bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring a Design Space of Graphical Adaptive Menus
Authors: Vanderdonckt Jean , Bouzit Sara , Calvary Gaëlle , Chêne Denis
Published: July 2019

Graphical Adaptive Menus are Graphical User Interface menus whose predicted items of immediate use can be automatically rendered in a prediction window. Rendering this prediction window is a key question for adaptivity to enable the end-user to efficiently differentiate predicted items from normal ones and to consequently select appropriate items. Adaptivity for graphical menus has been investigated more for normal screens, such as desktops, than for small screens, such as smartphones, where real estate imposes severe rendering constraints. To address this question, this article defines and explores a design space where graphical adaptive menus are structured based on Bertin’s eight visual variables (i.e., position, size, shape, value, color, orientation, texture, and motion) and their combination by comparing their rendering for small screens with respect to normal screens. Based on this design space, previously introduced graphical adaptive menus are revisited in terms of four stability properties (i.e., spatial, physical, format, and temporal), and new menu designs are introduced and discussed for both normal and small screens. The resulting set of graphical adaptive menu has been subject to a preference analysis from which a particular design emerged: the cloud menu, where predicted items are arranged in an adaptive tag cloud. We investigate empirically the effect of the cloud menu on the item selection time and the error rate with respect to a static menu and an adaptive linear menu. This article then suggests a set of usability guidelines for designers and practitioners to design graphical adaptive menus in general and cloud menus in particular.
Neural Network-based Detection of Self-Admitted Technical Debt
Authors: Ren Xiaoxue , Xing Zhenchang , Xia Xin , Lo David , Wang Xinyu , Grundy John
Published: July 2019

Technical debt is a metaphor to reflect the tradeoff software engineers make between short-term benefits and long-term stability. Self-admitted technical debt (SATD), a variant of technical debt, has been proposed to identify debt that is
intentionally introduced
during software development, e.g., temporary fixes and workarounds. Previous studies have leveraged human-summarized patterns (which represent n-gram phrases that can be used to identify SATD) or text-mining techniques to detect SATD in source code comments. However, several characteristics of SATD features in code comments, such as vocabulary diversity, project uniqueness, length, and semantic variations, pose a big challenge to the accuracy of pattern or traditional text-mining-based SATD detection, especially for cross-project deployment. Furthermore, although traditional text-mining-based method outperforms pattern-based method in prediction accuracy, the text features it uses are less intuitive than human-summarized patterns, which makes the prediction results hard to explain. To improve the accuracy of SATD prediction, especially for cross-project prediction, we propose a Convolutional Neural Network-- (CNN) based approach for classifying code comments as SATD or non-SATD. To improve the explainability of our model’s prediction results, we exploit the computational structure of CNNs to identify key phrases and patterns in code comments that are most relevant to SATD. We have conducted an extensive set of experiments with 62,566 code comments from 10 open-source projects and a user study with 150 comments of another three projects. Our evaluation confirms the effectiveness of different aspects of our approach and its superior performance, generalizability, adaptability, and explainability over current state-of-the-art traditional text-mining-based methods for SATD classification.
Susceptibility to Spear-Phishing Emails
Authors: Lin Tian , Capecci Daniel E. , Ellis Donovan M. , Rocha Harold A. , Dommaraju Sandeep , Oliveira Daniela S. , Ebner Natalie C.
Published: July 2019

Phishing is fundamental to cyber attacks. This research determined the effect of Internet user age and email content such as weapons of influence (persuasive techniques that attackers can use to lure individuals to fall for an attack) and life domains (a specific topic or aspect of an individual's life that attackers can focus an email on) on spear-phishing (targeted phishing) susceptibility. In total, 100 young and 58 older users received, without their knowledge, daily simulated phishing emails over 21 days. A browser plugin recorded their clicking on links in the emails as an indicator of their susceptibility. Forty-three percent of users fell for the simulated phishing emails, with older women showing the highest susceptibility. While susceptibility in young users declined across the study, susceptibility in older users remained stable. The relative effectiveness of the attacks differed by weapons of influence and life domains with age-group variability. In addition, older compared to young users reported lower susceptibility awareness. These findings support effects of Internet user demographics and email content on susceptibility to phishing and emphasize the need for personalization of the next generation of security solutions.
A Hybrid Material Point Method for Frictional Contact with Diverse Materials
Authors: Han Xuchen , Gast Theodore F. , Guo Qi , Wang Stephanie , Jiang Chenfanfu , Teran Joseph
Published: July 2019

We present a new hybrid Lagrangian Material Point Method for simulating elastic objects like hair, rubber, and soft tissues that utilizes a Lagrangian mesh for internal force computation and an Eulerian mesh for self collision as well as coupling with external materials. While recent Material Point Method (MPM) techniques allow for natural simulation of hyperelastic materials represented with Lagrangian meshes, they utilize an updated Lagrangian discretization where the Eulerian grid degrees of freedom are used to take variations of the potential energy. This often coarsens the degrees of freedom of the Lagrangian mesh and can lead to artifacts. We develop a hybrid approach that retains Lagrangian degrees of freedom while still allowing for natural coupling with other materials simulated with traditional MPM, e.g. sand, snow, etc. Furthermore, while recent MPM advances allow for resolution of frictional contact with codimensional simulation of hyperelasticity, they do not generalize to the case of volumetric materials. We show that our hybrid approach resolves these issues. We demonstrate the efficacy of our technique with examples that involve elastic soft tissues coupled with kinematic skeletons, extreme deformation, and coupling with multiple elastoplastic materials. Our approach also naturally allows for two-way rigid body coupling.
Fairness in responsive parallelism
Authors: Muller Stefan K. , Westrick Sam , Acar Umut A.
Published: July 2019

Research on parallel computing has historically revolved around compute-intensive applications drawn from traditional areas such as high-performance computing. With the growing availability and usage of multicore chips, applications of parallel computing now include interactive parallel applications that mix compute-intensive tasks with interaction, e.g., with the user or more generally with the external world. Recent theoretical work on responsive parallelism presents abstract cost models and type systems for ensuring and reasoning about responsiveness and throughput of such interactive parallel programs.

In this paper, we extend prior work by considering a crucial metric: fairness. To express rich interactive parallel programs, we allow programmers to assign priorities to threads and instruct the scheduler to obey a notion of fairness. We then propose the fairly prompt scheduling principle for executing such programs; the principle specifies the schedule for multithreaded programs on multiple processors. For such schedules, we prove theoretical bounds on the execution and response times of jobs of various priorities. In particular, we bound the amount, i.e., stretch, by which a low-priority job can be delayed by higher-priority work. We also present an algorithm designed to approximate the fairly prompt scheduling principle on multicore computers, implement the algorithm by extending the Standard ML language, and present an empirical evaluation.
The next 700 compiler correctness theorems (functional pearl)
Authors: Patterson Daniel , Ahmed Amal
Published: July 2019

Compiler correctness is an old problem, with results stretching back beyond the last half-century. Founding the field, John McCarthy and James Painter set out to build a "completely trustworthy compiler". And yet, until quite recently, even despite truly impressive verification efforts, the theorems being proved were only about the compilation of whole programs, a theoretically quite appealing but practically unrealistic simplification. For a compiler correctness theorem to assure complete trust, the theorem must reflect the reality of how the compiler will be used.

There has been much recent work on more realistic "compositional" compiler correctness aimed at proving correct compilation of components while supporting linking with components compiled from different languages using different compilers. However, the variety of theorems, stated in remarkably different ways, raises questions about what researchers even mean by a "compiler is correct." In this pearl, we develop a new framework with which to understand compiler correctness theorems in the presence of linking, and apply it to understanding and comparing this diversity of results. In doing so, not only are we better able to assess their relative strengths and weaknesses, but gain insight into what we as a community should expect from compiler correctness theorems of the future.
Approximate normalization for gradual dependent types
Authors: Eremondi Joseph , Tanter Éric , Garcia Ronald
Published: July 2019

Dependent types help programmers write highly reliable code. However, this reliability comes at a cost: it can be challenging to write new prototypes in (or migrate old code to) dependently-typed programming languages. Gradual typing makes static type disciplines more flexible, so an appropriate notion of gradual dependent types could fruitfully lower this cost. However, dependent types raise unique challenges for gradual typing. Dependent typechecking involves the execution of program code, but gradually-typed code can signal runtime type errors or diverge. These runtime errors threaten the soundness guarantees that make dependent types so attractive, while divergence spoils the type-driven programming experience.

This paper presents GDTL, a gradual dependently-typed language that emphasizes pragmatic dependently-typed programming. GDTL fully embeds both an untyped and dependently-typed language, and allows for smooth transitions between the two. In addition to gradual types we introduce
gradual terms
, which allow the user to be imprecise in type indices and to omit proof terms; runtime checks ensure type safety. To account for nontermination and failure, we distinguish between compile-time normalization and run-time execution: compile-time normalization is
approximate
but total, while runtime execution is
exact
, but may fail or diverge. We prove that GDTL has decidable typechecking and satisfies all the expected properties of gradual languages. In particular, GDTL satisfies the static and dynamic gradual guarantees: reducing type precision preserves typedness, and altering type precision does not change program behavior outside of dynamic type failures. To prove these properties, we were led to establish a novel
normalization gradual guarantee
that captures the monotonicity of approximate normalization with respect to imprecision.
Relational cost analysis for functional-imperative programs
Authors: Qu Weihao , Gaboardi Marco , Garg Deepak
Published: July 2019

Relational cost analysis aims at formally establishing bounds on the difference in the evaluation costs of two programs. As a particular case, one can also use relational cost analysis to establish bounds on the difference in the evaluation cost of the same program on two different inputs. One way to perform relational cost analysis is to use a relational type-and-effect system that supports reasoning about relations between two executions of two programs.

