bluuebunny/crossref_metadata_2025 huggingface dataset:
Presence of Brucella spp. in Milk and Dairy Products: A Comprehensive Review and Its Perspectives
Authors: Islam Md. Sadequl , Islam Md. Ariful , Rahman Md. Moshiur , Islam Khaleda , Islam Md. Mominul , Kamal Md. Murtuza , Islam Md. Nazrul
Published: April 2023

Consuming raw milk and milk-based products that have not been produced under strict control conditions can cause brucellosis, a highly contagious zoonotic disease. It is a significant global public health concern, particularly in regions with poor management and limited resources, such as Latin America, North and East Africa, the Middle East, and South and Central Asia. The study aims to summarize the occurrence of human brucellosis linked to milk and milk products and the presence of Brucella species in dairy foods. To achieve this goal, a meta-analysis was conducted on 69 studies ranging from 2001 to 2022, which were categorized into two groups: the incidence of Brucella species in milk and milk products and the prevalence of human brucellosis resulting from the consumption of contaminated milk. The following milk and milk products showed the highest incidence of Brucella species: cow milk (1.86%–81.7%), buffalo milk (10.4%–61.67%), camel milk (0%–24%), goat milk (0%–88.8%), and cheese (0%–39.1%). Consuming unpasteurized milk and milk products has been identified as the leading cause of human brucellosis, with incidence rates varying from 33.9% to 100%. Several human brucellosis cases have been linked to consuming raw milk and cheese in Spain, Israel, and other countries. Various serological techniques are employed to detect Brucella-specific antibodies in milk. The milk ring test (MRT) and enzyme-linked immunoassay (ELISA) are the two most widely utilized methods for detecting these antibodies in milk. Recently developed dual biosensors are a powerful approach for early diagnosis of Brucella from milk. Real-time PCR can rapidly detect organisms, reducing the risk of lab contamination and false positive results. To prevent and control brucellosis, essential steps include proper pasteurization of milk and dairy products, using the milk ring test (MRT) to detect Brucella in individual and bulk milk, immunization, education, and increasing public awareness of the disease. The consumption of raw milk and milk-made products that are not produced under strictly controlled conditions poses a significant risk to human health, mainly due to the high incidence of Brucella contamination. Therefore, ensuring strict control measures in producing milk and milk-made products is crucial to preventing the spread of this disease and safeguarding human health.
The Relationship betweenE-Semigroups andR-Semigroups
Authors: Gu Ze
Published: April 2023

A semigroup is called anE-semigroup (R-semigroup) if the set of all idempotents (the set of all regular elements) forms a subsemigroup. In this paper, we introduce the concept ofV-semigroups and establish the relationship between the three classes of semigroups.
Synergistic Interaction between Boesenbergia rotunda (L.) Mansf. Essential Oil and Cloxacillin on Methicillin‐Resistant Staphylococcus aureus (MRSA) Inhibition
Authors: Apinundecha Chittadech , Teethaisong Yothin , Suknasang Siriporn , Ayamuang Intu-orn , Eumkeb Griangsak
Published: April 2023

Currently, antibiotic resistance is widespread among bacteria. This problem requires greater awareness because bacterial resistance increases, reducing antibiotic use effectiveness. Consequently, new alternative treatments are needed because the treatment options for these bacteria are limited. This work aims to determine the synergistic interaction and mechanism of action of Boesenbergia rotunda essential oil (BREO) against methicillin‐resistant Staphylococcus aureus (MRSA). Gas chromatography‐mass spectrometry identified 24 BREO chemicals (GC‐MS). The main components of BREO were β‐ocimene (36.73%), trans‐geraniol (25.29%), camphor (14.98%), and eucalyptol (8.99%). BREO and CLX inhibited MRSA DMST 20649, 20651, and 20652 with a minimum inhibitory concentration (MIC) of 4 mg/mL and 512 µg/mL, respectively. The checkerboard method and the time‐kill assay revealed synergy between BREO and CLX with fractional inhibitory concentration (FIC) <0.5 and log reduction >2log10 CFU/mL at 24 hours compared to the most effective chemical. BREO inhibited biofilm formation and increased membrane permeability. Exposure alone to BREO or in combination with CLX inhibited biofilm formation and increased cytoplasmic membrane (CM) permeability. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results revealed that alterations in the cell walls, cytoplasmic membrane, and leakage of intracellular components of MRSA DMST 20651 after treatment with BREO alone and in combination with CLX were observed. These results indicate that BREO synergizes and could reverse the antibacterial activity of CLX against MRSA strains. The synergy of BREO may lead to novel drug combinations that increase the effectiveness of antibiotics against MRSA.
Electroencephalogram-Based Brain Connectivity Analysis in Prolonged Disorders of Consciousness
Authors: Wu Yuzhang , Li Zhitao , Qu Ruowei , Wang Yangang , Li Zhongzhen , Wang Le , Zhao Guangrui , Feng Keke , Cheng Yifeng , Yin Shaoya
Published: April 2023

Background. Prolonged disorders of consciousness (pDOC) are common in neurology and place a heavy burden on families and society. This study is aimed at investigating the characteristics of brain connectivity in patients with pDOC based on quantitative EEG (qEEG) and extending a new direction for the evaluation of pDOC. Methods. Participants were divided into a control group (CG) and a DOC group by the presence or absence of pDOC. Participants underwent magnetic resonance imaging (MRI) T1 three-dimensional magnetization with a prepared rapid acquisition gradient echo (3D-T1-MPRAGE) sequence, and video EEG data were collected. After calculating the power spectrum by EEG data analysis tool, DTABR (

