Transcription and DNA replication collisions lead to large tandem duplications and expose targetable therapeutic vulnerabilities in cancer.

Despite the abundance of somatic structural variations (SVs) in cancer, the underlying molecular mechanisms of their formation remain unclear. In the present study, we used 6,193 whole-genome sequenced tumors to study the contributions of transcription and DNA replication collisions to genome instability. After deconvoluting robust SV signatures in three independent pan-cancer cohorts, we detected transcription-dependent, replicated-strand bias, the expected footprint of transcription-replication collision (TRC), in large tandem duplications (TDs).

Securing commitment and control for the supply of plasma derivatives for public health systems. I: A short review of the global landscape.

The social market economies of the Western world considered the provision of plasma derivatives produced from publicly owned blood services as a legitimate state commitment and, until the last decades of the 20th century, many of the relevant jurisdictions maintained state-supported fractionation plants to convert publicly collected plasma into products for the public health system. This situation started to change in the 1990s, because of several converging factors, and currently, publicly owned/subsidized, not-for-profit fractionation activity has shrunk to a handful of players. However, the collection of plasma from publicly owned blood services has continued and recent developments have increased the interest of state authorities globally to increase the volume of plasma collected to increase the level of strategic independence in the supply of crucial plasma-derived medicines from commercial market pressures, particularly the global for-profit fractionation sector with its dominance of source plasma from paid donors in the United States.

Securing commitment and control for the supply of plasma derivatives for public health systems. II: A survey of national pathways.

Background And Objectives: Pressures on the supply of plasma-derived medicinal products (PDMPs) have led to the efforts to increase the level of plasma collected by public health authorities.

Materials And Methods: Public blood collectors were assessed regarding their routes towards domestically sourced plasma and PDMPs.

Results: The collectors' operations were specified and analysed.

Opioid-related mortality after occupational injury in Washington State: accounting for preinjury opioid use.

Objectives: To estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use.

Methods: We employed a retrospective cohort study design using Washington State workers' compensation data for 1994-2000 injuries linked to US Social Security Administration earnings and mortality data and National Death Index (NDI) cause of death data from 1994 to 2018. We categorised injuries as lost-time versus medical-only, where the former involved more than 3 days off work or permanent disability.

PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models.

Small-molecule inhibitors of the mono (ADP) ribosyl transferase PARP7 are being evaluated asmonotherapy for tumors overexpressing PARP7 and in combination with immune checkpoint blockade. We previously showed that sensitivity to the PARP7 inhibitor (PARP7i) RBN-2397 could be enhanced by cotreatment with agonists of the aryl hydrocarbon receptor (AHRa) in cell lines that show strong intrinsic sensitivity to RBN-2397. In this study, we demonstrated that a range of tumor cell lines that are relatively insensitive to PARP7i or AHRa as individual agents are unexpectedly profoundly sensitive to their combination.

Male Survivors of Institutional Child Sexual Abuse: A Review.

Male child sexual abuse is over-represented in institutional settings. This realization has increasingly come into public focus in recent decades initially through lived experience, often with male survivors' stories told in the media and subsequently through court cases and government inquiries. Beginning at the turn of the century with the Irish Commission to Inquire into Child Abuse (1999-2009), numerous national and state inquiries into institutional child abuse followed around the world.

Balancing Donor Health and Plasma Collection: A Systematic Review of the Impact of Plasmapheresis Frequency.

Most plasma used for manufacturing plasma-derived medicinal products (PDMPs) such as albumin, immunoglobulin (Ig), and clotting factors is obtained from source plasma collected via plasmapheresis, the majority of which is contributed by the United States (US). While the demand for PDMPs continues to rise, it remains unclear whether high-frequency plasmapheresis, such as the twice-weekly plasma donation allowed in the US, may have any (long-term) adverse health effects on the donor. To investigate the frequency at which plasma can be donated without harm to the donor, the current systematic review explores the impact of plasma donation frequency on cardiovascular health, protein depletion, and adverse events in healthy plasma donors.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses.

Willingness to pay for expanded non-invasive prenatal screening - An online discrete choice experiment from the perspective of women living in Western Australia.

Introduction: Ongoing advances in genetic technology may soon provide prenatal screening for multiple genetic conditions.