Building on this basic idea, we present a type-and-effect system, called ARel, for reasoning about the relative cost of array-manipulating, higher-order functional-imperative programs. The key ingredient of our approach is a new lightweight type refinement discipline that we use to track relations (differences) between two mutable arrays. This discipline combined with Hoare-style triples built into the types allows us to express and establish precise relative costs of several interesting programs which imperatively update their data. We have implemented ARel using ideas from bidirectional type checking.
Synthesizing symmetric lenses
Authors: Miltner Anders , Maina Solomon , Fisher Kathleen , Pierce Benjamin C. , Walker David , Zdancewic Steve
Published: July 2019

Lenses are programs that can be run both "front to back" and "back to front," allowing updates to either their source or their target data to be transferred in both directions. Since their introduction by Foster et al., lenses have been extensively studied, extended, and applied. Recent work has also demonstrated how techniques from type-directed program synthesis can be used to efficiently synthesize a simple class of lenses---so-called bijective lenses over string data---given a pair of types (regular expressions) and a small number of examples.

We extend this synthesis algorithm to a much broader class of lenses, called simple symmetric lenses, including all bijective lenses, all of the popular category of "asymmetric" lenses, and a rich subset of the more powerful "symmetric lenses" proposed by Hofmann et al. Intuitively, simple symmetric lenses allow some information to be present on one side but not the other and vice versa. They are of independent theoretical interest, being the largest class of symmetric lenses that do not rely on persistent internal state.

Synthesizing simple symmetric lenses is substantially more challenging than synthesizing bijective lenses: Since some of the information on each side can be "disconnected" from the other side, there will, in general, be many lenses that agree with a given example. To guide the search process, we use stochastic regular expressions and ideas from information theory to estimate the amount of information propagated by a candidate lens, generally preferring lenses that propagate more information, as well as user annotations marking parts of the source and target data structures as either irrelevant or essential.

We describe an implementation of simple symmetric lenses and our synthesis procedure as extensions to the Boomerang language. We evaluate its performance on 48 benchmark examples drawn from Flash Fill, Augeas, the bidirectional programming literature, and electronic file format synchronization tasks. Our implementation can synthesize each of these lenses in under 30 seconds.
A role for dependent types in Haskell
Authors: Weirich Stephanie , Choudhury Pritam , Voizard Antoine , Eisenberg Richard A.
Published: July 2019

Modern Haskell supports
zero-cost
coercions, a mechanism where types that share the same run-time representation may be freely converted between. To make sure such conversions are safe and desirable, this feature relies on a mechanism of
roles
to prohibit invalid coercions. In this work, we show how to incorporate roles into dependent types systems and prove, using the Coq proof assistant, that the resulting system is sound. We have designed this work as a foundation for the addition of dependent types to the Glasgow Haskell Compiler, but we also expect that it will be of use to designers of other dependently-typed languages who might want to adopt Haskell’s safe coercions feature.
Simply RaTT: a fitch-style modal calculus for reactive programming without space leaks
Authors: Bahr Patrick , Graulund Christian Uldal , Møgelberg Rasmus Ejlers
Published: July 2019

Functional reactive programming (FRP) is a paradigm for programming with signals and events, allowing the user to describe reactive programs on a high level of abstraction. For this to make sense, an FRP language must ensure that all programs are causal, and can be implemented without introducing space leaks and time leaks. To this end, some FRP languages do not give direct access to signals, but just to signal functions.

Recently, modal types have been suggested as an alternative approach to ensuring causality in FRP languages in the synchronous case, giving direct access to the signal and event abstractions. This paper presents
Simply RaTT
, a new modal calculus for reactive programming. Unlike prior calculi, Simply RaTT uses a Fitch-style approach to modal types, which simplifies the type system and makes programs more concise. Echoing a previous result by Krishnaswami for a different language, we devise an operational semantics that safely executes Simply RaTT programs without space leaks.

We also identify a source of time leaks present in other modal FRP languages: The unfolding of fixed points in delayed computations. The Fitch-style presentation allows an easy way to rules out these leaks, which appears not to be possible in the more traditional dual context approach.
A mechanical formalization of higher-ranked polymorphic type inference
Authors: Zhao Jinxu , Oliveira Bruno C. d. S. , Schrijvers Tom
Published: July 2019

Modern functional programming languages, such as Haskell or OCaml, use sophisticated forms of type inference. While an important topic in the Programming Languages research, there is little work on the mechanization of the metatheory of type inference in theorem provers. In particular we are unaware of any complete formalization of the type inference algorithms that are the backbone of modern functional languages.

