bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Interior Design and Space Layout Optimization Based on Multi-Intelligent Decision-Making
Authors: Dong Jian , Ran Meng
Published: May 2022

In order to meet people’s diverse, complex, and changeable living requirements and aesthetic requirements, it is necessary to rationalize the design of indoor three-dimensional space. The optimization of the indoor environmental space layout is affected by the energy consumption and rationality of functional areas, resulting in indoor environmental space The performance of the layout optimization system deteriorates. In order to improve the performance of the indoor environment spatial layout and meet the living needs of more people, this paper proposes an optimal design of a spatial layout based on multi-intelligence decision-making. The research results of the article show that (1) the average confidence and the average recognition time of logo set

B

are both smaller than those of logo set

A

, indicating that logo set

B

is easier to be recognized by users in the same commercial building environment and can be more quickly recognized. In terms of discrimination, the time used to correct the misrecognition of identification set

B

is shorter than that of identification set

A

, which means that the different types of identifications in identification set

B

are easier to distinguish. (2) The spatial positioning algorithm proposed in this paper has good reliability and practicability, high positioning accuracy, and small error for indoor spatial coordinate positioning. Compared with the traditional method, the projection method of this paper has a significantly smaller error, and the maximum error is only 0.272, which makes the indoor space design more rational. (3) Comparing the energy consumption coefficients of the three spatial layout optimization systems, it can be seen that the indoor environmental spatial layout optimization system based on multi-intelligence decision-making has the lowest energy consumption when optimizing the indoor environmental spatial layout, because the system is in the design process. The indoor environment space layout model is designed, which effectively reduces the energy consumption of the indoor environment space layout optimization. When the indoor environment space layout optimization system based on multi-intelligence decision-making is used to optimize the indoor environment space layout, the average optimization accuracy is 98.32%, while the average indoor environment space layout optimization accuracy of the space layout optimization system with curved shading space layout optimization is 42.2% %, the layout optimization of binocular stereo vision space. When optimizing the indoor space layout, the average optimization accuracy is 70.87%.
Modeling the Liquid-Phase Adsorption of Cephalexin onto Coated Iron Nanoparticles Using Response Surface and Molecular Modeling
Authors: Ahmadi Shabnam , Ghosh Soumya , Malloum Alhadji , Bornman Charné , Osagie Christian , Mohammadi Leili , Igwegbe Chinenye Adaobi
Published: May 2022

In order to assess the interactions between process factors, the experiments involving the liquid-phase adsorption of cephalexin (CEX) onto silicon-coated iron nanoparticles (Fe3O4@SIO2) were designed using the Box-Behnken Design-Response surface methodology (BBD-RSM). Optimal circumstances were used to investigate the synergistic influence on the process’s efficiency. In addition, the data was used to test and fit an artificial neural network (ANN) model. Molecular-level DFT calculations on the CEX molecule were carried out. The PW6B95D3/Def2-TZVP level of theory was used to build DFT-based descriptors for the CEX molecule. At 25°C, pH 5.83, 37.67 min, a dosage of 0.8 g Fe3O4@SIO2 and 118.01 mg/L CEX, the removal efficiency achieved a maximum of 99.01 percent. For example, we found that OH --- O, NH --- O, CH --- O hydrogen bonds, NH --- π, OH --- π, CH --- π interactions as well as dipole-dipole interactions between CEX and the nanoparticles could all be used to connect the CEX and the nanoparticles. There is a strong correlation between the output and target values acquired by BBD-RSM and ANN fits. Fe3O4@SIO2 proved to be an excellent tool for eliminating CEX.
Cyberattacks on Self-Driving Cars and Surgical and Eldercare Robots
Authors: Alshamrani Sultan S. , Alkhudadi Bdour A. , Almtrafi Sara M.
Published: May 2022

Robots have improved human life and increased the efficiency of performance in tasks that require precision and effort. For example, surgical robots are now used to perform precise surgical procedures and give accurate results. Moreover, robots are also used in elderly care to ease their lives. Perhaps there can even be self-driving cars that could deliver a person to their destination without the need of a driver. So it is very important to mention that these robots should be secure in terms of security for human life. Hence, this paper aims to explore the published studies on robots and their various security vulnerabilities. We review the most prominent weaknesses in the robotic operating system (ROS) and discuss some types of attacks against these robots. Also, this paper discusses the security enhancements to protect ROS that researchers have suggested protecting against some of the attacks and vulnerabilities that may occur on these robots. The primary findings of this work are to generate system copies for backup as well as encryption to protect against information disclosure. Also, a dynamic model is needed to detect and mitigate attacks that may occur in a physical manner, such as injecting malware into robots.
Comparative Analysis of Synthesis and Characterization of Silver Nanoparticles Extracted Using Leaf, Flower, and Bark of Hibiscus rosasinensis and Examine Its Antimicrobicidal Activity
Authors: Periasamy Sakthi , Jegadeesan Uma , Sundaramoorthi Kiruthika , Rajeswari Tanniru , Tokala Venkata Naga Baji , Bhattacharya Sumanta , Muthusamy Sivachitra , Sankoh Martin , Nellore Manoj Kumar
Published: May 2022

