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Since the discovery of a flux of high-energy astrophysical neutrinos, searches for their origins have focused primarily at TeV-PeV energies. Compared to sub-TeV searches, high-energy searches benefit from an increase in the neutrino cross section, improved angular resolution on the neutrino direction, and a reduced background from atmospheric neutrinos and muons. However, the focus on high energy does not preclude the existence of sub-TeV neutrino emission where IceCube retains sensitivity. Here we present the first all-flavor search from IceCube for transient emission of low-energy neutrinos, focusing on the energy region of 5.6-100 GeV using three years of data obtained with the IceCube-DeepCore detector. We find no evidence of transient neutrino emission in the data, thus leading to a constraint on the volumetric rate of astrophysical transient sources in the range of ∼ 705-2301 Gpc-3 yr-1 for sources following a subphotospheric energy spectrum with a mean energy of 100 GeV and a bolometric energy of 1052 erg.

ImportanceIdentifying the optimal long-term biologic therapy for patients with psoriasis is often done through trial and error.ObjectiveTo identify the optimal biologic therapy for individual patients with psoriasis using predictive statistical and machine learning models.Design, Setting, and ParticipantsThis population-based cohort study used data from Danish nationwide registries, primarily DERMBIO, and included adult patients treated for moderate-to-severe psoriasis with biologics. Data were processed and analyzed between spring 2021 and spring 2022.Main Outcomes and MeasuresPatient clusters of clinical relevance were identified and their success rates estimated for each drug. Furthermore, predictive prognostic models to identify optimal biologic treatment at the individual level based on data from nationwide registries were evaluated.ResultsAssuming a success criterion of 3 years of sustained treatment, this study included 2034 patients with a total of 3452 treatment series. Most treatment series involved male patients (2147 [62.2%]) originating from Denmark (3190 [92.4%]), and 2414 (69.9%) had finished an education longer than primary school. The average ages were 24.9 years at psoriasis diagnosis and 45.5 years at initiation of biologic therapy. Gradient-boosted decision trees and logistic regression were able to predict a specific cytokine target (eg, interleukin-17 inhibition) associated with a successful treatment with accuracies of 63.6% and 59.2%, and top 2 accuracies of 95.9% and 93.9%. When predicting specific drugs resulting in success, gradient boost and logistic regression had accuracies of 48.5% and 44.4%, top 2 accuracies of 77.6% and 75.9%, and top 3 accuracies of 89.9% and 89.0%.Conclusions and RelevanceOf the treatment prediction models used in this cohort study of patients with psoriasis, gradient-boosted decision trees performed significantly better than logistic regression when predicting specific biologic therapy (by drug as well as target) leading to a treatment duration of at least 3 years without discontinuation. Predicting the optimal biologic could benefit patients and clinicians by minimizing the number of failed treatment attempts.

Background Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. Objectives To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. Methods We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. Results A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95Á1%), dicloxacillin (n = 194; 86Á2%), tetracycline (n = 145; 64Á4%) and rifampicin/clindamycin (n = 111; 49Á3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4Á0 (SD 1Á3) different systemic therapies, across a mean of 16Á9 (SD 11Á3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15Á3 (SD 5Á1) years [8Á2 (SD 5Á9) years when excluding penicillin and dicloxacillin]. Conclusions Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression.What is already known about this topic?• The treatment journey leading to biologic therapy in patients with HS has not previously been investigated.