bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LT003: Endothelin-1 drives invadopodia and cross-talk with submesothelial matrix invasion cell through ILK
Authors: Masi Ilenia , Caprara Valentina , Spadaro Francesca , Chellini Lidia , Sestito Rosanna , Zancla Andrea , Rainer Alberto , Bagnato Anna , Rosanò Laura 
Published: March 2021

Abstract
During the metastatic progression, invading cells might achieve degradation and invasion into the extracellular matrix (ECM) using invadopodia, actin-based protrusions. Several growth factors, among other stimuli, might induce invadopodia, generating signaling cues implicated from the initial steps of anchoring and protein recruitment to the final steps of matrix degradation or structure dissembling. In this context, the endothelin A receptor (ETAR) a drives invadopodia in serous ovarian cancer (SOC) cells through the scaffolding function of β-arrestin1 (β-arr1), although the coordinated signaling network is not fully explored. Growing evidence demonstrated that integrins and associated proteins, such as integrin-linked kinase (ILK), operate in the same subcellular compartments to control invadopodium maturation and ECM degradation. Since endothelin-1 (ET-1) through ETAR regulated by ILK, in this study whether ET-1/β-arr1-driven ILK signaling could provide additional mean to enhance invadopodium activity in ovarian cancer progression. We found that β-arr1 functions as a linker for ILK/βPIX (Pax-interacting exchange factor beta) complex, required for activation of Rac3 GTPase, emerging at a crossroad between adhesion and proteolytic signaling, resulting to be overexpressed in tumour compared normal ovarian tissues. Rac3 operates the phosphorylation of PAK1 and cofilin, and regulates invadopodia-dependent ECM degradation and invasion. Moreover, ETAR/ILK/Rac3-dependent signaling supports the communication of SOC cells with mesothelial cells, favouring adhesion and transmigration to. In vivo, ambrisentan, an ETAR antagonist, inhibits the adhesion of HG-SOC cells to intraperitoneal organs, and their spreading, associated with a reduction of invadopodia markers. Finally, high ETAR/ILK expression positively correlates with poor prognosis, representing SOC prognostic factors. Our findings uncover a paradigm indicating where ET-1R/β-arr1/ILK pathway integrates adhesive and proteolytic signaling to invadopodia-mediated ECM degradation, favouring cancer-stroma interactions and SOC metastatic behaviour.
Citation Format: Ilenia Masi, Valentina Caprara, Francesca Spadaro, Lidia Chellini, Rosanna Sestito, Andrea Zancla, Alberto Rainer, Anna Bagnato, Laura Rosanò. Endothelin-1 drives invadopodia and cross-talk with submesothelial matrix invasion cell through ILK [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT003.
Abstract PO005: Hepatic stellate cells suppress NK cell sustained breast cancer dormancy
Authors: Correia Ana Luisa 
Published: March 2021

Abstract
The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a singular therapeutic window to prevent metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of dormant DTC reservoirs is imperative. Here we reveal tissue-specific microenvironments that restrain or concede progression of breast cancer in the liver, a frequent site of metastasis and most times associated with patients’ cause of death. Using mouse models, we show that the dormant milieu features a selective accumulation of natural killer (NK) cells. Preserving the NK cell pool with adjuvant interleukin-15-based immunotherapy prevents hepatic metastases and prolongs survival. Exit from dormancy follows a dramatic contraction of the NK cell compartment, and concurrent accumulation of activated stellate cells. Our data identify the interplay between NK cells and activated stellate cells as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing DTC outgrowth and metastasis.
Citation Format: Ana Luisa Correia. Hepatic stellate cells suppress NK cell sustained breast cancer dormancy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO005.
Abstract PO007: Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma
Authors: Wenthe Sophia , Schulte Ashley J. , Angelos Mathew G. , Kaufman Dan S. , Modiano Jaime F. , Kim Jong Hyuk 
Published: March 2021

Abstract
Angiosarcoma (AS) is a highly aggressive, rare soft-tissue sarcoma that forms malignant blood vessels. Approximately half of patients have metastatic or unresectable disease with a median overall survival of less than 6 months, and tumor-related mortality is high. Inflamed tissue is frequently seen in angiosarcomas, and immune cells are key components that contribute to the landscape of the tumor microenvironment. Hemangiosarcoma (HSA) occurs commonly in companion dogs, and it shares clinical and morphological features with human AS. Recurrent mutations in TP53 and genes involved in PI3K pathway such as PIK3CA, and PIK3R1 were observed in both human AS and canine HSA, and the mutational landscape was associated with distinct molecular tumor subtypes; in particular, differing immunophenotypes. Recently, we have shown that human AS and canine HSA establish convergent transcriptional programs driven by angiogenic fusion genes and TP53 mutation. However, these vascular tumors are genomically complex, and molecular mechanisms that establish the tumor microenvironment are incompletely known. In this study, we analyzed RNA-seq transcriptomic data generated from human AS tissues (n=13) and canine HSA tissues (n=76) and HSA cell lines (n=11). The data showed that the tumors of both species enriched gene signatures associated with maintenance of hematopoietic stem cells. Then, we found that canine HSA cells supported expansion and differentiation of human CD34+ umbilical cord blood cells using long-term culture-initiating cell and colony-forming unit assays. We also developed xenograft models of canine HSA that facilitate myelopoiesis and macrophage infiltration in the tumor tissue. Our data showed that gene signatures of monocytes and naïve macrophages were detectable in canine HSA cells. In human ASs, macrophage-associated genes, in particular M2 macrophage signatures were significantly enriched, compared to normal tissues. Collectively, our data suggest that human AS and canine HSA have cell-autonomous capacity to govern hematopoietic progenitors and immune cells, potentially establishing the tumor immune niche. We engineered HSA cells to induce homozygous H1047R mutations in PIK3CA gene using CRISPR-Cas9 system. Our ongoing work is to determine if regulating PI3K pathway in the tumor cells contributes to the molecular programs that create the tumor niche of the vascular malignancy.
Citation Format: Sophia Wenthe, Ashley J. Schulte, Mathew G. Angelos, Dan S. Kaufman, Jaime F. Modiano, Jong Hyuk Kim. Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO007.
Teleconnections Governing the Interannual Variability of Great Plains Low-Level Jets in May
Authors: Agrawal Shubhi , Ferguson Craig R. , Bosart Lance , Burrows D. Alex 
Published: March 2021

AbstractA spectral analysis of Great Plains 850-hPa meridional winds (V850) from ECMWF’s coupled climate reanalysis of 1901–2010 (CERA-20C) reveals that their warm season (April–September) interannual variability peaks in May with 2–6-yr periodicity, suggestive of an underlying teleconnection influence on low-level jets (LLJs). Using an objective, dynamical jet classification framework based on 500-hPa wave activity, we pursue a large-scale teleconnection hypothesis separately for LLJs that are uncoupled (LLJUC) and coupled (LLJC) to the upper-level jet stream. Differentiating between jet types enables isolation of their respective sources of variability. In the U.S. south-central plains (SCP), May LLJCs account for nearly 1.6 times more precipitation and 1.5 times greater V850 compared to LLJUCs. Composite analyses of May 250-hPa geopotential height (Z250) conditioned on LLJC and LLJUC frequencies highlight a distinct planetary-scale Rossby wave pattern with wavenumber 5, indicative of an underlying circumglobal teleconnection (CGT). An index of May CGT is found to be significantly correlated with both LLJC (r = 0.62) and LLJUC (r = −0.48) frequencies. Additionally, a significant correlation is found between May LLJUC frequency and NAO (r = 0.33). Further analyses expose decadal-scale variations in the CGT–LLJC and CGT–LLJUC teleconnections that are linked to the PDO. Dynamically, these large-scale teleconnections impact LLJ class frequency and intensity via upper-level geopotential anomalies over the western United States that modulate near-surface geopotential and temperature gradients across the SCP.
Emergency Department Length of Stay and Mortality in Critically Injured Patients
Authors: Stey Anne M. , Kanzaria Hemal K. , Dudley R. Adams , Bilimoria Karl Y. , Knudson M. Margaret , Callcut Rachael A. 
Published: March 2021

Objective: Multicenter data from 2 decades ago demonstrated that critically ill and injured patients spending more than 6 hours in the emergency department (ED) before transfer to the intensive care unit (ICU) had higher mortality rates. A contemporary analysis of ED length of stay in critically injured patients at American College of Surgeons’ Trauma Quality Improvement Program (ACS-TQIP) centers was performed to test whether prolonged ED length of stay is still associated with mortality. Methods: This was an observational cohort study of critically injured patients admitted directly to ICU from the ED in ACS-TQIP centers from 2010-2015. Spending more than 6 hours in the ED was defined as prolonged ED length of stay. Patients with prolonged ED length of stay were matched to those with non-prolonged ED length of stay and mortality was compared. Main Results: A total of 113,097 patients were directly admitted from the ED to the ICU following injury. The median ED length of stay was 167 minutes. Prolonged ED length of stay occurred in 15,279 (13.5%) of patients. Women accounted for 29.4% of patients with prolonged ED length of stay but only 25.8% of patients with non-prolonged ED length of stay, P < 0.0001. Mortality rates were similar after matching—4.5% among patients with prolonged ED length of stay versus 4.2% among matched controls. Multivariable logistic regression of the matched cohorts demonstrated prolonged ED length of stay was not associated with mortality. However, women had higher adjusted mortality compared to men Odds Ratio = 1.41, 95% Confidence Interval 1.28 -1.61, P < 0.0001. Conclusion: Prolonged ED length of stay is no longer associated with mortality among critically injured patients. Women are more likely to have prolonged ED length of stay and mortality.
Indicators and determinants of the years of working life lost: a narrative review
Authors: Shiri Rahman , Hiilamo Aapo , Lallukka Tea 
Published: March 2021

Objective: This narrative review summarizes the available indicators for working life expectancy and years of working life lost (YWLL) and their determinants. Methods: We searched PubMed and Embase databases from their inception until August 2020 and screened all studies proposing an indicator for working life expectancy or YWLL. We also reviewed studies focusing on sociodemographic, lifestyle and work-related determinants of working life expectancy and YWLL. The results were synthesized narratively. Results: We identified 13 different indicators for the length of working life or YWLL. The most frequently used indicators were ‘working life expectancy’, ‘healthy working life expectancy’, and YWLL. Working life expectancy and healthy working life expectancy are longer for men than women. Working life expectancy at the age of 50 has been increasing since the mid-90s, and the increase has been larger for women, reducing the sex difference. Working life is shorter for people with a low level of education, in lower occupational classes, for people exposed to high physical work demands, those living in the most socioeconomically deprived areas, people with overweight or obesity, smokers, people who are inactive during leisure time and in people with a chronic health problem. Conclusions: Despite increasing interest in understanding the determinants of YWLL, only a few studies have simultaneously considered multiple exit routes from the labour market. We propose a new measure for total YWLL considering all relevant exit routes from employment. This comprehensive measure can be used to assess the effect of given policy changes on prolonging working life.
Who and how many can work from home? Evidence from task descriptions
Authors: Holgersen Henning , Jia Zhiyang , Svenkerud Simen 
Published: March 2021

AbstractThe Covid-19 crisis has forced great societal changes, including forcing many to work from home (WFH) in an effort to limit the spread of the disease. The ability to work from home has long been considered a perk, but we have few estimates of how many jobs are actually possible to be performed from home. This paper proposes a method to estimate the share of these jobs. For each occupation, we obtain a WFH friendly measure by asking respondents from Amazon Mechanical Turk (MTurk) to evaluate whether the corresponding tasks can be performed from home based on the descriptions from the International Standard Classification of Occupations 2008 (ISCO-08) standard. The share of WFH friendly jobs in an economy can then be estimated by combining these measures with the labor statistics on occupational employments. Using Norway as an illustrating example, we find that approximately 38% of Norwegian jobs can be performed from home. The Norwegian results also suggest that the pandemic and the government’s attempts to mitigate this crisis may have a quite uneven impact on the working population. Those who are already disadvantaged are often less likely to have jobs that can be performed from home.
The epidemiology of carbapenem resistance in Acinetobacter baumannii complex in Germany (2014–2018): an analysis of data from the national Antimicrobial Resistance Surveillance system
Authors: Said Dunja , Willrich Niklas , Ayobami Olaniyi , Noll Ines , Eckmanns Tim , Markwart Robby 
Published: March 2021

Abstract
Background
Carbapenem-resistant Acinetobacter baumannii complex (CRABC) has globally emerged as a serious public health challenge. This study aimed to describe epidemiological trends and risk factors of carbapenem resistance in A. baumannii complex isolates in Germany between 2014 and 2018.

Methods
We analysed 43,948 clinical A. baumannii complex isolates using 2014 to 2018 data from the German Antimicrobial Resistance Surveillance system. We applied descriptive statistics and uni- and multivariable regression analyses to investigate carbapenem resistance in A. baumannii complex isolates.

Results
The proportion of carbapenem resistance in clinical A. baumannii complex isolates declined from 7.6% (95% confidence interval [95% CI] 4.4–12.7%) in 2014 to 3.5% (95% CI 2.5–4.7%) in 2018 (adjusted OR [aOR] 0.85 [95% CI 0.79–0.93, p ≤ 0.001]). Higher mean CRABC proportions for 2014 to 2018 were observed in secondary care hospitals (4.9% [95% CI 3.2–7.5%], aOR 3.6 [95% CI 2.4–5.3, p ≤ 0.001]) and tertiary care hospitals (5.9% [95% CI 3.0–11.2%], aOR 5.4 [95% CI 2.9–10.0, p ≤ 0.001) compared to outpatient clinics (1.3% [95% CI 1.1–1.6%]). CRABC proportions in hospitals varied between German regions and ranged between 2.4% (95% CI 1.6–3.5%) in the Southeast and 8.8% (95% CI 4.2–17.3%) in the Northwest. Lower CRABC proportions were observed in younger patients (< 1 year: 0.6% [95% CI 0.2–1.3%]; 1–19 years: 1.3% [95% CI 0.7–2.5%]) than adults (20–39 years: 7.7% [95% CI 4.4–13.0%]; 40–59 years: 6.2% [4.2–8.9%]; 60–79 years: 5.8% [95% CI 4.0–8.3%]). In the 20–39 year old patient age group, CRABC proportions were significantly higher for men than for women (14.6% [95% CI 8.6–23.6%] vs. 2.5% [95% CI 1.3–4.5%]). A. baumannii complex isolates from lower respiratory infections were more likely to be carbapenem-resistant than isolates from upper respiratory infections (11.4% [95% CI 7.9–16.2%] vs. 4.0% [95% CI 2.7–6.0%]; adjusted OR: 1.5 [95% CI 1.2–1.9, p ≤ 0.001]).

Conclusions
In contrast to many other regions worldwide, carbapenem resistance proportions among clinical A. baumannii complex isolates are relatively low in Germany and have declined in the last few years. Ongoing efforts in antibiotic stewardship and infection prevention and control are needed to prevent the spread of carbapenem-resistant A. baumannii complex in Germany.
Lymphatic filariasis, infection status in Culex quinquefasciatus and Anopheles species after six rounds of mass drug administration in Masasi District, Tanzania
Authors: Lupenza Eliza , Gasarasi Dinah B. , Minzi Omary M. 
Published: March 2021

Abstract
Background
Lymphatic filariasis (LF) elimination program in Tanzania started in 2000 in response to the Global program for the elimination of LF by 2020. Evidence shows a persistent LF transmission despite more than a decade of mass drug administration (MDA). It is advocated that, regular monitoring should be conducted in endemic areas to evaluate the progress towards elimination and detect resurgence of the disease timely. This study was therefore designed to assess the status of Wuchereria bancrofti infection in Culex quinqefasciatus and Anopheles species after six rounds of MDA in Masasi District, South Eastern Tanzania.