This paper presents the first full mechanical formalization of the metatheory for higher-ranked polymorphic type inference. The system that we formalize is the bidirectional type system by Dunfield and Krishnaswami (DK). The DK type system has two variants (a declarative and an algorithmic one) that have been
manually
proven
sound
,
complete
and
decidable
. We present a mechanical formalization in the Abella theorem prover of DK’s declarative type system with a novel algorithmic system. We have a few reasons to use a new algorithm. Firstly, our new algorithm employs
worklist judgments
, which precisely capture the scope of variables and simplify the formalization of scoping in a theorem prover. Secondly, while DK’s original formalization comes with very well-written manual proofs, there are several details missing and some incorrect proofs, which complicate the task of writing a mechanized proof. Despite the use of a different algorithm we prove the same results as DK, although with significantly different proofs and proof techniques. Since such type inference algorithms are quite subtle and have a complex metatheory, mechanical formalizations are an important advance in type-inference research.
An efficient algorithm for type-safe structural diffing
Authors: Miraldo Victor Cacciari , Swierstra Wouter
Published: July 2019

Effectively computing the difference between two version of a source file has become an indispensable part of software development. The
de facto
standard tool used by most version control systems is the UNIX diff utility, that compares two files on a line-by-line basis without any regard for the
structure
of the data stored in these files.

This paper presents an alternative
datatype generic
algorithm for computing the difference between two values of
any
algebraic datatype. This algorithm maximizes sharing between the source and target trees, while still running in linear time.

Finally, this paper demonstrates that by instantiating this algorithm to the Lua abstract syntax tree and mining the commit history of repositories found on GitHub, the resulting patches can often be merged automatically, even when existing technology has failed.
Teaching the art of functional programming using automated grading (experience report)
Authors: Hameer Aliya , Pientka Brigitte
Published: July 2019

Online programming platforms have immense potential to improve students' educational experience. They make programming more accessible, as no installation is required; and automatic grading facilities provide students with immediate feedback on their code, allowing them to to fix bugs and address errors in their understanding right away. However, these graders tend to focus heavily on the functional correctness of a solution, neglecting other aspects of students' code and thereby causing students to miss out on a significant amount of valuable feedback.

In this paper, we recount our experience in using the Learn-OCaml online programming platform to teach functional programming in a second-year university course on programming languages and paradigms. Moreover, we explore how to leverage Learn-OCaml's automated grading infrastructure to make it easy to write more expressive graders that give students feedback on properties of their code beyond simple input/output correctness, in order to effectively teach elements of functional programming style. In particular, we describe our extensions to the Learn-OCaml platform that evaluate students on test quality and code style.

By providing these tools and a suite of our own homework problems and associated graders, we aim to promote functional programming education, enhance students' educational experience, and make teaching and learning typed functional programming more accessible to instructors and students alike, in our community and beyond.
One-Hop Out-of-Band Control Planes for Multi-Hop Wireless Sensor Networks
Authors: Gu Chaojie , Tan Rui , Lou Xin
Published: July 2019

Separation of Control and Data Planes (SCDP) is a desirable paradigm for low-power multi-hop wireless sensor networks requiring high network performance and manageability. Existing SCDP networks generally adopt an
in-band
control plane scheme in that the control-plane messages are delivered by their data-plane networks. The physical coupling of the two planes may lead to undesirable consequences. Recently, multi-radio platforms (e.g., TI CC1350 and OpenMote B) are increasingly available, which make the physical separation of the control and data planes possible. To advance the network architecture design, we propose to leverage on the long-range communication capability of the Low-Power Wide-Area Network (LPWAN) radios to form one-hop out-of-band control planes. LoRaWAN, an open, inexpensive, and ISM band based LPWAN radio, is chosen to prototype our out-of-band control plane called LoRaCP. Several characteristics of LoRaWAN such as downlink-uplink asymmetry and primitive ALOHA media access control need to be dealt with to achieve high reliability and efficiency. To address these challenges, a TDMA-based multi-channel transmission control is designed, which features an urgent channel and negative acknowledgment. On a testbed of 16 nodes, LoRaCP is applied to physically separate the control-plane network of the Collection Tree Protocol (CTP) from its Zigbee-based data-plane network. Extensive experiments show that LoRaCP increases CTP’s packet delivery ratio from 65% to 80% in the presence of external interference, while consuming a per-node average radio power of 2.97mW only.
Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells
Authors: Velásquez Carlos , Mansouri Sheila , Mora Carla , Nassiri Farshad , Suppiah Suganth , Martino Juan , Zadeh Gelareh , Fernández-Luna José L.
Published: July 2019

