bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPERIMENTAL AND STATISTICAL INVESTIGATION OF THE EFFECTS OF CUTTING PARAMETERS ON KERF QUALITY AND SURFACE ROUGHNESS IN LASER CUTTING OF Al 5083 ALLOY
Authors: ÖZLÜ BARIŞ
Published: July 2021

In this study, the effect of cutting parameters on kerf quality and surface roughness in laser cutting of Al 5083 alloyed material was investigated both experimentally and statistically (Taguchi & Gray Taguchi). Experimental design was determined using the Taguchi L[Formula: see text] (21x 3[Formula: see text] orthogonal array. Experiments were carried out by using two different gas pressures (GP) (8 and 10 bar), three different cutting speeds (CS) (3500, 4000 and 4500[Formula: see text]mm[Formula: see text][Formula: see text][Formula: see text]min[Formula: see text] and laser power (P) (2600, 3100 and 3600[Formula: see text]W) in the cutting of Al 5083 alloyed material. As a result of the study, top kerf width (TKW), bottom kerf width (BKW) and average surface roughness (Ra) were measured as output parameter values. Using the measured top and BKW results, kerf taper (KT) was calculated. The lowest values of TKW, BKW, KT and Ra were 2.219[Formula: see text]mm, 2.010[Formula: see text]mm, 0.984∘ and 2.394[Formula: see text][Formula: see text]m, respectively. To determine the optimum values of laser cutting parameters for minimum output parameters, signal-noise (S/N) ratio, variance and regression analysis, validity experiments and GRA methods were used. When S/N ratios were examined, the most ideal cutting parameters were determined as A1B3C1 for TKW and BKW, A2B1C3 for KT and A2B3C3 for Ra. When the variance results were examined, it was determined that the most effective processing parameter for TKW, BKW and KT was at 46.04%, 50.58% and 56.45% CS, respectively, and the most effective processing parameter for Ra was laser power with 46.57%. According to gray relationship analysis, optimum laser cutting parameters for the smallest values of all output parameters were determined as A1B3C1. According to gray relationship analysis, optimum laser cutting parameters for the smallest values of all output parameters were determined as A1B3C1.
The Mechanics of Creative Cognition: Orchestrating the Productive Interplay of Procedural and Conceptual Knowledge in STEM Education
Authors: Euler Manfred
Published: July 2021

As a reaction to the growing economical, ecological and societal demands on education innumerous efforts and programs have been initiated throughout the educational chain to improve the quality of teaching and learning in the STEM field. On that background we sketch a framework to foster creative engagement in learning to promote scientific inquiry and modeling processes. In the theoretical part the article presents a dualistic perspective on the grounding of creative cognition in concrete experience, highlighting the productive and reflexive interplay of procedural and conceptual knowing. Their entanglement is pivotal to successful knowledge construction and application in science and technology. The ‘mechanics’ of creativity is elaborated exemplarily in a project based learning sequence that starts from investigating and modeling elastic forces as a basic paradigm of creative model construction. The creative part refers to conceptual expansions of the elastic spring model that assist in modeling emergent mechanical properties in hard and soft condensed matter. With additional moderate instructional input this knowledge is productive in creating basic models of the self-organized dynamics of biomolecular systems that orchestrate life at the cellular level. The sequence demonstrates how the interplay of hands-on experience and conceptual modeling can promote near and far transfer.
Creativity in Action: Exploring Cross-Cutting Models of Self-Organization and Emergence in Science and Technology
Authors: Euler Manfred
Published: July 2021

This review presents a sequence of exemplary experience-based encounters with self-organizing systems on different levels of difficulty. Based on hands-on experiments and creative modeling it provides a viable educational road to build up a deeper understanding of self-organization principles and their comprehensive nature. Theories of self-organization describe how patterns, structures and new types of behavior emerge in energetically open systems, resulting from the local interaction of many components. As an external control instance is missing, the underlying philosophy is counterintuitive to our habits of causal thinking. This thematic and conceptual framework impacts on many STEM domains and presents a blueprint for modeling emergent structures and complex functions in natural and technological systems. It reveals unifying principles that can help in reducing, in structuring and, finally, in understanding and controlling the emerging complexity. An overview across diverse STEM domains highlights the role of this overarching concept. This cross-disciplinary approach can help in improving the dialogue and the knowledge exchange between the individual fields. Moreover, in a self-referential fashion, the modeling of self-organization provides us with fresh perspectives to reflect our own creative processes.
Explainable Embodied Agents Through Social Cues
Authors: Wallkötter Sebastian , Tulli Silvia , Castellano Ginevra , Paiva Ana , Chetouani Mohamed
Published: July 2021

The issue of how to make embodied agents explainable has experienced a surge of interest over the past 3 years, and there are many terms that refer to this concept, such as transparency and legibility. One reason for this high variance in terminology is the unique array of social cues that embodied agents can access in contrast to that accessed by non-embodied agents. Another reason is that different authors use these terms in different ways. Hence, we review the existing literature on explainability and organize it by (1) providing an overview of existing definitions, (2) showing how explainability is implemented and how it exploits different social cues, and (3) showing how the impact of explainability is measured. Additionally, we present a list of open questions and challenges that highlight areas that require further investigation by the community. This provides the interested reader with an overview of the current state of the art.
Impact of Surface Hydrophilicity of Gas-Diffusion-Type Biocathodes on Their Oxygen Reduction Ability for Biofuel Cells
Authors: Tatara Ryoichi , Sakai Shun , Horiba Tatsuo , Komaba Shinichi
Published: July 2021

