Phase 2 Study of Low-Dose Paclitaxel and Cisplatin in Combination With Split-Course Concomitant Twice-Daily Reirradiation in Recurrent Squamous Cell Carcinoma of the Head and Neck: Long-term Follow-up of NRG Oncology Radiation Therapy Oncology Group Protocol 9911.

Purpose: Locoregionally recurrent squamous cell carcinoma of the head and neck and second primary tumors (SPTs) in previously irradiated fields, if not resectable, are virtually always fatal. Chemotherapy alone yields a median survival of 10 to 11 months and 5-year overall survival (OS) rates of <5%. Concurrent reirradiation and chemotherapy constitutes an alternative, nonstandard strategy.

Membrane Permeability of Sucrose Calculated from Equilibrium Time-Correlation Functions Using Molecular Dynamics Simulations with Enhanced Sampling.

A computational framework for rigorously computing the membrane permeability of small molecules from unbiased molecular dynamics simulations is presented. The method in its optimized form exploits the committor probability within the transition path theory framework and is applicable to molecules with free energy barriers for which a determination of the permeability coefficient from spontaneous crossings during equilibrium simulations would be unfeasible. A novel computational protocol is implemented through which the equilibrium time-correlation function is calculated from a combination of enhanced sampling to determine the equilibrium potential of mean force of the permeant molecule and a reweighted ensemble of short unbiased trajectories.

A Cyclic-di-AMP Adjuvanted CPAF Protein Vaccine Is Immunogenic in Swine, but It Fails to Reduce Genital Burden.

: () is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and potential for serious health complications, no vaccine has been licensed.

Repeatability of wildlife surveys for estimating abundance: A method to assess the consistency of detection probability and animal availability.

A primary consideration of abundance studies that use unmarked animals is whether survey counts accurately reflect the population size or if unknown variation in animal movement or detection probability biases counts irrespective of population size. We posited that high repeatability in counts among temporally replicated surveys would indicate that counts are a good index of abundance. We temporally replicated 49 nocturnal spotlight surveys of white-tailed deer (Odocoileus virginianus) up to three times each (n = 128 total samples) to test the repeatability of this commonly used wildlife monitoring technique.

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology.

Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question.

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Purpose: Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer.

Methods: Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT.

Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer.

Purpose: NFE2L2/KEAP1/CUL3 mutations have been validated for radioresistance in cell-based assays and animal models. However, clinical validation of these biomarkers has been challenging because of multimodality treatment regimens. This study aims to investigate the association between NFE2L2/KEAP1/CUL3 mutations and patient outcomes, including local failure, locoregional failure, disease-free survival (DFS), and overall survival, using samples from a phase III trial in which patients were treated with radiation monotherapy at two controlled doses.

Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration.

Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial.

Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.

Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America.

Broad-scale predictions of herpetofauna occupancy and colonization in an agriculturally dominated landscape.

Predictions of species occurrence allow land managers to focus conservation efforts on locations where species are most likely to occur. Such analyses are rare for herpetofauna compared to other taxa, despite increasing evidence that herptile populations are declining because of landcover change and habitat fragmentation. Our objective was to create predictions of occupancy and colonization probabilities for 15 herptiles of greatest conservation need in Iowa.

Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice.

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice.

Stability and antigenicity of Chlamydia muridarum major outer membrane protein antigen at body temperature.

Chlamydia is an obligate intracellular bacterial pathogen responsible for disease and infertility across multiple species. Currently vaccines are being studied to help reduce the prevalence of this disease. The main advantage of protein subunit vaccines is their high degree of safety although this is traded off with the requirement for multiple booster doses to achieve complete protection.

Neural Models for Generating Natural Language Summaries from Temporal Personal Health Data.

With an increased interest in the production of personal health technologies designed to track user data (e.g., nutrient  intake, step counts), there is now more opportunity than ever to surface meaningful behavioral insights to everyday users in the form of natural language.

A TriAdj-Adjuvanted CPAF Protein Vaccine Is Highly Immunogenic in Pigs.

() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as () in pigs.

Erratum: Survey of Conductive Polymers for the Fabrication of Conformation Switching Nucleic Acid-Based Electrochemical Biosensors.

[This corrects the article DOI: 10.1021/acsapm.3c02206.

A rare form of calcinosis in patients with systemic sclerosis-myositis overlap: report of four cases.

Objectives: Calcinosis is a well-described entity that occurs in patients with systemic sclerosis (SSc) and dermatomyositis (DM). Calcinosis in SSc typically occurs over pressure points and is usually nodular. We present a case series of four patients with SSc with a much rarer, diffuse form of calcinosis to illustrate this poorly recognized pattern of extensive and debilitating disease.

Correlation of Experimental and Calculated Inhibition Constants of Protease Inhibitor Complexes.

Predicting the potency of inhibitors is key to in silico screening of promising synthetic or natural compounds. Here we describe a predictive workflow that provides calculated inhibitory values, which concord well with empirical data. Calculations of the free interaction energy ΔG with the YASARA plugin FoldX were used to derive inhibition constants K from PDB coordinates of protease-inhibitor complexes.

How is Membrane Permeation of Small Ionizable Molecules Affected by Protonation Kinetics?

According to the pH-partition hypothesis, the aqueous solution adjacent to a membrane is a mixture of the ionization states of the permeating molecule at fixed Henderson-Hasselbalch concentrations, such that each state passes through the membrane in parallel with its own specific permeability. An alternative view, based on the assumption that the rate of switching ionization states is instantaneous, represents the permeation of ionizable molecules via an effective Boltzmann-weighted average potential (BWAP). Such an assumption is used in constant-pH molecular dynamics simulations.

Season of radiotherapy and outcomes of head & neck cancer patients in the MACH-NC & MARCH meta-analyses.

Background: A single institution retrospective study suggested that head and neck squamous cell cancer (HNSCC) patients receiving radiotherapy (RT) during "dark" season (fall/winter) may have better outcomes than those treated during "light" season (spring/summer), possibly secondary to seasonal variations in cell cycle progression. We investigated the impact of season of RT in two large, multi-institutional, prospective datasets of randomized trials.

Methods: Individual patient data from the MACH-NC and MARCH meta-analyses were analyzed.

Evaluating differences in density estimation for central Iowa butterflies using two methodologies.

The Pollard-Yates transect is a widely used method for sampling butterflies. Data from these traditional transects are analyzed to produce density estimates, which are then used to make inferences about population status or trends. A key assumption of the Pollard-Yates transect is that detection probability is 1.

Radiotherapy Plus Cisplatin With or Without Lapatinib for Non-Human Papillomavirus Head and Neck Carcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC.

Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS).

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).

Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.

Design, Setting, And Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS.