bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized patients
Authors: Basting Christopher M. , Langat Robert , Broedlow Courtney A. , Guerrero Candace R. , Bold Tyler D. , Bailey Melisa , Velez Adrian , Schroeder Ty , Short-Miller Jonah , Cromarty Ross , Mayer Zachary J. , Southern Peter J. , Schacker Timothy W. , Safo Sandra E. , Bramante Carolyn T. , Tignanelli Christopher J. , Schifanella Luca , Klatt Nichole R. 
Published: September 2024

ABSTRACT

Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host–microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including
Faecalibacterium prausnitzii
and an increased abundance of the opportunistic pathogens
Eggerthella lenta
and
Hungatella hathewayi
. Furthermore, the oral pathogen
Scardovia wiggsiae
was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both
H. hathewayi
and
S. wiggsiae
correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.

IMPORTANCE
Outcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes.
Evaluating the duration of antimicrobial therapy for the treatment of orthopedic hardware infections
Authors: Asim Rija , Fuchs Christian J. , Summers Nathan A. 
Published: September 2024

ABSTRACT

The optimal duration of antimicrobial therapy for orthopedic hardware infections is unclear. We identified 216 patients with orthopedic hardware infections, of whom 42 (19%) later had relapsed infection. Chronic suppressive antimicrobial therapy beyond 12 weeks was not significantly associated with lower odds of relapse.

IMPORTANCE
There is debate about how long to continue antibiotics after initial treatment of bone and joint infections when hardware remains in place. This study found no benefit from continuing antibiotics longer than 12 weeks when trying to prevent recurrent infection.
The effect of
Asparagopsis taxiformis
,
Ascophyllum nodosum
, and
Fucus vesiculosus
on ruminal methanogenesis and metagenomic functional profiles
in vitro
Authors: Yergaliyev Timur , Künzel Susanne , Hanauska Anna , Rees Antonia , Wild Katharina J. , Pétursdóttir Ásta H. , Gunnlaugsdóttir Helga , Reynolds Christopher K. , Humphries David J. , Rodehutscord Markus , Camarinha-Silva Amélia 
Published: September 2024

ABSTRACT

The ruminant-microorganism symbiosis is unique by providing high-quality food from fibrous materials but also contributes to the production of one of the most potent greenhouse gases—methane. Mitigating methanogenesis in ruminants has been a focus of interest in the past decades. One of the promising strategies to combat methane production is the use of feed supplements, such as seaweeds, that might mitigate methanogenesis via microbiome modulation and direct chemical inhibition. We conducted
in vitro
investigations of the effect of three seaweeds (
Ascophyllum nodosum
,
Asparagopsis taxiformis
, and
Fucus vesiculosus
) harvested at different locations (Iceland, Scotland, and Portugal) on methane production. We applied metataxonomics (16S rRNA gene amplicons) and metagenomics (shotgun) methods to uncover the interplay between the microbiome’s taxonomical and functional states, methanogenesis rates, and seaweed supplementations. Methane concentration was reduced by
A. nodosum
and
F. vesiculosus
, both harvested in Scotland and
A. taxiformis
, with the greatest effect of the latter.
A. taxiformis
acted through the reduction of archaea-to-bacteria ratios but not eukaryotes-to-bacteria. Moreover,
A. taxiformis
application was accompanied by shifts in both taxonomic and functional profiles of the microbial communities, decreasing not only archaeal ratios but also abundances of methanogenesis-associated functions.
Methanobrevibacter
“SGMT” (
M. smithii, M. gottschalkii, M. millerae
or
M. thaueri
; high methane yield) to “RO” (
M. ruminantium
and
M. olleyae
; low methane yield) clades ratios were also decreased, indicating that
A. taxiformis
application favored
Methanobrevibacter
species that produce less methane. Most of the functions directly involved in methanogenesis were less abundant, while the abundances of the small subset of functions that participate in methane assimilation were increased.

IMPORTANCE

The application of
A. taxiformis
significantly reduced methane production
in vitro
. We showed that this reduction was linked to changes in microbial function profiles, the decline in the overall archaeal community counts, and shifts in ratios of
Methanobrevibacter
“SGMT” and “RO” clades.
A. nodosum
and
F. vesiculosus
, obtained from Scotland, also decreased methane concentration in the total gas, while the same seaweed species from Iceland did not.
Spatial variability of bacterial biofilm communities in a wastewater effluent-impacted suburban stream ecosystem
Authors: Veach Allison M. , Steinbrecher Aimee , Le Michelle 
Published: September 2024

