TP53 mutations and the association with platinum resistance in high grade serous ovarian carcinoma.

Objectives: Alterations in the tumor suppressor TP53 gene are the most common mutations in high grade serous ovarian carcinoma. The impact of TP53 mutations on clinical outcomes and platinum resistance is controversial. We sought to evaluate the genomic profile of high grade serous ovarian carcinoma and explore the association of TP53 mutations with platinum resistance.

Midlife sensory and motor functions improve prediction of blood-based measures of neurodegeneration and Alzheimer's disease in late middle-age.

Introduction: We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10-year changes in biomarkers of neurodegeneration and Alzheimer's disease.

Methods: Longitudinal data of  = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5-year, and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10-year incidence of biomarker positivity of serum-based neurofilament light chain (NfL) and amyloid beta (Aβ)/Aβ using logistic regression.

A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer.

Purpose: To determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiation therapy preserves pulmonary function compared with standard radiation therapy for non-small cell lung cancer (NSCLC).

Methods And Materials: This single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiation therapy with either stereotactic body radiation therapy or conventionally fractionated radiation therapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiation therapy or functional lung avoidance radiation therapy.

Midlife sensory and motor functions improve long-term predictions of cognitive decline and incidence of cognitive impairment.

Introduction: We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10-year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS).

Methods: Longitudinal data of  = 1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10-year cognitive decline or cognitive impairment incidence using logistic regressions.

Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia.

Purpose: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown.

Effect of Neurotoxin Exposure on Blood Biomarkers of Neurodegeneration and Alzheimer Disease.

Aim: To determine whether exposure to neurotoxins in midlife is associated with changes in blood-based biomarkers of neurodegeneration and Alzheimer disease pathology.

Methods: Blood cadmium, lead, neurofilament light (NfL) chain, total tau (TTau), and amyloid beta (Aβ) 40 and Aβ42 concentrations were measured in 1516 participants in the Beaver Dam Offspring Study. Linear mixed-effect models were used to determine associations between baseline cadmium and lead levels and baseline NfL, TTau, and Aβ42/Aβ40, and 10-year change in concentrations using repeated measures of these biomarkers as the outcome.

Toxicity and Patient-Reported Quality-of-Life Outcomes After Prostate Stereotactic Body Radiation Therapy With Focal Boost to Magnetic Resonance Imaging-Identified Prostate Cancer Lesions: Results of a Phase 2 Trial.

Purpose: In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk.

Methods And Materials: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.

Associations of sensory and motor function with blood-based biomarkers of neurodegeneration and Alzheimer's disease in midlife.

Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (Aβ)).

Quantification of very late xerostomia in head and neck cancer patients after irradiation.

Objective: Radiation therapy (RT) for head and neck cancer (HNC) can result in severe xerostomia, or the subjective feeling of dry mouth. Characterizing xerostomia is critical to designing future clinical trials investigating how to improve HNC patients' quality of life (QoL). Few studies have investigated the very late (>5 years post-RT) effects of RT for HNC.

Log-Rank Test vs MaxCombo and Difference in Restricted Mean Survival Time Tests for Comparing Survival Under Nonproportional Hazards in Immuno-oncology Trials: A Systematic Review and Meta-analysis.

Importance: The log-rank test is considered the criterion standard for comparing 2 survival curves in pivotal registrational trials. However, with novel immunotherapies that often violate the proportional hazards assumptions over time, log-rank can lose power and may fail to detect treatment benefit. The MaxCombo test, a combination of weighted log-rank tests, retains power under different types of nonproportional hazards.

Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking.

Experimental Design: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed.

Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel.

Paclitaxel (Taxol) is a cornerstone of cancer treatment. However, its mechanism of cytotoxicity is incompletely understood and not all patients benefit from treatment. We show that patients with breast cancer did not accumulate sufficient intratumoral paclitaxel to induce mitotic arrest in tumor cells.

Effects of simvastatin on white matter integrity in healthy middle-aged adults.

Background: The brain is the most cholesterol-rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol-lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol-rich brain white matter (WM) is largely unknown.

Methods: We used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin-naïve, middle-aged adults during an 18-month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38).

Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values.

Introduction: Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods.

Methods: A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios.

A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis.

Background: Immunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.

Objective: To perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.

Methods: A literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines.

Chemical Inactivation of Prions Is Altered by Binding to the Soil Mineral Montmorillonite.

Environmental routes of transmission contribute to the spread of the prion diseases chronic wasting disease of deer and elk and scrapie of sheep and goats. Prions can persist in soils and other environmental matrices and remain infectious for years. Prions bind avidly to the common soil mineral montmorillonite, and such binding can dramatically increase oral disease transmission.

Lidocaine patches for postcesarean pain control in obese women: a pilot randomized controlled trial.

Background: Obesity increases the risk of opioid-related morbidity. Lidocaine patches have been shown to reduce postoperative pain after noncesarean surgeries.

Objective: This study aimed to determine whether the application of lidocaine patches around the cesarean incision in women with obesity reduces the total dose of opioids administered in the first 24 hours after cesarean delivery.

Latent Factor Structure and Measurement Invariance of the NIH Toolbox Cognition Battery in an Alzheimer's Disease Research Sample.

Objective: This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer's disease (AD) research sample.

Method: The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45-94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA).

Liberalizing the killing of endangered wolves was associated with more disappearances of collared individuals in Wisconsin, USA.

Although poaching (illegal killing) is an important cause of death for large carnivores globally, the effect of lethal management policies on poaching is unknown for many populations. Two opposing hypotheses have been proposed: liberalizing killing may decrease poaching incidence ('tolerance hunting') or increase it ('facilitated poaching'). For gray wolves in Wisconsin, USA, we evaluated how five causes of death and disappearances of monitored, adult wolves were influenced by policy changes.

Comparison of survival distributions in clinical trials: A practical guidance.

Background: In randomized clinical trials with censored time-to-event outcomes, the logrank test is known to have substantial statistical power under the proportional hazards assumption and is widely adopted as a tool to compare two survival distributions. However, the proportional hazards assumption is impossible to validate in practice until the data are unblinded. However, the statistical analysis plan of a randomized clinical trial and in particular its primary analysis method must be pre-specified before any unblinded information may be reviewed.

Centrosome amplification is a frequent event in circulating tumor cells from subjects with metastatic breast cancer.

Centrosome amplification (CA) is a common phenomenon in cancer, promotes genomic stability and cancer evolution, and has been reported to promote metastasis. CA promotes a stochastic gain/loss of chromosomes during cell division, known as chromosomal instability (CIN). However, it is unclear whether CA is present in circulating tumor cells (CTCs), the seeds for metastasis.

A Prospective Multi-Institutional Phase I/II Trial of Step-Wise Dose-per-Fraction Escalation in Low and Intermediate Risk Prostate Cancer.

Purpose: This phase I/II, multi-institutional trial explored the tolerance and efficacy of stepwise increasing hypofractionation (HPFX) radiation therapy regimens for fraction sizes up to 4.3 Gy in localized prostate cancer.

Methods And Materials: Three escalating dose-per-fraction schedules were designed to yield similar predicted tumor control while maintaining equivalent predicted late toxicity.