bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research on Knowledge Navigation Model Based on Users’ Tolerance Zone During the Process of R&D Achievements Delivery
Authors: Tao Na 
Published: May 2022

How to promote deep knowledge transfer and knowledge application during the process of R&D achievements delivery? This paper takes knowledge transfer as the research object. First of all, the path of knowledge transfer during the process of R&D achievements delivery is drawn. Next, the status of knowledge transfer is assessed by constructing users’ tolerance zone model by selecting key factors in the path of knowledge transfer. Empirical research finds the following conclusions: knowledge transfer experience[Formula: see text], knowledge transfer distance and knowledge transfer carrier have a positive influence on the actual service level of knowledge transfer. Knowledge transfer experience[Formula: see text], continuous strengthening behavior and knowledge service commitment have a positive impact on the ideal service level of knowledge transfer. Then, based on knowledge transfer path and users’ tolerance zone model, this paper explores the knowledge navigation model from the environment, main structure and transmission mode. Finally, from the perspective of knowledge transfer environment, knowledge transfer subject, knowledge transfer object and knowledge transfer mode, the relevant strategies were put forward to reduce knowledge retention, and promote the deep knowledge absorption and transformation during the process of R&D achievements delivery.
Risk Prediction of IoT Devices Based on Vulnerability Analysis
Authors: Oser Pascal , van der Heijden Rens W. , Lüders Stefan , Kargl Frank 
Published: May 2022

Internet of Things (IoT) devices are becoming more widespread not only in areas such as smart homes and smart cities but also in research and office environments. The sheer number, heterogeneity, and limited patch availability provide significant challenges for the security of both office networks and the Internet in general. The systematic estimation of device risks, which is essential for mitigation decisions, is currently a skill-intensive task that requires expertise in network vulnerability scanning, as well as manual effort in firmware binary analysis.

This article introduces SAFER,

1

the Security Assessment Framework for Embedded-device Risks, which enables a semi-automated risk assessment of IoT devices in any network. SAFER combines information from network device identification and automated firmware analysis to estimate the current risk associated with the device. Based on past vulnerability data and vendor patch intervals for device models, SAFER extrapolates those observations into the future using different automatically parameterized prediction models. Based on that, SAFER also estimates an indicator for future security risks. This enables users to be aware of devices exposing high risks in the future.

One major strength of SAFER over other approaches is its scalability, achieved through significant automation. To demonstrate this strength, we apply SAFER in the network of a large multinational organization, to systematically assess the security level of hundreds of IoT devices on large-scale networks.
Results indicate that SAFER successfully identified 531 out of 572 devices leading to a device identification rate of 92.83 %, analyzed 825 firmware images, and predicted the current and future security risk for 240 devices.
An FPGA Overlay for CNN Inference with Fine-grained Flexible Parallelism
Authors: Choudhury Ziaul , Shrivastava Shashwat , Ramapantulu Lavanya , Purini Suresh 
Published: May 2022

Increasingly, pre-trained convolutional neural networks (CNNs) are being deployed for inference in various computer vision applications, both on the server-side in the data centers and at the edge. CNN inference is a very compute-intensive task. It is a challenge to meet performance metrics such as latency and throughput while optimizing power. Special-purpose ASICs and FPGAs are suitable candidates to meet these power and performance budgets simultaneously. Rapidly evolving CNN architectures involve novel convolution operations such as point convolutions, depth separable convolutions, and so on. This leads to substantial variation in the computational structure across CNNs and layers within a CNN. Because of this, FPGA reconfigurability provides an attractive tradeoff compared to ASICs. FPGA-based hardware designers address the structural variability issue by generating a network-specific accelerator for a single network or a class of networks. However, homogeneous accelerators are network agnostic and often sacrifice throughput and FPGA LUTs for flexibility.
In this article, we propose an FPGA overlay for efficient processing of CNNs that can be scaled based on the available compute and memory resources of the FPGA. The overlay is configured on the fly through control words sent by the host on a per-layer basis. Unlike current overlays, our architecture exploits all forms of parallelism inside a convolution operation. A constraint system is employed at the host end to find out the per-layer configuration of the overlay that uses all forms of parallelism in the processing of the layer, resulting in the highest throughput for that layer.

We studied the effectiveness of our overlay by using it to process AlexNet, VGG16, YOLO, MobileNet, and ResNet-50 CNNs targeting a Virtex7 and a bigger Ultrascale+VU9P FPGAs. The chosen CNNs have a mix of different types of convolution layers and filter sizes, presenting a good variation in model size and structure. Our accelerator reported a maximum throughput of 1,200 GOps/second on the Virtex7, an improvement of 1.2

\( \times \)

to 5

\( \times \)

over the recent designs. Also, the reported performance density, measured in giga operations per second per KLUT, is 1.3

\( \times \)

to 4

\( \times \)

improvement over existing works. Similar speed-up and performance density is also observed for the Ultrascale+VU9P FPGA.
Hemoglobin I from Lucina pectinata on Collagen Scaffold: A Prospective Hydrogen Sulfide Scavenger
Authors: Santiago Jennifer Vargas , Cheeseborough Anibal Quintana , López-Garriga Juan 
Published: May 2022

Hydrogen sulfide (H2S), independently of being a toxic gas with a characteristic smell of rotten eggs, is a crucial signaling molecule with significant physiological functions. Given the rapid diffusivity of the gas, it is a challenge to develop robust sensors and biomarkers to quantify free or bound H2S. In addition, there is the need to further develop a robust biosystem to efficiently trap or scavenge H2S from different producing environments. The work presented here uses recombinant met-aquo rHbI (rHbI-H2O) immobilization techniques on collagen to determine its ability to bind H2S due to its high affinity (

1.24
×

10

8

M-1). The hemeprotein will function as a scavenger on this scaffold system. UV-Vis absorption and UV-Vis diffuse reflectance (%R) spectroscopy of rHbI-H2O and rHbI-sulfide (rHbI-H2S) complex in solution and collagen scaffold demonstrated that the heme chromophore retains its reactivity and properties. UV-Vis diffuse reflectance measurements, transformed using the Kubelka-Munk function (K-M function), show a linear correlation (

R

2

=
0.9987

and 0.9916) of rHbI-H2O and rHbI-H2S within concentrations from 1 μM to 35 μM for derivatives. The extraordinary affinity of rHbI-H2O for H2S suggests recombinant met-aquo HbI in a collagen scaffold is an excellent scavenger moiety for hydrogen sulfide. These findings give insight into H2S trapping using the rHbI-H2O-collagen scaffold, where the rHbI-H2S concentration can be determined. Future pathways are to work toward the development of a met-aquo rHbI collagen solution capable of being printed as single drops on polymer, cotton or chromatographic paper. Upon exposure of these matrixes to H2S, the rHbI-H2S complex is formed and its concentration determined using UV-Vis diffuse reflectance technique.
B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Authors: Wang Sophia S. , Vajdic Claire M. , Linet Martha S. , Slager Susan L. , Voutsinas Jenna , Nieters Alexandra , Casabonne Delphine , Cerhan James R. , Cozen Wendy , Alarcón Graciela , Martínez-Maza Otoniel , Brown Elizabeth E. , Bracci Paige M. , Turner Jennifer , Hjalgrim Henrik , Bhatti Parveen , Zhang Yawei , Birmann Brenda M. , Flowers Christopher R. , Paltiel Ora , Holly Elizabeth A. , Kane Eleanor , Weisenburger Dennis D. , Maynadié Marc , Cocco Pierluigi , Foretova Lenka , Breen Elizabeth Crabb , Lan Qing , Brooks-Wilson Angela , De Roos Anneclaire J. , Smith Martyn T. , Roman Eve , Boffetta Paolo , Kricker Anne , Zheng Tongzhang , Skibola Christine F. , Clavel Jacqueline , Monnereau Alain , Chanock Stephen J. , Rothman Nathaniel , Benavente Yolanda , Hartge Patricia , Smedby Karin E. 
Published: May 2022

Abstract

Background:
A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non–Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes.

Methods:
In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell–mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression.

Results:
We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59–2.07; P-trend (Ptrend) &lt; 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell–mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend &lt; 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction.

Conclusions:
Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions.

