Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.

Background: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.

Non-invasive Physical Plasma Modulates Macrophage Polarization: A Potential Strategy for Tumor Microenvironment Remodeling.

Background/aim: Non-invasive physical plasma (NIPP) has shown promise in the treatment of cancer. However, conflicting results have been reported regarding the effect of NIPP on macrophage polarization. As tumor-associated macrophages (TAMs) are essential in the regulation of cancer development, this study aimed to determine the role of NIPP treatment in macrophage polarization and tumor-microenvironment (TME) remodeling.

Neuropilin2 in Mesenchymal Stromal Cells as a Potential Novel Therapeutic Target in Myelofibrosis.

Bone marrow fibrosis in myeloproliferative neoplasm (MPN), myelodysplastic syndromes (MDS), MPN/MDS overlap syndromes and acute myeloid leukemia (AML) is associated with poor prognosis and early treatment failure. Myelofibrosis (MF) is accompanied by reprogramming of multipotent bone marrow mesenchymal stromal cells (MSC) into osteoid and fiber-producing stromal cells. We demonstrate NRP2 and osteolineage marker NCAM1 (neural cell adhesion molecule 1) expression within the endosteal niche in normal bone marrow and aberrantly in MPN, MDS MPN/MDS overlap syndromes and AML ( = 99), as assessed by immunohistochemistry.

Patients with cocaine use disorder exhibit reductions in delay discounting with episodic future thinking cues regardless of incarceration history.

Research examining episodic future thinking (EFT; i.e., imagining oneself in future contexts) in community samples has demonstrated reduced discounting of delayed rewards when personalized event cues are included to prompt EFT related to reward latencies.

Unusual paraneoplastic syndromes in pancreatic cancer: a case report of Lambert-Eaton myasthenic syndrome (LEMS) associated with intraductal papillary mucinous cancer of the pancreas.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction. It can occur as a paraneoplastic disorder associated with various types of carcinomas, usually small cell lung cancer or as an autoimmune disease. LEMS can be misdiagnosed as myasthenia gravis or as an oncological sequela, causing delays in diagnosis.

Development and Characterization of a Novel Neuropilin-2 Antibody for Immunohistochemical Staining of Cancer and Sarcoidosis Tissue Samples.

Neuropilin-2 (NRP2) is a cell surface receptor that plays key roles in lymphangiogenesis, but also in pathophysiological conditions such as cancer and inflammation. NRP2 targeting by efzofitimod, a novel immunomodulatory molecule, is currently being tested for the treatment of pulmonary sarcoidosis. To date, no anti-NRP2 antibodies are available for companion diagnostics.

Telehealth-Based Contingency Management Targeting Stimulant Abstinence: A Case Series From the COVID-19 Pandemic.

Objective: Contingency management (CM) is the gold standard treatment for stimulant use disorder but typically requires twice- to thrice-weekly in-person treatment visits to objectively verify abstinence and deliver therapeutic incentives. There has been growing interest in telehealth-based delivery of CM to support broad access to this essential intervention--a need that has been emphatically underscored by the COVID-19 pandemic. Herein, we present observations from initial efforts to develop and test a protocol for telehealth-based delivery of prize-based CM treatment incentivizing stimulant abstinence.

Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma.

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail.

Predicting outcome in acute respiratory admissions using patterns of National Early Warning Scores.

Aims: Accurately predicting risk of patient deterioration is vital. Altered physiology in chronic disease affects the prognostic ability of vital signs based early warning score systems. We aimed to assess the potential of early warning score patterns to improve outcome prediction in patients with respiratory disease.

Effect of implementing the NEWS2 escalation protocol in a large acute NHS trust: a retrospective cohort analysis of mortality, workload and ability of early warning score to predict death within 24 hours.

Objectives: To describe the inpatient population, establish patterns in admission and mortality over a 4-year period in different cohorts and assess the prognostic ability and workload implications of introducing the National Early Warning Score 2 (NEWS2) and associated escalation protocol.

Design: Retrospective cohort analyses of medical and surgical inpatient admissions.

Setting: Large teaching hospital with tertiary inpatient care and a major trauma centre employing an electronic observations platform, initially with a local early warning score, followed by NEWS2 introduction in June 2019.

Barriers to Long-acting Injectable Antipsychotic Adherence During the COVID-19 Pandemic: Observations From One Site.

Objective: Long-acting injectable antipsychotics (LAI-As) are a crucial treatment option for individuals with serious mental illness. However, due to the necessity of in-person administration of LAI-As, pandemics pose unique challenges for continuity of care in the population prescribed these medications. This project investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on LAI-A adherence at a Veterans Health Administration medical facility in the United States, as well as changes in LAI-A prescribing and administration practices during this period.

Androgen Receptor Splice Variants Contribute to the Upregulation of DNA Repair in Prostate Cancer.

Background: Canonical androgen receptor (AR) signaling regulates a network of DNA repair genes in prostate cancer (PCA). Experimental and clinical evidence indicates that androgen deprivation not only suppresses DNA repair activity but is often synthetically lethal in combination with PARP inhibition. The present study aimed to elucidate the impact of AR splice variants (AR-Vs), occurring in advanced or late-stage PCA, on DNA repair machinery.

Threats to external validity in the neuroprediction of substance use treatment outcomes.

Tools predicting individual relapse risk would invaluably inform clinical decision-making (e.g. level-of-care) in substance use treatment.

The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance.

Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI.

Dynamic early warning scores for predicting clinical deterioration in patients with respiratory disease.

Background: The National Early Warning Score-2 (NEWS-2) is used to detect patient deterioration in UK hospitals but fails to take account of the detailed granularity or temporal trends in clinical observations. We used data-driven methods to develop dynamic early warning scores (DEWS) to address these deficiencies, and tested their accuracy in patients with respiratory disease for predicting (1) death or intensive care unit admission, occurring within 24 h (D/ICU), and (2) clinically significant deterioration requiring urgent intervention, occurring within 4 h (CSD).

Methods: Clinical observations data were extracted from electronic records for 31,590 respiratory in-patient episodes from April 2015 to December 2020 at a large acute NHS Trust.

Perceived impact of formulating, implementing and enacting national mental health policies recommendations in practice: An exploratory qualitative study within child and adolescent mental health services in Scotland.

Objective: To understand the process of formulating, implementing and enacting national recommendations into practice, by exploring the interactions between government policymakers and national and local organisations supporting and delivering policy implementation within a Child and Adolescent Mental Health Service (CAMHS) context in Scotland.

Methods: Data collection involved 16 semi-structured individual and four focus group interviews with a purposeful sample of policymakers, national health and social care stakeholders and local outpatient and inpatient CAMHS teams representing three NHS health boards in Scotland.

Results: Study participants highlighted the challenges of navigating through evolving and often conflicting policy agendas, seen to not acknowledging the current evidence base or experiential learning from services and prior evaluations.

Increasing the Impact of Interventions Incentivizing Psychiatric Treatment Engagement: Challenges and Opportunities.

Individuals with psychiatric disorders often struggle to initiate and engage in treatment. Financial incentives improve treatment engagement, including treatment attendance, medication adherence, and abstinence from substance use. The U.

Electrophysiological predictors and indicators of contingency management treatment response: Rationale and design for the ways of rewarding abstinence project (WRAP).

Background: Electrophysiological measures can predict and reflect substance use treatment response. Veterans are disproportionately affected by disorders of addiction; cocaine use disorder (CUD) being particularly problematic due to high relapse rates and the absence of approved pharmacotherapies. Prize-based Contingency Management (PBCM) is an evidence-based behavioral intervention for CUD, involving incentives for cocaine abstinence but treatment response is variable.

Classification of acute appendicitis (CAA): treatment directed new classification based on imaging (ultrasound, computed tomography) and pathology.

Purpose: Acute appendicitis (AA) is amongst the most common causes of acute abdominal pain. In spite of progress based on risk stratifications, "negative" appendectomies are performed in up to 30% of patients whilst the appendix perforates in others. Preoperative classification of AA based on imaging is therefore recommended.

A Double Metachronous Ureter Metastasis following Curative Resection of Rectal Cancer.

A malignant ureteral obstruction is most often due to primary tumors of the ureter. However, it can occur secondary due to external tumor compression or metastatic infiltration. Distant metastases to the ureter are extremely rare.

Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer.

Urothelial bladder cancer ranks among the 10 most frequently diagnosed cancers worldwide. In our previous study, the transmembrane protein neuropilin-2 (NRP2) emerged as a predictive marker in patients with bladder cancer. NRP2 consists of several splice variants; the most abundant of these, NRP2a and NRP2b, are reported to have different biological functions in lung cancer progression.

Risk factors for perforated marginal ulcers following pancreaticoduodenectomy and prospective analysis of marginal ulcer development.

Background: Perforated marginal ulcers (PMUs) are a feared long-term complication following pancreaticoduodenectomy (PD), which always require relaparotomy compared to marginal ulcers.

Methods: First, we performed a retrospective chart review for all patients who underwent PD from 2007-2016 to identify incidence and risk factors associated with PMUs. Second, we analyzed follow up gastroscopies in all patients undergoing PD from 2007-2011 to identify the overall incidence of marginal ulcers.

Evaluating effects of episodic future thinking on valuation of delayed reward in cocaine use disorder: a pilot study.

: Episodic future thinking (EFT; i.e., envisioning oneself in future contexts) has been demonstrated to reduce discounting of future reward in healthy adults.