Digital pathology, deep learning, and cancer: a narrative review.

Background And Objective: Cancer is a leading cause of morbidity and mortality worldwide. The emergence of digital pathology and deep learning technologies signifies a transformative era in healthcare. These technologies can enhance cancer detection, streamline operations, and bolster patient care.

Physiologically-based pharmacokinetic modeling of the drug-drug interaction between ivacaftor and lefamulin in cystic fibrosis patients.

Lefamulin is being evaluated as a treatment for bacterial exacerbations in cystic fibrosis (CF). Ivacaftor is approved for the treatment of patients with CF. Lefamulin is a moderate CYP3A inhibitor and co-administration with ivacaftor may result in a drug-drug interaction (DDI).

Application of a Forensic DNA Extraction System for Cannabis sativa Seed Identification.

Identification of seeds is crucial for law authorities fighting drug abuse and global trafficking. However, because they lack chemicals that are routinely used to pinpoint plants, their identification becomes far more challenging. Germinating the seeds requires tremendous resources, is time consuming and is not effective when dealing with nonviable seeds.

Proximate, physico-chemical, functional and sensory properties OF quinoa and amaranth flour AS potential binders in beef sausages.

There is an increase in demand for sausages in developing countries, however, accessibility and cost of binders are a challenge. Amaranth and quinoa flours were evaluated for use as alternative binders to corn-starch. Proximate composition, functional and thermal properties of the flours were determined.

What is she doing here? Klinefelter syndrome in forensic casework.

In this case report, we describe a sexual assault incident in which the male victim's seminal fluid contained no sperm cells, as indicated by sperm cell staining and microscopic screening, and DNA profiling results from the non-sperm cell fraction showed a major/minor DNA mixture that could be interpreted as female and male. DNA profiling of a sample from a disposable drinking cup used by the victim at the crime scene provided a single source profile, and showed a 2:1 imbalance between the heights of the X and Y chromosomes, respectively. The victim's DNA reference sample showed a similar imbalance of the X and Y chromosomes.

Concordance testing between Powerplex ESI 16 Fast System and VeriFiler Express.

DNA profiles generated by different STR kits may show different alleles for identical amplified loci. This well-known phenomenon affects the smooth transition of data generated by new STR kits to a database or casework laboratory or cross-laboratory comparison of STR profiles. As in other DNA databases throughout the world, it has become clear that the number of the analyzed loci should be expanded for a variety of reasons, such as partial profiles resulting from low copy-number DNA template or degraded samples, working with mixtures or when prevalence of familial inbreeding.

Translational approach from preclinical to clinical: comparison of dose finding methods of a new Bcl2 inhibitor using PK-PD modeling and interspecies extrapolation.

The attrition rate of anticancer drugs during the clinical development remains very high. Interspecies extrapolation of anticancer drug pharmacodynamics (PD) could help to bridge the gap between preclinical and clinical settings and to improve drug development. Indeed, when combined with a physiologically-based-pharmacokinetics (PBPK) approach, PD interspecies extrapolation could be a powerful tool for predicting drug behavior in clinical trials.

Prediction of Human Nonlinear Pharmacokinetics of a New Bcl-2 Inhibitor Using PBPK Modeling and Interspecies Extrapolation Strategy.

S 55746 ((S)--(4-hydroxyphenyl)-3-(6-(3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzo[d][1,3]dioxol-5-yl)--phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide) is a new selective Bcl-2 (B-cell lymphoma 2) inhibitor developed by Servier Laboratories and used to restore apoptosis functions in cancer patients. The aim of this work was to develop a translational approach using physiologically based (PB) pharmacokinetic (PK) modeling for interspecies extrapolation to anticipate the nonlinear PK behavior of this new compound in patients. A PBPK mouse model was first built using a hybrid approach, defining scaling factors (determined from in vitro data) to correct in vitro clearance parameters and predicted (partition coefficient) values.

[Alberic Pont, the great war and the "broken faces"].

The First World War and the number of facial injuries made specialized trauma centers necessary. Alberic Pont was trained both in medicine and dentistry. He founded in Lyon one of the first French specialized wards, which received more than 7000 soldiers overall.

Laundry in a washing machine as a mediator of secondary and tertiary DNA transfer.

The aim of this work was to investigate the possibility of secondary and tertiary DNA transfer during laundry. The modes of transfer tested were mixed and separate laundry of worn and unworn garments in household and public washing machines. In addition, the possibility of a background DNA carry-over from a washing machine's drum was investigated.

[Étienne Destot (1864-1918) or the other father of French radiology].

Étienne Destot is a French physician from Burgundy who benefited, during his studies in Lyon, from the quality of teaching of the best specialists of the time: Augagneur for hygiene, Testut for anatomy, Ollier for surgery, Lépine for the medical applications of electricity and the Lumière brothers for the technological development. During its experiments, he met Despeignes, the first radiation oncologist, Regaud pioneer of radiobiology and Bouchacourt who pointed out individual radiosensitivity. Less than two months after the X-rays discovery by Roentgen, he produced one of the first French radiographic views that were at the origin of our current knowledge in bone and cartilage anatomy and traumatology.

Improvement of Parameter Estimations in Tumor Growth Inhibition Models on Xenografted Animals: Handling Sacrifice Censoring and Error Caused by Experimental Measurement on Larger Tumor Sizes.

The purpose of this study was to explore the impact of censoring due to animal sacrifice on parameter estimates and tumor volume calculated from two diameters in larger tumors during tumor growth experiments in preclinical studies. The type of measurement error that can be expected was also investigated. Different scenarios were challenged using the stochastic simulation and estimation process.

Improvement of Parameter Estimations in Tumor Growth Inhibition Models on Xenografted Animals: a Novel Method to Handle the Interval Censoring Caused by Measurement of Smaller Tumors.

The purpose of this study was to explore the interval censoring induced by caliper measurements on smaller tumors during tumor growth experiments in preclinical studies and to show its impact on parameter estimations. A new approach, the so-called interval-M3 method, is proposed to specifically handle this type of data. Thereby, the interval-M3 method was challenged with different methods (including classical methods for handling below quantification limit values) using Stochastic Simulation and Estimation process to take into account the censoring.

The relations between reading and spelling: an examination of subtypes of reading disability.

Three groups of reading-disabled children were found in studies of English, German, and French: a group with a double deficit in reading and spelling, a group with a single spelling deficit, and a more rarely reported group presenting a single reading deficit. This study set out to examine whether these groups can be found in adults, readers and spellers of Hebrew, which differs from the previously studied orthographies in many aspects. To this end, Hebrew-speaking adults with or without reading disability were administered various literacy and literacy-related tests.

Reading improvement in English- and Hebrew-speaking children with reading difficulties after reading acceleration training.

A reading acceleration program known to improve reading fluency in Hebrew-speaking adults was tested for its effect on children. Eighty-nine Hebrew- and English-speaking children with reading difficulties were divided into a waiting list group and two training groups (Hebrew and English) and underwent 4 weeks of reading acceleration training. Results of pre- and post-testing of reading abilities point to a significant main effect of the test, demonstrating improvements in silent contextual reading speed, reading comprehension, and speed of processing in both Hebrew and English training groups as compared to their performance before the intervention.

T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial.

Background: T-cell vaccination (TCV) for multiple sclerosis (MS) refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled.

Aim: To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial.

Busulfan pharmacokinetics following intravenous and oral dosing regimens in children receiving high-dose myeloablative chemotherapy for high-risk neuroblastoma as part of the HR-NBL-1/SIOPEN trial.

Introduction: Busulfan is widely used in a neuroblastoma setting, with several studies reporting marked inter-patient variability in busulfan pharmacokinetics and pharmacodynamics. The current study reports on the pharmacokinetics of oral versus intravenous (IV) busulfan in high-risk neuroblastoma patients treated on the European HR-NBL-1/SIOPEN study.

Methods: Busulfan was administered four times daily for 4 days to children aged 0.

A Y-chromosome STR marker should be added to commercial multiplex STR kits.

Autosomal short tandem repeat (STR) analysis has become highly relevant in the identification of victims from mass disasters and terrorist attacks. In such events, gender misidentification can be of grave consequences, yet the list reporting amelogenin amplification failure using STR multiplex kits continues to grow. Presented here are three such examples.

Follow-up of osteochondral plug transfers in a goat model: a 6-month study.

Background: Osteochondral transfer procedures are increasingly used to resurface full-thickness articular cartilage defects. There has not been long-term assessment/description of autogenous donor and recipient sites.

Hypothesis: The healing process occurs at the donor/host cartilage and bone interfaces.

Egr-1 upregulates the Alzheimer's disease presenilin-2 gene in neuronal cells.

Regulation of the Alzheimer's disease (AD)-related gene, presenilin-2 (PSEN2), was analyzed in neuronal (SK-N-SH) and non-neuronal (human embryonic kidney 293, HEK293) cells. We show that the PSEN2 regulatory region includes two separate promoter elements, each located upstream of multiple transcription start sites in the first and second exons. The stronger upstream promoter, P1, has housekeeping characteristics: it resides in a CpG island, is TATA-less, and up to 83% of PSEN2-P1 activity depends on a stimulating protein 1 (Sp1) site at the most 5' initiation site.

Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model.

Background: Intra-articular (IA) hyaluronan (HA) injections are approved for the treatment of knee osteoarthritis (OA) pain. One of the currently available products is approved for repeat treatment courses. While HA is classed as a symptom-modifying agent, there is substantial evidence that this therapeutic modality also possesses disease-modifying activity.