δ
+
θ

/

α
+
β

ratio), Pearson’s correlation coefficient (Pearson

r

), Granger’s causality, and phase transfer entropy (PTE), we performed statistical analysis between two groups. Finally, receiver operating characteristic (ROC) curves of connectivity metrics were made. Results. The proportion of power in frontal, central, parietal, and temporal regions in the DOC group was lower than that in the CG. The percentage of delta power in the DOC group was significantly higher than that in the CG, the DTABR in the DOC group was higher than that in the CG, and the value was inverted. The Pearson

r

of the DOC group was higher than that of CG. The Pearson

r

of the delta band (

Z
=
−
6.71

,

P
<
0.01

), theta band (

Z
=
−
15.06

,

P
<
0.01

), and alpha band (

Z
=
−
28.45

,

P
<
0.01

) were statistically significant. Granger causality showed that the intensity of directed connections between the two hemispheres in the DOC group at the same threshold was significantly reduced (

Z
=
−
82.43

,

P
<
0.01

). The PTE of each frequency band in the DOC group was lower than that in the CG. The PTE of the delta band (

Z
=
−
42.68

,

P
<
0.01

), theta band (

Z
=
−
56.79

,

P
<
0.01

), the alpha band (

Z
=
−
35.11

,

P
<
0.01

), and beta band (

Z
=
−
63.74

,

P
<
0.01

) had statistical significance. Conclusion. Brain connectivity analysis based on EEG has the advantages of being noninvasive, convenient, and bedside. The Pearson

r

of DTABR, delta, theta, and alpha bands, Granger’s causality, and PTE of the delta, theta, alpha, and beta bands can be used as biological markers to distinguish between pDOC and healthy people, especially when behavior evaluation is difficult or ambiguous; it can supplement clinical diagnosis.
Simulation Experiment Study on Impacting the δD Value of Aromatic Compounds
Authors: Duan Yi , Wu Yingzhong , Xing Lantian , Wu Yingqin , Zhao Yang , Li Zhongping , Ma Lanhua
Published: April 2023

Little is known about the effects of sedimentary environment and maturity on δD values of aromatic compounds deposited in geological bodies. Our simulation experiments showed that the δD value of pyrolytic polycyclic aromatic hydrocarbons (PAHs) was significantly different between the studied samples from high and low latitude regions. Comparative studies showed that the δD values of PAHs produced by pyrolysis were related to those of water in the two regions. With increasing maturity, the δD value of the PAHs becomes higher. Additionally, it was observed that some PAHs exhibited a propensity to increase the δD value upon demethylation. The thermodynamic fractionation of hydrogen isotopes between the PAHs produced by pyrolysis and both the n-alkanes and methane produced by pyrolysis indicated that the hydrogen isotopic value of the PAHs was higher than that of the n-alkanes or methane. The long-chain alkylbenzene produced by pyrolysis has a higher mean δD value compared with the n-alkanes produced by pyrolysis, but it is lower than that of the PAHs in the same sample. The lowest δD value among the aromatics was found in the ring A monoaromatic steroids produced by pyrolysis. The low δD values of these steroids should originate from isotopic fractionation during isoprenoid lipid biosynthesis.
Learning Diverse Policies with Soft Self‐Generated Guidance
Authors: Wang Guojian , Wu Faguo , Zhang Xiao , Liu Jianxiang
Published: April 2023

Reinforcement learning (RL) with sparse and deceptive rewards is a significant challenge because nonzero rewards are rarely obtained, and hence, the gradient calculated by the agent can be stochastic and without valid information. Recent work demonstrates that using memory buffers of previous experiences can lead to a more efficient learning process. However, existing methods usually require these experiences to be successful and may overly exploit them, which can cause the agent to adopt suboptimal behaviors. This study develops an approach that exploits diverse past trajectories for faster and more efficient online RL, even if these trajectories are suboptimal or not highly rewarded. The proposed algorithm merges a policy improvement step with an additional policy exploration step by using offline demonstration data. The main contribution of this study is that by regarding diverse past trajectories as guidance, instead of imitating them, our method directs its policy to follow and expand past trajectories, while still being able to learn without rewards and gradually approach optimality. Furthermore, a novel diversity measurement is introduced to maintain the diversity of the team and regulate exploration. The proposed algorithm is evaluated on a series of discrete and continuous control tasks with sparse and deceptive rewards. In comparison with the existing RL methods, the experimental results indicate that our proposed algorithm is significantly better than the baseline methods in terms of diverse exploration and avoiding local optima.
Accident Detection and Flow Prediction for Connected and Automated Transport Systems
Authors: Zhang Yi , Liu Fang , Yue Sheng , Li Yuxuan , Dong Qianwei
Published: April 2023

Effective accident detection and traffic flow forecasting are of great importance for quick respond, impact elimination and intelligent control of the traffic flow consisting of autonomous vehicles. This paper proposes a traffic accident detection method for connected and automated transport systems by conducting a grid-based parameter extracting and SVC-based traffic state classification. Allowing for the dynamic spread of traffic flow over time, from upstream to downstream and from accident lanes to other lanes, a spatiotemporal Markov model is established to predict the evolution of traffic flow after accident by introducing the grid as state detection unit and fitting the spatiotemporal evolution with the parameter space mean speed to match the need of both detection accuracy and monitoring scope. Compared with actual accident data, the validation results indicate that the proposed methods present a good performance in accident detection with the accident detection rate as 87.72% and a higher precision rate than both SVM (support vector machine) and ANN (artificial neural network) models in traffic flow prediction. With the active traffic accident identification and dynamic traffic flow prediction, it is beneficial to shorten detection time, reduce possible impacts of traffic accidents and carbon emissions from congestion. The methods can be implied to traffic state recognition and traffic flow prediction, which is one of the significant sections of connected and automated transport systems, and serve as references for accident handling and urban traffic management.
A Fuzzy Intelligent Computing Approach for Energy/Voltage Control of Microgrids
Authors: Xu Aoqi , Bouteraa Yassine , Kausar Nasreen , Mohammadzadeh Ardashir , Pamucar Dragan , Abdullah Salman Mohammed
Published: April 2023

The control and energy management problems of microgrids (MGs) are challenging due to the high level of uncertainties and disturbances such as changes in demands, mechanical powers, and solar energies. So, intelligent computing is needed to be developed for these systems. This paper uses an optimal and robust fuzzy controller for automatic voltage and frequency regulation. The fuzzy logic develops the resistance against uncertainties and disturbances such as irradiation, wind power changes, and load demand variation. The introduced controller uses appropriate and effective criteria that include rising time, settling time, overshoot, and the degree of resistance of the control system to uncertainties and perturbation effects. Through simulations and compassion with conventional regulators, the better accuracy of the suggested approach is demonstrated.
Size and Morphology-Mediated Antiproliferative Activity of Hydroxyapatite Nanoparticles in Human Breast Cancer Cells
Authors: Fukada Moeko , Chhetri Tilak , Suresh Agasthya , Upendran Anandhi , Afrasiabi Zahra
Published: April 2023

Hydroxyapatite nanoparticles (nHAPs) have been recognized for potent antitumor effects in certain cancer cells, making them good candidates as drug delivery agents and tumor therapeutics with fewer than normal side effects. This study is aimed to correlate cell proliferation inhibition with the size and morphology of nHAPs in a human breast cancer cell line as well as in normal tissue cells. We present our in vitro experimental evidence that nHAPs with sizes smaller than 50 nm have high inhibitory activity against human MCF-7 breast cancer cell lines. Based on our experimental data, normal fibroblast cells (NIH 3T3) were relatively more viable upon treatment with the nanoconstructs. The present study indicates that nHAPs can be engineered as nontoxic specific inhibitors as efficient breast cancer therapeutics in humans.
Measuring Quality of Life in Residential Aged Care Using the EQ-5D-5L: A Cross-Sectional Study on the Impact of Cognition Level and Proxy Perspective on Interrater Agreement
Authors: Hutchinson Claire , Whitehurst David G. T. , Crocker Matthew , Lay Kiri , Engel Lidia , Ratcliffe Julie
Published: April 2023

Quality of life (QoL) is an important outcome in aged care, but self-report is not always possible due to the high prevalence of cognitive impairment in older aged care residents. This study aims to assess the impact of family member proxy perspective (proxy-proxy or proxy-person) on interrater agreement with resident self-report by different cognition levels. The influence of proxy perspective and cognition level is a significant gap in the extant literature which this study seeks to address. A cross-sectional study was undertaken with residents classified into cognition subgroups according to the Mini Mental State Examination. Residents completed the self-report EQ-5D-5L, a well-established generic measure of health-related quality of life (HRQoL). Family member proxies completed EQ-5D-5L proxy version 1 (proxy-proxy perspective, where the proxy responds based on their own opinions) and proxy version 2 (proxy-person perspective, where the proxy responds as they believe the person would). Interrater agreement was assessed using the concordance correlation coefficient (CCC) for utility scores and the weighted kappa for dimension-level responses. Sixty-three residents (n = 22 no cognitive impairment, n = 27 mild impairment, and n = 14 moderate impairment) and proxies participated. EQ-5D-5L utility scores were lower for proxies compared with residents (self-report = 0.522, proxy-proxy = 0.299, and proxy-person = 0.408). Interrater agreement with self-report was higher for proxy-person (CCC = 0.691) than for proxy-proxy (CCC = 0.609). Agreement at the dimension level was higher for more easily observable dimensions, such as mobility, compared to less observable dimensions, such as anxiety/depression. Resident self-reported and proxy family member-reported HRQoL assessments, using the EQ-5D-5L, are different but may be more closely aligned when the proxy is specifically guided to respond from the person’s perspective. Further research is needed to address the impact of divergences in self-report and proxy-report ratings of HRQoL for quality assessment and economic evaluation in aged care.
Complex Dynamic Analysis, Circuit Design and Simplified Predefined Time Synchronization for a Jerk Absolute Memristor Chaotic System
Authors: Liu Jindong , Wang Zhen , Tian Huaigu , Xie Fei
Published: April 2023

In this parper, a 4D absolute memristor Jerk chaotic system is proposed. Firstly, complex dynamics are studied by phase diagram, Poincaré section, power spectrum, bifurcation diagram, 0-1 test, and Lyapunov exponent spectrum. Then, the period doubling bifurcation, degradation, and offset boosting are revealed. For the feasibility of practical application, the analog circuit and FPGA digital circuit are designed. Finally, a simplified predefined time synchronization scheme is proposed; comparing with the full control input synchronization scheme, the simplified predefined time synchronization scheme can not only reduce the controller inputs but also predefine the synchronization time.
A New Unsaturated Aliphatic Anhydride from Aspergillus candidus T1219W1, an Endophytic Fungus, from Pittosporum mannii Hook f.
Authors: Talle Juidzou Gaëlle , Gisèle Mouafo Anoumedem Elodie , Kehdinga Sema Denis , Flaure Tsague Tankeu Virginie , Bosco Leutcha Peron , Yetendje Chimi Larissa , Paul Dzoyem Jean , Kouam Fogue Simeon , Sewald Norbert , Choudhary M. Iqbal , Meli Lannang Alain
Published: April 2023

A new unsaturated aliphatic anhydride derivative (Z)-(12Z)-heptadec-12-enoic-2′-hydroxypropanoic anhydride (1) and ten known compounds, three flavonoids (2–4), two terphenyllins (5-6), four triterpenoids (7-8, 10-11), and one n-fatty acid (9), were isolated from the EtOAc extract of Aspergillus candidus T1219W1, an endophytic fungus, inhabiting Pittosporum mannii. All the isolated compounds were characterized using 1D- and 2D-NMR and HR-EI experiments together with the reported literature. p-terphenyls are suggested to be the chemophenetic marker of the genus Aspergillus. The ethyl acetate crude extract as well as some isolated compounds of A. candidus was assayed for antibiofilm activity, anti-inflammatory (ROS) activity, and cytotoxicity on brine shrimps and the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay on 3T3 cell lines. The tested sample showed good antibiofilm activity with the lowest MBEC50 obtained at 64 μg/mL. Compounds showed low anti-inflammatory activity even at high concentration (250 μg·mL−1 with an IC50 of 59.6 ± 0.1 μg·mL−1) with moderate cytotoxicity on brine shrimps at high concentration (1000 μg·mL−1, with 46.67% mortality). However, no cytotoxic activity was observed against 3T3 cell lines.
Effect of Season and Increased Temperature on Survival, Roe Enhancement, and Reproductive Cycle of the Green Sea Urchin (Strongylocentrotus droebachiensis) Collected from Four Relatively Close Sites in Northern Norway
Authors: James Philip , Evensen Tor , Johansson Gunhild
Published: April 2023

A series of three trials were conducted in the North of Norway at different times of the year. The trials consisted of harvesting sea urchins from four sites, situated within 5 km of each other and then holding them in land-based enhancement facilities. They were held at ambient seawater temperatures as well as ambient plus 3.0°C. Samples were taken from the wild at the time of collection and at the end of the enhancement period as well as from the enhanced sea urchins from each site. Results showed that utilising the sea urchins from a variety of sites, even from areas where there is an abundance of sea urchins (sea urchin barrens) and the Gonad Index (GI) is almost always low, is viable in terms of the final, post roe enhancement GI. The results of the study indicate that differences in initial and final GI and the increase in GI between the sites, despite the relatively close proximity, show site selection is most likely not as important as ease of harvesting and sea urchin availability and the positive environmental impact from removal of sea urchins and these are the factors that harvesting strategies should focus on. The study has shown that it is possible to have a relatively consistent roe enhancement from S. droebachiensis from the North of Norway regardless of seasonality (time of year), site selection, and initial GI. Relatively small changes (up to 3°C) in the seawater temperature appear to have a slightly negative impact on enhancement efforts. However, this may vary when larger differences in temperature are experienced.
Range-Anxiety Reduction Strategies for Extended-Range Electric Vehicle
Authors: Lakshmi Prasad Shana , Gudipalli Abhishek
Published: April 2023

Transportation is the leading source of logistics, and people contribute the significant primary emissions for increasing global warming, so we should avoid such a situation and concentrate on zero emissions. The range of the vehicle is the major problem (range-anxiety) in electric vehicles. Nowadays, researchers focus on range extender optimization since range extenders significantly improve the range of the vehicle with an auxiliary power unit (APU), which can prove consumer satisfaction. However, range extenders can recover energy by proposing the various configurations and systems of extended-range electric vehicles (EREV). Many industries and researchers summarize these efforts to optimize and find the solution for range-extenders. This paper reviewed the most suitable technologies for energy recovery and state-of-the-art topological constructions. The analysis of the study primarily concentrated on optimizing the cost of the systems, fewer emissions, and more fuel economy. The research is based on the range-extenders evaluation and summary for electric vehicles to guide automakers and researchers to invent other state-of-the-art configurations and topologies to obtain optimized EV ranges, namely, enhanced functionality and fewer emissions. A survey on specific extend-range electric vehicles and classification of EREV technologies, the performance of APUs, different control strategies of energy management in EREVs, and various existing difficulties are discussed and further enhanced for the future researcher EREV forecast offered by advanced technologies.
Dynamic Path Optimization Based on Improved Ant Colony Algorithm
Authors: Cheng Juan
Published: April 2023

