bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry
Authors: Sun Dapeng , Jia Baixue , Tong Xu , Kan Peter , Huo Xiaochuan , Wang Anxin , Raynald  , Ma Gaoting , Ma Ning , Gao Feng , Mo Dapeng , Song Ligang , Sun Xuan , Liu Lian , Deng Yiming , Li Xiaoqing , Wang Bo , Luo Gang , Wang Yongjun , Ren Zeguang , Miao Zhongrong 
Published: January 2022

BackgroundParenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT).ObjectiveTo investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO).MethodsSubjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score.ResultsOf the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12–36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001).ConclusionsIn Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting.Trial registration numberNCT03370939.
Applied genomics for identification of virulent biothreats and for disease outbreak surveillance
Authors: Nwadiugwu Martin C , Monteiro Nelson 
Published: January 2022

Abstract
Fortifying our preparedness to cope with biological threats by identifying and targeting virulence factors may be a preventative strategy for curtailing infectious disease outbreak. Virulence factors evoke successful pathogenic invasion, and the science and technology of genomics offers a way of identifying them, their agents and evolutionary ancestor. Genomics offers the possibility of deciphering if the release of a pathogen was intentional or natural by observing sequence and annotated data of the causative agent, and evidence of genetic engineering such as cloned vectors at restriction sites. However, to leverage and maximise the application of genomics to strengthen global interception system for real-time biothreat diagnostics, a complete genomic library of pathogenic and non-pathogenic agents will create a robust reference assembly that can be used to screen, characterise, track and trace new and existing strains. Encouraging ethical research sequencing pathogens found in animals and the environment, as well as creating a global space for collaboration will lead to effective global regulation and biosurveillance.
Neuromuscular recovery from severe- and extreme-intensity exercise in men and women
Authors: Alexander Andrew M. , Hammer Shane M. , Didier Kaylin D. , Huckaby Lillie M. , Barstow Thomas J. 
Published: January 2022

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90 s following extreme-intensity exercise. However, methodological limitations mask important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120 s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed 2 severe-intensity (40, 50% MVC) and 2 extreme-intensity (70, 80% MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150 s of recovery. Each intensity significantly reduced MVC and Qpot compared with baseline. MVC was greater at Tlim (p < 0.01) and at 150 s of recovery (p = 0.004) following exercise at 80% MVC compared with severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150 s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150 s of recovery following exercise at 80% MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly. Novelty: Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.
Dynamical robustness of collective neuronal activity upon targeted damage in interdependent networks
Authors: Faci-Lázaro Sergio , Lor Tatiana , Ródenas Guillermo , Mazo Juan J. , Soriano Jordi , Gómez-Gardeñes Jesús 
Published: January 2022

AbstractIn the last decades, the availability of data about the structure of social, technological and biological systems has provided important insights on the mechanisms governing their correct functioning and robustness. These mechanisms are grounded on the complex backbone of interactions among the constituents of the system, which include both topological and dynamical aspects. Here, we analyze interdependent networks composed of two layers of interacting neuronal units and explore their robustness when these synthetic cultures are subjected to damage in the form of either targeted attack or failure. Our results show that the functionality of these networks does not decrease monotonically with damage but, on the contrary, they are able to increase their level of activity when the experienced damage is sufficiently strong.
Verified compilation of C programs with a nominal memory model
Authors: Wang Yuting , Zhang Ling , Shao Zhong , Koenig Jérémie 
Published: January 2022

Memory models play an important role in verified compilation of imperative programming languages. A representative one is the block-based memory model of CompCert---the state-of-the-art verified C compiler. Despite its success, the abstraction over memory space provided by CompCert's memory model is still primitive and inflexible. In essence, it uses a fixed representation for identifying memory blocks in a global memory space and uses a globally shared state for distinguishing between used and unused blocks. Therefore, any reasoning about memory must work uniformly for the global memory; it is impossible to individually reason about different sub-regions of memory (i.e., the stack and global definitions). This not only incurs unnecessary complexity in compiler verification, but also poses significant difficulty for supporting verified compilation of open or concurrent programs which need to work with contextual memory, as manifested in many previous extensions of CompCert.
To remove the above limitations, we propose an enhancement to the block-based memory model based on nominal techniques; we call it the nominal memory model. By adopting the key concepts of nominal techniques such as atomic names and supports to model the memory space, we are able to 1) generalize the representation of memory blocks to any types satisfying the properties of atomic names and 2) remove the global constraints for managing memory blocks, enabling flexible memory structures for open and concurrent programs.
To demonstrate the effectiveness of the nominal memory model, we develop a series of extensions of CompCert based on it. These extensions show that the nominal memory model 1) supports a general framework for verified compilation of C programs, 2) enables intuitive reasoning of compiler transformations on partial memory; and 3) enables modular reasoning about programs working with contextual memory. We also demonstrate that these extensions require limited changes to the original CompCert, making the verification techniques based on the nominal memory model easy to adopt.
On incorrectness logic and Kleene algebra with top and tests
Authors: Zhang Cheng , de Amorim Arthur Azevedo , Gaboardi Marco 
Published: January 2022

Kleene algebra with tests (KAT) is a foundational equational framework for reasoning about programs, which has found applications in program transformations, networking and compiler optimizations, among many other areas. In his seminal work, Kozen proved that KAT subsumes propositional Hoare logic, showing that one can reason about the (partial) correctness of while programs by means of the equational theory of KAT.
In this work, we investigate the support that KAT provides for reasoning about incorrectness, instead, as embodied by O'Hearn's recently proposed incorrectness logic. We show that KAT cannot directly express incorrectness logic. The main reason for this limitation can be traced to the fact that KAT cannot express explicitly the notion of codomain, which is essential to express incorrectness triples. To address this issue, we study Kleene Algebra with Top and Tests (TopKAT), an extension of KAT with a top element. We show that TopKAT is powerful enough to express a codomain operation, to express incorrectness triples, and to prove all the rules of incorrectness logic sound. This shows that one can reason about the incorrectness of while-like programs by means of the equational theory of TopKAT.
Static prediction of parallel computation graphs
Authors: Muller Stefan K. 
Published: January 2022

Many algorithms for analyzing parallel programs, for example to detect deadlocks or data races or to calculate the execution cost, are based on a model variously known as a cost graph, computation graph or dependency graph, which captures the parallel structure of threads in a program. In modern parallel programs, computation graphs are highly dynamic and depend greatly on the program inputs and execution details. As such, most analyses that use these graphs are either dynamic analyses or are specialized static analyses that gather a subset of dependency information for a specific purpose.
This paper introduces graph types, which compactly represent all of the graphs that could arise from program execution. Graph types are inferred from a parallel program using a graph type system and inference algorithm, which we present drawing on ideas from Hindley-Milner type inference, affine logic and region type systems. We have implemented the inference algorithm over a subset of OCaml, extended with parallelism primitives, and we demonstrate how graph types can be used to accelerate the development of new graph-based static analyses by presenting proof-of-concept analyses for deadlock detection and cost analysis.
A dual number abstraction for static analysis of Clarke Jacobians
Authors: Laurel Jacob , Yang Rem , Singh Gagandeep , Misailovic Sasa 
Published: January 2022

We present a novel abstraction for bounding the Clarke Jacobian of a Lipschitz continuous, but not necessarily differentiable function over a local input region. To do so, we leverage a novel abstract domain built upon dual numbers, adapted to soundly over-approximate all first derivatives needed to compute the Clarke Jacobian. We formally prove that our novel forward-mode dual interval evaluation produces a sound, interval domain-based over-approximation of the true Clarke Jacobian for a given input region.
Due to the generality of our formalism, we can compute and analyze interval Clarke Jacobians for a broader class of functions than previous works supported – specifically, arbitrary compositions of neural networks with Lipschitz, but non-differentiable perturbations. We implement our technique in a tool called DeepJ and evaluate it on multiple deep neural networks and non-differentiable input perturbations to showcase both the generality and scalability of our analysis. Concretely, we can obtain interval Clarke Jacobians to analyze Lipschitz robustness and local optimization landscapes of both fully-connected and convolutional neural networks for rotational, contrast variation, and haze perturbations, as well as their compositions.
Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy
Authors: Guix Ines , Liu Qi , Pujana Miquel Angel , Ha Patrick , Piulats Josep , Linares Isabel , Guedea Ferran , Mao Jian-Hua , Lazar Ann , Chapman Jocelyn , Yom Sue S. , Ashworth Alan , Barcellos-Hoff Mary Helen 
Published: January 2022

Abstract

Purpose:
Loss of TGFβ signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGFβ and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, βAlt, predicts patient outcome in response to genotoxic therapy. Here we sought to verify this biology in live specimens and additional datasets.

Experimental Design:
Human head and neck squamous carcinoma (HNSC) explants were treated in vitro to test whether the signatures report TGFβ signaling, indicated by SMAD2 phosphorylation, and unrepaired DNA damage, indicated by persistent 53BP1 foci after irradiation or olaparib. A custom NanoString assay was implemented to analyze the signatures’ expression in explants. Each signature gene was then weighted by its association with functional responses to define a modified score, βAltw, that was retested for association with response to genotoxic therapies in independent datasets.

Results:
Most genes in each signature were positively correlated with the expected biological response in tumor explants. Anticorrelation of TGFβ and alt-EJ signatures measured by NanoString was confirmed in explants. βAltw was significantly (P &lt; 0.001) better than βAlt in predicting overall survival in response to genotoxic therapy in The Cancer Genome Atlas (TCGA) pancancer patients and in independent HNSC and ovarian cancer patient datasets.