Nanotechnology is emerging with the biosynthesis of silver nanoparticles which is toxic free and friendly with the environment. Out of all the biosynthesis methods, plant extracts are more predominantly used which is readily available, and it is a least cost method. The plants have secondary metabolites such as phenolic compounds named as flavonoids; tannins are turned to be the reluctant to synthesize silver nanoparticles (AgNPs) from silver nitrate. The plant chosen to synthesize silver nanoparticles is the Hibiscus rosasinensis for the reason of the presence of various biomolecules. The reduction and stabilization process are performed due to the biomolecules. Silver nanoparticles produced from the Hibiscus plant are easier than the conventional method. The formation of nanoparticle of silver is indicated by the maximum absorbance peak at a wavelength of 458 nm obtained from the leaf and the bark extracts. The antimicrobicidal effects on various microbes were examined, and it is proved that bark produced better results.
Efficient Linkable Ring Signature Scheme over NTRU Lattice with Unconditional Anonymity
Authors: Ye Qing , Wang Mengyao , Meng Hui , Xia Feifei , Yan Xixi
Published: May 2022

In cloud and edge computing, senders of data often want to be anonymous, while recipients of data always expect that the data come from a reliable sender and they are not redundant. Linkable ring signature (LRS) can not only protect the anonymity of the signer, but also detect whether two different signatures are signed by the same signer. Today, most lattice-based LRS schemes only satisfy computational anonymity. To the best of our knowledge, only the lattice-based LRS scheme proposed by Torres et al. can achieve unconditional anonymity. But the efficiency of signature generation and verification of the scheme is very low, and the signature length is also relatively long. With the preimage sampling, trapdoor generation, and rejection sampling algorithms, this study proposed an efficient LRS scheme with unconditional anonymity based on the e-NTRU problem under the random oracle model. We implemented our scheme and Torres et al.’s scheme, as well as other four efficient lattice-based LRS schemes. It is shown that under the same security level, compared with Torres et al.’s scheme, the signature generation time, signature verification time, and signature size of our scheme are reduced by about 94.52%, 97.18%, and 58.03%, respectively.
Review on Surface Polishing Methods of Optical Parts
Authors: Xie Mingli , Pan Yipeng , An Zijun , Huang Shijun , Dong Min
Published: May 2022

With the extensive application of optical parts in many high-tech fields such as high-power laser, space optics, and aerospace, the requirements for the surface quality of optical parts are also increasing, which requires not only high surface qualities but also low defects including low subsurface damage and strict wavefront errors. As an essential link in the precision and ultraprecision optical manufacturing, various surface polishing methods and techniques have always attracted researchers’ continuous study and exploration. Considering the development of optical part surface polishing technology in recent years, this study analyzes the principle and development process of typical processing methods represented by each kind of polishing technology, expounds the specific research progress of optical part surface polishing technology, including the iterative renewal of traditional technologies and the research development of new technologies, and gives examples for typical applications. Finally, the development trend of optical part surface polishing technology is prospected, which provides a reference for follow-up intensive research in optical manufacturing.
Effect of Heptaflourane Inhalation and Anesthesia Induction on Hemodynamics of Elderly Patients Undergoing Elective Gastrointestinal Tumor Surgery
Authors: Ren Guozhang , Li Chen , Wei Xiaoxia , Wang Jing
Published: May 2022

Gastrointestinal stromal tumors (GISTs) are rare malignancies that begin in specific cells in the GI tract’s (also known as the digestive tract’s) wall. The microenvironment of gastrointestinal cancers has gotten a lot of interest in the last decade. There are various obstacles connected with providing care to individuals with gastrointestinal cancers, especially the elderly. The physiological reserves of elderly individuals are generally depleted, and comorbidities might limit treatment options and increase problems. Surgeons and anesthesiologists must be aware of the measures that must be used while dealing with this fragile population. Anesthesia is a term that refers to the use of drugs to alleviate pain during the surgery and other treatments. Anesthesia is crucial to a patient’s successful treatment and recovery. To induce and maintain general anesthesia in the operating room, inhalation anesthetics (isoflurane, halothane, nitrous oxide, sevoflurane, and desflurane, the most commonly used agents in practice today) are utilized. Inhalation anesthetics are drugs used to give general anesthesia for surgery in the operating room. Anesthetics have the potential to cause substantial cardiac depression as well as hemodynamic instability. In this study, we propose the SBWOA (spark bumper whale optimization algorithm), which is used to assess the patient’s risk before surgery. The entire experiment was run through Matlab simulations.
Design of Search Service System for Multimedia Music Resources Based on BS Music Performance
Authors: Lv Yuanyuan
Published: May 2022

