Identification of Filovirus Entry Inhibitors from Marine Fungus-Derived Indole Alkaloids.

Filoviruses, mainly consisting of the two genera of and , are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these diseases. To search for effective drugs, we have identified three marine indole alkaloids that exhibit potent activities against filovirus infection.

Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.

The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP).

Quantifying Hydraulic Geometry and Whitewater Coverage for Steep Proglacial Streams to Support Process-Based Stream Temperature Modelling.

At-a-station hydraulic geometry (AASHG) relationships describe the dependence of a river's width, mean depth and mean velocity on discharge at a given location, and are typically modelled as power-law functions. They are often used when modelling stream temperature under unsteady flow conditions. Deriving AASHG relationships is challenging for steep proglacial streams due to the combination of complex morphology and velocity distributions, and rapidly varying flow.

Risk of late radiation necrosis more than 5 years after stereotactic radiosurgery.

Objective: Radiation necrosis (RN) is a well-recognized late complication most commonly occurring within 2 years of stereotactic radiosurgery (SRS); however, late RN (LRN), RN occurring or recurring > 5 years after SRS, has been poorly described. This study analyzes the incidence of and risk factors for LRN occurring > 5 years after SRS.

Methods: This retrospective analysis included patients treated with linear accelerator-based SRS for tumors or arteriovenous malformations with > 5 years of clinical and serial MRI follow-up.

Discovery of a nasal spray steroid, tixocortol, as an inhibitor of SARS-CoV-2 main protease and viral replication.

Coronaviruses rely on the viral-encoded chymotrypsin-like main protease (M or 3CL) for replication and assembly. Our previous research on M of SARS-CoV-2 identified cysteine 300 (Cys300) as a potential allosteric site of M inhibition. Here, we identified tixocortol (TX) as a covalent modifier of Cys300 which inhibits M activity as well as in a cell-based M expression assay.

Radiomic Analysis of Treatment Effect for Patients with Radiation Necrosis Treated with Pentoxifylline and Vitamin E.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN).

Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE.

Characterization of therapeutic antibody efficacy against multiple SARS-CoV-2 variants in the hamster model.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and onset of the coronavirus disease-19 (COVID-19) pandemic led to an immediate need for therapeutic treatment options. Therapeutic antibodies were developed to fill a gap when traditional antivirals were not available. In late 2020, the United States Government undertook an effort to compare candidate therapeutic antibodies in virus neutralization assays and in the hamster model of SARS-CoV-2 infection.

Initial experience and patient tolerance of proton stereotactic body radiotherapy.

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment.

Patients And Methods: From Sep. 2019 to Dec.

RBD design increases the functional antibody titers elicited by SARS-CoV-2 spike vaccination.

Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination.

ECHO+: An Innovative Technology-Enabled Collaborative Learning and Quality Improvement Program Strengthening Rural Primary Care in Arkansas, West Virginia, and Oklahoma.

In this paper, we describe the Project Extension for Community Healthcare Outcomes+ (ECHO+) model and evaluation plan for incorporating changes to primary care delivery, improving patient and clinician outcomes, and making long-term system improvements.

Patterns of Treatment Failure in Primary Central Nervous System Lymphoma.

Objectives: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement.

Methods: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease.

Primary Diffuse Leptomeningeal Melanomatosis in a Child with Extracranial Metastasis: Case Report.

Primary meningeal melanomatosis is an extremely rare tumor with very few documented responses to treatment. A 3-year-old male with a complex past medical history, including prematurity and shunted hydrocephalus, was diagnosed with primary meningeal melanomatosis with peritoneal implants. Molecular testing revealed an NRAS Q61R mutation.

Risks of Spinal Abnormalities and Growth Impairment After Radiation to the Spine in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

Purpose: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children.

Methods And Materials: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients).

Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8 T cells in persons with previous COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hybrid immunity is more protective than vaccination or previous infection alone. To investigate the kinetics of spike-reactive T (T) cells from SARS-CoV-2 infection through messenger RNA vaccination in persons with hybrid immunity, we identified the T cell receptor (TCR) sequences of thousands of index T cells and tracked their frequency in bulk TCRβ repertoires sampled longitudinally from the peripheral blood of persons who had recovered from coronavirus disease 2019 (COVID-19). Vaccinations led to large expansions in memory T cell clonotypes, most of which were CD8 T cells, while also eliciting diverse T cell clonotypes not observed before vaccination.

The Pediatric Proton and Photon Therapy Comparison Cohort: Study Design for a Multicenter Retrospective Cohort to Investigate Subsequent Cancers After Pediatric Radiation Therapy.

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially.

The impact of radiation therapy variables on pediatric high-grade glioma outcomes: A National Cancer Database analysis.

Purpose: The purpose of this analysis is to report patterns of care for pediatric patients with high-grade glioma (pHGG) and evaluate the impact of radiotherapy (RT) variables on outcomes using the National Cancer Database (NCDB).

Methods: Eligibility criteria included age < 22 years, histologically diagnosed WHO grade III-IV gliomas treated with ≥50 Gy and < 76 Gy RT between 2004 and 2013, and RT initiation within 90 days of diagnosis. RT variables including RT dose, RT timing, and RT modality were analyzed along with baseline demographic, tumor, and treatment variables to assess the impact on overall survival.

Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients.

In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations-EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022.

Use of Perirectal Hyaluronic Acid Spacer Prior to Radiotherapy in a Pediatric Patient With Bladder Rhabdomyosarcoma: A Case Report.

Rhabdomyosarcoma (RMS) treatment involves surgery, chemotherapy, and radiotherapy. A radioprotective space between the bladder/prostate and rectum reduces postradiation complications, as reported in adult patients. Describe pediatric preradiotherapy perirectal hyaluronic acid (HA) spacer injection for bladder/prostate RMS.

Early in vivo Radiation Damage Quantification for Pediatric Craniospinal Irradiation Using Longitudinal MRI for Intensity Modulated Proton Therapy.

Purpose: Proton vertebral body sparing craniospinal irradiation (CSI) treats the thecal sac while avoiding the anterior vertebral bodies in an effort to reduce myelosuppression and growth inhibition. However, robust treatment planning needs to compensate for proton range uncertainty, which contributes unwanted doses within the vertebral bodies. This work aimed to develop an early in vivo radiation damage quantification method using longitudinal magnetic resonance (MR) scans to quantify the dose effect during fractionated CSI.

Identification of a Novel Fusion with Targeted Therapeutic Implications in Locally Advanced Pediatric Cholangiocarcinoma: A Case Report.

Locally advanced cholangiocarcinoma has a poor prognosis, with long-term survival only for patients where complete surgical resection is achieved. Median overall survival with chemotherapy alone is less than 1 year. Novel strategies combining conventional chemotherapy and radiotherapy followed by targeted agents can lead to durable treatment responses and are applicable to cholangiocarcinoma management.

Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy.

Purpose: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI).

Methods: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96).

Spectroscopic MRI-Guided Proton Therapy in Non-Enhancing Pediatric High-Grade Glioma.

Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor.