bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Method for Full Shaking Force Balancing of Planar Linkages by a Few Finite Positions
Authors: Yang Ting-Li , Zhang Ming , Jin Qiong 
Published: February 2021

Abstract
A new method called “Finite Position Method” is presented in this paper. By means if this method, it is easy to obtain the condition for full shaking force balancing of planar linkages (FSFBPL), to derive the counter theorem and the minimum number of counterweights. The balancing condition could be generated easily via establishing and solving a system of linear equations using a few finite position data of the linkage. The basic principle of this method could be expanded to the study for balancing theory of the spatial linkages.
Copper- and cobalt-rich, ultrapotassic bittern brines responsible for the formation of the Nkana-Mindola deposits, Zambian Copperbelt
Authors: Davey James , Roberts Stephen , Wilkinson Jamie J. 
Published: February 2021

Abstract
The Central African Copperbelt (CACB) is Earth’s largest repository of sediment-hosted copper and cobalt. The criticality of these elements in battery technology and electricity transmission establishes them as fundamental components of the carbon-free energy revolution, yet the nature and origin of the hydrothermal fluids responsible for ore formation in the CACB remain controversial. Here, we present microthermometric, scanning electron microscopy and laser ablation–inductively coupled plasma–mass spectrometry analyses of fluid inclusions from the Nkana-Mindola deposits in Zambia. We find that base metal concentrations vary by one to two orders of magnitude between “barren” and “ore” fluids, with concomitant distinctions in major salt chemistry. Primary fluid inclusions, hosted by pre- to synkinematic mineralized quartz veins, are characterized by high homogenization temperatures (∼200–300 °C) and salinities, with K/Na &gt;0.8 and elevated metal concentrations (102 to 103 ppm Cu and Co). Conversely, barren, postkinematic vein quartz contains lower homogenization temperature (∼110–210 °C) and lower-salinity primary inclusions, characterized by K/Na &lt;0.8 with low metal contents (&lt;102 ppm Cu and Co). We propose a model in which high-temperature, sulfate-deficient, metalliferous, potassic residual brines, formed during advanced evaporation of CaCl2-rich, mid-Neoproterozoic seawater, were responsible for ore formation. During basin closure, lower-temperature, halite-undersaturated fluids interacted with evaporites and formed structurally controlled, sodic metasomatism. Reconciliation of these fluid chemistries and base metal concentrations with reported alteration assemblages from a majority of Zambian Copperbelt deposits suggests highly evolved, residual brines were critical to the formation of this unique metallogenic province.
Timeout procedure in paediatric surgery: effective tool or lip service? A randomised prospective observational study
Authors: Muensterer Oliver J , Kreutz Hendrik , Poplawski Alicia , Goedeke Jan 
Published: February 2021

BackgroundFor over a decade, the preoperative timeout procedure has been implemented in most paediatric surgery units. However, the impact of this intervention has not been systematically studied. This study evaluates whether purposefully introduced errors during the timeout routine are detected and reported by the operating team members.MethodsAfter ethics board approval and informed consent, deliberate errors were randomly and clandestinely introduced into the timeout routine for elective surgical procedures by a paediatric surgery attending. Errors were randomly selected among wrong name, site, side, allergy, intervention, birthdate and gender items. The main outcome measure was how frequent an error was reported by the team and by whom.ResultsOver the course of 16 months, 1800 operations and timeouts were performed. Errors were randomly introduced in 120 cases (6.7%). Overall, 54% of the errors were reported; the remainder went unnoticed. Errors were pointed out most frequently by anaesthesiologists (64%), followed by nursing staff (28%), residents-in-training (6%) and medical students (1%).ConclusionErrors in the timeout routine go unnoticed by the team in almost half of cases. Therefore, even if preoperative timeout routines are strictly implemented, mistakes may be overlooked. Hence, the timeout procedure in its current form appears unreliable. Future developments may be useful to improve the quality of the surgical timeout and should be studied in detail.
Radiological dynamics and SITC-defined resistance types of advanced melanoma during anti-PD-1 monotherapy: an independent single-blind observational study on an international cohort
Authors: Bai Xue , Kim Michelle , Kasumova Gyulnara , Si Lu , Tang Bixia , Cui Chuanliang , Yang Xiaoling , Wei Xiaoting , Cohen Justine , Lawrence Donald , Freedman Christine , Fadden Riley , Rubin Krista , Sharova Tatyana , Frederick Dennie , Flaherty Keith , Sullivan Ryan , Guo Jun , Boland Genevieve 
Published: February 2021

