Sequencing Strategy to Ensure Accurate Plasmid Assembly.

Despite the wide use of plasmids in research and clinical production, the need to verify plasmid sequences is a bottleneck that is too often underestimated in the manufacturing process. Although sequencing platforms continue to improve, the method and assembly pipeline chosen still influence the final plasmid assembly sequence. Furthermore, few dedicated tools exist for plasmid assembly, especially for assembly.

Survival following adjuvant trastuzumab-based treatment among older patients with HER2-positive early invasive breast cancer: A national population-based cohort study using routine data.

Background: Randomised controlled trials (RCTs) reported adjuvant trastuzumab-based treatment improved overall survival (OS) among patients with HER2-positive early invasive breast cancer (EIBC). Few RCTs included older patients or those with comorbidity/frailty. This study aimed to determine whether the effect of adjuvant trastuzumab-based treatment on survival outcomes varies by patient age and fitness, using national data from routine care.

Symmetry, separation, and stability: Physical properties for effective dosimetric space with a stabilized hyaluronic acid spacer.

Background: The proximity of the rectum to the prostate in radiation therapy (RT) for prostate cancer presents a significant dosimetric challenge, leading to high rectal doses and resulting in detrimental side effects. Perirectal tissue spacing reduces rectal dose and gastrointestinal toxicities by mechanically separating these organs. A variety of materials have been explored for use as rectal spacers, most recently, a stabilized hyaluronic acid (HA) gel, which can be formed into deliberate a shape, and retains the definition of that shape, while remaining flexible, unlike polyethylene glycol (PEG) hydrogels.

Survival outcomes after breast cancer surgery among older women with early invasive breast cancer in England: population-based cohort study.

Background: This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer.

Methods: Women aged over 50 years with early invasive breast cancer diagnosed in England (2014-2019) who had breast surgery were identified from Cancer Registry data. Survival estimates were calculated from a flexible parametric survival model.

Ten simple rules for managing laboratory information.

Information is the cornerstone of research, from experimental (meta)data and computational processes to complex inventories of reagents and equipment. These 10 simple rules discuss best practices for leveraging laboratory information management systems to transform this large information load into useful scientific findings.

Evaluating the Quality-of-Life Effect of Apical Spacing with Hyaluronic Acid Prior to Hypofractionated Prostate Radiation Therapy: A Secondary Analysis.

Purpose: Recently, a randomized trial demonstrated that a hyaluronic acid (HA) spacer placed before prostate hypofractionated intensity modulated radiation therapy improved rectal dosimetry and reduced acute grade 2+ gastrointestinal toxicity. However, 26.5% of patients receiving the spacer experienced a minimal clinically important decline (MCID) in bowel quality-of-life (QOL).

Mastectomy patterns among older women with early invasive breast cancer in England and Wales: A population-based cohort study.

Introduction: Older women with early invasive breast cancer (EIBC) are more likely to receive a mastectomy compared with younger women. This study assessed factors associated with receiving a mastectomy among older women with EIBC, with a particular focus on comorbidity and frailty.

Materials And Methods: Women diagnosed with EIBC (stages I-IIIa) aged ≥50 years from 2014 to 2019 in English and Welsh NHS organisations who received breast surgery were identified from cancer registration datasets linked to routine hospital data.

Evidence into practice: a national cohort study of NICE-recommended oncological drug therapy utilisation among women diagnosed with invasive breast cancer in England.

Background: Multiple drug treatments are approved for invasive breast cancer (IBC). We investigated uptake of NICE-recommended oncological drugs and variation by age, comorbidity burden and geographical region.

Methods: Women (aged 50+ years) diagnosed with IBC from 2014 to 2019, were identified from England Cancer Registry data and drug utilisation from Systemic Anti-Cancer Therapy data.

Completeness of endocrine therapy information in the Primary Care Prescription Database (PCPD) and secondary care treatment datasets: A national population-based cohort study using routine healthcare data.

Background: Endocrine therapy (ET) is a widely used treatment for breast cancer. In the UK, use is typically initiated in secondary care, with subsequent treatment in primary care. Evaluating use of ET depends on data sources containing accurate and complete information.

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer.

Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression.

Concordance of cancer drug therapy information derived from routinely collected hospital admissions data and the Systemic Anti-Cancer Therapy (SACT) dataset, for older women diagnosed with early invasive breast cancer in England.

Background: Evaluating uptake of oncological treatments, and subsequent outcomes, depends on data sources containing accurate and complete information about cancer drug therapy (CDT). This study aimed to evaluate the consistency of CDT information in the Hospital Episode Statistics Admitted Patient Care (HES-APC) and Systemic Anti-Cancer Therapy (SACT) datasets for early invasive breast cancer (EIBC).

Methods: The study included women (50 + years) diagnosed with EIBC in England from 2014 to 2019 who had surgery within six months of diagnosis.

Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial.

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.

Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.

Design, Setting, And Participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up.

Unravelling the Role of Kinases That Underpin Androgen Signalling in Prostate Cancer.

The androgen receptor (AR) signalling pathway is the key driver in most prostate cancers (PCa), and is underpinned by several kinases both upstream and downstream of the AR. Many popular therapies for PCa that target the AR directly, however, have been circumvented by AR mutation, such as androgen receptor variants. Some upstream kinases promote AR signalling, including those which phosphorylate the AR and others that are AR-regulated, and androgen regulated kinase that can also form feed-forward activation circuits to promotes AR function.

Sentinel lymph node biopsy alone compared to systematic lymphadenectomy in patients with uterine carcinosarcoma.

Objective: To assess survival among patients diagnosed with uterine carcinosarcoma (CS) who underwent sentinel lymph node (SLN) biopsy alone vs. systematic lymph node dissection (LND).

Methods: We identified newly diagnosed CS patients who underwent primary surgical management from January 1996-December 2019.

The association between guideline adherence, age and overall survival among women with non-metastatic breast cancer: A systematic review.

Introduction: Conformity with treatment guidelines should benefit patients. Studies have reported variation in adherence to breast cancer (BC) guidelines, particularly among older women. This study investigated (i) whether adherence to treatment guideline recommendations for women with non-metastatic BC improves overall survival (OS), (ii) whether that relationship varies by age.

Identification of intrinsic primary afferent neurons in mouse jejunum.

Background: The gut is the only organ system with intrinsic neural reflexes. Intrinsic primary afferent neurons (IPANs) of the enteric nervous system initiate intrinsic reflexes, form gut-brain connections, and undergo considerable neuroplasticity to cause digestive diseases. They remain inaccessible to study in mice in the absence of a selective marker.

Increasing hay inclusion in silage-based receiving diets and its effects on performance and energy utilization in newly weaned beef steers.

The influence of grass hay (GH) inclusion in replacement of corn silage in receiving diets on growth performance and dietary net energy (NE) utilization was evaluated in newly weaned beef steers ( = 162 Charolais-Red Angus cross steers; initial body weight BW] = 278 ± 13.4 kg). Treatments were (DM basis): 1) 0% GH, 2) 10% GH, or 3) 20% GH inclusion in replacement of corn silage in receiving diets fed to newly weaned beef steers for 56 d.

Correcting an instance of synthetic lethality with a pro-survival sequence.

A human cDNA encoding the LIM domain containing 194 amino acid cysteine and glycine rich protein 3 (CSRP3) was identified as a BAX suppressor in yeast and a pro-survival sequence that abrogated copper mediated regulated cell death (RCD). Yeast lacks a CSRP3 orthologue but it has four LIM sequences, namely RGA1, RGA2, LRG1 and PXL1. These are known regulators of stress responses yet their roles in RCD remain unknown.

Expectations of Hepato-Pancreato-Biliary Fellows; Do We Meet Them?

Objective: There are 16 accredited hepatopancreatobiliary (HPB) fellowships in North America. The purpose of this study is to portray the expectations of the incoming HPB fellows about their training and its implication on their career.

Design: A 29-questions survey was sent out to all HPB fellows starting in August 2017.

Common elements in opioid use disorder guidelines for buprenorphine prescribing.

Objectives: This study sought to formulate a consolidation of guidelines representing best practices related to office-based opioid treatment (OBOT) of opioid use disorder (OUD) using buprenorphine. It also demonstrates how a set of evidence-based guidelines may be linked with claims data to leverage analytic techniques that drive cost-effective, positive health outcomes.

Study Design: Literature review of US and international guidelines for OBOT using buprenorphine for OUD.

Intracellular second messengers mediate stress inducible hormesis and Programmed Cell Death: A review.

Alterations in the levels of numerous second messengers are ubiquitous responses to all stresses that lead to apoptotic or hormetic responses. The sheer number and vast diversity of different second messenger systems activated in response to stresses belies a complexity that is often overlooked. This negligence is in large part due to the excessive focus on classical stress responsive second messenger mediators of stress especially Reactive Oxygen Species (ROS) but also others like calcium and ceramide.

Stress is an agonist for the induction of programmed cell death: A review.

The prevailing models of stress induced Programmed Cell Death (PCD) posit that excess extracellular chemicals interact with or enter cells and disrupts cellular homeostasis. This activates signalling cascades involving the mitochondria, an increase in the steady state levels of Reactive Oxygen Species (ROS) as well as the activation of Bax and caspases. Further, the increased ROS also causes cellular damage that triggers or enhances PCD responses.

Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice.

Background & Aims: Muscularis propria macrophages lie close to cells that regulate gastrointestinal motor function, including interstitial cells of Cajal (ICC) and myenteric neurons. In animal models of diabetic gastroparesis, development of delayed gastric emptying has been associated with loss of macrophages that express cytoprotective markers and reduced networks of ICC. Mice with long-term diabetes and normal gastric emptying have macrophages that express anti-inflammatory markers and have normal gastric ICC.

Introducing a post-operative proforma for elective lower limb arthroplasty patients - improving patient care and junior doctor confidence.

The assessment of post-operative patients is vital to identify early complications and ensure patient safety. Good clinical record keeping is essential for effective continuity of care and patient safety in the post-operative period. A group of foundation year 2 (FY2) doctors noted a disparity in levels of confidence and ability in performing this assessment.