Impact:
Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.
Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer
Authors: Yam Clinton , Abuhadra Nour , Sun Ryan , Adrada Beatriz E. , Ding Qing-Qing , White Jason B. , Ravenberg Elizabeth E. , Clayborn Alyson R. , Valero Vicente , Tripathy Debu , Damodaran Senthilkumar , Arun Banu K. , Litton Jennifer K. , Ueno Naoto T. , Murthy Rashmi K. , Lim Bora , Baez Luis , Li Xiaoxian , Buzdar Aman U. , Hortobagyi Gabriel N. , Thompson Alistair M. , Mittendorf Elizabeth A. , Rauch Gaiane M. , Candelaria Rosalind P. , Huo Lei , Moulder Stacy L. , Chang Jeffrey T. 
Published: May 2022

AbstractPurpose:Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.Experimental Design:To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide–based neoadjuvant therapy.Results:Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience a pCR (23% vs. 40%; P = 0.07), had shorter event-free survival (29.4 vs. 32.2 months, P = 0.15), metastasis-free survival (30.3 vs. 32.4 months, P = 0.22); and overall survival (32.6 vs. 34.3 months, P = 0.21). This heterogeneity is mirrored in the molecular profiling. Mutations in PI3KCA (23% vs. 9%, P = 0.07) and its pathway (41% vs. 18%, P = 0.02) were frequently observed and enriched in MpBCs. The gene expression profiles of each histologically defined subtype were distinguishable and characterized by distinctive gene signatures. Among nonmetaplastic (non-Mp) TNBCs, 10% possessed a metaplastic-like gene expression signature and had pCR rates and survival outcomes similar to MpBC.Conclusions:Further investigations will determine if metaplastic-like tumors should be treated more similarly to MpBC in the clinic. The 23% pCR rate in this study suggests that patients with MpBC should be considered for NAT. To improve this rate, a pathway analysis predicted enrichment of histone deacetylase (HDAC) and RTK/MAPK pathways in MpBC, which may serve as new targetable vulnerabilities.
Concurrent Inhibition of ERK and Farnesyltransferase Suppresses the Growth of HRAS Mutant Head and Neck Squamous Cell Carcinoma
Authors: Javaid Sehrish , Schaefer Antje , Goodwin Craig M. , Nguyen Victoria V. , Massey Frances L. , Pierobon Mariaelena , Gambrell-Sanders Da'Jhnae , Waters Andrew M. , Lambert Kathryn N. , Diehl J. Nathaniel , Hobbs G. Aaron , Wood Kris C. , Petricoin Emanuel F. , Der Channing J. , Cox Adrienne D. 
Published: May 2022

Abstract
Human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide with an unmet need for more effective, less toxic treatments. Currently, both the disease and the treatment of HNSCC cause significant mortality and morbidity. Targeted therapies hold new promise for patients with HPV-negative status whose tumors harbor oncogenic HRAS mutations. Recent promising clinical results have renewed interest in the development of farnesyltransferase inhibitors (FTIs) as a therapeutic strategy for HRAS-mutant cancers. With the advent of clinical evaluation of the FTI tipifarnib for the treatment of HRAS-mutant HNSCC, we investigated the activity of tipifarnib and inhibitors of HRAS effector signaling in HRAS-mutant HNSCC cell lines. First, we validated that HRAS is a cancer driver in HRAS-mutant HNSCC lines. Second, we showed that treatment with the FTI tipifarnib largely phenocopied HRAS silencing, supporting HRAS as a key target of FTI antitumor activity. Third, we performed reverse-phase protein array analyses to profile FTI treatment-induced changes in global signaling, and conducted CRISPR/Cas9 genetic loss-of-function screens to identify previously unreported genes and pathways that modulate sensitivity to tipifarnib. Fourth, we determined that concurrent inhibition of HRAS effector signaling (ERK, PI3K, mTORC1) increased sensitivity to tipifarnib treatment, in part by overcoming tipifarnib-induced compensatory signaling. We also determined that ERK inhibition could block tipifarnib-induced epithelial-to-mesenchymal transition, providing a potential basis for the effectiveness of this combination. Our results support future investigations of these and other combination treatments for HRAS mutant HNSCC.
A Preclinical Study to Repurpose Spironolactone for Enhancing Chemotherapy Response in Bladder Cancer
Authors: Xu Dongbo , Cao Qiang , Wang Li , Wang Jianmin , Xu Bo , Attwood Kristopher , Wei Lei , Wu Yue , Smith Gary J. , Katsuta Eriko , Takabe Kazuaki , Chatta Gurkamal , Guru Khurshid A. , Goodrich David W. , Li Qiang J. 
Published: May 2022

AbstractNeoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard-of-care for patients with muscle-invasive bladder cancer (MIBC). Defects in nucleotide excision repair (NER) are associated with improved responses to NAC. Excision Repair Cross-Complementation group 3 (ERCC3) is a key component of NER process. No NER inhibitors are available for treating patients with bladder cancer. We have developed an ex vivo cell-based assay of 6–4 pyrimidine–pyrimidinone (6–4PP) removal as a surrogate measure of NER capacity in human bladder cancer cell lines. The protein expression of ERCC3 was examined in human MIBC specimens and cell lines. Small molecule inhibitors were screened for NER inhibition in bladder cancer cell lines. Spironolactone was identified as a potent NER inhibitor. Combined effects of spironolactone with chemo-drugs were evaluated in vitro and in vivo. The efficacy between platinum and spironolactone on cytotoxicity was determined by combination index. A correlation between NER capacity and cisplatin sensitivity was demonstrated in a series of bladder cancer cell lines. Further, siRNA-mediated knockdown of ERCC3 abrogated NER capacity and enhanced cisplatin cytotoxicity. Spironolactone inhibited ERCC3 protein expression, abrogated NER capacity, and increased platinum-induced cytotoxicity in bladder cancer cells in vivo and in patient-derived organoids. Moreover, spironolactone exhibited the potential synergism effects with other clinical chemotherapy regimens in bladder cancer cell lines. Our data support the notion of repurposing spironolactone for improving the chemotherapy response of NAC in patients with MIBC. Further clinical trials are warranted to determine the safety and efficacy of spironolactone in combination with chemotherapy.
CD74-NRG1 Fusions Are Oncogenic In Vivo and Induce Therapeutically Tractable ERBB2:ERBB3 Heterodimerization
Authors: Werr Lisa , Plenker Dennis , Dammert Marcel A. , Lorenz Carina , Brägelmann Johannes , Tumbrink Hannah L. , Klein Sebastian , Schmitt Anna , Büttner Reinhard , Persigehl Thorsten , Shokat Kevan M. , Wunderlich F. Thomas , Schram Alison M. , Peifer Martin , Sos Martin L. , Reinhardt H. Christian , Thomas Roman K. 
Published: May 2022

Abstract
NRG1 fusions are recurrent somatic genome alterations occurring across several tumor types, including invasive mucinous lung adenocarcinomas and pancreatic ductal adenocarcinomas and are potentially actionable genetic alterations in these cancers. We initially discovered CD74-NRG1 as the first NRG1 fusion in lung adenocarcinomas, and many additional fusion partners have since been identified. Here, we present the first CD74-NRG1 transgenic mouse model and provide evidence that ubiquitous expression of the CD74-NRG1 fusion protein in vivo leads to tumor development at high frequency. Furthermore, we show that ERBB2:ERBB3 heterodimerization is a mechanistic event in transformation by CD74-NRG1 binding physically to ERBB3 and that CD74-NRG1–expressing cells proliferate independent of supplemented NRG1 ligand. Thus, NRG1 gene fusions are recurrent driver oncogenes that cause oncogene dependency. Consistent with these findings, patients with NRG1 fusion-positive cancers respond to therapy targeting the ERBB2:ERBB3 receptors.
Diaminobutoxy-substituted Isoflavonoid (DBI-1) Enhances the Therapeutic Efficacy of GLUT1 Inhibitor BAY-876 by Modulating Metabolic Pathways in Colon Cancer Cells
Authors: Guo Lichao , Zhang Wen , Xie Yanqi , Chen Xi , Olmstead Emma E. , Lian Mengqiang , Zhang Baochen , Zaytseva Yekaterina Y. , Evers B. Mark , Spielmann H. Peter , Liu Xifu , Watt David S. , Liu Chunming 
Published: May 2022

Abstract
Cancer cells undergo significant “metabolic remodeling” to provide sufficient ATP to maintain cell survival and to promote rapid growth. In colorectal cancer cells, ATP is produced by mitochondrial oxidative phosphorylation and by substantially elevated cytoplasmic glucose fermentation (i.e., the Warburg effect). Glucose transporter 1 (GLUT1) expression is significantly increased in colorectal cancer cells, and GLUT1 inhibitors block glucose uptake and hence glycolysis crucial for cancer cell growth. In addition to ATP, these metabolic pathways also provide macromolecule building blocks and signaling molecules required for tumor growth. In this study, we identify a diaminobutoxy-substituted isoflavonoid (DBI-1) that inhibits mitochondrial complex I and deprives rapidly growing cancer cells of energy needed for growth. DBI-1 and the GLUT1 inhibitor, BAY-876, synergistically inhibit colorectal cancer cell growth in vitro and in vivo. This study suggests that an electron transport chain inhibitor (i.e., DBI-1) and a glucose transport inhibitor, (i.e., BAY-876) are potentially effective combination for colorectal cancer treatment.
МАРКЕРИ ЛАЙМ-БОРЕЛІОЗУ, БАРТОНЕЛЬОЗУ І ЛЯМБЛІОЗУ У ПАЦІЄНТІВ ІЗ КРОПИВ’ЯНКОЮ
Authors: Петрук А. М. , Івахів О. Л. , Качор В. О. , Жулкевич І. В. , Корда М. М. , Кліщ І. М. 
Published: May 2022

Мета дослідження – з’ясувати частоту виявлення серологічних і паразитологічних маркерів збудників деяких інфекційних хвороб (Лайм-бореліозу, бартонельозу і лямбліозу) в пацієнтів із кропивʼянкою.
Пацієнти і методи. Обстежено 52 хворих на кропивʼянку віком від 18 до 70 років, які протягом 2019-2022 рр. перебували на амбулаторному і стаціонарному лікуванні у КНП «Старокостянтинівська багатопрофільна лікарня» Хмельницької області. Чоловіків було 16 (30,8 %), жінок – 36 (69,2 %).
У сироватках крові усіх обстежених методом імуноферментного аналізу (ІФА) визначали антитіла до антигенів комплексу B. burgdorferi s. l., застосувавши тест-системи компанії Euroimmun AG (Німеччина): класу IgМ − тест-системою Anti-Borrelia burgdorferi ELISA (IgM), класу IgG − Anti-Borrelia plus VIsE ELISA (IgG). Отримані результати оцінювали як позитивні, проміжні або негативні та інтерпретували відповідно до рекомендацій виробника.
Сироваткові антитіла класу IgG до збудників бартонельозу (B. henselae / B. quintana) визначали в сироватці крові хворих за допомогою методу непрямої імунофлуоресценції (НІФ), застосувавши тест-системи «Mosaic for Bartonella henselae / Bartonella quintana (IgG)» компанії Euroimmun AG (Німеччина), вироблені за технологією «Біочіп».
Для виявлення лямблій готували мазок нативного матеріалу фекалій, який досліджували у світлооптичному мікроскопі при малому і великому збільшенні (об. ×8, ×40, ок. ×10), шукали цистні форми паразита. Антитіла класу IgM до антигенів лямблій у сироватках крові пацієнтів із кропив’янкою визначали методом імуноферментного аналізу (ІФА), використавши набори «Лямблія-IgM-ІФА-Бест».
Результати досліджень та їх обговорення. При дослідженні за допомогою ІФА сироваток крові пацієнтів з кропив’янкою позитивні або проміжні результати наявності антитіл класів M і/або G до комплексу B. burgdorferi s. l. отримано у 22 (42,3 %) осіб із 52, негативні результати – у 30 (57,7 %).
Методом непрямої імунофлуоресценції в сироватках 4 (7,7 %) хворих із кропив’янкою діагностували специфічні імуноглобуліни класу G лише до B. henselaе.
При паразитологічному дослідженні фекалій хворих із кропив’янкою цисти лямблій знайдено у 12 (23,1 %) осіб із 52 обстежених. За допомогою методу ІФА специфічні сироваткові антитіла класу М до антигенів лямблій виявили у 3 (5,8 %) пацієнтів із кропив’янкою з 52 обстежених.
Висновки. Діагностування лямбліозу у 14 із 38 пацієнтів (36,8 %) з ідіопатичною кропив’янкою дає підстави вважати цей паразитоз тригерним фактором виникнення кропив’янки. Наявність у хворих на кропив’янку антитіл до B. burgdorferi s. l. та B. henselae може свідчити про причетність зазначених збудників кліщових інфекцій до виникнення цієї недуги. Такі обстеження пацієнтів з кропив’янкою у Хмельницькій області проведені вперше.