bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus
Authors: Bao Shengfang , Huang Hua , Jin Yingying , Ding Fei , Yang Zhen , Xu Xuemei , Liu Chenxi , Lu Jingyi , Jin Yanliang
Published: April 2023

Objective

To explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).

Methods

Eighty-seven patients with JSLE were retrospectively collected and divided into subgroups via a two-step cluster based on the status of nine autoantibodies (double-stranded-DNA (dsDNA), nucleosome, histone, ribosomal P protein, Smith (Sm), u1-ribonucleoprotein (RNP), Sjögren’s syndrome antigen A (SSA)/Ro52, SSA/Ro60, Sjögren’s syndrome antigen B (SSB)/La). The final model selected in this study was based on adequate goodness of fit of the Silhouette coefficient and clinical interpretability. Clinical manifestations, organ involvements and disease activity were compared among the subgroups. Fluctuation in autoantibody status was also collected and analysed. Flare-free survival rates of the patients with positive/negative seroconversion and patients without seroconversion were studied by the Kaplan-Meier method and compared using a log-rank test.

Results

Two clusters were identified: subgroup 1 (positive anti-Sm/RNP group) and subgroup 2 (negative anti-Sm/RNP group). There were more lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) cases in subgroup 1 than in subgroup 2. Patients in subgroup 1 exhibited higher SLE Disease Activity Index scores compared with those in subgroup 2. Furthermore, anti-ribosomal P protein (61.1%), anti-nucleosome (58.3%) and anti-dsDNA (54%) were most commonly positive autoantibodies. A progressive decrease in the frequency of patients with positive results was demonstrated during the follow-up years. The decrease was notable for anti-dsDNA, anti-nucleosome and anti-ribosomal P protein (remaining 27.27%, 38.89% and 45.00% positive in the fifth year, respectively). While for those negative at baseline diagnosis, the decrease in the frequency of negative results was progressive but modest. Kaplan-Meier curve showed that the flare-free survival of patients with positive seroconversion was significantly lower than those without seroconversion and those with negative seroconversion (p<0.001).

Conclusions

In children with SLE, subgroups based on autoantibody profile can be applied to differentiate phenotypes and disease activity. Two important organ involvements, LN and NPSLE, are more common in patients with positive anti-Sm/RNP autoantibodies. Positive seroconversion may provide a valuable perspective for assessing flare, and it is worthwhile to retest the array of autoantibodies during follow-up.
Evaluation of the LFA-REAL clinician-reported outcome (ClinRO) and patient-reported outcome (PRO): prespecified analysis of the phase III ustekinumab trial in patients with SLE
Authors: Askanase Anca D , Tang Wei , Zuraw Qing , Gordon Robert , Brotherton Betsy , Merrill Joan T
Published: April 2023

Objective

The Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) system is a novel and simple SLE disease activity instrument, consisting of a tandem clinician-reported (ClinRO) and patient-reported (PRO) outcome measure. The aim of this study was to compare the LFA-REAL system with other SLE activity measures in the phase III trial of ustekinumab in patients with active SLE.

Methods

This was a prespecified analysis of data from a randomised, double-blind, placebo-controlled, parallel-group trial conducted at 140 sites in 20 countries. Correlations were evaluated between the LFA-REAL ClinRO and PRO with a panel of clinician-reported and patient-reported disease activity measures commonly used in SLE clinical trials at baseline, week 24 and week 52. All p values are reported as nominal.

Results

Trial participants included 516 patients with SLE with a mean (SD) age of 43.5 (8.9), of whom 482 (93.4%) were female. The LFA-REAL ClinRO correlated with Physician Global Assessment (r=0.39, 0.65 and 0.74, p<0.001), British Isles Lupus Assessment Group Index (r=0.43, 0.67 and 0.73, p<0.001) and SLE Disease Activity Index-2000 (r=0.35, 0.60 and 0.62, p<0.001). The LFA-REAL ClinRO arthralgia/arthritis score correlated well with active joint counts (r=0.54, 0.73 and 0.68, p<0.001) and the mucocutaneous global score correlated strongly with Cutaneous Lupus Erythematosus Disease Area and Severity Index total activity (r=0.57, 0.77 and 0.81, p<0.001). The LFA-REAL PRO demonstrated a moderate correlation with Functional Assessment of Chronic Illness Therapy-Fatigue (r=−0.60, –0.55 and –0.58, p<0.001), Lupus QoL physical health (r=−0.42, –0.47 and −0.46, p<0.001), SF-36v2 vitality (r=−0.40, –0.43 and −0.58, p<0.001) and SF-36v2 Physical Component Summary (r=−0.45, –0.53 and −0.53, p<0.001). The LFA-REAL ClinRO and PRO showed a moderate correlation with each other (r=0.32, 0.45 and 0.50, p<0.001).