The invasive capacity of GBM is one of the key tumoral features associated with treatment resistance, recurrence, and poor overall survival. The molecular machinery underlying GBM invasiveness comprises an intricate network of signaling pathways and interactions with the extracellular matrix and host cells. Among them, PI3k/Akt, Wnt, Hedgehog, and NFkB play a crucial role in the cellular processes related to invasion. A better understanding of these pathways could potentially help in developing new therapeutic approaches with better outcomes. Nevertheless, despite significant advances made over the last decade on these molecular and cellular mechanisms, they have not been translated into the clinical practice. Moreover, targeting the infiltrative tumor and its significance regarding outcome is still a major clinical challenge. For instance, the pre- and intraoperative methods used to identify the infiltrative tumor are limited when trying to accurately define the tumor boundaries and the burden of tumor cells in the infiltrated parenchyma. Besides, the impact of treating the infiltrative tumor remains unclear. Here we aim to highlight the molecular and clinical hallmarks of invasion in GBM.
Eucommia ulmoides Oliv. Leaf Extract Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats by Protecting Endothelial Function and Ameliorating Hypothalamic-Pituitary-Gonadal Axis Function
Authors: Fu Hui , Bai Xue , Le Liang , Tian Dong , Gao Hai , Qi Li-xin , Hu Ke-ping
Published: July 2019

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Eucommia ulmoides Oliv. is used as a traditional medicine for male impotence, but no systematic study has examined its effect on diabetes-associated ED. In this study, we investigated the effects of Eucommia ulmoides Oliv. leaf extract (EULE) on restoring erectile function in streptozotocin (STZ)-induced diabetic rats model. After 16 weeks of treatment, EULE administration had significantly increased intracavernosal pressure, nitric oxide (NO) levels, and cyclic guanosine monophosphate (cGMP) concentrations. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were markedly higher and serum malondialdehyde (MDA) levels were lower in the EULE-treated groups than in the diabetic model group. EULE restored NO biosynthesis by significantly increasing protein kinase B (Akt) and endothelial NO synthase (eNOS) activation. Furthermore, EULE is likely to benefit the hypothalamic-pituitary-gonadal (HPG) axis, as it increased gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations as well as hormone receptors Gnrhr, Fshr, and Lhr expression levels. Hence, EULE attenuates oxidative stress, increases NO production, and activates the Akt-eNOS pathway to restore endothelial function; moreover, EULE enhances the HPG axis to improve erectile function. These results suggest that EULE may represent a new therapeutic avenue for diabetes-associated ED.
Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders?
Authors: Zhou Youlian , Xu Haoming , Huang Hongli , Li Yingfei , Chen Huiting , He Jie , Du Yanlei , Chen Ye , Zhou Yongjian , Nie Yuqiang
Published: July 2019

Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.
Current State of Modern Biotechnological-BasedAeromonas hydrophilaVaccines for Aquaculture: A Systematic Review
Authors: Mzula Alexanda , Wambura Philemon N. , Mdegela Robinson H. , Shirima Gabriel M.
Published: July 2019

This systematic review describes what “the cutting edge vaccines forAeromonas hydrophilaare”. The focus is on types of high tech biotechnological based vaccines, target gene or antigen in developing these vaccines, and challenge model fish species used in vaccines efficacy testing. Vaccines delivery methods, immune response, and their efficacy, adjuvant or carrier systems used, and the overall experimental setup or design of the vaccines under investigation are also described. The search for the original papers published between 2009 and 2018 was conducted in June of 2018, using the PubMed and Google scholar electronic database. Twenty-three (23/4386) studies were included in the final assembly using PRISMA guidelines (Protocol not registered). Recombinant protein vaccines were the highly experimented type of the modern biotechnological based vaccines identified in the selected studies (16/23; 70%). Outer membrane proteins (OMPs) of differentβ-barrels were shown to be a potential antigenic entity forA. hydrophilavaccines (57%). Intraperitoneal route with conventional carries or adjuvants was the highly applied delivery system while very few studies used herbal based vaccine adjuvants and nanomaterial as a vaccine carrier. Variation was observed in terms of protection levels in the selected studies. The experimental designs partly contributed to the observed variation. Therefore, recombinant vaccines that use new carrier system technologies and delivered through oral route in feeds would have been of great value for use in the prevention and control ofA. hydrophilainfections in fish. Despite the usefulness as academic tools to identify what is important in pathogenicity of the etiological agent to the host fish, these vaccines are only economically viable in very high-value animals. Therefore, if vaccination is a good option forA. hydrophilagroup, then simple autogenous vaccines based on accurate typing and evidence-based definition of the epidemiological unit for their use would be the most viable approach in terms of both efficacy and economic feasibility especially in low and middle-income countries (LMIC).
The Effect of rTMS over the Different Targets on Language Recovery in Stroke Patients with Global Aphasia: A Randomized Sham-Controlled Study
Authors: Ren Caili , Zhang Guofu , Xu Xinlei , Hao Jianfeng , Fang Hui , Chen Ping , Li Zhaohui , Ji Yunyun , Cai Qingjie , Gao Fei
Published: July 2019