ABSTRACT

Wastewater discharge is a global threat to freshwater resources. Streams, in particular, are receiving waterbodies that are directly impacted chemically and biologically due to effluent discharge. However, it is largely unknown how wastewater serves as a subsidy or a stressor to aquatic biodiversity, particularly microbiota, over space. Nutrient-diffusing substrata (NDS) were deployed; NDS release nutrients through diffusion into the water column into a wastewater-dependent stream across three reaches. We used N, P, and N + P treatments for the measurement of single nutrient and co-nutrient limitation, and a no-nutrient control. Both algal and total biofilm biomass was measured and the 16S ribosomal RNA genes via targeted amplicon sequencing was used to assess bacterial/archaeal community diversity. Data indicated that total organic matter in biofilms differs spatially with the greatest organic matter (OM) concentrations in the confluence downstream of wastewater inputs. Biofilm OM concentrations were greatest in P and N + P treatments in the confluence site relative to control or N-only treatments. This indicates heterotrophic microbial communities—likely bacteria that dominate stream biofilms—are P-limited in this ecosystem even with upstream wastewater inputs. In conjunction, bacteria/archaeal communities differed the greatest among nutrient treatments versus spatially and had several indicator taxa belonging to
Flavobacterium
spp. in N treatments relative to controls. Collectively with historical water quality data, we conclude that this wastewater-fed stream is primarily N-enriched but potentially P-limited, which results in significant shifts in biofilm bacterial communities and likely their overall biomass in this urban watershed.

IMPORTANCE
Streams in arid and semi-arid biomes are often dependent on their flow from municipal sources, such as wastewater effluent. However, wastewater has been shown to contain high concentrations of nutrients and chemical pollutants that can potentially harm aquatic ecosystems and their biota. Understanding if and the type of microorganisms that respond to pollution sources, specifically effluent from wastewater treatment facilities, in regions where flow is predominantly from treatment facilities, is critical for developing a predictive monitoring approach for eutrophication or other ecological degradation states for freshwaters.
Veillonella parvula
acts as a pathobiont promoting the biofilm virulence and cariogenicity of
Streptococcus mutans
in adult severe caries
Authors: Wei Yuan , Zhang Yu , Zhuang Yuan , Tang Yifei , Nie Hua , Haung Yequan , Liu Ting , Yang Weidong , Yan Fuhua , Zhu Yanan 
Published: September 2024

ABSTRACT

Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the
S. mutans
. Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and
gtf
(glucosyltransferase) gene expression of
S. mutans
cocultured with
V. parvula
which was identified as ASC-related dominant bacterium. The bioﬁlm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the
in vivo
cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was
V. parvula
.
In vitro
experiments found that
V. parvula
can effectively promote
S. mutans
mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that
V. parvula
was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of
S. mutans
when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that
V. parvula
may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of
S. mutans
in the context of ASC.

IMPORTANCE

Adult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between
V. parvula
and
S. mutans
augments the severity of dental caries
in vivo
, suggesting
V. parvula
may act as a synergistic pathobiont exacerbating biofilm virulence of
S. mutans
in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies.
Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma
Authors: Salié Henrike , Wischer Lara , D’Alessio Antonio , Godbole Ira , Suo Yuan , Otto-Mora Patricia , Beck Juergen , Neumann Olaf , Stenzinger Albrecht , Schirmacher Peter , Fulgenzi Claudia A M , Blaumeiser Andreas , Boerries Melanie , Roehlen Natascha , Schultheiß Michael , Hofmann Maike , Thimme Robert , Pinato David J , Longerich Thomas , Bengsch Bertram 
Published: September 2024

BackgroundThe determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.ObjectiveWe hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.DesignWe conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.ResultsBioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.
Single-arm trial of neoadjuvant ipilimumab plus nivolumab with chemoradiotherapy in patients with resectable and borderline resectable lung cancer: the INCREASE study
Authors: Bahce Idris , Dickhoff Chris , Schneiders Famke L , Veltman Joris , Heineman David J , Hashemi Sayed M S , Vrijmoet Anne , Houda Ilias , Ulas Ezgi B , Bakker Joyce , van de Ven Peter , Bouwhuis Natalja , Meijboom Lilian J , Oprea-Lager Daniela E , van Maldegem Febe , Fransen Marieke F , de Gruijl Tanja D , Radonic Teodora , Senan Suresh 
Published: September 2024

BackgroundIn non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and borderline resectable NSCLC.MethodsThis single-arm, phase-II trial enrolled operable T3-4N0–2 patients with NSCLC without oncogenic drivers. Primary study endpoints were safety, major pathological response (MPR) and pCR. Treatment encompassed platinum-doublet concurrent CRT, IPI 1 mg/kg intravenous and NIVO 360 mg intravenous on day-1, followed by chemotherapy plus NIVO 360 mg 3 weeks later. Thoracic radiotherapy was 50 or 60 Gy, in once-daily doses of 2 Gy. Resections were 6 weeks post-radiotherapy.ResultsIn a total of 30 patients in the intention-to-treat (ITT) population, grades 3–4 treatment-related adverse events (TRAEs) occurred in 70%, one TRAE grade 5 late-onset pneumonitis on day 96 post-surgery (1/30, 3.3%) occurred, and one non-TRAE COVID-19 death (1/30, 3.3%). pCR and MPR were achieved in 50% (15/30) and 63% (19/30) of the ITT; and in 58% (15/26) and 73% (19/26) of the 26 patients who underwent surgery, respectively. Postoperative melanoma was seen in one non-pCR patient. The R0 rate was 100% (26/26), and no patient failed surgery due to TRAEs. In peripheral blood, proliferative CD8+T cells were increased, while proliferative regulatory T cells (Tregs) were not. On-treatment, pCR-positives had higher CD8+CD39+T cells and lower HLA-DR+Tregs.ConclusionsNeoadjuvant IPI-NIVO-CRT in T3-4N0–2 NSCLC showed acceptable safety with pCR and MPR in 58% and 73% of operated patients, respectively. No patient failed surgery due to TRAEs.Trial registration numberNCT04245514.
Neutrino tomography of the earth: the earth total mass, moment of inertia and hydrostatic equilibrium constraints
Authors: Petcov S. T. 
Published: September 2024

