Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.

Background: Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.

Methods: Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients.

Enhancing the detection of clinically relevant biomarkers in advanced uterine and tubo-ovarian carcinomas through genome-wide analysis.

Background: Advanced-stage tube-ovarian cancers (TOC) and uterine cancers (UC) significantly contribute to cancer mortality. While surgery achieves clinical remission in most cases, recurrence often necessitates systemic therapy. Recent molecular phenotype studies have advanced targeted therapies.

Most large structural variants in cancer genomes can be detected without long reads.

Short-read sequencing is the workhorse of cancer genomics yet is thought to miss many structural variants (SVs), particularly large chromosomal alterations. To characterize missing SVs in short-read whole genomes, we analyzed 'loose ends'-local violations of mass balance between adjacent DNA segments. In the landscape of loose ends across 1,330 high-purity cancer whole genomes, most large (>10-kb) clonal SVs were fully resolved by short reads in the 87% of the human genome where copy number could be reliably measured.

Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers.

Homologous recombination (HR) deficiency is associated with DNA rearrangements and cytogenetic aberrations. Paradoxically, the types of DNA rearrangements that are specifically associated with HR-deficient cancers only minimally affect chromosomal structure. Here, to address this apparent contradiction, we combined genome-graph analysis of short-read whole-genome sequencing (WGS) profiles across thousands of tumours with deep linked-read WGS of 46 BRCA1- or BRCA2-mutant breast cancers.

Anxiety and Associated Factors during the COVID-19 Pandemic Confinement in the Moroccan Adult Celiac Disease Population.

Introduction: The widespread lockdown due to the COVID-19 pandemic was insured by Moroccan authorities in early 2020 to preserve the health of citizens. The lockdown and the pandemic imposed psychological effects on the population including anxiety. Celiac disease (CeD), a chronic disease among the most common inflammatory intestinal disorders, has been linked to adult emotional disturbances.

Comparative Analysis of Manual Dexterity of Dental Students at Ajman University following One Academic Year of Preclinical Training Sessions: A Longitudinal Cohort Study.

Objectives:  Dental students must complete two stages of training, namely, preclinical training on phantom head models and clinical training on actual patients to acquire the practical skills required by their Bachelor of Dental Surgery program.Our objectives are to evaluate the level of improvement of the manual skills obtained by third-year dental students after one full academic year of preclinical training courses using dexterity tests under direct and indirect vision and to compare the improvement among male and female dental students under the same conditions.

Materials And Methods:  A total of 72 preclinical students participated in our cohort trial, each of whom was assigned a random identification number that was only known to the researchers.

Ancestry-related distribution of Runs of homozygosity and functional variants in Qatari population.

Background: Describing how genetic history shapes the pattern of medically relevant variants could improve the understanding of how specific loci interact with each other and affect diseases and traits prevalence. The Qatari population is characterized by a complex history of admixture and substructure, and the study of its population genomic features would provide valuable insights into the genetic landscape of functional variants. Here, we analyzed the genomic variation of 186 newly-genotyped healthy individuals from the Qatari peninsula.

Automated Periotome versus Conventional Periotome in Intra-Alveolar Extraction of Sheep Jaw: An In Vitro Study.

Background: Atraumatic dental extraction is the way forward in modern dentistry. This study aims to compare the effectiveness of automated periotome with conventional periotome with regard to operating time, postoperative gingival laceration, and bone and tooth structure fractures.

Methods: This is an in vitro study of forty posterior teeth of sheep mandibles.

Extensively Drug-Resistant Salmonella typhi Infection: From Pill to Scalpel.

Water-borne infections like typhoid fever are common in the developing world. The emergence of extensively drug-resistant Salmonella typhi (XDR S. typhi) is of great concern for both local and global public health.

Somatic whole genome dynamics of precancer in Barrett's esophagus reveals features associated with disease progression.

While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures.

Paediatric mitral valve disease - from presentation to management.

Mitral valve diseases are relatively rare in the paediatric population; however, they can cause considerable mortality and morbidity worldwide. Acquired causes are a major contributor to cardiovascular disease burden in the paediatric population. Diseases can be detected before birth, at birth, or when the child is older and presents with symptoms of advanced heart failure.

An Automated Multicycle Immunoaffinity Enrichment Approach Developed for Sensitive Mouse IgG1 Antibody Drug Analysis in Mouse Plasma Using LC/MS/MS.

