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College enrollment unevenly declines in the U.S., Broadway eagerly awaits the day when the lights go back on, and a historic snowstorm strikes the American West.

[This corrects the article DOI: 10.1371/journal.pone.0252863.].

BackgroundMicvo (PYX-201) targets extra domain-B of fibronectin, an extracellular matrix protein highly expressed in tumors compared to normal tissues. It has a protease-cleavable linker conjugated to an Aur0101 payload. In animal models, micvo demonstrated compelling antitumor activity across patient-derived xenograft models including HNSCC. A mouse analog of micvo induced T-cell infiltration and increased PD-L1 expression in a syngeneic tumor model. The combination of micvo with a mouse analog of anti-PD-L1 resulted in sustained tumor regression. In the ongoing first-in-human study (NCT05720117), micvo monotherapy showed encouraging antitumor activity in heavily pretreated patients across multiple tumor types, particularly HNSCC, with a manageable safety profile. Therefore, exploring the combination of micvo with pembrolizumab in HNSCC is of strong interest.MethodsPYX-201-102 is a dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of micvo in combination with pembrolizumab in select solid tumors. As the micvo starting dose of 3.6 mg/kg Q3W is considered therapeutically active in recurrent/metastatic (R/M) HNSCC based on data from the monotherapy study (confirmed partial response in HNSCC at this dose), the focus of the combination therapy dose-escalation part is first line (1L) therapy in R/M HNSCC with PDL1 CPS ≥1. Eligible primary tumor sites include oropharynx (regardless of HPV status), oral cavity, hypopharynx, and larynx. Additionally, 2L+ HNSCC (including platinum-refractory disease or recurrence/progression ≤6 months from concurrent chemoradiation) and other tumor types that progressed on standard therapies are eligible during dose escalation. The primary objective of dose escalation is to determine MTD and RP2D. Pembrolizumab (200 mg IV) will be given with micvo at escalating doses starting at 3.6 mg/kg IV Q3W following a BOIN design. During dose escalation, additional participants with 1L HNSCC will be enrolled in 1 or more dose levels determined to be safe and tolerable (i.e., backfill enrollment). Approximately 60 participants across HNSCC and other tumor types will be enrolled in dose escalation to accurately characterize RP2D. For dose expansion, participants with 1L R/M HNSCC PD-L1 CPS≥1 will be enrolled first, with other indications added based on emerging data. The primary objective of dose expansion is to assess objective response rate per RECIST v1.1. The study opened for enrollment in January 2025. Clinical Trial Information: NCT06795412Ethics ApprovalThe study obtained Ethics Approval from the IRB board at each institution and all participants signed an informed consent before taking part in the study. Approval number for 4 active sites are as follows: • 2024-1995 • 25-075 • NXVIR24.61 • Pro00084051

Enhancing the role of private sector partners in education can lead to significant improvements in education service delivery. However, the realization of such benefits depends in great part on the design of the partnership between the public and private sectors, on the overall regulatory framework of the country, and on the governmental capacity to oversee and enforce its contracts with the private sector. Under the right terms, private sector participation in education can increase efficiency, choice, and access to education services, particularly for students who tend to fail in traditional education settings. Private-for-profit schools across the world are already serving a vast range of usersâ€\"from elite families to children in poor communities. Through balanced public-private partnerships (PPPs) in education, governments can leverage the specialized skills offered by private organizations as well as overcome operating restrictions such as salary scales and work rules that limit public sector responses. 'The Role and Impact of Public-Private Partnerships in Education' presents a conceptualization of the issues related to PPPs in education, a detailed review of rigorous evaluations, and guidleines on how to create successful PPPs. The book shows how this approach can facilitate service delivery, lead to additional financing, expand equitable access, and improve learning outcomes. The book also discusses the best way to set up these arrangements in practice. This information will be of particular interest to policymakers, teachers, researchers, and development practitioners.

Abstract INTRODUCTION Current randomized trials demonstrating superiority of mechanical thrombectomy for the treatment of acute ischemic stroke for anterior circulation large vessel occlusion, have enrolled patients with symptom onset up to 6 hours. Outcomes of thrombectomy beyond 6 hours have not been well studied. The Trevo Registry is designed to assess real world outcomes of the Trevo Retriever in patients experiencing acute ischemic stroke. Trevo registry has currently enrolled 1431 patients with 90-day outcome data. Outcomes of patients treated beyond 6 hours of symptom onset were studied. METHODS The study design is a prospective, open-label, consecutive enrollment, multi-center, global registry of all patients who undergo mechanical thrombectomy for acute stroke using the Trevo stent retriever as the initial device. Enrollment is expected to reach 2000 subjects at up to 100 sites. Subgroup analysis of enrolled patients treated beyond 6 hours of symptom onset and with 90-day follow-up was performed. RESULTS >As of March 24, 2017, a total of 1846 total patients were enrolled. Median NIHSS at admission was 15.5 (IQR 11–20). The majority of patients (67.4%) were treated at 6 hours or less from last known normal with a median procedure time of 50 minutes (8-286 minutes). In patients treated after 6 hours from time last known well, the revascularization rate was 93.7% with symptomatic ICH of 1.8% and 90-day mRS = 2 was 51.8%. Subgroup analysis of patients presenting within 6 hours and those presenting beyond 6 hours showed no significant difference in patient demographics or medical comorbidities. There was no difference in complication rate or 90-day outcome between the two groups. CONCLUSION The Trevo Retriever Registry represents the first look at real world data with stent retriever use in the era of clinical trials showing the overwhelming benefit of stent retrievers to treat acute ischemic stroke. This data represents real world use of the Trevo Retriever including those treated beyond 6 hours after stroke symptoms (33.8%), and this data adds to the results from recent trials with restricted eligibility criteria.