bluuebunny/crossref_metadata_2025_split huggingface dataset:
One down, 699 to go: or, synthesising compositional desugarings
Authors: Bartha Sándor , Cheney James , Belle Vaishak 
Published: October 2021

Programming or scripting languages used in real-world systems are seldom designed with a formal semantics in mind from the outset. Therefore, developing well-founded analysis tools for these systems requires reverse-engineering a formal semantics as a first step. This can take months or years of effort.
Can we (at least partially) automate this process? Though desirable, automatically reverse-engineering semantics rules from an implementation is very challenging, as found by Krishnamurthi, Lerner and Elberty. In this paper, we highlight that scaling methods with the size of the language is very difficult due to state space explosion, so we propose to learn semantics incrementally. We give a formalisation of Krishnamurthi et al.'s desugaring learning framework in order to clarify the assumptions necessary for an incremental learning algorithm to be feasible.
We show that this reformulation allows us to extend the search space and express rules that Krishnamurthi et al. described as challenging, while still retaining feasibility. We evaluate enumerative synthesis as a baseline algorithm, and demonstrate that, with our reformulation of the problem, it is possible to learn correct desugaring rules for the example source and core languages proposed by Krishnamurthi et al., in most cases identical to the intended rules. In addition, with user guidance, our system was able to synthesize rules for desugaring list comprehensions and try/catch/finally constructs.
Transitioning from structural to nominal code with efficient gradual typing
Authors: Muehlboeck Fabian , Tate Ross 
Published: October 2021

Gradual typing is a principled means for mixing typed and untyped code. But typed and untyped code often exhibit different programming patterns. There is already substantial research investigating gradually giving types to code exhibiting typical untyped patterns, and some research investigating gradually removing types from code exhibiting typical typed patterns. This paper investigates how to extend these established gradual-typing concepts to give formal guarantees not only about how to change types as code evolves but also about how to change such programming patterns as well.
In particular, we explore mixing untyped "structural" code with typed "nominal" code in an object-oriented language. But whereas previous work only allowed "nominal" objects to be treated as "structural" objects, we also allow "structural" objects to dynamically acquire certain nominal types, namely interfaces. We present a calculus that supports such "cross-paradigm" code migration and interoperation in a manner satisfying both the static and dynamic gradual guarantees, and demonstrate that the calculus can be implemented efficiently.
Rich specifications for Ethereum smart contract verification
Authors: Bräm Christian , Eilers Marco , Müller Peter , Sierra Robin , Summers Alexander J. 
Published: October 2021

Smart contracts are programs that execute in blockchains such as Ethereum to manipulate digital assets. Since bugs in smart contracts may lead to substantial financial losses, there is considerable interest in formally proving their correctness. However, the specification and verification of smart contracts faces challenges that rarely arise in other application domains. Smart contracts frequently interact with unverified, potentially adversarial outside code, which substantially weakens the assumptions that formal analyses can (soundly) make. Moreover, the core functionality of smart contracts is to manipulate and transfer resources; describing this functionality concisely requires dedicated specification support. Current reasoning techniques do not fully address these challenges, being restricted in their scope or expressiveness (in particular, in the presence of re-entrant calls), and offering limited means of expressing the resource transfers a contract performs.
In this paper, we present a novel specification methodology tailored to the domain of smart contracts. Our specifications and associated reasoning technique are the first to enable: (1) sound and precise reasoning in the presence of unverified code and arbitrary re-entrancy, (2) modular reasoning about collaborating smart contracts, and (3) domain-specific specifications for resources and resource transfers, expressing a contract's behaviour in intuitive and concise ways and excluding typical errors by default. We have implemented our approach in 2vyper, an SMT-based automated verification tool for Ethereum smart contracts written in Vyper, and demonstrated its effectiveness for verifying strong correctness guarantees for real-world contracts.
Building Machine Learning-based Threat Hunting System from Scratch
Authors: Chen Chung-Kuan , Lin Si-Chen , Huang Szu-Chun , Chu Yung-Tien , Lei Chin-Laung , Huang Chun-Ying 
Published: October 2021

