bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) Impregnated Activated Carbon for Removal of Hexavalent Chromium
Authors: Farhana Aisha , Jenifer Selvarani A. , Samrot Antony V. , Alsrhani Abdullah , Raji P. , Sahithya Chamarthy Sai , Jane Cypriyana P. J. , Senthilkumar P. , Ling Mok Pooi , Yishak Simon
Published: January 2022

Chromium (Cr) is a toxic heavy metal present in industrial effluent which could cause degenerative diseases on ingestion. Therefore, elimination of Cr from contaminated water becomes essential to preserve and sustain the quality of life. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were impregnated on activated carbon and checked for enhanced removal of Cr(VI). Thus, granular activated carbon (N‐GAC) of mesh size 8∗20 was impregnated with SPIONs to produce SPIONs impregnated activated carbon (Sp‐GAC) and characterized using UV‐VIS spectrophotometer, FT‐IR, SEM‐EDX, XRD, and VSM. Sp‐GAC was found to be possessing superparamagnetic behavior, and it was used in batch adsorption study where the adsorption parameters like pH, concentration of adsorbent, and adsorbent‐adsorbate were optimized. It was found that Cr(VI) adsorption was predominant at acidic pH (pH 3) for both cases; moreover, N‐GAC showed better adsorption comparatively. Both the N‐GAC and Sp‐GAC adsorption were found to be obeying to Langmuir.
Optimization of Heterogeneous Clustering Routing Protocol for Internet of Things in Wireless Sensor Networks
Authors: Yang Shun , Long Xian’ai , Peng Hao , Gao Haibo
Published: January 2022

Wireless sensor network technology is widely used in various modern scenarios, and various industries have higher and higher requirements for the performance indicators of wireless sensor networks. A reasonable and effective layout of wireless sensor networks is conducive to the monitoring of environmental quality, various transactions, and status and transmits a large number of sensing data to the data aggregation center for processing and analysis. However, the operation and development of traditional wireless sensor networks are extremely dependent on the energy supply of the network. When the corresponding supply energy is limited, the operation life of the corresponding wireless sensor network will be greatly reduced. Based on the above situation, this paper proposes a nonuniform clustering routing protocol optimization algorithm from the energy loss of cluster head and clustering form algorithm in wireless sensor networks. At the level of cluster head calculation in wireless sensor networks, firstly, based on the adaptive estimation clustering algorithm, the core density is used as the estimation element to calculate the cluster head radius of wireless sensor networks. At the same time, this paper creatively proposes a fuzzy logic algorithm to further solve the uncertainty of cluster head selection, integrate the residual energy of cluster head nodes, and finally complete the reasonable distribution of cluster heads and realize the balance of node energy consumption. In order to further reduce the algorithm overhead of transmission between cluster heads and realize energy optimization, an intercluster routing optimization algorithm based on the ant colony algorithm is proposed. The pheromone is updated and disturbed by introducing chaotic mapping to ensure the optimal solution of the algorithm, and the optimal path is selected from the perspective of energy dispersion coefficient and distance coefficient, so as to optimize the energy consumption between cluster heads. The experimental results show that compared with the traditional algorithm, the proposed nonuniform clustering routing protocol optimization algorithm prolongs the corresponding life cycle by 75% and reduces the total network energy consumption by about 20%. Therefore, the algorithm achieves the purpose of optimizing network energy consumption and prolonging network life to a certain extent and has certain practical value.
Obstacle Avoidance Path Planning for UAV Based on Improved RRT Algorithm
Authors: Yang Fan , Fang Xi , Gao Fei , Zhou Xianjin , Li Hao , Jin Hongbin , Song Yu
Published: January 2022

Obstacle avoidance path planning capability, as one of the key capabilities of UAV (Unmanned Aerial Vehicle) to achieve safe autonomous flight, has always been a hot research topic in UAV research filed. As a commonly used obstacle avoidance path planning algorithm, RRT (Rapid‐exploration Random Tree) algorithm can carry out obstacle avoidance path planning in real time and online. In addition, it can obtain the asymptotically optimal obstacle avoidance path on the premise of ensuring the completeness of probability. However, it has some problems, such as high randomness, slow convergence speed, long transit time, and curved flight trajectory, so that it cannot meet the flight conditions of the actual UAV. To solve these problems, the paper proposes an improved RRT algorithm. In the process of extending the random tree, ACO (ant colony optimization) is introduced to make the planning path asymptotically optimal. The optimized algorithm can set pheromones on the path obtained by RRT and select the next extension point according to the pheromone concentration. And then through a certain number of iterations, it converges to an ideal path scheme. In addition, this paper also uses MATLAB to verify the effectiveness and superiority of the algorithm: Although RRT is easy to fall into local optimization, since the optimization method in this paper can almost certainly converge to the optimal solution, when it is necessary to preplan the path before UAV takeoff, it can be used.
Security Analysis of Shadowsocks(R) Protocol
Authors: Ji Qingbing , Rao Zhihong , Chen Man , Luo Jie
Published: January 2022

