St. John's University
  • New York City, United States
Recent publications
Lexical predictability has been shown to be modulated by the global context, but it is unclear whether the global context has a similar modulating effect on the prediction of semantic features. Event-related potentials (ERP) should be helpful in addressing this question, as the N400 effect is sensitive to both lexical predictability and the prediction of semantic features during sentence comprehension. The present study manipulated the semantic similarity between unpredictable target words and expected words in experimental sentences. Different types of filler sentences (predictable vs. incongruous) were used to manipulate the global prediction reliability (GPR). The ERP results showed that, in the predictable filler block, the N400 was reduced when there was high semantic similarity between the unpredictable target word and expected word in the experimental sentences. However, this association was absent in the incongruous filler block, in which participants were discouraged from predicting the upcoming information. These results suggest that the prediction of semantic features of upcoming words could be modulated by the global context.
Brown algae adsorb a considerable amount of CO2 and store carbon in their biomass more than many other algae species. Nowadays, depletion of fossil fuel resources, greenhouse gas emissions, climate change, and the future of human food security have encouraged scientists and policymakers to develop safer and more sustainable alternatives of energy sources. Brown algae have attracted most of this attention in North American countries to generate a wide range of products and biomass for biorefinery. In this review paper, various aspects of brown algae cultivation and its biorefinery process are discussed. Main drivers of the sectors, opportunities, challenges, and future prospects of brown algae-based biofuels in North America have been taken into account; the most appropriate processes and pathways are compared to maximize the outputs and environmental benefits, and minimize costs and drawbacks of the industry. Analysis and predictions of renewable energy future in North American countries revealed that biomass-derived fuels, including brown algae biofuels, will play an important role especially in the transportation sector. These biofuels, including bioethanol and biodiesel are accompanied by various co-products and by-products in an optimized biorefinery system to convert every available component of brown algae. However, cultivation of brown algae to produce biomass at a commercial scale with minimum costs and market demands are the main challenges of algal biofuels. Finally, expanding the value chain of the brown algae biorefinery by producing more advanced biofuels such as aviation fuels and value-added co- and by-products would significantly impact North American countries' gross domestic product.
  • Suyash M. PatilSuyash M. Patil
  • Druva Sarika BarjiDruva Sarika Barji
  • Tejashri ChavanTejashri Chavan
  • [...]
  • Nitesh K. KundaNitesh K. Kunda
Tuberculosis (TB) is a contiguous airborne disease caused by Mycobacterium tuberculosis (M.tb), primarily affecting the human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become a global challenge toward eradicating TB. Conventional TB treatment involves frequent dosing and prolonged treatment regimens predominantly by an oral or invasive route, leading to treatment-related systemic adverse effects and patient’s noncompliance. Pulmonary delivery is an attractive option as we could reduce dose, limit systemic side-effects, and achieve rapid onset of action. Delamanid (DLD), an antituberculosis drug, has poor aqueous solubility, and in this study, we aim to improve its solubility using cyclodextrin complexation. We screened different cyclodextrins and found that HP-β-CD resulted in a 54-fold increase in solubility compared to a 27-fold and 13-fold increase by SBE-β-CD and HP-ɣ-CD, respectively. The stability constant (265 ± 15 M−1) and complexation efficiency (8.5 × 10−4) suggest the formation of a stable inclusion complex of DLD and HP-β-CD in a 2:1 ratio. Solid-state characterization studies (DSC, PXRD, and NMR) further confirmed successful complexation of DLD in HP-β-CD. The nebulized DLD-CD complex solution showed a mass median aerodynamic diameter of 4.42 ± 0.62 μm and fine particle fraction of 82.28 ± 2.79%, suggesting deposition in the respiratory airways. In bacterial studies, minimum inhibitory concentration of DLD-CD complex was significantly reduced (four-fold) compared to free DLD in M.tb (H37Ra strain). Furthermore, accelerated stability studies confirmed that the inclusion complex was stable for 4 weeks with 90%w/w drug content. In conclusion, we increased the aqueous solubility of DLD through cyclodextrin complexation and improved its efficacy in vitro.Graphical Abstract
Spatial and social behaviour are fundamental aspects of an animal's biology, and their social and spatial environments are indelibly linked through mutual causes and shared consequences. We define the ‘spatial–social interface’ as intersection of social and spatial aspects of individuals' phenotypes and environments. Behavioural variation at the spatial–social interface has implications for ecological and evolutionary processes including pathogen transmission, population dynamics, and the evolution of social systems. We link spatial and social processes through a foundation of shared theory, vocabulary, and methods. We provide examples and future directions for the integration of spatial and social behaviour and environments. We introduce key concepts and approaches that either implicitly or explicitly integrate social and spatial processes, for example, graph theory, density‐dependent habitat selection, and niche specialization. Finally, we discuss how movement ecology helps link the spatial–social interface. Our review integrates social and spatial behavioural ecology and identifies testable hypotheses at the spatial–social interface.
Medical misinformation is more pervasive today because of widespread and near instantaneous dissemination of information via the internet and social media platforms. Consequences of medical misinformation may include decreased uptake of needed health care resources, delays in seeking care, vaccine hesitancy, medication non‐compliance, increased disease outbreaks and/or burden, and increased hospitalization and mortality. It disproportionately impacts underserved populations, including Black patients, those who identify as LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and more), and patients with reduced health literacy skills or who are digitally disadvantaged. Medical misinformation challenges health care professionals not only to provide the best care possible, but to assist patients in finding accurate information. Preprint publications, although potentially beneficial in rapidly disseminating new scientific discoveries, often have not undergone peer review and may contribute to the widespread propagation of inaccurate or overstated results, thereby perpetuating the spread of medical misinformation when it exists. The coronavirus disease 2019 (COVID‐19) pandemic highlighted the importance of practicing evidence‐based medicine and the need for cautious review of preprint publications and articles from predatory publishers in addition to usual and customary literature evaluation techniques. Everyone plays a role in preventing the spread of medical misinformation, with pharmacists uniquely positioned as trusted and highly accessible professionals who may help combat its spread. The goal of this paper is to define medical misinformation and related terms, outline mechanisms by which it is spread, describe its clinical impact, highlight how it disproportionately impacts underserved populations, provide actionable strategies to prevent its spread, and give examples of practical tactics to help identify, correct, and alert individuals about the possible presence of medical misinformation. This article is protected by copyright. All rights reserved.
Hydrophobic tagging (HyT) is a potential therapeutic strategy for targeted protein degradation (TPD). Norbornene was discovered as an unprecedented hydrophobic tag in this study and was used to degrade the anaplastic lymphoma kinase (ALK) fusion protein by linking it to ALK inhibitors. The most promising degrader, Hyt‐9, potently reduced ALK levels through Hsp70 and the ubiquitin‒proteasome system (UPS) in vitro without compensatory upregulation of ALK. Furthermore, Hyt‐9 exhibited a significant tumor‐inhibiting effect in vivo with moderate oral bioavailability. More importantly, norbornene can also be used to degrade the intractable enhancer of zeste homolog 2 (EZH2) when tagged with the EZH2 inhibitor tazemetostat. Thus, the discovery of novel hydrophobic norbornene tags shows promise for the future development of TPD technology.
Hydrophobic tagging (HyT) is a potential therapeutic strategy for targeted protein degradation (TPD). Norbornene was discovered as an unprecedented hydrophobic tag in this study and was used to degrade the anaplastic lymphoma kinase (ALK) fusion protein by linking it to ALK inhibitors. The most promising degrader, Hyt‐9, potently reduced ALK levels through Hsp70 and the ubiquitin‒proteasome system (UPS) in vitro without compensatory upregulation of ALK. Furthermore, Hyt‐9 exhibited a significant tumor‐inhibiting effect in vivo with moderate oral bioavailability. More importantly, norbornene can also be used to degrade the intractable enhancer of zeste homolog 2 (EZH2) when tagged with the EZH2 inhibitor tazemetostat. Thus, the discovery of novel hydrophobic norbornene tags shows promise for the future development of TPD technology.
We conducted an observational study of a collection of interactive processes known as “demand‐withdraw” in relation to adolescent dating aggression. Couples (N = 209) aged 14–18 years participated in a challenging observational laboratory assessment to measure demands (i.e., pressures for a change), as well as demand → partner withdraw and demand → partner avoid sequences. Actor and partner effects were disentangled via dyadic data analyses. The results indicated a fairly consistent pattern in which demand → withdraw and demand → avoid sequences led by either partner were positively associated with both partners' physical and psychological aggression (measured via a dual informant questionnaire method). Further, higher quality demands (i.e., pressures for change that were specific and encouraged both members of the dyad to increase a given behavior) were inversely associated with aggression. Yet, all of the above associations were attenuated to the point of statistical nonsignificance after controlling for hostility. These results suggest two primary possibilities. The associations of demand → withdraw and demand → avoid sequences with dating aggression may be spurious, with the sequences merely markers for hostility, a known correlate of dating aggression. Alternatively, hostility may mediate the relations of demand → withdraw and demand → avoid sequences with dating aggression. Further research is required to test these competing explanations. Implications for preventive intervention are discussed.
Introduction: Alectinib is an oral anaplastic lymphoma kinase tyrosine kinase inhibitor with central nervous system activity. It is currently approved and a preferred first-line option for those with anaplastic lymphoma kinase-positive non-small cell lung cancer. Alectinib has been shown to cause anemia, usually mild. Case report: We report a case of alectinib-induced hemolytic anemia in a patient receiving alectinib as first-line treatment for anaplastic lymphoma kinase-positive non-small cell lung cancer. Management and outcome: The patient's dose was reduced from 600 mg twice daily to 450 mg twice daily and further down to 300 mg twice daily and eventually discontinued. At that point, the hemoglobin normalized. Discussion: Our case demonstrates objective evidence for hemolytic anemia induced by alectinib.
Ferroptosis is a regulated form of cell death driven by the lethal accumulation of lipid peroxides in cell membranes. Several regulators of ferroptosis have been identified using cancer cell lines. However, the cellular pathways of ferroptosis in neurons remain poorly characterized. In this study, we used a mouse embryonic stem cell-derived motor neuron model to investigate how motor neurons respond to ferroptosis inducers. Pharmacological and genetic inhibition of glutathione peroxidase 4 (GPx4) induced ferroptosis in motor neurons, while system xc - inhibition by erastin had no effect. RNA-seq analysis showed that the expression levels of several genes were altered during RSL3-induced ferroptosis. Subsequent bioinformatic analysis revealed alterations in several biological pathways during ferroptosis, including synaptogenesis and calcium signaling. Finally, we found that edaravone, an FDA-approved drug for treating amyotrophic lateral sclerosis (ALS) disease, rescued motor neurons from RSL3-induced ferroptosis. Our data highlight the crucial role of GPx4 in ferroptosis regulation, and demonstrate that stem cell-derived motor neuron culture is a valuable model to study ferroptosis at the single-cell level in a neuronal context.
Huntington disease (HD) is a progressive neurodegenerative disease that is debilitating for families worldwide. Inherited in an autosomal dominant manner, HD results from a CAG expansion in the gene encoding the huntingtin protein. This mutation leads to a host of motor, cognitive, and psychiatric symptoms that generally appear in middle age. While spiny projection neurons in the striatum are the most vulnerable cell type in HD, notable atrophy occurs throughout the brain, including the white matter; for this reason, HD is now considered to be a brain-wide disease. The clinical features, ethics, and neurobiology of HD are discussed in this chapter. The chapter also reviews the exciting approaches being employed today to advance understanding of underlying mechanisms in an effort to develop therapies that would delay the onset and slow progression of this disease.
Unlike the flat-view matrix, tensor provides an elegant representation to preserve the structure of data in the multidimensional nature. The wide use of tensor-based approaches highlights the limitation of matrix-based methods and has generated increasing needs in multidimensional data analytics. Driven by such demands, tensor decomposition with automatic rank determination has recently emerged as a promising tool for image processing, wireless communications and neural network compression. However, unlike the success in matrix-based schemes of exploring the correlation for performance improvement, existing tensor-based methods fail to consider the correlation structure in the tensor. In this paper, we propose to exploit the tensor intra-dimension correlation within the framework of sparse Bayesian learning. We provide the sparsity-inducing probabilistic models under both canonical polyadic decomposition and Tucker decomposition to capture the correlation structure effectively. We derive an efficient model inference method with a fast convergence rate based on the expectation-maximization algorithm. Furthermore, a complexity reduction method is proposed to speed up the computation by exploiting several properties of the Kronecker product. We further extend the proposed framework for the incomplete tensor corrupted by sparse outliers to achieve effective tensor completion and outlier mitigation. Simulation results demonstrate the superior performance of the proposed framework over those ignoring the intra-dimension correlation in terms of accuracy and sparsity.
Background As known, inhibition of phosphodiesterase 5 (PDE5) has the therapeutic effect on male erectile dysfunction (ED), and the processed folium of Epimedium sagittatum Maxim. (PFES) characterized by 8-isopentenyl flavonoids is a famous herb for treating ED. However, the main flavonoids inhibitory activities, structure–activity relationship (SAR) and signaling pathway have been not systematically studied so that its pharmacodynamic mechanism is unclear. Methods We aimed to initially reveal the PFES efficacy mechanism for treating ED. For the first time, 6 main 8-isopentenyl flavonoids (1–6) from PFES were isolated and identified. Then based on HPLC detection, we proposed a novel method to screen inhibitors among them. We further analyze the three-dimensional quantitative structure–activity relationship (3D-QSAR) for those inhibitors. Results The results were verified by cellular effects of the screened flavonoids. Among 6 compounds, Icariin: (1), 2-Oʹʹrhamnosylicaridide II (2) and Baohuoside I (3) were identified with significant activities (IC 50 = 8.275, 3.233, 5.473 μM). Then 3D-QSAR studies showed that the replacement of C8 with bulky steric groups as isopentenyl, C3 with positive charge groups and C4' with a hydrogen bond acceptor substituent could increase inhibitory effects. In contrast, the substitution of C7 with bulky steric groups or hydrophilic groups tended to decrease the efficacies. And compounds 1, 2, 3 could increase cGMP level and decrease cytoplasmic Ca ²⁺ of rat corpus cavernosum smooth muscle cells (CCSMCs)by activating PKG. Conclusion 8-isopentenyl flavonoids could be the main pharmacodynamic substances of PFES in the treatment for ED, and some had significant PDE5A1 inhibitory activities so as to activate cGMP/PKG/Ca ²⁺ signaling pathway in CCSMCs, that was related to the substituents at the key sites such as C8, C3, C4ʹ and C7 in the characteristic compounds.
Being the fourth most fatal malignancy worldwide, pancreatic cancer is on track to become the second leading cause of cancer-related deaths in the United States by 2030. Gemcitabine is a first-line chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine Elaidate (Gem Elaidate) is a lipophilic derivative which allows hENT1-independent intracellular delivery of gemcitabine and better pharmacokinetics and entrapment in a nanocarrier. Cancer cells and neovasculature are negatively charged compared to healthy cells. Palmitoyl-DL-carnitine chloride (PC) is a Protein kinase C (PKC) inhibitor which also provides a cationic surface charge to nanoliposomes for targeting tumor neovasculature and augmented anticancer potency. The objectives of our study are: (a) to develop and characterize a PKC inhibitor-anchored Gem Elaidate-loaded PEGylated nanoliposome (PGPLs) and (b) to investigate the anticancer activity of Gem Elaidate and PGPLs in 2D and 3D models of pancreatic cancer. The optimized PGPLs resulted in a particle size of 80 ± 2.31 nm, a polydispersity index of 0.15 ± 0.05 and a ζ-potential of +31.6 ± 3.54 mV, with a 93.25% encapsulation efficiency of Gem Elaidate in PGPLs. Our results demonstrate higher cellular uptake, inhibition in migration, as well as angiogenesis potential and significant apoptosis induced by PGPLs in 3D multicellular tumor spheroids of pancreatic cancer cells. Hence, PGPLs could be an effective and novel nanoformulation for the neovasculature-specific delivery of Gemcitabine Elaidate to treat PDAC.
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Fazel Keshtkar
  • Department of Computer Science, Mathematics and Science
Ali B. Mahmoud
  • The Peter J. Tobin College of Business
Louis Trombetta
  • Department of Pharmaceutical Sciences
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