Conclusions

The LFA-REAL ClinRO and PRO showed varied levels of correlations (weak to strong) with existing physician-based lupus disease activity measures and patient-reported outcome instruments, respectively and were able to more accurately capture organ-specific mucocutaneous and musculoskeletal manifestations. More analyses are needed to determine areas in which patient-reported outcomes are most similar or different to physician-reported end points and the basis for differences.
Research priorities relating to the delivery of cardiovascular prevention and rehabilitation programmes: results of a modified Delphi process
Authors: McHale Sheona , Cowie Aynsley , Brown Sarah , Butler Tom , Carver Kathryn , Dalal Hasnain M , Dawkes Susan , Deighan Carolyn , Doherty Patrick , Evans Jo , Hinton Sally , Jones Jennifer , Mills Joseph , Nichols Simon , Taylor Rod S
Published: April 2023

Objective

The purpose of this British Association for Cardiovascular Prevention and Rehabilitation (BACPR) research priority setting project (PSP) was to identify a top 10 list of priority research questions for cardiovascular prevention and rehabilitation (CVPR).

Methods

The PSP was facilitated by the BACPR clinical study group (CSG), which integrates as part of the British Heart Foundation Clinical Research Collaborative. Following a literature review to identify unanswered research questions, modified Delphi methods were used to engage CVPR-informed expert stakeholders, patients, partners and conference delegates in ranking the relevance of research questions during three rounds of an anonymous e-survey. In the first survey, unanswered questions from the literature review were ranked and respondents proposed additional questions. In the second survey, these new questions were ranked. Prioritised questions from surveys 1 and 2 were incorporated in a third/final e-survey used to identify the top 10 list.

Results

From 459 responses across the global CVPR community, a final top 10 list of questions were distilled from an overall bank of 76 (61 from the current evidence base and a further 15 from respondents). These were grouped across five broad categories: access and remote delivery, exercise and physical activity, optimising programme outcomes, psychosocial health and impact of the pandemic.

Conclusions

This PSP used a modified Delphi methodology to engage the international CVPR community to generate a top 10 list of research priorities within the field. These prioritised questions will directly inform future national and international CVPR research supported by the BACPR CSG.
Case report: crowned dens syndrome in a patient with seronegative rheumatoid arthritis
Authors: Ferraccioli Gianfranco , Zanardi Romeo , Gremese Elisa
Published: April 2023

Chondrocalcinosis (CC) is the one of the most common crystal pyrophosphate disease associated arthritis in the elderly. It has been shown to coexist with seronegative and seropositive rheumatoid arthritis (RA), yet mostly with seronegative RA. Among the localisation of CC, the deposition in the ligaments surrounding the odontoid process may remain asymptomatic for years or may lead to and acute severe symptomatology, which may mimic several clinical illnesses among which meningitis (fever, severe pain, acute phase reactants). This is called the ‘crowned dens syndrome (CDS)’, which has been reported to represent an important percentage of acute neck pain needing hospital admission in neurosurgery units. In this case, the rapid demonstration of ‘crowned dens’ through CT scan may allow to avoid lumbar puncture and cerebrospinal fluid examination. The coexistence of RA and CDS is very rare, and rarely reported in the literature, yet it may represent a clinical challenge. We describe here one case that while on therapy with methotrexate (MTX) and naproxen (NPX) had an acute neck pain, and peripheral arthritis flare, that responded well to colchicine given along with MTX and NPX.
Hydro-dynamically and thermally fully developed flow analysis of magneto-hydrodynamic fluid through annular duct
Authors: Ahmed Farhan , Akbar Noreen Sher , Tripathi Dharmendra
Published: April 2023

A hydro-dynamic thermal fully developed forced convective heat transfer analysis of magneto-hydrodynamics fluid flow through an annular sector duct is presented in this paper. Two types of thermal boundary conditions i.e., axially uniform heat flux along with peripherally uniform temperature (known as H1-condition) and, axially and peripherally uniform temperature (known as T condition), have been considered to carry out the thermal analysis of fluid. The velocity components along r and [Formula: see text] direction are transformed into algebraic form by using power law discretized scheme, whereas cross-sectional pressure [Formula: see text] is estimated with the help of well know technique [Formula: see text]. The governing partial differential equations are solved by numerically with the help of [Formula: see text] code. Furthermore, simulated results have been compared with the existing results of literature to validate the results. From the results, it is noted that hydro-dynamically and thermally impacts relate directly by increasing the Hartman number, (M). It is further reported that the effect of magnetic field becomes insignificant for the higher number of fins, N. The findings of the present analysis will be applicable in various types of thermal systems.
GepH: Entity Predictor for Hindi News
Authors: Bafna Prafulla B.
Published: April 2023

In this era, news is not only generated continuously with high speed but also growing in its amount by different web sources like talent hunt, news agencies, and so on. To predict the exact class of news depending on its topic, GepH (Grouped entity predictor for Hindi) is proposed using entity extraction and grouping. Entity extraction is popular for English corpus. Hindi is a national language due to its resource scarceness not being explored so much by researchers. More than 1,270 news are processed to apply entity extraction, clustering, and classification using the vector space model for Hindi (VSMH), Synset vector space model for Hindi (SVSMH), and grouped entity document matrix for Hindi (GEDMH). Synset-based dimension reduction techniques are used to get improved accuracy. Evaluation of HAC using three matrices shows the best performance of GEDMH for varied datasets. Thus labelled corpus obtained after applying HAC (Hierarchical agglomerative clustering) to GEDMH is used as a training dataset and predictions are done using random forest and Naïve Bayes. The Naïve Bayes classifier implemented using the proposed GEDMH performs the best. GepH shows 0.8 purity, 0.4 entropy, and 0.3 as error rate for 1,273 Hindi news.
KGFlex: Efficient Recommendation with Sparse Feature Factorization and Knowledge Graphs
Authors: Ferrara Antonio , Anelli Vito Walter , Mancino Alberto Carlo Maria , Di Noia Tommaso , Di Sciascio Eugenio
Published: April 2023

Collaborative filtering models have undoubtedly dominated the scene of recommender systems in recent years. However, due to the little use of content information, they narrowly focus on accuracy, disregarding a higher degree of personalization. Meanwhile, knowledge graphs are arousing considerable interest in recommendation models thanks to their ability to enrich the system with content features that captures subtle user-item relations. Nevertheless, with many high-quality features, the models become more complex and challenging to train. We extend KGFlex [
16
], a hybrid model that analyzes historical data to understand the semantic features the user decisions depend on. KGFlex represents item features as embeddings, and it models user-item interactions as a factorized entropy-driven combination of the item attributes relevant to the user, thus reducing the complexity and raising the degree of personalization. The method does not neglect long tail items, reducing the popularity bias and ensuring a high level of fairness. The user-item prediction is mediated by the user’s personal views of the embeddings that grant a high degree of expressiveness. This extension analyzes different entropy measurement strategies, an enhanced user negative decision modeling, and assesses the fairness of KGFlex and the impact of its hyperparameters. KGFlex is available at
https://split.to/kgflex
.
GLDAP: Global Dynamic Action Persistence Adaptation for Deep Reinforcement Learning
Authors: Tong Junbo , Shi Daming , Liu Yi , Fan Wenhui
Published: April 2023

In the implementation of deep reinforcement learning (DRL), action persistence strategies are often adopted so agents maintain their actions for a fixed or variable number of steps. The choice of the persistent duration for agent actions usually has notable effects on the performance of reinforcement learning algorithms. Aiming at the research gap of global dynamic optimal action persistence and its application in multi-agent systems, we propose a novel framework: global dynamic action persistence (GLDAP), which achieves global action persistence adaptation for deep reinforcement learning. We introduce a closed-loop method that is used to learn the estimated value and the corresponding policy of each candidate action persistence. Our experiment shows that GLDAP achieves an average of 2.5%~90.7% performance improvement and 3~20 times higher sampling efficiency over several baselines across various single-agent and multi-agent domains. We also validate the ability of GLDAP to determine the optimal action persistence through multiple experiments.
On-the-Go Adaptation of Implementation Approaches and Strategies in Health: Emerging Perspectives and Research Opportunities
Authors: Geng Elvin H. , Mody Aaloke , Powell Byron J.
Published: April 2023

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies that a full understanding of adaptation involves ( a) a sense of initial effects, ( b) conceptualizing and documenting content and rationale for changes in approach (e.g., alteration, intensification), and ( c) the effects of the changed approach (including how the latter effects depend on initial effects). Conceptualizing these steps can help researchers ask questions about adaptation (e.g., thresholds for change, dosing, potentiation, sequencing) to advance our understanding of implementation strategies.
Promoting Health Equity Through Preventing or Mitigating the Effects of Gentrification: A Theoretical and Methodological Guide
Authors: Cole Helen V.S. , Anguelovski Isabelle , Triguero-Mas Margarita , Mehdipanah Roshanak , Arcaya Mariana
Published: April 2023

Public health researchers are increasingly questioning the consequences of gentrification for population health and health equity, as witnessed in the rapid increase in public health publications on the health (equity) effects of gentrification. Despite methodological challenges, and mixed results from existing quantitative research, qualitative evidence to date points to the role of gentrification processes in exacerbating health inequities. Here we discuss past methodological and theoretical challenges in integrating the study of gentrification with public health research. We suggest taking an interdisciplinary approach, considering the conceptualization of gentrification in measurement techniques and conceiving this process as a direct exposure or as a part of broader neighborhood changes. Finally, we discuss existingpolicy approaches to mitigating and preventing gentrification and how these could be evaluated for effectiveness and as public health promotion and specifically as interventions to promote health equity.
Structural Characterization and Dielectric Properties of Flexible PVA/PANI/Ag Nanocomposite Materials
Authors: Al-Yousef Haifa A. , Atta A. , Abdeltwab E. , Abdel-Hamid M. M.
Published: April 2023

PVA/PANI/Ag composite materials made of silver (Ag), polyaniline (PANI), and polyvinyl alcohol (PVA) are prepared for applied in electrical devices. The structure of PVA/PANI/Ag composites was analyzed using XRD, which indicating the samples were successfully synthesized. The crystallite size of AgNPs changed from 12.1 nm to 16 nm by increasing the Ag content from 3 to 6% in the PVA/PANI blend. Moreover, in temperature range 293–353 K, the impacts of PANI as well as AgNPs on the conductivities, permittivity, as well as energy density of PVA were investigated. The conductivity of the films was enhanced with higher frequency due to charge carrier mobility. Furthermore, the density is increased from 1.96 × 10−6 J m−3 at 20 °C for PVA to 2.7 × 10−6 for PVA/PANI/Ag. These results show the prepared PVA/PANI/AgNPs can applied in in a wide range of electronic technologies like batteries, electronic circuits, as well as super capacitors.
Analysis of Bone Density and Bone Morphometry by Periapical Radiographs in Dental Implant Osseointegration Process
Authors: Lubis Ratih Trikusumadewi , Azhari Azhari , Pramanik Farina
Published: April 2023

Objective. This research aimed to analyze the differences in bone density and bone morphometry by periapical implant radiography in the dental implant osseointegration stages. Methods. This experimental research uses 12 periapical radiographs of tibial bones from a New Zealand white rabbit (Oryctolagus cuniculus). The analysis was performed on day 3, 14, and 28 of the osseointegration stages with density, trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), and trabecular number (Tb.N.) as parameters. The implant used is a titanium alloy and coated by SA (sunblasted with alumina acid) of 4 mm in diameter and 7 mm in length. The radiographic assessment of the osseointegration process is obtained with the region of interest (ROI) segmentation results. Additionally, each ROI was analyzed for bone density and morphometry using the open-source ImageJ software with the BoneJ plugin. The significant difference was evaluated by analysis of variance (F-test) with

p
<
0.05

and nonparametric Kruskal–Wallis test with

p
<
0.05

. Results. Analysis of the osseointegration images of dental implants at day 3, 14, and 28 with the periapical X-ray modality shows significant differences (

p
<
0.05

) in the parameters measuring density and trabecular thickness (Tb.Th.). In the variables of trabecular separation (Tb.Sp.) and number (Tb.N.) (

p
>
0.05

), there is no significant difference. Conclusion. Based on the results, density and trabecular thickness (Tb.Th.) showed a significant difference between healing times. However, trabecular separation (Tb.Sp.) and trabecular number (Tb.N.) showed no difference in healing time.
Polyurethane Application to Transform Screen-Printed Electrode for Rapid Identification of Histamine Isolated from Fish
Authors: Munir Muhammad Abdurrahman , Jamal Jamia Azdina , Said Mazlina Mohd , Ibrahim Sofian , Ahmad Mohamad Syahrizal
Published: April 2023

The toxicity of histamine has attracted numerous researchers to develop a method for histamine determination purposes. The Food and Drug Administration (FDA) unequivocally prohibits the consumption of histamine above 50 mg·kg−1. Thus, an innovation in histamine detection in fish has been developed in this research. The investigation of the histamine level in fish has been conducted by using an electrochemical sensor approach and producing a polymer via molecularly imprinted polymer (MIP) on a screen-printed electrode. The technique was validated by assessing the shifts in electron shifting using the cyclic voltammetry (CV) approach and electrochemical impedance spectroscopy (EIS), whereas differential pulse voltammetry (DPV) was applied to validate the sensor method. The instruments showed a linear response ranging from 1–1000 nmol·L−1, with a detection limit of MIP/SPE at 1.765 nmol·L−1 and 709 nmol·L−1 for the NIP/SPE, respectively. The sensing technique was employed to determine the histamine level in selected samples at room temperature (25°C). The outcomes of this study indicated that the validated chemical sensor allowed accurate and precise detection of fish samples and can be categorized as a simple approach. The instrument is inexpensive and suitable for on-site detection.
Combined Dynamic Route Guidance and Signal Timing Optimization for Urban Traffic Congestion Caused by Accidents
Authors: Zhang He , Guo Shanshan , Long Xuzhi , Hao Yuanyuan
Published: April 2023

When traffic congestion caused by accidents occurs on urban roads, the current signal control scheme may face failure. It is necessary to establish an effective dynamic route guidance scheme and formulate a reasonable signal timing scheme to alleviate the impact of the accident on urban traffic. In this paper, traffic congestion is divided into three states and the traffic evacuation strategies are formulated, respectively. Then, on the basis of analyzing the internal mechanism and spatiotemporal variation of queuing at intersections, a two-stage model is proposed to optimize the signal timing parameters. In the first stage, the basic timing parameters of each intersection, such as signal cycle and green ratio, are obtained. In the second stage, the offset optimization model is constructed to minimize the total delay time of the coordinated phase of all detour routes in the control scope, considering the early dissipation of queuing vehicles at the entrance of the intersection. This model is solved with a particle swarm optimization algorithm and simulated to the actual road network with VISSIM. As the experimental results show, this control method can greatly reduce the average vehicle delay, stop times, queue length, and the number of vehicles passing.
[Retracted] Painting Color Editing System Based on Virtual Reality Sensor Technology
Authors: Hu Chunda
Published: April 2023

In order to solve the problem of large color matching error in color matching system, this paper proposes a painting color editing system based on virtual reality sensing technology. Apply virtual reality technology (technology) to the proposed system design, and design the system framework based on the three‐tier architecture, which includes data access layer, business logic layer, and presentation layer. The hardware includes spectrophotometer, central processing unit, storage device, and virtual reality somatosensory interaction device. The software part takes BP neural network algorithm as the core, trains and processes the three color values, constructs the automatic matching model of painting colors according to the training results, and realizes the logical operation and analysis of the system software. The experimental results show that although there is still a certain error between the painting color matching output by the system and the actual color matching of the test samples, the maximum absolute error of the matching is relatively small, which is less than 0.05. The error between 6 groups of actual matching samples and predicted matching samples is <1.5. Although the designed system has some errors with the expected color matching, the error is small, so the color difference does not affect the visual presentation effect.
Cognitive Therapy for Children with Intellectual Disabilities: A New Look at Social Adaptation Skills and Interpersonal Relationships
Authors: Kulnazarova Gulnaz , Namazbaeva Zhamiliya , Butabayeva Laura , Tulepova Lazzat
Published: April 2023

The purpose of the study is to consider the factors influencing the development of the culture of interpersonal relationships and the effectiveness of the influence of cognitive therapy on improving social adaptation skills. The method of cognitive therapy included several types of activities. The first type of activities included group sessions, during which the weaknesses of the interaction and their correction were identified. The second type was conducted in the format of teaching standard models of interaction between people. The third type of activity aimed to teach children to build a dialogue with each other and express their desires and emotions. Classes were held 3 times a week throughout the year. The study was attended by pupils of 5-7 grades of Zhanuya boarding school and special correctional boarding school No. 7 for children with intellectual disabilities. The results of a randomized study demonstrated an increase in the indicators of teamwork skills, self-control, emotional stability, and independent decision-making. The indicators of cheerfulness, openness, sociability, and logical thinking also improved. But the factor of antisocial behavior decreased. All of these indicators directly affect socialization. This strategy can be applied in practice in various specialized boarding schools and schools for children with intellectual disabilities.
Treatment of Industrial Saline Wastewater Using Eco-Friendly Adsorbents
Authors: Al Ajmi Safiya , Ali Syed Murtuza , Shaik Feroz , Nayeemuddin Mohammed , Balakrishnan Deepanraj , Myneni Venkata Ratnam
Published: April 2023

The wastewater generated from the oil and gas sector is one of the major environmental issues. Varieties of techniques are employed for the treatment of generated wastewater. In this work, an attempt has been made to treat industrial saline wastewater from the oil and gas industry using a combination of synthesized biopolymer, chitosan, with graphene. Chitosan has been synthesized from a bioresource using marine spent. Chitosan was characterized using field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray (EDX) spectroscopy, and thermogravimetric analysis (TGA). Batch experiments were conducted by varying the composition of graphene viz 1, 2, 3, 4, and 5 w/w with respect to a fixed amount of chitosan. The percentage removal efficiency of chemical oxygen demand (COD), total dissolved solids (TDS), total suspended solids (TSS), turbidity, and oil and grease were evaluated. A combination of chitosan and graphene has effectively removed the pollutants present in oil produced water (OPW) compared to chitosan alone. The maximum percentage removal efficiencies of COD (84%), TDS (91%), TSS (80%), turbidity (95%), and oil and grease (99.9%) were obtained for a mixture of chitosan (0.5 g/100 mL) and 5 wt% graphenes. The Freundlich equilibrium isotherm model suited the adsorption data well.
Antibiotic Susceptibility of β-Glucuronidase-Positive Escherichia coli Isolated from Poultry Products in Morocco
Authors: Fazza Oumaima , Favard Ennachachibi Mireille , Ennassiri Houda , Hmyene Abdelaziz
Published: April 2023

Poultry products are one of the main foodstuffs consumed in Morocco. The deterioration of their hygienic quality and the emergence of antibiotic resistance are the major public health problems. This study was carried out to determine the level of emergence of antibiotic resistance. For that, between May 2021 and June 2022, poultry products (e.g., minced meat, sausage, and meat) were collected aseptically in sterile bags from retail stores in different cities of Morocco, labeled, and transported in chilled conditions to the laboratory. The bacterial analysis was performed within 24 hours. Isolation and identification of Escherichia coli were performed according to the Moroccan standard NM ISO 16649 2018. Antimicrobial susceptibility determination of 23 antibiotics was tested using the Kirby-Bauer disk diffusion method. The results showed a high level of antimicrobial resistance to amoxicillin (58%), amoxicillin-clavulanic acid (54%), piperacillin (63%), trimethoprim (32%), nalidixic acid (46%), and ofloxacin (43%). 58 isolates (60%) were positive for beta-lactamase class A (penicillinase) test detection, and 2 isolates (3%) produced extended-spectrum beta-lactamases. The high level of resistance demonstrated in this study should alert health organizations in the country. An establishment of surveillance programs to control the use and the administration of antibiotics in the poultry field and initiation of reliable methods to follow up on the latest updates on the emergence of bacterial resistance is a necessity.
Supplementary Figure S1 from Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules
Authors: Shome Mahasish , Gao Weimin , Engelbrektson Anna , Song Lusheng , Williams Stacy , Murugan Vel , Park Jin G. , Chung Yunro , LaBaer Joshua , Qiu Ji
Published: April 2023

Supplementary Figure S1 from Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules
Data from Enhanced Antitumor Effects by Chemical Modified IGb3 Analogues
Authors: Zhou Zhixia , Zhang Cai , Xia Chengfeng , Chen Wenlan , Zhu Huawei , Shang Pingping , Ma Fang , Wang Peng George , Zhang Jian , Xu Wenfang , Tian Zhigang
Published: April 2023

Abstract
Certain glycolipid antigens for natural killer T (NKT) cells can direct the overall cytokine balance of the immune response. However, the molecular mechanism of Th1- or Th2-biased cytokine secretion by NKT cells is still unknown. Previously, we synthesized isoglobotrihexosylceramide (iGb3) analogues by introducing a hydroxyl group at C4 on the ceramide portion of iGb3 to produce 4-HO-iGb3 or to further deoxylation on the terminal galactose to produce 4‴-dh-iGb3. Both modified iGb3, especially 4‴-dh-iGb3, stimulated more IFN-γ production by hepatic NKT cells, and thus elicited preferential Th1 responses. Here, we found that 4‴-dh-iGb3–loaded bone marrow–derived dendritic cells (DC) could significantly inhibit growth of subcutaneous melanoma and suppress lung metastasis in C57BL/6 mice compared with unmodified iGb3-loaded DCs. In investigating the mechanisms of this improved activity, we found that 4‴-dh-iGb3 stimulation increased STAT1 signaling by NKT cells, whereas the phosphorylation of Th2 type cytokine–associated transcription factor STAT6 signaling was not affected. Analysis of the structures of iGb3 and 4‴-dh-iGb3 revealed that 4‴-dh-iGb3 provides greater stability and affinity between glycolipid and CD1d or NKT TCR complex than iGb3. Thus, 4‴-dh-iGb3 can improve the antitumor effects of a DC-based vaccine possibly by stabilizing the CD1d/glycolipid/TCR complex and stimulating IFN-γ signaling of NKT cells. Furthermore, chemical modification of iGb3 can elicit Th1-biased responses by NKT cells, and 4‴-dh-iGb3 combined with a DC vaccine may serve as a potent new NKT-based therapy against tumors and infectious diseases. Mol Cancer Ther; 10(8); 1375–84. ©2011 AACR.
Data from MicroRNA Regulation of Oncolytic Adenovirus 6 for Selective Treatment of Castration-Resistant Prostate Cancer
Authors: Zhang Zhenwei , Zhang Xuemei , Newman Kam , Liu Xinyuan
Published: April 2023

Abstract
Almost all patients with advanced prostate cancer progress to castration-resistant stage with limited treatment options. Oncolytic adenoviruses have been actively pursued as potential agents for cancer treatment. Virtually all clinical trials on oncolytic adenovirus are based on serotype 5. However, viral replication in hepatocytes induces severe liver toxicity and limits its systemic administration for metastatic disease. Moreover, rapid clearance of viral particles injected intravenously further hinders the anticancer efficacy. Adenovirus 6 (Ad6) was previously reported to exhibit less liver toxicity and escape Kupffer cells absorption after systemic administration. To further improve its safety, we generated a novel oncolytic adenovirus Ad6miR, in which four copies of binding sites of a liver-specific microRNA miR122 were incorporated into E1A gene of Ad6. miR122 regulation significantly decreased Ad6 replication in hepatocytes and consequently hepatotoxicity because of the negative regulation of miR122. Cytotoxicity assay using primary or established prostate cancer cell lines showed robust oncolytic activity of Ad6miR. Systemic treatment of established tumors with Ad6miR showed strong antitumor activity, comparable with that of Ad6 or Ad5. Although Ad6 evaded Kupffer cells, its blood clearance rate was as rapid as Ad5. The vast majority of Ad6 particles intravenously injected localized in liver sinusoidal endothelial cells rather than previously reported Kupffer cells. Elevating Ad6miR injection dose increased circulating Ad6miR concentration and its antitumor efficacy. miR122 regulation of Ad6 significantly improves its safety profile after systemic administration, which allows increasing therapeutic doses leading to improved anticancer efficacy of systemic treatment of castration-resistant prostate cancer. Mol Cancer Ther; 11(11); 2410–8. ©2012 AACR.
Data from Prioritizing Candidate Disease miRNAs by Topological Features in the miRNA Target–Dysregulated Network: Case Study of Prostate Cancer
Authors: Xu Juan , Li Chuan-Xing , Lv Jun-Ying , Li Yong-Sheng , Xiao Yun , Shao Ting-Ting , Huo Xiao , Li Xiang , Zou Yan , Han Qing-Lian , Li Xia , Wang Li-Hua , Ren Huan
Published: April 2023

Abstract
Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target–dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis. Mol Cancer Ther; 10(10); 1857–66. ©2011 AACR.
Data from Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin
Authors: Bhagwat Shripad V. , Gokhale Prafulla C. , Crew Andrew P. , Cooke Andy , Yao Yan , Mantis Christine , Kahler Jennifer , Workman Jennifer , Bittner Mark , Dudkin Lorina , Epstein David M. , Gibson Neil W. , Wild Robert , Arnold Lee D. , Houghton Peter J. , Pachter Jonathan A.
Published: April 2023

Abstract
The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC50 values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K–AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. Mol Cancer Ther; 10(8); 1394–406. ©2011 AACR.
Data from Cyclin E2 Overexpression Is Associated with Endocrine Resistance but not Insensitivity to CDK2 Inhibition in Human Breast Cancer Cells
Authors: Caldon C. Elizabeth , Sergio C. Marcelo , Kang Jian , Muthukaruppan Anita , Boersma Marijke N. , Stone Andrew , Barraclough Jane , Lee Christine S. , Black Michael A. , Miller Lance D. , Gee Julia M. , Nicholson Rob I. , Sutherland Robert L. , Print Cristin G. , Musgrove Elizabeth A.
Published: April 2023

Abstract
Cyclin E2, but not cyclin E1, is included in several gene signatures that predict disease progression in either tamoxifen-resistant or metastatic breast cancer. We therefore examined the role of cyclin E2 in antiestrogen resistance in vitro and its potential for therapeutic targeting through cyclin-dependent kinase (CDK) inhibition. High expression of CCNE2, but not CCNE1, was characteristic of the luminal B and HER2 subtypes of breast cancer and was strongly predictive of shorter distant metastasis-free survival following endocrine therapy. After antiestrogen treatment of MCF-7 breast cancer cells, cyclin E2 mRNA and protein were downregulated and cyclin E2–CDK2 activity decreased. However, this regulation was lost in tamoxifen-resistant (MCF-7 TAMR) cells, which overexpressed cyclin E2. Expression of either cyclin E1 or E2 in T-47D breast cancer cells conferred acute antiestrogen resistance, suggesting that cyclin E overexpression contributes to the antiestrogen resistance of tamoxifen-resistant cells. Ectopic expression of cyclin E1 or E2 also reduced sensitivity to CDK4, but not CDK2, inhibition. Proliferation of tamoxifen-resistant cells was inhibited by RNAi-mediated knockdown of cyclin E1, cyclin E2, or CDK2. Furthermore, CDK2 inhibition of E-cyclin overexpressing cells and tamoxifen-resistant cells restored sensitivity to tamoxifen or CDK4 inhibition. Cyclin E2 overexpression is therefore a potential mechanism of resistance to both endocrine therapy and CDK4 inhibition. CDK2 inhibitors hold promise as a component of combination therapies in endocrine-resistant disease as they effectively inhibit cyclin E1 and E2 overexpressing cells and enhance the efficacy of other therapeutics. Mol Cancer Ther; 11(7); 1488–99. ©2012 AACR.
Data from Impact of APE1/Ref-1 Redox Inhibition on Pancreatic Tumor Growth
Authors: Fishel Melissa L. , Jiang Yanlin , Rajeshkumar N.V. , Scandura Glenda , Sinn Anthony L. , He Ying , Shen Changyu , Jones David R. , Pollok Karen E. , Ivan Mircea , Maitra Anirban , Kelley Mark R.
Published: April 2023

Abstract
Pancreatic cancer is especially a deadly form of cancer with a survival rate less than 2%. Pancreatic cancers respond poorly to existing chemotherapeutic agents and radiation, and progress for the treatment of pancreatic cancer remains elusive. To address this unmet medical need, a better understanding of critical pathways and molecular mechanisms involved in pancreatic tumor development, progression, and resistance to traditional therapy is therefore critical. Reduction–oxidation (redox) signaling systems are emerging as important targets in pancreatic cancer. AP endonuclease1/Redox effector factor 1 (APE1/Ref-1) is upregulated in human pancreatic cancer cells and modulation of its redox activity blocks the proliferation and migration of pancreatic cancer cells and pancreatic cancer-associated endothelial cells in vitro. Modulation of APE1/Ref-1 using a specific inhibitor of APE1/Ref-1′s redox function, E3330, leads to a decrease in transcription factor activity for NFκB, AP-1, and HIF1α in vitro. This study aims to further establish the redox signaling protein APE1/Ref-1 as a molecular target in pancreatic cancer. Here, we show that inhibition of APE1/Ref-1 via E3330 results in tumor growth inhibition in cell lines and pancreatic cancer xenograft models in mice. Pharmacokinetic studies also show that E3330 attains more than10 μmol/L blood concentrations and is detectable in tumor xenografts. Through inhibition of APE1/Ref-1, the activity of NFκB, AP-1, and HIF1α that are key transcriptional regulators involved in survival, invasion, and metastasis is blocked. These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. Mol Cancer Ther; 10(9); 1698–708. ©2011 AACR.
Data from Evaluating the Consistency of Differential Expression of MicroRNA Detected in Human Cancers
Authors: Gong Xue , Wu Ruihong , Wang Hongwei , Guo Xinwu , Wang Dong , Gu Yunyan , Zhang Yuannv , Zhao Wenyuan , Cheng Lixin , Wang Chenguang , Guo Zheng
Published: April 2023

