Experimental considerations for precise RNA-mediated insertion of transgenes.

Precise RNA-mediated insertion of transgenes (PRINT) is a pioneering method for site-specific, safe-harbor transgene supplementation of the human genome that harnesses a eukaryotic retroelement protein and relies solely on the delivery of RNA. Here we outline important considerations in the design of the two required RNAs, details for the production and transfection of these RNAs to cells, and read-outs for successful transgene addition. Throughout, tips and key concepts are laid out to enable general use of this method.

Structure and sequence at an RNA template 5' end influence insertion of transgenes by an R2 retrotransposon protein.

R2 non-long terminal repeat retrotransposons insert site-specifically into ribosomal RNA genes (rDNA) in a broad range of multicellular eukaryotes. R2-encoded proteins can be leveraged to mediate transgene insertion at 28S rDNA loci in cultured human cells. This strategy, recise NA-mediated sertion of ransgenes (PRINT), relies on the codelivery of an mRNA encoding R2 protein and an RNA template encoding a transgene cassette of choice.

Specific Association of Worry With Amyloid-β But Not Tau in Cognitively Unimpaired Older Adults.

Objective: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established.

Temporal allele frequency changes in large-effect loci reveal potential fishing impacts on salmon life-history diversity.

Fishing has the potential to influence the life-history traits of exploited populations. However, our understanding of how fisheries can induce evolutionary genetic changes remains incomplete. The discovery of large-effect loci linked with ecologically important life-history traits, such as age at maturity in Atlantic salmon (), provides an opportunity to study the impacts of temporally varying fishing pressures on these traits.

A potential neuromodulation target for PTSD in Veterans derived from focal brain lesions.

Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry causally linked to PTSD in military Veterans. After penetrating traumatic brain injury (n=193), lesions that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex (mPFC), amygdala, and anterolateral temporal lobe (cross-validation p=0.

Harnessing eukaryotic retroelement proteins for transgene insertion into human safe-harbor loci.

Current approaches for inserting autonomous transgenes into the genome, such as CRISPR-Cas9 or virus-based strategies, have limitations including low efficiency and high risk of untargeted genome mutagenesis. Here, we describe precise RNA-mediated insertion of transgenes (PRINT), an approach for site-specifically primed reverse transcription that directs transgene synthesis directly into the genome at a multicopy safe-harbor locus. PRINT uses delivery of two in vitro transcribed RNAs: messenger RNA encoding avian R2 retroelement-protein and template RNA encoding a transgene of length validated up to 4 kb.

Technical note: Errors introduced when using Dose Voxel Kernels for estimating absorbed dose from radiopharmaceutical therapies involving alpha emitters.

Background: In radiopharmaceutical therapies (RPT) involving beta emitters, absorbed dose (D) calculations often employ the use of dose voxel kernels (DVK). Such methods are faster and easier to implement than Monte Carlo (MC) simulations. Using DVK methods implies a non-stochastic distribution of particles.

A Novel Method for Real-Time Quantification of Radioligand Binding to Living Tumor Cells .

Real-time quantification of radioligand binding to cells under -like conditions improves evaluation of clinical potential. SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis.

Drivers and barriers of patients' acceptance of video consultation in cancer care.

Background: Due to digitization in the medical sector, many healthcare interactions are switched to online services. This study assessed the acceptance of video consultations (VCs) in cancer care, and determined drivers and barriers of acceptance.

Methods: A cross-sectional online-based survey study was conducted in Germany from February 2022 to February 2023.

Influence of loss- and restoration-oriented stressors on grief in times of COVID-19.

This study aimed to examine the influence of COVID-specific stressors on cross-sectional and longitudinal bereavement outcomes. According to the Dual Process Model of grief these stress-inducing factors can relate to the loss (loss-oriented stressors) or to manage everyday life (restoration-oriented stressors) and require coping in the grief process. A total of 491 participants (94.

What Does Cleft Lip and Palate Care Cost? The Time and Economic-Associated Burden of Care From Birth to Maturity.

This study aims to describe the burden of care (BoC) for the management of patients with nonsyndromic cleft lip and palate (CLP) by identifying provider burden, characterizing an interaction burden, and calculating an economic burden associated with their health system interactions. A retrospective chart review was conducted of patients with nonsyndromic CLP treated at a pediatric tertiary hospital between January 1, 1999, and April 30, 2021. Healthcare utilization data for inpatient and outpatient interactions were extracted.

