used in palaeoecology is relatively small, there is a wide range of coprophilous fungal taxa whose utility in palaeoenvironmental reconstruction remains under-researched. However, environmental and taphonomic factors influencing preservation and recovery of these spores are still poorly understood. Furthermore, our understanding of whether and how spores are transported across the landscape is limited.
Dung fungal spore presence appears to correlate well with megaherbivore presence. However, depending on the site, some limitations can remain to quantitative reconstructions of megaherbivore abundance from dung fungal spore records. The presence of dung fungal spores is often more significant than their absence and variation in abundance with time should be interpreted with caution. Correlation with other proxies may provide a promising way forward.
The majority of studies using dung fungal spores as an indicator for large herbivore abundance are of records of Late Pleistocene and Holocene age, with a focus on Late Quaternary megafaunal extinction. However, more research could potentially extend records further back in time.
A Positive Feedback Loop of AKR1C3-Mediated Activation of NF-κB and STAT3 Facilitates Proliferation and Metastasis in Hepatocellular Carcinoma
Authors: Zhou Qingqing , Tian Wei , Jiang Zhiyuan , Huang Tingting , Ge Chao , Liu Tengfei , Zhao Fangyu , Chen Taoyang , Cui Ying , Li Hong , Yao Ming , Li Jinjun , Tian Hua 
Published: December 2020

AbstractAKR1C3 is an enzyme belonging to the aldo-ketoreductase family, the members of which catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. AKR1C3 plays an important role in tumor progression and metastasis, however, little is known about the function and the molecular mechanism underlying the role of AKR1C3 in hepatocellular carcinoma (HCC). In this study, we report that AKR1C3 is significantly upregulated in HCC and that increased AKR1C3 is associated with poor survival. AKR1C3 positively regulated HCC cell proliferation and metastasis in vitro and in vivo. AKR1C3 promoted tumor proliferation and metastasis by activating NF-κB signaling. Furthermore, AKR1C3 regulated NF-κB activity by modulating TRAF6 and inducing its autoubiquitination in HCC cells. Activation of NF-κB released proinflammatory factors that facilitated the phosphorylation of STAT3 and increased tumor cell proliferation and invasion. Gain- and loss-of-function experiments showed that AKR1C3 promoted tumor proliferation and invasion via the IL6/STAT3 pathway. STAT3 also directly bound the AKR1C3 promoter and increased transcription of AKR1C3, thereby establishing a positive regulatory feedback loop. Treatment with the AKR1C3 inhibitors indocin and medroxyprogesterone acetate inhibited tumor growth and invasion and promoted apoptosis in HCC cells. Collectively, these results indicate that a AKR1C3/NF-κB/STAT3 signaling loop results in HCC cell proliferation and metastasis and could be a promising therapeutic target in HCC.Significance:These findings elucidate a novel AKR1C3-driven signaling loop that regulates proliferation and metastasis in HCC, providing potential prognostic and therapeutic targets in this disease.
Unraveling the Mysteries of PAX8 in Reproductive Tract Cancers
Authors: Chaves-Moreira Daniele , Morin Patrice J. , Drapkin Ronny 
Published: December 2020

Abstract
Paired Box 8 (PAX8) is a lineage-specific transcription factor that has essential roles during embryogenesis and tumorigenesis. The importance of PAX8 in the development of the reproductive system is highlighted by abnormalities observed upon the loss or mutation of this PAX family member. In cancer, PAX8 expression is deregulated in a key set of neoplasms, including those arising from the Müllerian ducts. The roles of PAX8 in oncogenesis are diverse and include epigenetic remodeling, stimulation of proliferation, inhibition of apoptosis, and regulation of angiogenesis. PAX8 can interact with different protein partners during cancer progression and may exhibit significant function-altering alternative splicing. Moreover, expression of PAX8 in cancer can also serve as a biomarker for diagnostic and prognostic purposes. In this review, we focus on the roles of PAX8 in cancers of the reproductive system. Understanding the diverse mechanisms of action of PAX8 in development and oncogenesis may identify new vulnerabilities in malignancies that currently lack effective therapies.
Immunotherapy with Immunocytokines and PD-1 Blockade Enhances the Anticancer Activity of Small Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX
Authors: Millul Jacopo , Krudewig Christiane , Zana Aureliano , Dakhel Plaza Sheila , Puca Emanuele , Villa Alessandra , Neri Dario , Cazzamalli Samuele 
Published: December 2020

