The Microbiome: From the Beginning to the End.

The human microbiota, a community of microorganisms in our bodies, is crucial for our health. This paper explores its development from birth through old age, highlighting some of the unique roles at key life stages-infancy, adulthood, and in the elderly years. Understanding the significant health impacts and consequences of changes in the microbiota offers insights for both the public and clinicians.

Online public response to emergency department diagnostic error report: A qualitative study.

Background: The 2022 study on diagnostic error in the emergency department (ED) published by the Agency for Healthcare Research and Quality (AHRQ) reported that one in every 18 ED patients is misdiagnosed. The report was methodologically critiqued by emergency physicians and researchers. However, little is known about public perception of error in the ED.

Distant relatives of a eukaryotic cell-specific toxin family evolved a complement-like mechanism to kill bacteria.

Cholesterol-dependent cytolysins (CDCs) comprise a large family of pore-forming toxins produced by Gram-positive bacteria, which are used to attack eukaryotic cells. Here, we functionally characterize a family of 2-component CDC-like (CDCL) toxins produced by the Gram-negative Bacteroidota that form pores by a mechanism only described for the mammalian complement membrane attack complex (MAC). We further show that the Bacteroides CDCLs are not eukaryotic cell toxins like the CDCs, but instead bind to and are proteolytically activated on the surface of closely related species, resulting in pore formation and cell death.

Bacterial cholesterol-dependent cytolysins and their interaction with the human immune response.

Purpose Of Review: Many cholesterol-dependent cytolysin (CDC)-producing pathogens pose a significant threat to human health. Herein, we review the pore-dependent and -independent properties CDCs possess to assist pathogens in evading the host immune response.

Recent Findings: Within the last 5 years, exciting new research suggests CDCs can act to inhibit important immune functions, disrupt critical cell signaling pathways, and have tissue-specific effects.

ISG15/USP18/STAT2 is a molecular hub regulating IFN I-mediated control of Dengue and Zika virus replication.

The establishment of a virus infection is the result of the pathogen's ability to replicate in a hostile environment generated by the host's immune system. Here, we found that ISG15 restricts Dengue and Zika viruses' replication through the stabilization of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signaling.

A sentiment analysis on online psychiatrist reviews to identify clinical attributes of psychiatrists that shape the therapeutic alliance.

Background: While online reviews from physician rating websites are increasingly utilized by healthcare providers to better understand patient needs, it remains difficult to objectively identify areas for improvement in providing psychiatric care.

Objectives: To quantitatively characterize the sentiment of online written reviews of psychiatrists to determine clinical attributes that can be strengthened to improve psychiatrists' therapeutic alliance with their patients.

Materials And Methods: Sentiment scores of 6,400 written reviews of 400 US-based psychiatrists on a US-based online physician rating website were obtained through a natural-language-processing-based sentiment analysis.

Manipulation by Plasmodium Parasites of Anopheles Mosquito Behavior and Human Odors.

Purpose: The phenomenon of parasites manipulating host phenotypes is well documented; the best-known examples are manipulations of host behavior. More recently, there has been interest in whether parasites can manipulate host odor phenotypes to enhance their attractiveness to vectors. We review here evidence that Plasmodium-infected mosquitoes have enhanced attraction to human hosts, especially when the parasite is sufficiently developed to be transmissible.

Cross-modal attention for multi-modal image registration.

In the past few years, convolutional neural networks (CNNs) have been proven powerful in extracting image features crucial for medical image registration. However, challenging applications and recent advances in computer vision suggest that CNNs are limited in their ability to understand the spatial correspondence between features, which is at the core of image registration. The issue is further exaggerated when it comes to multi-modal image registration, where the appearances of input images can differ significantly.

The association of sexual orientation with prostate, breast, and cervical cancer screening and diagnosis.

Purpose: Data on heterogeneity in cancer screening and diagnosis rates among lesbians/gays and bisexuals (LGBs) is lacking. Recent studies showed that LGBs have decreased healthcare utilization compared to heterosexual counterparts. Few studies have examined how sexual orientation impacts cancer screening and prevalence.

Artificial Intelligence in Kidney Cancer.

Artificial intelligence is rapidly expanding into nearly all facets of life, particularly within the field of medicine. The diagnosis, characterization, management, and treatment of kidney cancer is ripe with areas for improvement that may be met with the promises of artificial intelligence. Here, we explore the impact of current research work in artificial intelligence for clinicians caring for patients with renal cancer, with a focus on the perspectives of radiologists, pathologists, and urologists.

Polar transform network for prostate ultrasound segmentation with uncertainty estimation.

Automatic and accurate prostate ultrasound segmentation is a long-standing and challenging problem due to the severe noise and ambiguous/missing prostate boundaries. In this work, we propose a novel polar transform network (PTN) to handle this problem from a fundamentally new perspective, where the prostate is represented and segmented in the polar coordinate space rather than the original image grid space. This new representation gives a prostate volume, especially the most challenging apex and base sub-areas, much denser samples than the background and thus facilitate the learning of discriminative features for accurate prostate segmentation.

Shadow-Consistent Semi-Supervised Learning for Prostate Ultrasound Segmentation.

