Naive state

In December 2021, long-acting injectable pre-exposure prophylaxis (LAI-PrEP) was approved for the prevention of HIV in at-risk adults and adolescents. LAI-PrEP may address adherence issues of daily oral daily PrEP and PrEP stigma. However, studies assessing LAI-PrEP willingness among PrEP naive Black and Hispanic sexual and gender minority (SGM) persons- a group disproportionately impacted by the HIV epidemic in the United States - is rare. To assess the extent of and characteristics of willingness to use LAI-PrEP in a national sample of Black and Hispanic SGM who are self-reported that they have never used PrEP...

OBJECTIVE: To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US). BACKGROUND: Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US. METHODS: A retrospective, cross-sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt-in online survey that identified respondents (aged ≥18 years) in the US with self-reported physician-diagnosed migraine...

BACKGROUND: Although dopaminergic disturbances are well-known in schizophrenia, the understanding of dopamine-related brain dynamics remains limited. This study investigates the dynamic coactivation patterns (CAPs) associated with the substantia nigra (SN), a key dopaminergic nucleus, in first-episode treatment-naïve patients with schizophrenia (FES). METHODS: Resting-state fMRI data were collected from 84 FES and 94 healthy controls (HCs). Frame-wise clustering was implemented to generate CAPs related to SN activation or deactivation...

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus...

In this study, a three-layered multicenter ONIOM approach is implemented to characterize the naive folding pathway of bovine pancreatic trypsin inhibitor (BPTI). Each layer represents a distinct level of theory, where the initial layer, encompassing the entire protein, is modeled by a general all-atom force-field GFN-FF. An intermediate electronic structure layer consisting of three multicenter fragments is introduced with the state-of-the-art semiempirical tight-binding method GFN2- x TB. Higher accuracy, specifically addressing the breaking and formation of the three disulfide bonds, is achieved at the innermost layer using the composite DFT method r2 SCAN-3c...

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes...

After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples...

There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status...

The structural organization of eukaryotic genomes is contingent upon the fractionation of DNA into transcriptionally active euchromatin and repressive heterochromatin. However, we have a limited understanding of how these distinct states are first established during animal embryogenesis. Histone 3 lysine 9 trimethylation (H3K9me3) is critical to heterochromatin formation and bulk establishment of this mark is thought to help drive large-scale remodeling of an initially naive chromatin state during animal embryogenesis...

The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells...

OBJECTIVE: To examine the association of prescription opioid fills over the year prior to surgery with postoperative outcomes. BACKGROUND: Nearly one third of patients report opioid use in the year preceding surgery, yet an understanding of how opioid exposure influences patient-reported outcomes after surgery remains incomplete. Therefore, this study was designed to test the hypothesis that preoperative opioid exposure may impede recovery in the postoperative period...

BACKGROUND: Previous preclinical studies have demonstrated sex-specific alterations in the gut microbiome following traumatic injury or sepsis alone; however, the impact of host sex on dysbiosis in the setting of postinjury sepsis acutely is unknown. We hypothesized that multicompartmental injury with subsequent pneumonia would result in host sex-specific dysbiosis. METHODS: Male and proestrus female Sprague-Dawley rats (n = 8/group) were subjected to either polytrauma (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), PT plus 2-hours daily restraint stress (PT/RS), PT with postinjury day 1 pseudomonas aeruginosa pneumonia (PT + PNA), PT/RS with pneumonia (PT/RS + PNA), or naive controls...

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are derived from pre- and post-implantation embryos, representing the initial "naïve" and final "primed" states of pluripotency, respectively. In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580. The rPSCs exhibited domed clones and expressed key pluripotency genes, with both X chromosomes active in female cells...

PURPOSE: Depth estimation in robotic surgery is vital in 3D reconstruction, surgical navigation and augmented reality visualization. Although the foundation model exhibits outstanding performance in many vision tasks, including depth estimation (e.g., DINOv2), recent works observed its limitations in medical and surgical domain-specific applications. This work presents a low-ranked adaptation (LoRA) of the foundation model for surgical depth estimation. METHODS: We design a foundation model-based depth estimation method, referred to as Surgical-DINO, a low-rank adaptation of the DINOv2 for depth estimation in endoscopic surgery...

Genomes encode for genes and non-coding DNA, both capable of transcriptional activity. However, unlike canonical genes, many transcripts from non-coding DNA have limited evidence of conservation or function. Here, to determine how much biological noise is expected from non-genic sequences, we quantify the regulatory activity of evolutionarily naive DNA using RNA-seq in yeast and computational predictions in humans. In yeast, more than 99% of naive DNA bases were transcribed. Unlike the evolved transcriptome, naive transcripts frequently overlapped with opposite sense transcripts, suggesting selection favored coherent gene structures in the yeast genome...

Despite the fact that there is a remarkable achievement on multifocus image fusion, most of the existing methods only generate a low-resolution image if the given source images suffer from low resolution. Obviously, a naive strategy is to independently conduct image fusion and image super-resolution. However, this two-step approach would inevitably introduce and enlarge artifacts in the final result if the result from the first step meets artifacts. To address this problem, in this article, we propose a novel method to simultaneously achieve image fusion and super-resolution in one framework, avoiding step-by-step processing of fusion and super-resolution...

Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical interventions have remained elusive. The heterogeneous nature of the primary tumor of origin, complications in drug delivery across the blood-brain barrier, and the distinct microenvironment collectively pose formidable clinical challenges in developing new treatments for patients with brain metastasis. Although current preclinical models have deepened our basic understanding of the disease, much of the existing research on brain metastasis has employed a reductionist approach...

One of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naive pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naive protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent hypoxic growth conditions as required by naive hESCs, in which some RSeT cells (e.g., H1 cells) exhibit much lower single cell plating efficiency, having altered or much retarded cell growth under both normoxia and hypoxia...

Quiescence in stem cells is traditionally considered as a state of inactive dormancy or with poised potential. Naive mouse embryonic stem cells (ESCs) can enter quiescence spontaneously or upon inhibition of MYC or fatty acid oxidation, mimicking embryonic diapause in vivo. The molecular underpinning and developmental potential of quiescent ESCs (qESCs) are relatively unexplored. Here we show that qESCs possess an expanded or unrestricted cell fate, capable of generating both embryonic and extraembryonic cell types (e...

BACKGROUND: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge...