Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Science to go: An analysis of a virtural , hands-on STEM program's impact on science accessibility
No full textDue to the COVID-19 pandemic, students’ ability to participate in hands-on science activities has been greatly limited. As a result, the Smithsonian Environmental Research Center (SERC), in partnership with the Anne Arundel Public Library system launched a virtual, hands-on STEM program called Science to Go (STG). In addition to STEM programming for children, SERC utilized STG materials for professional development (PD) for teachers. This helped increase access to science education by providing educators with additional training, free materials, and relevant curricular activities. This issue of science accessibility historically has been, and still is, an issue for students across the United States, but especially for students from disadvantaged backgrounds (those from low-income households, students with disabilities, and English language learners).This thesis provides information on best practices for virtual, hands-on STEM education and evaluates user feedback for existing Science to Go programs, in order to provide suggestions to improve future iterations of this offering. User feedback was collected through anonymous, online surveys and through virtual interviews. It was discovered that while STG was an accessible and successful program, the logistics of STG are unsustainable in the long-term, as currently designed. Thus, moving forward, STG should be re-structured as a hybrid (in-person- virtual) model for the public library and PD programs. Public library STG programs should collaborate with local citizen scientists and high school STEM programs for both enrichment purposes, and to alleviate logistical issues. PD programs should occur in-person at the host- organization’s site and offer the lecture component to be virtual for teachers who cannot/do not wish to attend in person. Additionally, PD workshops should align with school year timelines, to coincide with curriculums, which will enhance student learning and alleviate teacher burdens, as well as organization logistics. All of these adjustments will help Science to Go operate more efficiently and continue to increase the program’s accessibility
When Moods and Behaviors Do Not Add Up: The Many Masks of Alcohol Use Disorder
No full textThis case report presents a 40-year-old man presenting with mixed mental health symptoms including depression, anxiety, euphoria, sleep cycle disturbances, and alcohol use over several years. Multiple providers see the patient in varying specialties, initially focusing on depression, anxiety, and, later, substance use. Alcohol misuse can shadow underlying mental disorders. Therefore, early recognition and collaborative management are imperative to unveil the possibility of comorbid mental health disorders
Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype
No full textNoncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of
IL-6
,
ICAM-1
,
CXCL-8
, and
SCGB1A1
inflammatory factors;
MUC5AC
and
MUC5B
mucins; and
SPDEF
,
FOXA3
, and
FOXJ1
transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or
LASI
was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and
LASI
lncRNA. Notably, blocking
LASI
lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select
LASI
-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus,
LASI
lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response.
•
COVID19 airway mucoinflammatory response strongly correlates with
LASI
lncRNA level
•
Silencing
LASI
lncRNA suppresses SARS-CoV-2 viral load and associated inflammation
•
LASI
lncRNA shows a potential direct interaction with SARS-CoV-2 spike viral RNA
•
Hosts of airway epithelial miRNAs are modulated by
LASI
to regulate inflammation
Molecular biology; Molecular mechanism of gene regulation; Immunology; Virolog
Targeting RARA Overexpression with Tamibarotene, a Potent and Selective RARα Agonist, is a Novel Approach in AML
No full textA super-enhancer at the retinoic acid receptor alpha (RARA) gene is associated with RARA mRNA overexpression in approximately 30% of non-acute promyelocytic leukemia (non-APL) acute myeloid leukemia (AML) and in approximately 50% of myelodysplastic syndromes (MDS). RARA overexpression is an actionable target for treatment with tamibarotene, an oral potent and selective RARα agonist. Sensitivity to the RARα agonist tamibarotene was demonstrated in RARA-high but not RARA-low preclinical AML models. The combination of oral tamibarotene plus azacitidine was evaluated in a Phase 2 clinical study in 51 newly diagnosed unfit AML patients identified as RARA-positive (N = 22) or RARA-negative (N = 29) for RARA mRNA overexpression in peripheral blasts with a blood-based biomarker test. In 18 response evaluable RARA-positive patients, complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 61%, CR rate was 50%, and time to initial composite CR was rapid at 1.2 months. Transfusion independence was attained by 72% of RARA-positive patients. In contrast, 28 response evaluable RARA-negative patients had response rates that were consistent with azacitidine monotherapy. Tamibarotene in combination with azacitidine was well-tolerated. The majority of non-hematologic adverse events (AEs) were low grade and hematologic AEs were comparable to single agent azacitidine, demonstrating that there was no additional myelosuppression when tamibarotene was combined with azacitidine. These results support further evaluation of tamibarotene-based treatment strategies in AML and MDS patients with RARA overexpression to provide a targeted approach with the goal of improving patient outcomes. This trial is registered at www.clinicaltrials.gov as NCT02807558.
