bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the antispike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies
Authors: Zendt Mackenzie , Bustos Carrillo Fausto A. , Kelly Sophie , Saturday Taylor , DeGrange Maureen , Ginigeme Anita , Wu Lurline , Callier Viviane , Ortega-Villa Ana , Faust Mondreakest , Chang-Rabley Emma , Bugal Kara , Kenney Heather , Khil Pavel , Youn Jung-Ho , Osei Gloria , Regmi Pravesh , Anderson Victoria , Bosticardo Marita , Daub Janine , DiMaggio Thomas , Kreuzburg Samantha , Pala Francesca , Pfister Justina , Treat Jennifer , Ulrick Jean , Karkanitsa Maria , Kalish Heather , Kuhns Douglas B. , Priel Debra L. , Fink Danielle L. , Tsang John S. , Sparks Rachel , Uzel Gulbu , Waldman Meryl A. , Zerbe Christa S. , Delmonte Ottavia M. , Bergerson Jenna R. E. , Das Sanchita , Freeman Alexandra F. , Lionakis Michail S. , Sadtler Kaitlyn , van Doremalen Neeltje , Munster Vincent , Notarangelo Luigi D. , Holland Steven M. , Ricotta Emily E.
Published: October 2023

Research on coronavirus disease 2019 vaccination in immune-deficient/disordered people (IDP) has focused on cancer and organ transplantation populations. In a prospective cohort of 195 IDP and 35 healthy volunteers (HV), antispike immunoglobulin G (IgG) was detected in 88% of IDP after dose 2, increasing to 93% by 6 months after dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed one-third that of HV. IgG binding to Omicron BA.1 was lowest among variants. Angiotensin-converting enzyme 2 pseudo-neutralization only modestly correlated with antispike IgG concentration. IgG levels were not significantly altered by receipt of different messenger RNA–based vaccines, immunomodulating treatments, and prior severe acute respiratory syndrome coronavirus 2 infections. While our data show that three doses of coronavirus disease 2019 vaccinations induce antispike IgG in most IDP, additional doses are needed to increase protection. Because of the notably reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population.
Early sea ice decline off East Antarctica at the last glacial–interglacial climate transition
Authors: Sadatzki Henrik , Opdyke Bradley , Menviel Laurie , Leventer Amy , Hope Janet M. , Brocks Jochen J. , Fallon Stewart , Post Alexandra L. , O’Brien Philip E. , Grant Katharine , Armand Leanne
Published: October 2023

Antarctic climate warming and atmospheric CO
2
rise during the last deglaciation may be attributed in part to sea ice reduction in the Southern Ocean. Yet, glacial–interglacial Antarctic sea ice dynamics and underlying mechanisms are poorly constrained, as robust sea ice proxy evidence is sparse. Here, we present a molecular biomarker-based sea ice record that resolves the spring/summer sea ice variability off East Antarctica during the past 40 thousand years (ka). Our results indicate that substantial sea ice reduction culminated rapidly and contemporaneously with upwelling of carbon-enriched waters in the Southern Ocean at the onset of the last deglaciation but began at least ~2 ka earlier probably driven by an increasing local integrated summer insolation. Our findings suggest that sea ice reduction and associated feedbacks facilitated stratification breakup and outgassing of CO
2
in the Southern Ocean and warming in Antarctica but may also have played a leading role in initializing these deglacial processes in the Southern Hemisphere.
Nanofiber embedded bioinspired strong wet friction surface
Authors: Guo Yurun , Zhang Liwen , Wang Yan , Liang Jing , Liu Xiaolin , Jiang Yonggang , Jiang Lei , Chen Huawei
Published: October 2023

Robust and reversible wet attachments are important for medical engineering and wearable electronics. Although ultrastrong capillarity from interfacial nano-thick liquid bridges creates tree frog’s strong wet friction, its unstable nano-liquid characteristic challenges further wet friction enhancement. Here, unique hierarchical micro-nano fibrous pillars have been discovered on Chinese bush crickets exhibiting a robust wet friction ~3.8 times higher than tree frog’s bulk pillar. By introducing a nano-fibrous pillar array covered with thin films (NFPF), the pillar’s separation position switches from the rear to front side compared with bulk pillars, indicating the interfacial contact stress shifting from compressing to stretching. This largely decreases the interfacial separation stress to form more stable and larger nano-liquid bridges. The NFPF array with self-splitting of interfacial liquid and contact stress further guards such interfacial stress shifting to ensure a ~1.9 times friction enhancement. Last, the theories are established, and the applications on wearable electronics are validated.
Probiotic-guided CAR-T cells for solid tumor targeting
Authors: Vincent Rosa L. , Gurbatri Candice R. , Li Fangda , Vardoshvili Ana , Coker Courtney , Im Jongwon , Ballister Edward R. , Rouanne Mathieu , Savage Thomas , de los Santos-Alexis Kenia , Redenti Andrew , Brockmann Leonie , Komaranchath Meghna , Arpaia Nicholas , Danino Tal
Published: October 2023

