sc-SPLASH provides ultra-efficient reference-free discovery in barcoded single-cell sequencing.

Typical high-throughput single-cell RNA-sequencing (scRNA-seq) analyses are primarily conducted by (pseudo)alignment, through the lens of annotated gene models, and aimed at detecting differential gene expression. This misses diversity generated by other mechanisms that diversify the transcriptome such as splicing and V(D)J recombination, and is blind to sequences missing from imperfect reference genomes. Here, we present sc-SPLASH, a highly efficient pipeline that extends our SPLASH framework for statistics-first, reference-free discovery to barcoded scRNA-seq (10x Chromium) and spatial transcriptomics (10x Visium); we also provide its optimized module for preprocessing and -mer counting in barcoded data, BKC, as a standalone tool.

Using intrahost single nucleotide variant data to predict SARS-CoV-2 detection cycle threshold values.

Over the last four years, each successive wave of the COVID-19 pandemic has been caused by variants with mutations that improve the transmissibility of the virus. Despite this, we still lack tools for predicting clinically important features of the virus. In this study, we show that it is possible to predict the PCR cycle threshold (Ct) values from clinical detection assays using sequence data.

Integrative genomic, virulence, and transcriptomic analysis of emergent subspecies (SDSE) type isolates causing human infections.

Unlabelled: subspecies (SDSE) is a Gram-positive bacterial pathogen that infects humans and is closely related to group A streptococcus (GAS). Compared with GAS, far less is known about SDSE pathobiology. Increased rates of invasive SDSE infections have recently been reported in many countries.

ICESp1109, a novel hybrid Integrative Conjugative Element of macrolide-resistant Streptococcus pyogenes serotype M77 collected between 2003 and 2017 in Poland.

Objectives: Genetic characterization of the antibiotic resistance determinants and associated mobile genetic elements (MGEs) among Streptococcus pyogenes [Group A streptococci (GAS)] clinical isolates of an M77 serotype collected in Poland between 2003 and 2017.

Methods: The genomes of 136 M77 GAS isolates were sequenced using Illumina, and selected with long-read approach (Oxford Nanopore). Whole genome sequences were analyzed to determine the presence of macrolide resistance determinants, and their genetic context.

Increase in invasive M1 infections with close evolutionary genetic relationship, Iceland and Scotland, 2022 to 2023.

Group A isolates of the recently described M1 clade have emerged to cause human infections in several European countries and elsewhere. Full-genome sequence analysis of M1 isolates discovered a close genomic relationship between some isolates from Scotland and the majority of isolates from Iceland causing serious infections in 2022 and 2023. Phylogenetic analysis strongly suggests that an isolate from or related to Scotland was the precursor to an M1 variant responsible for almost all recent M1 infections in Iceland.

Molecular profiling of sponge deflation reveals an ancient relaxant-inflammatory response.

A hallmark of animals is the coordination of whole-body movement. Neurons and muscles are central to this, yet coordinated movements also exist in sponges that lack these cell types. Sponges are sessile animals with a complex canal system for filter-feeding.

Micropulse cyclophotocoagulation compared to continuous wave cyclophotocoagulation for the management of refractory pediatric glaucoma.

Introduction: Micropulse cyclophotocoagulation (MPCPC) has been shown in adults to offer a favorable post-operative safety profile compared to continuous wave transscleral cyclophotocoagulation (CWCPC) in the management of glaucoma. The purpose of this study is to evaluate the long term efficacy, safety, and effectiveness of MPCPC in the management of pediatric glaucoma when compared to CWCPC.

Methods: IRB approved retrospective chart review of patients with pediatric glaucoma that underwent MPCPC and CWCPC at 2 separate institutions.

SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave.

Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence.

Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP).

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

Background: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19.

Objective: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups.

Design: Retrospective observational study utilizing electronic health record data from four health systems.

Molecular profiling of sponge deflation reveals an ancient relaxant-inflammatory response.

A hallmark of animals is the coordination of whole-body movement. Neurons and muscles are central to this, yet coordinated movements also exist in sponges that lack these cell types. Sponges are sessile animals with a complex canal system for filter-feeding.

Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories.

Pelagic larval stages are widespread across animals, yet it is unclear whether larvae were present in the last common ancestor of animals or whether they evolved multiple times due to common selective pressures. Many marine larvae are at least superficially similar; they are small, swim through the beating of bands of cilia, and sense the environment with an apical organ. To understand these similarities, we have generated single-cell atlases for marine larvae from two animal phyla and have compared their cell types.

Cross-phyla protein annotation by structural prediction and alignment.

Background: Protein annotation is a major goal in molecular biology, yet experimentally determined knowledge is typically limited to a few model organisms. In non-model species, the sequence-based prediction of gene orthology can be used to infer protein identity; however, this approach loses predictive power at longer evolutionary distances. Here we propose a workflow for protein annotation using structural similarity, exploiting the fact that similar protein structures often reflect homology and are more conserved than protein sequences.

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes.

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice.

Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes.

Design, Setting, And Participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah.

Analysis of the Genomics and Mouse Virulence of an Emergent Clone of Streptococcus dysgalactiae Subspecies .

Streptococcus dysgalactiae subsp. is a bacterial pathogen that is increasingly recognized as a cause of severe human infections. Much less is known about the genomics and infection pathogenesis of S.

Prospective Long-term Health-related Quality of Life Outcomes After Surgery, Radiotherapy, or Active Surveillance for Localized Prostate Cancer.

Background: Localized prostate cancer (PCa) treatment is associated with reduced health-related quality of life (HRQoL). Current literature is limited by short-term follow-up.

Objective: To prospectively evaluate the 5-yr HRQoL outcomes in men undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), or active surveillance (AS).

SARS-CoV-2 Omicron (B.1.1.529) Infection of Wild White-Tailed Deer in New York City.

There is mounting evidence of SARS-CoV-2 spillover from humans into many domestic, companion, and wild animal species. Research indicates that humans have infected white-tailed deer, and that deer-to-deer transmission has occurred, indicating that deer could be a wildlife reservoir and a source of novel SARS-CoV-2 variants. We examined the hypothesis that the Omicron variant is actively and asymptomatically infecting the free-ranging deer of New York City.

Genome-Wide Transposon Mutagenesis Screens Identify Group A Streptococcus Genes Affecting Susceptibility to β-Lactam Antibiotics.

Group A streptococcus (GAS) is a Gram-positive human bacterial pathogen responsible for more than 700 million infections annually worldwide. Beta-lactam antibiotics are the primary agents used to treat GAS infections. Naturally occurring GAS clinical isolates with decreased susceptibility to beta-lactam antibiotics attributed to mutations in PBP2X have recently been documented.

The effect of race on treatment patterns and subsequent health-related quality of life outcomes in men undergoing treatment for localized prostate cancer.

Introduction: Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT).

Methods: Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified.

Characterization of M-Type-Specific Pilus Expression in Group A Streptococcus.

In addition to providing a typing mechanism for group A Streptococcus (GAS) isolates (T typing), cell surface pilus production impacts GAS virulence characteristics, including adherence and immune evasion. The pilus biosynthesis genes are located in the fibronectin- and collagen-binding T-antigen (FCT) region of the genome, and nine different FCT types, encoding more than 20 different T types, have been described. GAS isolates are not uniform in their degree or pattern of pilus expression, as highlighted by pilus production being thermoregulated in isolates that harbor the FCT-type FCT-3 (e.

Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance.

The COVID-19 pandemic has resulted in extensive surveillance of the genomic diversity of SARS-CoV-2. Sequencing data generated as part of these efforts can also capture the diversity of the SARS-CoV-2 virus populations replicating within infected individuals. To assess this within-host diversity of SARS-CoV-2 we quantified low frequency (minor) variants from deep sequence data of thousands of clinical samples collected by a large urban hospital system over the course of a year.

Crustacean leg regeneration restores complex microanatomy and cell diversity.

Animals can regenerate complex organs, yet this process frequently results in imprecise replicas of the original structure. In the crustacean , embryonic and regenerating legs differ in gene expression dynamics but produce apparently similar mature structures. We examine the fidelity of leg regeneration using complementary approaches to investigate microanatomy, sensory function, cellular composition, and cell molecular profiles.

Impact of camphor on the in vitro mixed ruminal microorganism fermentation from goats selected for consumption of low and high levels of spp. 1.

Encroaching plant species in West Texas continues to significantly reduce livestock production capacity and cause an imbalance between plant and livestock ecology. and are encroaching species rarely used by browsing animals, mainly due to phytochemical defenses. spp.