Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

Health-related quality of life and symptom-specific functional impairment among patients treated with parenterally administered complement inhibitors for paroxysmal nocturnal hemoglobinuria.

This study describes the health-related quality of life (HRQoL) and symptom-specific functional impairment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in a real-world setting. US-based adults with PNH treated with a parenterally administered complement inhibitor (PACI) for ≥ 6 months completed an online, cross-sectional, observational survey; a subset of patients also participated in semi-structured qualitative interviews. The survey included the PROMIS 29 + 2 Profile v2.

Canonical and Non-Canonical Roles of Human DNA Polymerase η.

DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is mediated by specialised DNA polymerases that can accommodate altered DNA structures during DNA synthesis, and are important in allowing replication to proceed after fork arrest, preventing fork collapse that can generate more deleterious double-strand breaks in the genome.

Using qualitative exit interviews to explore schizophrenia burden and treatment experience in clinical trial patients.

Introduction: Qualitative research methods can be used to obtain a deeper understanding of patient experience by collecting information in the patients' own words about their encounters, perspectives, and feelings. In this study, patients with schizophrenia were interviewed to capture their voice and to complement the quantitative data typically obtained in clinical trials.

Methods: Semi-structured exit interviews were conducted with 41 patients who completed or prematurely discontinued from a phase 3, open-label trial (NCT02873208).

A framework for best practices in clinical outcome assessment (COA) concept mapping: a case study.

Purpose: Mapping or matching the items in a clinical outcome assessment (COA) to concepts that define a condition is a common method for evaluating a COA's concept coverage. The purpose of this research was to address the lack of formal guidance for conducting this task by developing a framework for best practices in COA concept mapping and applying it to a case study.

Methods: To develop the framework, we examined the literature and created a draft set of best practices which was then reviewed by experienced researchers through focus groups before being finalized.

Continuous neural control of a bionic limb restores biomimetic gait after amputation.

For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However, biological gait requires coordinated volitional and reflexive motor control by complex afferent and efferent neural interplay, making its neuroprosthetic emulation challenging after limb amputation. Here we hypothesize that continuous neural control of a bionic limb can restore biomimetic gait after below-knee amputation when residual muscle afferents are augmented.

A time-adjusted control chart for monitoring surgical outcome variations.

Background: Statistical Process Control (SPC) tools providing feedback to surgical teams can improve patient outcomes over time. However, the quality of routinely available hospital data used to build these tools does not permit full capture of the influence of patient case-mix. We aimed to demonstrate the value of considering time-related variables in addition to patient case-mix for detection of special cause variations when monitoring surgical outcomes with control charts.

The Use of Unlisted Billing Codes for Microsurgical Breast Reconstruction and Implications for Code Consolidation.

Background:  Private insurers have considered consolidating the billing codes presently available for microvascular breast reconstruction. There is a need to understand how these different codes are currently distributed and used to help inform how coding consolidation may impact patients and providers.

Methods:  Using the Massachusetts All-Payer Claims Database between 2016 and 2020, patients who underwent microsurgical breast reconstruction following mastectomy for cancer-related indications were identified.

The impact of age on outcome 2 years after traumatic brain injury: Case control study.

Background: Age is associated with outcome after traumatic brain injury (TBI). However, there are mixed findings across outcome domains and most studies lack controls.

Objectives: This cross-sectional study examined the association between age group (15-24 years, 25-34 years, 35-44 years, 45-54 years, 55-64 years, and 65 years or more) and outcomes 2 years after TBI in independence in daily activities, driving, public transportation use, employment, leisure activities, social integration, relationships and emotional functioning, relative to healthy controls.

Considering the Importance of Personal and Injury Factors Influencing Outcome After Traumatic Brain Injury.

Objective: Given the high variability in traumatic brain injury (TBI) outcomes and relative lack of examination of the influence of noninjury factors on outcome, this study aimed to examine factors associated with functional outcome at 1 and 2 years after moderate to severe TBI, including both preinjury and injury-related factors.

Design: Observational cohort study.

Setting: Inpatient hospital recruitment with outpatient follow-up at 1 and 2 years post injury.

The Agonist-Antagonist Myoneural Interface in a Transtibial Amputation.

Background: The agonist-antagonist myoneural interface (AMI) technique at the time of transtibial amputation involves the use of agonist-antagonist muscle pairs to restore natural contraction-stretch relationships and to improve proprioceptive feedback when utilizing a prosthetic limb.

Description: Utilizing the standard incision for a long posterior myofasciocutaneous flap, the lateral and medial aspects of the limb are dissected, identifying and preserving the superficial peroneal and saphenous nerve, respectively. The tendons of the tibialis anterior and peroneus longus are transected distally to allow adequate length for the AMI constructs.