Machine learning has been widely used for solving challenging problems in diverse areas. However, to the best of our knowledge, seldom literature has discussed in-depth how machine learning approaches can be used effectively to “hunt” (identify) threats, especially
advanced persistent threats (APTs)
, in a monitored environment. In this study, we share our past experiences in building machine learning-based threat-hunting models. Several challenges must be considered when a security team attempts to build such models. These challenges include (1) weak signal, (2) imbalanced data sets, (3) lack of high-quality labels, and (4) no storyline. In this study, we propose Fuchikoma and APTEmu to demonstrate how we tackle the above-mentioned challenges. The former is a proof of concept system for demonstrating the ideas behind autonomous threat-hunting. It is a machine learning-based anomaly detection and threat hunting system which leverages
natural language processing (NLP)
and graph algorithms. The latter is an APT emulator, which emulates the behavior of a well-known APT called APT3, which is the target used in the first round of MITRE ATT&CK Evaluations. APTEmu generates attacks on Windows machines in a virtualized environment, and the captured system events can be further used to train and enhance Fuchikoma’s capabilities. We illustrate the steps and experiments we used to build the models, discuss each model’s effectiveness and limitations of each model, and propose countermeasures and solutions to improve the models. Our evaluation results show that machine learning algorithms can effectively assist threat hunting processes and significantly reduce security analysts’ efforts. Fuchikoma correctly identifies malicious commands and achieves high performance in terms of over 80% True Positive Rate and True Negative Rate and over 60% F3. We believe our proposed approaches provide valuable experiences in the area and shed light on automated threat-hunting research.
Stressors of Nursing Interns and Their Influencing Factors: A Cross-Sectional Study
Authors: Wang Xiaoqing , Han Yu , Chai Runyu , Chai Rong 
Published: October 2021

Objective. It is still unknown whether the stress level and stressors in Chinese nursing interns are influenced by teacher-related factors. This research was carried out for better understanding of the stress in nursing interns and distribution of stressors during their clinical practice and targeted measures to unwind the stress of nursing interns. Methods. A questionnaire survey, titled Questionnaire on Stressors of Nursing Interns during Clinical Practice, was conducted on nursing interns at a 3A Grade Hospital in Shandong Province. Characteristics of the nursing interns and stressors of nursing interns were collected. A multiple-linear regression model was used to explore the influencing factors of nursing interns’ scores. Results. A total of 132 nursing interns were investigated in this study, and the overall stress scores were calculated. The stressors during the internship include the nature and content of the job, role orientation, workload, conflict between study and work, practice preparation, and interpersonal relationships. Gender, education level, instructor encouragement, and parents engaged in the medical industry were adjusted in the multiple-linear regression model as covariates. All of these factors had significant impacts on the scores of stressors (

P

< 0.05), with the partial regression coefficient values of 13.38, −10.52, −5.02, 3.4, −9.89, −14.77, and −15.83 for factors like female, undergraduates, graduate students, never obtained encouragement from teachers, obtained encouragement from teachers occasionally, obtained encouragement from teachers frequently, and parents engaged in the medical industry, respectively. Conclusion. The stressors of nursing interns are mostly work-wise, and teachers’ encouragement is an important protective factor for nursing interns to reduce stress. Therefore, clinical instructors should take targeted measures in teaching methods and work arrangements according to the needs of interns.
Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer
Authors: Ray Upasana , Jung Deok-Beom , Jin Ling , Xiao Yinan , Dasari Subramanyam , Sarkar Bhattacharya Sayantani , Thirusangu Prabhu , Staub Julie K. , Roy Debarshi , Roy Bhaskar , Weroha S. John , Hou Xiaonan , Purcell James W. , Bakkum-Gamez Jamie N. , Kaufmann Scott H. , Kannan Nagarajan , Mitra Anirban K. , Shridhar Viji 
Published: October 2021