BackgroundAlthough the Society for Immunotherapy of Cancer (SITC) Immunotherapy Resistance Taskforce recently defined primary and secondary resistance to anti-programmed cell death protein 1 (anti-PD-1) therapy, there is lack of real-world data regarding differences in these resistance subtypes with respect to radiological dynamics and clinical manifestations.MethodsWe performed single-blind re-evaluations of radiological images by independent radiologists on a retrospectively assembled cohort of patients with advanced melanoma (n=254, median follow-up 31 months) receiving anti-PD-1 monotherapy at Massachusetts General Hospital and Peking University Cancer Hospital. Radiological characteristics and timing at multiple crucial time points were analyzed and correlated with each other and with survival. Primary and secondary resistance was defined as per the SITC Immunotherapy Resistance Taskforce definitions.ResultsThe most significant target lesion measurement change took place within the first 3 months after anti-PD-1 initiation. Patients with stable disease with versus without tumor shrinkage at the initial evaluation exhibited distinct disease trajectory, as the rate of further upgrade to a partial or complete remission (CR/PR) was 44% and 0%, respectively. Eleven per cent of PR patients ultimately achieved a CR. In multivariate analyses, deeper response depth was independently associated with a more limited progression pattern, fewer involved organs, lower tumor burden, slower growth rate at disease progression (PD) (all p≤0.001), and longer post-progression survival (PPS) (bivariate analysis, p=0.005). Compared with primary resistance, secondary resistance was associated with less widespread PD pattern, lower tumor burden and slower tumor growth (all p≤0.001). Patients with secondary resistance were less likely to receive further systemic therapy (28% vs 57%, p<0.001) yet had significantly better PPS (HR 0.503, 95% CI 0.288 to 0.879, p=0.02).ConclusionsRadiological dynamics were variable, yet significantly correlated with survival outcomes. SITC-defined primary and secondary resistance are distinct clinical manifestations in patients with melanoma, suggesting the possibility of resistance-type-based therapeutic decision-making and clinical trial design, once further validated by future prospective studies.
Doughnut vertebroplasty for circumferential aggressive vertebral hemangiomas
Authors: Roscop Cecile , Gariel Florent , Kieser David Christopher , Bouyer Benjamin , Gille Olivier , Marnat Gaultier , Berge Jerome 
Published: February 2021

BackgroundTo assess the feasibility, safety and efficacy of a percutaneous doughnut vertebroplasty of circumferential aggressive vertebral hemangiomas (VHs).MethodsWe retrospectively reviewed our prospectively collected database of patients with VHs treated with vertebroplasty between January 2009 and January 2018. Patient demographics, clinical presentations and procedural details were recorded. All patients underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI). All vertebroplasties were performed under conscious sedation in the prone position, predominantly using biplane fluoroscopic guidance. A clinical and imaging evaluation (early CT scan and MRI) as well as a final follow-up clinical assessment was performed.ResultsTwenty-two patients with aggressive VHs who underwent circumferential vertebroplasty with cementation of the entire vertebral body and at least one posterior hemi-arch were included (six males, mean age 53 years). At 3 months follow-up, nine patients (41%) had complete, 11 (50%) had partial and two (9%) had no resolution of pain. Nine of 14 patients had a decrease in venous swelling on MRI. No complications were observed. Five patients (23%) underwent adjunctive surgery within 1 year for persistence or worsening of neurological symptoms. Clinical and radiographic improvements were maintained to final follow-up.ConclusionsDoughnut vertebroplasty offers a mini-invasive, safe and effective treatment of aggressive circumferential VHs. This technique improves pain in over 90% of patients as well as a reduction in radicular and neurological symptoms associated with a tendency to regression of the compressive epidural venous component of these lesions.
Balloon guide catheter improvements in thrombectomy outcomes persist despite advances in intracranial aspiration technology
Authors: Blasco Jordi , Puig Josep , Daunis-i-Estadella Pepus , González Eva , Fondevila Monso Juan Jose , Manso Xabier , Oteros Rafael , Jimenez-Gomez Elvira , Bravo Rey Isabel , Vega Pedro , Murias Eduardo , Jimenez Jose Maria , López-Rueda Antonio , Renú Arturo , Aixut Sonia , Chirife Chaparro Oscar , Rosati Santiago , Moreu Manuel , Remollo Sebastian , Aguilar Tejedor Yeray , Terceño Mikel , Mosqueira Antonio , Nogueira Raul G , San Roman Luis 
Published: February 2021