Abstract
Small molecule–drug conjugates (SMDCs) represent an alternative to conventional antitumor chemotherapeutic agents, with the potential to improve the therapeutic window of cytotoxic payloads through active delivery at the site of the disease. In this article, we describe novel combination therapies consisting of anti-carbonic anhydrase IX SMDCs combined with different immunomodulatory products. The therapeutic effect of the SMDCs was potentiated by combination with PD-1 blockade and with tumor-homing antibody–cytokine fusions in mouse models of renal cell carcinoma and colorectal cancer. The combination with L19-IL12, a fusion protein specific to the alternatively spliced EDB domain of fibronectin containing the murine IL12 moiety, was also active against large established tumors. Analysis of the microscopic structures of healthy organs performed 3 months after tumor eradication confirmed absence of pathologic abnormalities in the healthy kidney, liver, lung, stomach, and intestine. Our findings may be of clinical significance as they provide motivation for the development of combinations based on SMDCs and immunotherapy for the treatment of renal cell carcinoma and hypoxic tumors.
mDKN-01, a Novel Anti-DKK1 mAb, Enhances Innate Immune Responses in the Tumor Microenvironment
Authors: Haas Michael S. , Kagey Michael H. , Heath Heidi , Schuerpf Franziska , Rottman James B. , Newman Walter 
Published: December 2020

Abstract

Dickkopf-1 (DKK1), a secreted modulator of Wnt signaling, is overexpressed in many cancers, is often associated with worse clinical outcomes, and has been shown to have immunosuppressive effects. DKN-01 is an IgG4 clinical stage antibody that potently and specifically neutralizes human and murine DKK1 and has recently completed a promising study in combination with pembrolizumab in patients with gastric/gastroesophageal junction cancer. The purpose of this study is to characterize a murine version of DKN-01 (mDKN-01) and to better understand its mechanism of action. We examined the efficacy of mDKN-01 in both melanoma and metastatic breast cancer models. Immune depletion experiments revealed a requirement for natural killer (NK) but not B and T cells for tumor growth inhibition. mDKN-01 treatment promotes the induction of the NK-activating cytokines IL15 and IL33 as well as an enhanced recruitment of CD45+ cells. Other treatment-related changes include a reduction of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSC) in the tumor and spleen and the upregulation of PD-L1 on MDSCs. In addition, mDKN-01 has a marked effect at reducing pulmonary metastases in the mouse 4T1 breast cancer model. Finally, the mDKN-01/anti-PD-1 combination was more effective at inhibiting melanoma growth than mDKN-01 alone. Taken together, our data demonstrate that mDKN-01 has efficacy by blocking the immunosuppressive effects of DKK1 in the tumor microenvironment (TME) and provides insight into the clinical activity observed with DKN-01–based treatment.

Implications:
mDKN-01 reverses a DKK1-mediated innate immune suppression in the TME and has additive efficacy with a PD-1 inhibitor.
IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D
Authors: Kiss Máté , Vande Walle Lieselotte , Saavedra Pedro H.V. , Lebegge Els , Van Damme Helena , Murgaski Aleksandar , Qian Junbin , Ehling Manuel , Pretto Samantha , Bolli Evangelia , Keirsse Jiri , Bardet Pauline M.R. , Arnouk Sana M. , Elkrim Yvon , Schmoetten Maryse , Brughmans Jan , Debraekeleer Ayla , Fossoul Amelie , Boon Louis , Raes Geert , van Loo Geert , Lambrechts Diether , Mazzone Massimiliano , Beschin Alain , Wullaert Andy , Lamkanfi Mohamed , Van Ginderachter Jo A. , Laoui Damya 
Published: December 2020

AbstractIL1β is a central mediator of inflammation. Secretion of IL1β typically requires proteolytic maturation by the inflammasome and formation of membrane pores by gasdermin D (GSDMD). Emerging evidence suggests an important role for IL1β in promoting cancer progression in patients, but the underlying mechanisms are ill-defined. Here, we have shown a key role for IL1β in driving tumor progression in two distinct mouse tumor models. Notably, activation of the inflammasome, caspase-8, as well as the pore-forming proteins GSDMD and mixed lineage kinase domain–like protein in the host were dispensable for the release of intratumoral bioactive IL1β. Inflammasome-independent IL1β release promoted systemic neutrophil expansion and fostered accumulation of T-cell–suppressive neutrophils in the tumor. Moreover, IL1β was essential for neutrophil infiltration triggered by antiangiogenic therapy, thereby contributing to treatment-induced immunosuppression. Deletion of IL1β allowed intratumoral accumulation of CD8+ effector T cells that subsequently activated tumor-associated macrophages. Depletion of either CD8+ T cells or macrophages abolished tumor growth inhibition in IL1β-deficient mice, demonstrating a crucial role for CD8+ T-cell–macrophage cross-talk in the antitumor immune response. Overall, these results support a tumor-promoting role for IL1β through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for release of this cytokine in tumors.