Are Positive Biopsy Margins in Melanoma Significant?: A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

Background: Presence of positive biopsy margins in melanoma can provoke anxiety over potential disease progression from delays to surgical excision, but their impact on outcomes is unknown. We aimed to compare the presence of residual melanoma in the surgical excision specimen and survival between patients with negative, microscopically positive, and macroscopically positive biopsy margins.

Methods: Patients with cutaneous melanoma who underwent surgical excision over a 13-year period were included.

An intron endonuclease facilitates interference competition between coinfecting viruses.

Introns containing homing endonucleases are widespread in nature and have long been assumed to be selfish elements that provide no benefit to the host organism. These genetic elements are common in viruses, but whether they confer a selective advantage is unclear. In this work, we studied intron-encoded homing endonuclease gp210 in bacteriophage ΦPA3 and found that it contributes to viral competition by interfering with the replication of a coinfecting phage, ΦKZ.

A mobile intron facilitates interference competition between co-infecting viruses.

Mobile introns containing homing endonucleases are widespread in nature and have long been assumed to be selfish elements that provide no benefit to the host organism. These genetic elements are common in viruses, but whether they confer a selective advantage is unclear. Here we studied a mobile intron in bacteriophage ΦPA3 and found its homing endonuclease gp210 contributes to viral competition by interfering with the virogenesis of co-infecting phage ΦKZ.

Prioritizing Melanoma Surgeries to Prevent Wait Time Delays and Upstaging of Melanoma during the COVID-19 Pandemic.

Prompt diagnosis and surgical management of melanoma strongly impact prognosis. Considering the limited resources, emergency closures, and staffing shortages during the COVID-19 pandemic in Canada, our institution implemented a dedicated care pathway to prioritize cancer surgeries. We aim to assess whether this strategy was effective at preventing surgical wait time delays and upstaging of melanoma.

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study.

Objective: Ustekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness of ustekinumab in UC in a real-world setting.

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage.

To protect themselves from the constant threat of bacteriophage (phage) infection, bacteria have evolved diverse immune systems including restriction-modification, CRISPR-Cas, and many others. Here, we describe the discovery of a two-protein transcriptional regulator module associated with hundreds of CBASS immune systems and demonstrate that this module drives the expression of its associated CBASS system in response to DNA damage. We show that the helix-turn-helix transcriptional repressor CapH binds the promoter region of its associated CBASS system to repress transcription until it is cleaved by the metallopeptidase CapP.

Structure and activity of a bacterial defense-associated 3'-5' exonuclease.

The widespread CBASS (cyclic oligonucleotide-based anti-phage signaling system) immune systems in bacteria protect their hosts from bacteriophage infection by triggering programmed cell death. CBASS systems all encode a cyclic oligonucleotide synthase related to eukaryotic cGAS but use diverse regulators and effector proteins including nucleases, phospholipases, and membrane-disrupting proteins to effect cell death. Cap18 is a predicted 3'-5' exonuclease associated with hundreds of CBASS systems, whose structure, biochemical activities, and biological roles remain unknown.

Control of bacterial immune signaling by a WYL domain transcription factor.

Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how they are regulated to avoid cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW.

Perceptions of using infographics for scientific communication on social media for COVID-19 topics: a survey study.

Navigating for accurate information, especially health- and science-related content, on social media has been challenging during the COVID-19 pandemic. Although infographics are a popular medium for simplifying text-based information into visual components, their usefulness during a global health crisis has not been explored. The study aims to explore the perceptions of infographics in conveying scientific information related to COVID-19 on social media.

Evidence-based lifestyle medicine interventions to enhance the mental health of law enforcers in Hong Kong: A pilot randomized controlled trial.

Law enforcers are stressed, but they may be reluctant to seek psychological support due to the stigmatization of mental illness in the law enforcement culture. Given the relatively stigma-free lifestyle medicine intervention, a two-arm pilot randomized controlled trial was conducted in the Hong Kong police force to examine the efficacy of integrated lifestyle medicine practices in enhancing the mental health of law enforcers. A total of 18 participants were randomly assigned to the intervention and waitlist control groups.

Predictors of self-monitoring of blood glucose among noninsulin-treated patients with type 2 diabetes in a primary care setting in Hong Kong: A cross-sectional study.

Objectives: The current study aimed to examine the relationship between patient characteristics (internal psychological, external psychological, internal physical, external physical, and educational) and self-monitoring of blood glucose among noninsulin-treated patients with type 2 diabetes in a local primary care setting.

Methods: This was a cross-sectional study, in which data were collected by a structured questionnaire. Correlational and multivariate multiple regression analyses were performed.

Biallelic inheritance in a single Pakistani family with intellectual disability implicates new candidate gene RDH14.

In a multi-branch family from Pakistan, individuals presenting with palmoplantar keratoderma segregate in autosomal dominant fashion, and individuals with intellectual disability (ID) segregate in apparent autosomal recessive fashion. Initial attempts to identify the ID locus using homozygosity-by-descent (HBD) mapping were unsuccessful. However, following an assumption of locus heterogeneity, a reiterative HBD approach in concert with whole exome sequencing (WES) was employed.

Genomics, Exometabolomics, and Metabolic Probing Reveal Conserved Proteolytic Metabolism of and Three Candidate Species From China and Japan.

JAD2, the only cultured representative of the order , is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing " Thermoflexus japonica," " Thermoflexus tengchongensis," and " Thermoflexus sinensis.

Pannexin 1 mutation found in melanoma tumor reduces phosphorylation, glycosylation, and trafficking of the channel-forming protein.

Pannexin 1 (PANX1) is a glycoprotein that forms large pore channels capable of passing ions and metabolites such as ATP for cellular communication. PANX1 has been implicated in many diseases including breast cancer and melanoma, where inhibition or deletion of PANX1 reduced the tumorigenic and metastatic properties of the cancer cells. We interrogated the effect of single amino acid changes in various PANX1 domains using naturally occurring variants reported in cancer patient tumors.

Gastrointestinal Surgery for Inflammatory Bowel Disease Persistently Lowers Microbiome and Metabolome Diversity.

Background: Many studies have investigated the role of the microbiome in inflammatory bowel disease (IBD), but few have focused on surgery specifically or its consequences on the metabolome that may differ by surgery type and require longitudinal sampling. Our objective was to characterize and contrast microbiome and metabolome changes after different surgeries for IBD, including ileocolonic resection and colectomy.

Methods: The UC San Diego IBD Biobank was used to prospectively collect 332 stool samples from 129 subjects (50 ulcerative colitis; 79 Crohn's disease).

HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity.

Bacteria are continually challenged by foreign invaders, including bacteriophages, and have evolved a variety of defenses against these invaders. Here, we describe the structural and biochemical mechanisms of a bacteriophage immunity pathway found in a broad array of bacteria, including E. coli and Pseudomonas aeruginosa.

Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.

Bacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer.

The Effects of Acoustic Variation on the Perception of Lexical Tone in Cantonese-Speaking Congenital Amusics.

Purpose Congenital amusia is an inborn neurogenetic disorder of fine-grained pitch processing. This study attempted to pinpoint the impairment mechanism of speech processing in tonal language speakers with amusia. We designed a series of perception tasks aiming at selectively probing low-level pitch processing and relatively high-level phonological processing of lexical tones, with an aim to illuminate the deficiency mechanism underlying tone perception in amusia.

Web of microbes (WoM): a curated microbial exometabolomics database for linking chemistry and microbes.

Background: As microbiome research becomes increasingly prevalent in the fields of human health, agriculture and biotechnology, there exists a need for a resource to better link organisms and environmental chemistries. Exometabolomics experiments now provide assertions of the metabolites present within specific environments and how the production and depletion of metabolites is linked to specific microbes. This information could be broadly useful, from comparing metabolites across environments, to predicting competition and exchange of metabolites between microbes, and to designing stable microbial consortia.