Abstract
Differential expression of microRNA (miRNA) is involved in many human diseases and could potentially be used as a biomarker for disease diagnosis, prognosis, and therapy. However, inconsistency has often been found among differentially expressed miRNAs identified in various studies when using miRNA arrays for a particular disease such as a cancer. Before broadly applying miRNA arrays in a clinical setting, it is critical to evaluate inconsistent discoveries in a rational way. Thus, using data sets from 2 types of cancers, our study shows that the differentially expressed miRNAs detected from multiple experiments for each cancer exhibit stable regulation direction. This result also indicates that miRNA arrays could be used to reliably capture the signals of the regulation direction of differentially expressed miRNAs in cancer. We then assumed that 2 differentially expressed miRNAs with the same regulation direction in a particular cancer play similar functional roles if they regulate the same set of cancer-associated genes. On the basis of this hypothesis, we proposed a score to assess the functional consistency between differentially expressed miRNAs separately extracted from multiple studies for a particular cancer. We showed although lists of differentially expressed miRNAs identified from different studies for each cancer were highly variable, they were rather consistent at the level of function. Thus, the detection of differentially expressed miRNAs in various experiments for a certain disease tends to be functionally reproducible and capture functionally related differential expression of miRNAs in the disease. Mol Cancer Ther; 10(5); 752–60. ©2011 AACR.
Data from E7080 Suppresses Hematogenous Multiple Organ Metastases of Lung Cancer Cells with Nonmutated Epidermal Growth Factor Receptor
Authors: Ogino Hirokazu , Hanibuchi Masaki , Kakiuchi Soji , Trung Van The , Goto Hisatsugu , Ikuta Kenji , Yamada Tadaaki , Uehara Hisanori , Tsuruoka Akihiko , Uenaka Toshimitsu , Wang Wei , Li Qi , Takeuchi Shinji , Yano Seiji , Nishioka Yasuhiko , Sone Saburo
Published: April 2023

Abstract
While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors improve the prognosis of patients with EGFR mutant lung cancer, the prognosis of patients with nonmutant EGFR lung cancer, especially those with metastases, is still extremely poor. We have assessed the therapeutic efficacy of E7080, an orally available inhibitor of multiple tyrosine kinases including VEGF receptor 2 (VEGFR-2) and VEGFR-3, in experimental multiple organ metastasis of lung cancer cell lines without EGFR mutations. E7080 markedly inhibited the in vitro proliferation of VEGF-stimulated microvascular endothelial cells. Intravenous inoculation into natural killer cell–depleted severe combined immunodeficient mice of the small cell lung cancer cell lines H1048 (producing low amounts of VEGF) and SBC-5 (producing intermediate amounts of VEGF) resulted in hematogenous metastases into multiple organs, including the liver, lungs, kidneys, and bones, whereas intravenous inoculation of PC14PE6, a non–small cell lung cancer cell line producing high amounts of VEGF, resulted in lung metastases followed by massive pleural effusion. Daily treatment with E7080 started after the establishment of micrometastases significantly reduced the number of large (>2 mm) metastatic nodules and the amount of pleural effusion, and prolonged mouse survival. Histologically, E7080 treatment reduced the numbers of endothelial and lymph endothelial cells and proliferating tumor cells and increased the number of apoptotic cells in metastatic nodules. These results suggest that E7080 has antiangiogenic and antilymphangiogenic activity and may be of potential therapeutic value in patients with nonmutant EGFR lung cancer and multiple organ metastases. Mol Cancer Ther; 10(7); 1218–28. ©2011 AACR.
Data from Human Monoclonal Antibody Fragments Binding to Insulin-like Growth Factors I and II with Picomolar Affinity
Authors: Zhao Qi , Feng Yang , Zhu Zhongyu , Dimitrov Dimiter S.
Published: April 2023

Abstract
The type 1 insulin-like growth factor receptor (IGF1R) and its ligands (IGF-I and IGF-II) have been implicated in a variety of physiologic processes and in diseases such as cancer. In addition to IGF1R, IGF-II also activates the insulin receptor (IR) isoform A, and therefore, antibodies against IGF-II can inhibit cell proliferation mediated by the signaling through both IGF1R and IR triggered by IGF-II. We identified a new human monoclonal antibody (mAb), m708.2, which is bound to IGF-I and IGF-II but not to insulin. m708.2 potently inhibited signal transduction mediated by the interaction of IGF-I or IGF-II with the IGF1R and IGF-II with the IR. It also inhibited the growth of the breast cancer cell line MCF-7. An affinity-matured derivative of m708.2, m708.5, bound to IGF-I with equilibrium dissociation constant, KD = 200 pmol/L and to IGF-II with KD = 60 pmol/L. m708.5 inhibited signal transduction mediated by IGF-I and IGF-II and cancer cell growth more potently than m708.2. These results suggest that m708.5 could have potential as a candidate therapeutic for cancers driven by the IGF-I and IGF-II interactions with IGF1R and IR. Mol Cancer Ther; 10(9); 1677–85. ©2011 AACR.