bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical use and misuse of psychoactive prescription medications among US youth and young adults
Authors: Agaku Israel , Odani Satomi , Nelson Jantel 
Published: February 2021

ObjectiveTo investigate prevalence and correlates of medical use and misuse of psychoactive prescription medications among US youth and young adults.DesignCross-sectional, self-reported surveys from the 2015–2018 National Survey of Drug Use and Health. Sampling was probabilistic and nationally representative.SettingThe target population included individuals from households, non-institutional group quarters (eg, college dormitories) and civilians living on military bases. Questionnaires were completed using computer-assisted self-interview methods.ParticipantsOur analytical sample included youth and young adults aged 12–25 years (n=110 556). Psychoactive prescription medication misuse was a report by the respondent that they had used psychoactive prescription medications in the past year in any way not directed or prescribed for them. Medical use was defined as past-year use without a report of misuse. Because certain variables were assessed only among adults, our multivariable analysis to identify correlates of misuse was restricted to young adults aged 18–25 years (n=55 690).ResultsAmong US youth aged 12–17 years, 25.0% reported use of any psychoactive prescription medication assessed, and 5.7% reported past-year use of at least two psychoactive prescription medications. Among youth who used any psychoactive prescription medications, 20.9% (1.3 million) reported misuse; 3.4% were classified as having substance use disorder. Past-year use of each psychoactive prescription medication was: opioids (19.0%), stimulants (7.2%), tranquillisers (4.3%) and sedatives (2.2%). Among users of each psychoactive prescription medication, the estimated percentage reporting misuse was as follows: opioids (17.6%, 0.8 million), stimulants (24.2%, 0.4 million), tranquillisers (40.1%, 0.4 million) and sedatives (14.2%, 80 000). Among users of each psychoactive prescription medication, the estimated percentage having substance use disorder was as follows: opioids 2.6%, stimulants 3.0%, tranquillisers 7.0% and sedatives 3.6%. Analyses among young adults aged 18–25 years revealed that, compared with never users of non-prescription substances (including alcohol, tobacco, marijuana, cocaine, heroin), opioid misuse increased with: more recent use of non-prescription substances (adjusted prevalence ratios (APRs)=8.26, 2.75 and 2.41 for past ≤30-day, ≤12-month and >12-month use, respectively); and a higher number of substances used (APRs=1.69, 3.44, 6.82, 10.60 and 20.60 for 1, 2, 3, 4 and 5+ substances, respectively) (all p<0.05). Similar patterns were seen for stimulants, tranquillisers and sedatives.ConclusionsIt is important to monitor the diversity of medication misuse behaviours among youth and young adults, given their potential for abuse liability. Modifiable risk factors for prescription substance misuse, such as tobacco and other non-prescription substance use, underscore the need for comprehensive approaches towards health promotion among youth and young adults.
An investigation on the possibility to improve the corrosion and cavitation resistance of SS304 steel by NiTi coatings
Authors: Zeng Qunfeng , Khanlari Khashayar , Lin Naiming 
Published: February 2021

Equiatomic and near equiatomic NiTi alloys, showing good mechanical and thermal shape memory properties, are widely exploited in different industrial applications. In addition, NiTi alloys have promising anti-cavitation and corrosion-resistance properties. These advantages have provided opportunities to exploit NiTi alloys as the coatings for protecting materials used in the industrial applications. This study is a preliminary investigation aiming to evaluate the feasibility to form NiTi alloy coatings on SS304 steel by tungsten inert argon arc welding (TIG) technology. The microstructure analysis shows that the crystalline phases in NiTi coatings on SS 304 steel are TiNi-B2, TiNi-B19’ and Ni3Ti. The potential of the NiTi coatings to enhance the corrosion resistance and cavitation resistance behaviors of steel exposed to seawater is studied. NiTi coatings, with two different thicknesses of about 1.2 and 2 mm, having homogenous microstructures were successfully deposited on SS304 steel using TIG technology. Results of tests, done in aqueous solutions simulating seawater, showed that the formation of the oxide films on the surface of NiTi coatings increased the corrosion resistance and wear resistance and decreased the damage caused by the cavitation. Moreover, it was understood that the NiTi coatings with 2 mm in thickness show the superior performances than those with 1.2 mm in thickness. The tribological mechanisms responsible for the unique properties of NiTi alloy coatings were investigated. The wear-resistance behaviors of NiTi alloy coatings are greatly influenced by the friction conditions. Increasing load decreased CoF and the wear rate of the coatings were almost constant, which was attributed to the pseudoelasticity of NiTi alloy. The attractive properties of NiTi alloys that makes it most influential materials for industrial applications have also been discussed.
Combined mental task and metaboreflex impair cerebral oxygenation in patients with type 2 diabetes mellitus
Authors: Pinna Virginia , Doneddu Azzurrra , Roberto Silvana , Magnani Sara , Ghiani Giovanna , Mulliri Gabriele , Sanna Irene , Serra Stefano , Hosseini Kakhak Seyed Alireza , Milia Raffaele , Fadda Daniela , Lecis Romina , Guicciardi Marco , Crisafulli Antonio 
Published: February 2021

Cardiovascular regulation is altered by type 2 diabetes mellitus (DM2), producing an abnormal response to muscle metaboreflex. During physical exercise, cerebral blood flow is impaired in patients with DM2, and this phenomenon may reduce cerebral oxygenation (COX). We hypothesized that the simultaneous execution of a mental task (MT) and metaboreflex activation would reduce COX in patients with DM2. Thirteen individuals suffering from DM2 (6 women) and 13 normal age-matched controls (CTL, 6 women) participated in this study. They underwent five different tests, each lasting 12 min: postexercise muscle ischemia (PEMI) to activate the metaboreflex, control exercise recovery (CER), PEMI + MT, CER + MT, and MT alone. COX was evaluated using near-infrared spectroscopy with sensors applied to the forehead. Central hemodynamics was assessed using impedance cardiography. We found that when MT was superimposed on the PEMI-induced metaboreflex, patients with DM2 could not increase COX to the same extent reached by the CTL group (101.13% ± 1.08% vs. 104.23% ± 2.51%, P < 0.05). Moreover, patients with DM2 had higher mean blood pressure and systemic vascular resistance as well as lower stroke volume and cardiac output levels compared with the CTL group, throughout our experiments. It was concluded that patients with DM2 had reduced capacity to enhance COX when undertaking an MT during metaboreflex. Results also confirm that patients with DM2 had dysregulated hemodynamics during metaboreflex, with exaggerated blood pressure response and vasoconstriction. This may have implications for these patients’ lack of inclination to exercise.
Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer
Authors: De Angelis Carmine , Fu Xiaoyong , Cataldo Maria Letizia , Nardone Agostina , Pereira Resel , Veeraraghavan Jamunarani , Nanda Sarmistha , Qin Lanfang , Sethunath Vidyalakshmi , Wang Tao , Hilsenbeck Susan G. , Benelli Matteo , Migliaccio Ilenia , Guarducci Cristina , Malorni Luca , Litchfield Lacey M. , Liu Jiangang , Donaldson Joshua , Selenica Pier , Brown David N. , Weigelt Britta , Reis-Filho Jorge S. , Park Ben H. , Hurvitz Sara A. , Slamon Dennis J. , Rimawi Mothaffar F. , Jansen Valerie M. , Jeselsohn Rinath , Osborne C. Kent , Schiff Rachel 
Published: February 2021

Abstract

Purpose:
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor–positive (ER+)/HER2− breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.

Experimental Design:
Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation–resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.

Results:
Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an “IFN-related palbociclib-resistance Signature” (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2− tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.

Conclusions:
Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.
Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth
Authors: Cheng Jonathan D. , Valianou Matthildi , Canutescu Adrian A. , Jaffe Eileen K. , Lee Hyung-Ok , Wang Hao , Lai Jack H. , Bachovchin William W. , Weiner Louis M. 
Published: February 2021

Abstract
Tumor-associated fibroblasts are functionally and phenotypically distinct from normal fibroblasts that are not in the tumor microenvironment. Fibroblast activation protein is a 95 kDa cell surface glycoprotein expressed by tumor stromal fibroblasts, and has been shown to have dipeptidyl peptidase and collagenase activity. Site-directed mutagenesis at the catalytic site of fibroblast activation protein, Ser624 → Ala624, resulted in an ∼100,000-fold loss of fibroblast activation protein dipeptidyl peptidase (DPP) activity. HEK293 cells transfected with wild-type fibroblast activation protein, enzymatic mutant (S624A) fibroblast activation protein, or vector alone, were inoculated subcutaneously into immunodeficient mouse to assess the contribution of fibroblast activation protein enzymatic activity to tumor growth. Overexpression of wild-type fibroblast activation protein showed growth potentiation and enhanced tumorigenicity compared with both fibroblast activation protein S624A and vector-transfected HEK293 xenografts. HEK293 cells transfected with fibroblast activation protein S624A showed tumor growth rates and tumorigenicity potential similar only to vector-transfected HEK293. In vivo assessment of fibroblast activation protein DPP activity of these tumors showed enhanced enzymatic activity of wild-type fibroblast activation protein, with only baseline levels of fibroblast activation protein DPP activity in either fibroblast activation protein S624A or vector-only xenografts. These results indicate that the enzymatic activity of fibroblast activation protein is necessary for fibroblast activation protein–driven tumor growth in the HEK293 xenograft model system. This establishes the proof-of-principle that the enzymatic activity of fibroblast activation protein plays an important role in the promotion of tumor growth, and provides an attractive target for therapeutics designed to alter fibroblast activation protein–induced tumor growth by targeting its enzymatic activity.
Abstract IA03: Engineering artificial antigen presenting cells, aAPC, for cancer immunotherapy: From bench to bedside
Authors: Schneck Jonathan P. 
Published: February 2021

Abstract
Adoptive Cellular Therapies, ACT, are promising immunotherapeutic approaches for treatment of cancer that, clinically, have had significant successes and yet many challenges remain that prevent ACT approaches from becoming front line therapy. In this presentation we will discuss the challenges associated with current approaches and show how artificial Antigen Presenting Cells, aAPC-based approaches help overcome those challenges. Thus, aAPC based approaches represent an off-shelf, scalable approach to production of clinical scale and grade T cells for the adoptive immunotherapy of cancer.
Citation Format: Jonathan P. Schneck. Engineering artificial antigen presenting cells, aAPC, for cancer immunotherapy: From bench to bedside [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA03.
Abstract PO019: CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
Authors: de Lara Paulino Tallón , Cuadrado Héctor Castañón , Vermeer Marijne , Núñez Nicolás , Silina Karina , Sobottka Bettina , Urdínez Joaquín , Cecconi Virginia , Attar Farkhondeh Movahedian , Hiltbrunner Stefanie , Glarner Isabelle , Moch Holger , Tugues Sònia , Becher Burkhard , van den Broek Maries 
Published: February 2021

Abstract
Some breast tumors metastasize aggressively whereas others remain in a state of metastatic dormancy for months or even years. The mechanism governing such metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping, we identified a discrete population of CD39+PD-1+CD8+ T cells present both in primary tumors and in dormant metastasis, which was hardly found in aggressively metastasizing tumors. Of note, the adoptive transfer of purified CD39+PD-1+CD8+ T cells prevented metastatic outgrowth. Stimulation of CD39+PD-1+CD8+ T cells with PD-1 blockade reduced the number of disseminated dormant cells. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not of total CD8+ T cells correlated with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+ T cells for controlling experimental and human breast cancer. Furthermore, density of CD39+PD-1+CD8+ T cells may serve as a novel biomarker and may serve as a potential immunotherapy target. Here, we discovered that a primary breast tumor primes a systemic, CD39+PD-1+CD8+ T cell response that is essential for metastatic dormancy in the lungs.
Citation Format: Paulino Tallón de Lara, Héctor Castañón Cuadrado, Marijne Vermeer, Nicolás Núñez, Karina Silina, Bettina Sobottka, Joaquín Urdínez, Virginia Cecconi, Farkhondeh Movahedian Attar, Stefanie Hiltbrunner, Isabelle Glarner, Holger Moch, Sònia Tugues, Burkhard Becher, Maries van den Broek. CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO019.
Abstract PO039: Cancer cells educate natural killer cells to a metastasis-promoting cell state
Authors: Chan Isaac S. , Knútsdóttir Hildur , Ramakrishnan Gayathri , Padmanaban Veena , Warrier Manisha , Ramirez Juan Carlos , Dunworth Matthew , Zhang Hao , Jaffee Elizabeth M. , Bader Joel S. , Ewald Andrew J. 
Published: February 2021

Abstract
Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer cells escape NK cell surveillance. Using ex vivo and in vivo models of metastasis, we establish that keratin-14+ breast cancer cells are vulnerable to NK cells. We then discovered that exposure to cancer cells causes NK cells to lose their cytotoxic ability and promote metastatic outgrowth. Gene expression comparisons revealed that healthy NK cells have an active NK cell molecular phenotype, whereas tumor-exposed (teNK) cells resemble resting NK cells. Receptor–ligand analysis between teNK cells and tumor cells revealed multiple potential targets. We next showed that treatment with antibodies targeting TIGIT, antibodies targeting KLRG1, or small-molecule inhibitors of DNA methyltransferases (DMNT) each reduced colony formation. Combinations of DNMT inhibitors with anti-TIGIT or anti-KLRG1 antibodies further reduced metastatic potential. We propose that NK-directed therapies targeting these pathways would be effective in the adjuvant setting to prevent metastatic recurrence.
Citation Format: Isaac S. Chan, Hildur Knútsdóttir, Gayathri Ramakrishnan, Veena Padmanaban, Manisha Warrier, Juan Carlos Ramirez, Matthew Dunworth, Hao Zhang, Elizabeth M. Jaffee, Joel S. Bader, Andrew J. Ewald. Cancer cells educate natural killer cells to a metastasis-promoting cell state [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO039.
Abstract PO043: Layer-by-layer nanoparticles for non-toxic delivery of interleukin 12 to disseminated syngeneic ovarian tumors
Authors: Smith Sean G. , Barberio Antonio E. , Pires Ivan S. , Melo Mariane , Irvine Darrell J. , Hammond Paula T. 
Published: February 2021

Abstract
Ovarian cancer presents a notable challenge for cancer immunotherapy with less than a 10% objective response rate to checkpoint inhibitors (CPI). One strategy to augment the impact of checkpoint therapy is to initiate the infiltration of leukocytes into the tumor prior to CPI using pro-inflammatory cytokines. One particularly potent and promising cytokine is interleukin-12 (IL-12) – the hallmark Th-1 cytokine known to drive an influx of antigen presenting cells, expansion of cytotoxic T-cells, and NK-cell activation in a variety of solid tumors. Unfortunately, IL-12 has been hampered clinically by toxicity issues when administered systemically – a necessity for disseminated tumors such as advanced ovarian cancer. We have previously shown that nanoparticles engineered for cytokine delivery target human ovarian tumors in mouse models and that delivery of IL-12 using those particles enables the non-toxic delivery of IL-12 when given intratumorally to syngeneic tumors. In this study we demonstrate that these particles given systemically continue to limit IL-12 toxicity, accumulate within syngeneic, orthotopic models of ovarian tumors, induce tumor regressions, and reshape the immune microenvironment within those tumors. IL-12 was loaded onto the surface of negatively charged liposomes using the Ni-His interaction. The layer-by-layer process was then used to add layers of poly-L-arginine and poly-L-glutamine producing a final diameter of 120 nm and zeta potential of -60 mV. These layered nanoparticles (LNPs) preferentially accumulated in intraperitoneal HM-1 ovarian tumor nodules when given intravenously and intraperitoneally with a 30% increase in concentration over unlayered nanoparticles (ULNPs) as measured via fluorescence. IL-12 accumulation measured using ELISA was shown to correlate with NP accumulation for LNPs but not ULNPs. LNPs were non-toxic (via weight loss) at doses deemed toxic with ULNPs or free IL-12. Intraperitoneal treatment with LNPs extended survival and caused tumor regression in 30% of mice at a dose deemed toxic for free IL-12 or ULNPs (10 µg IL-12 given once daily for 5 days). Flow cytometry revealed a marked increase in memory T-cells and a decrease in granulocytes. The LNPs also induced substantial upregulation of exhaustion markers in the infiltrating T-cells – especially the TIM3+TIGIT+PD1+ highly exhausted phenotype suggesting potential for future combination therapies.
Citation Format: Sean G. Smith, Antonio E. Barberio, Ivan S. Pires, Mariane Melo, Darrell J. Irvine, Paula T. Hammond. Layer-by-layer nanoparticles for non-toxic delivery of interleukin 12 to disseminated syngeneic ovarian tumors [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO043.
Abstract PO091: Armed Myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors
Authors: Franco Lina S. , Torres-Dominguez Lino E. , Mamola Joseph , de Matos Ana L. , Abrantes Mario , Walker Benjamin S. , Tacner Zachary , Kien Cassandra , Elliott Natalie M. , McFadden Grant , Sharp Leslie L. 
Published: February 2021

Abstract
Oncolytic Viruses (OV) selectively replicate in and lyse tumor cells and provide stimulation to the immune system. This represents a promising therapeutic option for cancer patients that do not respond well to treatment with immune checkpoint inhibitors. Myxoma virus (MYXV) is a member of the Poxviridae family of double stranded DNA viruses. The natural host of MYXV is a subset of lagomorphs, but MYXV can infect cancer cell lines of humans and other species. The genome of MYXV is relatively large and is amenable to engineering for expression of transgenes making it an excellent oncolytic virus for introduction of immunomodulatory proteins. The current work describes the oncolytic activity, transgene production capability, in vivo activity and immunomodulatory mechanism of actions following intratumoral and intravenous administration of armed myxoma viruses in murine cancer models. Additional combination therapy with clinically relevant immune checkpoint inhibitors is demonstrated.
Citation Format: Lina S. Franco, Lino E. Torres-Dominguez, Joseph Mamola, Ana L. de Matos, Mario Abrantes, Benjamin S. Walker, Zachary Tacner, Cassandra Kien, Natalie M. Elliott, Grant McFadden, Leslie L. Sharp. Armed Myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO091.