The surface hydrophilicity of a gas-diffusion-type biocathode, in which bilirubin oxidase was immobilized, was regulated by varying the polymer binder hygroscopicity and UV-ozone treatment time of carbon composite electrodes. The surface hydrophilicity was found to influence its oxygen reduction activity by affecting the penetration of the electrolyte and O2 gas into the electrode layer. The oxygen reduction activity was maximized at an intermediate surface hydrophilicity because of the trade-off between enzyme utilization and oxygen diffusion. A glucose/O2 biofuel cell was fabricated by combining the optimal biocathode with a suitable bioanode fabricated with carboxylic acid-functionalized carbon nanotubes. We demonstrated that the glucose/O2 gas-diffusion-type biofuel cell exhibited a maximum current density of 3.0 mA cm−2 and a maximum power density of 0.66 mW cm−2.
Intelligent Recognition and Teaching of English Fuzzy Texts Based on Fuzzy Computing and Big Data
Authors: Liu Ling , Tsai Sang-Bing
Published: July 2021

In this paper, we conduct in‐depth research and analysis on the intelligent recognition and teaching of English fuzzy text through parallel projection and region expansion. Multisense Soft Cluster Vector (MSCVec), a multisense word vector model based on nonnegative matrix decomposition and sparse soft clustering, is constructed. The MSCVec model is a monolingual word vector model, which uses nonnegative matrix decomposition of positive point mutual information between words and contexts to extract low‐rank expressions of mixed semantics of multisense words and then uses sparse. It uses the nonnegative matrix decomposition of the positive pointwise mutual information between words and contexts to extract the low‐rank expressions of the mixed semantics of the polysemous words and then uses the sparse soft clustering algorithm to partition the multiple word senses of the polysemous words and also obtains the global sense of the polysemous word affiliation distribution; the specific polysemous word cluster classes are determined based on the negative mean log‐likelihood of the global affiliation between the contextual semantics and the polysemous words, and finally, the polysemous word vectors are learned using the Fast text model under the extended dictionary word set. The advantage of the MSCVec model is that it is an unsupervised learning process without any knowledge base, and the substring representation in the model ensures the generation of unregistered word vectors; in addition, the global affiliation of the MSCVec model can also expect polysemantic word vectors to single word vectors. Compared with the traditional static word vectors, MSCVec shows excellent results in both word similarity and downstream text classification task experiments. The two sets of features are then fused and extended into new semantic features, and similarity classification experiments and stack generalization experiments are designed for comparison. In the cross‐lingual sentence‐level similarity detection task, SCLVec cross‐lingual word vector lexical‐level features outperform MSCVec multisense word vector features as the input embedding layer; deep semantic sentence‐level features trained by twin recurrent neural networks outperform the semantic features of twin convolutional neural networks; extensions of traditional statistical features can effectively improve cross‐lingual similarity detection performance, especially cross‐lingual topic model (BL‐LDA); the stack generalization integration approach maximizes the error rate of the underlying classifier and improves the detection accuracy.
Big NB-IoT Data: Enhancing Portability of Handheld Narrow-Band Internet of Things Performance on Big Data Technology
Authors: Xu Jie
Published: July 2021

The Narrow Band-Internet of Things (NB-IoT) is a wideband radio technology developed for the Internet of Things that enables smoother- and farther-reaching connectivity between IoT devices. In addition to traditional network optimization devices, Bluetooth and Wi-Fi, its virtue is low cost, and it consumes less energy and has high coverage and extended battery life. In order to secure the balance of task execution latency across NB-IoT devices, in this research work, we design a handheld NB-IoT wireless communication device. Furthermore, we provide realistic resource-sharing methods between multimedia and sensor data in NB-IoT wireless deployment by our accurate analytical methodology. In addition, we have considerably enhanced technology for gathering Big Data from several scattered sources, in combination with advancements in big data processing methodologies. The proposed handheld terminal has a wide variety of commercial applications in intelligent manufacturing and smart parking. Simulation outcomes illustrate the benefits of our handheld terminal, which provides practical solutions for network optimization, improving market share and penetration rate.
Intraoperative Endoscopy in Transient Adult Jejunojejunal Intussusception
Authors: Okamoto Takeshi , Suzuki Hidekazu , Fukuda Katsuyuki
Published: July 2021

Despite improvements in imaging modalities, causative lead points in adult intussusception may be difficult to diagnose. Such lead points can be malignant, causing recurrence or metastases if left unresected. We describe a case of transient adult jejunojejunal intussusception, in which intraoperative endoscopy was used to confirm the absence of a lead point. A 39-year-old woman with a history of laparoscopic oophorectomy presented with epigastric pain, nausea, and vomiting. Contrast computed tomography revealed jejunojejunal intussusception, with no visible lead point. Spontaneous reduction was confirmed during exploratory laparoscopy. After lysis of adhesions, intraoperative peroral jejunoscopy was performed with the surgeons’ assistance. Endoscopy confirmed the absence of tumor, and bowel resection was avoided. No recurrence has been observed during 24 months of follow-up. Intraoperative endoscopy may provide additional reassurance for the absence of a lead point in cases where preoperative enteroscopy cannot be performed and no lead points can be identified on imaging.
Opportunities of Artificial Intelligence and Machine Learning in the Food Industry
Authors: Kumar Indrajeet , Rawat Jyoti , Mohd Noor , Husain Shahnawaz
Published: July 2021

The food processing and handling industry is the most significant business among the various manufacturing industries in the entire world that subsidize the highest employability. The human workforce plays an essential role in the smooth execution of the production and packaging of food products. Due to the involvement of humans, the food industries are failing to maintain the demand-supply chain and also lacking in food safety. To overcome these issues of food industries, industrial automation is the best possible solution. Automation is completely based on artificial intelligence (AI) or machine learning (ML) or deep learning (DL) algorithms. By using the AI-based system, food production and delivery processes can be efficiently handled and also enhance the operational competence. This article is going to explain the AI applications in the food industry which recommends a huge amount of capital saving with maximizing resource utilization by reducing human error. Artificial intelligence with data science can improve the quality of restaurants, cafes, online delivery food chains, hotels, and food outlets by increasing production utilizing different fitting algorithms for sales prediction. AI could significantly improve packaging, increasing shelf life, a combination of the menu by using AI algorithms, and food safety by making a more transparent supply chain management system. With the help of AI and ML, the future of food industries is completely based on smart farming, robotic farming, and drones.
Systematic Review and Meta-Analysis on Randomized Controlled Trials on Efficacy and Safety of Panax Notoginseng Saponins in Treatment of Acute Ischemic Stroke
Authors: Wang Liu-ding , Xu Zhen-min , Liang Xiao , Qiu Wen-ran , Liu Shao-jiao , Dai Ling-ling , Wang Ye-fei , Guo Chun-yan , Qi Xiang-hua , Wang Jian , Ding Yan-bing , Zhang Yun-ling , Liao Xing
Published: July 2021

Importance. Panax Notoginseng Saponins (PNS) are proven to have antiplatelet effects in patients with acute ischemic stroke (AIS). Objective. To assess the efficacy and safety of PNS on antiplatelet therapy in the treatment of AIS. Methods. We searched 7 literature databases and 2 clinical studies databases for randomized controlled studies (RCTs) evaluating PNS as an adjuvant therapy for AIS. Relevant studies were retrieved and screened, and data were extracted independently by two reviewers. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was carried out with the Rev Man 5.4 software. Results. Of 8267 records identified, 43 RCTs met our inclusion criteria (n = 4170 patients). Patients assigned to PNS with conventional treatments (CTs) had improved functional independence at 90 days compared with those assigned to CTs alone (RR = 1.87, 95% CI = 1.37, to 2.55,

P
<
0.0001

). Patients who received PNS combined with CTs showed significantly high improvements in neurological function among individuals with AIS on the neurologic deficit score (NDS) (MDCSS = −5.71, 95% CI = −9.55 to −1.87,

P
=
0.004

; MDNIHSS = −3.94, 95% CI = −5.65 to −2.23,

P
<
0.00001

). The results also showed PNS contributed to a betterment in activities of daily living (ADL) on the Barthel index (MDday10 BI = 4.86, 95% CI = 2.18, to 7.54,

P
<
0.00001

; MDday 14 BI = 13.92, 95% CI = 11.46 to 16.38,

P
<
0.00001

; MDday 28 BI = 7.16, 95% CI = 0.60, to 13.72,

P
<
0.00001

). In addition, PNS, compared with CTs alone, could significantly improve overall response rate (ORR) (RRNIHSS = 1.20, 95% CI = 1.16, to 1.24,

P
<
0.00001

; RRCSS = 1.15, 95% CI = 1.08, to 1.24,

P
<
0.0001

), hemorheological parameters, maximum platelet aggregation rate (MPAR) (MD = −6.82, 95% CI = −9.62 to −4.02,

P
<
0.00001

), platelet parameters (MDPLT = 4.85, 95% CI = 1.82 to 7.84,

P
=
0.002

; MDMPV = −0.79, 95% CI = −1.09 to −0.48,

P
<
0.00001

), and serum CD62P (MD = −0.21, 95% CI = −0.29 to −0.13,

P
<
0.00001

). The incidence of adverse reactions in PNS was lower than that in the control group (RR = 0.62, 95% CI = 0.39 to 0.97,

P
=
0.04

). Adverse reactions in the PNS were mild adverse reactions. Conclusion. PNS may be effective and safe in treating AIS on ameliorating neurological deficit, improving activities of daily living function, and enhancing antiplatelet effects. However, more high-quality evidence is needed before it can be recommended for routine antiplatelet therapy in patients with AIS.
Factors Influencing the Serum Uric Acid in Gout with Cerebral Infarction
Authors: Li Yi , Yang Hongyi , Tian Yao , Duan Lihua
Published: July 2021