Impact of Prepectoral vs. Subpectoral Tissue Expander Placement on Post-mastectomy Radiation Therapy Delivery: A Retrospective Cohort Study.

Background: Implant-based reconstruction is the most common method of postmastectomy reconstruction. Many patients require postmastectomy radiation (PMRT). Tissue expanders (TEs), typically inserted as a first stage, have historically been placed subpectorally.

Let's talk about it: an exploration of the comparative use of three different digital platforms to gather patient-reported outcome measures.

Background: Patient-reported outcome (PRO) measures provide valuable evidence in clinical trials; however, poor compliance with PRO measures is a notable and long-standing problem, resulting in missing data that potentially impact the interpretation of trial results. Interactive, patient-centric platforms may increase participants' motivation to complete PRO measures over the course of a clinical trial. Thus, the aim of this study was to evaluate and optimize the usability of 3 popular consumer technologies-a traditional app-based interface, a chatbot interface, and a speech-operated interface-that may be used to improve user engagement and compliance with PRO measures.

Association Between Hematologic Response and Change in Health-Related Quality of Life Among Patients with Light-Chain (AL) Amyloidosis.

Purpose: The purpose of this secondary data analysis was to examine the association between hematologic response and health-related quality of life (HRQoL) among patients with light-chain (AL) amyloidosis.

Patients And Methods: Data for this secondary analysis were collected through a non-interventional, longitudinal, online self-report survey of patients with AL amyloidosis. Patients completed an initial online survey, with follow-up surveys administered 1, 6, 12, 18, and 24 months after completion of the initial survey.

Autophagy and jasmonate fight nematode blight.

Plant-parasitic nematodes (PPNs) pose a serious threat to world crop production and global food security. However, our understanding of the molecular mechanisms underlying plant defense against PPNs remains very limited. Recently, Zou et al.

Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis.

This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[]perimidines, phenoxazinones, benz[]pyrido[1,2-]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-]naphthoquinones, hypothesised as prodrugs.

The Transthyretin Amyloidosis - Quality of Life (ATTR-QOL) Questionnaire: Development of a Conceptual Model and Disease-Specific Patient-Reported Outcome Measure.

Purpose: Patients with transthyretin amyloidosis (ATTR) experience a wide variety of symptoms and impacts on health-related quality of life (HRQoL). However, the lack of an ATTR-specific patient-reported outcome (PRO) measure has made consistent measurement of HRQoL in ATTR challenging. This paper describes the development of a conceptual model and subsequent content for the Transthyretin Amyloidosis - Quality of Life Questionnaire (ATTR-QOL), an ATTR-specific PRO measure.

Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.

Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation.

Blood pressure surge with alarm is reduced after exercise and diet intervention in firefighters.

Background: Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response.

Excess mortality among non-COVID-19 surgical patients attributable to the exposure of French intensive and intermediate care units to the pandemic.

Purpose: The mobilization of most available hospital resources to manage coronavirus disease 2019 (COVID-19) may have affected the safety of care for non-COVID-19 surgical patients due to restricted access to intensive or intermediate care units (ICU/IMCUs). We estimated excess surgical mortality potentially attributable to ICU/IMCUs overwhelmed by COVID-19, and any hospital learning effects between two successive pandemic waves.

Methods: This nationwide observational study included all patients without COVID-19 who underwent surgery in France from 01/01/2019 to 31/12/2020.

Control Charts Usage for Monitoring Performance in Surgery: A Systematic Review.

Objectives: The control chart is a graphical tool for data interpretation that detects aberrant variations in specific metrics, ideally leading to the identification of special causes that can be resolved. A clear assessment of control chart utilization and its potential impact in surgery is required to justify recommendations for its dissemination. This review aims to describe how performance monitoring using control charts was used over time in surgery.

Left Internal Mammary Vein Size and Its Impact on Microsurgical Breast Reconstruction.

Unlabelled: The internal mammary vessels are the preferred recipient during free-flap breast reconstruction (FFBR). Previous studies have demonstrated that the left internal mammary vein (IMV) is consistently smaller than the right, but with unclear clinical implications. This study explores the impact of IMV size difference on FFBR complication rates.

Blood pressure responses are dependent on call type and related to hypertension status in firefighters.

Background: Impaired cardiovascular health is a concern for firefighters, with over 50% of line-of-duty deaths having cardiac causes. Many firefighters have hypertension and <25% have their blood pressure (BP) controlled. The alarm response could be an unidentified cardiac risk, but interestingly, the BP response to different calls and on-the-job activity is unknown.