In the immuno-oncology field, surrogate mouse monoclonal antibodies are often preferred in establishing proper PK/PD/efficacy correlations as well as supporting anticipated mouse to human translation. Thus, a highly sensitive and specific bioanalytical method is needed in quantifying those surrogate mouse antibodies after dosing in mice. Unfortunately, when specific reagents, such as recombinant target antigen and anti-idiotypic antibody, are not available, measuring mouse surrogate antibody drugs in mice is very challenging for ligand binding assay (LBA) due to the severe cross reactivity potential.

A Multicenter Analysis of Wide Excision and Reconstruction for Severe Anogenital Hidradenitis Suppurativa.

Background: An appropriate reconstruction strategy after wide excision for severe cases of anogenital hidradenitis suppurativa (aHS) is important to optimize outcomes, but there is no consensus on which reconstruction strategy should be preferred.

Objective: Evaluate which reconstruction strategy after wide excision in patients with severe aHS is associated with the best outcomes in terms of recurrence rate, complications and patient-reported outcomes on range of motion, pain, appearance, sexual health and satisfaction.

Methods: Multicenter retrospective analysis between 2009 and 2019 of wide excision and reconstruction by primary closure, secondary intention healing, split-thickness skin grafts or fasciocutaneous flaps (FCF).

Impact of Access Cavity Design on Fracture Resistance of Endodontically Treated Molars: A Systematic Review.

Objective: The main aim of this present systematic review is to ascertain whether a conservative endodontic cavity (ConsAC) has a better fracture resistance than a traditional access cavity (TradAC) in endodontically treated molars.

Materials And Methods: Three independent reviewers researched without limits in multiple engines: PubMed, ScienceDirect, Scopus, ResearchGate, EBSCOhost, Wiley Online Library, and Google Scholar, in addition to reference and hand search. Articles were chosen according to a certain inclusion and exclusion criteria, which, in brief, are in vitro studies assessing the fracture resistance difference between ConsAC and TradAC performed on extracted sound human molar teeth.

Distinct Classes of Complex Structural Variation Uncovered across Thousands of Cancer Genome Graphs.

Cancer genomes often harbor hundreds of somatic DNA rearrangement junctions, many of which cannot be easily classified into simple (e.g., deletion) or complex (e.

A Citrulline-Based Translational Population System Toxicology Model for Gastrointestinal-Related Adverse Events Associated With Anticancer Treatments.

Gastrointestinal (GI)-related adverse events (AEs) are commonly observed in the clinic during cancer treatments. Citrulline is a potentially translatable biomarker of GI AEs. In this study, irinotecan-induced citrulline changes were studied for a range of doses and schedules in rats.

Next-generation characterization of the Cancer Cell Line Encyclopedia.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers.

Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant.

Introduction: The cellular events that contribute to generation of donor-specific anti-HLA antibodies (DSA) post-kidney transplantation (KTx) are not well understood. Characterization of such mechanisms could allow tailoring of immunosuppression to benefit sensitized patients.

Methods: We prospectively monitored circulating T follicular helper (cT) cells in KTx recipients who received T-cell depleting (thymoglobulin,  = 54) or T-cell nondepleting (basiliximab,  = 20) induction therapy from pre-KTx to 1 year post-KTx and assessed their phenotypic changes due to induction and DSA occurrence, in addition to healthy controls ( = 13), for a total of 307 blood samples.

The Effect of Light on Sleep and Sleep-Related Physiological Factors Among Patients in Healthcare Facilities: A Systematic Review.

Objectives: Lighting is one of the environmental factors which can improve patient sleep in healthcare environments. Due to the high degree of variation in study designs and results on this topic, the implications have been difficult to interpret. This review consolidates studies on the impact of bright light exposure on sleep to identify lighting conditions that can be applied and researched in future healthcare environments.

An LC/MS based method to quantify DNA adduct in tumor and organ tissues.

Highly potent DNA damaging agents have become a key class of toxins for antibody-drug conjugate (ADC) based targeted therapy. However, until recently, no quantitative bioanalytical method was available to measure the toxin in the form of DNA adducts. In this work, a novel microwave assisted organic solvent extraction and LC-MS/MS based bioanalytical method was developed to extract and quantify DNA-bound toxin IGN-P1 in tissue samples.

Exploring the Concept of Healing Spaces.

Evidence-based design (EBD) research has demonstrated the power of environmental design to support improved patient, family, and staff outcomes and to minimize or avoid harm in healthcare settings. While healthcare has primarily focused on fixing the body, there is a growing recognition that our healthcare system could do more by promoting overall wellness, and this requires expanding the focus to healing. This article explores how we can extend what we know from EBD about health impacts of spatial design to the more elusive goal of healing.