Molecular Pharmaceutics最新文献

{"title":"Leveraging Molecular Interactions to Develop a Generalized Design Framework for Coamorphous Drug-Drug Mixtures Exhibiting Elevated Glass Transition Temperatures.","authors":"Dani Lakshman Yarlagadda, Kohsaku Kawakami, Satyavrata Samavedi","doi":"10.1021/acs.molpharmaceut.5c00006","DOIUrl":"10.1021/acs.molpharmaceut.5c00006","url":null,"abstract":"<p><p>Coamorphous mixtures (CAMs) prepared with two drugs have the potential to enhance the oral absorption of poorly soluble drugs and achieve combination therapy. From a practical standpoint, improving the glass transition temperature (<i>T</i>_g) of CAMs is desirable as it enhances stability and extends shelf life during storage. Toward the eventual goal of developing highly stable CAMs, this study establishes a generalized framework that systematically relates elevated <i>T</i>_g values of CAMs to intermolecular interactions based on specific functional groups. CAMs were prepared via quench-cooling using various combinations of indomethacin, ketoprofen, flurbiprofen, flufenamic acid, aripiprazole, bifonazole, and clotrimazole. CAMs prepared with drugs containing the COOH group exhibited significant positive deviations from the <i>T</i>_g values predicted by the Gordon-Taylor equation (i.e., ideal mixing behavior). COOH-associated hydrogen bonding was determined to be a key factor for <i>T</i>_g elevation, with synergistic contributions from π-π interactions and halogen bonding. In CAMs exhibiting the largest <i>T</i>_g deviations, contributions from ionic bonding were crucial, and were likely favored by differences in the p<i>K</i>_a values of the constituent drugs. Continuity in <i>T</i>_g as a function of varying molar ratios indicated that stoichiometric pairing had a relatively minor contribution, while a decrease in the width of the glass transition suggested enhancement of molecular cooperativity as a possible mechanism for CAM stabilization. In contrast, non-COOH hydrogen bonding, π-π interactions, and halogen bonding on their own did not result in any meaningful <i>T</i>_g deviations from theoretical predictions. Systematic correlations between <i>T</i>_g deviations and molecular interactions reported in this study can lead to generalized design rules for the development of stable CAMs.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"3084-3096"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radionuclide-Aided Improvement of the Therapeutic Efficacy of Novel Antibody-Drug Conjugates against HER2-Expressing Cancers.","authors":"Chi Soo Kang, Do Hyeon Kim, Hwisoo Lim, Sunkyo Kim, Muath Almaslamani, Choong Mo Kang, Sang-Keun Woo","doi":"10.1021/acs.molpharmaceut.5c00043","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00043","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have drawn a lot of attention in the field of cancer therapy due to their improved efficacy and reduced side effects compared to traditional therapeutic antibodies or chemotherapeutics. However, cancer patients still develop resistance against ADCs and there is an urgent need for the development of strategies to reinforce ADC efficacy. Radiolabeling of an antibody with therapeutic radioisotopes (e.g., ¹⁷⁷Lu or ²²⁵Ac) can be considered an option. Herein, we synthesized radiolabeled ADCs and evaluated their potential therapeutic efficacies in vitro and in vivo for cancer therapy. New trastuzumab-based ADCs utilizing fendiline or gemifloxacin as drug moieties were developed, and they were decorated with therapeutic radionuclide ¹⁷⁷Lu or ²²⁵Ac. Anticancer effects of radiolabeled ADCs were evaluated using human epidermal growth factor receptor 2 (HER2) expressing cancer cells and compared to that of cold ADCs. Radiolabeled versions of newly synthesized ADCs showed significantly improved anticancer efficacy compared to unlabeled ADCs, especially when they were armed with ²²⁵Ac, demonstrating the great potential of radiolabeled ADCs in cancer therapy. This study offers an effective strategy for improving the therapeutic efficacy of ADCs by fortifying them with radionuclides.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iodixanol-Loaded Thermosensitive Liposomes: A Novel Imaging Contrast Agent for Precision Hepatocellular Carcinoma Ablation.","authors":"Kejin Liu, Rourou Zuo, Yalian Yu, Chen Xu, Tianci Wang, Linge Xie, Hongzan Sun, Meng Niu, Hongbo Wang","doi":"10.1021/acs.molpharmaceut.5c00527","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00527","url":null,"abstract":"<p><p>In hepatocellular carcinoma ablation, unclear tumor boundaries and localization often lead to incomplete treatment. Traditional iodinated contrast agents, although effective in distinguishing tumors, have rapid metabolism, limiting sustained visualization during ablation. Iodixanol-loaded thermosensitive liposomes were prepared by using the thin-film hydration method. Their temperature-responsive properties and CT imaging performance were validated through in vitro experiments, while in vivo studies were conducted to evaluate their CT imaging efficacy and potential as an auxiliary imaging agent in ablation therapy. This study successfully created stable, iodixanol-loaded thermosensitive liposomes that effectively outline HCC boundaries and accurately show the ablation zone during treatment. Iodixanol-loaded thermosensitive liposomes enable precise localization of ablation margins, facilitating more accurate clinical assessment of therapeutic outcomes and treatment end points.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Peptides Expressed by the Polyaminoglycoside Nanosystem for Bacterial Peritonitis Management via Inflammation Modulation.","authors":"Rui Ju, Bingran Yu, Dandan Sui, Fu-Jian Xu","doi":"10.1021/acs.molpharmaceut.5c00509","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00509","url":null,"abstract":"<p><p>Peritonitis, a prevalent and dangerous condition, can result from trauma, surgery, liver cirrhosis, peritoneal dialysis, and gastrointestinal issues. If not effectively managed, it can cause systemic infection, leading to complications, such as sepsis and bacteremia. LL37, an antimicrobial peptide of the innate immune system, exhibits broad-spectrum antibacterial activity and potent immune-modulating functions, serving as a critical defense against infections. In this study, we developed a combined system delivering a therapeutic plasmid (pLL37) via cationic poly(aminoglycoside) (SS-HPT) to treat bacterial peritonitis in immunocompromised populations. This system combines direct antimicrobial action and inflammation modulation. The SS-HPT carrier, containing tobramycin, provides immediate antibacterial effects by inhibiting the bacterial protein synthesis. Simultaneously, the expressed LL37 peptide enhances bacterial membrane disruption and modulates the inflammatory response by regulating cytokine release and immune cell differentiation. Treatment efficacy was comprehensively evaluated using survival rate assessments, clinical symptom analysis, inflammatory marker detection, histopathological observation, and molecular biological methods. Results indicated that the system significantly improved survival rates, reduced inflammatory responses, and ameliorated histopathological damage, effectively preventing and treating bacterial peritonitis and its complications. In conclusion, the SS-HPT/pLL37 system offers a promising new strategy for the treatment of bacterial peritonitis.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of [¹⁸F]AlF-RESCA-H006 as a Novel Molecular Probe for 5T4 Tumor Imaging and Exploration of Its Application in Pancreatic Adenocarcinoma.","authors":"Jinping Kong, Huixia Zhang, Ruhua Tian, Wenjie Ge, Yingfang He, Tengxiang Chen, Junbin Han","doi":"10.1021/acs.molpharmaceut.5c00430","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00430","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is an extremely lethal cancer, making early detection and precise staging essential for extending survival. Upregulation of 5T4 mRNA was detected in bioinformatics analysis using data from the Cancer Genome Atlas and Genotype-Tissue Expression. In the current work, we confirmed the overexpression of 5T4 protein in tumor samples of PAAD compared with the corresponding paraneoplastic tissue. To visualize 5T4 via positron emission tomography (PET) noninvasively, we successfully developed [¹⁸F]AlF-RESCA-H006 based on a single-domain antibody fragment. The radiotracer demonstrated high binding affinity toward 5T4 antigens <i>in vitro</i> and remained stable in the final formulation for up to 4 h storage at room temperature. In two preclinical mouse models of pancreatic cancer, [¹⁸F]AlF-RESCA-H006 clearly identified the tumor sites, showing a radioactivity accumulation of 2.43 ± 0.46% ID/g in Balb/C mice with BxPC-3 xenografts and 2.88 ± 1.02% ID/g in NCG mice with PANC-1 xenografts. Taken together, [¹⁸F]AlF-RESCA-H006 is a promising PET tracer for detecting 5T4 antigen alteration in PAAD. Further investigations are required to assess its defluorination level in higher species and its permeability through the dense extracellular matrix of pancreatic cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Clinically Used and Trialed Photosensitizers for Antitumor Photodynamic Therapy.","authors":"Liyun Chen, Yuxin Lin, Shangli Ding, Mingdong Huang, Longguang Jiang","doi":"10.1021/acs.molpharmaceut.5c00110","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00110","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) has gained significant attention as a minimally invasive cancer treatment that induces localized cytotoxicity with limited systemic side effects. When activated by light, typically in the visible or near-infrared spectrum, photosensitizers generate reactive oxygen species (ROS), leading to direct tumor cell death, vascular disruption, and stimulation of antitumor immune responses. This review provides an in-depth overview of the current understanding of PDT's antitumor mechanisms, focusing on ROS-induced cell death, immunogenic cell death, and tumor microenvironment modulation. Additionally, this review provides a critical evaluation of both clinically approved and investigational photosensitizers, detailing their chemical structures, photophysical properties, and therapeutic applications. We also discuss recent advances in combination strategies that integrate PDT with chemotherapy, radiotherapy, or immunotherapy to achieve enhanced therapeutic outcomes. Special emphasis is placed on emerging smart photosensitizers and tumor-targeted delivery systems that respond to microenvironmental stimuli, enhancing therapeutic precision and efficacy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melittin-Loaded Nanoparticle Microneedles Targeting M1 Macrophage for Arthritis Treatment.","authors":"Jitong Wang, Fan Zhao, Yu Zhang, Yuting Wen, Wenxu Wang, Jinru Hu, Chun Qiao, Ruixiang Li, Ruofei Du","doi":"10.1021/acs.molpharmaceut.4c01383","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.4c01383","url":null,"abstract":"<p><p>Arthritis is a joint inflammatory disease with multiple types that significantly compromises patients' quality of life. Current therapeutic efficiency is frequently constrained by the necessity for high dosages, the requirement for frequent administration, substantial side effects, and the risk of drug resistance. New therapeutic strategies are urgently needed. Melittin (Mel), a principal component of bee venom, has potent anti-inflammatory properties; however, its clinical application is limited by its hemolytic activity. To overcome the shortage, we developed targeted nanoparticles carrying Mel (MSC@NP-FA) with 68.3 ± 1.8% encapsulation efficiency, which were loaded within a microneedle (MN) to create MSC@NP-FA-MN. This strategy allows for precise anti-inflammatory therapy while reducing the risk of hemolysis. Both <i>in vitro</i> and <i>in vivo</i> studies demonstrated that MSC@NP-FA has lower hemolytic activity than Mel (<i>p</i> < 0.0001) and can target inflammatory macrophages to exert anti-inflammatory effects. <i>In vitro</i> transdermal test showed that more nanoparticles were delivered by the MNs (84.32 ± 6.97%) than bare nanoparticles (26.30 ± 2.55%) within 24 h. Furthermore, MSC@NP-FA-MN exhibited significant therapeutic efficacy without systemic toxicity or skin irritation in an adjuvant-induced arthritis (AIA) mouse model. Our findings highlight MSC@NP-FA-MN as a promising drug delivery system and suggest a new approach for safe and precise arthritis treatment.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid-State Pharmaceutics Research in India: Present and Future.","authors":"Arvind K Bansal, Dinesh Kumar","doi":"10.1021/acs.molpharmaceut.5c00534","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00534","url":null,"abstract":"<p><p>The pharmaceutical industry not only plays a crucial role in the healthcare system but also contributes significantly to the economy of a country. It is interesting to note that in 2024, a Danish pharmaceutical company held the title of Europe's most valuable company. Novo Nordisk, riding on popularity of a weight-loss drug, had a valuation of $600 billion in 2024, outweighing the GDP of Denmark <i>Nat Med</i> <b>2024</b>, <i>30</i>, 2049. Indian companies have achieved global recognition in generics, thus earning India the title of the \"pharmacy of the world\". This position was further strengthened during the COVID-19 pandemic when India supported the global needs with its high-capacity manufacturing and efficient supply chain management. However, despite these awards, the total valuation of the Indian pharmaceutical market, including its export values, is less than $100 billion. This highlights the focus