With the rise of the Internet, traditional music performances have been unable to meet people’s needs for entertainment in life, and music performances based on computer networks have become the trend of the times. Nowadays, online multimedia resources, consisting of a combination of text, audio, video, graphics, and animation, are the easiest way of enjoying from music by providing entertainment in attractive and interactive manner. Aiming at the defects of monotonous images or text in traditional music performances, this paper designs a music resource search service platform based on computer systems to meet the needs of the user. The platform employs B/S service architecture, which allows users to audition or transmit music on websites, as well as the ability to search the website’s resources, to improve service and experience for people’s lives and pleasure. The technology has therefore made lives much better than before with quite fun.
Zero-Trust-Based Protection Scheme for Users in Internet of Vehicles
Authors: Fang Letian , Wu Chunshang , Kang Yukun , Ou Wei , Zhou Donghao , Ye Jun
Published: May 2022

At present, the Internet of Vehicles technology is developing rapidly, but in the process of networking it may be attacked by hackers. In view of the tampering attack on the user’s device and identity, we establish a multifactor authentication scheme to achieve dual identity authentication through device fingerprint authentication and PKI authentication. In response to the attack by hackers in the application of data transmission, we use the SM series of state secret algorithms for data encryption and take advantage of the immutable and decentralized characteristics of blockchain to ensure the security and integrity of data collection and transmission. Through the zero-trust security network architecture, the security level of the system in the process of data transmission is effectively improved, the identity-centered dynamic access control is carried out, the user’s behavior is monitored in real time, and the malicious nodes are screened and eliminated, which improves the stability and security of the Internet of Vehicles data transmission system. By adopting the identity authentication pass rate, fingerprint authentication pass rate, API authentication pass rate, and SPA packet transmission acceptance rate as the factor set, the evaluation level of the vehicles is calculated. The experimental results show that compared with the traditional boundary-centered security protection, our scheme can protect a wider range of application security, even if there are security problems, the loss is less. Through the training simulation of the convolutional neural network, the classification accuracy of the trust level is improved.
Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab
Authors: Rosenblat Todd L. , McDevitt Michael R. , Carrasquillo Jorge A. , Pandit-Taskar Neeta , Frattini Mark G. , Maslak Peter G. , Park Jae H. , Douer Dan , Cicic Dragan , Larson Steven M. , Scheinberg David A. , Jurcic Joseph G.
Published: May 2022

Purpose:

The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.

Patients and Methods:

Eighteen patients (median age, 64 years; range, 45–80) with relapsed or refractory AML received a single infusion of 225Ac-lintuzumab at activities of 18.5 to 148 kBq/kg.

Results:

The maximum tolerated dose was 111 kBq/kg. Dose-limiting toxicities included myelosuppression lasting > 35 days in one patient receiving 148 kBq/kg and death from sepsis in two patients treated with 111 and 148 kBq/kg. Myelosuppression was the most common toxicity. Significant extramedullary toxicities were limited to transient grade 3 liver function abnormalities. Pharmacokinetics were determined by gamma counting serial whole blood, plasma, and urine samples at energy windows for the 225Ac daughters, francium-221 and bismuth-213. Two-phase elimination kinetics were seen with mean plasma t1/2 − α and t1/2 − β of 1.9 and 38 hours, respectively. Peripheral blood blasts were eliminated in 10 of 16 evaluable patients (63%) but only at doses of ≥ 37 kBq/kg. Bone marrow blasts were reduced in 10 of 15 evaluable patients (67%), including 3 patients with marrow blasts ≤ 5% and one patient with a morphologic leukemia-free state.

Conclusions:

Therapy for AML with the targeted α-particle generator 225Ac-lintuzumab was feasible with an acceptable safety profile. Elimination of circulating blasts or reductions in marrow blasts were observed across all dose levels.
Dexamethasone, a Synthetic Glucocorticoid, Induces the Activity of Androgen Receptor in Human Dermal Papilla Cells
Authors: Kwack Mi Hee , Ben Hamida Ons , Kim Moon Kyu , Kim Jung Chul , Sung Young Kwan
Published: May 2022

Psychosocial stress stimulates the secretion of glucocorticoids (GCs), which are stress-related neurohormones. GCs are secreted from hair follicles and promote hair follicle regression by inducing cellular apoptosis. Moreover, the androgen receptor (AR) is abundant in the balding scalp, and androgens suppress hair growth by binding to AR in androgenetic alopecia. First, by using immunofluorescence, we investigated whether the treatment of dermal papilla (DP) cells with dexamethasone (DEX), a synthetic GC, causes the translocation of the glucocorticoid receptor (GR) into the nucleus. DEX treatment causes the translocation of the GR into the nucleus. Next, we investigated whether stress-induced GCs affect the AR, a key factor in male pattern baldness. In this study, we first assessed that DEX increases the expression of AR mRNA in non-balding DP cells, which rarely express AR without androgen. RU486, a GR antagonist, attenuated DEX-inducible AR mRNA expression and AR activation in human non-balding DP cells. In addition, AR translocated into the nucleus after DEX treatment. Furthermore, we indeed showed that the expression of AR was induced in the nucleus by DEX in DP cells of human and mouse hair follicles. Our results first suggest that stress-associated hair loss may be due to increased AR expression and activity induced by DEX. These results demonstrate that hair loss occurs in non-balding scalps with low AR expression.
O movimento sem terra e a educação escolar: a trajetória de uma pedagogia para além dos muros da escola
Authors: Machado Vitor
Published: May 2022

Este artigo desenvolveu algumas reflexões sobre o modelo de educação e de escola do ensino fundamental implantada nos acampamentos e assentamentos do Movimento Sem terra (MST), entre a última década do século XX e o início da primeira década do século XXI. As discussões foram realizadas adotando-se como referência alguns textos publicados no Caderno de Educação nº 13, que se intitula “Dossiê MST Escola”. Por meio de uma análise sintetizada desses documentos, verificamos que o MST defende uma educação teórica e prática, voltada para a realidade do aluno assentado, que seja baseada em princípios humanistas e na cooperação, sendo capaz de criar no educando uma consciência crítica, capaz de torná-lo um sujeito de ação transformadora.
Avaliação de cursos de educação superior à distância
Authors: Rodrigues Cecília Carmen Pontes , Aprile Maria Rita
Published: May 2022

Desde meados dos anos de 1990, o Estado vem incentivando e criando facilidades para a abertura e expansão de instituições privadas de ensino superior. O crescimento gradativo dessas instituições tem concorrido para o aumento da oferta de cursos de graduação presenciais e a distância, em todo o país. Em relação à modalidade a distância, a questão central que se coloca é: como avaliar adequadamente a sua qualidade tendo em vista a insuficiência do formato tradicional de avaliação usado em cursos presenciais? O presente artigo sistematiza informações referentes a um conjunto de categorias que constituem um referencial importante para os processos de regulação de cursos de educação superior a distância. Essas categorias resultaram na proposição de uma matriz de avaliação que inclui aspectos pertinentes à coordenação, docência, tutoria, equipe técnica e alunos e elementos como: material didático, ambiente de veiculação da programação e suporte técnico, entre outros. Para além da melhoria da qualidade, a proposição de intervenções visando alterações e/ou aperfeicoamento das programações a distância constitui uma medida social e política de democratização do acesso à educação superior.
A Response to Paolo Euron’s “Uncanny Beauty: Aesthetics of Companionship, Love, and Sex Robots”
Authors: O’Sullivan Maria
Published: May 2022

The emergence of sex robots raises important issues about what it means to be human and the commodification of love, companionship, and sex. This commentary discusses the following question: If some members of society relate to robots as “humans,” what does this mean for society’s conceptualisation of personhood and intimate relationships? How love is expressed between individuals is normally considered a very private expression of companionship that should remain in the private sphere. This article examines whether sex robots should be subject to public regulation given the broader societal impacts of their ability to emotionally connect and elicit empathy from humans.
QBO Wind Influence on MJO-Induced Temperature Anomalies in the Upper Troposphere and Lower Stratosphere in an Idealized Model
Authors: Lim Yuna , Son Seok-Woo
Published: May 2022

The dynamical mechanism by which the quasi-biennial oscillation (QBO) might influence the temperature anomaly, associated with the Madden–Julian oscillation (MJO), in the equatorial upper troposphere and lower stratosphere (UTLS) is examined by conducting a series of initial-value experiments using a dry primitive equation model. The observed temperature response to the MJO convection becomes colder and more in phase with the convection during easterly QBO (EQBO) than westerly QBO (WQBO) phases. This QBO-dependent MJO temperature anomaly in the UTLS is qualitatively reproduced by model experiments in which EQBO or WQBO background state is artificially imposed above 250 hPa while leaving the troposphere unaltered. As in the observations, the localized cold anomaly in the UTLS becomes strengthened and steepened with EQBO-like background state than WQBO-like one. It turns out that the QBO zonal wind, instead of temperature, plays a major role in determining the localized UTLS temperature anomaly by modulating wave energy dispersion.
New Insights on the Formation and Breaking Mechanism of Convective Cyclonic Cones in the South Adriatic Pit during Winter 2018
Authors: Pirro A. , Mauri E. , Gerin R. , Martellucci R. , Zuppelli P. , Poulain P. M.
Published: May 2022