Dynamic path optimization is an important part of intelligent transportation systems (ITSs). Aiming at the shortcomings of the current dynamic path optimization method, the improved ant colony algorithm was used to optimize the dynamic path. Through the actual investigation and analysis, the influencing factors of the multiobjective planning model were determined. The ant colony algorithm was improved by using the analytic hierarchy process (AHP) to transform path length, travel time, and traffic flow into the comprehensive weight-influencing factor. Meanwhile, directional guidance and dynamic optimization were introduced to the improved ant colony algorithm. In the simulated road network, the length of the optimal path obtained by the improved ant colony algorithm in the simulation road network is 3.015, which is longer than the length of the optimal path obtained by the basic ant colony algorithm (2.902). The travel time of the optimal path obtained by the improved ant colony algorithm (376 s) is significantly shorter than that of the basic ant colony algorithm (416.3 s). The number of iterations of the improved ant colony algorithm (45) is less than that of the basic ant colony algorithm (58). In the instance network, the number of iterations of the improved ant colony algorithm (18) is less than that of the basic ant colony algorithm (26). The travel time of the optimal path obtained by the improved ant colony algorithm (377.1 s) is significantly shorter than that of the basic ant colony algorithm (426 s) and the spatial shortest distance algorithm (424 s). Compared with the basic ant colony algorithm and the spatial shortest distance algorithm, the results of the optimal path obtained by the improved ant colony algorithm were more accurate, and the effectiveness of the improved ant colony algorithm was verified.
A Double-Tuned Pendulum Mass Damper Employing a Pounding Damping Mechanism for Vibration Control of High-Rise Structures
Authors: Wang Wenxi , Yu Tianfu , Yang Zhilin , Zhang Hongyi , Hua Xugang
Published: April 2023

Recently, enhancing conventional tuned mass dampers (TMDs) with a pounding damping mechanism is demonstrated to be an efficient way for vibration control of flexible structures. In this paper, a double-tuned pendulum mass damper employing a pounding damping mechanism (DTPMD-PD) is proposed. DTPMD-PD dissipates energy through the collision between distributed balls with a smaller mass and viscoelastic (VE) boundary, which can effectively reduce noise during operation compared to conventional impact dampers. Moreover, DTPMD-PD utilizes a double-tuning mechanism, and its control performance is significantly enhanced. The motion equations of a multiple degree of freedom (MDOF) structure equipped with DTPMD-PD are formulated. Based on the H∞ optimization criterion, a numerical optimization is performed to obtain the optimal design parameters of DTPMD-PD. Additionally, the pounding dissipation capacity and the parametric identification of the impact force model are investigated through free pounding experiments, and the control performance and robustness of DTPMD-PD are experimentally studied in the laboratory. The results show that the proposed numerical modeling method has considerable accuracy through experimental verifications. The restitution coefficient of the pounding layer has a significant influence on the performance of proposed DTPMD-PD. Optimized DTPMD-PD has better effectiveness than conventional TMDs under harmonic and seismic loads.
Use of Finite Element Method for Free Convection of Nanofluids between a Rectangular Enclosure and a Sinusoidal Cylinder Using Buongiorno’s Two-Phase Model
Authors: Alhashash Abeer , Saleh Habibis
Published: April 2023

In this study, the free convection of nanofluids between a rectangular enclosure and a sinusoidal cylinder is numerically analyzed using the finite element method (FEM). Two-phase Buongiorno’s formulation was used to model the fluid layer, and Brinkman-Forchheimer equation was used to formulate the porous layer. The enclosure has a low temperature, while the cylinder is maintained at a high temperature. The governing equations are expressed in PDEs and converted into weak formulations (Galerkin FEM). In numerical simulations, the average concentration, the amplitude of undulated cylinder, the number of undulated, and the Rayleigh number are investigated. It is observed that the homogeneous nanofluid model could be valid for low heating intensity with higher waviness frequency and/or higher amplitude. The higher the alumina concentration, the higher the heat transfer rate. The heat transfer rate can be boosted by up to 13% by suspending 1% alumina particles. The heat transfer enhancement decreases with increasing the amplitude and/or increasing the waviness number.
A Degenerate Primer Design Method Based on Ant Colony Optimization
Authors: Wang Xianghe , Ning Jiaxu , Jiang Yueqiu , Liu Ruhui , Zhang Xinyuan , Wu Jiaxuan
Published: April 2023

For the existed biological degenerate primer design problem, a solution method based on an ant colony optimization algorithm is proposed, in which an optimization model considers primer coverage as well as degeneracy while allowing for a small number of base mismatches. Using the construction graph model, the algorithm makes full use of the dynamic change information during the iterative optimal path optimization process, strengthens the explored new path pheromone, and selects the primers that meet the constraints. The results of DNA template sequence matching experiments show that the degenerate primers designed by the proposed algorithm outperform existing approaches.
Atom Search Optimization-Based PV Array Reconfiguration Technique under Partial Shading Condition
Authors: Li Dahu , Zhou Hongyu , Zhou Yue , Rao Yuze , Yao Wei
Published: April 2023

Photovoltaic (PV) reconfiguration is an effective solution for reducing the hot spot effect caused by partial shadows on PV arrays. This paper proposed an efficient atom search optimization- (ASO-) based PV reconfiguration method. The analysis and comparison with the other four reconfiguration methods were performed by three evaluation criteria, which are mismatch loss, fill factor, and standard deviation, respectively. The conclusion can be drawn that the efficiency, rapidity, and reliability of ASO are superior to those of other methods. Besides, a moving cloud shadow mode of 9 × 9-scaled PV array is designed in this paper, which can be widely recommended to thoroughly study a PV reconfiguration approach.
Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer
Authors: Gou Xuxu , Kim Beom-Jun , Anurag Meenakshi , Lei Jonathan T. , Young Meggie N. , Holt Matthew V. , Fandino Diana , Vollert Craig T. , Singh Purba , Alzubi Mohammad A. , Malovannaya Anna , Dobrolecki Lacey E. , Lewis Michael T. , Li Shunqiang , Foulds Charles E. , Ellis Matthew J.
Published: April 2023

Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen–binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)–based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET–resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were concordantly inhibited by the selective RET inhibitor pralsetinib to a similar extent as the CDK4/6 inhibitor palbociclib. Together, these findings provide preclinical rationale for clinical evaluation of RET inhibition for the treatment of ESR1-TAF–driven ET-resistant breast cancer.

Significance:

Kinome analysis of ESR1 translocated and mutated breast tumors using drug bead-based mass spectrometry followed by drug-sensitivity studies nominates RET as a therapeutic target.

See related commentary by Wu and Subbiah, p. 3159
Supplementary Table 2 from Prevalence and Prognostic Significance of Malnutrition in Patients with Brain Metastasis
Authors: Liu Zheran , Zhang Yu , Pei Yiyan , He Yan , Yu Jiayi , Zhang Renjie , Wang Jingjing , Chong Weelic , Hai Yang , Peng Xingchen , Fang Fang
Published: April 2023

Supplementary Table 2 Baseline Characteristics of included patients stratified by CONUT (A), PNI (B), and NRI (C) categories.
Supplementary Table S2 from Early On-treatment Changes in Circulating Tumor DNA Fraction and Response to Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer
Authors: Tolmeijer Sofie H. , Boerrigter Emmy , Sumiyoshi Takayuki , Kwan Edmond M. , Ng Sarah W.S. , Annala Matti , Donnellan Gráinne , Herberts Cameron , Benoist Guillemette E. , Hamberg Paul , Somford Diederik M. , van Oort Inge M. , Schalken Jack A. , Mehra Niven , van Erp Nielka P. , Wyatt Alexander W.
Published: April 2023

Evidence for ctDNA estimates per patient per timepoint
Supplementary Figure S1 from G-CSF Is a Novel Mediator of T-Cell Suppression and an Immunotherapeutic Target for Women with Colon Cancer
Authors: Ray Anita L. , Saunders Apryl S. , Nofchissey Robert A. , Reidy Megan A. , Kamal Maria , Lerner Megan R. , Fung Kar-Ming , Lang Mark L. , Hanson Joshua A. , Guo Shaoxuan , Urdaneta-Perez Maria G. , Lewis Samara E. , Cloyde Michael , Morris Katherine T.
Published: April 2023

Supplementary Figure S1
Supplemental Figure 8 from Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor
Authors: Rossi Ferdinand , Liu Mengyuan , Tieniber Andrew , Etherington Mark S. , Hanna Andrew , Vitiello Gerardo A. , Param Nesteene J. , Do Kevin , Wang Laura , Antonescu Cristina R. , Zeng Shan , Zhang Jennifer Q. , DeMatteo Ronald P.
Published: April 2023

Supplemental Figure 8.Relative MYLK mRNA expression by qPCR in GIST PDGFRA D842V PDXs treated with vehicle(Veh) or imatinib (IM) for 2 weeks.
Supplementary Tables S1-S4 from Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort: Results from the Randomized SweBCG91RT Trial
Authors: Stenmark Tullberg Axel , Sjöström Martin , Niméus Emma , Killander Fredrika , Chang S. Laura , Feng Felix Y. , Speers Corey W. , Pierce Lori J. , Kovács Anikó , Lundstedt Dan , Holmberg Erik , Karlsson Per
Published: April 2023

Supplementary Table S1 Demographics of the training cohortsSupplementary Table S2 Immunscore modelSupplementary Table S3 Proliferative Index ModelSupplementary Table S4 Immunescore:Proliferative Index
Data from Early on-treatment changes in circulating tumor DNA fraction and response to enzalutamide or abiraterone in metastatic castration-resistant prostate cancer
Authors: Tolmeijer Sofie H. , Boerrigter Emmy , Sumiyoshi Takayuki , Kwan Edmond M. , Ng Sarah , Annala Matti , Donnellan Grainne , Herberts Cameron , Benoist Guillemette E. , Hamberg Paul , Somford Diederik M. , van Oort Inge M. , Schalken Jack A. , Mehra Niven , van Erp Nielka P. , Wyatt Alexander W.
Published: April 2023

Abstract
Purpose: Androgen receptor pathway inhibitors (ARPI) are standard of care for treatment-naive metastatic castration-resistant prostate cancer (mCRPC), but rapid resistance is common. Early identification of resistance will improve management strategies. We investigated whether changes in circulating tumor DNA (ctDNA) fraction during ARPI treatment are linked with mCRPC clinical outcomes. Experimental Design: Plasma cell-free DNA was collected from 81 patients with mCRPC at baseline and after 4-weeks of first-line ARPI treatment during two prospective multi-centre observational studies (NCT02426333;NCT02471469). CtDNA fraction was calculated from somatic mutations in targeted sequencing and genome copy number profiles. Samples were classified into detected vs. undetected ctDNA. Outcome measurements were progression-free survival (PFS) and overall survival (OS). Non-durable treatment response was defined as PFS ≤ 6 months. Results: CtDNA was detected in 48/81 (59%) baseline and 29/81 (36%) 4-week samples. CtDNA fraction for samples with detected ctDNA was lower at 4-weeks vs. baseline (median 5.0% vs. 14.5%, P=0.017). PFS and OS was shortest for patients with persistent ctDNA at 4 weeks (univariate hazard ratio 4.79 (95%CI, 2.62-8.77) and 5.49 (95%CI, 2.76-10.91), respectively), independent of clinical prognostic factors. For patients exhibiting change from detected to undetected ctDNA by 4-weeks, there was no significant PFS difference versus patients with baseline undetected ctDNA. CtDNA change had a positive predictive value of 88% and negative predictive value of 92% for identifying non-durable responses. Conclusions: Early changes in ctDNA% are strongly linked to duration of first-line ARPI treatment benefit and survival in mCRPC and may inform early therapy switches or treatment intensification.
Data from Granulocyte colony stimulating factor is a novel mediator of T cell suppression and an immunotherapeutic target for women with colon cancer
Authors: Ray Anita L. , Saunders Apryl S. , Nofchissey Robert A. , Reidy Megan A. , Kamal Maria , Lerner Megan R. , Fung Kar-Ming , Lang Mark L. , Hanson Joshua A. , Guo Shaoxuan , Urdaneta-Perez Maria G. , Lewis Samara E. , Cloyde Michael , Morris Katherine T.
Published: April 2023

Abstract
Purpose: Granulocyte colony stimulating factor (GCSF) enhances colon cancer development. This study defines the prevalence and effects of increased GCSF signaling in human colon cancers and investigates GCSF inhibition as an immunotherapeutic strategy against metastatic colon cancer. Experimental Design: Patient samples were used to evaluate GCSF and GCSF receptor (GCSFR) levels by immunohistochemistry with sera used to measure GCSF levels. PBMCs were used to assess the rate of GCSFR+ T cells and interferon γ (IFNγ) responses to chronic ex vivo GCSF. An immune competent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of GCSF inhibition (αGCSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry. Results: GCSF and GCSFR are increased in human colon cancer samples as compared to patient-matched normal colon. High patient serum GCSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express GCSFR at double the rate of T cells from controls. Prolonged GCSF exposure decreases T cell IFNγ production. Treatment with αGCSF shifts both the adaptive and innate compartments of the TME and increases survival (HR=0.46, p=0.0237) and tumor T cell infiltration, activity, and IFNγ response with greater effects in female mice. A negative correlation exists between serum GCSF levels and tumor infiltrating T cells in patient samples from women. Conclusions: These findings support GCSF as an immunotherapeutic target against colon cancer with greater potential benefit in women.
Data from A phase 2 study of epacadostat and pembrolizumab in patients with advanced sarcoma
Authors: Kelly Ciara M. , Qin Li-Xuan , Whiting Karissa A. , Richards Allison L. , Avutu Viswatej , Chan Jason E. , Chi Ping , Dickson Mark A. , Gounder Mrinal M. , Keohan Mary Louise. , Movva Sujana , Nacev Benjamin A. , Rosenbaum Evan , Adamson Travis , Singer Samuel , Bartlett Edmund K. , Crago Aimee M. , Yoon Sam S. , Hwang Sinchun , Erinjeri Joseph P. , Antonescu Cristina R. , Tap William D. , D'Angelo Sandra P.
Published: April 2023

Abstract
Purpose: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes. Experimental Design: This phase 2 study enrolled patients with advanced sarcoma into five cohorts including i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, ii) liposarcoma (LPS), iii) leiomyosarcoma (LMS), iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and v) other subtypes. Patients received epacadostat 100 mg twice daily plus pembrolizumab at 200 mg/dose every 3 weeks. The primary endpoint was best objective response rate (ORR), defined as complete response (CR) and partial response (PR), at 24 weeks by Response Evaluation Criteria In Solid Tumors (RECIST v.1.1). Results: Thirty patients were enrolled (60% male; median age 54 years [range, 24–78]). The best ORR at 24 weeks was 3.3% (PR, n=1 [leiomyosarcoma]; two-sided 95% CI, 0.1%–17.2%). The median PFS was 7.6 weeks (two-sided 95% CI: 6.9–26.7). Treatment was well tolerated. Grade 3 treatment-related adverse events occurred in 23% (n=7) of patients. In paired pre- and post-treatment tumor samples, no association was found between treatment and PD-L1 or IDO1 tumor expression or IDO-pathway–related gene expression by RNA sequencing. No significant changes in serum tryptophan or kynurenine levels were observed after baseline. Conclusions: Combination epacadostat and pembrolizumab was well tolerated and showed limited antitumor activity in sarcoma. Correlative analyses suggested that inadequate IDO1 inhibition was achieved.
Data from FDA Oncology Center of Excellence crowdsourcing initiative: outreach to the scientific community to identify research questions for pooled analyses of oncology clinical trial data
Authors: Schneider Julie A. , Eckstein Julia , Goldberg Kirsten B. , Ascione Mark C. , Bailey Thamar , Taylor Kimberly , Coffey Aisha M. , Satchi Darshini , Philips Howard , Sridhara Rajeshwari , Nair Abhilasha , Pazdur Richard , Theoret Marc R.
Published: April 2023

Abstract
The FDA Oncology Center of Excellence recently launched a crowdsourcing pilot to request ideas from the scientific community for research questions that FDA could address with pooled analyses of clinical trial data submitted to the agency for regulatory purposes. This effort builds on FDA’s track record of publishing pooled analyses to explore scientific questions that cannot be addressed in a single trial due to limited sample size. The research crowdsourcing pilot tested a new approach for obtaining external input on regulatory science activities, because FDA is generally unable to share patient-level data outside of the agency due to federal disclosure laws and regulations protecting different types of data submitted in regulatory applications. We received 29 submissions over the 28-day crowdsourcing campaign, including one research idea that we are exploring for possible follow up. Based on our experience with this pilot, we learned that crowdsourcing is a promising new approach to gather external input and feedback. We identified opportunities to build understanding in the external oncology community about the types of data typically included in regulatory applications and expand dissemination of published FDA pooled analyses to help inform future drug development and clinical practice.
Supplementary Figure 6 from BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis
Authors: Agarwal Sumit , Afaq Farrukh , Bajpai Prachi , Behring Michael , Kim Hyung-Gyoon , Varambally Amith , Chandrashekar Darshan S. , Peter Shajan , Diffalha Sameer Al , Khushman Moh'd , Seeber Andreas , Varambally Sooryanarayana , Manne Upender
Published: April 2023

S6. MYC regulates BZW2 in CRC cells.
Supplementary Figure 3 from BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis
Authors: Agarwal Sumit , Afaq Farrukh , Bajpai Prachi , Behring Michael , Kim Hyung-Gyoon , Varambally Amith , Chandrashekar Darshan S. , Peter Shajan , Diffalha Sameer Al , Khushman Moh'd , Seeber Andreas , Varambally Sooryanarayana , Manne Upender
Published: April 2023

S3. BZW2-knockdown reduces cell invasion.
Supplementary Figure 2 from BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis
Authors: Agarwal Sumit , Afaq Farrukh , Bajpai Prachi , Behring Michael , Kim Hyung-Gyoon , Varambally Amith , Chandrashekar Darshan S. , Peter Shajan , Diffalha Sameer Al , Khushman Moh'd , Seeber Andreas , Varambally Sooryanarayana , Manne Upender
Published: April 2023

S2. BZW2 expression in CRC.
Supplementary Data from BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis
Authors: Agarwal Sumit , Afaq Farrukh , Bajpai Prachi , Behring Michael , Kim Hyung-Gyoon , Varambally Amith , Chandrashekar Darshan S. , Peter Shajan , Diffalha Sameer Al , Khushman Moh'd , Seeber Andreas , Varambally Sooryanarayana , Manne Upender
Published: April 2023

Supplementary figure legends 1-8, and supplementary tables 1-5
Supplementary Data from T Cells Expressing a Modified FcγRI Exert Antibody-Dependent Cytotoxicity and Overcome the Limitations of CAR T-cell Therapy against Solid Tumors
Authors: Rasoulouniriana Diana , Santana-Magal Nadine , Gutwillig Amit , Farhat-Younis Leen , Tal Lior , Amar Sarah , Milyavsky Michael , Muddineni Siva Sai Naga Anurag , Solomon Neta , Shpilt Hana , Dotan Shahar , Pilpel Noam , Waskow Claudia , Feinmesser Meora , Rider Peleg , Carmi Yaron
Published: April 2023

Supplementary tables and figures
Figure S3 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

CAPRIN-1 is not expressed on the cell surface of hematologic cancer cells.
Figure S1 from Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950
Authors: Okano Fumiyoshi , Saito Takanori , Minamida Yoshitaka , Kobayashi Shinichi , Ido Takayoshi , Miyauchi Yasushi , Wasai Ukei , Akazawa Daisuke , Kume Masahiko , Ishibashi Masaki , Jiang Ke , Aicher Alexandra , Heeschen Christopher , Yonehara Tetsu
Published: April 2023

Anti-CAPRIN-1 antibodies
Supplementary File 10 from Integrative metatranscriptomic analysis reveals disease-specific microbiome-host interactions in oral squamous cell carcinoma
Authors: Jain Vinay , Baraniya Divyashri , Elhadedy Doaa E , Chen Tsute , Slifker Michael J. , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy Naidu , Fundakowski Christopher , Al-hebshi Nezar
Published: April 2023

Host gene-microbial genus global_correlations, rs>=0.6 and FDR=<0.05
Supplementary File 1 from Integrative metatranscriptomic analysis reveals disease-specific microbiome-host interactions in oral squamous cell carcinoma
Authors: Jain Vinay , Baraniya Divyashri , Elhadedy Doaa E , Chen Tsute , Slifker Michael J. , Alakwaa Fadhl , Cai Kathy Q. , Chitrala Kumaraswamy Naidu , Fundakowski Christopher , Al-hebshi Nezar
Published: April 2023

Quantity and quality of the DNA and RNA extracts and the seqeuncing libraries.
Supplementary Table 6 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

ST_6 ChIP-Seq Motif
Supplementary Table 3 from African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A
Authors: Siddappa Manjunath , Hussain Shahid , Wani Sajad A. , White Jason , Tang Hancong , Gray Jaimie S. , Jafari Hedieh , Wu Hsu-Chang , Long Mark D. , Elhussin Isra , Karanam Balasubramanyam , Wang Honghe , Morgan Rebecca , Hardiman Gary , Adelani Isaacson B. , Rotimi Solomon O. , Murphy Adam R. , Nonn Larisa , Davis Melissa B. , Kittles Rick A. , Hughes Halbert Chanita , Sucheston-Campbell Lara E. , Yates Clayton , Campbell Moray J.
Published: April 2023

ST_3 ATAC-Seq