Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccineAS Darrigade, MD1, H Théophile, MD2, P Sanchez-Pena, MD2, B Milpied, MD1, M Colbert4, MD, S Pedeboscq5, MD, T Pistone6, MD, ML Jullié, MD7, J Seneschal, MD, PhD1,31 : Department of Adult and Pediatric Dermatology, Bordeaux University Hospitals, France2 : Department of pharmacovigilancy, Bordeaux University Hospitals, France3 : Research Unit INSERM U10354 : Department of geriatry, Clinic Bordeaux Nord, Bordeaux, France5 : Department of pharmacology, Bordeaux University Hospitals, France6: Department of infectious disease, Bordeaux University Hospitals, France7: Department of anatomopathology, Bordeaux University Hospitals, FranceManuscript word count: 607Key words : sweet syndrome, SARS-CoV-2, Pfizer-BioNTech mRNA vaccine, delayed hypersensitivity, IDRCorresponding author: A.S. Darrigade, Dermatology Department, Saint-André Hospital, 1, rue Jean Burguet 33000 Bordeaux, FrancePhone: +33556794705Fax: +33556794975anne-sophie.darrigade@chu-bordeaux.frFunding source: No financial disclosuresFinancial Disclosure: No external funding for this manuscriptTo the editor,A 45-year-old woman, without any past medical history or allergy presented in our clinic with a rapid onset of diffuse skin eruptions. Five days earlier, she received the first injection of the SARS-CoV-2 Pfizer-BioNTech mRNA. Concomitantly she took 1000mg paracetamol to prevent any post-vaccination syndrome. She well tolerated the preceding vaccines (influenza every year) before this one.The eruption started 24h after vaccine injection and was composed at time of the clinical exam of erythematous infiltrated papulosis located all over the body, without face involvement (Figure 1). No other extracutaneous symptoms were noted. Blood exams showed increased blood count levels with increased neutrophils count (8.77G/l), hepatic cytolysis (AST 67UI/L and ALT 116UI/l) with high level of PCR (115mg/l). SARS-CoV-2 PCR test and serology were negative. Viral tests for EBV, CMV, parvovirus B19, and Herpes simplex/Herpes zoster showed only a slight EBV reactivation. Histopathological examination of the skin biopsy showed a hyperplastic epidermis with an edematous papillary dermis. A superficial and deep dermal perivascular, periadnexal and interstitial dense infiltrate composed of neutrophils, eosinophils and lymphocytes was also a feature. Leukocytoclastic vasculitis was also seen (Figure 2A-2B). Clinical and pathological exams were compatible with the diagnosis of SS induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Systemic steroid therapy (prednisone 0.5mg/kg/d) for five days was started and led to rapid improvement of the skin condition without any recurrence after treatment discontinuation. She did not receive the second vaccine injection.Patch-tests performed (14 days after steroid treatment stop, one month after SS) on both on healed and normal skin with pur SARS-CoV-2 Pfizer-BioNTech mRNA vaccine prepared less than 4 hours before were negative (Figure 1C 2-3). Then, intradermoreaction (IDR) with vaccine diluted at 1/10 on normal skin was positive in delayed reading (Figure 1C 1). Cutaneous biopsy was realized on the positive IDR reaction, showing an abundant inflammatory infiltrate predominantly with lymphocytes (Figure 2C).Cutaneous reactions after vaccine injection are rare, and heterogenous1. They could be related to the vaccine or the adjuvant. In addition, vaccine could trigger flares of chronic inflammatory conditions as it was previously reported1. At that time, minor local side effects are reported with SARS-CoV-2 vaccines such as pain, swelling or redness; hypersensitivity reactions were anaphylactic reaction but no severe delayed hypersensitivity are reported2-3. Three cases of acute febrile neutrophilic dermatosis are reported in the international bank of WHO, one in United Kingdom, one in United States of America and our case. Under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine four cases of vasculitis had been reported after injection. In France one case of relapse of neutrophilic disorder was reported one day after SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. The adjuvant associated with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine is polyethylene glycol (PEG) 20003. However our patient never received infusion containing PEG or polysorbate before. Patch-tests with PEG or polysorbate alone were not performed because of the negativity of the patch-test with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Only 10 cases of SS induced by vaccine are published so far including: 3 with seasonal influenza, 1 with influenza A, 2 with pneumococcal, 2 tuberculosis, 2 small pox4. SS is an acute inflammatory skin disease associated with important infiltration of neutrophils. Leukocytoclastic vasculitis could be present in SS5. One case of SS in a patient receiving pneumococcal vaccine showed the presence of dermal vasculitis associated with infiltration of neutrophils6. In case of anaphylactic reaction under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine, the risk of relapse with the Moderna SARS-CoV-2 mRNA vaccine or SARS-CoV-2 vaccines with an adenovirus carrier and protein subunit remains unknown3, in case of SS even more.To conclude we report the first case of SS induce by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine confirmed by positive IDR.

