Monovalent and Divalent Designs of Copper Radiotheranostics Targeting Fibroblast Activation Protein in Cancer.

: Fibroblast activation protein (FAP)-targeted theranostic radiopharmaceuticals have shown desired tumor-to-background organ selectivity due to the ubiquitous presence of FAP within the tumor microenvironment. However, suboptimal tumor retention and fast clearance have hindered their use to deliver effective cancer therapies. With well-documented FAP-targeting moieties and linkers appending them to optimal chelators, the development of copper radiopharmaceuticals has attracted considerable interest, given the fact that an ideal theranostic pair of copper radionuclides (Cu: t = 12.

LONG-TERM SURVIVAL AFTER LAPAROSCOPIC TOTAL GASTRECTOMY FOR EARLY AND ADVANCED GASTRIC CANCER. SINGLE CENTER EXPERIENCE IN 100 CASES.

Background: Laparoscopic gastrectomy offers advantages in the postoperative period compared to the open approach. Most studies have been performed on distal gastrectomies; however, laparoscopic total gastrectomy (LTG) is not universally accepted. AIM: The aim of this study was to assess the results of LTG, on postoperative morbidity outcomes and long-term survival.

A single-point mutation in the rubella virus E1 glycoprotein promotes rescue of recombinant vesicular stomatitis virus.

Rubella virus (RuV) is an enveloped plus-sense RNA virus and a member of the genus. RuV infection in pregnant women can lead to miscarriage or an array of severe birth defects known as congenital rubella syndrome. Novel rubiviruses were recently discovered in various mammals, highlighting the spillover potential of other rubiviruses to humans.

A Deeply Quiescent Subset of CML LSC depend on FAO yet Avoid Deleterious ROS by Suppressing Mitochondrial Complex I.

Background And Objective: Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are therapy resistant and the cause of relapse. A state of deep quiescence appears to enable cancer stem cells (CSC) to acquire new somatic mutations essential for disease progression and therapy resistance.

Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

Background: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy.

Study Design: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared.

Cancer Stem Cell and Hepatic Stellate Cells in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common liver cancer. It is highly lethal and has high recurrence. Death among HCC patients occur mainly due to tumor progression, recurrence, metastasis, and chemoresistance.

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer.

After androgen deprivation therapy, a significant number of prostate cancer cases progress with a therapy-resistant neuroendocrine phenotype (NEPC). This represents a challenge for diagnosis and treatment. Based on our previously reported design of theranostic small-molecule prodrug conjugates (T-SMPDCs), herein we report a T-SMPDC tailored for targeted positron emission tomography (PET) imaging and chemotherapy of NEPC.

HER2 classification in breast cancer cells: A new explainable machine learning application for immunohistochemistry.

The immunohistochemical (IHC) evaluation of epidermal growth factor 2 (HER2) for the diagnosis of breast cancer is still qualitative with a high degree of inter-observer variability, and thus requires the incorporation of complementary techniques such as fluorescent hybridization (FISH) to resolve the diagnosis. Implementing automatic algorithms to classify IHC biomarkers is crucial for typifying the tumor and deciding on therapy for each patient with better performance. The present study aims to demonstrate that, using an explainable Machine Learning (ML) model for the classification of HER2 photomicrographs, it is possible to determine criteria to improve the value of IHC analysis.

Development of Cu(ii)-specific peptide shuttles capable of preventing Cu-amyloid beta toxicity and importing bioavailable Cu into cells.

Copper (Cu) in its ionic forms is an essential element for mammals and its homeostasis is tightly controlled. Accordingly, Cu-dyshomeostasis can be lethal as is the case in the well-established genetic Wilson's and Menkes diseases. In Alzheimer's disease (AD), Cu-accumulation occurs in amyloid plaques, where it is bound to the amyloid-beta peptide (Aβ).

Why the Ala-His-His Peptide Is an Appropriate Scaffold to Remove and Redox Silence Copper Ions from the Alzheimer's-Related Aβ Peptide.

The progressive, neurodegenerative Alzheimer's disease (AD) is the most widespread dementia. Due to the ageing of the population and the current lack of molecules able to prevent or stop the disease, AD will be even more impactful for society in the future. AD is a multifactorial disease, and, among other factors, metal ions have been regarded as potential therapeutic targets.

The centromeric histone CenH3 is recruited into the tombusvirus replication organelles.

Tombusviruses, similar to other (+)RNA viruses, exploit the host cells by co-opting numerous host components and rewiring cellular pathways to build extensive virus-induced replication organelles (VROs) in the cytosol of the infected cells. Most molecular resources are suboptimal in susceptible cells and therefore, tomato bushy stunt virus (TBSV) drives intensive remodeling and subversion of many cellular processes. The authors discovered that the nuclear centromeric CenH3 histone variant (Cse4p in yeast, CENP-A in humans) plays a major role in tombusvirus replication in plants and in the yeast model host.

A Novel Use of Latent Class Analysis to Identify Patterns of Workplace Hazards among Informally Employed Domestic Workers in 14 Cities, United States, 2011-2012.

Introduction: Few studies, mostly descriptive, have quantitatively analyzed the working conditions of domestic workers (DWers) informally employed by private households in the USA. These workers are explicitly or effectively excluded from numerous workplace protections, and scant data exist on their exposures or how best to categorize them.

Methods: We analyzed data from the sole nationwide survey of informally employed US DWers with work-related hazards data, conducted by the National Domestic Workers Alliance, the University of Illinois Chicago Center for Urban Economic Development, and the DataCenter in 14 US cities (2011-2012; N = 2086).

Gut and vaginal microbiomes on steroids: implications for women's health.

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity.

Severe outbreak of Fusarium wilt on common beans (Phaseolus vulgaris) caused by Fusarium oxysporum in the Maule Region, central Chile.

Common bean (Phaseolus vulgaris L.) is an important grain legume cultivated worldwide as food for humans and livestock (Schwartz et al., 2005).

Radioiodine-Induced Salivary Gland Damage Detected by Ultrasonography in Patients Treated for Papillary Thyroid Cancer: Radioactive Iodine Activity and Risk.

An important side effect of radioactive iodine (RAI) therapy in patients treated for papillary thyroid cancer (PTC) is chronic sialadenitis. Neck ultrasonography (US) easily recognizes radioiodine-induced salivary gland abnormalities. The objectives of this study were to determine the prevalence of US-detected sialadenitis caused by RAI and to identify the risk factors associated with this damage.

A terbium(iii) luminescent ATCUN-based peptide sensor for selective and reversible detection of copper(ii) in biological media.

The measurement of exchangeable Cu2+ levels in biological samples is gaining interest in the context of copper-related pathologies. Here, we report a Tb3+ luminescent turn-off sensor for Cu2+ based on the specific and suitable-affinity Xxx-Zzz-His (ATCUN) peptide motif, enabling Cu2+ detection in the presence of a biological fluorescent background.

RISK FACTORS FOR SEVERE POSTOPERATIVE COMPLICATIONS AFTER GASTRECTOMY FOR GASTRIC AND ESOPHAGOGASTRIC JUNCTION CANCERS.

Background: Gastrectomy is the main treatment for gastric and Siewert type II-III esophagogastric junction (EGJ) cancer. This surgery is associated with significant morbidity. Total morbidity rates vary across different studies and few have evaluated postoperative morbidity according to complication severity.

Enhancement of the Antioxidant Activity and Neurotherapeutic Features through Pyridol Addition to Tetraazamacrocyclic Molecules.

Alzheimer's and other neurodegenerative diseases are chronic conditions affecting millions of individuals worldwide. Oxidative stress is a consistent component described in the development of many neurodegenerative diseases. Therefore, innovative strategies to develop drug candidates that overcome oxidative stress in the brain are needed.

Dialing in on pharmacological features for a therapeutic antioxidant small molecule.

The pyridinophane molecule L2 (3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol) has shown promise as a therapuetic for neurodegenerative diseases involving oxidative stress and metal ion misregulation.

Effects of pericytes and colon cancer stem cells in the tumor microenvironment.

Colorectal cancer (CRC) is one type of tumor with the highest frequency and mortality worldwide. Although current treatments increase patient survival, it is important to detect CRC in early stages; however, most CRC, despite responding favorably to treatment, develop resistance and present recurrence, a situation that will inevitably lead to death. In recent years, it has been shown that the main reason for drug resistance is the presence of colon cancer stem cells (CSC).

Triggering Cu-coordination change in Cu(ii)-Ala-His-His by external ligands.

Copper(ii) forms well-known and stable complexes with peptides having histidine at position 2 (Xxx-His) or 3 (Xxx-Zzz-His). Their properties differ considerably due to the histidine positioning. Here we report that in the hybrid motif Xxx-His-His, the Cu(ii)-complexes can be switched between the Xxx-His and the Xxx-Zzz-His coordination modes by addition of external ligands.

La Von Economo’s encephalitis lethargica and the Spanish flu pandemic in Bogotá and Medellín (Colombia): An historic review one hundred years after.

Von Economo’s encephalitis is a neuropsychiatric disorder of possible autoimmune origin, which affects basal ganglia. This reaction may occur secondary to infection by different viral or bacterial agents. Given that it appears after the acute episode has disappeared, molecular mimetism has been proposed to explain the autoimmune lesion.