Methods
Mosquitoes were collected between June and July 2019 using Center for Diseases Control (CDC) light traps and gravid traps for indoor and outdoor respectively. The collected mosquitoes were morphologically identified into respective species. Dissections and PCR were carried out to detect W. bancrofti infection. Questionnaire survey and checklist were used to assess vector control interventions and household environment respectively. A Poisson regression model was run to determine the effects of household environment on filarial vector density.

Results
Overall, 12 452 mosquitoes were collected of which 10 545 (84.7%) were filarial vectors. Of these, Anopheles gambiae complex, An. funestus group and Cx. quinquefasciatus accounted for 0.1%, 0.7% and 99.2% respectively. A total of 365 pools of Cx. quinquefasciatus (each with 20 mosquitoes) and 46 individual samples of Anopheles species were analyzed by PCR. For Cx. quinquefasciatus pools, 33 were positive for W. bancrofti, giving an infection rate of 0.5%, while the 46 samples of Anopheles species were all negative. All 1859 dissected mosquitoes analyzed by microscopy were also negative. Households with modern latrines had less mosquitoes than those with pit latrines [odds ratio (OR) = 0.407, P < 0.05]. Houses with unscreened windows had more mosquitoes as compared to those with screened windows (OR = 2.125, P < 0.05). More than 80% of the participants own bednets while 16.5% had no protection.

Conclusions
LF low transmission is still ongoing in Masasi District after six rounds of MDA and vector control interventions. The findings also suggest that molecular tools may be essential for xenomonitoring LF transmission during elimination phase.
Associations between the cortisol awakening response and patient-evaluated stress and mood instability in patients with bipolar disorder: an exploratory study
Authors: Faurholt-Jepsen Maria , Frøkjær Vibe Gedsø , Nasser Arafat , Jørgensen Niklas Rye , Kessing Lars Vedel , Vinberg Maj 
Published: March 2021

Abstract
Objective
The Cortisol Awakening Response (CAR) measured as the transient increase in cortisol levels following morning awakening appears to be a distinct feature of the HPA axis. Patients with bipolar disorder (BD) experience daily stress, mood instability (MI) and studies have shown disrupted HPA-axis dynamics. Aims: to evaluate (1) patient-evaluated stress against the CAR, (2) associations between the CAR and mood symptoms, and (3) the effect of smartphone-based treatment on the CAR.

Methods
Patients with BD (n = 67) were randomized to the use of daily smartphone-based monitoring (the intervention group) or to the control group for six months. Clinically rated symptoms according to the Hamilton Depression Rating Scale 17-items (HDRS), the Young Mania Rating Scale (YMRS), patient-evaluated perceived stress using Cohen’s Perceived Stress Scale (PSS) and salivary awakening cortisol samples used for measuring the CAR were collected at baseline, after three and six months. In the intervention group, smartphone-based data on stress and MI were rated daily during the entire study period.

Results
Smartphone-based patient-evaluated stress (B: 134.14, 95% CI: 1.35; 266.92, p = 0.048) and MI (B: 430.23, 95% CI: 52.41; 808.04, p = 0.026) mapped onto increased CAR. No statistically significant associations between the CAR and patient-evaluated PSS or the HDRS and the YMRS, respectively were found. There was no statistically significant effect of smartphone-based treatment on the CAR.

Conclusion
Our data, of preliminary character, found smartphone-based patient-evaluations of stress and mood instability as read outs that reflect CAR dynamics. Smartphone-supported clinical care did not in itself appear to disturb CAR dynamics.