Objective.To evaluate and compare the effects of repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis of the posterior inferior frontal gyrus (pIFG) and the right posterior superior temporal gyrus (pSMG) in global aphasia following subacute stroke.Methods.Fifty-four patients with subacute poststroke global aphasia were randomized to 15-day protocols of 20-minute inhibitory 1 Hz rTMS over either the right triangular part of the pIFG (the rTMS-b group) or the right pSTG (the rTMS-w group) or to sham stimulation, followed by 30 minutes of speech and language therapy. Language outcomes were assessed by aphasia quotient (AQ) scores obtained from the Chinese version of the Western Aphasia Battery (WAB) at baseline and immediately after 3 weeks (15 days) of experimental treatment.Results.Forty-five patients completed the entire study. The primary outcome measures include the changes in WAB-AQ score, spontaneous speech, auditory comprehension, and repetition. These measures indicated significant main effect between the baseline of the rTMS-w, rTMS-b, and sham groups and immediately after stimulation (P<0.05). Compared with the sham group, the increases were significant for auditory comprehension, repetition, and AQ in the rTMS-w group (P<0.05), whereas the changes in repetition, spontaneous speech, and AQ tended to be higher in the rTMS-b group (P<0.05).Conclusions.Inhibitory rTMS targeting the right pIFG and pSTG can be an effective treatment for subacute stroke patients with global aphasia. The effect of rTMS may depend on the stimulation site. Low-frequency rTMS inhibited the right pSTG and significantly improved language recovery in terms of auditory comprehension and repetition, whereas LF-rTMS inhibited the right pIFG, leading to apparent changes in spontaneous speech and repetition.
MicroRNAs as Potential Biomarkers for Chemoresistance in Adenocarcinomas of the Esophagogastric Junction
Authors: Just Christina , Knief Juliana , Lazar-Karsten Pamela , Petrova Ekaterina , Hummel Richard , Röcken Christoph , Wellner Ulrich , Thorns Christoph
Published: July 2019

Concerning adenocarcinomas of the esophagogastric junction, neoadjuvant chemotherapy is regularly implemented, but patients’ response varies greatly, with some cases showing no therapeutic effect, being deemed as chemoresistant. Small, noncoding RNAs (miRNAs) have evolved as key players in biological processes, including malignant diseases, often promoting tumor growth and expansion. In addition, specific miRNAs have been implicated in the development of chemoresistance through evasion of apoptosis, cell cycle alterations, and drug target modification. We performed a retrospective study of 33 patients receiving neoadjuvant chemotherapy by measuring their miRNA expression profiles. Histologic tumor regression was evaluated using resection specimens, while miRNA profiles were prepared using preoperative biopsies without prior therapy. A preselected panel of 96 miRNAs, known to be of importance in various malignancies, was used to test for significant differences between responsive (chemosensitive) and nonresponsive (chemoresistant) cases. The cohort consisted of 12 nonresponsive and 21 responsive cases with the following 4 miRNAs differentially expressed between both the groups: hsa-let-7f-5p, hsa-miRNA-221-3p, hsa-miRNA-31-5p, and hsa-miRNA-191-5p. The former 3 showed upregulation in chemoresistant cases, while the latter showed upregulation in chemosensitive cases. In addition, significant correlation between high expression of hsa-miRNA-194-5p and prolonged survival could be demonstrated (pvalue <0.0001). In conclusion, we identified a panel of 3 miRNAs predicting chemoresistance and a single miRNA contributing to chemosensitivity. These miRNAs might function as prognostic biomarkers and enable clinicians to better predict the effect of one or more reliably select patients benefitting from (neoadjuvant) chemotherapy.
Symptomatic Clitoral Neuroma within an Epidermal Inclusion Cyst at the Site of Prior Female Genital Cutting
Authors: Zoorob Dani , Kristinsdottir Kristrun , Klein Thomas , Seo-Patel Sonyoung
Published: July 2019

Background. Clitoral neuromas occurring after female genital mutilation/cutting (FGM/C) can vary in presentation and may require surgical management. Case. A 39-year-old East African female with a history of FGM/C presented during pregnancy with a progressively enlarging mass and worsening periclitoral pain. Postpartum surgical excision restored cosmesis and resolved the discomfort with pathology confirming the presence of a neuroma within the epidermal inclusion cyst. Conclusion. We present the first published case of a symptomatic clitoral neuroma within an epidermal inclusion cyst. This unique pathology demonstrates that complications of female genital cutting can present in complex and varied ways. Considering the prevalence of FGM/C and increasing rates of emigration from countries in which FGM/C is performed, complex clitoral neuromas are an important long-term complication which providers in Africa or internationally must be aware of.
Cooccurrence of NDM-1, ESBL, RmtC, AAC(6′)-Ib, and QnrB in Clonally Related Klebsiella pneumoniae Isolates Together with Coexistence of CMY-4 and AAC(6′)-Ib in Enterobacter cloacae Isolates from Saudi Arabia
Authors: Al-Agamy Mohamed H. , El-Mahdy Taghrid S. , Radwan Hesham H. , Poirel Laurent
Published: July 2019

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6′)-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The blaNDM-1 gene was always identified on a 70-kb plasmid, whereas the blaVIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6′]-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.
Antioxidant Effects ofSatureja hortensisL. Attenuate the Anxiogenic Effect of Cisplatin in Rats
Authors: Kumburovic Igor , Selakovic Dragica , Juric Tatjana , Jovicic Nemanja , Mihailovic Vladimir , Stankovic Jelena Katanic , Sreckovic Nikola , Kumburovic Davor , Jakovljevic Vladimir , Rosic Gvozden
Published: July 2019

Numerous adverse effects of cisplatin-based therapy are usually accompanied by enhanced oxidative damage and cell apoptosis in various tissues. Even neurotoxic manifestations of cisplatin administration, such as the anxiogenic effect, appear along with the increased oxidative stress and apoptotic indicators in certain brain regions. Thirty-five Wistar albino male rats were divided into seven groups: control, cisplatin (received a single dose of cisplatin: 7.5 mg/kg), three groups with oral administration ofSatureja hortensisL. methanolic extract (SH) (low: 50 mg/kg, middle: 100 mg/kg, and high dose: 200 mg/kg) along with cisplatin application, a group with the extract in high dose alone, and a silymarin group (cisplatin and silymarin: 100 mg/kg), in order to evaluate the antioxidant effects of SH on cisplatin-induced increase in the anxiety level. After completing 10-day pretreatments, behavioral testing was performed in the open field and the elevated plus maze, followed by an investigation of oxidative stress and apoptosis parameters in hippocampal tissue samples. Cisplatin administration resulted in anxiogenic-like behavior, increased lipid peroxidation, and proapoptotic markers accompanied by the decline in antioxidant and antiapoptotic defense. The administration of extract alone did not significantly alter any of the estimated parameters. When applied along with cisplatin, SH in a dose of 100 mg/kg induced the significant anxiolytic effect with concomitant recovery of antioxidant and antiapoptotic activity indicators, while both lower and higher doses of the extract failed to improve the adverse effects of cisplatin administration. The beneficial effects of the middle dose of SH were equivalent to the same dose of silymarin, as a “golden standard.” Our results indicate that the antioxidant supplementation with SH in an optimal dose significantly improved the oxidative status and it had antiapoptotic effect in the rat hippocampus disturbed by cisplatin administration, which was accompanied with attenuation of cisplatin-induced anxiogenic effect.
Effects of Systematic Categorization Training on Cognitive Performance in Healthy Older Adults and in Adults with Traumatic Brain Injury
Authors: Constantinidou Fofi
Published: July 2019

This study investigated the effects of hierarchical cognitive training using the categorization program (CP), designed initially for adults with cognitive deficits associated with traumatic brain injury (TBI). Fifty-eight participants were included: a group of fifteen young adults with TBI (ages 18-48), another group of fifteen noninjured young adults (ages 18-50), and two groups of adults over 60 randomly assigned into the experimental group (n=14) or the control group (n=14). Following neuropsychological testing, the two young adult groups and the experimental older adult group received the CP training for 10-12 weeks. The CP training consisted of 8 levels targeting concept formation, object categorization, and decision-making abilities. Two CP tests (administered before and after the training) and three probe tasks (administered at specified intervals during the training) assessed skills relating to categorization. All treated groups showed significant improvement in their categorization performance, although younger participants (with or without TBI) demonstrated greater gains. Gains on the categorization measures were maintained by a subgroup of older adults up to four months posttraining. Implications of these findings in terms of adult cognitive learning and directions for future research on adult cognitive rehabilitation and cognitive stimulation programs are discussed.
IgE, IgG1, and IgG4 Reactivity toDermatophagoides pteronyssinusGlycosylated Extract in Allergic Patients
Authors: Resende Rafael de Oliveira , Ynoue Leandro Hideki , Miranda Juliana Silva , de Almeida Karine Cristine , Silva Deise Aparecida de Oliveira , Sopelete Monica Camargo , Alves Ronaldo , Gennari-Cardoso Margareth Leitão , Taketomi Ernesto Akio
Published: July 2019