The deepwater formation in the northern part of the South Adriatic Pit (Mediterranean Sea) is investigated using a unique oceanographic dataset. In situ data collected by a glider along the Bari–Dubrovnik transect captured the mixing and the spreading/restratification phase of the water column in winter 2018. After a period of about 2 weeks from the beginning of the mixing phase, a homogeneous convective area of ∼300-m depth breaks up due to the baroclinic instability process in cyclonic cones made of geostrophically adjusted fluid. The base of these cones is located at the bottom of the mixed layer, and they extend up to the theoretical critical depth Zc. These cones, with a diameter on the order of internal Rossby radius of deformation (∼6 km), populate the ∼110-km-wide convective site, develop beneath it, and have a short lifetime of weeks. Later on, the cones extend deeper and intrusion from deep layers makes their inner core denser and colder. These observed features differ from the long-lived cyclonic eddies sampled in other ocean sites and formed at the periphery of the convective area in a postconvection period. So far, to the best of our knowledge, only theoretical studies, laboratory experiments, and model simulations have been able to predict and describe our observations, and no other in situ information has yet been provided.
Orographic Effects on Landfalling Lake-Effect Systems
Authors: Gowan Thomas M. , Steenburgh W. James , Minder Justin R.
Published: May 2022

Landfalling lake- and sea-effect (hereafter lake-effect) systems often interact with orography, altering the distribution and intensity of precipitation, which frequently falls as snow. In this study, we examine the influence of orography on two modes of lake-effect systems: long-lake-axis-parallel (LLAP) bands and broad-coverage, open-cell convection. Specifically, we generate idealized large-eddy simulations of a LLAP band produced by an oval lake and broad-coverage, open-cell convection produced by an open lake (i.e., without flanking shorelines) with a downstream coastal plain, 500-m peak, and 2000-m ridge. Without terrain, the LLAP band intersects a coastal baroclinic zone over which ascent and hydrometeor mass growth are maximized, with transport and fallout producing an inland precipitation maximum. The 500-m peak does not significantly alter this structure, but slightly enhances precipitation due to orographic ascent, increased hydrometeor mass growth, and reduced subcloud sublimation. In contrast, a 2000-m ridge disrupts the band by blocking the continental flow that flanks the coastlines. This, combined with differential surface heating between the lake and land, leads to low-level flow reversal, shifting the coastal baroclinic zone and precipitation maximum offshore. In contrast, the flow moves over the terrain in open lake, open-cell simulations. Over the 500-m peak, this yields an increase in the frequency of weaker (<1 m s−1) updrafts and weak precipitation enhancement, although stronger updrafts decline. Over the 2000-m ridge, however, buoyancy and convective vigor increase dramatically, contributing to an eightfold increase in precipitation. Overall, these results highlight differences in the influence of orography on two common lake-effect modes.

Significance Statement

Landfalling lake- and sea-effect snowstorms frequently interact with hills, mountains, and upland regions, altering the distribution and intensity of snowfall. Using high-resolution numerical modeling with simplified lake shapes and terrain features, we illustrate how terrain features affect two common types of lake-effect storms and why long-lake-axis-parallel (LLAP) bands can feature high precipitation rates but weaker orographic enhancement than broad-coverage, open-cell convection.
Scroll-like and platy molybdenite-3R from the Ufaley metamorphic block, South Urals: EBSD, XRD, SEM, EPMA and ICP-MS study
Authors: Belogub Elena V. , Shilovskikh Vladimir V. , Rassomakhin Michail A. , Plotinskaya Olga Yu. , Savichev Alexandr N. , Filippova Ksenia A. , Kirichenko Sergey , Spratt John , Seltmann Reimar
Published: May 2022

Scroll-like crystals of molybdenite, 2–5 mm in size, were found in phengite rock from the outer contact of the granular quartz vein of the Kyshtym quartz deposit. Platy and partly scrolled molybdenite occur in the same phengite rock from the outer contact of the quartz–feldspar pegmatite of the Slyudyanogorsk mica deposit. Both occurrences are located in the Ufaley metamorphic block in the South Urals. Scroll-like molybdenite crystals can associate with platy and partly twisted crystals in the same samples. The chemical composition of molybdenite was studied by inductively coupled plasma mass spectrometry (ICP-MS) and electron probe microanalysis (EPMA). Polytypes of molybdenite were identified with electron back-scattered diffraction (EBSD) and X-ray diffraction (XRD). Both scroll-like and platy molybdenite crystals are only represented by the 3R polytype, are enriched in Re up to 1 wt.% and contain no other significant impurities. Scroll-like molybdenite is twisted mainly around the crystallographic axis X. Twinning with a rotation of 60 degrees around the Z crystallographic axis is fixed in the plane (ab). The most probable origin of scroll molybdenites is the consequent growth of molybdenite around nucleation centres, which are commonly represented by mica crystals. The formation of the 3R polytype is caused by the difference in dimension of the layers enriched and depleted in rhenium.
Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL
Authors: Diorio Caroline , Murray Ryan , Naniong Mark , Barrera Luis , Camblin Adam , Chukinas John , Coholan Lindsey , Edwards Aaron , Fuller Tori , Gonzales Claudia , Grupp Stephan A. , Ladd Alden , Le Melissa , Messana Angelica , Musenge Faith , Newman Haley , Poh Yeh-Chuin , Poulin Henry , Ryan Theresa , Shraim Rawan , Tasian Sarah K. , Vincent Tiffaney , Young Lauren , Zhang Yingying , Ciaramella Giuseppe , Gehrke Jason , Teachey David T.
Published: May 2022

Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using gene editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target editing outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G to T•A point mutations in T cells, with between 90% and 99% efficiency to silence gene expression without creating DSBs, greatly reducing or eliminating undesired editing outcomes following multiplexed editing as compared with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using CBE, we developed 7CAR8, a CD7-directed allogeneic CART created using 4 simultaneous base edits. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation, or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells, with high potential for clinical translation for relapsed and refractory T-ALL.
CAR T-cell therapy in highly aggressive B-cell lymphoma: emerging biological and clinical insights
Authors: Ali Alaa , Goy Andre , Dunleavy Kieron
Published: May 2022

Recently, significant progress has been made in identifying novel therapies, beyond conventional immunochemotherapy strategies, with efficacy in B-cell lymphomas. One such approach involves targeting the CD19 antigen on B cells with autologous-derived chimeric antigen receptor (CAR) cells. This strategy is highly effective in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), as evidenced by recent regulatory approvals. Recent reports suggest that this is an effective strategy for high-grade B-cell lymphoma. The biological underpinnings of these entities and how they overlap with each other and DLBCL continue to be areas of intense investigation. Therefore, as more experience with CAR T-cell approaches is examined, it is interesting to consider how both tumor cell–specific and microenvironmental factors that define these highly aggressive subsets influence susceptibility to this approach.
RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop
Authors: Xiao Chengwu , Zhang Wei , Hua Meimian , Chen Huan , Yang Bin , Wang Ye , Yang Qing
Published: May 2022

Background

RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progression of RCC have not been explored.

Methods

Bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot were conducted to determine the expression of RNF7 in RCC tissues and cell lines. Knockdown and overexpression experiments were performed to examine the effects of RNF7 on cell viability, apoptosis, and glycolysis in vitro and on tumor growth in nude mice in vivo.

Results

The elevated RNF7 expression in tumor tissues of patients with RCC was correlated with poor survival. RNF7 overexpression inhibited apoptosis and promoted glycolysis in vitro and increased tumor growth in vivo by activating the JAK/STAT3 signaling pathway by ubiquitination of SOCS1. Moreover, RNF7 overexpression affected the sensitivity of RCC cells to sunitinib. Finally, STAT3 activation was necessary for transcriptional induction of RNF7.

Conclusion

These results demonstrate that RNF7 inhibited apoptosis, promoted glycolysis, and inhibited sunitinib sensitivity in RCC cells via ubiquitination of SOCS1, thus activating STAT3 signaling. These suggest the potential for targeting the RNF7-SOCS1/JAK/STAT3 pathway for RCC treatment.
Assessment of stormwater discharge contamination and toxicity for a cold-climate urban landscape
Authors: Popick H. , Brinkmann M. , McPhedran Kerry
Published: May 2022

Background

Stormwater is water resulting from precipitation events and snowmelt running off the urban landscape, collecting in storm sewers, and typically being released into receiving water bodies through outfalls with minimal to no treatment. Despite a growing body of evidence observing its deleterious pollution impacts, stormwater management and treatment in cold climates remains limited, partly due to a lack of quality and loading data and modeling parameters. This study examines the quality of stormwater discharging during the summer season in a cold-climate, semi-arid Canadian city (Saskatoon, Saskatchewan).

Results

Seven stormwater outfalls with mixed-land-use urban catchments > 100 km2 were sampled for four summer (June–August 2019) storm events and analyzed for a suite of quality parameters, including total suspended solids (TSS), chemical oxygen demand (COD), dissolved organic carbon (DOC), metals, and targeted polyaromatic hydrocarbons (PAHs). In addition, assessment of stormwater toxicity was done using the two toxicity assays Raphidocelis subcapitata (algae) and Vibrio fischeri (bacteria). Notable single-event, single-outfall contaminant pulses included of arsenic (420 µg/L), cadmium (16.4 µg/L), zinc (924 µg/L), fluorene (4.95 µg/L), benzo[a]pyrene (0.949 µg/L), pyrene (0.934 µg/L), phenanthrene (1.39 µg/L), and anthracene (1.40 µg/L). The IC50 in both R. subcapitata and V. fischeri was observed, if at all, above expected toxicity thresholds for individual contaminant species. Principal component analysis (PCA) showed no clear trends for individual sampling sites or sampling dates. In contrast, parameters were correlated with each other in groups including DOC, COD, TSS, and reduced algal toxicity; and total dissolved solids (TDS), sum of metals, and pH.