Aims: The aims were to investigate what prenatal screening test characteristics women prioritise and their willingness to pay for these tests.

Methods: We designed an online survey incorporating a series of discrete choice scenarios.

Promoting men-inclusive maternity services: exploring the expectations, experiences and needs of men as fathers.

Aim: This study aimed to explore the 'real time' expectations, experiences and needs of men who attend maternity services to inform the development of strategies to enhance men's inclusion.

Methods: A qualitative descriptive design was adopted for the study. Semi-structured face-to-face or telephone interviews were conducted with 48 men attending the Royal Brisbane and Women's Hospital before and after their partner gave birth.

Demonstrating the use of population level data to investigate trends in the rate, radiation dose and cost of Computed Tomography across clinical groups: Are there any areas of concern?

Introduction: Increases in computed tomography (CT) use may not always reflect clinical need or improve outcomes. This study aimed to demonstrate how population level data can be used to identify variations in care between patient groups, by analysing system-level changes in CT use around the diagnosis of new conditions.

Methods: Retrospective repeated cross-sectional observational study using West Australian linked administrative records, including 504,723 adults diagnosed with different conditions in 2006, 2012 and 2015.

Biomechanical Motion Changes in Adjacent and Noncontiguous Segments Following Single-Level Anterior Cervical Discectomy and Fusion: A Computed Tomography-Based 3D Motion Capture Study.

Background: Anterior cervical discectomy and fusion (ACDF) is known to elicit adverse biomechanical effects on immediately adjacent segments; however, its impact on the kinematics of the remaining nonadjacent cervical levels has not been understood. This study aimed to explore the biomechanical impact of ACDF on kinematics beyond the immediate fusion site. We hypothesized that compensatory motion following single-level ACDF is not predictably distributed to adjacent segments due to compensation from noncontiguous levels.

Intersections of Intimate Partner Violence and Natural Disasters: A Systematic Review of the Quantitative Evidence.

Natural disasters and extreme weather events are increasing in both intensity and frequency. Emerging evidence suggests that there is a relationship between intimate partner violence (IPV) and natural disasters. However, there is a scarcity of methodologically sound research in this area with no systematic review to date.

Large tandem duplications in cancer result from transcription and DNA replication collisions.

Despite the abundance of somatic structural variations (SVs) in cancer, the underlying molecular mechanisms of their formation remain unclear. Here, we use 6,193 whole-genome sequenced tumors to study the contributions of transcription and DNA replication collisions to genome instability. After deconvoluting robust SV signatures in three independent pan-cancer cohorts, we detect transcription-dependent replicated-strand bias, the expected footprint of transcription-replication collision (TRC), in large tandem duplications (TDs).

Cognitive Behavioral Therapy for Chronic Pelvic Pain: What Is It and Does It Work?

Purpose: Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome in women and men and chronic prostatitis/chronic pelvic pain syndrome in men, is a common, often disabling urological disorder that is neither well understood nor satisfactorily treated with medical treatments. The past 25 years have seen the development and validation of a number of behavioral pain treatments, of which cognitive behavioral therapy (CBT) is arguably the most effective. CBT combines strategies of behavior therapy, which teaches patients more effective ways of behaving, and cognitive therapy, which focuses on correcting faulty thinking patterns.

Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

Background: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+).

Methods: A retrospective multicentre study was performed.

A feasibility assessment of a traumatic brain injury predictive modelling tool at Kilimanjaro Christian Medical Center and Duke University Hospital.

Traumatic brain injury (TBI) is the most common cause of death and disability globally. TBI, which disproportionately affects low middle-income countries (LMIC), uses significant amounts of health system resources in costly care and management. Innovative solutions are required to address this high burden of TBI.

Six month incidence of major adverse cardiovascular events among adults with HIV in northern Tanzania: a prospective observational study.

Objectives: We aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient preferences for cardiovascular care and education.

Design: A prospective observational study.

Novel approach to prenatal predictors of outcomes for fetuses with severe Ebstein anomaly.

Objective: Ebstein anomaly (EA) is a cardiac malformation with highly variable presentation and severity with limited perinatal management options. We present incorporation of fetal lung measurements into a multidisciplinary evaluation for counseling and predicting postnatal outcomes in patients with severe EA.

Methods: Five fetuses with severe fetal EA were reviewed.