EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus.

Background: EDP-938 is an oral once-daily RSV nucleoprotein (N) inhibitor with potent antiviral activity. In a human RSV challenge trial, EDP-938 significantly reduced viral load and symptom severity. During antiviral development, it is critical to understand the propensity for resistance to develop.

Dynamics of Purcell-type microswimmers with active-elastic joints.

Purcell's planar three-link microswimmer is a classic model of swimming in low-Reynolds-number fluid, inspired by motion of flagellated microorganisms. Many works analyzed this model, assuming that the two joint angles are directly prescribed in phase-shifted periodic inputs. In this work, we study a more realistic scenario by considering an extension of this model which accounts for joints' elasticity and mechanical actuation of periodic torques so that the joint angles are dynamically evolving.

The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo.

The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses.

Managing the kinetic energy of descending greywater in tall buildings and converting them into a valuable source.

Harnessing energy from descending greywater (GW) in tall buildings (TBs) is an innovative concept that combines water management with renewable energy generation and applying simulation methods. This study proposes a novel approach to enhancing sustainable energy recovery in TBs by capitalizing on the kinetic energy inherent in descending GW. Greywater, derived from non-toilet fixtures such as showers, bathroom sinks, and washing machines, offers a readily accessible source of potential energy due to its gravity-driven flow through the plumbing system.

Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis.

Radiology trainee retirement programs: Options and participation.

Background: Financial security and retirement planning are essential for all medical professionals including radiology residents. Given the available discretionary income during residency it is crucial to have insights into investment. We aimed to assess the prevalence of retirement plans offered to radiology residents, the available choices, and their degree of participation.

A new method for endometrial dating using computerized virtual pathology.

Endometrial dating (ED) is the process by which the menstrual cycle day is estimated and is an important tool for the evaluation of uterine status. To date, ED methods remain inaccurate and controversial. We demonstrate how the rise of computerized virtual histology changes the state of affairs and introduce a new ED method.

Nonlinear dynamics and bifurcations of a planar undulating magnetic microswimmer.

Swimming microorganisms such as flagellated bacteria and sperm cells have fascinating locomotion capabilities. Inspired by their natural motion, there is an ongoing effort to develop artificial robotic nanoswimmers for potential in-body biomedical applications. A leading method for actuation of nanoswimmers is by applying a time-varying external magnetic field.

Delineating the heterogeneity of embryo preimplantation development using automated and accurate morphokinetic annotation.

Purpose: Our objective was to design an automated deep learning model that extracts the morphokinetic events of embryos that were recorded by time-lapse incubators. Using automated annotation, we set out to characterize the temporal heterogeneity of preimplantation development across a large number of embryos.

Methods: To perform a retrospective study, we used a dataset of video files of 67,707 embryos from four IVF clinics.

Revealing the uterine blood vessel network via virtual pathology.

Background: The distribution of the blood vessel network at any point in time in any body tissue, may provide valuable information with regards to the tissue condition and its angiogenesis functionality. The blood vessel three-dimensional network of the endometrium goes through a process of change over a relatively short period of 4 weeks on average. It is well accepted that this angiogenesis is closely related to the success or failure of the implantation of the embryo Objective and rationale: Our study aims to present a method to follow the three-dimensional evolution of the superficial blood vessel distribution in the endometrium throughout the uterine cycle.

Systematic review of personal finance training for physicians and a proposed curriculum.

Background: Many physicians complete medical school and graduate medical education (GME) burdened by high debt and financial illiteracy. This places them at increased risk for ill-informed financial decisions, which can result in increased stress and anxiety and a lower quality of life. Furthermore, financial concerns impact physicians' specialty selections and may partly explain the scarcity of primary care practitioners.

Embryo classification beyond pregnancy: early prediction of first trimester miscarriage using machine learning.

Purpose: First trimester miscarriage is a major concern in IVF-ET treatments, accounting for one out of nine clinical pregnancies and for up to one out of three recognized pregnancies. To develop a machine learning classifier for predicting the risk of cleavage-stage embryos to undergo first trimester miscarriage based on time-lapse images of preimplantation development.

Methods: Retrospective study of a 4-year multi-center cohort of 391 women undergoing intra-cytoplasmatic sperm injection (ICSI) and fresh single or double embryo transfers.

CD8 + T cell memory is sustained in mice by hepatic stellate cells.

Background And Aims: Long-lasting immunological memory is the ultimate goal of vaccination. Homeostatic maintenance of memory CD8 + cytotoxic T cells (MemCD8TCs) is thought to be mediated by IL-15/IL-15R heterodimer (15HD)-expressing myeloid cells. Nonmyeloid hepatic stellate cells (HSCs) also express 15HD, but their role in maintaining MemCD8TC homeostasis is unknown.

High Levels of Progesterone Receptor B in MCF-7 Cells Enable Radical Anti-Tumoral and Anti-Estrogenic Effect of Progestin.

The widely reported conflicting effects of progestin on breast cancer suggest that the progesterone receptor (PR) has dual functions depending on the cellular context. Cell models that enable PR to fully express anti-tumoral properties are valuable for the understanding of molecular determinant(s) of the anti-tumoral property. This study evaluated whether the expression of high levels of PR in MCF-7 cells enabled a strong anti-tumoral response to progestin.

Tetratricopeptide repeat domain 9A knockout induces social anxiety and impairs offense behaviors in female mice.

Objectives: The involvement of tetratricopeptide repeat domain 9A (TTC9A) in anxiety-like behaviors through estrogen action has been reported in female mice, this study further investigated its effects on social anxiety and aggressive behaviors.

Materials And Smethods: Using female Ttc9a knockout () mice, the role of TTC9A in anxiety was investigated in non-social and social environments through home-cage emergence and social interaction tests, respectively, whereas aggressive behaviors were examined under the female intruder test.

Results: We observed significant social behavioral deficits with pronounced social and non-social anxiogenic phenotypes in female mice.

The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: a systematic review and meta-analysis.

Study Question: Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles?

Summary Answer: The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes.

What Is Known Already: There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently.

Study Design, Size, Duration: A systematic review with meta-analysis was performed.

Pseudo contrastive labeling for predicting IVF embryo developmental potential.

In vitro fertilization is typically associated with high failure rates per transfer, leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points.

Fluid-Driven Traveling Waves in Soft Robots.

Many marine creatures, gastropods, and earthworms generate continuous traveling waves in their bodies for locomotion within marine environments, complex surfaces, and inside narrow gaps. In this work, we study theoretically and experimentally the use of embedded pneumatic networks as a mechanism to mimic nature and generate bidirectional traveling waves in soft robots. We apply long-wave approximation to theoretically calculate the required distribution of pneumatic network and inlet pressure oscillations needed to create desired moving wave patterns.

Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape.

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs.

Helical Klinotactic Locomotion of Two-Link Nanoswimmers with Dual-Function Drug-Loaded Soft Polysaccharide Hinges.

Inspired by the movement of bacteria and other microorganisms, researchers have developed artificial helical micro- and nanorobots that can perform corkscrew locomotion or helical path swimming under external energy actuation. In this paper, for the first time the locomotion of nonhelical multifunctional nanorobots that can swim in helical klinotactic trajectories, similarly to rod-shaped bacteria, under rotating magnetic fields is investigated. These nanorobots consist of a rigid ferromagnetic nickel head connected to a rhodium tail by a flexible hydrogel-based hollow hinge composed of chemically responsive chitosan and alginate multilayers.

EDP-938, a novel nucleoprotein inhibitor of respiratory syncytial virus, demonstrates potent antiviral activities in vitro and in a non-human primate model.

EDP-938 is a novel non-fusion replication inhibitor of respiratory syncytial virus (RSV). It is highly active against all RSV-A and B laboratory strains and clinical isolates tested in vitro in various cell lines and assays, with half-maximal effective concentrations (EC50s) of 21, 23 and 64 nM against Long (A), M37 (A) and VR-955 (B) strains, respectively, in the primary human bronchial epithelial cells (HBECs). EDP-938 inhibits RSV at a post-entry replication step of the viral life cycle as confirmed by time-of-addition study, and the activity appears to be mediated by viral nucleoprotein (N).

Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth.

Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation.