A Mechanistic Analysis of the Neural Modulation of the Inflammatory System Through Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis assessing the antiinflammatory effects of various VNS methods while exploring multiple antiinflammatory pathways. MATERIALS AND METHODS: We included clinical trials that used electrical stimulation of the vagus nerve and assessed inflammatory markers up to October 2022. We excluded studies lacking control groups, those with combined interventions, or abstracts without full text. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews. For each inflammatory marker, a random-effects meta-analysis using the inverse variance method was performed. Methods used include transcutaneous auricular VNS (taVNS), transcutaneous cervical VNS (tcVNS), invasive cervical VNS (iVNS), and electroacupuncture VNS (eaVNS). Main reported outcomes included tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, C-reactive protein (CRP), and IL-10. Risk of bias was evaluated using the Cochrane Collaboration Tool (RoB 2.0). RESULTS: This review included 15 studies, involving 597 patients. No statistically significant general VNS effect was observed on TNF-α, IL-6, and IL-1ß. However, CRP, IL-10, and interferon (IFN)-γ were significantly modulated by VNS across all methods. Subgroup analysis revealed specific stimulation techniques producing significant results, such as taVNS effects in IL-1ß and IL-10, and iVNS in IL-6, whereas tcVNS and eaVNS did not convey significant pooled results individually. Cumulative exposure to VNS, higher risk of bias, study design, and pulse width were identified as effect size predictors in our meta-regression models. CONCLUSIONS: Pooling all VNS techniques indicated the ability of VNS to modulate inflammatory markers such as CRP, IL-10, and IFN-γ. Individually, methods such as taVNS were effective in modulating IL-1ß and IL-10, whereas iVNS modulated IL-6. However, different VNS techniques should be separately analyzed in larger, homogeneous, and powerful studies to achieve a clearer and more consistent understanding of the effect of each VNS method on the inflammatory system.

Steroid Components of Marine-Derived Fungal Strain Penicillium levitum N33.2 and Their Biological Activities.

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3ß,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC50 values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial.

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Loaded and unloaded timed stair tests as tools for assessing advanced functional mobility in people with stroke.

BACKGROUND: The Timed Stair Test (TST) was originally designed to measure advanced functional mobility in patients who have undergone a total hip replacement. Its psychometric properties have not been examined systematically in people with stroke. AIM: The aims of this study were to: 1) determine the intra-rater reliability of TST under loaded and unloaded condition; 2) identify the minimal detectable changes (MDCs) in TST completion times; 3) investigate the concurrent validity between TST completion times and stroke-specific outcome measures; and 4) determine the cut-off TST completion time to differentiate the performance between people with stroke and healthy older adults. DESIGN: Cross-sectional study. SETTING: A university-based rehabilitation center. POPULATION: Ninety-four people with stroke and 34 healthy older adults. METHODS: TSTs were conducted under loaded and unloaded conditions. Two trials of the TST for each of the two conditions were performed on the same day. The Fugl-Meyer Assessment of Lower Extremity (FMA-LE), lower-limb muscle strength test assessed by a hand held dynamometer, Berg Balance Scale (BBS), Limit of Stability (LOS) Test, Timed Up and Go (TUG) Test, and the Cantonese version of the Community Integration Measure (CIM) were also used to assess the subjects. RESULTS: Excellent intra-rater reliability was demonstrated for TST completion times under loaded (intraclass correlation coefficient [ICC2,1]=0.991) and unloaded (ICC2,1=0.985) conditions. The MDCs in TST completion times were 6.55 seconds and 7.25 seconds under loaded and unloaded conditions, respectively. FMA-LE scores, mean strength of the affected-side dorsiflexors and plantar flexors, BBS scores, and LOS movement velocity and maximum excursion scores demonstrated fair to excellent negative correlations with TST completion times under both loaded (r=-0.314 to -0.786) and unloaded (r=-0.296 to -0.794) conditions. TUG results demonstrated good to excellent positive correlations with TST completion times under both loaded (r=0.875, P<0.001) and unloaded (r=0.872, P<0.001) conditions. The TST completion times of 26.3 seconds and 23.4 seconds under loaded and unloaded conditions, respectively, differentiated between people with stroke and healthy older adults. CONCLUSIONS: The TST is a reliable clinical tool for evaluating advanced functional mobility in people with stroke. CLINICAL REHABILITATION IMPACT: TST is a fast and simple test that does not require sophisticated equipment, making it suitable for busy hospital and rehabilitation settings.

Estimating unconfirmed COVID-19 infection cases and multiple waves of pandemic progression with consideration of testing capacity and non-pharmaceutical interventions: A dynamic spreading model.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has unique epidemiological characteristics that include presymptomatic and asymptomatic infections, resulting in a large proportion of infected cases being unconfirmed, including patients with clinical symptoms who have not been identified by screening. These unconfirmed infected individuals move and spread the virus freely, presenting difficult challenges to the control of the pandemic. To reveal the actual pandemic situation in a given region, a simple dynamic susceptible-unconfirmed-confirmed-removed (D-SUCR) model is developed taking into account the influence of unconfirmed cases, the testing capacity, the multiple waves of the pandemic, and the use of non-pharmaceutical interventions. Using this model, the total numbers of infected cases in 51 regions of the USA and 116 countries worldwide are estimated, and the results indicate that only about 40% of the true number of infections have been confirmed. In addition, it is found that if local authorities could enhance their testing capacities and implement a timely strict quarantine strategy after identifying the first infection case, the total number of infected cases could be reduced by more than 90%. Delay in implementing quarantine measures would drastically reduce their effectiveness.