Falling off the screening grid-Predictors for postponed utilization of psycho-oncological support in cancer patients and its implications for distress assessment and management.

Objective: Distress assessment of cancer patients is considered state-of-the-art. In addition to distress scores, individual care needs are an important factor for the initiation of psycho-oncological interventions. In a mono-centric, observational study, we aimed for characterization of patients indicating a subjective need but declining to utilize support services immediately to facilitate implementation of adapted screenings.

Public knowledge and attitudes about mental health in older age in Germany - Focus on dementia and late-life depression.

Older people with mental disorders represent a particularly vulnerable group in the health care system. Despite this, mental disorders in this group often remain undiagnosed or are not treated in accordance with guidelines, potentially due to a lack of knowledge or unfavorable attitudes regarding mental disorders in older individuals. Therefore, in an anonymous online survey of 1,284 participants (71.

The effect of aging on facial emotion recognition in bipolar disorder.

Objective: Convergent data point to an exaggerated negativity bias in bipolar disorder (BD), and little is known about whether people with BD experience the 'positivity effect' with increasing age.

Method: This is a cross sectional study of 202 participants with BD aged 18-65, and a sample (n = 53) of healthy controls (HCs). Participants completed the CANTAB Emotion Recognition Task (ERT).

Comparing performance between clinics of an embryo evaluation algorithm based on time-lapse images and machine learning.

Purpose: This article aims to assess how differences in maternal age distributions between IVF clinics affect the performance of an artificial intelligence model for embryo viability prediction and proposes a method to account for such differences.

Methods: Using retrospectively collected data from 4805 fresh and frozen single blastocyst transfers of embryos incubated for 5 to 6 days, the discriminative performance was assessed based on fetal heartbeat outcomes. The data was collected from 4 clinics, and the discrimination was measured in terms of the area under ROC curves (AUC) for each clinic.

Evaluation of a male-specific psychotherapeutic program for major depressive disorder compared to cognitive behavioral therapy and waitlist: study protocol for a six-arm randomized clinical superiority trial examining depressed eugonadal and hypogonadal men receiving testosterone.

Background: Treatment of major depressive disorder (MDD) in men is complicated by the endorsement of traditional masculinity ideologies (TMI) often leading to reluctance toward psychotherapy, therapy interfering processes, or premature termination. In addition, it has been shown that men with MDD have a significantly increased risk of being hypogonadal (e.g.

Impact of Clouds and Blowing Snow on Surface and Atmospheric Boundary Layer Properties Over Dome C, Antarctica.

Clouds and blowing snow (BLSN) occur frequently over Antarctica, where it is critical to understand their feedbacks to surface and atmospheric boundary layer processes. Dome C, an elevated East Antarctic station, dominated by lengthy periods of surface longwave (LW) radiative cooling, is selected to reveal cloud and BLSN impacts within a largely stable environment. The sky condition is classified as clear, cloudy, or BLSN, using 3 years of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations satellite data.

Astatine-211 based radionuclide therapy: Current clinical trial landscape.

Astatine-211 (At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.

From spawner habitat selection to stock-recruitment: Implications for assessment.

The relationship between the spawning stock size and subsequent number of recruits is a central concept in fisheries ecology. The influence of habitat selection of spawning individuals on the stock-recruitment relationship is poorly known. Here we explore how each of four different spawner behaviors might influence the stock-recruitment relationship and estimates of its parameters in the two most commonly used stock-recruitment functions (Beverton-Holt and Ricker).

Impact of radiopharmaceutical therapy (Lu, Ac) microdistribution in a cancer-associated fibroblasts model.

Background: The aim of this study is to elucidate the difference in absorbed dose (D) patterns in radiopharmaceutical therapies between alpha emitters (Ac) and beta emitters (Lu) when targeting cancer-associated fibroblasts (CAF) or tumor cells. Five spherical models with 3 mm diameter were created, representing spherical tumor masses that contain tumor clusters, interspersed with CAFs. The mean distance from a tumor cell to the nearest CAF (L) varied throughout these models from 92 to 1030 µm.

Psychobiological Evaluation of Day Clinic Treatment for People Living With Dementia - Feasibility and Pilot Analyses.

Background: Hospitalization is often stressful and burdensome for people living with dementia (PwD) and their informal caregivers (ICs). Day clinic treatment may provide a suitable alternative, but is often precluded by a diagnosis of dementia. Furthermore, it is often caregiver-based ratings that measure treatment success as the validity of self-reports in PwD is critically discussed.