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)–T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.
Transcriptomic diversity of cell types across the adult human brain
Authors: Siletti Kimberly , Hodge Rebecca , Mossi Albiach Alejandro , Lee Ka Wai , Ding Song-Lin , Hu Lijuan , Lönnerberg Peter , Bakken Trygve , Casper Tamara , Clark Michael , Dee Nick , Gloe Jessica , Hirschstein Daniel , Shapovalova Nadiya V. , Keene C. Dirk , Nyhus Julie , Tung Herman , Yanny Anna Marie , Arenas Ernest , Lein Ed S. , Linnarsson Sten
Published: October 2023

The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. Astrocytes and oligodendrocyte-lineage cells also exhibited regional diversity at multiple scales. The transcriptomic census of the entire human brain presented in this work provides a resource for understanding the molecular diversity of the human brain in health and disease.
Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Authors: Chartrand Thomas , Dalley Rachel , Close Jennie , Goriounova Natalia A. , Lee Brian R. , Mann Rusty , Miller Jeremy A. , Molnar Gabor , Mukora Alice , Alfiler Lauren , Baker Katherine , Bakken Trygve E. , Berg Jim , Bertagnolli Darren , Braun Thomas , Brouner Krissy , Casper Tamara , Csajbok Eva Adrienn , Dee Nick , Egdorf Tom , Enstrom Rachel , Galakhova Anna A. , Gary Amanda , Gelfand Emily , Goldy Jeff , Hadley Kristen , Heistek Tim S. , Hill DiJon , Jorstad Nik , Kim Lisa , Kocsis Agnes Katalin , Kruse Lauren , Kunst Michael , Leon Gabriela , Long Brian , Mallory Matthew , McGraw Medea , McMillen Delissa , Melief Erica J. , Mihut Norbert , Ng Lindsay , Nyhus Julie , Oláh Gáspár , Ozsvár Attila , Omstead Victoria , Peterfi Zoltan , Pom Alice , Potekhina Lydia , Rajanbabu Ramkumar , Rozsa Marton , Ruiz Augustin , Sandle Joanna , Sunkin Susan M. , Szots Ildiko , Tieu Michael , Toth Martin , Trinh Jessica , Vargas Sara , Vumbaco David , Williams Grace , Wilson Julia , Yao Zizhen , Barzo Pal , Cobbs Charles , Ellenbogen Richard G. , Esposito Luke , Ferreira Manuel , Gouwens Nathan W. , Grannan Benjamin , Gwinn Ryder P. , Hauptman Jason S. , Jarsky Tim , Keene C. Dirk , Ko Andrew L. , Koch Christof , Ojemann Jeffrey G. , Patel Anoop , Ruzevick Jacob , Silbergeld Daniel L. , Smith Kimberly , Sorensen Staci A. , Tasic Bosiljka , Ting Jonathan T. , Waters Jack , de Kock Christiaan P.J. , Mansvelder Huib D. , Tamas Gabor , Zeng Hongkui , Kalmbach Brian , Lein Ed S.
Published: October 2023

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.
Single-cell analysis of prenatal and postnatal human cortical development
Authors: Velmeshev Dmitry , Perez Yonatan , Yan Zihan , Valencia Jonathan E. , Castaneda-Castellanos David R. , Wang Li , Schirmer Lucas , Mayer Simone , Wick Brittney , Wang Shaohui , Nowakowski Tomasz Jan , Paredes Mercedes , Huang Eric J. , Kriegstein Arnold R.
Published: October 2023

We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.
A comparative atlas of single-cell chromatin accessibility in the human brain
Authors: Li Yang Eric , Preissl Sebastian , Miller Michael , Johnson Nicholas D. , Wang Zihan , Jiao Henry , Zhu Chenxu , Wang Zhaoning , Xie Yang , Poirion Olivier , Kern Colin , Pinto-Duarte Antonio , Tian Wei , Siletti Kimberly , Emerson Nora , Osteen Julia , Lucero Jacinta , Lin Lin , Yang Qian , Zhu Quan , Zemke Nathan , Espinoza Sarah , Yanny Anna Marie , Nyhus Julie , Dee Nick , Casper Tamara , Shapovalova Nadiya , Hirschstein Daniel , Hodge Rebecca D. , Linnarsson Sten , Bakken Trygve , Levi Boaz , Keene C. Dirk , Shang Jingbo , Lein Ed , Wang Allen , Behrens M. Margarita , Ecker Joseph R. , Ren Bing
Published: October 2023

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer’s disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.
A chlorophyll
c
synthase widely co-opted by phytoplankton
Authors: Jiang Yanyou , Cao Tianjun , Yang Yuqing , Zhang Huan , Zhang Jingyu , Li Xiaobo
Published: October 2023

Marine and terrestrial photosynthesis exhibit a schism in the accessory chlorophyll (Chl) that complements the function of Chl
a
: Chl
b
for green plants versus Chl
c
for most eukaryotic phytoplankton. The enzymes that mediate Chl
c
biosynthesis have long remained elusive. In this work, we identified the CHLC dioxygenase (Phatr3_J43737) from the marine diatom
Phaeodactylum tricornutum
as the Chl
c
synthase. The
chlc
mutants lacked Chl
c
, instead accumulating its precursors, and exhibited growth defects. In vitro, recombinant CHLC protein converted these precursors into Chl
c
, thereby confirming its identity. Phylogenetic evidence demonstrates conserved use of CHLC across phyla but also the existence of distinct Chl
c
synthases in different algal groups. Our study addresses a long-outstanding question with implications for both contemporary and ancient marine photosynthesis.
No U.S. shutdown, but dim outlook for science funding
Authors: Mervis Jeffrey
Published: October 2023

Congress faces strong pressure to hold down 2024 spending
Third retraction looms for superconductivity physicist
Authors: Garisto Dan
Published: October 2023

Ranga Dias’s co-authors request retraction after doubts cast on key data in blockbuster room-temperature claim
Sculptors of short light pulses win physics Nobel
Authors: Cho Adrian , Clery Daniel
Published: October 2023

Researchers share prize for attosecond laser flashes that capture the motion of electrons
In Science Journals
Authors: Grocholski Brent , Maroso Mattia , Yeston Jake S. , Ross Sarah H. , Lavine Marc S. , Hallberg Dorothy L. , Funk Michael A. , Vignieri Sacha , Alderton Gemma , Kelly Priscilla N. , Foley John F.
Published: October 2023

Highlights from the
Science
family of journals
In Other Journals
Authors: Seale Madeleine , Lopez Bianca , Simonti Corinne , McCartney Melissa , Lavine Marc S. , Fregoso Elisa Collado , Maroso Mattia
Published: October 2023

Editors’ selections from the current scientific literature
The bat man takes a stand
Authors: Stone Richard , Pérez Ortega Rodrigo
Published: October 2023

Mexican biologist Rodrigo Medellín Legorreta is fighting political headwinds to preserve his country’s natural heritage—and his own legacy
Groundhog Day
Authors: Thorp H. Holden
Published: October 2023

As a long-time academic and university administrator in the United States, I’ve attended more meetings than I can remember about what “counts” toward faculty hiring, promotion, tenure, and other rewards at institutions of higher education. These meetings always followed a similar pattern— and sadly, still do. A wise colleague referred to these meetings as “Groundhog Day,” after the movie about a single day that repeats over and over again. The process of assessing faculty success has not changed in about 70 years, despite a lot of talk to change things. Why can’t universities break out of these ossified patterns?
Plan to move Kew herbarium roils plant world
Authors: Stokstad Erik
Published: October 2023

Botanists say transferring specimens to distant site is unnecessary and will hamper research
Makers of tiny, tunable points of light win chemistry Nobel
Authors: Clery Daniel , Kean Sam
Published: October 2023

Researchers share award for developing quantum dots, which fluoresce in vivid colors determined by their size
In ‘proof of concept,’ CRISPR-edited chickens shrug off flu
Authors: Cohen Jon
Published: October 2023

Edits to one gene can’t completely stop infections, however
Risk-taking health agency places first bets
Authors: Kaiser Jocelyn
Published: October 2023

ARPA-H aims to be unlike NIH, director says
Case Commentary: An espresso, a free puppy, and multidrug-resistant
Campylobacter
Authors: Musick William L.
Published: October 2023

Campylobacter
species infections in immunocompromised patients have the potential to progress to bacteremia and other extra-intestinal diseases. There is a sparsity of robust data, including antibiotic susceptibility data for contemporary agents, upon which to base treatment decisions. Moreover, intrinsic antimicrobial resistance in
Campylobacter
spp. further limits treatment options. The current publication by Bonilla-Moreno et al. elaborates on this clinical dilemma through the development, treatment, and molecular investigation of the putative mechanisms of carbapenem resistance in an immunocompromised patient with
Campylobacter coli
bacteremia.
4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1
Authors: Ribó-Molina Pau , Weiss Hauke J. , Susma Balasubramanian , van Nieuwkoop Stefan , Persoons Leentje , Zheng Yunan , Ruzek Melanie , Daelemans Dirk , Fouchier Ron A. M. , O'Neill Luke A. J. , van den Hoogen Bernadette G.
Published: October 2023

In recent years, especially since the outbreak of the severe acute respiratory syndrome coronavirus 2 pandemic, the cell-permeable itaconate derivative 4-octyl itaconate (4-OI) has gained traction as a potential antiviral agent. Here, we demonstrate that 4-OI inhibits replication of multiple influenza A viruses (IAV) by restricting nuclear export of viral ribonucleoproteins, a key step in the IAV replication cycle. This nuclear retention is achieved by deactivation and subsequent degradation of chromosomal maintenance 1 protein (CRM1), also known as exportin 1 (XPO1), a host cell protein exploited by IAV during replication. 4-OI-mediated deactivation of CRM1 resulted in the accumulation of the IAV nucleoprotein, the Rev protein of feline immunodeficiency virus, as well as the natural CRM1 cargos p53 and p65, in the nucleus of treated cells. Further mechanism of action studies revealed that, similar to known CRM1 inhibitors, 4-OI modifies a key cysteine in the cargo binding pocket of CRM1 at position 528 through an alkylation reaction called 2,3-dicarboxypropylation. Subsequent studies in a cell line in which the cysteine at position 528 in CRM1 protein was substituted by a serine confirmed that modification of this residue was indeed the cause for the observed inhibitory effect induced by 4-OI on CRM1 function. Overall, this study demonstrated a mechanism through which 4-OI directly interferes with the replication cycle of CRM1-dependent viruses, which contributes to the understanding of the antiviral and anti-inflammatory properties of this multifaceted immuno-metabolite.

IMPORTANCE

Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.
Coding-complete genome sequences of rotavirus A reference strains EDIM, Ph158, and CC425
Authors: Casey-Moore Mary C. , Katz Eric , Mijatovic-Rustempasic Slavica , Jaimes Jose , Gautam Rashi , Bowen Michael D.
Published: October 2023

This study reports the coding-complete genome sequences of three rotavirus A (RVA) reference strains previously adapted in tissue culture: RVA/Mouse-tc/USA/EDIM/XXXX/G16P[16] with a G16-P[16]-I7-R7-C7-M8-A7-N7-T10-E7-H9 genotype constellation, RVA/Human-tc/USA/Ph158/1998/G9P[6] with a G9-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation, and RVA/Human-tc/USA/CC425/1998/G3P[9] with a G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 genotype constellation.
Defining microbial community functions in chronic human infection with metatranscriptomics
Authors: Adekoya Aanuoluwa E. , Kargbo Hoody A. , Ibberson Carolyn B.
Published: October 2023

Chronic polymicrobial infections (cPMIs) harbor complex bacterial communities with diverse metabolic capacities, leading to competitive and cooperative interactions. Although the microbes present in cPMIs have been established through culture-dependent and culture-independent methods, the key functions that drive different cPMIs and the metabolic activities of these complex communities remain unknown. To address this knowledge gap, we analyzed 102 published metatranscriptomes collected from cystic fibrosis (CF) sputum and chronic wound infections (CW) to identify key bacterial members and functions in cPMIs. Community composition analysis identified a high prevalence of pathogens, particularly
Staphylococcus
and
Pseudomonas
, and anaerobic members of the microbiota, including
Porphyromonas
,
Anaerococcus
, and
Prevotella
. Functional profiling with HUMANn3 and SAMSA2 revealed that while functions involved in bacterial competition, oxidative stress response, and virulence were conserved across both chronic infection types, >40% of the functions were differentially expressed. Higher expression of antibiotic resistance and biofilm functions was observed in CF, while tissue-destructive enzymes and oxidative stress response functions were highly expressed in CW samples. Of note, strict anaerobes had negative correlations with traditional pathogens in both CW and CF samples, and they significantly contributed to the expression of these functions. Additionally, we show that microbial communities have unique expression patterns, and distinct organisms fulfill the expression of key functions in each site, indicating that the infection environment strongly influences bacterial physiology and that community structure influences function. Collectively, our findings indicate that community composition and function should guide treatment strategies for cPMIs.

IMPORTANCE

The microbial diversity in polymicrobial infections (PMIs) allows for community members to establish interactions with one another, which can result in enhanced disease outcomes such as increased antibiotic tolerance and chronicity. Chronic PMIs result in large burdens on health systems, as they affect a significant proportion of the population and are expensive and difficult to treat. However, investigations into physiology of microbial communities in actual human infection sites are lacking. Here, we highlight that the predominant functions in chronic PMIs differ, and anaerobes, often described as bystanders, may be significant in the progression of chronic infections. Determining the community structure and functions in PMIs is a critical step toward understanding the molecular mechanisms that increase the virulence potential of the microbial community in these environments.
Bacteriological and molecular characterization of temperature- and CO
2
-dependent
Streptococcus pneumoniae
serotype 24F ST162 isolated from Japanese children
Authors: Kobayashi Jun , Ohkusu Misako , Matsumoto Takehisa , Kubota Noriko , Ishiwada Naruhiko
Published: October 2023

Streptococcus pneumoniae
serotype 24F is one of the most prevalent non-vaccine serotypes that causes invasive pneumococcal disease (IPD) in many countries, including Japan. This study aimed to analyze the bacteriological and molecular characteristics of serotype 24F sequence type (ST) 162, which has been increasingly isolated from pediatric patients with IPD in Japan recently. The examination of growth conditions, sequencing of genes associated with the CO
2
dependence, and antimicrobial susceptibility testing at 35°C under 5% CO
2
were performed for 10 isolates obtained from Japanese children with IPD caused by serotype 24F ST162. All isolates failed to grow at 35°C in ambient air; however, they showed growth at 30°C in ambient air and at 35°C under 5% CO
2
. Sequencing of
murF
involved in cell wall synthesis indicated that all isolates had a single amino acid substitution, MurF
A179V
. Additionally, all isolates were sensitive to penicillin G and resistant to trimethoprim-sulfamethoxazole. Furthermore, 25 non-capnophilic strains were obtained from all CO
2
-dependent isolates, and their
murF
sequences were compared. Thirteen of the 25 non-capnophilic strains displayed a different amino acid substitution, MurF
V179A
, whereas the other 12 presented the previously described MurF
A179V
. This suggests that a proportion of the CO
2
-dependent phenotype of serotype 24F ST162 may have been conferred by MurF
A179V
; however, the mechanism for the CO
2
dependence of these isolates warrants further investigation. The CO
2
-dependent serotype 24F ST162 pneumococcal isolates shared common characteristics in terms of growth patterns, molecular basis, and antimicrobial susceptibility; therefore, future epidemiological trends of this clone must be closely monitored.

