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Nasopharyngeal stenosis following curative chemoradiation therapy for oropharyngeal cancer in a patient with active oral lichen

Case Report:

Lichen planus is an inflammatory disorder of immune dysregulation that affects the skin and mucosa. Oral lichen planus (OLP) is a chronic variant characterized by white mucosal lesions,1 most commonly with bilateral buccal mucosa involvement and frequently involving the tongue and gingiva as well.2 Although the underlying cause remains obscure, OLP is thought to have an autoimmune etiology and has been linked with genetic factors, hypertension, diabetes mellitus, hepatitis C virus, and thyroid dysfunction.3

OLP onset involves the activation of immune pathways leading to migration and activation of T cells and the destruction of keratinocytes.4 It is thought that oral mucosal keratinocytes are activated by the expression of unknown antigens, which recruit lymphocytes. This T-cell-mediated response is coupled with the simultaneous nonspecific response of matrix metalloproteases, chemokines and mast cells, together causing apoptosis of the basal keratinocytes by various mechanisms.

OLP can undergo malignant transformation to oral squamous cell carcinoma (OSCC) in a small subset of OLP patients (1%), more commonly in smokers, alcoholics, and hepatitis C patients.5 It is thus considered an OSCC precursor lesion. Topical steroids are the first-line treatment, but systemic steroids and topical calcineurin inhibitors can be used to manage recalcitrant cases.6

Delta Radiomics and Tumor Size: A New Predictive Radiomics Model for Chemotherapy Response in Liver Metastases from Breast and Colorectal Cancer

Background/Objectives: Radiomic features exhibit a correlation with tumor size on pretreatment images. However, on post-treatment images, this association is influenced by treatment efficacy and varies between responders and non-responders. This study introduces a novel model, called baseline-referenced Delta radiomics, which integrates the association between radiomic features and tumor size into Delta radiomics to predict chemotherapy response in liver metastases from breast cancer (BC) and colorectal cancer (CRC). Materials and Methods: A retrospective study analyzed contrast-enhanced computed tomography (CT) scans of 83 BC patients and 84 CRC patients. Among these, 57 BC patients with 106 liver lesions and 37 CRC patients with 109 lesions underwent post-treatment imaging after systemic chemotherapy. Radiomic features were extracted from up to three lesions per patient following manual segmentation. Tumor response was assessed by measuring the longest diameter and classified according to RECIST 1.1 criteria as progressive disease (PD), partial response (PR), or stable disease (SD). Classification models were developed to predict chemotherapy response using pretreatment data only, Delta radiomics, and baseline-referenced Delta radiomics. Model performance was evaluated using confusion matrix metrics. Results: Baseline-referenced Delta radiomics performed comparably or better than established radiomics models in predicting tumor response in chemotherapy-treated patients with liver metastases. The sensitivity, specificity, and balanced accuracy in predicting response ranged from 0.66 to 0.97, 0.81 to 0.97, and 80% to 90%, respectively. Conclusions: By integrating the relationship between radiomic features and tumor size into Delta radiomics, baseline-referenced Delta radiomics offers a promising approach for predicting chemotherapy response in liver metastases from breast and colorectal cancer.

Ribociclib Plus Endocrine Therapy in Hormone Receptor–Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial

In a 4-year analysis of the NATALEE trial, adjuvant ribociclib plus NSAI continued to provide invasive disease-free survival benefit over NSAI alone in patients with hormone receptor–positive/ERBB2-negative early breast cancer, with stable safety outcomes observed.

This exploratory 4-year analysis demonstrated a consistent iDFS benefit with ribociclib plus NSAI with additional follow-up, with a 28.5% reduction in the risk of recurrence over NSAI alone and confidence intervals that continue to narrow. The absolute improvement in iDFS with ribociclib plus NSAI continued to increase from 2.7% at 3 years to 4.9% at 4 years. The iDFS, DDFS, RFS, and DRFS benefits were observed with ribociclib plus NSAI over NSAI alone beyond the planned 3-year ribociclib treatment duration, as all patients were no longer receiving ribociclib treatment at the data cutoff. A sustained iDFS benefit with ribociclib plus NSAI was seen across subgroups, including anatomic stage and nodal status, with a consistent reduction in risk of distant recurrences across subgroups. The safety profile remained unchanged with additional follow-up.

In prior analyses, an iDFS benefit was observed with ribociclib plus NSAI over NSAI alone.10,21 However, at the time of those analyses, all patients had not yet discontinued ribociclib treatment (54.0% in the second interim efficacy analysis and 78.3% in the protocol-specified final analysis were no longer receiving treatment).10,21 Thus, the efficacy of ribociclib beyond the planned treatment period was unknown. In this analysis, all patients had stopped ribociclib treatment, with 62.8% of patients having completed the planned 3-year treatment duration. At 4 years, the absolute improvement in iDFS increased and the Kaplan-Meier curves continue to separate with additional follow-up, suggesting a persistent benefit of adjuvant ribociclib beyond the planned 3-year treatment duration.

An iDFS benefit was observed with ribociclib plus NSAI over NSAI alone in patients with high-risk N0 disease. While this subgroup of patients in NATALEE do not have nodal involvement, enrolled patients with stage IIA node-negative (T2N0) disease were required to have additional high-risk features, including grade 3 disease or grade 2 disease with Ki-67 20% or higher or high genomic risk. Previous meta-analyses and population-based studies have shown risk of recurrence across patients with and without nodal involvement; however, many of the patient samples in these studies were enrolled decades prior to the follow-up analyses.5, 24 The cohorts in these long-term studies may not be reflective of contemporary treatment standards, which has the potential to overinflate the recurrence risk among some subgroups.

Hidden weakness makes prostate cancer self-destruct

Scientists found a hidden flaw in prostate cancer’s survival system. Researchers have discovered that prostate cancer depends on two key enzymes, PDIA1 and PDIA5, to survive and resist therapy. When blocked, these enzymes cause the androgen receptor to collapse, killing cancer cells and enhancing the effects of drugs like enzalutamide. They also disrupt the cancer’s energy system, striking it on multiple fronts. This breakthrough could open a new path to overcoming drug $resistance in advanced prostate cancer.

An international team of researchers has identified a new weakness in prostate cancer cells that could lead to more effective treatments for one of the most common cancers among men.

The study, published in the Proceedings of the National Academy of Sciences (PNAS), was led by scientists from Flinders University in Australia and South China University of Technology. Their findings highlight two enzymes, PDIA1 and PDIA5, that play a key role in helping prostate cancer cells grow, survive, and resist existing treatments.

Preconfigured Neuronal Firing in Human Brain Organoids

In a groundbreaking study poised to reshape our understanding of brain development, researchers have unveiled the existence of preconfigured neuronal firing sequences within human brain organoids. These firing patterns, traditionally thought to arise from sensory experience and environmental stimuli, appear to be innately programmed during neurodevelopment, challenging long-held assumptions about the brain’s early information processing architecture. This revelation not only deepens our grasp of neuronal circuit formation but also elevates the value of brain organoids as faithful models for investigating the complexities of human neurobiology.

Neuronal firing sequences—the precise order and timing of action potentials within neural circuits—form the fundamental building blocks by which the brain encodes, processes, and transmits information. Until now, the developmental timeline and origins of these sequences remained largely unknown, with the prevailing hypothesis attributing their emergence to experience-dependent plasticity, shaped dynamically by sensory inputs during early life. However, the new findings presented by van der Molen et al. point to an alternative mechanism rooted in intrinsic developmental programs.

Human brain organoids, three-dimensional cellular models derived from pluripotent stem cells, have surged in popularity as cutting-edge platforms for modeling human brain development in vitro. By replicating key aspects of brain tissue organization and cellular diversity, these organoids serve as invaluable proxies for investigating neuronal circuit assembly under controlled conditions. Importantly, this study compared both unguided human brain organoids and those directed toward forebrain identity, alongside ex vivo slices from neonatal mouse somatosensory cortex, offering a robust cross-species and methodological validation of their observations.

In defence of Stephen Wolfram

You like Stephen Wolfram, right?

I mean, if he’s to be believed, he has reinvented physics, not to mention philosophy.

How could you not like such a thinker?

Well… it turns out that there are plenty of people who don’t like Stephen Wolfram… or his physics… or his philosophy.

Here are four criticisms of Stephen Wolfram I regularly hear…

…and here’s why these criticisms, though they hint at uncomfortable truths, nonetheless miss the mark.

Continue reading “In defence of Stephen Wolfram” | >

Rules that Reality Plays By — Dr. Stephen Wolfram, DemystifySci #343

Stephen Wolfram is a physicist, mathematician, and programmer who believes he has discovered the computational rules that organize the universe at the finest grain. These rules are not physical rules like the equations of state or Maxwell’s equations. According to Wolfram, these are rules that govern how the universe evolves and operates at a level at least one step down below the reality that we inhabit. His computational principles are inspired by the results observed in cellular automata systems, which show that it’s possible to take a very simple system, with very simple rules, and end up at complex patterns that often look organic and always look far more intricate than the black and white squares that the game started with. He believes that the hyperspace relationships that emerge when he applies a computational rule over and over again represent the nature of the universe — and that the relationships that emerge contain everything from the seed of human experience to the equations for relativity, evolution, and black holes. We sit down with him for a conversation about the platonic endeavor that he has undertaken, where to draw the line between lived experience and the computational universe, the limits of physics, and the value of purpose and the source of consciousness.

MAKE HISTORY WITH US THIS SUMMER:
https://demystifysci.com/demysticon-2025

PATREON
/ demystifysci.

PARADIGM DRIFT
https://demystifysci.com/paradigm-drift-show.

Material solutions to quantum spookiness: https://www.youtube.com/@MaterialAtomics.

00:00 Go!

Continue reading “Rules that Reality Plays By — Dr. Stephen Wolfram, DemystifySci #343” | >

What is Time? Stephen Wolfram’s Groundbreaking New Theory

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What is time? Is it just a ticking clock, or is it something more profound?

In this thought-provoking episode of Into the Impossible, Stephen Wolfram challenges everything we know about time, offering a revolutionary computational perspective that could forever change how we understand the universe.

Stephen Wolfram is a computer scientist, physicist, and businessman. He is the founder and CEO of Wolfram Research and the creator of Mathematica, Wolfram Alpha, and Wolfram Language. Over the course of 4 decades, he has pioneered the development & application of computational thinking. He has been responsible for many discoveries, inventions & innovations in science, technology, and business.

He argues that time is the inevitable progress of computation in the universe, where simple rules can lead to complex behaviors. This concept, termed computational irreducibility, implies that time has a rigid structure and that our perception of it is limited by our computational capabilities. Wolfram also explores the relationship between time, space, and gravity, suggesting that dark matter might be a feature of the structure of space.

Tune in to discover the true nature of time.

Continue reading “What is Time? Stephen Wolfram’s Groundbreaking New Theory” | >
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