BackgroundFirst-pass effect (FPE) has been established as a key metric for technical success and strongly correlates with better clinical outcomes. Most data supporting improved outcomes with the use of a balloon guide catheter (BGC) predate the advent of last-generation large-bore intracranial aspiration catheters. We aim to evaluate the impact of BGC in FPE and clinical outcomes in a large cohort of patients treated with contemporary technology.MethodsPatients were recruited from the prospectively ongoing ROSSETTI registry. This registry includes all consecutive patients with anterior circulation large-vessel occlusion (LVO) from 10 comprehensive stroke centers in Spain. Demographic, clinical, angiographic, and clinical outcome data were compared between BGC and non-BGC groups. FPE was defined as the achievement of mTICI2c–3 after a single device pass.Results426 patients were included out of which 271 (63.62%) used BCG. BGC-treated patients had higher FPE rate (45.8% vs 27.7%; P<0.001), higher final mTICI ≥2 c recanalization rate (76.8% vs 50.3%, respectively; P<0.001), shorter procedural time [median (IQR), 30 (19–58) vs 43 (33–71) min; P<0.001], higher NIHSS difference from admission to 24 hours [median (IQR), 8 (2–12) vs 3 (0–10); P=0.001], and lower mortality rate (17.6% vs 29.8%, P=0.026) compared with non-BGC patients. BGC use was an independent predictor of FPE (OR 2.197, 95% CI 1.436 to 3.361; P<0.001), and excellent clinical outcome at 3 months (OR 0.34, 95% CI 0.17 to 0.68; P=0.002).ConclusionsOur results support the benefit of BGC use on angiographic and clinical outcomes in anterior circulation LVO ischemic stroke remain significant even when considering recent improvements in intracranial aspiration technology.
Stream diatom assemblages in an Arctic catchment: diversity and relationship to ecosystem-scale primary production
Authors: Riley Breena , Seekell David 
Published: February 2021

We quantified benthic diatom diversity in streams in the Miellajokka catchment, about 200 km north of the Arctic circle in Sweden. Beta diversity among sites was related to local-scale environmental heterogeneity (occurring on the order of 1 km or less), and its magnitude was equal (Sørensen Index = 0.62) to levels previously reported for rivers on regional environmental gradients across hundreds of kilometres of Arctic Fennoscandia. Species turnover was the dominant (77%) component of beta diversity in the Miellajokka catchment. Small, stress-tolerant taxa dominated the assemblages, and there were no clear patterns of functional class among sites. Site ordinates from non-metric dimensional scaling were most strongly correlated with flood frequency (r = 0.83) and water temperature (r = 0.89), which was higher in harsh tundra sites than below treeline. Additionally, site ordinates were correlated (r = 0.83) with ecosystem-scale gross primary production — indicative of a link between diatom diversity and ecosystem function. Our results advance understanding of patterns diatom diversity in Arctic streams by quantifying local-scale variation that is understudied in this region, and by identifying the consequences of this local-scale diversity for an ecosystem-scale process.
Considerations of variability and power for long-term monitoring of stream fish assemblages
Authors: George Scott D. , Stich Daniel S. , Baldigo Barry P. 
Published: February 2021

Little attention has been given to optimizing statistical power for monitoring stream fish assemblages. We explored the relationship between temporal variability and statistical power using 34 metrics from fish community data collected annually at six sites over 10 years via electrofishing. Metric variability differed by the life stage and group of species considered, use of abundance or mass data, and data standardization technique. Lower variability was associated with community data, abundance data, and time-based standardizations, while greater variability was associated with young-of-the-year data, mass data, and area-based standardizations. Simulation-based power analysis indicated metric choice, and to a lesser degree, monitoring design (annual, biennial, endpoints, or haphazard sampling) influenced power to detect change. Across a fixed number of surveys (N = 60), endpoints sampling performed best. The N needed to detect change was heavily dependent upon metric choice for all monitoring designs, with the most biologically specific metrics requiring greater N. Large savings in effort and resource expenditure can be obtained utilizing biologically relevant metrics that are robust to temporal noise within an appropriate sampling design.
Abstract IA016: Cellular senescence in cancer therapy: Friend or foe?
Authors: Demaria Marco 
Published: March 2021

