• New DEEL Community Podcast: Episode 1

      New Democratic Ethical Educational Leadership (DEEL) Community (Temple University) (2020-07-20)
    • No more business as usual: Agile and effective responses to emerging pathogen threats require open data and open analytics

      Baker, Dannon; van den Beek, Marius; Blankenberg, Daniel; Bouvier, Dave; Chilton, John; Coraor, Nate; Coppens, Frederik; Eguinoa, Ignacio; Gladman, Simon; Grüning, Björn; Keener, Nicholas; Larivière, Delphine; Lonie, Andrew; Pond, Sergei; Maier, Wolfgang; Nekrutenko, Anton; Taylor, James; Weaver, Steven; 0000-0003-4817-4029; 0000-0002-6931-7191 (2020-08-13)
      The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.
    • Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System

      Hauck, Ellen S.; Hecker, James G. (2022-01-11)
      Appropriate gene delivery systems are essential for successful gene therapy in clinical medicine. Lipid-mediated nucleic acid delivery is an alternative to viral vector-mediated gene delivery and has the following advantages. Lipid-mediated delivery of DNA or mRNA is usually more rapid than viral-mediated delivery, offers a larger payload, and has a nearly zero risk of incorporation. Lipid-mediated delivery of DNA or RNA is therefore preferable to viral DNA delivery in those clinical applications that do not require long-term expression for chronic conditions. Delivery of RNA may be preferable to non-viral DNA delivery in some clinical applications, since transit across the nuclear membrane is not necessary, and onset of expression with RNA is therefore even faster than with DNA, although both are faster than most viral vectors. Delivery of RNA to target organ(s) has previously been challenging due to RNA’s rapid degradation in biological systems, but cationic lipids complexed with RNA, as well as lipid nanoparticles (LNPs), have allowed for delivery and expression of the complexed RNA both in vitro and in vivo. This review will focus on the non-viral lipid-mediated delivery of RNAs, including mRNA, siRNA, shRNA, and microRNA, to the central nervous system (CNS), an organ with at least two unique challenges. The CNS contains a large number of slowly dividing or non-dividing cell types and is protected by the blood brain barrier (BBB). In non-dividing cells, RNA-lipid complexes demonstrated increased transfection efficiency relative to DNA transfection. The efficiency, timing of the onset, and duration of expression after transfection may determine which nucleic acid is best for which proposed therapy. Expression can be seen as soon as 1 h after RNA delivery, but duration of expression has been limited to 5–7 h. In contrast, transfection with a DNA lipoplex demonstrates protein expression within 5 h and lasts as long as several weeks after transfection.
    • Novel approach for low‐dose pulmonary delivery of hydroxychloroquine in COVID‐19

      Fassihi, Safa C.; Nabar, Neel R.; Fassihi, Reza; 0000-0002-6952-7017 (2020-06-19)
    • Novel Knowledge-Based Transcriptomic Profiling of Lipid Lysophosphatidylinositol-Induced Endothelial Cell Activation

      Center for Cardiovascular Research (Temple University); Center for Microbiology and Immunology (Temple University); Alzheimer's Center (Temple University); Center for Inflammation and Lung Research (Temple University) (2021-11-29)
      To determine whether pro-inflammatory lipid lysophosphatidylinositols (LPIs) upregulate the expressions of membrane proteins for adhesion/signaling and secretory proteins in human aortic endothelial cell (HAEC) activation, we developed an EC biology knowledge-based transcriptomic formula to profile RNA-Seq data panoramically. We made the following primary findings: first, G protein-coupled receptor 55 (GPR55), the LPI receptor, is expressed in the endothelium of both human and mouse aortas, and is significantly upregulated in hyperlipidemia; second, LPIs upregulate 43 clusters of differentiation (CD) in HAECs, promoting EC activation, innate immune trans-differentiation, and immune/inflammatory responses; 72.1% of LPI-upregulated CDs are not induced in influenza virus-, MERS-CoV virus- and herpes virus-infected human endothelial cells, which hinted the specificity of LPIs in HAEC activation; third, LPIs upregulate six types of 640 secretomic genes (SGs), namely, 216 canonical SGs, 60 caspase-1-gasdermin D (GSDMD) SGs, 117 caspase-4/11-GSDMD SGs, 40 exosome SGs, 179 Human Protein Atlas (HPA)-cytokines, and 28 HPA-chemokines, which make HAECs a large secretory organ for inflammation/immune responses and other functions; fourth, LPIs activate transcriptomic remodeling by upregulating 172 transcription factors (TFs), namely, pro-inflammatory factors NR4A3, FOS, KLF3, and HIF1A; fifth, LPIs upregulate 152 nuclear DNA-encoded mitochondrial (mitoCarta) genes, which alter mitochondrial mechanisms and functions, such as mitochondrial organization, respiration, translation, and transport; sixth, LPIs activate reactive oxygen species (ROS) mechanism by upregulating 18 ROS regulators; finally, utilizing the Cytoscape software, we found that three mechanisms, namely, LPI-upregulated TFs, mitoCarta genes, and ROS regulators, are integrated to promote HAEC activation. Our results provide novel insights into aortic EC activation, formulate an EC biology knowledge-based transcriptomic profile strategy, and identify new targets for the development of therapeutics for cardiovascular diseases, inflammatory conditions, immune diseases, organ transplantation, aging, and cancers.
    • Novel Scalable and Simplified System to Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells

      Center for Metabolic Disease Research (Temple University) (2021-07-05)
      Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.
    • Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses

      Kainth, Mundeep K.; Fishbein, Joanna S.; Aydillo, Teresa; Escalera, Alba; Odusanya, Rachael; Grammatikopoulos, Kalliopi; Scotto, Tiffany; Sethna, Christine B.; Garcia-Sastre, Adolfo; Deutschman, Clifford S. (2022-01-11)
      The most effective intervention for influenza prevention is vaccination. However, there are conflicting data on influenza vaccine antibody responses in obese children. Cardio-metabolic parameters such as waist circumference, cholesterol, insulin sensitivity, and blood pressure are used to subdivide individuals with overweight or obese BMI into ‘healthy’ (MHOO) or ‘unhealthy’ (MUOO) metabolic phenotypes. The ever-evolving metabolic phenotypes in children may be elucidated by using vaccine stimulation to characterize cytokine responses. We conducted a prospective cohort study evaluating influenza vaccine responses in children. Participants were identified as either normal-weight children (NWC) or overweight/obese using BMI. Children with obesity were then characterized using metabolic health metrics. These metrics consisted of changes in serum cytokine and chemokine concentrations measured via multiplex assay at baseline and repeated at one month following vaccination. Changes in NWC, MHOO and MUOO were compared using Chi-square/Fisher’s exact test for antibody responses and Kruskal–Wallis test for cytokines. Differences in influenza antibody responses in normal, MHOO and MUOO children were statistically indistinguishable. IL-13 was decreased in MUOO children compared to NWC and MHOO children (p = 0.04). IL-10 approached a statistically significant decrease in MUOO compared to MHOO and NWC (p = 0.07). Influenza vaccination does not provoke different responses in NCW, MHOO, or MUOO children, suggesting that obesity, whether metabolically healthy or unhealthy, does not alter the efficacy of vaccination. IL-13 levels in MUO children were significantly different from levels in normal and MHOO children, indicating that the metabolically unhealthy phenotypes may be associated with an altered inflammatory response. A larger sample size with greater numbers of metabolically unhealthy children may lend more insight into the relationship of chronic inflammation secondary to obesity with vaccine immunity.
    • One Year of COVID-19 Pandemic in Italy: Effect of Sedentary Behavior on Physical Activity Levels and Musculoskeletal Pain among University Students

      Roggio, Federico; Trovato, Bruno; Ravalli, Silvia; Di Rosa, Michelino; Maugeri, Grazia; Bianco, Antonino; Palma, Antonio; Musumeci, Giuseppe; Musumeci|0000-0002-8260-8890 (2021-08-17)
      The COVID-19 outbreak forced Italian students to reduce their daily activities, inducing a seden-tary attitude that was worsened by distanced learning. This study aimed to survey the physical activity levels that were maintained before and during the social restrictions following the pan-demic, their correlation to musculoskeletal pain, as well as analyzing the impact of these COVID-19 restrictions on pain and fatigue that affects daily life activities. A total of 2044 students completed the online questionnaire, of which the results of 1654 participants were eligible. Before the pandemic, the levels of physical activity were distributed as: 19.9% no activity, 30.1% light ac-tivity, 21.5% moderate activity, and 28.5% high activity. After one year of the pandemic, 30.6% of the participants were inactive, 48.1%, 10.9%, and 10.5% stated as maintaining, respectively, light, moderate and high levels of physical activity. Furthermore, 43.5% reported neck pain and 33.5% stated to experience low back pain. Physical activity levels lower than 150 min/week may have predisposed students to suffer from neck pain (1.95 OR at 95% CI, 1.44–2.64) and low back pain (1.79 OR at 95% CI, 1.29–2.49). A positive correlation between physical activity levels, Verbal Descriptive Scale (VDS), and pain frequency have been observed for neck and low back pain (p-value < 0.05). Finally, low physical activity levels were associated with musculoskeletal pain onset and pain worsening.
    • Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators

      Centers for Cardiovascular Research (Temple University); Alzheimer's Center (Temple University); Metabolic Disease Research, Inflammation, Translational & Clinical Lung Research (Temple University); Thrombosis Research (Temple University) (2021-07-22)
      To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum–MT, MT fusion, autophagosome–lysosome fusion, and autophagosome/endosome–lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome–lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)–MT contact, ER– plasma membrane (PM) junction, autophagosome/endosome–lysosome fusion, sarcoplasmic reticulum–MT, autophagosome–endosome/lysosome fusion, and ER–Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25− T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.
    • Patient clinical documentation in telehealth environment: are we collecting appropriate and sufficient information for best practice?

      Houser, Shannon H.; Flite, Cathy A.; Foster, Susan L.; Hunt, Thomas J.; Morey, Angela; Palmer, Miland N.; Peterson, Jennifer; Pope, Roberta Darnez; Sorenson, Linda (2022-01-20)
      Background: During the COVID-19 pandemic, the use of telehealth for patient visits grew rapidly and served an important role as a valuable and necessary resource. Although clinical documentation is critical for telehealth patient visits, there is limited information about how healthcare facilities manage telehealth patient visit documentation, technology used for telehealth visits, and challenges encountered with telehealth patient visit documentation. This study aimed to assess the use of telehealth during the pandemic, the quality of clinical documentation in telehealth practice and to identify challenges and issues encountered with telehealth patient visits in order to develop a strategy for best practices for telehealth documentation and data management. Methods: Data were collected for this cross-sectional study in January-February 2021 via a self-designed survey of administrators/managers from physicians’ offices and mental health facilities. Survey questions included four categories: health organization demographic information; telehealth visits; clinical documentation for telehealth visit; and challenges and barriers related to telehealth documentation technology use. Results: Of 76 respondents, more than half (62%) of the healthcare facilities started using telehealth for patient visits within one year of the onset of the COVID-19 pandemic, with 94% of respondents indicating an increased use of telehealth for patient visits since the pandemic. The most common types of telehealth patient care provided during the pandemic included pediatrics, primary care, cardiology, and women’s health. The most consistent data documentation of telehealth visits included: date of service, patient identification number, communication methods, patient informed consent, diagnosis and impression, evaluation results, and recommendations. The telehealth visit data was most commonly used for patient care and clinical practice, billing and reimbursement, quality improvement and patient satisfaction, and administrative planning. The top barriers to telehealth use by the healthcare professionals included patient challenges with telehealth services, such as inequities in quality of technology, lack of patient understanding, and lack of patient satisfaction; this was followed by frustration with constant updates of telehealth guidelines and procedures, understanding required telehealth documentation for reimbursement purposes, payer denial for telehealth visits, and legal and risk issues. Conclusions: Findings from this study can assist government entities, policymakers, and healthcare organizations in developing and advocating best practices in telehealth usage and clinical documentation improvement strategies.
    • Patient Experiences with the Transition to Telephone Counseling during the COVID-19 Pandemic

      Kang, Augustine W.; Walton, Mary; Hoadley, Ariel; DelaCuesta, Courtney; Hurley, Linda; Martin, Rosemarie; Hoadley|0000-0003-1360-0358 (2021-06-02)
      Background: To identify and document the treatment experiences among patients with opioid use disorder (OUD) in the context of the rapid move from in-person to telephone counseling due to the COVID-19 pandemic. Methods: Participants (n = 237) completed a survey with open-ended questions that included the following domains: (1) satisfaction with telephone counseling, (2) perceived convenience, (3) changes to the therapeutic relationship, (4) perceived impact on substance use recovery, and (5) general feedback. Responses were coded using thematic analysis. Codes were subsequently organized into themes and subthemes (covering 98% of responses). Interrater reliability for coding of participants’ responses ranged from 0.89 to 0.95. Results: Overall, patients reported that telephone counseling improved the therapeutic experience. Specifically, 74% of respondents were coded as providing responses consistently indicating “positive valency”. “Positive valency” responses include: (1) feeling supported, (2) greater comfort and privacy, (3) increased access to counselors, and (4) resolved transportation barriers. Conversely, “negative valency” responses include: (1) impersonal experience and (2) reduced privacy. Conclusions: Telephone counseling presents its own set of challenges that should be investigated further to improve the quality of care and long-term patient outcomes.
    • Perspectives on Humanizing and Liberatory Qualitative Research with Racially/Ethnically Minoritized Youth

      Savage, Shawn S.; Johnson, Royel M.; Kenney, Alex J.; Haynes, DaVonti' D. (2021-10-01)
      The visible impacts of COVID-19 and racial injustice have resulted in renewed funding commitments and research within minoritized communities. However, this work is too often anchored in deficit and damage-centered research approaches and practices. In this brief, we call on the qualitative research community to reframe their perspectives and terminate harmful, pain-driven research. We underscore the importance of humanizing and liberatory approaches to research with youth who are racially/ethnically minoritized. Specifically, we contend that the emotional health and overall well-being of youth are impacted by the approaches employed by researchers and the experiences racially/ethnically minoritized youth have with research. Thus, we offer specific anti-oppressive strategies and recommendations for qualitative researchers to consider in their work with racial/ethnically minoritized youth and communities.
    • Physical Activity Levels and Related Energy Expenditure during COVID-19 Quarantine among the Sicilian Active Population: A Cross-Sectional Online Survey Study

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-05-26)
      Background: During the coronavirus disease 2019 (COVID-19) pandemic, the Italian government has adopted containment measures to control the virus’s spread, including limitations to the practice of physical activity (PA). The aim of this study was to estimate the levels of PA, expressed as energy expenditure (MET–minute/week), among the physically active Sicilian population before and during the last seven days of the COVID-19 quarantine. Furthermore, the relation between this parameter and specific demographic and anthropometric variables was analyzed. Methods: 802 Sicilian physically active participants (mean age: 32.27 ± 12.81 years; BMI: 23.44 ± 3.33 kg/m2) were included in the study and grouped based on gender, age and BMI. An adapted version of the International Physical Activity Questionnaire—short form (IPAQ-SF) was administered to the participants through an online survey. The Wilcoxon signed-rank test and the Kruskal-Wallis rank-sum test were used for statistical analyses. Results: As expected, we observed a significant decrease of the total weekly energy expenditure during the COVID-19 quarantine (p < 0.001). A significant variation in the MET–min/wk in the before quarantine condition (p = 0.046) and in the difference between before and during quarantine (p = 0.009) was found for males and females. The male group decreased the PA level more than the female one. Moreover, a significant difference in the MET–min/wk was found among groups distributions of BMI (p < 0.001, during quarantine) and of age (p < 0.001, both before and during quarantine). In particular, the highest and the lowest levels of PA were reported by the young and the elderly, respectively, both before and during quarantine. Finally, the overweight group showed the lowest level of PA during quarantine. Conclusion: Based on our outcomes, we can determine that the current quarantine has negatively affected the practice of PA, with greater impacts among males and overweight subjects. In regards to different age groups, the young, young adults and adults were more affected than senior adults and the elderly.
    • Pneumothorax bei COVID-19-Erkrankung – Inzidenz und klinische Merkmale

      Zantah, Massa; Dominguez-Castillo, Eduardo; Townsend, Ryan; Dikengil, Fusun; Criner, Gerard J. (2021-02)
      Background: Spontaneous pneumothorax is a rarely occurring complication of viral pneumonia in COVID-19. The exact incidence and risk factors are still unclear. In the present work we examine the incidence and outcomes of more than 3,000 patients with pneumothorax who were admitted to our clinic with suspected COVID-19 pneumonia. METHODS: We retrospectively reviewed the cases of COVID-19 patients admitted to our clinic. To calculate the incidence of this event, patients diagnosed with spontaneous pneumothorax were identified and their clinical features were extensively documented. Clinical outcome data were collected. The individual cases are each presented in the form of a short summary. Results: Between March 1st and March 8th June 2020, 3368 patients with suspected COVID-19 pneumonia were admitted to our clinic; of these, 902 patients had a positive nasopharyngeal smear. Six COVID-19 patients who developed spontaneous pneumothorax were identified (0.66%). Baseline imaging showed diffuse bilateral frosted glass opacities and consolidations in these patients, predominantly in the posterior and peripheral lung regions. Four of the six patients were mechanically ventilated. Chest drainage was required in all patients. In all cases there was no direct relationship between the pneumothorax and mortality (66.6%). Conclusion: Spontaneous pneumothorax is a rare complication of viral pneumonia in COVID-19 that can occur without mechanical ventilation.
    • Pneumothorax in COVID-19 disease- incidence and clinical characteristics

      Zantah, Massa; Dominguez Castillo, Eduardo; Townsend, Ryan; Dikengil, Fusun; Criner, Gerard J.; 0000-0002-3030-6639; 0000-0002-1828-6524 (2020-09-16)
      Background: Spontaneous pneumothorax is an uncommon complication of COVID-19 viral pneumonia. The exact incidence and risk factors are still unknown. Herein we review the incidence and outcomes of pneumothorax in over 3000 patients admitted to our institution for suspected COVID-19 pneumonia. Methods: We performed a retrospective review of COVID-19 cases admitted to our hospital. Patients who were diagnosed with a spontaneous pneumothorax were identified to calculate the incidence of this event. Their clinical characteristics were thoroughly documented. Data regarding their clinical outcomes were gathered. Each case was presented as a brief synopsis. Results: Three thousand three hundred sixty-eight patients were admitted to our institution between March 1st, 2020 and June 8th, 2020 for suspected COVID 19 pneumonia, 902 patients were nasopharyngeal swab positive. Six cases of COVID-19 patients who developed spontaneous pneumothorax were identified (0.66%). Their baseline imaging showed diffuse bilateral ground-glass opacities and consolidations, mostly in the posterior and peripheral lung regions. 4/6 cases were associated with mechanical ventilation. All patients required placement of a chest tube. In all cases, mortality (66.6%) was not directly related to the pneumothorax. Conclusion: Spontaneous pneumothorax is a rare complication of COVID-19 viral pneumonia and may occur in the absence of mechanical ventilation. Clinicians should be vigilant about the diagnosis and treatment of this complication.
    • Policing and public health calls for service in Philadelphia

      Ratcliffe, Jerry; Ratcliffe|0000-0002-0730-6761 (2021-03-02)
      This contribution outlines various spatial and temporal aspects of medical or public-health related calls for service from the public to police in Philadelphia in 2019. These incidents comprise about 8% of the police department’s workload that originates from the public. Calls appear to be highly concentrated in a few areas, and specifically the Center City and Kensington neighborhoods. They are also more likely to occur late afternoon and evening. The article shows that some medical or public health activity initially masquerades as crime or other policing work and some events eventually determined to be police/crime activity can initially appear to be public health related. About 20% of activity in this area does not appear predictable from the initial call type as handled by police dispatch.
    • Population health science as a unifying foundation for translational clinical and public health research

      Cullen, Mark R.; Baiocchi, Michael; Chamberlain, Lisa; Chu, Isabella; Horwitz, Ralph I.; Mello, Michelle; O'Hara, Amy; Roosz, Sam (2022-03-01)
      Separated both in academics and practice since the Rockefeller Foundation effort to “liberate” public health from perceived subservience to clinical medicine a century ago, research in public health and clinical medicine have evolved separately. Today, translational research in population health science offers a means of fostering their convergence, with potentially great benefit to both domains. Although evidence that the two fields need not and should not be entirely distinct in their methods and goals has been accumulating for over a decade, the prodigious efforts of biomedical and social sciences over the past year to address the COVID-19 pandemic has placed this unifying approach to translational research in both fields in a new light. Specifically, the coalescence of clinical and population-level strategies to control disease and novel uses of population-level data and tools in research relating to the pandemic have illuminated a promising future for translational research. We exploit this unique window to re-examine how translational research is conducted and where it may be going. We first discuss the transformation that has transpired in the research firmament over the past two decades and the opportunities these changes afford. Next, we present some of the challenges—technical, cultural, legal, and ethical— that need attention if these opportunities are to be successfully exploited. Finally, we present some recommendations for addressing these challenges.
    • Predicting the mutational drivers of future SARS-CoV-2 variants of concern

      Institute for Genomics and Evolutionary Medicine (iGEM) (Temple University) (2021-06-22)
      SARS-CoV-2 evolution threatens vaccine- and natural infection-derived immunity, and the efficacy of therapeutic antibodies. Herein we sought to predict Spike amino acid changes that could contribute to future variants of concern. We tested the importance of features comprising epidemiology, evolution, immunology, and neural network-based protein sequence modeling. This resulted in identification of the primary biological drivers of SARS-CoV-2 intra-pandemic evolution. We found evidence that resistance to population-level host immunity has increasingly shaped SARS-CoV-2 evolution over time. We identified with high accuracy mutations that will spread, at up to four months in advance, across different phases of the pandemic. Behavior of the model was consistent with a plausible causal structure wherein epidemiological variables integrate the effects of diverse and shifting drivers of viral fitness. We applied our model to forecast mutations that will spread in the future, and characterize how these mutations affect the binding of therapeutic antibodies. These findings demonstrate that it is possible to forecast the driver mutations that could appear in emerging SARS-CoV-2 variants of concern. This modeling approach may be applied to any pathogen with genomic surveillance data, and so may address other rapidly evolving pathogens such as influenza, and unknown future pandemic viruses.
    • Preliminary predictive criteria for COVID-19 cytokine storm

      COVID-19 Research Group (Temple University) (2020-09-25)
      Objectives: To develop predictive criteria for COVID-19-associated cytokine storm (CS), a severe hyperimmune response that results in organ damage in some patients infected with COVID-19. We hypothesised that criteria for inflammation and cell death would predict this type of CS. Methods: We analysed 513 hospitalised patients who were positive for COVID-19 reverse transcriptase PCR and for ground-glass opacity by chest high-resolution CT. To achieve an early diagnosis, we analysed the laboratory results of the first 7 days of hospitalisation. We implemented logistic regression and principal component analysis to determine the redictive criteria. We used a ’genetic algorithm’ to derive the cut-offs for each laboratory result. We validated the criteria with a second cohort of 258 patients. Results: We found that the criteria for macrophage activation syndrome, haemophagocytic lymphohistiocytosis and the HScore did not identify the COVID-19 cytokine storm (COVID-CS). We developed new predictive criteria, with sensitivity and specificity of 0.85 and 0.80, respectively, comprising three clusters of laboratory results that involve (1) inflammation, (2) cell death and tissue damage, and (3) prerenal electrolyte imbalance. The criteria identified patients with longer hospitalisation and increased mortality. These results highlight the relevance of hyperinflammation and tissue damage in the COVID-CS. Conclusions: We propose new early predictive criteria to identify the CS occurring in patients with COVID-19. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen,block the hyperimmune response and possibly decrease mortality.
    • Preschoolers Benefit Equally From Video Chat, Pseudo-Contingent Video, and Live Book Reading: Implications for Storytime During the Coronavirus Pandemic and Beyond

      Gaudreau, Caroline; King, Yemimah A.; Dore, Rebecca A.; Puttre, Hannah; Nichols, Deborah; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; 0000-0003-2947-4544 (2020-09-03)
      During the unprecedented coronavirus disease (COVID-19) crisis, virtual education activities have become more prevalent than ever. One activity that many families have incorporated into their routines while at home is virtual storytime, with teachers, grandparents, and other remote adults reading books to children over video chat. The current study asks how dialogic reading over video chat compares to more traditional forms of book reading in promoting story comprehension and vocabulary learning. Fifty-eight 4-year-olds (Mage = 52.7, SD = 4.04, 31 girls) were randomly assigned to one of three conditions (Video chat, Live, and Prerecorded). Across conditions, children were read the same narrative storybook by a female experimenter who used the same 10 scripted dialogic reading prompts during book reading. In the Video chat (n = 21) and Live conditions (n = 18), the experimenter gave the scripted prompts and interacted naturally and contingently, responding in a timely, relevant manner to children’s behaviors. In the Prerecorded condition (n = 19), children viewed a video of an experimenter reading the book. The Prerecorded condition was pseudo-contingent; the reader posed questions and paused for a set period of time as if to wait for a child’s response. After reading, children completed measures of vocabulary and comprehension. Results revealed no differences between conditions across six different outcome measures, suggesting that children comprehended and learned from the story similarly across book formats. Further, children in the three experimental conditions scored significantly higher on measures than children in a fourth condition (control) who had never read the book, confirming that children learned from the three different book formats. However, children were more responsive to the prompts in the Live and Video chat conditions than the Prerecorded condition, suggesting that children recognized that these interactions were contingent with their responses, a feature that was lacking in the Prerecorded condition. Results indicate that children can comprehend books over video chat, suggesting that this technology is a viable option for reading to children, especially during the current pandemic.