The vast amount of data contained in a single genome represents a detailed record of past events in that lineage and may forecast its evolutionary potential in the face of environmental changes. Here we employed whole-genome sequence (WGS) data to infer the demographic history and assess signals of recent inbreeding in jaguar (Panthera onca) populations. We analyzed whole genomes from 13 individuals (nine of which are reported here for the first time) sampled in seven different biomes across the species’ range, including its northernmost extreme in the Mexico/USA border region. We modelled demographic history using the PSMC method, and analyzed long runs of homozygosity (ROH) to assess signals of population bottlenecks and inbreeding. PSMC plots were very consistent among individuals, indicating that the jaguar lineage had an effective population size of up 100,000 individuals ca. 1 million years ago, then sharply declined and rebounded during the Late Pleistocene, followed by a more gradual decline in the last 40,000 years. This decline was more pronounced in the North/Central American genomes, likely reflecting population bottlenecks during the south-north colonization towards the edge of the species’ current range. The ROH analysis revealed a relatively small burden for most jaguars, indicating a recent history of outbreeding and large-scale connectivity among regional populations. However, northern range-edge individuals and those from severely fragmented populations showed signals of recent bottlenecks and, in the latter case, inbreeding. Our results illustrate the power of WGS data to survey and monitor the genetic erosion triggered by anthropogenic habitat fragmentation.

Afforestation; Soil ecoenzymatic C: N: P; Specific enzyme activities; Soil C and N contents.

We report a case of colonic metastasis due to pancreatic adenocarcinoma.

Histone is a scaffold protein that constitutes nucleosomes with DNA in the cell nucleus. When forming histone, hetero octamer is assisted by histone chaperone proteins. As a histone chaperone protein, the crystal structure of yeast nucleosome assembly protein (yNap1) has been determined. For yNap1, a nuclear export signal/sequence (NES) has been identified as a part of the long -helix. Experimental evidence via mutagenesis on budding yeast suggests the NES is necessary for transport out from the cell nucleus. However, the NES is masked by a region defined as an accessory domain (AD). In addition, the role of the AD in nuclear transport has not been elucidated yet. To address the role of the AD, we focused on phosphorylation in the AD because proteome experiments have identified multiple phosphorylation sites of yNap1. To computationally treat phosphorylation, we performed all-atom molecular dynamics (MD) simulations for a set of non-phosphorylated and phosphorylated yNap1 (Nap1-nonP and Nap1-P). As an analysis, we addressed how the NES is exposed to the protein surface by measuring its solvent-access surface area (SASA). As a result, there was a difference in the SASA distributions between both systems. Quantitatively, the median of the SASA distribution of Nap1-P was greater than that of Nap1-nonP, meaning that phosphorylation in the AD exposed to the NES, resulting in increasing its accessibility. In conclusion, yNap1 might modulate the accessibility of the NES by dislocating the AD through phosphorylation.

Peer-review and subject-matter editing is the backbone of scientific publishing. However, early career researchers (ECRs) are given few opportunities to participate in the editorial process beyond reviewing articles. Thus, a disconnect exists: science needs high-quality editorial talent to conduct, oversee, and improve the publishing process, yet we dedicate few resources to building editorial talent nor giving ECRs formal opportunities to influence the publishing landscape from within. Here, we describe a “two-way” fellowship model that gives ECRs a “seat” at the editorial table of a field-leading journal. We describe both the necessary framework and benefits that can stem from editorial fellowships for ECRs, editors, journals, and the scientific community.

Background: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed bland thrombus, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, the role of anticoagulation is less clear. Procedure/Methods: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010-2020 at Texas Children’s Hospital were identified and their medical records were reviewed. Results: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, there were two patients who presented with pulmonary embolism (PE). Inferior Vena Cava extension was noted in 36% of the patients and 24% patients had an intracardiac tumor thrombus. Hepatoblastoma (26%) was the most common malignancy associated with tumor thrombus. Anticoagulation was initiated in 10 patients (20%). Only 2 of these 10 patients showed response to anticoagulation. However, 40% (4/10) patients in the anticoagulation cohort were noted to have bleeding complications (p <.05). Conclusion: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.

It has been a challenge in automated analysis of medical and chemical knowledge to extract represent quantitative structure–activity relationship (QSAR) using intelligent computing in drug discovery. One of many domain-specific bottlenecks in drug discovery is robust conformation search in three-dimensional (3D) space for flexible drug candidates. The process involves researchers and machines working together to achieve their own strengths for greater outcome. The present study has been developing a method for conformational sampling conformers in the class of 4-anilinoquinazoline derivatives for epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs). We use AG-1478 to demonstrate how the new intelligent computing method helps to quantum mechanically determine 22 target drug conformer clusters and their properties from conformational sampling, based on density functional theory (DFT) method, time-dependent (TD)-DFT in solvents and clustering analysis (CA). The UV-vis spectra of the preferred conformers agree well with earlier experimental measurements in which the conformer dependent UV-Vis spectral shift of AG-1478 can be as large as approximately 15 nm. We are further developing this method to study and design new 4-anilinoquinazoline derivatives of EGFR TKIs.

Introduction Some patients fail to respond to persistent atrial fibrillation (PeAF) catheter ablation in spite of multiple procedures and ablation strategies, including low voltage area (LVA)-guided, linear, and complex fractionated atrial electrogram (CFAE)-guided ablation procedures. We hypothesized that LVA extent could predict non-response to PeAF catheter ablation in spite of multiple procedures. Methods This study included 510 patients undergoing initial ablation procedures for PeAF. LVAs were defined as regions with bipolar peak-to-peak voltages of <0.50 mV after PVI during sinus rhythm. Patients were categorized by LVA size into groups A (0-5 cm2), B (5-20 cm2), and C (over 20 cm2). The primary endpoint was AF-free survival after the last procedure. Results During a median follow-up of 25 (17, 36) months, AF recurrence was observed in 101 (20%) patients after 1.4±0.6 ablation procedures (maximum 4). A Kaplan-Meier analysis showed the AF-free survival rate significantly differed by LVA size. Conclusion Extensive LVA after initial PVI was associated with a poor clinical outcome even following multiple procedures.

Objective: Surgical closure of ventricular septal defect is still the most common pediatric cardiac surgical procedure. The aim of this study was to define the risk factors of the complications of ventricular septal defect surgery. Methods: We evaluated the preoperative, perioperative, and postoperative data from echocardiography reports, perfusion reports, and clinical, inpatient, and operative notes of all the patients. The following were the outcome variables for this study: in-hospital death; duration of mechanical ventilation in hours; duration of pediatric intensive care unit stay in days; and duration of hospital stay in days. Herein, we report our single pediatric cardiac center experience between October 2015 and October 2018. Results: A total of 108 patients underwent surgical ventricular septal defect closure during the study period. Prolonged pediatric intensive care unit stay, hospital stay and mechanical ventilation time was associated with younger age and low weight. The patients with genetic syndromes had statistically longer mechanical ventilation time (p < 0.001), pediatric intensive care unit stay (p < 0.001), and hospital stay (p = 0.002). Conclusion: Although genetic syndromes did not affect the complication rates, it affected the lengths of hospital and pediatric intensive care unit stays and mechanical ventilation duration. Young age and lower body weight was a risk factor of prolonged hospitalization, prolonged pediatric intensive care unit stay and prolonged mechanical ventilation. Therefore, these situations should be considered in the postoperative follow-up of patients with ventricular septal defect.

The Andes range in Ecuador presents high biodiversity and characteristic altitudinal gradients, which are frequently threatened by deforestation and farming. In particular, forest have developed in the high inter-Andean alley on volcanic soils forming a unique ecoregion. Little is known on the fungal biodiversity of soil in such high Andean gallery forest submitted to strong degradation pressures. Therefore, in this study we evaluated wether the soil mycobiome was associated with altitudinal gradients during the dry season. Three representative locations were selected based on altitude: A (3,309 meters above the sea level, masl), B (3,809 masl) and C (4,409 masl). High performance sequencing (NGS) of the ITS region of ribosomal DNA genes with Illumina technology was used to explore the fungal taxonomic composition in the soil samples. Our results showed changes in the structure of fungal communities in the different locations, related to the relative abundance of Amplicon Sequence Variants (ASV). Higher fungal diversity was related with the altitudinal gradient with average taxa ranging from 675, 626 and 556 ASVs, respectively from location A to C. The results highlight the complexity and diversity of fungal communities in high Andean forest and the need to protect these unique mycobiomes. The findings in this ecosystem of Ecuador will improve our understanding of distribution, diversity, ecology, and biological perspectives for the restoration of terrestrial microbiomes.

Coronavirus disease 2019 (COVID-19) has been tied to many complications such as hypercoagulability. It is more commonly seen in patients admitted to intensive care unit. Herein, we report a case of an end stage renal disease patient who developed recurrent arteriovenous graft thrombosis in the setting of COVID-19.

Aim: This study was conducted to evaluate the effect of postoperative early mobilization in patients who underwent radical cystectomy (RC) and ileal conduit in terms of healing process and QOL. Methods: This multicenter prospective randomized controlled study was conducted with 40 patients who were randomly divided into two groups. The intervention group was mobilized within the first 16 hours postoperatively in accordance with the mobilization procedure which determined according to literature. Data were collected using the case report form, HADS and SF-36 QoL scale. Results: Postoperative hospitalization, duration of narcotic analgesic administration, first oral food intake, flatus, defecation and NG tube termination time were shorter in the intervention group. In the control group blood glucose and pulse values were higher after mobilization. SF-36 physical function, physical role difficulty and general perception of health were higher in intervention group at the postoperative first and third month (p <0.05). Conclusion: Our study showed that early mobilization contributed to the healing process positively and improved the quality of life in the patients who underwent radical cystectomy (RC) and ileal conduit surgery. Keywords: Early Mobilization, Radical Cystectomy, Ileal conduit, Quality of Life, Convalescence

1 Conflicts of interestESC has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma; is a member of the healthcare advisory board for Food Allergy Canada; was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Guidelines for Peanut Allergy Prevention; and was co-lead of the CSACI oral immunotherapy guidelines.SJ has been on speaker’s bureaus for Aralez, Novartis, Astra Zeneca, and Sanofi, and on the advisory board for Sanofi.MH has provided speaker services for Pfizer, Pediapharm, and has been part of an advisory board for ALK and provides privately funded OIT.VC has been a participant on advisory boards for Sanofi Genzyme, Bausch Health, and ALK, speaker services for Aralez Pharmaceuticals and CSL Behring.DM has provided consultation and speaker services for Pfizer, Aimmune, Kaleo, Merck, Covis and Pediapharm, and has been part of an advisory board for Pfizer and Bausch Health. He sits on the editorial board for the Journal of Food Allergy.EA Section Head of Anaphylaxis/Food Allergy for the Canadian Society of Allergy and Clinical Immunology; sits on steering committee for Canada’s National Food Allergy Action Plan; moderator/speaker fees from Novartis, GSK, Sanofi, AstraZeneca.LS NoneTW speaking engagements for Pfizer and Stallergenes Greer, Advisory Board member for ALK and Leo PharmaJP is the Section Head of Allied Health for the Canadian Society of Allergy and Clinical Immunology; and sits on the steering committee for Canada’s National Food Allergy Action Plan

A predictive model based on Fick’s second law for radial diffusion is proposed and validated for modeling the diffusion of fragrances. A pure component, two binary systems, and a ternary system were used for validation. The model combines the prediction model to represent the liquid phase non-idealities, using the UNIFAC group contribution method, with the Fickian radial diffusion approach. The experimental headspace concentrations were measured in a diffusion chamber using the solid-phase microextraction (SPME) technique and quantified using gas chromatography with a flame ionization detector (GC-FID). The numerical solutions were obtained along with an analytical model considering constant surface concentration. The odor intensities of the studied systems were calculated using Stevens’ power law and the strongest component model, respectively. The numerical simulation presented good adherence to the experimental gas concentration data. The proposed methodology is an efficient and validated tool to assess the radial diffusion of fragrance and volatile systems.

Centrifugal pumps are used in several industrial processes. It is common the operation of this equipment with gas-liquid mixtures, which is the case of the electrical submersible pumping artificial lift method used in the oil industry. The increase of free gas fraction inside the pump may lead to unstable operation and problems such as surging and gas locking phenomena to occur. In this study a drift-flux model is proposed for the gas-liquid flow subjected to centrifugal fields using the impeller as an example. The model is closed with experimental data of bubble diameter, displacements and velocities acquired via high-speed camera at several different rotational speeds and gas mass flow rates using water as the continuous medium. From the modeling and the forces balance in the bubbles, a quantitative criterion for the start point of surging and gas locking conditions was proposed.

A young man was admitted to our hospital for diabetic ketoacidosis. On admission, HbA1c，GADA, serum amylase were negative. After 2 weeks of insulin therapy, serum amylase，and were GADA still negative. This report concerns a case of FT1D with normal serum.

Introduction: With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes. Methods: We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity. Results: There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (26.6%) patients had severe PARDS. 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher median FSS score at both PICU and hospital discharge compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS was not a risk factor for acquired morbidity. Conclusion: Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection usually causes no or mild coryzal symptoms in the paediatric population. In this letter, we describe a 21-month-old boy infected with SARS-CoV-2 who presented atypically with features compatible with croup. With the current Coronavirus Disease 2019 (COVID-19) pandemic, infection control measures need to be appropriately heightened and early diagnostic sampling for SARS-CoV-2 should be carried out even in symptomatology that is atypical of COVID-19.

Objective: This study aimed to assess the possible role of dermoscopy in the diagnosis of different nail disorders compared with the clinical and histopathological diagnosis. Methods: This study included 104 patients with any nail disorders of both sex and any age. All the patients were subjected to a detailed medical history taken, clinical general examination, clinical and dermoscopic examinations of 20 nails. Potassium hydroxide examination was used to examine all patients with suspicious of onychomycosis. Histopathological evaluation was used to examine of clinically ambiguous nail disorders. Results: The most common nail diseases were onychomycosis (54.81%) followed by nail psoriasis (19.2%), and nail lichen planus (3.8%). Conclusion: Clinical evaluation was an important in diagnosis of different nail diseases. Nail dermoscopy could confirm clinical diagnosis and help in getting an accurate diagnosis of nail diseases and guide in the management of nail diseases by permitting better visualization of nail structure and pathology. Histopathological examination provided the most definitive method in reaching an accurate diagnosis due to it could provide etiologic, diagnostic, and prognostic information. There was good agreement between clinical, dermoscopic, and histopathological examinations for accurate diagnosis of different nail diseases.

SCN5A gene variants are associated with both Brugada syndrome and conduction disturbances, sometimes expressing an overlapping phenotype. Functional consequences of SCN5A variants assessed by patch clamp electrophysiology are particularly beneficial for a correct pathogenic classification and are related to disease penetrance and severity. Here, we identify a novel SCN5A loss of function variant, p.1449Y>H, which presented with high penetrance and complete left bundle branch block, totally masking the typical findings on the electrocardiogram. We highlight the possibility of this overlap combination that makes impossible an electrocardiographic diagnosis and, through a functional analysis, associate the p.1449Y>H variant to SCN5A pathogenicity.

Letter to the Editor

Background: Chemokine (C-C motif) receptor 2 (CCR2) contributes to autoimmune pathogenesis. However, the effect of CCR2 on B cell signaling and its role in autoimmunity remains unclear. Herein, we investigated the role of CCR2 in the B cell receptor (BCR) signaling pathway and aimed to illustrate its potential molecular mechanisms of action. Methods: To investigate the alterations in B cell signaling and the immune response, we used flow cytometry, western blotting, microscopic techniques, Seahorse assay, and immunofluorescence assay on samples from C57BL/6 mice and germinal CCR2-deletion mice. Results: The absence of CCR2 disturbed follicular B cell development. Furthermore, CCR2 absence was correlated with increased mTORC1-mediated energy metabolism and enhanced early B cell activation, which were induced by the up-regulation of BCR proximal signaling and F-actin accumulation. Mst1 and STAT1 were key factors in up-regulating the B cell activation in CCR2 deficient mice. The disrupted peripheral B cell differentiation and enhanced B cell signaling were associated with the inhibition mTORC1, Mst1, and STAT1. Moreover, loss of CCR2 caused a weakened T cell dependent antigen response, resulting in decreased antibody secreting cells and diminished antigen specific IgM levels. Conclusion: CCR2 is involved in the regulation of BCR signaling pathway by sequentially activating signaling pathways dominated by Mst1, mTORC1, and STAT1. Our study suggests that CCR2 might represent a novel therapeutic targeted for autoimmune diseases.

New drugs are urgently needed for parasitic protozoan infections and repurposing drugs is a promising approach for the drug development process. New and emerging data support the repurposing of the FDA-approved drug disulfiram along with zinc supplement as an anti-parasitic agent (Figure 1).The drug repurposing approach identifies new therapeutic uses for approved drugs outside of their original indication. Drug repurposing is an attractive alternative strategy because of the high failure rate, significant cost, and long time-consuming task for new drug discovery and development \cite{Farha_2019}. Current therapies for parasitic infections are unsatisfactory due to drug resistance, toxicity, limited treatment options, and poor efficacy \cite{De_Rycker_2018}. Therefore, new drugs are urgently needed for these infections which contribute significantly to global morbidity and mortality, and drug repurposing may help address this need.