Abstract
Most used anti-cancer therapeutic approaches are based on impairing mitosis and targeting highly proliferative cells. The non-specificity of these interventions often leads to transient and chronic side effects, and a general accelerated aging phenotype. Cellular senescence - a complex stress response whereby cells lose irreversibly their capacity to proliferate – is potent tumor suppressive mechanism and a desired outcome of anti-cancer therapies. Our data show that chemotherapy agents induce senescent cells in both mice and humans. However, chemotherapy-induced senescent cells develop a strong secretory phenotype (SASP) and contribute to chemotoxicity in mice including bone marrow suppression, cardiac decline, decreased physical activity and cancer relapse. Interestingly, chemotherapy treatment combined to genetic or pharmacological senolysis delays or prevents the onset of several pathologies. We also show that similar to genotoxic chemotherapy, inhibitors of Cyclin-Dependent Kinases (CDK)-4/6 induce a p53-mediated senescence program. Interestingly, using RNAseq, cytokine arrays and in-tissue analyses we demonstrate that CDKi-induced senescent cells are characterized by a strongly reduced SASP. CDKi-induced senescent cells fail to promote paracrine detrimental effects, and do not lead to adverse effects in mice. Moreover, transient treatment with CDK4/6i in combination with chemotherapy is sufficient to reduce SASP and improve healthspan. Together, our data suggest that modulating the senescence response is a potent strategy to limit the toxicity of ant-cancer treatments. This effect can be achieved either by eliminating detrimental senescent cells or by designing drugs that can promote stable growth arrest without strong paracrine effects. Importantly, the phenotypical characterization of these different senescent cells could predict toxicity and side effects associated to standard oncological drugs.
Citation Format: Marco Demaria. Cellular senescence in cancer therapy: Friend or foe? [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 IA016.
Abstract IA017: Age against the machine: How the aging tumor microenvironment governs tumor progression
Authors: Weeraratna Ashani 
Published: March 2021

Abstract
Cancer is a disease of aging. Most cancers arise after the age of 50, and in our increasingly aging population, this poses a significant public health burden. The molecular mechanisms that underlie the age-induced progression of cancer are not well understood. We have discovered that aged fibroblasts in the tumor microenvironment secrete, or stop secreting, key molecules that affect multiple aspects of tumorigenesis. These include: the loss of molecules that maintain ECM integrity, resulting in changes in mechanotransduction and increased metastasis; the secretion of molecules that increase resistance to targeted therapy; the uptake of macromolecules such as lipids by melanoma cells in the aged microenvironment, affecting tumor cell metabolism; changes in the aged immune tumor microenvironment and the secretion of non-canonical Wnt molecules that affect cell signaling leading to angiogenesis, metastasis, and therapy resistance. These changes drive tumor progression and affect response to therapy in the elderly. Our data suggest that patient age is an important factor in the response to therapy, which is not reflected in most preclinical studies and therapeutic approaches.
Citation Format: Ashani Weeraratna. Age against the machine: How the aging tumor microenvironment governs tumor progression [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 IA017.
Abstract LT013: Endocrine-exocrine signaling is a driver of obesity-associated pancreatic ductal adenocarcinoma
Authors: Garcia Cathy , Singh Jaffarguriqbal , Lawres Lauren , Agabiti Sherry , Burkhardt Daniel B. , Tong Alexander , Cardone Rebecca , Kibbey Richard G. , Krishnaswamy Smita , Muzumdar Mandar D. 
Published: March 2021

Abstract
Obesity is a major modifiable host risk factor for pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer death in the United States and a major cause of morbidity and mortality worldwide. Despite the rapid rise in the prevalence of obesity, surprisingly little is known about how it drives tumor progression. Therefore, deciphering these mechanisms is not only a societal imperative but also represents a key untapped target to develop novel strategies for PDAC prevention and therapy. Motivated by this gap in knowledge, we developed a rapid and reversible autochthonous mouse model of obesity-associated PDAC that recapitulates the genetic and histologic features of the human disease. We showed that obesity accelerates pancreatic tumorigenesis, while genetic or dietary weight loss intercepts tumor development, consistent with a causal and reversible role for obesity in early PDAC progression. By analyzing human and murine biospecimens, we defined obesity-driven microenvironmental alterations that foster tumorigenesis rather than new driver mutations, including significant inflammation, fibrosis, and islet adaptation. Specifically, we identified aberrant pancreatic beta cell expression of the hormone cholecystokinin (CCK) in response to obesity and showed that islet CCK itself promotes oncogenic Kras-driven pancreatic cancer. We further observed that CCK expression and tumor progression correlated with hyperglycemia, beta cell dysfunction, and reduced insulin secretion, suggesting that islet adaptations apart from insulin may drive tumorigenesis in obesity. By performing single-cell RNA-sequencing of islets from genetic and diet-induced obesity models, we have further nominated molecular mechanisms of CCK induction in beta cells and are testing their functional role in PDAC progression. Together, our findings argue that PDAC development is driven by local obesity-associated alterations in the tumor microenvironment, implicate a previously unappreciated endocrine-exocrine signaling axis beyond insulin in this process, and highlight the possibility of targeting the endocrine pancreas as a novel approach to intercept pancreatic exocrine tumorigenesis.
Citation Format: Cathy Garcia, Jaffarguriqbal Singh, Lauren Lawres, Sherry Agabiti, Daniel B. Burkhardt, Alexander Tong, Rebecca Cardone, Richard G. Kibbey, Smita Krishnaswamy, Mandar D. Muzumdar. Endocrine-exocrine signaling is a driver of obesity-associated pancreatic ductal adenocarcinoma [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 LT013.