Validation of the monocyte activation test with three therapeutic monoclonal antibodies.

Pharmaceutical products intended for parenteral use must be free from pyrogenic (fever-inducing) contamination. Pyrogens comprise endotoxins from Gram-negative bacteria and non-endotoxin pyrogens from Gram-positive bacteria, viruses, and fungi. The longstanding compendial test for pyrogens is the rabbit pyrogen test, but in 2010 the monocyte acti-vation test (MAT) for pyrogenic and pro-inflammatory contaminants was introduced into the European Pharmacopoeia (Ph. Eur.) as a non-animal replacement for the rabbit pyrogen test. The present study describes the first product-specific Good Manufacturing Practice validation of Ph. Eur. MAT, Quantitative Test, Method A for the testing of three therapeutic monoclonal antibodies. The study used the MAT version with cryo-preserved peripheral blood mononuclear cells and interleukin-6 as the readout. Much of the data presented here for one of the antibodies was included in a successful product license application to the European Medicines Agency.

Lymphohistiocytic Myocarditis Possibly Due to Moderna mRNA-1273 Vaccine.

OBJECTIVES: Despite the clear benefits of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in mitigating the impact of the coronavirus disease 2019 pandemic, there are emerging reports of postvaccination myocarditis, the majority of which are diagnosed based on the clinical and radiologic findings without biopsy confirmation. We report a case of biopsy-confirmed lymphohistiocytic myocarditis after Moderna mRNA-1273 vaccination. METHODS: We describe a case of a previously healthy 45-year-old woman who had palpitations, exercise intolerance, and syncope 1 week after her first mRNA-1273 vaccine dose. Laboratory tests and cardiac imaging were compatible with myocarditis. Given her unusual clinical presentation, an endomyocardial biopsy was performed to exclude other potential etiologies. RESULTS: The endomyocardial biopsy specimen showed patchy endocardial and intramyocardial lymphohistiocytic infiltrates with scattered eosinophils and focal myocyte injury. CD3 and CD68 immunostains confirmed the lymphocytic and histiocytic nature of the infiltrate, respectively. A focal histiocytic collection suggestive of an ill-defined granuloma was present. The histologic and immunohistochemical findings of a lymphohistiocytic myocarditis were highly suggestive of a postvaccination hypersensitivity reaction. CONCLUSIONS: Myocarditis following SARS-CoV-2 vaccination is a rare adverse event. The findings of a lymphohistiocytic myocarditis with scattered eosinophils and a possible ill-defined granuloma are highly suggestive of a hypersensitivity reaction. The mechanism by which this inflammation occurs remains uncertain. Despite our findings, the benefits of SARS-CoV-2 vaccination far outweigh the risks.

Overview of the Role of Pharmacological Management of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) remains a prominent disease state characterized by the recurrent collapse of the upper airway while sleeping. To date, current treatment may include continuous positive airway pressure (CPAP), lifestyle changes, behavioral modification, mandibular advancement devices, and surgical treatment. However, due to the desire for a more convenient mode of management, pharmacological treatment has been thoroughly investigated as a means for a potential alternative in OSA treatment. OSA can be distinguished into various endotypic or phenotypic classes, allowing pharmacological treatment to better target the root cause or symptoms of OSA. Some medications available for use include antidepressants, CNS stimulants, nasal decongestants, carbonic anhydrase inhibitors, and potassium channel blockers. This review will cover the findings of currently available and future study medications that could potentially play a role in OSA therapy.

An adolescent female with a testosterone-secreting ovarian teratoma: a case report.

Ovarian neoplasms constitute 1% of childhood tumors. The majority of them are teratomas and usually are asymptomatic or present with paraneoplastic syndromes. Our case is a 16-year-old female who presented with chronic abdominal pain, virilization and oligomenorrhea and found to have a complex cystic mass of the left ovary, more likely cystic teratoma on abdomen and pelvis CT. Further work-up revealed significantly elevated serum total and free testosterone. The patient subsequently underwent left salpingo-oophorectomy confirming the radiological findings. Within two week after surgery, serum testosterone normalized and the patient started having regular menstrual cycles. In summary, ovarian teratomas should be include in the differential diagnosis of abdominal pain and menstrual abnormalities in female adolescents. Further studies are needed to determine the role of ovarian-sparing surgery in this patient population.

Comparative Study of COVID-19 Pandemic Progressions in 175 Regions in Australia, Canada, Italy, Japan, Spain, U.K. and USA Using a Novel Model That Considers Testing Capacity and Deficiency in Confirming Infected Cases.

Not identified as being exposed or infected, the group of asymptomatic and presymptomatic patients has become the key source of infectious hosts for the COVID-19 pandemic, triggering the re-emergence of outbreaks. Acknowledging the impacts of movement of unidentified patients and the limited testing capacity on understanding the spread of the virus, an augmented Susceptible-Exposed-Infectious-Confirmed-Recovered (SEICR) model integrating intercity migration data and testing capacity is developed to probe into the number of unidentified COVID-19 infected patients. This model allows evaluation of the effectiveness of active interventions, and more accurate prediction of the pandemic progression in a country, region or city. A pseudo-coevolutionary algorithm is adopted in the model fitting to provide an effective estimation of high-dimensional unknown parameter sets using a limited amount of historical data. The model is applied to 175 regions in Australia, Canada, Italy, Japan, Spain, the UK and USA to estimate the number of unconfirmed cases using limited historical data. Results showed that the actual number of infected cases could be 4.309 times as many as the official confirmed number. By implementing mass COVID-19 testing, the number of infected cases could be reduced by about 50%.

Who should get vaccinated first? An effective network information-driven priority vaccination strategy

Approval of emergency use of the Novel Coronavirus Disease 2019 (COVID-19) vaccines in many countries has brought hope to ending the COVID-19 pandemic sooner. Considering the limited vaccine supply in the early stage of COVID-19 vaccination programs in most countries, a highly relevant question to ask is: who should get vaccinated first? In this article we propose a network information-driven vaccination strategy where a small number of people in a network (population) are categorized, according to a few key network properties, into priority groups. Using a network-based SEIR model for simulating the pandemic progression, the network information-driven vaccination strategy is compared with a random vaccination strategy. Results for both large-scale synthesized networks and real social networks have demonstrated that the network information-driven vaccination strategy can significantly reduce the cumulative number of infected individuals and lead to a more rapid containment of the pandemic. The results provide insight for policymakers in designing an effective early-stage vaccination plan.

Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial.

BACKGROUND: Treatment of poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting. PATIENTS AND METHODS: This multicentre, randomised, open-label, phase II trial recruited patients with ARPI-naive mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1 : 1 to receive cabazitaxel plus prednisone (group A) or physician's choice of enzalutamide or abiraterone plus prednisone (group B) at standard doses. Patients could cross over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as prostate-specific antigen response ≥50%, radiographic response, or stable disease ≥12 weeks). RESULTS: Ninety-five patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in group A versus group B (80% versus 62%, P = 0.039). Overall survival was not different between groups A and B (median 37.0 versus 15.5 months, hazard ratio (HR) = 0.58, P = 0.073) nor was time to progression (median 5.3 versus 2.8 months, HR = 0.87, P = 0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% versus ARPI 0%), diarrhoea (9% versus 0%), infection (9% versus 0%), and fatigue (7% versus 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, P < 0.001; HR = 4.03, P < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, P < 0.001). CONCLUSIONS: Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naive poor prognosis mCRPC. ctDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Presenting stage and risk group in men dying of prostate cancer.

Introduction: Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods: The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. Results: A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions: This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

Modeling and prediction of the 2019 coronavirus disease spreading in China incorporating human migration data.

This study integrates the daily intercity migration data with the classic Susceptible-Exposed-Infected-Removed (SEIR) model to construct a new model suitable for describing the dynamics of epidemic spreading of Coronavirus Disease 2019 (COVID-19) in China. Daily intercity migration data for 367 cities in China were collected from Baidu Migration, a mobile-app based human migration tracking data system. Early outbreak data of infected, recovered and death cases from official source (from January 24 to February 16, 2020) were used for model fitting. The set of model parameters obtained from best data fitting using a constrained nonlinear optimisation procedure was used for estimation of the dynamics of epidemic spreading in the following months. The work was completed on February 19, 2020. Our results showed that the number of infections in most cities in China would peak between mid February to early March 2020, with about 0.8%, less than 0.1% and less than 0.01% of the population eventually infected in Wuhan, Hubei Province and the rest of China, respectively. Moreover, for most cities outside and within Hubei Province (except Wuhan), the total number of infected individuals is expected to be less than 300 and 4000, respectively.

Prediction of COVID-19 spreading profiles in South Korea, Italy and Iran by data-driven coding.

This work applies a data-driven coding method for prediction of the COVID-19 spreading profile in any given population that shows an initial phase of epidemic progression. Based on the historical data collected for COVID-19 spreading in 367 cities in China and the set of parameters of the augmented Susceptible-Exposed-Infected-Removed (SEIR) model obtained for each city, a set of profile codes representing a variety of transmission mechanisms and contact topologies is formed. By comparing the data of an early outbreak of a given population with the complete set of historical profiles, the best fit profiles are selected and the corresponding sets of profile codes are used for prediction of the future progression of the epidemic in that population. Application of the method to the data collected for South Korea, Italy and Iran shows that peaks of infection cases are expected to occur before mid April, the end of March and the end of May 2020, and that the percentage of population infected in each city or region will be less than 0.01%, 0.5% and 0.5%, for South Korea, Italy and Iran, respectively.