IMPORTANCE

We characterized
Streptococcus pneumoniae
serotype 24F sequence type (ST) 162 isolated from Japanese children with invasive pneumococcal disease (IPD). Owing to its highly invasive nature, serotype 24F is expected to be isolated from clinically significant cases. Serotype 24F ST162 isolates tested in the present study did not grow at 35°C in ambient air. Therefore, antimicrobial susceptibility testing using the broth microdilution method, which is usually conducted in ambient air, cannot be performed, posing a clinical challenge. Clinical practitioners and laboratory personnel should be aware of the epidemiological, bacteriological, and molecular characteristics of serotype 24F ST162. We believe that our findings can help diagnose and treat IPD caused by serotype 24F ST162, a serotype expected to become problematic in the post-13 valent pneumococcal conjugate vaccine era.
Hybrid RNA sequencing of broad bean wilt virus 2 from faba beans
Authors: Maina Solomon , Norton Sally L. , Rodoni Brendan C.
Published: October 2023

High-throughput sequencing (HTS) is an important tool for plant virus detection and discovery. HTS technologies such as Nanopore sequencing has been rapidly developing in recent years, and offers new possibilities for fast routine diagnostic applications. This study compared MiSeq (Illumina) RNA-Seq with the MinION sequencer (Oxford Nanopore Technologies) (ONT) direct-RNA-Seq methods to detect and sequence the broad bean wilt virus 2 (BBWV2) genome. The Illumina BBWV2 RNA1 and RNA2 genome segments were intact and matched with ONT with 99.1% and 98.8% nucleotide identity (nt) match, respectively. The RNA1 genome derived from ONT had deletions within the nucleoside-triphosphate binding and protease factor open-reading frames, and the upstream of five untranslated regions. However, its RNA2 was intact, and no sequencing errors were observed. The ONT and Illumina RNA1 and RNA 2 BBWV2 genome segments clustered together phylogenetically along with other none-
Fabaceae
species, BBWV2 RNA1 NCBI accession
KC790225
, and RNA 2
MW556592
both from China. This is the first BBWV2 genome study reported in Australia and forms part of the strategy to integrate versatile diagnostic genomics tools at the border to safeguard the Australian grains industry.

IMPORTANCE

Globally, viral diseases impair the growth and vigor of cultivated crops such as grains, leading to a significant reduction in quality, marketability, and competitiveness. As an island nation, Australia has a distinct advantage in using its border to prevent the introduction of damaging viruses, which threaten the continental agricultural sector. However, breeding programs in Australia rely on imported seeds as new sources of genetic diversity. As such, it is critical to remain vigilant in identifying new and emerging viral pathogens, by ensuring the availability of accurate genomic diagnostic tools at the grain biosecurity border. High-throughput sequencing offers game-changing opportunities in biosecurity routine testing. Genomic results are more accurate and informative compared to traditional molecular methods or biological indexing. The present work contributes to strengthening accurate phytosanitary screening, to safeguard the Australian grains industry, and expedite germplasm release to the end users.
Microbisporicin (NAI-107) protects
Galleria mellonella
from infection with
Neisseria gonorrhoeae
Authors: Hofkens Nele , Gestels Zina , Abdellati Said , De Baetselier Irith , Gabant Philippe , Martin Anandi , Kenyon Christopher , Manoharan-Basil Sheeba Santhini
Published: October 2023

Due to the increasing incidence of antibiotic-resistant bacterial pathogens, the need for the development of alternative compounds is of utmost importance. Bacteriocins are considered a promising alternative to antibiotics. In this study, we determined the
in vitro
activities of 65 bacteriocins from the PARAGEN collection along with microbisporicin (NAI-107) against 14 WHO reference isolates of
Neisseria gonorrhoeae
, one isolate of
Neisseria meningitidis
, and four commensal
Neisseria
spp. The initial screening of the bacteriocins was carried out using a spot-on-lawn assay wherein 12 bacteriocins (12/66) showed a zone of inhibition against the WHO-P
N. gonorrhoeae
isolate. Four bacteriocins (4/12), Garvicin KS (GarKS) (ABC), lacticin (lcn) Q, lcn Z, and NAI-107, demonstrated higher activity, and minimum inhibitory concentrations (MICs) using agar dilutions were determined for 19
Neisseria
spp. GarKS (ABC), lcn Q, and lcn Z had an MIC range of 4–16 µg/mL, whereas NAI-107 had an MIC range of <0.25 to 2 µg/mL. Using an
in vivo Galleria mellonella
model, we determined the efficacy of GarKS (ABC), lcn Z, and NAI-107. GarKS (ABC) and lcn Z displayed no
in vivo
toxicity but showed no
in vivo
activity against WHO-P
N. gonorrhoeae
. In contrast, NAI-107 was as effective as ceftriaxone and significantly increased the survival rate of WHO-P
N. gonorrhoeae
-infected
G. mellonella
larvae. In conclusion, NAI-107 exhibited potent
in vitro
and
in vivo
activities against
N. gonorrhoeae
. To our knowledge, this is the first study to demonstrate that NAI-107 possesses anti-gonococcal activity
in vivo
.

IMPORTANCE

We screened 66 bacteriocins to see if they exhibited anti-gonococcal activity. We found 12 bacteriocins with anti-gonococcal effects, and 4 bacteriocins showed higher anti-gonococcal activity. Three bacteriocins, lacticin Z, lacticin Q, and Garvicin KS (ABC), showed
in vitro
anti-gonococcal activity but no
in vivo
inhibitory effects against the
Neisseria gonorrhoeae
(WHO-P) isolate. On the other hand, NAI-107 showed
in vivo
anti-gonococcal activity. The findings suggest that NAI-107 is a promising alternative to treat gonorrhea infections.
Supplemental Material: Anthropogenic impact on sediment transfer in the upper Missouri River catchment detected by detrital zircon analysis
Authors: Thomson Kelly D. , al. et
Published: October 2023

Excel spreadsheets containing sample locations and full detrital zircon U-Pb isotopic ratios and age results. Text file containing detailed description of detrital zircon U-Pb results and three supplemental figures.
Magnetic Structure and the Spin-Crossover Mechanism in Ludwigite Со3BO5
Authors: Zamkova N. G. , Zhandun V. S. , Ovchinnikov S. G.
Published: October 2023

A spin-crossover mechanism in ludwigite Со3BO5 is proposed on the basis of the DFT calculation with SCAN potentials. The role of separate exchange interactions in the establishment of the long-range magnetic order is demonstrated within the Monte Carlo method.
Establishment of prediction models to predict survival among patients with cervical cancer based on socioeconomic factors: a retrospective cohort study based on the SEER Database
Authors: Jia Xiaoping , Zhou Jing , Fu Yanyan , Ma Cailing
Published: October 2023

Objective

To construct and validate predictive models based on socioeconomic factors for predicting overall survival (OS) in cervical cancer and compare them with the American Joint Council on Cancer (AJCC) staging system.

Design

Retrospective cohort study.

Setting and participants

We extracted data from 5954 patients who were diagnosed with cervical cancer between 2007 and 2011 from the Surveillance, Epidemiology, and End Results Database. This database holds data related to cancer incidence from 18 population-based cancer registries in the USA.

Outcome measures

1-year and 5-year OS.

Results

Of the total 5954 patients, 5820 patients had 1-year mortality and 5460 patients had 5-year mortality. Lower local education level [Hazard ratios (HR): 1.15, 95% confidence interval (CI): 1.04 to 1.27, p= 0.005] and being widowed (HR 1.28, 95% CI 1.06 to 1.55, p=0.009) were associated with a worse OS for patients with cervical cancer. Having insurance (HR 0.75, 95% CI 0.62 to 0.90, p=0.002), earning a local median annual income of ≥US$56 270 (HR 0.83, 95% CI 0.75 to 0.92, p<0.001) and being married (HR 0.79, 95% CI 0.69 to 0.89, p<0.001) were related to better OS in patients with cervical cancer. The predictive models based on socioeconomic factors and the AJCC staging system had a favourable performance for predicting OS in cervical cancer compared with the AJCC staging system alone.

Conclusion

Our proposed predictive models exhibit superior predictive performance, which may highlight the potential clinical application of incorporating socioeconomic factors in predicting OS in cervical cancer.
Second opinion and time to knee arthroplasty: a prospective cohort study of 142 patients
Authors: Kisch Rebecca , Grill Eva , Müller Martin , Pietzner Jens , Paulus Alexander C , Weigl Martin
Published: October 2023

Objective

The objective of this study was to determine the impact of obtaining a second opinion consultation on time to knee arthroplasty (KA). We further examined the frequency of KA and the determinants of KA following the second opinion.

Design

Prospective cohort study.

Setting

The second opinion programme was implemented at the Ludwig Maximilian University Hospital in Munich.

Participants

Participants comprised patients with knee osteoarthritis who were insured with one of the largest statutory health insurance Allgemeine Ortskrankenkasse Bayern (mean age 64.3±9.6 years). Patients participated in a second-opinion programme and completed questionnaires on site before and after personal presentation for the second opinion consultation. Follow-up questionnaires were delivered by post at 3 and 12 months after the second opinion consultation. Of the 142 patients included in the study, 47 (33.1%) underwent KA within 12 months after obtaining the second opinion.

Primary outcome measures

Primary outcome measure was time until patients received KA. Cox proportional hazard modelling was used to calculate the associations between the selected predictors and time that elapsed between receipt of the second opinion to KA.

Results

Mean time until KA was 17 weeks. Kaplan-Meier curves showed significant differences in time to KA according to the recommendation given at second opinion consultation, knee-related quality of life and Kellgren-Lawrence grade. In multivariate Cox proportional hazard modelling, second opinion recommendation (HR 5.33, 95% CI 1.16, 24.41) and knee-related quality of life (HR 1.03, 95% CI 1.01, 1.06) were significant predictors of time from second opinion to KA.

Conclusions

Obtaining a second opinion had significant impact on time to knee replacement. Those who were recommended immediate surgery also underwent surgery more quickly after the second opinion. The effect of knee-related quality of life supports the importance of patient-reported outcome measures in the decision for or against KA.
Evaluating kidney function and the associated risk factors among patients with type 2 diabetes mellitus: a cross-sectional study at a tertiary hospital in Jordan
Authors: Al-Momany Abass , Almomani Ensaf Y , Almomani Huda Y , Al-Azzam Sayer I , Qablan Ahmad
Published: October 2023

Background

The diabetes prevalence is escalating in Jordan; as a consequence, the risk of developing diabetic kidney diseases is also increasing.

Objective

This study evaluated the effect of risk factors and comorbidities on kidney function in patients with type 2 diabetes mellitus (T2DM).

Design

A cross-sectional, survey-based study.

Setting

Participants were recruited from the endocrinology and cardiology clinics of a tertiary hospital in Jordan.

Participants

Patients with T2DM aged 18 years and more who had undergone a kidney function test within a year before data collection.

Outcome measures

The estimated GFR (eGFR) mean values and proteinuria presence were used to evaluate the impact of risk factors on kidney function. Descriptive and analytical statistical approaches were used to calculate mean, prevalence and correlations. The SPSS software was used with a p value<0.05 for significance.

Results

Of the total 331 study participants, 54.1% were men and 45.9% were women. The mean age was 60 years. The eGFR mean values were significantly reduced in patients with T2DM with hypertension, hyperlipidaemia and proteinuria (p<0.01). The correlation analysis results showed that the eGFR was positively correlated with hypertension and hyperlipidaemia presence (rs=0.253, 0.220), and negatively correlated with age, body mass index and diabetes duration (rs=−0.395, –0.151, −0.221), respectively. However, the eGFR did not corelate with income, sex, smoking and anaemia. Of note, about 68% of the patients with T2DM had uncontrolled diabetes.

Conclusions

Kidney function were severely affected in patients with T2DM in the presence of risk factors and comorbidities. It is highly recommended to control diabetes through medications and life style, and to regularly check for kidney function to halt the deteriorations in kidney function.
Myocardial infarction and physical function: the REasons for Geographic And Racial Differences in Stroke prospective cohort study
Authors: Levitan Emily B , Goyal Parag , Ringel Joanna Bryan , Soroka Orysya , Sterling Madeline R , Durant Raegan W , Brown Todd M , Bowling C Barrett , Safford Monika M
Published: October 2023

Objective

To examine associations between myocardial infarction (MI) and multiple physical function metrics.

Methods

Among participants aged≥45 years in the REasons for Geographic And Racial Differences in Stroke prospective cohort study, instrumental activities of daily living (IADL), activities of daily living (ADL), gait speed, chair stands and Short Form-12 physical component summary (PCS) were assessed after approximately 10 years of follow-up. We examined associations between MI and physical function (no MI (n=9472), adjudicated MI during follow-up (n=288, median 4.7 years prior to function assessment), history of MI at baseline (n=745), history of MI at baseline and adjudicated MI during follow-up (n=70, median of 6.7 years prior to function assessment)). Models were adjusted for sociodemographic characteristics, health behaviours, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension and urinary albumin to creatinine ratio. We examined subgroups defined by age, gender and race.

Results

The average age at baseline was 62 years old, 56% were women and 35% were black. MI was significantly associated with worse IADL and ADL scores, IADL dependency, chair stands and PCS, but not ADL dependency or gait speed. For example, compared with participants without MI, IADL scores (possible range 0–14, higher score represents worse function) were greater for participants with MI during follow-up (difference: 0.37 (95% CI 0.16 to 0.59)), MI at baseline (0.26 (95% CI 0.12 to 0.41)) and MI at baseline and follow-up (0.71 (95% CI 0.15 to 1.26)), p<0.001. Associations tended to be greater in magnitude among participants who were women and particularly black women.

Conclusion

MI was associated with various measures of physical function. These decrements in function associated with MI may be preventable or treatable.
The role of physiology in the contemporary management of coronary artery disease
Authors: Rubino Francesca , Pompei Graziella , Brugaletta Salvatore , Collet Carlos , Kunadian Vijay
Published: October 2023

Coronary physiology assessment, including epicardial and microvascular investigations, is a fundamental tool in the contemporary management of patients with coronary artery disease. Coronary revascularisation guided by functional evaluation has demonstrated superiority over angiography-only-guided treatment. In patients with chronic coronary syndrome, revascularisation did not demonstrate prognostic advantage in terms of mortality over optimal medical therapy (OMT). However, revascularisation of coronary stenosis, which induces myocardial ischaemia, has demonstrated better outcome than OMT alone. Pressure wire (PW) or angiography-based longitudinal coronary physiology provides a point-by-point analysis of the vessel to detect the atherosclerotic pattern of coronary disease. A careful evaluation of this disease pattern allows clinicians to choose the appropriate management strategy.

Patients with diffuse disease showed a twofold risk of residual angina after percutaneous coronary intervention (PCI) than those with focal disease. Therefore, OMT alone or coronary artery bypass graft might be considered over PCI. In addition, the post-PCI physiological assessment aims to optimise the result revealing residual myocardial ischaemia. Improvement in post-PCI PW or angiography-based functional indices has been associated with better quality of life and reduced risk of cardiac events and residual angina. Therefore, the information obtained from coronary physiology allows for an optimised treatment strategy, which ultimately leads to improve patient’s prognosis and quality of life. This review provides an overview of the latest available evidence in the literature regarding the use of functional assessment of epicardial coronary stenosis in different settings in the contemporary patient-tailored management of coronary disease.
Echocardiographic estimation of pulmonary pressure in patients with severe tricuspid regurgitation
Authors: Lemarchand Léo , Auffret Vincent , Le Breton Hervé , Bedossa Marc , Boulmier Dominique , Galli Elena , Donal Erwan , Leurent Guillaume
Published: October 2023

Objectives

The estimation of systolic pulmonary artery pressure (sPAP) by transthoracic echocardiography (TTE) is challenging in patients with severe tricuspid regurgitation (TR). The study aimed to determine the reliability of the assessment of sPAP by TTE in this population.

Methods

This study was a single-centre analysis of consecutive patients at the University Hospital of Rennes with right heart catheterisation and TTE, performed with a maximum delay of 48 hours. Lin’s concordance coefficient (LCC) and Bland-Altman analysis were used to compare the values.

Results

After applying the exclusion criteria, 236 patients were included in the analysis (age 71±11.5 years old; male 56%). The two principal indications were TR (34.3%) and mitral regurgitation (32.2%). The correlation between the two procedures was good in the total population (LCC=0.80; 95% limits of agreement (LOA): 0.74, 0.84), but weaker in the 78 patients (33%) with severe TR (LCC=0.67; 95% LOA: 0.49, 0.80), with a propensity to an underestimation by TTE. An elevated right atrial pressure (RAP) was associated with an underestimation by TTE of about 8 mmHg. The presence of a ‘V-wave cut-off’ sign on continuous-wave Doppler (OR=3.74; 95% CI 1.48, 9.30; p<0.01), found exclusively in patients with severe TR, was an independent predictor of sPAP misestimation by TTE.

Conclusion

The reliability of the estimation of sPAP in patients with severe TR could be altered by high RAP which cannot be estimated with current thresholds.
Peak oxygen consumption by smartwatches compared with cardiopulmonary exercise test in complex congenital heart disease
Authors: Tran Tomio , Steiner Jill Marie , Venkateswaran Aparajithan , Buber Jonathan
Published: October 2023

Objective

To evaluate for correlation between exercise capacity as assessed by peak oxygen consumption (pVO2) measurement during a cardiopulmonary exercise test (CPET) and smartwatches reporting this parameter in patients with adult congenital heart disease (ACHD) complex lesions.

Methods

A prospective study that included patients with ACHD either a Fontan circulation or a right ventricle supporting the systemic circulation who underwent two separate CPETs at least 1 year apart. Generalised estimating equations linear regression was performed to identify factors associated with correlation between smartwatch and CPET-derived pVO2.

Results

48 patients (71% with a Fontan circulation, 42% females, mean age 33±9 years) underwent two CPETs between May 2018 and May 2022 with echocardiograms performed within 6 months of each CPET. Apple Watch was the predominant smartwatch used (79%). Smartwatch and CPET measured peak heart rate (Pearson correlation=0.932, 95% CI (0.899, 0.954)) and pVO2(0.8627, 95% CI (0.8007, 0.9064) and 0.8634, 95% CI (0.7676, 0.9215) in the first and second CPET, respectively) correlated well, with smartwatch-measured pVO2values measuring higher by a mean of 3.146 mL/kg/min (95% CI (2.559, 3.732)). Changes in pVO2between the first and the second CPET also correlated well (Pearson correlation=0.9165, 95% CI (0.8549, 0.9525)), indicating that for every 1 mL/(min kg) change in CPET-measured pVO2, there was a corresponding 0.896 mL/(min kg) change in the smartwatch-measured pVO2.

Conclusion

Both absolute values and changes over time in pVO2as measured by smartwatches and CPETs correlate well in patients with complex ACHD.
Nutritional support in palliative cancer care: quality of life in oral versus tube feeding
Authors: Santos Larissa Pereira , Calixto-Lima Larissa , de Oliveira Livia Costa , Wiegert Emanuelly Varea Maria
Published: October 2023

Background

Nutritional support (NS) offered through oral nutritional supplements (ONS) or enteral nutrition (EN) and its impact on quality of life (QoL) is a controversial topic in patients with cancer receiving palliative care (PC).

Aims

To compare the QoL of patients without and with use of NS, including ONS or EN in patients with incurable cancer receiving PC.

Methods

Cross-sectional analysis with patients that were evaluated at PC Unit between June 2021 and February 2023. QoL was assessed using the Quality of Life Questionnaire Core 15. Patients were classified into three groups according to the NS: ONS (n=72; 33%), EN (n=61; 28%) and control group (CG) (n=87; 39%), the last one being formed by patients not using NS. Adjusted logistic regression models were used to verify the association of the domains of QoL with the type of NS.

Results

A total of 220 patients were included, with a median age of 64 (58–70) years, predominantly male (54.1%). The EN group had worse scores in physical function when compared with the ONS group (p=0.037) and appetite loss when compared with the CG (p=0.013). The ONS (OR: 2.70; 95% CI 1.32 to 5.49) and EN groups (OR: 2.61; 95% CI 1.24 to 5.49) were independently associated with a higher chance of presenting appetite loss in relation to the CG.

Conclusion

In general, there was no difference in the QoL of patients using NS when compared with patients not using NS. However, patients using NS have more chance of having appetite loss.