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We present an exquisite 30 minute cadence Kepler (K2) light curve of the Type Ia supernova (SN Ia) 2018oh (ASASSN-18bt), starting weeks before explosion, covering the moment of explosion and the subsequent rise, and continuing past peak brightness. These data are supplemented by multi-color Panoramic Survey Telescope (Pan-STARRS1) and Rapid Response System 1 and Cerro Tololo Inter-American Observatory 4 m Dark Energy Camera (CTIO 4-m DECam) observations obtained within hours of explosion. The K2 light curve has an unusual two-component shape, where the flux rises with a steep linear gradient for the first few days, followed by a quadratic rise as seen for typical supernovae (SNe) Ia. This "flux excess" relative to canonical SN Ia behavior is confirmed in our i-band light curve, and furthermore, SN 2018oh is especially blue during the early epochs. The flux excess peaks 2.14 ± 0.04 days after explosion, has a FWHM of 3.12 ± 0.04 days, a blackbody temperature of K, a peak luminosity of , and a total integrated energy of . We compare SN 2018oh to several models that may provide additional heating at early times, including collision with a companion and a shallow concentration of radioactive nickel. While all of these models generally reproduce the early K2 light curve shape, we slightly favor a companion interaction, at a distance of ∼ based on our early color measurements, although the exact distance depends on the uncertain viewing angle. Additional confirmation of a companion interaction in future modeling and observations of SN 2018oh would provide strong support for a single-degenerate progenitor system.

Introduction: The Geostationary Lightning Mapper (GLM) instrument [1] onboard the GOES 16 and 17 satellites has been shown to be capable of detecting bolides in the atmosphere [2]. Due to its large, continuous field of view and immediate public data availability, GLM provides a unique opportunity to detect a large variety of bolides, including those in the 0.1 to 3 m diameter range that complements current ground-based meteor detection systems, which are typically sensitive to smaller objects. We have deployed a machine learning (ML) based bolide detection and light curve generation pipeline [3] on the NASA Advanced Supercomputer Facility, with detections being promptly published on a NASA hosted publicly available website, https://neo-bolide.ndc.nasa.gov. The goal is to generate a large catalog of calibrated bolide light curves to provide an unprecedented data set for three main purposes: 1) to inform meteor entry models on how incoming bodies interact with the atmosphere, 2) to infer the pre-entry properties of the impacting bodies and 3) to statistically analyze bolide impact populations across the globe. The pipeline has now been operational for over 3 years and we have amassed a catalogue of over 3500 bolides. Pipeline Architecture and ML training: As is common practice in machine learning, an iterative approach was taken to the pipeline development. Work began by utilizing classic filter design where human-derived heuristics were considered to create a set of detection filters tuned to what a human would expect for a bolide event in GLM data [4]. This manually tuned detector had a detection precision of about 1.5%. The resulting detection set was therefore 98.5% false positives. Manual human vetting then labeled the small number of legitimate bolides. Once the initial training set was obtained machine learning training could begin. After training each new classifier, the GLM data was reprocessed, and a subset was again manually labeled. After several iterations, progressively more competent ML classifiers were developed. Our current best classifier utilizes a random forest [5] and has a detection precision of 88%, meaning almost nine out of ten automated detections are legitimate. Final human vetting is still performed before publication on the website. By utilizing the NASA Advanced Supercomputing Facility, we can capitalize on massive parallelization and reprocess the full historical dataset in a matter of hours. Statistical Analysis of Detected Bolides: To date, we have posted 3549 bolides on our public website, all being manually vetted by a human before publishing. Effort has been made to identify and eliminate all systematic biases in the detection pipeline. A principal source of false positives is solar glints, where sun glare reflects off the Earth producing a signal in GLM that appears bolide-like. Solar power generation farms, in particular, can cause large numbers of concentrated false positives at specific locations on the globe. After removing these biases in the data, we can begin to statistically analyze the bolide distributions. We wish to measure the distribution of bolides as a function of latitude to assess various theories of bolide impact distributions. A marked increase in detection is very apparent during meteor showers. We are particularly sensitive to the Leonid meteor shower and found the volume of bolides in 2020 to be considerably higher than in 2019 or 2021. After experimentation, we have not found a systematic detection bias in our pipeline and so the increase appears to be legitimately in the data. We have also found a strong bias for detection during the night hours for each satellite, as would be expected. Outlook: Our ultimate goal is near 100% precision and automatic posting of detections with no human intervention. We will then be able to potentially post bolides within a minute of impact. Critical to this goal is automation of the manual human validation step. The human vetting utilizes the GOES Advanced Baseline Imager (ABI) [6] data to identify and remove false positives due to lightning and LEO satellites. We intend to develop a deep learningbased classifier of ABI images, along with other external data streams, to automate the human validation step. [ABSTRACT FROM AUTHOR]

Background: Studies have found a higher risk of comorbid anxiety and depression among patients with inflammatory bowel disease (IBD) compared with healthy individuals. If left untreated, comorbid depression and anxiety in patients with IBD can lead to poorer health outcomes and an increased healthcare utilization. The goal of this work was to develop a consensus statement to begin to address patient and provider needs and responsibilities related to screening and treatment of depression and anxiety symptoms among patients with IBD., Methods: A literature scan was conducted to gather evidence-based background information and recommendations on the screening, diagnosis, and treatment of anxiety and depression in patients with IBD. This was followed by the engagement of a panel of IBD and mental health experts and patient advocates using a modified Delphi process to synthesize the literature and distill the information into a core set of statements to support provider actions and care delivery., Results: Six statements were distilled from the literature and consensus process that link to the general management, screening, and treatment of anxiety and depression in patients with IBD., Conclusions: Mental healthcare and support for IBD patients is critical; the statements included in this article represent practical considerations for IBD healthcare professionals in addressing key issues on provider awareness, knowledge and behaviors, screening and treatment resources, and patient education., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

We overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads. To assess WRIC validity seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events. Sixteen participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose in a crossover design. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and carbohydrate oxidation. Postprandial carbohydrate oxidation trajectories for each participant and condition were modeled using Bayesian Hierarchical Modeling. Mean total error in infusions were 1.27 ± 0.67% and 0.42 ± 0.70% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions ([Formula: see text] = 1.05 ± 0.03 kcal/min, p = 0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p = 0.29), postprandial carbohydrate oxidation parameters were significantly lower for dextrose compared with sucrose or fructose. We provide evidence validating our WRIC and a novel application of statistical methods useful for research using WRIC., Competing Interests: “Our affiliation with MEI Research, Ltd., does not alter our adherence to all PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Baugh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Pediatric inflammatory bowel disease (IBD) is a chronic illness with various treatments, including ostomy surgery. Ostomy-related medical decision-making (MDM) is complex for multidisciplinary healthcare professionals (HCPs). This study sought to understand national multidisciplinary HCPs' perceptions about pediatric IBD ostomy surgery in the United States., Methods: This cross-sectional REDCap survey recruited HCPs in pediatric IBD HCP roles from the ImproveCareNow (ICN) Learning Health System. The survey gathered data on, (1) demographics, (2) participants' perspectives on patients/families' ostomy perceptions, (3) participants' own perspectives on ostomies, and (4) participants' perspectives on multidisciplinary collaboration in ostomy surgery., Results: Participants ( n  = 69, across n  = 30 American ICN sites) were 84% White, 62% female, and 54% gastroenterologists. In reflecting on patients/families' perceptions, participants endorsed most (86%) view ostomies as a "failure," various psychosocial concerns (e.g., 97% endorsed body image concerns), and most (81%) have moderate to significant stigma about ostomies. In reflecting on their own perceptions, nearly half (44%) endorsed some to moderate stigma about ostomies and felt ostomy discussions were difficult when families had negative perceptions (88%). Over half (54%) endorsed currently having multidisciplinary care for pediatric IBD surgery. Most (70%) endorsed variability in the amount and/or quality of multidisciplinary collaboration., Conclusion: MDM related to pediatric IBD ostomy surgery presents nuanced clinical complexities for HCPs. This work underscores interest in multidisciplinary care, notable ostomy-related psychosocial needs, and ostomy-related stigma. Future work should develop systematic approaches to multidisciplinary pediatric IBD ostomy care, bolster psychosocial support, and evaluate how systematic care may impact psychosocial, and healthcare utilization outcomes., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To provide an overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads., Methods: Seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events to assess WRIC validity. In a crossover design, 16 participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and CO (CO). Bayesian Hierarchical Modeling was also used to model postprandial CO trajectories for each participant and condition., Results: Mean total error in infusions were 1.27 ± 1.16% and 0.42 ± 1.21% for VO 2 and VCO 2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions ( x ¯ = 1.05 ± 0.03   kcal / min , p =0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p =0.29), postprandial CO parameters were significantly lower for dextrose compared with sucrose or fructose., Conclusions: Our WRIC validation and novel application of statistical methods presented here provide important foundations for new research directions using WRIC., Competing Interests: Disclosures: All authors declare no conflict of interest. JM and EWK are employees of MEI Research, Ltd.

Background: Tumor necrosis factor-alpha inhibitors (anti-TNFs) are a primary treatment for inflammatory bowel disease. Pharmaceutical expenditures and usage of specialty drugs are increasing. In the United States, biosimilars continue to be underutilized, despite opportunities for health care cost savings. Through quality improvement (QI) methodology, we aimed to increase biosimilar utilization among eligible patients initiating intravenous (IV) anti-TNF therapy and describe patient outcomes and associated cost savings., Methods: Beginning in July 2019, all patients initiating IV anti-TNF therapy were identified and tracked. Using the Institute of Healthcare Improvement Plan-Do-Study-Act cycle, a four-stage problem-solving model used for carrying out change, we trialed interventions to increase biosimilar utilization, including provider, staff, and family education, and utilization of a clinical pharmacist and insurance specialist. Statistical process control charts were used to show improvement over time. Patients' clinical outcome and cost savings were reviewed., Results: Using QI methodology, we increased biosimilar utilization from a baseline of 1% in June 2019 to 96% by February 2021, with sustained improvement. The originator (infliximab) was the insurance company's preferred product for 20 patients (20%). Patient outcomes (IV anti-TNF levels, absence of antidrug antibodies, and physician global assessment) between biosimilars and originators were similar. Estimated cost savings over the project duration were nearly $381,000 (average sales price) and $651,000 (wholesale acquisition cost)., Conclusions: Through QI methodology, we increased biosimilar utilization from 1% to 96% with sustained improvement, without compromising patient outcomes or safety. Estimated cost savings were substantial. Similar methodology could be implemented at other institutions to increase biosimilar utilization and potentially decrease health care costs., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Breast cancer is the second most common cancer amongst women in the United States following non-melanoma skin cancer. There were an estimated 276,480 new cases and 42,170 deaths in 2020. The lifetime risk for developing breast cancer in females is about 13%. In the United States this year approximately 284,200 people out of which 281,550 women and 2,650 men, will be diagnosed with invasive breast cancer. In recent years, treatment options with novel mechanisms have emerged. Cyclin dependent kinase (CDK) 4/6 inhibitors, namely palbociclib, ribociclib and abemaciclib, are relatively new targeted therapies for treating breast cancers express estrogen receptors (ER) and/or progesterone receptors (PR). CDKs are important regulatory enzymes in cell cycle transitions and cell division. Selective inhibition of CDK4/6 causes cell cycle to arrest in the G1 phase, resulting in reduced cell viability and tumor response. Abemaciclib is the only one approved as monotherapy. Palbociclib and ribociclib must be used as adjunctive therapy to endocrine therapy such as tamoxifen, aromatase inhibitors or fulvestrant. Common side effects include neutropenia, thrombocytopenia, fatigue, nausea, and vomiting. A black box warning for all CDK inhibitors is a rare but possibly fatal severe inflammation of the lungs, called pneumonitis. We present a fatal case of severe pneumonitis with superimposed fungal respiratory infection in the setting of hypogammaglobulinemia in a 65-year-old female with metastatic ER and PR positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer who received abemaciclib., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-21-19/coif). The authors have no conflicts of interest to declare., (2022 Translational Breast Cancer Research. All rights reserved.)

Pure red cell aplasia (PRCA) is a rare disorder mainly affecting the erythroid precursor cells. It presents with severe isolated reticulocytopenia with relatively normal counts in the myeloid and megakaryocytic lineages. It has been attributed to numerous congenital and acquired causes. DNA Methyl Transferase 3 Alpha (DNMT3A) mutation has been typically associated with myeloid and lymphoid malignancies. There is a scarcity of data regarding the association of DNMT3A mutation with PRCA. We report a case of a 73-year-old man who initially presented with anemia and reticulocytopenia. After a thorough evaluation and eventual bone marrow biopsy, he was diagnosed with PRCA. Further genetic testing identified a DNMT3A mutation. We are reporting this rare case to highlight the fact that DNMT3A mutation can also present as isolated PRCA in and of itself without the co-occurrence of leukemia, lymphoma, or myelodysplastic syndrome (MDS).

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas that are often associated with neurofibromatosis type-1. These tumors share common immunohistochemistry findings which can make diagnosis difficult. We present the case of a woman who presented with a diagnosis of metastatic melanoma of the index finger of her left hand but was eventually diagnosed with primary epithelioid malignant peripheral nerve sheath tumor. We will be highlighting the diagnostic challenge of differentiating between these two very different malignancies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Biglow et al.)

Extraosseous Ewing sarcoma is an uncommon entity in the adult population. Cardiac metastases or local invasion of a tumor into the heart is a known but also infrequent occurrence for most malignancies. We present a case of a patient with a history of extraosseous Ewing sarcoma who presented to the emergency room with chest pain and was found to have an inferior ST-elevation myocardial infarction and systemic emboli and was found to have recurrence of sarcoma invading the left atrium., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2020 Jennifer Dotson et al.)

Objectives: Adequate serum drug levels of tumor necrosis factor-alpha inhibitors (anti-TNF) have been shown to improve outcomes in patients with inflammatory bowel disease. We aim to describe the quality improvement (QI) methods used at our institution to improve post-induction therapeutic drug monitoring (TDM) in children initiating anti-TNF therapy (infliximab and adalimumab) and describe the frequency of subtherapeutic anti-TNF levels., Methods: Beginning in February 2016, all patients initiating anti-TNF therapy were identified and tracked. Interventions to improve TDM, including the initiation of therapy plans for infliximab, real-time reminders for practitioners, and scheduling modifications for those initiating anti-TNF therapies were implemented using the Institute for Healthcare Improvement Plan-Do-Study-Act cycle approach. Statistical process control charts were used to demonstrate improvement over time. Anti-TNF levels and presence of antidrug antibodies were also recorded., Results: Using QI methodology, we improved post-induction anti-TNF TDM from a baseline of 43% in 2015 to >80% by the end of 2017, with sustained improvement. Infliximab post-induction TDM improved from a baseline of 59% to 82%, whereas adalimumab post-induction TDM improved from baseline of 14% to 79%. In total, 36% of all anti-TNF post-induction levels were <5 μg/mL, with nearly 60% of post-induction infliximab levels being <5 μg/mL., Conclusions: Through incremental QI approaches, we improved the utilization of anti-TNF post-induction TDM with sustained improvement, approaching our goal of 90%. Subtherapeutic post-induction infliximab levels were common, indicating a strong need for anti-TNF TDM and an opportunity for dose optimization.

A subdural hygroma is an accumulation of cerebrospinal fluid in the subdural space that may occur secondary to trauma and surgery, or for iatrogenic reasons, such as a lumbar puncture. Lumbar puncture is a procedure used commonly for intrathecal chemotherapy for patients with B-cell acute lymphocytic leukemia (B-ALL) though subdural hygroma is a very rare complication. We present a case of a fatal, refractory subdural hygroma in a patient with B-ALL., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (Copyright © 2019 Mina Shenouda et al.)

Neutropenic enterocolitis mostly affects patients with acute myeloid leukemia (AML) who get treated with intensive chemotherapy which is associated with prolonged neutropenia; its pathogenesis is not well understood and the main factors in this life-threatening condition appear to be neutropenia, mucosal injury and a weakened immune system as a consequence of intensive chemotherapeutic agents. Midostaurin in combination with chemotherapy became the standard of care for FLT3 mutant AML since its approval by the United States Food and Drug Administration (FDA) in April 2017. Anecdotally in our institution, we noticed the common occurrence of neutropenic colitis in three out of three patients who were treated with midostaurin as part of induction chemotherapy for AML.

Idelalisib is a delta isoform-specific, phosphoinositide 3-kinase (PI3-K) inhibitor. It has been used as a single agent for the treatment of relapsed or refractory small lymphocytic lymphoma (SLL), follicular non-Hodgkin's lymphoma (NHL), and in combination with rituximab for patients with chronic lymphocytic leukemia (CLL). We present a case of a 77-year-old man diagnosed with SLL and was treated with multiple chemotherapeutic regimens in the past. Considering multiple relapses, he was started on idelalisib monotherapy almost 12 months ago. The treatment was stopped due to worsening neutropenia as well as mixed response on the scans. Almost, within one week of stopping the medication, he presented with complaints of altered mental status, hematuria, and worsening of generalized lymphadenopathy. This time, the patient was started on venetoclax (BCL-2 inhibitor) and rituximab which he is tolerating well without any complications., Competing Interests: The authors have declared that no competing interests exist.

Disseminated Nocardia infections are a rare occurrence that typically occur in immunocompromised hosts. Chronic lymphocytic leukemia (CLL) is a hematologic malignancy which makes patients susceptible to infections through various mechanisms. The treatments for CLL also target immunologic pathways which can contribute to infections. Ibrutinib is a commonly utilized tyrosine kinase inhibitor for CLL which targets the Bruton tyrosine kinase pathway. Although it is generally well tolerated, patients sometimes experience infections while on this medication, however, opportunistic infections are unusual. We present a rare, fatal case of a patient who developed simultaneous infections with bronchopulmonary Aspergillus and disseminated Nocardiosis to the subcutaneous tissues, lymph nodes and central nervous system while on treatment with ibrutinib for CLL., Competing Interests: The authors have declared that no competing interests exist.

High grade astrocytomas such as anaplastic astrocytoma and glioblastoma multiforme are aggressive central nervous system malignancies with a poor prognosis. Due to shortened survival times, their devastating effects are usually localized intracranially and rarely metastasize outside of the central nervous system. When metastases occur, they usually present in patients with longer survival times and they typically coincide with a primary site recurrence. We present a rare case of metastases from a high-grade astrocytoma/glioblastoma to the pleura, bones and liver within six months of diagnosis, without primary site recurrence., Competing Interests: The authors have declared that no competing interests exist.

Objective: The Cancer Care Index (CCI), a single metric that sums the number of undesirable patient events in a given time frame (either preventable harm events or missed opportunities to provide optimal care), resulted in a 42% improvement in performance. Our objective was to test the index concept in other service lines to determine whether similar performance improvement occurred., Study Design: Care indices were developed and introduced in 3 additional service lines: Nephrology (Chronic Kidney Disease Care Index; CKDCI), Pulmonology (Lung Transplantation Care Index; LTCI), and Otolaryngology (Tracheostomy Care Index; TCI). After reaching agreement on specific harms to be avoided and elements of optimal care that should be reliably delivered, these items were compiled into indices that were updated monthly. Reports included each element individually and the total for all elements. Baseline performance was calculated retrospectively for the previous year., Results: Significant improvement in performance occurred in each program following implementation of the clinical indices. The CKDCI was decreased by 63.2% (P < .001), the LTCI was decreased by 89.5% (P < .001), and the TCI was decreased by 53.0% (P < .001). Surveyed staff indicated satisfaction with use of the metric., Conclusions: Clinical indices are useful for evaluating and managing the overall reliability of a program's ability to deliver optimal care, and are associated with improved clinical performance and satisfaction by service line staff when incorporated into a program's operation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Inhibitors targeting the activating mutants of the epidermal growth factor receptor (EGFR) have found success in the treatment of EGFR mutant positive non-small-cell lung cancer. A secondary point mutation (T790M) in the inhibitor binding site has been linked to the acquired resistance against those first generation therapeutics. Herein, we describe the lead optimization of a series of reversible, pan-mutant (L858R, del 746-750, T790M/L858R, and T790M/del 746-750 ) EGFR inhibitors. By use of a noncovalent double mutant (T790M/L858R and T790M/del 746-750 ) selective EGFR inhibitor (2) as a starting point, activities against the single mutants (L858R and del 746-750 ) were introduced through a series of structure-guided modifications. The in vitro ADME-PK properties of the lead molecules were further optimized through a number of rational structural changes. The resulting inhibitor (21) exhibited excellent cellular activity against both the single and double mutants of EGFR, demonstrating target engagement in vivo and ADME-PK properties that are suitable for further evaluation. The reversible, noncovalent inhibitors described complement the covalent pan-mutant EGFR inhibitors that have shown encouraging results in recent clinical trials.

In breast cancer, there are two widely used paclitaxel-based adjuvant chemotherapies, either dose dense paclitaxel (ddP) or weekly paclitaxel (wP). To our knowledge, the comparisons of toxicity and tolerability between the two regimens have never been reported in the literature. This is a retrospective single-institution charts review of breast cancer patients who were treated with paclitaxel-based chemotherapy either ddP or wP. In total, 76 and 45 patients with breast cancer received adjuvant standard ddP and wP, respectively. Patient characteristics in both groups were comparable. Our results showed no statistical significant difference in toxicity profile and tolerability between the two regimens. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) was equally observed in both schedules. Furthermore, grade 3 and 4 CIPN was observed in 17 and 18 %, respectively (p = 0.93). In terms of tolerability, both regimens resulted in similar rates of hospitalization and treatment discontinuation. Our data analysis indicates no significant difference in toxicity profile between the two standard paclitaxel regimens in breast cancer. However, this is a small sample-sized retrospective study and further prospective trial with a larger sample size is warranted.

The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein.