A prospective evaluation of AI-augmented epidemiology to forecast COVID-19 in the USA and Japan.

The COVID-19 pandemic has highlighted the global need for reliable models of disease spread. We propose an AI-augmented forecast modeling framework that provides daily predictions of the expected number of confirmed COVID-19 deaths, cases, and hospitalizations during the following 4 weeks. We present an international, prospective evaluation of our models' performance across all states and counties in the USA and prefectures in Japan. Nationally, incident mean absolute percentage error (MAPE) for predicting COVID-19 associated deaths during prospective deployment remained consistently <8% (US) and <29% (Japan), while cumulative MAPE remained <2% (US) and <10% (Japan). We show that our models perform well even during periods of considerable change in population behavior, and are robust to demographic differences across different geographic locations. We further demonstrate that our framework provides meaningful explanatory insights with the models accurately adapting to local and national policy interventions. Our framework enables counterfactual simulations, which indicate continuing Non-Pharmaceutical Interventions alongside vaccinations is essential for faster recovery from the pandemic, delaying the application of interventions has a detrimental effect, and allow exploration of the consequences of different vaccination strategies. The COVID-19 pandemic remains a global emergency. In the face of substantial challenges ahead, the approach presented here has the potential to inform critical decisions.

Multiple myeloma presenting as mandibular pain.

INTRODUCTION: Multiple myeloma (MM) is a systemic malignancy of plasma cells defined by monoclonal production of circulating immunoglobulins. Bone pain is a presenting feature in the majority of cases. Treatment may involve intravenous use of bisphosphonates, chemotherapy or haematopoietic stem cell transplantation. Here, we illustrate a first presentation of MM in a patient with mandibular pain and discuss radiographic, diagnostic and treatment challenges of orofacial issues in patients with MM. CASE REPORT: A 69-year-old lady presented to an emergency oral surgery clinic with a month-long history of unilateral left-sided pain in her jaw. Examination revealed a buccolingual swelling of 2cm diameter in the lower left premolar region. Radiographic images demonstrated a 2cm lytic lesion in her mandible corresponding with the symptomatic region. Aspiration of the lesion was performed and histological analysis indicated an abundance of atypical plasma cells. Subsequent biopsy revealed sheets of plasmacytoid cells suggesting evidence of a plasmacytoma. Skeletal survey, bone marrow biopsy and serum analysis confirmed the presence of MM. DISCUSSION: MM, although a systemic malignancy, can present via a variety of orofacial manifestations. The presence of a lytic lesion on plain radiographs should alert the dental practitioner to the possibility of the diagnosis. Treatment of orofacial bone pain may respond to intravenous bisphosphonates but care must be taken to avoid osteonecrosis of the jaw. CONCLUSION: This case is an important reminder of the potential oral presentations of MM and underlines the importance of radiographic evaluation in patients with atypical symptoms and presentations.

A scalable synthesis of an azabicyclooctanyl derivative, a novel DPP-4 inhibitor.

A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.