Abstract

Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show that LRRC15, a type-I 15-leucine–rich repeat-containing membrane protein, highly overexpressed in ovarian cancer bowel metastases compared with matched primary tumors and acts as a potent promoter of omental metastasis. Complementary models of ovarian cancer demonstrated that LRRC15 expression leads to inhibition of anoikis-induced cell death and promotes adhesion and invasion through matrices that mimic omentum. Mechanistically, LRRC15 interacted with β1-integrin to stimulate activation of focal adhesion kinase (FAK) signaling. As a therapeutic proof of concept, targeting LRRC15 with the specific antibody–drug conjugate ABBV-085 in both early and late metastatic ovarian cancer cell line xenograft models prevented metastatic dissemination, and these results were corroborated in metastatic patient-derived ovarian cancer xenograft models. Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting ovarian cancer metastasis and suggest a novel and promising therapy to target ovarian cancer metastases.

Significance: This study identifies that LRRC15 activates β1-integrin/FAK signaling to promote ovarian cancer metastasis and shows that the LRRC15-targeted antibody–drug conjugate ABBV-085 suppresses ovarian cancer metastasis in preclinical models.
Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer
Authors: Pitter Michael R. , Zou Weiping 
Published: October 2021

Abstract
Immune checkpoint blockade involves the targeted antagonism of immunosuppressive interactions between antigen-presenting cells and/or tumor cells and effector T cells. Blockade of B7-H1, also known as programmed death-ligand 1 (PD-L1), prevents the ligation of inhibitory PD-L1 molecules to programmed cell death receptor 1 (PD-1) on T cells, engendering a potentiated response of tumor-specific T cells against tumor cells. In a Cancer Research article, Hirano and colleagues showed that T-cell–mediated tumor immunity becomes impaired when tumor cells interact with T cells via PD-L1 in the mouse tumor microenvironment. They showed that targeting PD-L1 or PD-1 with mAbs increased tumor cell lysis by T cells and suggested that tumor PD-L1 forms a “shield” preventing tumor cell lysis. Alongside other original mouse and human studies, this work generated scientific rationales for a new generation of cancer treatment focused on targeting the inhibitory PD-1/PD-L1 signaling pathway in the tumor microenvironment.
See related article by Hirano and colleagues, Cancer Res 2005;65:1089–1096.
Enhanced Vulnerability of LKB1-Deficient NSCLC to Disruption of ATP Pools and Redox Homeostasis by 8-Cl-Ado
Authors: Galan-Cobo Ana , Stellrecht Christine M. , Yilmaz Emrullah , Yang Chao , Qian Yu , Qu Xiao , Akhter Ishita , Ayres Mary L. , Fan Youhong , Tong Pan , Diao Lixia , Ding Jie , Giri Uma , Gudikote Jayanthi , Nilsson Monique , Wierda William G. , Wang Jing , Skoulidis Ferdinandos , Minna John D. , Gandhi Varsha , Heymach John V. 
Published: October 2021

Abstract

Loss-of-function somatic mutations of STK11, a tumor suppressor gene encoding LKB1 that contributes to the altered metabolic phenotype of cancer cells, is the second most common event in lung adenocarcinomas and often co-occurs with activating KRAS mutations. Tumor cells lacking LKB1 display an aggressive phenotype, with uncontrolled cell growth and higher energetic and redox stress due to its failure to balance ATP and NADPH levels in response to cellular stimulus. The identification of effective therapeutic regimens for patients with LKB1-deficient non–small cell lung cancer (NSCLC) remains a major clinical need. Here, we report that LKB1-deficient NSCLC tumor cells displayed reduced basal levels of ATP and to a lesser extent other nucleotides, and markedly enhanced sensitivity to 8-Cl-adenosine (8-Cl-Ado), an energy-depleting nucleoside analog. Treatment with 8-Cl-Ado depleted intracellular ATP levels, raised redox stress, and induced cell death leading to a compensatory suppression of mTOR signaling in LKB1-intact, but not LKB1-deficient, cells. Proteomic analysis revealed that the MAPK/MEK/ERK and PI3K/AKT pathways were activated in response to 8-Cl-Ado treatment and targeting these pathways enhanced the antitumor efficacy of 8-Cl-Ado.

Implications:
Together, our findings demonstrate that LKB1-deficient tumor cells are selectively sensitive to 8-Cl-Ado and suggest that therapeutic approaches targeting vulnerable energy stores combined with signaling pathway inhibitors merit further investigation for this patient population.
Ecology of the facultative phytotelmic crab Platychirarma buettikoferi (De Man, 1883) (Decapoda, Brachyura, Sesarmidae)
Authors: Fusi Marco , Bayi Joseph , Ngo-Massou Vanessa , Din Ndongo , Sacchi Angela , Guebas Farid Dahdouh , Cannicci Stefano 
Published: October 2021

Abstract
The mangrove forests surrounding Douala, Cameroon, have a long history of human impact due to rapid urbanization, resulting in patches of true mangrove forest interspersed with areas dominated by the mangrove-associated Pandanus species. A survey carried out to assess the possible shift in crab fauna composition and dominance between mangrove and Pandanus dominated areas revealed an undescribed phytotelmic habitat for Platychirarma buettikoferi. This species was found colonizing the natural reservoirs of fresh water represented by Pandanus spp. Our results show P. buettikoferi to be ecologically dependent upon Pandanus spp., and absent on the mangrove floor and trees, strongly indicating a phytotelmic adaptation. Our data suggest that this species is a facultative phytotelmic species well adapted to Pandanus spp. dominated areas. Further studies on the reproductive biology and feeding behaviour of P. buettikoferi may shed light on this unique phytotelmic lifestyle and its role in mangrove ecosystem functioning.
Histologic Analysis of Porcine Dermal Graft Augmentation in Treatment of Rotator Cuff Tears
Authors: Christian Robert A. , Stabile Kathryne J. , Gupta Anil K. , Leckey Bruce D. , Cardona Diana M. , Nowinski Robert J. , Kelly James D. , Toth Alison P. 
Published: October 2021

Background: Biologic augmentation via extracellular matrix (ECM) scaffolds has been utilized to address rotator cuff tears with poor-quality tissue. Purpose: To evaluate the cellular changes in graft explants taken from patients treated with porcine dermal grafts for rotator cuff tears. Study Design: Case series; Level of evidence, 4 Methods: Four graft biopsy specimens were obtained from patients treated with porcine dermal grafts in an interposition technique for rotator cuff tears and compared with a nonimplanted graft and a normal rotator cuff specimen. Biopsy of the graft site was performed at 18 days, 3 months, 7 months, and 10.5 months after implantation. Hematoxylin and eosin staining was used to evaluate for cellular and vascular changes. Picrosirius red (PSR) stain with 90° polarized light was performed to evaluate collagen fibril size and orientation. All biopsy specimens were analyzed by a pathologist. Results: There was evidence of progressive remodeling of the porcine dermal grafts. The most mature grafts demonstrated vessel infiltration and extensive remodeling without evidence of inflammation, foreign body reaction, or tissue rejection. PSR demonstrated increased organization of collagen domains, resembling normal tendon by 10.5 months postoperatively. Conclusion: This series suggests that ECM grafts may serve as an effective scaffold for host cell infiltration, collagen reorganization, and vascularization as a result of histologic changes demonstrated with retrieval of specimens from patients with rotator cuff tears that were augmented with porcine dermal grafts.
Novel Polyimide-block-poly(dimethyl siloxane) copolymers: Effect of time on the synthesis and thermal properties
Authors: Xiao Shengdong , Iroh Jude O 
Published: October 2021

Polyimide-block-poly(dimethyl siloxane) copolymer was synthesized by a two-step process, initiated by coupling anhydride terminated poly(amic acid), AT-PAA with amino terminated poly(dimethyl siloxane), (NH2)2-PDMS to form poly(amic acid)-block-poly(dimethyl siloxane). The resulting copolymer is then thermally treated to produce polyimide-block-poly(dimethyl siloxane), PI-PDMS. Because of the high glass transition temperature, Tg of polyimide, it is usually cured at a high temperature of about 300°C for over 2.5 h. Copolymerization of polyimide with polysiloxane, reduces the imidization temperature while maintaining high thermomechanical properties. A series of instruments were used to monitor the progress of copolymerization. The time-based analysis of the product of copolymerization enables the optimization of the structure and properties of the copolymers. The chemical structure and composition of the copolymer were studied by Fourier Transform Infrared Spectroscopy, (FT-IR). The incorporation of PDMS blocks into the copolymer and the degree of imidization of the polyimide block increased with increasing reaction time. The change in the viscosity of the copolymerizing solution was monitored by simple shear viscometry conducted with the Brookfield Viscometer. The reported increase in solution viscosity with increasing copolymerization time is associated with increasing molecular weight of the copolymer. The intrinsic viscosity of the copolymer solution was measured as a function of copolymerization time and it was found that the intrinsic viscosity of the copolymer solution increased with increasing reaction time. The glass transition temperature (Tg) and the thermal stability of the copolymer were determined by differential scanning calorimetry, DSC and thermogravimetric analysis, and TGA, respectively. Between 25°C and 420°C, the copolymers synthesized in this study show two glass transition temperatures due to the polyimide, PI block at around 380°C and another peak associated with PDMS plasticized polyimide at about 290–300°C. The two Tg peaks observed in the DSC thermogram are believed to be indicative of the structure of a block copolymer. TGA analysis shows that the thermoxidative stability of the copolymers increased with increasing reaction time, due to the incorporation of increased amount of PDMS unit into the copolymer. The combination of increasing molecular weight of copolymer, higher degree of imidization of polyimide blocks and enhanced thermoxidative stability may translate into improved flame retardancy of copolymers. This suggested enhancement in flame retardancy in air atmosphere, is believed to be due the incorporated PDMS blocks, which can be converted into silica, SiO2, a recognized thermally stable material.
Recurrent lupus enteritis in a child—chase the calm before the storm
Authors: Patra Pratap Kumar , Bhattarai Dharmagat , Banday Aaqib Zaffar , Gupta Anju , Peters Nitin James , Bal Amanjit , Saxena Akshay 
Published: October 2021

Systemic lupus erythematosus (SLE) is a complex multisystemic autoimmune disease. Lupus enteritis (LE), one of the less commonly described manifestations of childhood SLE, presents with relatively nonspecific clinical and laboratory features. In addition, recurrent episodes of LE occurring in temporal proximity are rare in children. Presence of disease activity at other sites (which may not be seen universally) supports the diagnosis of LE in an appropriate setting. Because of its potential role to cause ischemic complications, early recognition and prompt treatment are necessary for a good outcome. Herein, we describe a child with recurrent LE with an interval of about 3 months between the first and the second episode. The first episode correlated with systemic disease activity and bowel thickening was noted on abdominal ultrasonography. This episode was successfully managed with intravenous methylprednisolone pulse therapy. Conversely, the second episode was not associated with significant clinical and laboratory evidence of disease activity at other sites and the initial abdominal ultrasonography was non-contributory. Diagnostic and therapeutic delays, hence, led to the development of fatal complications. We highlight that a high index of suspicion of LE and a timely aggressive treatment is imperative for optimal outcomes even in rare pediatric cases of recurrent LE that may have normal imaging findings initially and may not be associated with systemic lupus erythematosus disease activity index (SLEDAI).