Machine learning to predict completion of treatment for pancreatic cancer.

Background: Chemotherapy enhances survival rates for pancreatic cancer (PC) patients postsurgery, yet less than 60% complete adjuvant therapy, with a smaller fraction undergoing neoadjuvant treatment. Our study aimed to predict which patients would complete pre- or postoperative chemotherapy through machine learning (ML).

Methods: Patients with resectable PC identified in our institutional pancreas database were grouped into two categories: those who completed all intended treatments (i.

Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

Introduction: Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities.

Methods: Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables.

Prenatal programming of environmental sensitivity.

According to several theories, people differ in their sensitivity to environmental influences with some more susceptible than others to both supportive and adverse contextual conditions. Such differences in environmental sensitivity have a genetic basis but are also shaped by environmental factors. Herein we narratively build on our previous work proposing that prenatal experiences contribute to the development of environmental sensitivity.

A Learning Healthcare System for pregnant and breastfeeding women: what do women during preconception, pregnancy, and nursing think? - A qualitative study : A contribution from the ConcePTION project.

Background: Most medications lack evidence-based information about its safety and efficacy during pregnancy and breastfeeding, because pregnant women are often not included in clinical research. Another way to generate evidence is by using a Learning Healthcare System (LHS) approach. In an LHS, care and research are aligned in such a way that it can accelerate evidence generation and outcomes for patients, based on real-life medication use.

Preclinical Development of the Class-I-Selective Histone Deacetylase Inhibitor OKI-179 for the Treatment of Solid Tumors.

Histone deacetylases (HDACs) play critical roles in epigenomic regulation, and histone acetylation is dysregulated in many human cancers. Although HDAC inhibitors are active in T-cell lymphomas, poor isoform selectivity, narrow therapeutic indices, and a deficiency of reliable biomarkers may contribute to the lack of efficacy in solid tumors. In this article, we report the discovery and preclinical development of the novel, orally bioavailable, class-I-selective HDAC inhibitor, OKI-179.

Investigating the effects of a novel rumen-protected folic acid supplement on feedlot performance and carcass characteristics of beef steers.

Angus-crossbred steers ( = 180; 292 ± 18 kg) from a single ranch were used to investigate the effects of a novel rumen-protected folic acid (RPFA) supplement on feedlot performance and carcass characteristics. On d 0, steers were blocked by body weight to pens (5 steers/pen), and pens within a block were randomly assigned to dietary treatments ( = 6 pens/treatment): target intake of 0 (CON), 30 (RPFA-30), 60 (RPFA-60), 90 (RPFA-90), 120 (RPFA-120), or 150 (RPFA-150) mg RPFA·steer·d. Steers were weighed before feeding on d -1, 0, 55, 56, 86, 87, 181, and 182.

WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA damaging therapies commonly used in PDAC treatment. The purpose of this study was to identify combination partners for AZD1775, including standard chemotherapy or targeted agents, in PDAC preclinical models.

Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents.

Infant temperament, early-childhood parenting, and early-adolescent development: Testing alternative models of Parenting × Temperament interaction.

Here we evaluate whether infant difficult temperament (6 months) functions as a vulnerability or more general plasticity factor when investigating effects of early-childhood parenting (8-42 months) on both positive and negative early-adolescent socioemotional development (age 8-11 years). Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC, = 14,541) and a re-parameterized model-testing approach to distinguish alternative person × environment conceptual models, results indicated that temperament × parenting interacted in predicting externalizing (i.e.

RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited systemic treatment options. RX-5902 is a novel anti-cancer agent that inhibits phosphorylated-p68 and thus attenuates nuclear β-catenin signaling. The purpose of this study was to evaluate the ability of β-catenin signaling blockade to enhance the efficacy of anti-CTLA-4 and anti-PD-1 immune checkpoint blockade in immunocompetent, preclinical models of TNBC.

Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype defined by lack of hormone receptor expression and non-amplified HER2. Adavosertib (AZD1775) is a potent, small-molecule, ATP-competitive inhibitor of the Wee1 kinase that potentiates the activity of many DNA-damaging chemotherapeutics and is currently in clinical development for multiple indications. The purpose of this study was to investigate the combination of AZD1775 and capecitabine/5FU in preclinical TNBC models.

Testing three hypotheses about effects of sensitive-insensitive parenting on telomeres.

Telomeres are the protective DNA-protein sequences appearing at the ends of chromosomes; they shorten with each cell division and are considered a biomarker of aging. Shorter telomere length and greater erosion have been associated with compromised physical and mental health and are hypothesized to be affected by early life stress. In the latter case, most work has relied on retrospective measures of early life stressors.

Does prenatal stress amplify effects of postnatal maternal depressive and anxiety symptoms on child problem behavior?

Emerging evidence suggests that prenatal stress does not solely undermine child functioning but increases developmental plasticity to both negative and positive postnatal experiences. Here we test this proposition using the Norwegian Mother and Child Cohort study while implementing an extreme-group (i.e.

Complete Genome Sequence of Salmonella enterica Serovar Enteritidis Siphophage Seafire.

Bacteriophages infecting subsp. serovar Enteritidis may be used as biocontrol agents in food products or animals for preventing foodborne diseases caused by this pathogen. The complete genome sequence of phage Seafire, a T5-like siphophage infecting Enteritidis, is described in this report.

First-in-Class Phosphorylated-p68 Inhibitor RX-5902 Inhibits β-Catenin Signaling and Demonstrates Antitumor Activity in Triple-Negative Breast Cancer.

RX-5902 is a first-in-class anticancer agent targeting phosphorylated-p68 and attenuating nuclear shuttling of β-catenin. The purpose of this study was to evaluate the efficacy of RX-5902 in preclinical models of triple-negative breast cancer (TNBC) and to explore effects on β-catenin expression. A panel of 18 TNBC cell lines was exposed to RX-5902, and changes in proliferation, apoptosis, cellular ploidy, and effector protein expression were assessed.

Barriers and facilitators of mental health programmes in primary care in low-income and middle-income countries.

Integration of services into primary health care for people with common mental disorders is considered a key strategy to improve access to mental health care in low-income and middle-income countries, yet services at the primary care level are largely unavailable. We did a systematic review to understand the barriers and facilitators in the implementation of mental health programmes. We searched five databases and included studies published between Jan 1, 1990, and Sept 1, 2017, that used qualitative methods to assess the implementation of programmes for adults with common mental disorders at primary health-care settings in low-income and middle-income countries.

Prenatal stress enhances postnatal plasticity: The role of microbiota.

Separate fields of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are themselves associated with increased susceptibility to both positive and negative environmental influences. Collectively, this work supports Pluess and Belsky's (Psychopathology, 2011, 23, 29) claim that prenatal stress fosters, promotes or "programs" postnatal developmental plasticity. Herein, we review animal and human evidence consistent with this hypothesis before advancing the novel idea that infant intestinal microbiota may be one candidate mechanism for instantiating developmental plasticity as a result of prenatal stress.