•Tamibarotene plus azacitidine was associated with a high CR rate and a rapid onset of response in RARA-positive newly diagnosed unfit AML.•Tamibarotene-based treatment in AML overexpressing RARA is a novel targeted approach with potential to improve upon current therapy
Catchment Areas, Community Outreach and Engagement Revisited: The 2021 Guidelines for Cancer Center Support Grants from the National Cancer Institute
No full textNew guidelines for Cancer Center Support Grants have recently been issued by the NCI that require increased attention to cancer center catchment areas and their community outreach and engagement activities [PAR-21-321]. Past experience with these requirements has engendered some confusion and frustration on the part of both researchers and reviewers that these new guidelines aim to dispel. In this commentary we, as experienced cancer center leaders in population sciences, offer our views on the most important aspects of the new guidelines and provide three examples of the kinds of programs that can apply cancer prevention and control research to improve cancer population health. With 71 NCI-Designated Cancer Centers in 36 states, the potential for broad impact on the reduction of the nation's cancer burden is enormous if the intended application of cancer center research to individuals and populations is fulfilled
Nanomedicine and nanobiotechnology applications of magnetoelectric nanoparticles
No full textUnlike any other nanoparticles known to date, magnetoelectric nanoparticles (MENPs) can generate relatively strong electric fields locally via the application of magnetic fields and, vice versa, have their magnetization change in response to an electric field from the microenvironment. Hence, MENPs can serve as a wireless two-way interface between man-made devices and physiological systems at the molecular level. With the recent development of room-temperature biocompatible MENPs, a number of novel potential medical applications have emerged. These applications include wireless brain stimulation and mapping/recording of neural activity in real-time, targeted delivery across the blood-brain barrier (BBB), tissue regeneration, high-specificity cancer cures, molecular-level rapid diagnostics, and others. Several independent in vivo studies, using mice and nonhuman primates models, demonstrated the capability to deliver MENPs in the brain across the BBB via intravenous injection or, alternatively, bypassing the BBB via intranasal inhalation of the nanoparticles. Wireless deep brain stimulation with MENPs was demonstrated both in vitro and in vivo in different rodents models by several independent groups. High-specificity cancer treatment methods as well as tissue regeneration approaches with MENPs were proposed and demonstrated in in vitro models. A number of in vitro and in vivo studies were dedicated to understand the underlying mechanisms of MENPs-based high-specificity targeted drug delivery via application of d.c. and a.c. magnetic fields. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologie
Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments
No full textOver the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes
Multifunctional MEN-Doped Adhesives: Strengthening, Bond Quality Evaluation, and Variations in Magnetic Signal with Environmental Exposure
No full textFeatured Application Non-destructive evaluation of bond quality using magneto-electric nanoparticles.
Adhesive bonding of polymer matrix composites offers various advantages over traditional fasteners, such as a uniform stress state, reduced weight, and delay of composite delamination. However, adhesive bonding has limited implementation due to challenges in the prediction of durability. This work introduces a new method to monitor an adhesively bonded composite joint by dispersing magneto-electric nanoparticles (MENs) into the polymer precursor and monitoring changes in their surface charge density by evaluating the output magnetic signal under an applied magnetic field. Real-time monitoring of the curing process of a polymer adhesive was performed and corroborated via thermal analysis and mechanical testing. Lap shear and end notch flexure testing showed that adding 1 vol% MENs led to a similar to 23% increase in shear strength and a similar to 12% increase in mode II critical energy release rates compared to the undoped adhesive. Adding 5 vol% MENs also increased the adhesive's peak tensile stress by similar to 8%. Strengthening mechanisms of the doped adhesive were monitored using in situ electron microscopy. A correlation between water ingression and a change in the magnetic moment was observed. Results show the MENs' potential as a structural health-monitoring tool for a wide range of materials and applications
Quantifying Radiosensitization of PSMA-Targeted Gold Nanoparticles on Prostate Cancer Cells at Megavoltage Radiation Energies by Monte Carlo Simulation and Local Effect Model
No full textActive targeting gold nanoparticles (AuNPs) are a very promising avenue for cancer treatment with many publications on AuNP mediated radiosensitization at kilovoltage (kV) photon energies. However, uncertainty on the effectiveness of AuNPs under clinically relevant megavoltage (MV) radiation energies hinders the clinical translation of AuNP-assisted radiation therapy (RT) paradigm. The aim of this study was to investigate radiosensitization mediated by PSMA-targeted AuNPs irradiated by a 6 MV radiation beam at different depths to explore feasibility of AuNP-assisted prostate cancer RT under clinically relevant conditions. PSMA-targeted AuNPs (PSMA-AuNPs) were synthesized by conjugating PSMA antibodies onto PEGylated AuNPs through EDC/NHS chemistry. Confocal fluorescence microscopy was used to verify the active targeting of the developed PSMA-AuNPs. Transmission electron microscopy (TEM) was used to demonstrate the intracellular biodistribution of PSMA-AuNPs. LNCaP prostate cancer cells treated with PSMA-AuNPs were irradiated on a Varian 6 MV LINAC under varying depths (2.5 cm, 10 cm, 20 cm, 30 cm) of solid water. Clonogenic assays were carried out to determine the in vitro cell survival fractions. A Monte Carlo (MC) model developed on TOPAS platform was then employed to determine the nano-scale radial dose distribution around AuNPs, which was subsequently used to predict the radiation dose response of LNCaP cells treated with AuNPs. Two different cell models, with AuNPs located within the whole cell or only in the cytoplasm, were used to assess how the intracellular PSMA-AuNP biodistribution impacts the prostate cancer radiosensitization. Then, MC-based microdosimetry was combined with the local effect model (LEM) to calculate cell survival fraction, which was benchmarked against the in vitro clonogenic assays at different depths. In vitro clonogenic assay of LNCaP cells demonstrated the depth dependence of AuNP radiosensitization under clinical megavoltage beams, with sensitization enhancement ratio (SER) of 1.14 ± 0.03 and 1.55 ± 0.05 at 2.5 cm depth and 30 cm depth, respectively. The MC microdosimetry model showed the elevated percent of low-energy photons in the MV beams at greater depth, consequently resulting in increased dose enhancement ratio (DER) of AuNPs with depth. The AuNP-induced DER reached ~5.7 and ~8.1 at depths of 2.5 cm and 30 cm, respectively. Microdosimetry based LEM accurately predicted the cell survival under 6 MV beams at different depths, for the cell model with AuNPs placed only in the cell cytoplasm. TEM results demonstrated the distribution of PSMA-AuNPs in the cytoplasm, confirming the accuracy of MC microdosimetry based LEM with modelled AuNPs distributed within the cytoplasm. We conclude that AuNP radiosensitization can be achieved under megavoltage clinical radiotherapy energies with a dependence on tumor depth. Furthermore, the combination of Monte Carlo microdosimetry and LEM will be a valuable tool to assist with developing AuNP-aided radiotherapy paradigm and drive clinical translation
Common Variants Near ZIC1 and ZIC4 in Autopsy-Confirmed Multiple System Atrophy
No full textBackground Multiple System Atrophy is a rare neurodegenerative disease with alpha-synuclein aggregation in glial cytoplasmic inclusions and either predominant olivopontocerebellar atrophy or striatonigral degeneration, leading to dysautonomia, parkinsonism, and cerebellar ataxia. One prior genome-wide association study in mainly clinically diagnosed patients with Multiple System Atrophy failed to identify genetic variants predisposing for the disease. Objective Since the clinical diagnosis of Multiple System Atrophy yields a high rate of misdiagnosis when compared to the neuropathological gold standard, we studied only autopsy-confirmed cases. Methods We studied common genetic variations in Multiple System Atrophy cases (N = 731) and controls (N = 2898). Results The most strongly disease-associated markers were rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 with P-values below 5 x 10(-6), all of which were supported by at least one additional genotyped and several imputed single nucleotide polymorphisms. The genes closest to the chromosome 3 locus are ZIC1 and ZIC4 encoding the zinc finger proteins of cerebellum 1 and 4 (ZIC1 and ZIC4). Interpretation Since mutations of ZIC1 and ZIC4 and paraneoplastic autoantibodies directed against ZIC4 are associated with severe cerebellar dysfunction, we conducted immunohistochemical analyses in brain tissue of the frontal cortex and the cerebellum from 24 Multiple System Atrophy patients. Strong immunohistochemical expression of ZIC4 was detected in a subset of neurons of the dentate nucleus in all healthy controls and in patients with striatonigral degeneration, whereas ZIC4-immunoreactive neurons were significantly reduced inpatients with olivopontocerebellar atrophy. These findings point to a potential ZIC4-mediated vulnerability of neurons in Multiple System Atrophy. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