Publications by authors named "David Beer"

Article Synopsis
  • The study focused on creating consensus recommendations for managing neonatal pain during surgery, emphasizing evidence-based strategies to enhance recovery and minimize opioid use.
  • An international guideline development committee involved paediatric anaesthesiologists, surgeons, and ERAS experts in defining patient eligibility and selecting relevant pain management topics.
  • Ultimately, the committee recommended using regular acetaminophen and considering locoregional analgesia, while noting a need for further research on non-opioid options for effective pain control in neonates.
View Article and Find Full Text PDF

Importance: Neonates requiring surgery are often cared for in neonatal intensive care units (NICUs). Despite a breadth of surgical pathology, neonates share many perioperative priorities that allow for the development of unit-wide evidence-based Enhanced Recovery After Surgery (ERAS) recommendations.

Observations: The guideline development committee included pediatric surgeons, anesthesiologists, neonatal nurses, and neonatologists in addition to ERAS content and methodology experts.

View Article and Find Full Text PDF

Frequent (>70%) TP53 mutations often promote its protein stabilization, driving esophageal adenocarcinoma (EAC) development linked to poor survival and therapy resistance. We previously reported that during Barrett's esophagus progression to EAC, an isoform switch occurs in the E3 ubiquitin ligase RNF128 (aka GRAIL-gene related to anergy in lymphocytes), enriching isoform 1 (hereby GRAIL1) and stabilizing the mutant p53 protein. Consequently, GRAIL1 knockdown degrades mutant p53.

View Article and Find Full Text PDF

Immunosuppression is a common feature of esophageal adenocarcinoma (EAC) and has been linked to poor overall survival (OS). We hypothesized that upstream factors might negatively influence CD3 levels and T cell activity, thus promoting immunosuppression and worse survival. We used clinical data and patient samples of those who progressed from Barrett's to dysplasia to EAC, investigated gene (RNA-Seq) and protein (tissue microarray) expression, and performed cell biology studies to delineate a pathway impacting CD3 protein stability that might influence EAC outcome.

View Article and Find Full Text PDF

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied.

View Article and Find Full Text PDF

Usually, the clustering process is the first step in several data analyses. Clustering allows identify patterns we did not note before and helps raise new hypotheses. However, one challenge when analyzing empirical data is the presence of covariates, which may mask the obtained clustering structure.

View Article and Find Full Text PDF

Aims: Circular RNAs are widely expressed in various cancers and play important roles in tumorigenesis and tumor progression. The function and mechanism of circSMARCA5 in lung adenocarcinoma however remains unclear.

Main Methods: QRT-PCR analysis was applied for determining circSMARCA5 expression in lung adenocarcinoma patient tumor tissues and cells.

View Article and Find Full Text PDF

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment-naïve esophageal tissues ranging from premalignant Barrett's esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.

View Article and Find Full Text PDF

Studies demonstrate that long non-coding RNAs (lncRNAs) play vital roles in cancer progression. However, the expression pattern and molecular mechanisms of lncRNA in lung cancer remain largely unclear. Here, we analyzed expression in lung cancer tissues from three RNA-sequencing (RNA-Seq) datasets and validated these results using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in an independent set of lung adenocarcinoma.

View Article and Find Full Text PDF

Background: Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects.

Methods: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800.

View Article and Find Full Text PDF

CSE1L is involved in the cancer progression of several types of cancer. Its expression status, potential oncogenic role and underlying mechanism in lung cancer, however, are unclear. Here, we investigated CSE1L expression in primary lung adenocarcinoma based on multiple datasets and then investigated its oncologic role in lung cancer.

View Article and Find Full Text PDF

Background: Crouzon and Pfeiffer syndromes are rare genetic disorders characterized by craniosynostosis, exorbitism, and maxillary hypoplasia. Patients with these syndromes frequently require general anesthesia for various diagnostic and surgical procedures and may present a challenge to anesthetists with regard to airway management.

Aims: The primary aim of this study was to determine the incidence, timing, and management of perioperative upper airway obstruction in infants and children with Crouzon and Pfeiffer syndromes.

View Article and Find Full Text PDF

Background & Aims: TP53 mutations underlie Barrett's esophagus (BE) progression to dysplasia and cancer. During BE progression, the ubiquitin ligase (E3) RNF128/GRAIL switches expression from isoform 2 (Iso2) to Iso1, stabilizing mutant p53. However, the ubiquitin-conjugating enzyme (E2) that partners with Iso1 to stabilize mutant p53 is unknown.

View Article and Find Full Text PDF

Lung cancer is the leading cause of cancer-related deaths globally and is histologically defined as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), with the latter accounting for 80% of all lung cancers. The 5-year overall survival rate for lung cancer patients is low as it is often discovered at advanced stages when potential cure by surgical resection is no longer an option. To identify a biomarker and target for lung cancer, we performed analysis of multiple datasets of lung cancer gene expression data.

View Article and Find Full Text PDF

has been reported to be down-regulated in several cancers, but its expression pattern and roles in lung cancer is unclear. Given the crucial role of microRNAs in cancer progression, we examined the expression and function of in lung adenocarcinoma. expression in lung cancer tissues and cell lines was measured by qRT-PCR.

View Article and Find Full Text PDF

Background: As surgical systems are forced to adapt and respond to new challenges, so should the patient safety tools within those systems. We sought to determine how the WHO SSC might best be adapted during the COVID-19 pandemic.

Methods: 18 Panelists from five continents and multiple clinical specialties participated in a three-round modified Delphi technique to identify potential recommendations, assess agreement with proposed recommendations and address items not meeting consensus.

View Article and Find Full Text PDF

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to public health, yet no antiviral drug is available. We performed a high-throughput phenotypic screen using the Novartis compound library and identified candidate chemical inhibitors of DENV. This chemical series was optimized to improve properties such as anti-DENV potency and solubility.

View Article and Find Full Text PDF

High-throughput RNA-sequencing studies of tumor samples have identified a large number of long non-coding RNAs (lncRNAs) which are associated with various types of cancer. LncRNAs play key roles in regulating chromatin dynamics, gene expression, growth, differentiation and development. However, the role of in non-small cell lung cancer (NSCLC) tumorigenesis is not clear.

View Article and Find Full Text PDF

Long noncoding RNA (lncRNA) has been reported to be upregulated in lung cancer and related to poor patient survival. It can regulate cell proliferation and tumor growth in lung cancer as well as several other cancers. However, the underlying molecular mechanisms that are regulated by are unclear.

View Article and Find Full Text PDF

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a chronic inflammatory state that can progress through a series of transformative dysplastic states before tumor development. While molecular and genetic changes of EAC tumors have been studied, immune microenvironment changes during Barrett's progression to EAC remain poorly understood. In this study, we identify potential immunologic changes that can occur during BE-to-EAC progression.

View Article and Find Full Text PDF

The incidence of esophageal adenocarcinoma (EAC) and other gastrointestinal (GI) cancers have risen dramatically, thus defining the oncogenic drivers to develop effective therapies are necessary. Patients with Barrett's Esophagus (BE), have an elevated risk of developing EAC. Around 70%-80% of BE cases that progress to dysplasia and cancer have detectable TP53 mutations.

View Article and Find Full Text PDF

Introduction: Surgical resection is curative for some patients with early lung squamous cell carcinoma. Staging and clinical factors do not adequately predict recurrence risk. We sought to validate the discriminative performance of proposed prognostic gene expression signatures at a level of rigor sufficient to support clinical use.

View Article and Find Full Text PDF

Background: Enhanced Recovery After Surgery (ERAS) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS Society guidelines. We created an ERAS guideline designed to enhance quality of care in neonatal intestinal resection surgery.

View Article and Find Full Text PDF