of Indian pharmaceutical companies on generics, which generally generates less revenue with high volumes <i>Journal of Positive School Psychology</i> <b>2022</b>, 9285. In contrast, innovative products can generate a high revenue and accelerate economic growth. Innovative companies spend a good amount of their funds on research and development. It is well-recognized that a synergy between academic research institutions and pharmaceutical companies supports innovative outcomes <i>Res. Policy</i> <b>1991</b>, <i>20</i>, 1-12. In this perspective, we discuss the prominent areas of pharmaceutical research in Indian academia and also analyze the status of solid-state pharmaceutics (SSP) and pharmaceutical crystal engineering research. The article discusses the evolution of research in SSP, its status, and future prospects. Authors emphasize the need for improvement of the research ecosystem for SSP, thus ensuring availability of optimal human resources for this critical component of the pharmaceutical industry. There is a need to create a \"solid-state pharmaceutics research cluster\" in India to accelerate the research and support the growth of the Indian pharmaceutical industry.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiobioconjugate of Kadcyla with Radioactive Gold Nanoparticles for Targeted Therapy of HER2-Overexpressing Cancers.","authors":"Kinga Żelechowska-Matysiak, Kamil Wawrowicz, Mateusz Wierzbicki, Tadeusz Budlewski, Aleksander Bilewicz, Agnieszka Majkowska-Pilip","doi":"10.1021/acs.molpharmaceut.5c00288","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c00288","url":null,"abstract":"<p><p>One modern concept for cancer treatment is the use of antibody-drug conjugate (ADC). These therapies have shown promising results, especially in combination with other cancer treatment techniques. In this study, we propose the simultaneous use of β^- radiation (¹⁹⁸AuNPs) and trastuzumab emtansine (T-DM1; Kadcyla) for targeted therapy of cancers with established HER2 receptor overexpression. By utilizing ¹⁹⁸AuNPs-T-DM1, we aimed to reduce the required concentrations of T-DM1, which is advantageous given the associated emtansine-related side effects. In our study, we demonstrated the affinity of conjugated ¹⁹⁸AuNPs-T-DM1 for HER2 receptors and its effective internalization. <i>In vitro</i> studies indicate a synergistic therapeutic effect at doses of 10 MBq/mL or 20 MBq/mL of radiation and low concentrations of Kadcyla ranging from 0.015 to 0.124 μg/mL. Treatment with ¹⁹⁸AuNPs-T-DM1 at 20 MBq/mL and T-DM1 concentration of 0.031 μg/mL disintegrated 3D spheroid structures within seven days. The synthesized ¹⁹⁸AuNP-T-DM1 radiobioconjugate has potential applications in nuclear medicine for treating breast or ovarian cancers with HER2 receptor overexpression.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cu²⁺/Zn²⁺ \"Antimicrobial Chamber\" with Self-Enhanced Photothermal Activity Supports Infected Wound Healing.","authors":"Hanzhu Shi, Xue Zhou, Jue Wang, Xiuhong Zhou, Chenwei Dai, Lu Li, Xuechao Dong","doi":"10.1021/acs.molpharmaceut.5c00089","DOIUrl":"10.1021/acs.molpharmaceut.5c00089","url":null,"abstract":"<p><p>Wound healing of drug-resistant bacterial infection is a major challenge in clinical practice, and existing treatments suffer from the drawbacks of high dosage, low efficiency, and insufficient biosafety. Herein, we coated ultrasmall copper sulfide nanoparticles (CuS NPs) into zeolitic imidazolate framework-8 (ZIF-8) and modified them with polydopamine (PDA) to obtain CuS@ZIF-8@PDA NPs for bacterial infection wound treatment. Due to the presence of CuS and the degradability of ZIF-8, CuS@ZIF-8@PDA NPs can continuously release Cu²⁺ and Zn²⁺ in a slightly acidic environment under near-infrared (NIR) irradiation. Furthermore, the introduction of PDA endows it with an excellent photothermal property. The synergistic effect of dual ions/photothermal enables it to effectively eradicate <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Escherichia coli</i> (<i>E. coli</i>). Moreover, <i>in vivo</i> experimental results confirm that released Cu²⁺ and Zn²⁺ can promote epithelial regeneration, thereby accelerating wound healing. In the bacterially infected mouse model, CuS@ZIF-8@PDA NPs exhibit excellent synergistic antimicrobial and wound healing effects, while having no toxic side effects on major organs. The study of the dual-ion/photothermal synergistic antibacterial strategy based on CuS@ZIF-8@PDA NPs provides a new insight into bacterial infection wound repair.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}