AbstractWe investigate the implications of the constraints following from the precise knowledge of the total Earth mass, $$M_\oplus $$

M
⊕

, and moment of inertia, $$I_\oplus $$

I
⊕

, and from the requirement that Earth be in hydrostatic equilibrium (EHE), in the neutrino tomography studies of the Earth density structure. In order to estimate the sensitivity of a given neutrino detector to possible deviations of the inner core (IC), outer core (OC), core (IC + OC) and mantle Earth densities from those obtained using geophysical and seismological data and described by the preliminary reference Earth model (PREM), in the statistical analyses performed within the neutrino tomography studies one typically varies the density of each of these structures. These variations, however, must respect the $$M_\oplus $$

M
⊕

, $$I_\oplus $$

I
⊕

and EHE constraints. Working with PREM average densities we derive the $$M_\oplus $$

M
⊕

, $$I_\oplus $$

I
⊕

and EHE constraints on the possible density variations when one approximates the Earth density structure with (i) three layers – mantle, outer core and inner core, and (ii) four layers – upper mantle, lower mantle, outer core and inner core. We get drastically different results in the two cases.
There’s plenty of room in the middle: The unsung revolution of the renormalization group
Authors: Goldenfeld Nigel 
Published: September 2024

The remarkable technical contributions of Michael E. Fisher to statistical physics and the development of the renormalization group are widely known and deeply influential. But less well known is his early and profound appreciation of the way in which renormalization group created a revolution in our understanding of how physics — in fact, all science — is practiced and the concomitant adjustment that needs to be made to our conception of the purpose and philosophy of science. In this chapter, I attempt to redress this imbalance, with examples from Fisher’s writings and my own work. It is my hope that this tribute will help remove some of the confusion that surrounds the scientific usage of minimal models and renormalization group concepts, as well as their limitations, in the ongoing effort to understand emergence in complex systems.
Comparing the Physiological Responses to the 6‐Minute Walk Test, Timed Up and Go Test, and Treadmill Cardiopulmonary Exercise Test
Authors: Alves Eduardo S. , Bellet R. Nicole , Sharma Pramod , Balmain Bryce N. , Aitken Craig , Doering Thomas , Orola Leilani , Green Anita , Paim Tatiana , O’Connor Fergus , Morris Norman R. 
Published: September 2024

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6‐minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing.Methods: Heart rate (HR), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test.Results: Each test demonstrated a significant increase (p < 0.01) in the cardiopulmonary (V̇O2, V̇CO2 and V̇E, RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT (p < 0.01) and even smaller responses for the TUGT (p < 0.01 vs CPX and 6MWT).Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.
Determining the N-Glycan and Collagen/Extracellular Matrix Protein Compositions in a Novel Outcome Cohort of Prostate Cancer Tissue Microarrays Using MALDI-MSI
Authors: Hartig Jordan P. , Bejar Kaitlyn , Young Lyndsay E.A. , Grimsley Grace , Bethard Jennifer R. , Troyer Dean A. , Hernandez Javier , Wu Jennifer D. , Ippolito Joseph E. , Ball Lauren E. , Gelfond Jonathan A.L. , Johnson-Pais Teresa L. , Mehta Anand S. , Leach Robin J. , Angel Peggi M. , Drake Richard R. 
Published: September 2024

Abstract
Prostate cancer is a significant health concern, with metastasis posing major clinical challenges and resulting in poor patient outcome. Despite screening and treatment advances, a critical need for novel biomarkers to predict prostate cancer progression at the time of prostatectomy persists. Here, we assessed aberrant N-glycosylation patterns and alterations in extracellular matrix (ECM) proteins as potential biomarkers of predicting prostate cancer severity in a unique patient outcome cohort. Tissue microarray slides were assembled from primary prostatectomy specimens that were categorized into “no evidence of disease (NED)” and “metastasis (MET)” designations based on &gt;5-year disease progression outcomes. Serial mass spectrometry imaging techniques were performed to analyze N-glycans and ECM components in formalin-fixed paraffin-embedded cores. The results revealed a significant upregulation of bisecting and multiantennary core-fucosylated N-glycans in MET tissues when compared with NED tissues. Alterations in ECM composition in both NED and MET cohorts were observed, particularly in collagen species and the amount of hydroxyproline content. Results suggest a coordinated alteration of ECM protein and glycosylation content in prostate cancer tissues can be predictive for postprostatectomy disease progression.

Significance:
Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.