Shadowsocks(R) is a proxy software based on Socks5, which is the collective name of shadowsocks and shadowsocksR. Shadowsocks(R) is a private protocol without a handshake negotiation mechanism. Peng broke the confidentiality of shadowsocks by exploiting vulnerability in the shadowsocks protocol and decrypted the shadowsocks packets encrypted with none-AEAD encryption options using a redirection attack. Chen et al. started with the cryptographic algorithm used by shadowsocks(R) and preliminarily discussed the confidentiality of user data under the protection of shadowsocks(R) in theory. Based on Chen’s work, this paper further clarifies the shadowsocks(R) protocol format and studies the encryption mechanism of shadowsocks(R) from the perspective of protocol analysis. The vulnerability of the shadowsocks(R) encryption mechanism is found, and an attack method of shadowsocks(R) is proposed. The attack method is a passive attack and can decrypt the shadowsocks packets encrypted with any encryption option. Compared with Peng’s attack method, the method is more effective and more suitable for actual attacks. Finally, some methods to improve the protocol security of shadowsocks(R) are proposed.
A Common Feature of Pesticides: Oxidative Stress—The Role of Oxidative Stress in Pesticide-Induced Toxicity
Authors: Sule Rasheed O. , Condon Liam , Gomes Aldrin V.
Published: January 2022

Pesticides are important chemicals or biological agents that deter or kill pests. The use of pesticides has continued to increase as it is still considered the most effective method to reduce pests and increase crop growth. However, pesticides have other consequences, including potential toxicity to humans and wildlife. Pesticides have been associated with increased risk of cardiovascular disease, cancer, and birth defects. Labels on pesticides also suggest limiting exposure to these hazardous chemicals. Based on experimental evidence, various types of pesticides all seem to have a common effect, the induction of oxidative stress in different cell types and animal models. Pesticide-induced oxidative stress is caused by both reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are associated with several diseases including cancer, inflammation, and cardiovascular and neurodegenerative diseases. ROS and RNS can activate at least five independent signaling pathways including mitochondrial-induced apoptosis. Limited in vitro studies also suggest that exogenous antioxidants can reduce or prevent the deleterious effects of pesticides.
Construction of Grain Price Determinants Analysis Model Based on Structural Vector Autoregressive Model
Authors: Wang Shudong , Zhang Man , Wang Yuanzhuo , Meng Hui
Published: January 2022

In 2020, the sudden global epidemic of novel coronavirus pneumonia (COVID-19) caused abnormal fluctuations in the global grain market and posed severe challenges to world grain security. Therefore, it is very important for countries around the world to analyze the determinants of grain price and put forward corresponding strategies to ensure grain safety. In this paper, we theoretically discussed the relationship between financial liquidity, speculation, and grain price for the first time. Based on the analysis of Fisher’s equation, this paper argues that the theoretical basis of grain financialization is closer to the volatility theory of the money market. Then, we employ the structural vector autoregression model (SVAR) to explore the impulse response of grain price to the structural shock of world grain production, demand, financial liquidity, and speculation. Our empirical results show that the effects of financial liquidity and speculation on the grain price are more significant. Meanwhile, grain demand changes caused by the global economy have no significant impact on grain price.
Effect of Plant Spacing on Agronomic Performance and Fodder Quality of Four Tepary Bean (Phaseolus acutifolius A. Gray) Cultivars
Authors: Molosiwa Odireleng O. , Baleseng Leonard B. , Chirwa Rowland
Published: January 2022

Tepary bean is gaining interest around the world as a dryland field crop. A two-year field experiment was conducted to determine the effect of plant spacing on the agronomic performance and fodder quality of the crop. A split-plot design was used with three replications, four cultivars (GK010, GK011, GK012, and Motsumi) were assigned to main plots, while subplots were three intrarow plant spacing (10 cm, 20 cm, and 30 cm). Four agronomic variables and eight chemical compositions, including in vitro dry matter digestibility (IVDMD) of husk, stem, and leaf, were measured. Spacing significantly (

P
<
0.05

) influenced plant biomass, pod yield, harvest index, and seed yield, while cultivar affected only pod yield and seed yield. Plant biomass increased with plant spacing where 10 cm produced 936 kg/ha; 20 cm, 750 kg/ha; and 30 cm, 611 kg/ha for 2015–2016 while 10, 20, and 30 cm were observed for 1568 kg/ha, 1135 kg/ha, and 889 kg/ha, respectively, in 2016–2017 season. These trends are attributed to the higher plant population in the narrow row spacing. GK012 consistently outperformed other cultivars for plant biomass, pod yield, and seed yield and has a potential for further selection. Fodder nutritive qualities were not affected by cultivar, while spacing only influenced IVDMD. The three plant parts were significantly (

P
<
0.05

) different for all the nutritive qualities. Leaves had significantly (

P
<
0.05

) lower values of ADF, CF, and NDF compared to those of stem and husk an indication of relatively higher digestibility of the leaf. Acid detergent fiber (40%), neutral detergent fiber (53.65%), crude fiber (35.45%), ash content (12.29%), dry matter (93.09%), and IVDMD (70.66%) were recorded. This study revealed that tepary bean forage has good nutritional content, except for the low phosphorus level. For higher agronomic performance, tepary cultivars should be planted at a spacing of 10 cm without compromising forage quality.
The Expression Levels and Significance of GSH, MDA, SOD, and 8‐OHdG in Osteochondral Defects of Rabbit Knee Joints
Authors: Xiao Zhengjun , Yu Xuefeng , Zhang Shuai , Liang A.
Published: January 2022

Objective. To observe the dynamic changes in oxidative stress and the expression levels of antioxidant and oxidative parameters in the blood and synovial fluid in the osteochondral defects of the rabbit knee joints and to explore the significance. Methods. Thirty New Zealand white rabbits were randomly selected and divided into a blank control group (n = 10), a model control group (n = 10), and an osteochondral defect group (n = 10). The osteochondral defect model of rabbit knee joint was constructed by medial parapatellar arthrotomy. The expression levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and 8‐hydroxydeoxyguanosine (8‐OHdG) in peripheral venous blood and knee synovial fluid of the three groups were measured at the end of the 4th, 8th, and 12th weeks after treatment. Results. The expression levels of GSH and SOD in the blood and synovial fluid in the osteochondral defect group at the end of the 8th and 12th weeks were observably lower than those of the other two groups (P < 0.05); higher expression levels of MDA and 8‐OHdG in the blood and synovial fluid of the osteochondral defect group compared with those of the other two groups were obtained (P < 0.05). At the end of the 4th, 8th, and 12th weeks, the expression levels of MDA and 8‐OHdG in the blood and synovial fluid of the osteochondral defect group presented an upward trend (P < 0.05). Conclusion. The osteochondral defects initiate the oxidative stress in the body, which is presented as the decrease of GSH and SOD expression, and the upregulation of MDA and 8‐OHdG expression.
The Optimization of Automated Container Terminal Scheduling Based on Proportional Fair Priority
Authors: Lu Yiqin
Published: January 2022

With the goal of maximizing the efficiency of automated container terminals, taking the loading and unloading time as the research object, the integrated optimization of automated container terminal scheduling with proportional fair priority is established by setting the priority parameters under the premise of balancing the operation efficiency of each container ship at the berth. The model considers separate assignments of general containers and special containers in the actual operation at the automated container terminal, which is never considered in other literatures. A proportional fairness algorithm (PFA) is designed to solve the problem, taking the maximum of the ratio of quantities of remaining loading and unloading containers of each container ship to the distance of empty AGVs/YTs as the proportional fair priority. The priority of all current tasks is ranked, and the highest priority task is fulfilled first. Different from the published literature, the study of this paper can be presented in two aspects. One is in the modeling. This includes (i) formalizing the description of the purpose of the model and (ii) conducting a real-world coordination of four types of equipment that incorporate at automated container terminals which considers different operations between general goods and special goods in the actual automated terminal operations. The other is that PFA is applied to deal with the integrated scheduling whose results are better with the balance of efficiency and fairness.
Electroacupuncture Attenuated Anxiety and Depression-Like Behavior via Inhibition of Hippocampal Inflammatory Response and Metabolic Disorders in TNBS-Induced IBD Rats
Authors: Zhou Feini , Jiang Hao , Kong Ning , Lin Jiangnan , Zhang Fan , Mai Ting , Cao Zhijian , Xu Maosheng
Published: January 2022

This study was designed to explore the potential mechanisms of electroacupuncture (EA) in treating inflammatory bowel disease- (IBD-) related anxiety and mood disorders. A colitis model was induced in rats with 2, 4, 6-trinitrohydrosulfonic acid (TNBS), followed by ST36 and SP6 targeted therapy by EA or sham EA treatment. The elevated plus maze (EPM) and open-field test (OFT) were performed to assess the state of anxiety and depression-like behavior. Tests were carried out by 16S rDNA amplification sequence, 1H nuclear magnetic resonance (1H NMR) spectroscopy, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). The analyses detailed metabolic alterations and the Toll-like receptor 4 (TLR4) signaling pathway/NOD-like receptor protein 3 (NLRP3) inflammasome in rats’ hippocampal region. Furthermore, the activity of the hypothalamic-pituitary adrenal (HPA) axis and gut microbiome was assessed. As a result of treatment, EA significantly improved in the behavioral tests and altered the composition of the gut microbiome through a significant increase in the density of short chain fatty acids (SCFAs) producers mainly including Ruminococcaceae, Phascolarctobacterium, and Akkermansiaceae. EA upregulated the metabolites of the hippocampus mainly containing l-glutamine and gamma-aminobutyric acid (GABA), as well as ZO-1 expression. Whereas the treatment blocked the TLR4/nuclear factor- kappa B (NF-κB) signaling pathways and NLRP3 inflammasomes, along with downregulating the interleukin- (IL-) 1β level. The hyperactivity of the HPA axis was also diminished. In conclusion, EA at ST36 and SP6 attenuated anxiety and depression-like behavior in colitis model rats through their effects on the gut microbiome by modulating the hippocampal inflammatory response and metabolic disorders, as well as the HPA axis. This study provides evidence for clinical application of EA to serve as an adjunctive treatment for IBD-related anxiety and depression.
EEG‐Based Multiword Imagined Speech Classification for Persian Words
Authors: Asghari Bejestani M. R. , Mohammad Khani Gh. R. , Nafisi V. R. , Darakeh F.
Published: January 2022

This study focuses on providing a simple, extensible, and multiclass classifier for imagined words using EEG signals. Six Persian words, along with the silence (or idle state), were selected as input classes. The words can be used to control a mouse/robot movement or fill a simple computer form. The data set of this study was 10 recordings of five participants collected in five sessions. Each record had 20 repetitions of all words and the silence. Feature sets consist of normalized, 1 Hz resolution frequency spectrum of 19 EEG channels in 1 to 32 Hz bands. Majority rule on a bank of binary SVM classifiers was used to determine the corresponding class of a feature set. Mean accuracy and confusion matrix of the classifiers were estimated by Monte‐Carlo cross‐validation. According to recording the time difference of inter‐ and intraclass samples, three classification modes were defined. In the long‐time mode, where all instances of a word in the whole database are involved, average accuracies were about 58% for Word‐Silence, 60% for Word‐Word, 40% for Word‐Word‐Silence, and 32% for the seven‐class classification (6 Words+Silence). For the short‐time mode, when only instances of the same record are used, the accuracies were 96, 75, 79, and 55%, respectively. Finally, in the mixed‐time classification, where samples of every class are taken from a different record, the highest performance achieved with average accuracies was about 97, 97, 92, and 62%. These results, even in the worst case of the long‐time mode, are meaningfully better than random and are comparable with the best reported results of previously conducted studies in this area.
Mixed Cohesive Zone Modeling of Interface Debonding between Propellant and Insulation
Authors: Cui Huiru , Ma Weili
Published: January 2022

High-quality interface between propellant and insulation is the strict requirement difficult to quantify in solid rocket motor. In this study, the mixed mode delamination process of propellant and insulation interface is considered in double cantilever sandwich beam (DCSB) and single lap-joint (SLJ) test. The PPR cohesive zone model (CZM) and bilinear CZM in ABAQUS are introduced in this mixed fracture progress. In order to implement the PPR model in ABAQUS, user subroutine user element (UEL) is programmed for the novel CZM. Two simple pure mode I and mode II fracture problems are designed to check the accuracy of the UEL, and the result of verification is excellent. DCSB and SLJ test and their corresponding results are used again in the same inverse analysis with the two typical effective displacement-based and potential-based CZM. Base on the results, a series discussion and some conclusions are made. The debonding progress of the propellant and insulation interface in DCSB and SLJ test are mixed mode. The PPR CZM is prior in simulation than the bilinear CZM in ABAQUS because the PPR CZM is much more flexible with changeable traction-separation shape. The real normal and tangential displacement at damage initiation shows the unreasonable change in bilinear CZM in ABAQUS under mixed mode fracture. The PPR CZM and bilinear CZM in ABAQUS are all thickness-dependent model. The real initial stiffness and the critical displacement in the bilinear CZM and the real maximum traction in PPR model are dependent on the thickness of cohesive element. The different thickness dependence of the two model is caused by the implementation method.
In Vivo and In Silico Assessment of Diabetes Ameliorating Potentiality and Safety Profile of Gynura procumbens Leaves
Authors: Tahsin Md. Rafat , Tithi Tanzia Islam , Mim Sabiha Rahman , Haque Ehfazul , Sultana Arifa , Bahar Nasiba Binte , Ahmed Raju , Chowdhury Jakir Ahmed , Chowdhury Abu Asad , Kabir Shaila , Aktar Fahima , Uddin Md. Sahab , Amran Md. Shah
Published: January 2022