Conclusions:
Association of the TGFβ and alt-EJ signatures with their biological response validates TGFβ competency as a key mediator of DNA repair that can be readily assayed by gene expression. The predictive value of βAltw supports its development to assist in clinical decision making.
BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma
Authors: Mehnert Janice M. , Mitchell Tara C. , Huang Alexander C. , Aleman Tomas S. , Kim Benjamin J. , Schuchter Lynn M. , Linette Gerald P. , Karakousis Giorgos C. , Mitnick Sheryl , Giles Lydia , Carberry Mary , Frey Noelle , Kossenkov Andrew , Groisberg Roman , Hernandez-Aya Leonel F. , Ansstas George , Silk Ann W. , Chandra Sunandana , Sosman Jeffrey A. , Gimotty Phyllis A. , Mick Rosemarie , Amaravadi Ravi K. 
Published: January 2022

Abstract

Purpose:
Autophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) to inhibit autophagy in combination with dabrafenib 150 mg twice daily and trametinib 2 mg every day (D+T).

Patients and Methods:
We conducted a phase I/II clinical trial in four centers of HCQ + D+T in patients with advanced BRAFV600-mutant melanoma. The primary objectives were the recommended phase II dose (RP2D) and the one-year progression-free survival (PFS) rate of &gt;53%.

Results:
Thirty-four patients were evaluable for one-year PFS rate. Patient demographics were as follows: elevated lactate dehydrogenase: 47%; stage IV M1c/M1d: 52%; prior immunotherapy: 50%. In phase I, there was no dose-limiting toxicity. HCQ 600 mg orally twice daily with D+T was the RP2D. The one-year PFS rate was 48.2% [95% confidence interval (CI), 31.0%–65.5%], median PFS was 11.2 months (95% CI, 5.4–16.9 months), and response rate (RR) was 85% (95% CI, 64%–95%). The complete RR was 41% and median overall survival (OS) was 26.5 months. In a patient with elevated LDH (n = 16), the RR was 88% and median PFS and OS were 7.3 and 22 months, respectively.

Conclusions:
HCQ + D+T was well tolerated and produced a high RR but did not meet criteria for success for the one-year PFS rate. There was a high proportion of patients with pretreated and elevated LDH, an increasingly common demographic in patients receiving targeted therapy. In this difficult-to-treat population, the RR and PFS were encouraging. A randomized trial of D+T + HCQ or placebo in patients with BRAFV600-mutant melanoma with elevated LDH and previous immunotherapy is being conducted.
Hallmarks of Cancer: New Dimensions
Authors: Hanahan Douglas 
Published: January 2022

Abstract

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment.

Significance:
Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of “big data” about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
Existence of Sobokartti Building as A Physical Culture in Semarang City in Law Anthropology Approach
Authors: Handayani Emy , Wicaksono Satrio Adi 
Published: January 2022

Physical culture can be understood as objects created by human beings which are an embodiment of the growth and development of cultural values ​​in a particular society, in the form of buildings that have been designated as cultural heritage buildings in the city of Semarang. The building is the Semarang Sobokartti building on Jalan Dr. Cipto Semarang, which is a reflection of the development of humans to always preserve culture both Javanese culture and western or European culture
The approach used in this research is an empirical approach and a comparative approach to law anthropology. In an empirical approach, the sobokartti building is a physical culture which is a historic building that accommodates traditional arts which are closely related to Javanese culture, namely karawitan training, puppetry routine, puppetry courses, host courses, dancing courses and batik training. It should be appreciated because the community can maintain its preservation until now by showing the existence of Javanese culture with a love for culture that deserves to be preserved and for the nation's successor generation. Likewise with a comparative approach, it is said that the existence of physical culture in the sobokartti building is expected by the government to have regulations on cultural heritage objects, namely historic buildings or ancient buildings of the Sobokartti Semarang building as outlined in the Cultural Heritage Law No. 11 of 2010 to protect cultural heritage buildings with the aim of preserving, utilizing, and maintaining the beauty of a cultural heritage building Sobokartti Semarang.
Suggestions that will be used in this research that is the role of the Government and Society to maintain physical cultural wealth should be developed by the nation's next generation, with the utilization of the Sobokartti building can provide sustainable use. So that, the Government and the community have the desire to protect and preserve the function of the Sobokartti Semarang building.
Measurement Of Social Fund Assistance Program And Economic Indicators Of Bangka Belitung Islands In The Effort To Reduce Poverty Rate
Authors: Julia Julia , Khairiyansyah  
Published: January 2022

This study aims to analyze the relationship and influence of social assistance on the number of poor people in the Province of the Bangka Belitung Islands. There are control variables as comparison, namely; unemployment, central government debt, economic growth and poverty. The research method uses a quantitative approach with non-parametric statistics, annual data (2015-2020) and elasticity are used to measure the magnitude of change in the number of poor people due to additional social assistance. Spearman Rank test to examine the relationship of each variable (the number of unemployed, central government debt and economic growth) to the amount of poverty in Indonesia. The results of the study show that there is a very strong relationship between social assistance for Contribution Assistance Recipients and the Family Hope Program on the number of poor people. A negative sign indicates that social assistance can significantly reduce poverty, with the strongest impact being the program. There is a strong relationship between debt and the number of poor people. The slowdown in economic growth has been proven to be unrelated to the number of poor people. This means that, in the midst of an economic slowdown, the number of poverty in Indonesia can be reduced through social assistance programs, job creation as laborers and government debt is allocated for productive activities and economic activities that have a direct impact on the poor and the poor. vulnerable to poverty.