Prostate segmentation in transrectal ultrasound (TRUS) image is an essential prerequisite for many prostate-related clinical procedures, which, however, is also a long-standing problem due to the challenges caused by the low image quality and shadow artifacts. In this paper, we propose a Shadow-consistent Semi-supervised Learning (SCO-SSL) method with two novel mechanisms, namely shadow augmentation (Shadow-AUG) and shadow dropout (Shadow-DROP), to tackle this challenging problem. Specifically, Shadow-AUG enriches training samples by adding simulated shadow artifacts to the images to make the network robust to the shadow patterns.

A Cascaded Deep Learning-Based Artificial Intelligence Algorithm for Automated Lesion Detection and Classification on Biparametric Prostate Magnetic Resonance Imaging.

Rationale And Objectives: Prostate MRI improves detection of clinically significant prostate cancer; however, its diagnostic performance has wide variation. Artificial intelligence (AI) has the potential to assist radiologists in the detection and classification of prostatic lesions. Herein, we aimed to develop and test a cascaded deep learning detection and classification system trained on biparametric prostate MRI using PI-RADS for assisting radiologists during prostate MRI read out.

Prostate-specific Antigen Testing in Men with Disabilities: A Cross-sectional Analysis of the Health Information National Trends Survey.

Background: Patients with disabilities represent a unique minority population. The incidence of prostate-specific antigen (PSA) testing among this population is unknown.

Objective: To compare PSA testing rates and associated predictors among men with and without reported disabilities in the USA.

Is There a Role for Prone Computed Tomography Before Percutaneous Nephrolithotomy?

The majority of percutaneous nephrolithotomies (PCNLs) are performed prone, whereas most preoperative CT scans are done supine. The purpose of this pilot study is to determine if there is utility of prone CT scans in preoperative planning for prone PCNL by identifying patient populations at risk for organ injury and tract length-related complications. To represent typical preoperative planning using CT, two-dimensional (2D)-axial-prone/supine percutaneous tract measurements were performed by minimizing the distance from the target calix to the posterior-lateral skin in a single axial plane.

Clinically Advanced Pheochromocytomas and Paragangliomas: A Comprehensive Genomic Profiling Study.

Patients with clinically advanced paragangliomas (CA-Para) and pheochromocytomas (CA-Pheo) have limited surgical or systemic treatments. We used comprehensive genomic profiling (CGP) to compare genomic alterations (GA) in CA-Para and CA-Pheo to identify potential therapeutic targets. Eighty-three CA-Para and 45 CA-Pheo underwent hybrid-capture-based CGP using a targeted panel of 324 genes.

Anti-CD19 CAR T Cells That Secrete a Biparatopic Anti-CLEC12A Bridging Protein Have Potent Activity Against Highly Aggressive Acute Myeloid Leukemia and .

Refractory acute myeloid leukemia (AML) remains an incurable malignancy despite the clinical use of novel targeted therapies, new antibody-based therapies, and cellular therapeutics. Here, we describe the preclinical development of a novel cell therapy that targets the antigen CLEC12A with a biparatopic bridging protein. Bridging proteins are designed as "CAR-T cell engagers," with a CAR-targeted protein fused to antigen binding domains derived from antibodies.

Comprehensive genomic profiling of histologic subtypes of urethral carcinomas.

Background: Carcinoma of the urethra (UrthCa) is an uncommon Genitourinary (GU) malignancy that can progress to advanced metastatic disease.

Methods: One hundred twenty-seven metastatic UrthCa underwent hybrid capture-based comprehensive genomic profiling to evaluate all classes of genomic alterations (GA). Tumor mutational burden was determined on up to 1.

Harnessing clinical annotations to improve deep learning performance in prostate segmentation.

Purpose: Developing large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets.

Materials And Methods: We used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients).

Semi-enzymatic synthesis of pseudouridine.

Modifications of RNA molecules have a significant effect on their structure and function. One of the most common modifications is the isomerization from uridine to pseudouridine. Despite its prevalence in natural RNA sequences, organic synthesis of pseudouridine has been challenging because of the stereochemistry requirement and the sensitivity of reaction steps to moisture.

Rapidly Progressing Urothelial Carcinoma Due to a Rare TP53 (p.Arg110Pro) Mutation: A Case Report and Review of the Literature.

We present a case of a 69-year-old male patient diagnosed with high grade (T HG) urothelial carcinoma of the bladder who progressed rapidly towards muscle invasive disease and eventually death despite neoadjuvant chemotherapy and radical cystectomy. We postulate that this may be due to a deleterious underlying somatic gene mutation. Molecular pathologic data obtained on the initial, non-muscle invasive tumor and the final cystectomy specimen, revealed the same TP53 mutation (p.

Comprehensive genomic profiling of metastatic collecting duct carcinoma, renal medullary carcinoma, and clear cell renal cell carcinoma.

Introduction And Objective: Unlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.

Material And Methods: DNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626).

Risk of adverse pathology at prostatectomy in the era of MRI and targeted biopsies; rethinking active surveillance for intermediate risk prostate cancer patients.

Purpose: Men with intermediate risk (IR) prostate cancer (CaP) are often excluded from active surveillance (AS) due to higher rates of adverse pathology (AP). We determined our rate of AP in men who underwent multiparametric MRI (MpMRI) with combined biopsy (CB) consisting of targeted biopsy (TB) and systematic biopsy (SB) prior to radical prostatectomy (RP).

Methods: A retrospective review was conducted of men with Gleason Grade Group (GG) 2 disease who underwent RP after SB alone or after preoperative MRI with CB.