Conclusions

In general, stormwater characteristics were similar to those of previous studies, with a bulk of contamination carried by the first volume of runoff, influenced by a combination of rainfall depth, antecedent dry period, land use, and activity within the catchment. Roads, highways, and industrial areas contribute the bulk of estimated contaminant loadings. More intensive sampling strategies are necessary to contextualize stormwater data in the context of contaminant and runoff volume peaks.
Reducing overall herbicide use may reduce risks to humans but increase toxic loads to honeybees, earthworms and birds
Authors: Cech Ramona M. , Jovanovic Suzanne , Kegley Susan , Hertoge Koen , Leisch Friedrich , Zaller Johann G.
Published: May 2022

Background

Pesticide use has been associated with risks for human health and an overall decline in biodiversity. Although herbicides are the most commonly used pesticides worldwide, they have received less attention in this debate. We investigated the extent to which long-term trends in herbicide use in Austria influence potential toxic exposures to non-target organisms and potential risks to humans. We analyzed official sales data of 101 herbicide active ingredients (AIs) approved in Austria between 2010 and 2019 regarding their ecotoxicological properties based on lethal doses (LD50 and LC50) weighed by their persistence in the environment (DT50) for honeybees (Apis mellifera), earthworms (Eisenia fetida), and birds (Serinus serinus). Human health risks were qualitatively assessed based on official hazard statements for the AIs used.

Results

In Austria, herbicide amounts sold decreased significantly by 24% from 1480 to 1123 tonnes between 2010 and 2019. This also led to a considerable decrease in the amounts of AIs classified by H-statements of the EU Pesticides Database: − 71% acute inhalation toxicity, − 58% reproductive toxicity,− 47% specific target organ toxicity. Yet, 36% of herbicides used were still classified as highly hazardous pesticides according to the Pesticide Action Network. Surprisingly, over the same period, toxic loads to honeybees increased by 487% (oral exposure), while lethal toxic loads to earthworms increased by 498%, and to birds by 580%. This can be attributed to a shift toward the use of more acutely toxic and especially more persistent AIs. The most problematic AI for honeybees, earthworms, birds and humans was the highly persistent diquat. The further ranking of the most toxic herbicides varied considerably depending on the organism. It is important to note that this toxic load assessment, like official environmental risk assessments, evaluates the potential risk but not the actual fatalities or real-world exposure.

Conclusions

Our results show a trade-off between herbicide amounts and toxicological hazards to humans and other non-target organisms. These interdependencies need to be considered when implementing pesticide reduction targets to protect public health and biodiversity, such as the EU´s “farm-to-fork” strategy, which aims to reduce the amounts and risks of synthetic pesticides.
Global prediction model for COVID-19 pandemic with the characteristics of the multiple peaks and local fluctuations
Authors: Dai Haoran , Cao Wen , Tong Xiaochong , Yao Yunxing , Peng Feilin , Zhu Jingwen , Tian Yuzhen
Published: May 2022

Background

With the spread of COVID-19, the time-series prediction of COVID-19 has become a research hotspot. Unlike previous epidemics, COVID-19 has a new pattern of long-time series, large fluctuations, and multiple peaks. Traditional dynamical models are limited to curves with short-time series, single peak, smoothness, and symmetry. Secondly, most of these models have unknown parameters, which bring greater ambiguity and uncertainty. There are still major shortcomings in the integration of multiple factors, such as human interventions, environmental factors, and transmission mechanisms.

Methods

A dynamical model with only infected humans and removed humans was established. Then the process of COVID-19 spread was segmented using a local smoother. The change of infection rate at different stages was quantified using the continuous and periodic Logistic growth function to quantitatively describe the comprehensive effects of natural and human factors. Then, a non-linear variable and NO2 concentrations were introduced to qualify the number of people who have been prevented from infection through human interventions.

Results

The experiments and analysis showed the R2 of fitting for the US, UK, India, Brazil, Russia, and Germany was 0.841, 0.977, 0.974, 0.659, 0.992, and 0.753, respectively. The prediction accuracy of the US, UK, India, Brazil, Russia, and Germany in October was 0.331, 0.127, 0.112, 0.376, 0.043, and 0.445, respectively.

Conclusion

The model can not only better describe the effects of human interventions but also better simulate the temporal evolution of COVID-19 with local fluctuations and multiple peaks, which can provide valuable assistant decision-making information.
Development and evaluation of a Japanese prediction model for low anterior resection syndrome after rectal cancer surgery
Authors: Paku Masakatsu , Miyoshi Norikatsu , Fujino Shiki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Uemura Mamoru , Mizushima Tsunekazu , Yamamoto Hirofumi , Doki Yuichiro , Eguchi Hidetoshi
Published: May 2022

Background

Low anterior resection syndrome (LARS) is the most common complication after rectal cancer resection. We aimed to identify LARS' predictive factors and construct and evaluate a predictive model for LARS.

Methods

This retrospective study included patients with rectal cancer more than 1 year after laparoscopic or robotic-assisted surgery. We administered a questionnaire to evaluate the degree of LARS. In addition, we examined clinical characteristics with univariate and multivariate analysis to identify predictive factors for major LARS. Finally, we divided the obtained data into a learning set and a validation set. We constructed a predictive model for major LARS using the learning set and assessed the predictive accuracy of the validation set.

Results

We reviewed 160 patients with rectal cancer and divided them into a learning set (n = 115) and a validation set (n = 45). Univariate and multivariate analyses in the learning set showed that male (odds ratio [OR]: 2.88, 95% confidence interval [95%CI] 1.11–8.09, p = 0.03), age < 75 years (OR: 5.87, 95%CI 1.14–47.25, p = 0.03) and tumors located < 8.5 cm from the AV (OR: 7.20, 95%CI 2.86–19.49, p < 0.01) were significantly related to major LARS. A prediction model based on the patients in the learning set was well-calibrated.

Conclusions

We found that sex, age, and tumor location were independent predictors of major LARS in Japanese patients that underwent rectal cancer surgery. Our predictive model for major LARS could aid medical staff in educating and treating patients with rectal cancer before and after surgery.
Implementing and evaluating online advance care planning training in UK nursing homes during COVID-19: findings from the Necessary Discussions multi-site case study project
Authors: Cousins Emily , Preston Nancy , Doherty Julie , Varey Sandra , Harding Andrew , McCann Adrienne , Harrison Dening Karen , Finucane Anne , Carter Gillian , Mitchell Gary , Brazil Kevin
Published: May 2022

Background

Advance care planning in nursing homes is important to ensure the wishes and preferences of residents are recorded, especially during the COVID-19 pandemic. However, care staff and family members frequently report feeling unprepared for these conversations. More resources are needed to support them with these necessary discussions. This research aimed to develop, implement and evaluate a website intervention for care staff and family members to provide training and information about advance care planning during COVID-19.

Methods

The research was a primarily qualitative case study design, comprising multiple UK nursing home cases. Data collection included semi-structured interviews with care staff and family members which were coded and analysed thematically. A narrative synthesis was produced for each case, culminating in a thematic cross-case analysis of the total findings. Theoretical propositions were refined throughout the research.

Results

Eight nursing homes took part in the study, involving 35 care staff and 19 family members. Findings were reported according to the RE-AIM framework which identified the reach, effectiveness, adoption, implementation and maintenance of the intervention. Themes included: website content that was well received; suggestions for improvement; implementation barriers and facilitators; examples of organisational and personal impact.

Conclusions

Four theoretical propositions relating to advance care planning in nursing homes are presented, relating to: training and information needs, accessibility, context, and encouraging conversations. Implications for practice and training include an awareness of diverse learning styles, re-enforcing the right to be involved in advance care planning and encouraging opportunities for facilitated discussion.

Trial registration

ISRCTN registry (ID 18003630) on 19.05.21.
Is lobectomy superior to sub-lobectomy in non-small cell lung cancer with pleural invasion? A population-based competing risk analysis
Authors: Song Xue , Xie Yangyang , Zhu Yurou , Lou Yafang
Published: May 2022

Background

Pleural invasion (PL) has been regarded as an unfavorable prognostic factor for non-small cell lung cancer (NSCLC). But there was no agreement on the optimal surgical extent in NSCLC patients with PL. We aimed to compare the survival outcomes of lobectomy and sub-lobectomy in these patients.

Method

2717 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the lobectomy and sub-lobectomy groups. The propensity score matching (PSM) and competing risk analysis were implemented. Then the predictive nomogram was constructed and validated.

Results

2230 Patients received lobectomy while the other 487 patients underwent sub-lobectomy. After 1:1 PSM, the cumulative incidence of cancer-specific death (CSD) was lower in the lobectomy group compared with the sub-lobectomy group (1-year: 12% vs. 15%; 3-year: 30% vs. 37%, 5-year: 34% vs. 45%, P = 0.04). According to the subgroup analysis, the patients who underwent lobectomy suffered lower CSD in the N0–1 stage, adenocarcinoma, and PL-2 cohort (p < 0.05). And there was a significant relationship between the sub-lobectomy group and CSD in the multivariate competing risks regression analysis (HR, 1.26; 95%CI, 1.02–1.56; P = 0.034). Furthermore, a competing event nomogram was constructed to assess the 1-, 3-, and 5-year chances of CSD based on the variables from the multivariate analysis. The 1-, 3-, 5-year area under the receiver operating characteristic curve (AUC) values were 0.720, 0.706, and 0.708 in the training cohort, and 0.738, 0.696, 0.680 in the validation cohorts, respectively. And calibration curves demonstrated ideal consistency between the predicted and observed probabilities of CSD.

Conclusion

Lobectomy should be considered the preferred surgery compared to sub-lobectomy for NSCLC patients with PL. The proposed nomograms presented great prediction ability for these patients.