Background. Diabetes mellitus is one of the most notable health dilemmas. Analyzing plants for new antidiabetic remedies has become an impressive territory for life science researchers. Gynura procumbens has long been used to treat diabetes. Thus, we strived to ascertain the hypoglycemic potentiality of extract of leaves of G. procumbens by in vivo and in silico approaches. Methods. Fresh leaves of G. procumbens were collected and shade-dried to prepare ethanolic extracts to evaluate pharmacological parameters. Diabetes was induced in rats via injecting alloxan through the intraperitoneal route at a dose of 150 mg/kg body weight. Humalyzer 3000 was used to perform a biochemical assay of collected samples from rats. Anti-hyperglycemic activity study along with overdose toxicity test was performed. The pharmacological activity of this plant was also evaluated through a molecular docking study. This in silico study investigated the binding affinity of natural ligands from G. procumbens against glycoside hydrolase enzymes. Results. We detected a peak plasma concentration of G. procumbens at 3 hours 45 minutes that is roughly similar to the peak plasma concentration of metformin. Again, in OGTT and anti-hyperglycemic tests, it has been ascertained that both plant extract and metformin can exert significant

P
<
0.05

and highly significant

P
<
0.01

hypoglycemic activity in a dose-dependent manner. Metformin exhibited better therapeutic efficacy than that of plant extract, but it possessed null statistical significance. Also, our safety profile expressed that, similar to metformin, the plant extract can restore the disturbed pathological state in a dose-oriented approach with a wide safety margin. In silico study also validated the potentialities of natural constituents of G. procumbens. Conclusion. This study suggested that G. procumbens can be considered as potential antidiabetic plant. Robust and meticulous investigation regarding plant chemistry and pharmacology in the future may bring about a new dimension that will aid in discovering antidiabetic drugs from this plant in the diabetes management system.
Experimental Study on Permeability Anisotropy of Unsaturated Compacted Loess
Authors: Hao Yan Zhou , Cheng Lei , Xiao Wen Fang
Published: January 2022

This study investigates the permeability characteristics of unsaturated compacted loess by focusing on the anisotropy parallel and perpendicular to the compaction. Three tests are conducted on compacted loess: permeability test, soil‐water characteristic curve test, and scanning electron microscope (SEM) test. Samples are maintained and tested at different dry densities under optimal moisture conditions. Test results showed that the horizontal saturated permeability coefficient of compacted loess was larger than in the vertical direction, showing obvious anisotropy. Based on the saturated permeability coefficient, the permeability coefficient of unsaturated compacted loess can be predicted according to the soil‐water characteristic curve fitted using the van Genuchten model combined with the Childs and Collis‐Geroge model. The relational formula was established between the unsaturated permeability anisotropy ratio and the matrix suction through introducing a pore connectivity‐tortuosity parameter, which represents the relationship between unsaturated permeability anisotropy ratio and matrix suction. The difference of pore characteristics between horizontal and vertical directions of compacted loess is the main reason for the permeability anisotropy.
A Study on ψ‐Caputo‐Type Hybrid Multifractional Differential Equations with Hybrid Boundary Conditions
Authors: Fredj Fouad , Hammouche Hadda , Abdo Mohammed S. , Albalawi Wedad , Almaliki Abdulrazak H.
Published: January 2022

In this research paper, we investigate the existence, uniqueness, and Ulam–Hyers stability of hybrid sequential fractional differential equations with multiple fractional derivatives of ψ‐Caputo with different orders. Using an advantageous generalization of Krasnoselskii’s fixed point theorem, we establish results of at least one solution, whereas the uniqueness of solution is derived via Banach’s fixed point theorem. Besides, the Ulam–Hyers stability for the proposed problem is investigated by applying the techniques of nonlinear functional analysis. In the end, we provide an example to illustrate the applicability of our results.
Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations
Authors: Pollyea Daniel A. , DiNardo Courtney D. , Arellano Martha L. , Pigneux Arnaud , Fiedler Walter , Konopleva Marina , Rizzieri David A. , Smith B. Douglas , Shinagawa Atsushi , Lemoli Roberto M. , Dail Monique , Duan Yinghui , Chyla Brenda , Potluri Jalaja , Miller Catherine L. , Kantarjian Hagop M.
Published: January 2022

Purpose:

To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

Patients and Methods:

Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1–28) and azacitidine (75 mg/m2; days 1–7/28-day cycle).

Results:

In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group.

Conclusions:

Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.

See related commentary by Perl and Vyas, p. 2719
FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma
Authors: Sharma Poornima , Kanapuru Bindu , George Bindu , Lin Xue , Xu Zhenzhen , Bryan Wilson W. , Pazdur Richard , Theoret Marc R.
Published: January 2022

In March 2021, the FDA approved idecabtagene vicleucel, a chimeric antigen receptor T-cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DOR) in 100 adult patients with RRMM treated with idecabtagene vicleucel in a single-arm trial. Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Of the 100 patients in the efficacy evaluable population, ORR was 72% [95% confidence interval (CI), 62–81] with stringent CR rate of 28% (95% CI, 19–38). After median follow-up of 10.7 months, median DOR was 11 months (95% CI, 10.3–11.4) in responders (partial response or better) and 19 months [95% CI, 11.4 months, not estimable (NE)] in patients who achieved stringent CR. Serious adverse reactions occurred in 67% of 127 patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively, leading to a Risk Evaluation and Mitigation Strategy. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4%, with two fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% (3/127), with two fatalities.
Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants
Authors: Hofmann Marco H. , Gerlach Daniel , Misale Sandra , Petronczki Mark , Kraut Norbert
Published: January 2022

KRAS is the most frequently mutated oncogene, harboring mutations in approximately one in seven cancers. Allele-specific KRASG12C inhibitors are currently changing the treatment paradigm for patients with KRASG12C-mutated non–small cell lung cancer and colorectal cancer. The success of addressing a previously elusive KRAS allele has fueled drug discovery efforts for all KRAS mutants. Pan-KRAS drugs have the potential to address broad patient populations, including KRASG12D-, KRASG12V-, KRASG13D-, KRASG12R-, and KRASG12A-mutant or KRAS wild-type–amplified cancers, as well as cancers with acquired resistance to KRASG12C inhibitors. Here, we review actively pursued allele-specific and pan-KRAS inhibition strategies and their potential utility.

Significance:

Mutant-selective KRASG12C inhibitors target a fraction (approximately 13.6%) of all KRAS-driven cancers. A broad arsenal of KRAS drugs is needed to comprehensively conquer KRAS-driven cancers. Conceptually, we foresee two future classes of KRAS medicines: mutant-selective KRAS drugs targeting individual variant alleles and pan-KRAS therapeutics targeting a broad range of KRAS alterations.
RAS at 40: Update from the RAS Initiative
Authors: Nissley Dwight V. , McCormick Frank
Published: January 2022

The RAS Initiative was launched in 2013 to address unmet clinical needs of patients with KRAS-driven cancers. The Initiative is based at Frederick National Laboratory for Cancer Research in Frederick, MD, and involves multiple collaborations with the RAS research community in academia and industry with the shared goal of developing RAS therapies.
A Prospectivly Randomized Phase-II Trial of Axitinib versus Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma (BERAT Study)
Authors: Grünwald Viktor , Hilser Thomas , Meiler Johannes , Goebell Peter J. , Ivanyi Philipp , Strauss Arne , Hartmann Arndt , Bedke Jens , Bergmann Lothar
Published: January 2022

Introduction: Inhibition of neo-angiogenesis is a cornerstone of medical treatment in metastatic renal cell carcinoma (mRCC). While 1st line therapies were previously dominated by inhibitors of the vascular endothelial growth factor axis, 2nd line options were less clearly defined. We investigated the role of everolimus (EVE) or a tyrosine kinase inhibitor (TKI) in 2nd line treatment of mRCC patients. Methods: Key inclusion criteria were measurable mRCC, ECOG 0–1, IMDC risk: good or intermediate and adequate organ function. Patients who progressed on or were intolerant to bevacizumab + interferon were subject for randomization between TKI and EVE treatment. Cross-over occurred at time of progression during 2nd line treatment. Improvement of 2nd line progression-free survival (PFS) rate (PFR) at 6 months from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, objective response rate (ORR), overall survival (OS), safety, and patient reported outcomes. Results: In 2012–2015, a total of 22 patients were included. The study was stopped for poor accrual. Ten patients (46%) were randomized to receive 2nd line treatment with EVE (n = 5) or axitinib (n = 4)/sunitinib (n = 1). ECOG 0 was recorded in 20% (EVE) and 60% (TKI). Severe adverse events occurred in approx. 60% in each arm. ORR was 1/5 (20%) for TKI and 0/5 (0%) for EVE. PFR at 6 months was 20% in each arm. Median PFS was 3.7 months (EVE) and 2.2 months (TKI) (hazard ratio [HR] 1.0 [95% confidence interval [CI]: 0.26–3.85]). The OS was comparable between arms HR 1.12 (95% CI: 0.27–4.61). Conclusion: The rapid change of the treatment landscape, the limited use of bevacizumab and interferon in 1st line and the duration of 1st line treatment jeopardized BERAT trial recruitment. The small number of patients is a major limitation of our trial. Our observation indicated the poor prognosis in progressive patients and the limited efficacy of TKI or mTOR inhibitors in 2nd line treatment.
Pemulihan Ekonomi Nasional di Masa Pandemi Covid-19 Melalui Trans-formasi Strategi Bisnis UMKM
Authors: Hildawati
Published: January 2022

Prior to the Covid-19 pandemic, UMKM contributed to Indonesia's GDP up to 60%. This fact shows that it has been proven to be able to reduce poverty and be able to absorb more workers than other business entities, thereby reducing unemployment. The main problem of this research is how is the transformation of UMKM business strategy in the recovery of the national economy during the Covid-19 pandemic? The purpose of this study is to describe that by transforming business strategies, UMKM have the potential for national economic recovery during the Covid-19 pandemic. This research is a qualitative descriptive study. The data collection technique used is literature study. Sources of data in this study using textbooks, articles, journals and statistical data. Data analysis technique is descriptive analysis. The results of the study show that in dealing with the Covid-19 pandemic, one of the important steps that the government can take for the recovery of the national economy is to pay attention to the growth and development of UMKM in Indonesia. Along with the current digitalization era, to realize innovative, productive and adaptive UMKM in the midst of the Covid-19 pandemic, UMKM need to transform digital-based business strategies. The contributions of this research include theoretical contributions and methodological contributions. The implication of this research is that the transformation of business strategy is a simple concept that can be carried out in the recovery of the national economy during the Covid-19 pandemic.
Pembuktian Strategi Pengarusutamaan Gender (PuG): Analisis Capaian Indeks Pemberdayaan Gender di Indonesia
Authors: Yuslin Hasnidar
Published: January 2022

This study aims to prove the Gender Mainstreaming strategy which is analyzed from the achievements of the Gender Empowerment Index from 2010 to 2020. To prove the Gender Mainstreaming strategy, the author uses an index measurement approach from the indicators forming the Gender Empowerment Index which is then analyzed descriptively. It was found that the implementation of the Gender Mainstreaming strategy in Indonesia has not been optimal. The average achievement of the gender empowerment index from 2010 to 2020 was 71.39, which is still far from the perfect ratio of 100. Judging from its forming indicators, it was found that the representation of women in parliament from 2010 to 2020 was still below 30 percent, then women as the professional workforce are still growing at 40 percent which has not yet reached the 50 percent equality level, and the contribution of women's income has experienced an increasing trend which reflects that women have been included in the workforce, but the increase has been slow.
Analisis Keterkaitan Antar Industri di Sumatera Utara dan Pengaruhnya terhadap Perekonomian Indonesia Tahun 2016 (Analisis IO dan IRIO)
Authors: Arifah Luthfi Fajar , Sunarjo Deden Achmad
Published: January 2022

Sumatera Utara memiliki pengaruh terhadap perekonomian Indonesia, karena provinsi ini termasuk kedalam lima kontributor terbesar terhadap perekonomian Indonesia. Oleh karena itu, perlu diketahui industri-industri yang mampu menjadi leading sector dan industri unggulan untuk meningkatkan potensi perekonomian Sumatera Utara. Tujuan penelitian ini adalah untuk mengetahui keterkaitan antar industri, menentukan industri unggulan, dan dampak perekonomian Sumatera Utara terhadap provinsi lain di Indonesia. Selain itu, penelitian ini dilakukan untuk mengetahui provinsi unggulan di Indonesia. Data yang digunakan dalam penelitian ini adalah Tabel I-O Sumatera Utara Tahun 2016 dan Tabel IRIO Indonesia Tahun 2016. Data diperoleh dari BPS. Data dianalisis menggunakan analisis angka pengganda, indeks daya penyebaran dan indeks daya kepekaan. Hasil penelitian menunjukkan bahwa Industri Makanan dan Minuman merupakan leading sector dan merupakan salah satu industri unggulan di Sumatera Utara. Selain itu, hasil penelitian menunjukkan bahwa Provinsi Sumatera Utara merupakan salah satu Provinsi unggulan di Indonesia dan memiliki dampak terbesar terhadap output Provinsi DKI Jakarta.
Post–ST‐Segment–Elevation Myocardial Infarction Platelet Reactivity Is Associated With the Extent of Microvascular Obstruction and Infarct Size as Determined by Cardiac Magnetic Resonance Imaging
Authors: Massalha Eias , Oren Daniel , Goitein Orly , Brodov Yafim , Fardman Alex , Younis Anan , Berkovitch Anat , Raibman‐Spector Shir , Konen Eli , Maor Elad , Fefer Paul , Segev Amit , Beigel Roy , Matetzky Shlomi
Published: January 2022

Background

Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST‐segment–elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO.

Methods and Results

We prospectively evaluated 105 patients in 2 distinct periods (2012–2013 and 2016–2018) who presented with first ST‐segment–elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO (
P
<0.01 for each). Adjusted multivariable logistic regression model revealed that suboptimal response to DAPT is significantly associated with both greater late gadolinium enhancement (
P
<0.01) and MVO extent (odds ratio, 3.7 [95% CI, 1.3–10.5];
P
=0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1‐year follow‐up (37% versus 11%;
P
<0.01).

Conclusions

In patients undergoing primary percutaneous coronary intervention for ST‐segment–elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.
Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders
Authors: Wiertsema Clarissa J. , Jaddoe Vincent W. V. , Mulders Annemarie G. M. G. J. , Gaillard Romy
Published: January 2022

Background

Offspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life.

Methods and Results

In a population‐based cohort among 4777 mother–offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02–0.31] and 0.23 [95% CI, 0.08–0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (
P
values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (
P
values <0.05), with a comparable strength as maternal–offspring associations.

Conclusions

Gestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal–offspring and paternal–offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect.
Taming Digital Monopolies: A Comparative Account of the Evolution of Antitrust and Regulation in the European Union and the United States
Authors: Monti Giorgio
Published: January 2022

This paper offers a comparative account of how the European Union and the United States surveil dominant internet players in light of recent enforcement efforts by U.S. antitrust agencies and ongoing discussions about regulating digital giants in both jurisdictions. After setting out themes for comparative analysis, the paper turns to the two actions initiated in the United States against Google: the one filed by the Department of Justice (DOJ) is similar in focus to the European Commission’s Android decision and the one led by the State of Texas focuses on advertising markets in a manner similar to the European Commission’s AdSense decision. We observe that while there are similar intuitions about anticompetitive conduct in the manner both jurisdictions address the issues, the framing of the competition problem by the U.S. agencies is more sophisticated in relation to the understanding of the markets, the theories of harm, and the design of forward-looking remedies. The paper then compares the Commission’s proposal for a Digital Markets Act with several Bills proposing platform regulation presently discussed in the United States, examining what the two systems have in common, what they may learn from each other, and what regulatory gaps remain.
Alternative diagnoses and demographics associated with a raised quantitative faecal immunochemical test in symptomatic patients
Authors: Johnstone Mark S , Miller Gillian , Pang Grace , Burton Paul , Kourounis Georgios , Winter Jack , Crighton Emilia , Mansouri David , Witherspoon Paul , Smith Karen , McSorley Stephen T
Published: January 2022

Background

The faecal immunochemical test (FIT) has proven utility for colorectal cancer detection in symptomatic patients. However, most patients with a raised faecal haemoglobin (f-Hb) do not have colorectal cancer. We investigated alternative diagnoses and demographics associated with a raised f-Hb in symptomatic patients.

Methods

A retrospective, observational study was performed of patients with FIT submitted between August 2018 to January 2019 in NHS Greater Glasgow and Clyde followed by colonoscopy. Colonoscopy/pathology reports were searched for alternative diagnoses. Covariables were compared using the χ 2 test. Multivariate binary logistic regression identified independent predictors of a raised f-Hb.

Results

1272 patients were included. In addition to colorectal cancer (odds ratio (OR), 9.27 (95% confidence interval (CI): 3.61–23.83; p < 0.001)), older age (OR, 1.52 (95% CI: 1.00–2.32; p = 0.05)), deprivation (OR, 1.54 (95% CI: 1.21–1.94; p < 0.001)), oral anticoagulants (OR, 1.78 (95% CI: 1.01–3.15; p = 0.046)), rectal bleeding (OR, 1.47 (95% CI: 1.15–1.88; p = 0.002)), advanced adenoma (OR, 7.52 (95% CI: 3.90–14.49; p < 0.001)), non-advanced polyps (OR, 1.78 (95% CI: 1.33–2.38; p < 0.001)) and inflammatory bowel disease (IBD) (OR, 4.19 (95% CI: 2.17–8.07; p < 0.001)) independently predicted raised f-Hb. Deprivation (Scottish Index of Multiple Deprivation (SIMD) 1-2: OR, 2.13 (95% CI: 1.38–3.29; p = 0.001)) independently predicted a raised f-Hb in patients with no pathology found at colonoscopy.

Conclusions

An elevated f-Hb is independently associated with older age, deprivation, anticoagulants, rectal bleeding, advanced adenoma, non-advanced polyps and IBD in symptomatic patients. Deprivation is associated with a raised f-Hb in the absence of pathology. This must be considered when utilising FIT in symptomatic patients.
Modern slavery in global value chains: A global factory and governance perspective
Authors: Caspersz Donella , Cullen Holly , Davis Matthew C. , Jog Deepti , McGaughey Fiona , Singhal Divya , Sumner Mark , Voss Hinrich
Published: January 2022

‘Modern slavery’ describes various forms of severe relational labour exploitation. In the realm of global value chains and global factories that are led by multinational enterprises, modern slavery encompasses practices such as forced labour and debt bondage. Multinational enterprises organise and orchestrate global value chains into global factories that are highly adaptive to market pressures and changes in the external environment. We employ the global factory framework to conceptualise when and how global value chains become more vulnerable to modern slavery. We argue that combinations of the three global value chain characteristics: complexity, appropriation arrangements, and obligation cascadence, jointly form an environment in which modern slavery can evolve and take root. The degree to which forms of modern slavery become visible and recognisable depends on the particular combination of these characteristics. External factors can moderate the relationship between these factors (e.g. involvement of non-governmental organisations) or exaggerate their effect (e.g. a pandemic).