Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1.

Poly(ADP-ribose) Polymerase 2 (PARP2) is one of three DNA-dependent PARPs involved in the detection of DNA damage. Upon binding to DNA double-strand breaks, PARP2 uses nicotinamide adenine dinucleotide to synthesize poly(ADP-ribose) (PAR) onto itself and other proteins, including histones. PAR chains in turn promote the DNA damage response by recruiting downstream repair factors.

Simulation as a Tool for Teaching and Learning Epidemiologic Methods.

In aspiring to be discerning epidemiologists, we must learn to think critically about the fundamental concepts in our field and be able to understand and apply many of the novel methods being developed today. We must also find effective ways to teach both basic and advanced topics in epidemiology to graduate students, in a manner that goes beyond simple provision of knowledge. Here, we argue that simulation is one critical tool that can be used to help meet these goals, by providing examples of how simulation can be used to address 2 common misconceptions in epidemiology.

Single versus dual-rate learning when exposed to Coriolis forces during reaching movements.

When we reach for an object during a passive whole body rotation, a tangential Coriolis force is generated on the arm. Yet, within a few trials, the brain adapts to this force so it does not disrupt the reach. Is this adaptation governed by a single-rate or dual-rate learning process? Here, guided by state-space modeling, we studied human reach adaptation in a fully-enclosed rotating room.

Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers-results from the DELCODE study.

Background: Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuropsychiatric symptoms (NPS) have been proposed as potential markers for early manifestation of Alzheimer's disease (AD). We aimed to investigate the frequency of NPS in SCD, in other at-risk groups, in healthy controls (CO), and in AD patients, and to test the association of NPS with AD biomarkers, with a particular focus on cognitively unimpaired participants with or without SCD-related worries.

Temperature Screening for SARS-CoV-2 in Nursing Homes: Evidence from Two National Cohorts.

Background/objectives: Infection screening tools classically define fever as 38.0°C (100.4°F).

Cost-effectiveness of teduglutide in pediatric patients with short bowel syndrome: Markov modeling using traditional cost-effectiveness criteria.

Background: Teduglutide use in pediatric patients with short bowel syndrome can aid in the achievement of enteral autonomy, but with a price of >$400,000 per y.

Objective: The current study evaluated the cost-effectiveness of using teduglutide in conjunction with offering intestinal transplantation in US pediatric patients with short bowel syndrome.

Design: A Markov model was used to evaluate the costs (in US dollars) and effectiveness [in quality-adjusted life years (QALYs)] of using teduglutide compared with offering intestinal transplantation.

Expanding the Perseus Software for Omics Data Analysis With Custom Plugins.

The Perseus software provides a comprehensive framework for the statistical analysis of large-scale quantitative proteomics data, also in combination with other omics dimensions. Rapid developments in proteomics technology and the ever-growing diversity of biological studies increasingly require the flexibility to incorporate computational methods designed by the user. Here, we present the new functionality of Perseus to integrate self-made plugins written in C#, R, or Python.

Delirium definition influences prediction of functional survival in patients one-year postcardiac surgery.

Background: Delirium after cardiac surgery is associated with prolonged intensive care unit (ICU) and hospital length of stay and elevated rates of mortality. The Society of Thoracic Surgery National Database (STS-ND) includes delirium in routine data collection but restricts its definition to hyperactive symptoms. The objective is to determine whether the Confusion Assessment Method for ICU (CAM-ICU), which includes hypo- and hyperactive symptoms, is associated with improved prediction of poor 1-year functional survival following cardiac surgery.

Rapid cycle system improvement for COVID-19 readiness: integrating deliberate practice, psychological safety and vicarious learning.

Introduction: In the face of a rapidly advancing pandemic with uncertain pathophysiology, pop-up healthcare units, ad hoc teams and unpredictable personal protective equipment supply, it is difficult for healthcare institutions and front-line teams to invent and test robust and safe clinical care pathways for patients and clinicians. Conventional simulation-based education was not designed for the time-pressured and emergent needs of readiness in a pandemic. We used 'rapid cycle system improvement' to create a psychologically safe learning oasis in the midst of a pandemic.

Comparative Effectiveness of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in Older Nursing Home Residents After Myocardial Infarction: A Retrospective Cohort Study.

Background: Evidence regarding differences in outcomes between angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) among older nursing home (NH) residents after acute myocardial infarction (AMI) is limited.

Objectives: The purpose of our study was to estimate the post-AMI effects of ARBs versus ACEIs on mortality, rehospitalization, and functional decline outcomes in this important population.

Methods: This retrospective cohort study used national Medicare claims linked to Minimum Data Set assessments.

Defining and Identifying Per-protocol Effects in Randomized Trials.

In trials with noncompliance to assigned treatment, researchers might be interested in estimating a per-protocol effect-a comparison of two counterfactual outcomes defined by treatment assignment and (often time-varying) compliance with a well-defined treatment protocol. Here, we provide a general counterfactual definition of a per-protocol effect and discuss examples of per-protocol effects that are of either substantive or methodologic interest. In doing so, we seek to make more concrete what per-protocol effects are and highlight that one can estimate per-protocol effects that are more than just a comparison of always taking treatment in two distinct treatment arms.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper: Plant-based Milks.

Parents and caretakers are increasingly feeding infants and young children plant-based "milk" (PBM) alternatives to cow milk (CM). The US Food and Drug Administration currently defines "milk" and related milk products by the product source and the inherent nutrients provided by bovine milk. Substitution of a milk that does not provide a similar nutritional profile to CM can be deleterious to a child's nutritional status, growth, and development.

Temperature in Nursing Home Residents Systematically Tested for SARS-CoV-2.

Objectives: Many nursing home residents infected with SARS-CoV-2 fail to be identified with standard screening for the associated COVID-19 syndrome. Current nursing home COVID-19 screening guidance includes assessment for fever, defined as a temperature of at least 38.0°C.

Female reproductive tract has low concentration of SARS-CoV2 receptors.

There has been significant concern regarding fertility and reproductive outcomes during the SARS-CoV2 pandemic. Recent data suggests a high concentration of SARS-Cov2 receptors, or , in nasal epithelium and cornea, which explains person-to-person transmission. We investigated the prevalence of SARS-CoV2 receptors among reproductive tissues by exploring the single-cell sequencing datasets from uterus, myometrium, ovary, fallopian tube, and breast epithelium.

[The impact of radical cystectomy on health-related quality of life and potential for optimisation].

Radical cystectomy may have a major impact on the lives of affected patients. Older patients often have a reduced life expectancy after radical cystectomy. Therefore, aspects of health-related quality of life (HRQOL) have to be balanced against a solely tumour-directed therapy.

Microsimulation Model to Compare Enteral and Parenteral Iron Supplementation in Children With Intestinal Failure.

Background: Children with chronic intestinal failure have a high prevalence of anemia, commonly from iron deficiency, leading to frequent blood transfusions. No current guideline exists for iron supplementation in these children. In this analysis, we evaluate the effectiveness and the cost-effectiveness of using parenteral, enteral, and no iron supplementation to reduce blood transfusions.

Palliative Care Consultation Reduces Heart Failure Transitions: A Matched Analysis.

Background Palliative care supports quality of life, symptom control, and goal setting in heart failure (HF) patients. Unlike hospice, palliative care does not restrict life-prolonging therapy. This study examined the association between palliative care during hospitalization for HF on the subsequent transitions and procedures.

Probing the Conformational Changes Associated with DNA Binding to PARP1.

Poly(ADP-ribose) polymerase 1 (PARP1) is an important first responder in the mechanism of DNA repair in eukaryotic cells. It is also a validated drug target, with four different PARP inhibitors (PARPi) approved for the treatment of BRCA-negative cancers. Despite past efforts, many aspects of PARPi are poorly understood, in particular their ability to trap PARP1 on chromatin and the relationships between their potencies, cellular toxicities, and trapping efficiencies.

Managing psychological safety in debriefings: a dynamic balancing act.

Debriefings should promote reflection and help learners make sense of events. Threats to psychological safety can undermine reflective learning conversations and may inhibit transfer of key lessons from simulated cases to the general patient care context. Therefore, effective debriefings require high degrees of psychological safety-the perception that it is safe to take interpersonal risks and that one will not be embarrassed, rejected or otherwise punished for speaking their mind, not knowing or asking questions.

Heart Failure Outcomes and Associated Factors Among Veterans With Human Immunodeficiency Virus Infection.

Objectives: This study sought to investigate outcomes of heart failure (HF) in veterans living with human immunodeficiency virus (HIV).

Background: Data on outcomes of HF among people living with human immunodeficiency virus (PLHIV) are limited.

Methods: We performed a retrospective cohort study of Veterans Health Affairs data to investigate outcomes of HF in PLHIV.

IRE1α Disruption in Triple-Negative Breast Cancer Cooperates with Antiangiogenic Therapy by Reversing ER Stress Adaptation and Remodeling the Tumor Microenvironment.

Cancer cells exploit the unfolded protein response (UPR) to mitigate endoplasmic reticulum (ER) stress caused by cellular oncogene activation and a hostile tumor microenvironment (TME). The key UPR sensor IRE1α resides in the ER and deploys a cytoplasmic kinase-endoribonuclease module to activate the transcription factor XBP1s, which facilitates ER-mediated protein folding. Studies of triple-negative breast cancer (TNBC)-a highly aggressive malignancy with a dismal posttreatment prognosis-implicate XBP1s in promoting tumor vascularization and progression.

Embedding Social Workers In Veterans Health Administration Primary Care Teams Reduces Emergency Department Visits.

While an emerging body of evidence suggests that medical homes may yield more benefits than traditional care models do, the role of social workers within medical homes has yet to be evaluated separately. We assessed the impact of an initiative to add social workers to rural primary care teams in the Veterans Health Administration on patients' use of social work services, hospital admissions, and emergency department visits. We found that introducing a social worker increased social work encounters by 33 percent among all veterans who received care.