Delayed Surgery after Neoadjuvant Short-course Radiation for Rectal Cancer Improves Pathologic Outcomes without Impacting Survival: A National Cancer Database Analysis.

Purpose: Interval to surgery following short course radiotherapy (SCRT) for rectal cancer is not standardized. This study investigated pathologic outcomes and survival with varying intervals to surgery.

Methods: Using the National Cancer Database, adults who received SCRT from 2005 to 2020 were grouped by additional neoadjuvant chemotherapy.

Is Cognitive Flexibility Equivalent to Shifting? Investigating Cognitive Flexibility in Multiple Domains.

In the present exploratory study we investigate whether cognitive flexibility is a unitary mechanism underlying flexible behaviours across many domains or a domain-specific capacity. The literature on cognitive flexibility is divided into several research lines that do not converge. The most prominent one considers flexibility an executive function that represents the ability to switch among rules or tasks.

Combining RAS(ON) G12C-selective inhibitor with SHP2 inhibition sensitises lung tumours to immune checkpoint blockade.

Mutant selective drugs targeting the inactive, GDP-bound form of KRAS have been approved for use in lung cancer, but resistance develops rapidly. Here we use an inhibitor, (RMC-4998) that targets RAS in its active, GTP-bound form, to treat KRAS mutant lung cancer in various immune competent mouse models. RAS pathway reactivation after RMC-4998 treatment could be delayed using combined treatment with a SHP2 inhibitor, which not only impacts tumour cell RAS signalling but also remodels the tumour microenvironment to be less immunosuppressive.

Bidirectional activation of stem-like programs between metastatic cancer and alveolar type 2 cells within the niche.

A key step for metastatic outgrowth involves the generation of a deeply altered microenvironment (niche) that supports the malignant behavior of cancer cells. The complexity of the metastatic niche has posed a significant challenge in elucidating the underlying programs driving its origin. Here, by focusing on early stages of breast cancer metastasis to the lung in mice, we describe a cancer-dependent chromatin remodeling and activation of developmental programs in alveolar type 2 (AT2) cells within the niche.

How do students reason about statistical sampling with computer simulations? An integrative review from a grounded cognition perspective.

Interactive computer simulations are commonly used as pedagogical tools to support students' statistical reasoning. This paper examines whether and how these simulations enable their intended effects. We begin by contrasting two theoretical frameworks-dual processes and grounded cognition-in the context of people's conceptions about statistical sampling, setting the stage for the potential benefits of simulations in learning such conceptions.

Oncologic outcomes following transanal total mesorectal excision: the United States experience.

Aim: The benefits and short-term outcomes of transanal total mesorectal excision (taTME) for rectal cancer have been demonstrated previously, but questions remain regarding the oncologic outcomes following this challenging procedure. The purpose of this study was to analyze the oncologic outcomes following taTME at high-volume centers in the USA.

Methods: This was a multicenter, retrospective observational study of 8 tertiary care centers.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival.

CRISPR-Cas9 Screening Identifies KRAS-Induced COX2 as a Driver of Immunotherapy Resistance in Lung Cancer.

Oncogenic KRAS impairs antitumor immune responses. As effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive, a better understanding of the mechanisms by which oncogenic KRAS drives immune evasion is needed to identify approaches that could sensitize KRAS-mutant lung cancer to immunotherapy. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identified mechanisms by which oncogenic KRAS promotes immune evasion, most notably via upregulation of immunosuppressive COX2 in cancer cells.

COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history.

Background: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.

Causes of death in patients operated for colorectal cancer.

Background: Colorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants.

Methods: An Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution.

The psychophysics of home plate umpire calls.

We analyze the visual perception task that home plate umpires (N = 121) perform calling balls and strikes (N = 3,001,019) in baseball games, focusing on the topics of perceptual learning and bias in decision-making. In the context of perceptual learning, our results show that monitoring, training, and feedback improve skill over time. In addition, we document two other aspects of umpires' improvement that are revealing with respect to the nature of their perceptual expertise.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

Introduction: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients.

Methods: We compared 364 LARC patients who received conventional (50.

The Spread of Beliefs in Partially Modularized Communities.

Many life-influencing social networks are characterized by considerable informational isolation. People within a community are far more likely to share beliefs than people who are part of different communities. The spread of useful information across communities is impeded by echo chambers (far greater connectivity within than between communities) and filter bubbles (more influence of beliefs by connected neighbors within than between communities).

Metformin Does not Affect Outcomes in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Therapy and Resection.

Introduction: There is emerging evidence that metformin may have a protective effect in patients with cancer. However, its current evidence in locally advanced rectal cancer (LARC) is inconclusive. We aim to assess the effect of metformin on long-term outcomes in patients with LARC who received neoadjuvant therapy and surgical resection.

Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US.

Methods: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC.

High-throughput identification of Toxoplasma gondii effector proteins that target host cell transcription.

Intracellular pathogens and other endosymbionts reprogram host cell transcription to suppress immune responses and recalibrate biosynthetic pathways. This reprogramming is critical in determining the outcome of infection or colonization. We combine pooled CRISPR knockout screening with dual host-microbe single-cell RNA sequencing, a method we term dual perturb-seq, to identify the molecular mediators of these transcriptional interactions.

The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.

PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and an RNA recognition motif, however the RNA-processing function(s) were poorly investigated over the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1.

Implementation of a New Surgeon Onboarding Program in an Academic-affiliated Community Hospital.

Best practices in onboarding are well-established, but surgeons frequently receive suboptimal introductions to new practice settings. At the same time, increasing regionalization of surgical programs and strategic alignments between academic and community hospitals have increased the demand for surgeons to practice at multiple sites with variable resources and institutional cultures. In response to this growing problem, we developed and implemented a surgeon onboarding program in an academic-affiliated community hospital.

Perception and simulation during concept learning.

A key component of humans' striking creativity in solving problems is our ability to construct novel descriptions to help us characterize novel concepts. Bongard problems (BPs), which challenge the problem solver to come up with a rule for distinguishing visual scenes that fall into two categories, provide an elegant test of this ability. BPs are challenging for both human and machine category learners because only a handful of example scenes are presented for each category, and they often require the open-ended creation of new descriptions.