Background. Although the relationship between gout and cardiovascular has been well demonstrated, there is little information about the difference between gout with cerebrovascular disease and cardiovascular disease. In this study, the differences between gout with cerebral infarction (gout+CI) and gout with coronary heart disease (gout+CHD) and related factors that affect serum uric acid (sUA) levels in gout+CI were investigated by a cross-sectional study. Method. The patients from Jiangxi Provincial People’s Hospital with gout+CHD, gout+CI, and gout with coronary heart disease and cerebral infarction (gout+CHD+CI) between 2016 and 2020 were included in this study, and the medical record data were collected and analyzed. Results. We observed significant differences in age, drinking, hypertension, long-term use of diuretics and NSAIDs, sUA, CRE, and blood glucose in patients with gout+CHD and gout+CI. The sUA level was significantly positively correlated with smoking, CRE, and TG in the gout+CI group and was only positively correlated with CRE in the gout+CHD group and the gout+CHD+CI group (

p
<
0.05

). Interestingly, the sUA level was only negatively correlated with the age and gender in the gout+CI group (

p
<
0.05

). After excluding factors with no significant statistical effect, only age, gender, smoking, CRE, and TG were included in the multiple linear regression model. It suggested that smoking, CRE, and TG are positively correlated with the sUA level, while age was negatively correlated with the sUA level. Conclusions. There are many discrepancies in clinical characteristics between gout+CHD patients and gout+CI patients, especially that the factors that affect UA levels are significantly different. The data also suggested that uric acid-lowering therapy may need to be strengthened in the young gout+CI patients with a history of smoking.
Numerical Research of the Submerged High‐Pressure Cavitation Water Jet Based on the RANS‐LES Hybrid Model
Authors: Yang Yongfei , Shi Weidong , Tan Linwei , Li Wei , Chen Songping , Pan Bo
Published: July 2021

The submerged high‐pressure water jet has the characteristics of high velocity, strong turbulence, and severe cavitation. In order to reveal the formation mechanism of shear cavitation in the submerged high‐pressure water jet and to grasp the turbulent structure and velocity distribution characteristics in the jet, the prediction ability of different turbulence models is studied first. The models represent the RANS model and RANS‐LES hybrid model which are used to simulate the same cavitation jet, and the results are compared with the experimental results. The most reasonable model is then used to investigate the submerged high‐pressure cavitation jet with different cavitation numbers. It is found that the calculation accuracy for small‐scale vortexes has a great influence on the prediction accuracy of cavitation in the submerged jet. Both the DDES model and the SBES model can effectively capture the vortexes in the shear layer, and the SBES model can obtain more turbulence details. The result of the simulation under different cavitation numbers using the SBES model agrees well with the experimental result. Under the condition with low cavitation number, an intensive shear layer is formed at the exit of the nozzle, and small‐scale vortexes are distributed along the shear layer. Mass transfer rate is relatively high in the region with a stronger vortex, which confirms that the low pressure in the vortex center is the main reason for the generation of cavitation in the shear layer. With the decrease of the cavitation number, the cavitation intensity increases obviously, while the nondimensional velocity along the radial direction changes little, which follows an exponential function.
Composition Formulae for thek-Fractional Calculus Operator with theS-Function
Authors: Tadesse Hagos , Habenom Haile , Alaria Anita , Shimelis Biniyam
Published: July 2021

In this study, the S-function is applied to Saigo’sk-fractional order integral and derivative operators involving thek-hypergeometric function in the kernel; outcomes are described in terms of thek-Wright function, which is used to represent image formulas of integral transformations such as the beta transform. Several special cases, such as the fractional calculus operator and theS-function, are also listed.
Investigating the Effect of Viscous Yield Dampers on Concrete Structure Performance
Authors: Marzban Nima , Esmaeiltabar Nesheli Parisa
Published: July 2021

Viscous dampers are one of the most effective devices in the energy consumption of the buildings. The passive hybrid system progressive applications cause each of the dampers to compensate for the weakness of the other system, thus increasing the efficiency of passive control of the structure. Speed‐based viscous dampers will adjust the amount of depreciation force based on the acceleration and velocity entering the system. On the other hand, displacement‐based surge dampers adjust the amount of depreciation force based on the displacement required. Therefore, considering the different performances of these two dampers, the effect of using both of them in one structure can be investigated. In this study, by combining these two dampers, the seismic behavior of concrete structures has been evaluated. To study them, 5‐ and 10‐story structures have been designed using FE method and have been subjected to earthquake records. Historical analysis shows that the use of hybrid dampers reduces the amount of seismic input force to the structure and also the amount of floor drift is reduced due to the use of dampers and also the capacity of structures for these structures is increased. The results of the study show that the presence of dampers in the structure increases energy absorption and improves performance in the structure.
Self-Adaptive Particle Swarm Optimization of CT Images for Diagnosis of Severe Traumatic Brain Injury
Authors: Wu Zongtao , Ma Jingku , Zhou Xiaolong , Ma Xiumei
Published: July 2021

This paper aimed to explore the application values of computed tomography (CT) imaging in the treatment of patients with severe traumatic brain injury (STBI), to provide help in the treatment of STBI. In this study, 86 patients with STBI were selected as the research objects and examined by CT based on a self-adaptive particle swarm algorithm (APSO). Besides, patients were treated with hyperbaric oxygen, high-dose hormone shock, and naloxone hydrochloride. The results showed that there was a locally low-density brain contusion and laceration injury area, spot-like high-density hemorrhage, and subarachnoid hemorrhage in the images of CT examination. The ventricles of diffuse brain injury were compressed and reduced, and the white matter indicated that the ventricles and cisterns became smaller. Asymmetric hemorrhage and subarachnoid hemorrhage were scattered at the white matter junction. In short, subarachnoid hemorrhage, spot-like high-density hemorrhage at the injury site, and diminished ventricles were typical CT imaging manifestations of STBI. Naloxone hydrochloride method could effectively alleviate the matrix metalloproteinase-9 (MMP-9) (23.47 ± 3.45) and S100 calcium-binding protein B (S100B) (0.16 ± 0.06) of patients, which had reliable guiding significance for the later CT examination clinically.
Bursting Oscillations and Sliding Motion in Permanent Magnet Synchronous Motor Systems with Friction Factor
Authors: Qu Rui , Li Shaolong
Published: July 2021

The main purpose of this paper is to investigate the qualitative effects of external excitation and friction factor on the response of permanent magnet synchronous motor (PMSM) system. Three different modes of bursting oscillations are found. In particular, the introduction of friction function changes the governing equations from a smooth type to a nonsmooth (Filippov) type in which the special sliding motion is observed. The mechanism, attractor structure, vector field structure, and analytic bifurcation conditions of bursting oscillation and sliding motion are discussed in detail. The validity of theoretical results obtained is verified by numerical simulations and analysis.
Switched Finite-Time Source Seeking of an Underactuated Ship
Authors: Yang Yiwen , Zhang Jingming , Zhang Yingjie
Published: July 2021

In this paper, a switched finite-time source-seeking strategy is proposed for underactuated ships with a signal sensor. In practical application, for sensors in some complex environment, due to the lack of the ability to perceive the location of the source or its own position, we use the nonmodel gradient estimation of extremum seeking algorithm. This paper presents a three-step switching control method for the first time. In the first step, we prove that the closed-loop system of the underactuated ship is stable in a finite time with a constant yaw angular acceleration. In the second step, under the yaw angle acceleration controller, one of the position coordinates of the underactuated ship sensor is realized to be close to the center of the signal source through the average method. The third step is to drive the other position coordinates of the underactuated ship sensor to the center of the signal source under the action of the surge line speed controller. Simulation results show the effectiveness of the proposed strategy.
Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial
Authors: Bockorny Bruno , Macarulla Teresa , Semenisty Valerya , Borazanci Erkut , Feliu Jaime , Ponz-Sarvise Mariano , Abad David Gutierrez , Oberstein Paul , Alistar Angela , Muñoz Andres , Geva Ravit , Guillén-Ponce Carmen , Fernandez Mercedes Salgado , Peled Amnon , Chaney Marya , Gliko-Kabir Irit , Shemesh-Darvish Liron , Ickowicz Debby , Sorani Ella , Kadosh Shaul , Vainstein-Haras Abi , Hidalgo Manuel
Published: July 2021

Purpose:

Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC.

Patients and Methods:

Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with de novo metastatic PDAC and disease progression on front-line gemcitabine-based therapy (NCT02826486). Subjects received a priming phase of motixafortide daily on days 1–5, followed by repeated cycles of motixafortide twice a week; pembrolizumab every 3 weeks; and nanoliposomal irinotecan, fluorouracil, and leucovorin every 2 weeks (NAPOLI-1 regimen). The primary objective was objective response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), safety, and tolerability.

Results:

A total of 43 patients were enrolled. The ORR according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The DCR was 63.2% with median duration of clinical benefit of 5.7 months. In the intention-to-treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated, with toxicity comparable with the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection was 7%, lower than expected for this chemotherapy regimen.

Conclusions:

Triple combination of motixafortide, pembrolizumab, and chemotherapy was safe and well tolerated, and showed signs of efficacy in a population with poor prognosis and aggressive disease.
Overcoming Intrinsic Resistance of Cancer Cells to CAR T-Cell Killing
Authors: Lemoine Jean , Ruella Marco , Houot Roch
Published: July 2021

In the past few years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for cancers that failed standard treatments. Such therapies have already been approved in several blood cancers, such as B-cell leukemia and lymphoma. Despite this progress, a significant proportion of patients experience primary or secondary resistance to CAR T-cell therapy. Here, we review the mechanisms by which CAR T cells eliminate their target and how cancer cells may be insensitive to such killing (here referred to as intrinsic resistance). Recent studies suggest that the activation of apoptosis through death receptor signaling is responsible for a major part of CAR T-cell cytotoxicity in vivo. Indeed, cancer cells harboring aberrant apoptotic machinery may be insensitive to CAR T-cell killing. This intrinsic resistance of cancer cells to CAR T-cell killing could be responsible for a significant portion of treatment failure. Finally, we discuss strategies that may be envisioned to overcome such resistance to enhance CAR T-cell efficacy.
Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network
Authors: Akturk Guray , Parra Edwin R. , Gjini Evisa , Lako Ana , Lee J. Jack , Neuberg Donna , Zhang Jiexin , Yao Shen , Laface Ilaria , Rogic Anita , Chen Pei-Hsuan , Sanchez-Espiridion Beatriz , Valle Diane M. Del , Moravec Radim , Kinders Robert , Hudgens Courtney , Wu Catherine , Wistuba Ignacio I. , Thurin Magdalena , Hewitt Stephen M. , Rodig Scott , Gnjatic Sacha , Tetzlaff Michael T.
Published: July 2021

Purpose:

The Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative was established to provide correlative analyses for clinical trials in cancer immunotherapy, using state-of-the-art technology. Fundamental to this initiative is implementation of multiplex IHC assays to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. A critical unanswered question involves the relative fidelity of such assays to reliably quantify tumor-associated immune cells across different platforms.

Experimental Design:

Three CIMAC sites compared across their laboratories: (i) image analysis algorithms, (ii) image acquisition platforms, (iii) multiplex staining protocols. Two distinct high-dimensional approaches were employed: multiplexed IHC consecutive staining on single slide (MICSSS) and multiplexed immunofluorescence (mIF). To eliminate variables potentially impacting assay performance, we completed a multistep harmonization process, first comparing assay performance using independent protocols followed by the integration of laboratory-specific protocols and finally, validating this harmonized approach in an independent set of tissues.

Results:

Data generated at the final validation step showed an intersite Spearman correlation coefficient (r) of ≥0.85 for each marker within and across tissue types, with an overall low average coefficient of variation ≤0.1.

Conclusions:

Our results support interchangeability of protocols and platforms to deliver robust, and comparable data using similar tissue specimens and confirm that CIMAC-CIDC analyses may therefore be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.
Anti-CD19 CAR T Cells That Secrete a Biparatopic Anti-CLEC12A Bridging Protein Have Potent Activity Against Highly Aggressive Acute Myeloid Leukemia In Vitro and In Vivo
Authors: Rennert Paul D. , Dufort Fay J. , Su Lihe , Sanford Tom , Birt Alyssa , Wu Lan , Lobb Roy R. , Ambrose Christine
Published: July 2021

Refractory acute myeloid leukemia (AML) remains an incurable malignancy despite the clinical use of novel targeted therapies, new antibody-based therapies, and cellular therapeutics. Here, we describe the preclinical development of a novel cell therapy that targets the antigen CLEC12A with a biparatopic bridging protein. Bridging proteins are designed as “CAR-T cell engagers,” with a CAR-targeted protein fused to antigen binding domains derived from antibodies. Here, we created a CD19-anti-CLEC12A bridging protein that binds to CAR19 T cells and to the antigen CLEC12A. Biparatopic targeting increases the potency of bridging protein-mediated cytotoxicity by CAR19 T cells. Using CAR19 T cells that secrete the bridging protein we demonstrate potent activity against aggressive leukemic cell lines in vivo. This CAR-engager platform is facile and modular, as illustrated by activity of a dual-antigen bridging protein targeting CLEC12A and CD33, designed to counter tumor heterogeneity and antigen escape, and created without the need for extensive CAR T-cell genetic engineering. CAR19 T cells provide an optimal cell therapy platform with well-understood inherent persistence and fitness characteristics.
Fabrication and Characterization of Silk Fibroin-Based Nanofibrous Scaffolds Supplemented with Gelatin for Corneal Tissue Engineering
Authors: Sahi Ajay Kumar , Varshney Neelima , Poddar Suruchi , Gundu Shravanya , Mahto Sanjeev Kumar
Published: July 2021

Tissue engineering is a promising approach to overcome the severe worldwide shortage of healthy donor corneas. In this work, we have developed a silk-gelatin composite scaffold using electrospinning and permeation techniques to achieve the properties comparable to cornea analog. In particular, we present the fabrication and comparative evaluation of the novel gelatin sheets consisting of silk fibroin nanofibers, which are prepared using silk fibroin (SF) (in formic acid) and SF (in aqueous) electrospun scaffolds, for its suitability as corneal stromal analogs. All the fabricated samples were treated with ethanol vapor (T) to physically crosslink the silk nanofibers. Micro/nano-scale features of the fabricated scaffolds were analyzed using scanning electron microscopy micrographs. Fourier transform infrared spectroscopy revealed characteristic peaks of polymeric functional groups and modifications upon ethanol vapor treatment. Transparency of the scaffolds was determined using UV-visible spectra. Among all the fabricated samples, the gelatin-permeated SF (in formic acid; T) scaffold showed the highest level of transparency, i.e., 77.75 ± 2.3%, which is similar to that of the native cornea (∼70%–90% [variable with age group]) with healthy acute vision. Contact angle of the samples was studied to estimate the hydrophilicity of the scaffolds. All the scaffolds except non-treated SF (in aqueous; NT) were found to be significantly stable up to 14 days when incubated in phosphate buffered saline at 37°C. Treated samples showed significantly better stability, both physically and microscopically, in comparison to nontreated samples. Proliferation and viability assays of rabbit corneal fibroblast cells (SIRC) and mouse fibroblast cells (L929 RFP) when cultured on fabricated scaffolds revealed remarkable cellular compatibility with gelatin-permeated SF (in formic acid; T) scaffolds compared to SF (in aqueous; T). Unlike other reports in the existing literature, this work presents the design and development of a nanofibrous silk-gelatin composite that exhibits acceptable transparency, cellular biocompatibility, as well as improved mechanical stability comparable to that of native cornea. Therefore, we anticipate that the fabricated novel scaffold is likely to be a good candidate for corneal tissue construct. Moreover, among the fabricated scaffolds, the outcomes depict gelatin-permeated SF (in formic acid; T) composite scaffold to be a better candidate as a corneal stromal analog that carries properties of both the silk and gelatin, i.e., optimal transparency, better stability, and enhanced cytocompatibility.
Effects of Orthokeratology on Axial Length Elongation in Anisometropes
Authors: Xu Jing , Gao Bei , Tian Qingmei , Wu Qiuxin , Zhang Xiuyan , Lin Xiao , Zhang Ruixue , Song Jike , Bi Hongsheng
Published: July 2021

Introduction: This study aimed to investigate the therapeutic effects of overnight orthokeratology (OK) lenses on anisometropes. Methods: We enrolled 178 anisometropes from August 2015 to August 2017. We then divided these patients into 2 parts depending on them wearing either monocular or binocular OK lenses. In part one, 47 monocular myopic subjects (25 males and 22 females) were treated with OK lenses in the myopic eyes only. We also labeled the myopic eyes as the OK group and the contralateral nonmyopic eyes as the control group. The initial average wearing age of the subjects was 12.35 ± 2.37 years (8–16 years). The mean follow-up duration was 15.43 ± 4.88 months (7–25 months). The average spherical equivalent refraction (SER) was −2.31 ± 1.16 diopter (D) in the OK group and 0.15 ± 0.49 D in the control group (p < 0.001). In part 2, 131 binocular myopic anisometropes (56 males and 75 females) were involved in the study. The eyes with more severe myopia were assigned to the G group and the contralateral eyes to the L group. The initial average wearing age of the subjects was 12.92 ± 2.60 years ( 8–16 years). The mean follow-up duration was 17.83 ± 5.02 months (7–26 months). The average SER was −4.79 ± 1.90 D in the G group and −3.14 ± 1.88 D in the L group (p < 0.001). We calculated the axial length (AL) difference and AL elongation as our primary outcome measures. Results: In part one, the AL elongation in the OK group (0.21 ± 0.09 mm) was significantly lower than that in the control group (0.70 ± 0.17 mm) at 24 months (p < 0.001). Meanwhile, the AL difference exhibited a decrease of 0.50 ± 0.29 mm from a baseline of 1.08 ± 0.35 to 0.58 ± 0.25 mm at 24 months (F = 24.539, p < 0.001). In part 2, the AL had increased by 0.17 ± 0.13 mm in the G group and 0.24 ± 0.18 mm in the L group after 24-month follow-up, respectively (p < 0.001). While the AL difference decreased from 0.55 ± 0.11 mm at the baseline, to 0.48 ± 0.08 mm at 24 months, eliciting a decrement in AL difference of 0.07 ± 0.09 mm (F = 3.884, p = 0.030). Conclusions: OK lenses can slow down AL growth in anisometropes and has a greater effect on reducing AL elongation in the more severely affected myopic eyes of anisometropic patients.
Safety and Complications of Sedation Anesthesia during Pediatric Auditory Brainstem Response Testing
Authors: Urfali Senem , Urfali Boran , Sarac Elif Tugba , Koyuncu Onur
Published: July 2021

Objective: The auditory brainstem response (ABR) test has been widely used in childhood. Although it is a painless procedure, sedation can be needed in pediatric patients. Thus, this study aimed to evaluate safety and complications of sedation anesthesia applied in pediatric patients during ABR testing. Methods: Medical records of 75 children who underwent ABR testing between 2018 and 2020 were evaluated retrospectively in terms of applicability, safety, and complications of sedation anesthesia. Results: The ages ranged from 3 to 9 (mean 6.2) years. Comorbidity was detected in 20% (n = 15); 3 had multiple comorbidities, and the most common comorbidity was Down syndrome (4%). The drugs used in sedation anesthesia were midazolam in 81.3% (n = 61), a combination of propofol and ketamine in 14.7% (n = 11), and only propofol in 4% (n = 3) of the patients. An additional drug use was needed in 44% (n = 33). The mean procedure time was 40 (range 30–55) min. The mean anesthesia duration was 45 (range 35–60) min. The mean recovery time was 10 (range 5–15) min. Complications related to anesthesia developed in 4 (5.33%) of the patients; respiratory distress, agitation, cough, and nausea-vomiting were seen in one of the patients, respectively. Complications like bradycardia and respiratory or cardiac arrest were not seen at all. Conclusions: The complication rate of sedation anesthesia performed during ABR testing of pediatric patients is quite low. It may be more beneficial to use combinations of sedation drugs instead of using a single sedation drug. Although sedation anesthesia appears to be safe in general, the potentially life-threatening complications of sedative agents should be remembered, especially in children who have comorbidities.
Effects of Experimental Sleep Restriction on Ambulatory and Sleep Blood Pressure in Healthy Young Adults: A Randomized Crossover Study
Authors: Covassin Naima , Bukartyk Jan , Singh Prachi , Calvin Andrew D. , St Louis Erik K. , Somers Virend K.
Published: July 2021

Although insufficient sleep is associated with increased cardiovascular risk, evidence of a causal relationship is lacking. We investigated the effects of prolonged sleep restriction on 24-hour ambulatory blood pressure (BP) and other cardiovascular measures in 20 healthy young participants (aged 23.4±4.8 years, 9 females), who underwent a randomized, controlled, crossover, 16-day inpatient study consisting of 4 days of acclimation, 9 days of sleep restriction (4 hours of sleep/night) or control sleep (9 hours), and 3 days of recovery. Subjects consumed a weight maintenance diet with controlled nutrient composition throughout. A 24-hour BP (primary outcome) and cardiovascular biomarkers were measured repeatedly. Polysomnographic monitoring was continuous. Comparing sleep restriction versus control sleep, 24-hour mean BP was higher (adjusted mean difference, day 12: 2.1 mm Hg [95% CI, 0.6–3.6], corrected
P
=0.016), endothelial function was attenuated (
P
<0.001), and plasma norepinephrine increased (
P
=0.011). Despite increased deep sleep, BP was elevated while asleep during sleep restriction and recovery. Post hoc analysis revealed that 24-hour BP, wakefulness, and sleep BP increased during experimental and recovery phases of sleep restriction only in women, in whom 24-hour and sleep systolic BP increased by 8.0 (5.1–10.8) and 11.3 (5.9–16.7) mm Hg, respectively (both
P
<0.001). Shortened sleep causes persistent elevation in 24-hour and sleep-time BP. Pressor effects are evident despite closely controlled food intake and weight, suggesting that they are primarily driven by the shortened sleep duration. BP increases are especially striking and sustained in women, possibly suggesting lack of adaptation to sleep loss and thus greater vulnerability to its adverse cardiovascular effects.
A NOVEL APPROACH FOR GREEN SUPPLIER SELECTION PROBLEM: FUZZY AXIOMATIC DESIGN WITH RISK FACTORS
Authors: ÖZGÖRMÜŞ Elif , TAŞCI DURAK Zehra
Published: July 2021

Today’s environmental conscious world forces companies to be more about energy and water consumption. New trends in the world generally provide competitive advantage to the firms if they work on environmental issues. As a critical decision of companies, supplier selection problem needs to consider the environmental factors and economical factors simultaneously. This study proposes a novel solution methodology for green supplier selection problem: Fuzzy axiomatic design with risk factors. This method is applied in many decision-making problems in the literature successfully. A case study is presented to implement the method and the results are compared with traditional fuzzy axiomatic design and fuzzy TOPSIS. It has seen that the decision of the best supplier selection can be influenced by the risk factors such as the deviation in the economical conditions or the working conditions of the company.
An Analysis of the Rug-Washing Ceremony in Mashhad-e Ardehāl, Kāshān
Authors: Sadat Bidgoli Sayyed Mahmood , Melvin-Koushki Matthew
Published: July 2021

The Iranian religious ceremony of rug-washing (qāli-shuyān), commemorating the martyrdom of Emāmzāda Soltān-ʿAli b. Mohammad Bāqer (d. 734/116), is held every year in the second week of autumn in Mashhad-e Ardehāl, a village of Kāshān, Esfahān Province. This ceremony is unique amongst Twelver Shiʿis for its observance in accordance with the solar calendar rather than the lunar. The objective of the present article is to analyze this ceremony and explain its features. The necessary data for this research have been collected from fieldwork on the historical geography of the region and related historical documents. In the analysis of this ceremony, attention is paid to its time, place, and mode of performance. This study suggests that the rug-washing ceremony is at least partly descended from an ancient Mithraic ritual, to which some Zoroastrian features were added in the pre-Islamic period, such as the limiting of its performance to priests; during the Islamic era, ritual Shiʿi elements were further added thereto. As currently performed, this ceremony, exclusive to Ardehāl and dating to the Qajar and possibly Safavid periods, thus bears certain similarities to rituals performed at Karbalāʾ.
Resurrection of Lamium ponticum (Lamiaceae) with a new subspecies, Lamium ponticum subsp. anatolicum, from Turkey
Authors: CELEP FERHAT , KARAER FERGAN , DUMAN HAYRI
Published: July 2021

Lamium ponticum, known from central and eastern Black Sea region of Turkey, is an endemic species with white flowers. However, it was evaluated as a synonym of L. moschatum subsp. micranthum in the last taxonomic revision the genus. During our revisional studies on the genus, we concluded that L. ponticum is completely different from L. moschatum subsp. micranthum. In addition, we collected some specimens from western Black Sea region of Turkey with pink-rose colored flowers, pinkish-purplish inflorescence and calyx, and greenish-pinkish bracts with pinkish-white spots at base, that looks quite different from the typical L. ponticum. Therefore, in this paper, we resurrected L. ponticum and described a new subspecies from western Black Sea region of Turkey. IUCN red list category, notes on biogeography and ecology of the new subspecies are also given.
Senecio sennikovii, a new replacement name for the Mexican endemic Senecio bracteatus Klatt (Asteraceae: Senecioneae)
Authors: KOTTAIMUTHU RAMALINGAM , VIMALA MURUGAN , RAJENDRAN KUPPU , BASU MUTHURAMALINGAM JOTHI
Published: July 2021

The cosmopolitan genus Senecio Linnaeus (1753: 866) is one of the most species-rich genera in Asteraceae, comprising about 1426 species (POWO 2021); the main centres of its diversity are South Africa, Chile and the Mediterranean Basin (Calvo et al. 2015). About 63 species of Senecio are known to occur in Mexico, of which 44 species are endemic to the country (Villaseñor 2016).