Background. House dust mites are important allergen sources and some of these allergenic proteins may contain carbohydrate moieties, which are able to be isolated using lectins, as Concanavalin A (ConA). This study aimed to investigate allergenicity (IgE) and antigenicity (IgG1 and IgG4) of ConA-unbound and ConA-boundDermatophagoides pteronyssinus(Dpt) crude extracts using sera of mite-allergic patients as well as inhibition capacity of antibody binding.Material and Methods. We obtained mannose-enriched and mannose-depleted fractions from Dpt by ConA affinity chromatography. Both ConA-bound and ConA-unbound fractions were evaluated by ELISA and Western Blotting for specific IgE, IgG1, and IgG4 reactivity with sera obtained from 95 mite-allergic patients (DP+) and 92 nonallergic (NA) subjects. Inhibition ELISA was used to assess cross-reactivity between Dpt extract and its fractions.Results. Among the DP+ patients, no difference was found between ConA-unbound and ConA-bound fractions regarding the levels of specific IgE, IgG1, and IgG4. Nonallergic subjects had the same levels of specific IgG1 to both ConA-unbound and ConA-bound fractions, although for specific IgG4, values were higher for ConA-bound. A positive correlation was found among specific IgE, IgG1, and IgG4 levels when Dpt was compared to ConA-unbound and ConA-bound fractions. Recognition of crude Dpt by IgE, IgG1, and IgG4 was highly inhibited by ConA-unbound and ConA-bound fractions. Western Blotting revealed a broad spectrum of bands ranging from 14 to 116 kDa recognized by specific IgE and IgG4. However, IgG1 reached higher frequency values on high molecular weight polypeptides.Conclusion. ConA-unbound and ConA-bound fractions derived fromD. pteronyssinuscrude extract revealed important components involved in the IgE recognition in allergic patients as well as IgG1 and/or IgG4 in allergic and healthy subjects.
Some Properties of Canonical Dual K-Bessel Sequences for Parseval K-Frames
Authors: Xiang Zhong-Qi
Published: July 2019

The concept of canonical dual K-Bessel sequences was recently introduced, a deep study of which is helpful in further developing and enriching the duality theory of K-frames. In this paper we pay attention to investigating the structure of the canonical dual K-Bessel sequence of a Parseval K-frame and some derived properties. We present the exact form of the canonical dual K-Bessel sequence of a Parseval K-frame, and a necessary and sufficient condition for a dual K-Bessel sequence of a given Parseval K-frame to be the canonical dual K-Bessel sequence is investigated. We also give a necessary and sufficient condition for a Parseval K-frame to have a unique dual K-Bessel sequence and equivalently characterize the condition under which the canonical dual K-Bessel sequence of a Parseval K-frame admits a unique dual K⁎-Bessel sequence. Finally, we obtain a minimal norm property on expansion coefficients of elements in the range of K resulting from the canonical dual K-Bessel sequence of a Parseval K-frame.
A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System
Authors: Kilic Pelin , Bay Meltem , Yildirim Yasin , Coskun Oznur , Seker Sukran , Baydin Pinar , Lalegul Ulker Ozge , Parmaksiz Mahmut , Cubukcuoglu Deniz Gunseli , Yilmazer Acelya , Dalva Klara , Elcin Ayse Eser , Akcali Kamil Can , Ilhan Osman , Gurman Gunhan
Published: July 2019

Allogeneic stem cell transplantation applications have improved tremendously over the past quarter of a century. The use of new immunosuppressive protocols and elimination of T cells by CD34+ cell enrichment or T cell depletion on apheresis products increases the chance of using partially matched or haploidentical grafts. This is without increasing the risk of graft-versus-host disease, which is observed as a major complication of hematopoietic stem cell transplantation. The aim of this protocol is to evaluate the results obtained from 6 different process cycles performed on 6 different days. We used the CliniMACS Plus system located in our Cell and Tissue Manufacturing Center Quality Control Unit which is already calibrated as a class D room and includes a class A microbiological safety cabinet inside. The average purity of the end products was 95.66%, excluding only one end product which was 70%; this was higher than the values in current studies in the field. Superior to the reported studies, the CD3 quantity in each end product was below the dedicated thresholds. BactecTM FX40 blood culture system test results were detected as negative for each end product. Endotoxin testing suggested the absence of endotoxin within the products. The consistent outcomes obtained from these 6 different process cycles confirmed that the CliniMACS® Plus process cycles performed in accordance with our well-defined quality management system procedure is sufficient for the routine application of high-quality and safe CD34+ enrichment processes within our clean room area.