bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial combinations against
Helicobacter pylori
including benzoxadiazol-based flavodoxin inhibitors:
in vitro
characterization
Authors: Beyria Lilha , Gourbeyre Ophelie , Salillas Sandra , Mahía Alejandro , Díaz de Villegas María Dolores , Aínsa José Antonio , Sancho Javier , Bousquet-Mélou Alain , Ferran Aude A. 
Published: December 2023

ABSTRACT

Antimicrobial resistance of
Helicobacter pylori
(
Hp
) threatens currently available treatment regimens and prompts the development of antimicrobial drugs against new bacterial targets. One such class of drugs is
Hp
-flavodoxin (
Hp
-fld) inhibitors, which target an essential metabolic pathway in
Hp
. The aim of this study was to characterize the effects of these inhibitors against
Hp
over time when used alone or combined with conventional antibiotics. Four benzoxadiazol-based fld inhibitors were initially tested for their
in vitro
potency, with compound IV displaying the highest efficacy. This compound was then combined with clarithromycin, metronidazole, amoxicillin, levofloxacin, and rifampicin in further experiments. Checkerboard assays indicated that compound IV exhibited additive activity when combined with these antibiotics. The study further investigated the time course of antibacterial effects by exposing a high inoculum of
Hp
to compound IV and each antibiotic, alone or in combination. At just four times the minimum inhibitory concentration, compound IV demonstrated bactericidal effects within 6 h. However, the regrowth of bacteria occurred between 24 and 48 h of exposure. Similar patterns of killing followed by regrowth were observed for conventional antibiotics alone. However, the addition of compound IV to the antibiotics clearly limited regrowth over 72 h. These findings suggest that compound IV can effectively eliminate spontaneous mutants that are resistant to conventional antibiotics or prevent new mutations during drug exposure.
Hp
-fld inhibitors, such as compound IV, hold promise as new drugs to be integrated into
Hp
infection treatment, potentially reducing the development of resistance and shortening the duration of treatment.

IMPORTANCE

The antimicrobial resistance of
Helicobacter pylori
(
Hp
) currently poses a threat to available treatment regimens. Developing antimicrobial drugs targeting new bacterial targets is crucial, and one such class of drugs includes
Hp
-flavodoxin (
Hp
-fld) inhibitors that target an essential metabolic pathway in
Hp
. Our study demonstrated that combining these new drugs with conventional antibiotics used for
Hp
infection treatment prevented the regrowth observed with drugs used alone.
Hp
-fld inhibitors show promise as new drugs to be incorporated into the treatment of
Hp
infection, potentially reducing the development of resistance and shortening the treatment duration.
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Authors: Keller Matthew W. , Keong Lisa M. , Rambo-Martin Benjamin L. , Hassell Norman , Lacek Kristine A. , Wilson Malania M. , Kirby Marie K. , Liddell Jimma , Owuor D. Collins , Sheth Mili , Madden Joseph , Lee Justin S. , Kondor Rebecca J. , Wentworth David E. , Barnes John R. 
Published: December 2023

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is a highly immunogenic and mutable protein that is the target of vaccine prevention and antibody therapeutics. This makes the encoding S-gene an important sequencing target. The SARS-CoV-2 sequencing community overwhelmingly adopted tiling amplicon-based strategies for sequencing the entire genome. As the virus evolved, primer mismatches inevitably led to amplicon dropout. Given the exposure of the spike protein to host antibodies, mutation occurred here most rapidly, leading to amplicon failure over the most insightful region of the genome. To mitigate this, we developed a targeted method to amplify and sequence the S-gene. We evaluated 20 distinct primer designs through iterative
in silico
and
in vitro
testing to select the optimal primer pairs and run conditions. Once selected, periodic
in silico
analysis monitors primer conservation as SARS-CoV-2 evolves. Despite being designed during the beta wave, the selected primers remain >99% conserved through Omicron as of 19 October 2023. To validate the final design, we compared targeted S-gene data to National SARS-CoV-2 Strain Surveillance whole-genome data for 321 matching samples. Consensus sequences for the two methods were highly identical (99.998%) across the S-gene. This method can serve as a complement to whole-genome surveillance or can be leveraged where only S-gene sequencing is of interest.

IMPORTANCE
The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection.
Microbial network and fermentation modulation of Napier grass and sugarcane top silage in southern Africa
Authors: Du Zhumei , Yamasaki Seishi , Oya Tetsuji , Nguluve Damiao , Euridse Denise , Tinga Benedito , Macome Felicidade , Cai Yimin 
Published: December 2023

ABSTRACT

To effectively alleviate the shortage of animal feed in the tropics, we applied a screening lactic acid bacteria (LAB) strain (
Lactiplantibacillus plantarum
MO1) and a commercial inoculant (
L. plantarum
LP1) to prepare silage from early flowering Napier grass and after harvest sugarcane tops in southern Africa. The microbial community structure, co-occurrence network, and fermentation characteristics of silage were analyzed using PacBio single-molecule real-time sequencing technology. Strain MO1, isolated from corn silage, was characterized by strong acid tolerance and the ability to produce lactic acid. Before ensiling, the dominant microbial community in both Napier grass and sugarcane top were Gram-negative harmful microbes. After ensiling, the main microbial community shifted from Gram-negative to Gram-positive bacteria, and the microbial alpha diversity of all silages significantly decreased (
P
< 0.05). Compared to the control, fermentation of the LAB-treated silages was accelerated and
L. plantarum
became the dominant microbial community, while the lactic acid content increased (
P
< 0.05) and the pH was reduced (
P
< 0.05). In the MO1-treated silages, the relative abundance of LAB was markedly increased and formed a co-occurrence microbial network with
L. plantarum
as the dominant microorganism. It also led to the global and overview maps, as a special class of metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes database was enhanced and the carbohydrate metabolism and amino acid metabolism pathways were weakened, thereby improving the flavor and quality of the silages compared to the LP1-treated ones. Strain MO1 can modulate the microbial community and metabolic pathways and achieve clean fermentation. It is of great significance to alleviate feed shortage and promote sustainable production of livestock.

IMPORTANCE

Feed shortage in the tropics is a major constraint to the production of livestock products such as milk and meat. In order to effectively utilize of local feed resources, the selected lactic acid bacteria (LAB) strain was used to prepare Napier grass and sugarcane top silage. The results showed that the two silages inoculated with LAB formed a co-occurrence microbial network dominated by
Lactiplantibacillus
during the fermentation process, regulated the microbial community structure and metabolic pathways, and improved the silage fermentation quality. This is of great significance for alleviating feed shortage and promoting sustainable production of livestock.
Endometriosis with colonic mucosal colonisation: a diagnostic confounder
Authors: Adler Jeremy , Algashaamy Khaled , Garcia de Buitrago Monica T , Pinto Andre , Montgomery Elizabeth Anne 
Published: December 2023

AimsSecondary mucosal colonisation by a carcinoma originating from a distant site is a pattern of metastasis to the intestines and hepatobiliary tract and a mimic of primary neoplasia. Although endometriosis is considered benign, its ability to spread widely underscores its quasi-neoplastic nature. After noting that endometriotic glands can colonise the colonic mucosa along the basement membrane, mimicking metastatic disease, we conducted an intradepartmental review of intestinal specimens showing endometriosis obtained from 2016 to 2023 to characterise and quantify the incidence of this phenomenon.MethodsMaterial from 38 lower gastrointestinal specimens with a primary or ancillary diagnosis of endometriosis was identified from our surgical pathology database. Slides were reviewed, documenting the extent and micro-anatomic location affected by endometriosis, with a focus on identifying examples showing mucosal colonisation.ResultsThe most common site of involvement was the distal colon (23 cases; 11 of rectum, 9 of sigmoid colon and 3 of rectosigmoid) followed by the appendix (N=10), cecum (N=2), small intestine (N=2) and ‘colon not otherwise specified’ (N=1). Mucosal involvement was identified in eight cases (21%), half of which demonstrated seamless colonisation of the epithelium by endometriotic glands. In two of these, the procedure was prompted by the presence of a rectal mass or stricture with concern for malignancy.ConclusionEndometriosis occasionally (4/38; 10.5%) colonises colonic epithelium, potentially mimicking a metastasis or intraepithelial neoplasia/dysplasia. Although unusual, this phenomenon was observed in half of specimens from patients with mucosal involvement in whom a mass or stricture suggested malignancy, a potentially misleading pattern of endometriosis.
Potential contribution of vaccination uptake to occupational differences in risk of SARS-CoV-2: analysis of the ONS COVID-19 Infection Survey
Authors: Rhodes Sarah , Demou Evangelia , Wilkinson Jack , Cherrie Mark , Edge Rhiannon , Gittins Matthew , Katikireddi Srinivasa Vittal , Kromydas Theocharis , Mueller William , Pearce Neil , van Tongeren Martie 
Published: December 2023

ObjectivesTo assess variation in vaccination uptake across occupational groups as a potential explanation for variation in risk of SARS-CoV-2 infection.DesignWe analysed data from the UK Office of National Statistics COVID-19 Infection Survey linked to vaccination data from the National Immunisation Management System in England from 1 December 2020 to 11 May 2022. We analysed vaccination uptake and SARS-CoV-2 infection risk by occupational group and assessed whether adjustment for vaccination reduced the variation in risk between occupational groups.ResultsEstimated rates of triple vaccination were high across all occupational groups (80% or above), but were lowest for food processing (80%), personal care (82%), hospitality (83%), manual occupations (84%) and retail (85%). High rates were observed for individuals working in health (95% for office based, 92% for those in patient-facing roles) and education (91%) and office-based workers not included in other categories (90%). The impact of adjusting for vaccination when estimating relative risks of infection was generally modest (ratio of hazard ratios across all occupational groups reduced from 1.37 to 1.32), but was consistent with the hypothesis that low vaccination rates contribute to elevated risk in some groups.ConclusionsVariation in vaccination coverage might account for a modest proportion of occupational differences in infection risk. Vaccination rates were uniformly very high in this cohort, which may suggest that the participants are not representative of the general population. Accordingly, these results should be considered tentative pending the accumulation of additional evidence.
A variational framework for higher order perturbations
Authors: Chiaffredo Federico , Fatibene Lorenzo , Ferraris Marco , Ricossa Emanuele , Usseglio Davide 
Published: December 2023

A covariant, global, variational framework for perturbations in field theories is presented. Perturbations are obtained as vertical vector fields on the configuration bundle and they drag, exactly, solution into solutions. The flow of a perturbation drags solutions into solutions and the dragged perturbed solutions can be expanded in a series with respect to the flow parameter, hence it contains perturbations at any order. Mechanics is included as a special case. As a simple application, we recover the well-known discussion about stability of geodesics on a sphere [Formula: see text].
Cancer in 2023
Authors:   AACR Cancer Progress Report 2023 Steering Committee
Published: December 2023

Summary:
Excerpts from the 13th edition of the annual AACR Cancer Progress Report (https://cancerprogressreport.aacr.org/progress/) to U.S. Congress and the public highlight current challenges in achieving the goal of the Cancer Moonshot to reduce the cancer death rate in the United States by 50% by 2047 and a call to action for robust, sustained support of medical research funding is issued.
Precision Oncology: 2023 in Review
Authors: Murciano-Goroff Yonina R. , Suehnholz Sarah P. , Drilon Alexander , Chakravarty Debyani 
Published: December 2023

Summary:
This article presents a review of recent major advances in precision oncology and the future implications of these advances, specifying the iterative progress achieved from the end of 2022 through 2023. We discuss the different classes of precision oncology drugs and associated biomarkers as well as the improvements in clinical trial design that have enabled the efficient testing of these drugs.
Macromolecular Complex Including MLL3, Carabin and Calcineurin Regulates Cardiac Remodeling
Authors: Pane Roberto , Laib Loubna , Formoso Karina , Détrait Maximin , Sainte-Marie Yannis , Bourgailh Florence , Ruffenach Nolan , Faugeras Hanamée , Simon Ilias , Lhuillier Emeline , Lezoualc’h Frank , Conte Caroline 
Published: December 2023

BACKGROUND:
Cardiac hypertrophy is an intermediate stage in the development of heart failure. The structural and functional processes occurring in cardiac hypertrophy include extensive gene reprogramming, which is dependent on epigenetic regulation and chromatin remodeling. However, the chromatin remodelers and their regulatory functions involved in the pathogenesis of cardiac hypertrophy are not well characterized.

METHODS:
Protein interaction was determined by immunoprecipitation assay in primary cardiomyocytes and mouse cardiac samples subjected or not to transverse aortic constriction for 1 week. Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) experiments were performed on the chromatin of adult mouse cardiomyocytes.

RESULTS:
We report that the calcium-activated protein phosphatase CaN (calcineurin), its endogenous inhibitory protein carabin, the STK24 (STE20-like protein kinase 3), and the histone monomethyltransferase, MLL3 (mixed lineage leukemia 3) form altogether a macromolecular complex at the chromatin of cardiomyocytes. Under basal conditions, carabin prevents CaN activation while the serine/threonine kinase STK24 maintains MLL3 inactive via phosphorylation. After 1 week of transverse aortic constriction, both carabin and STK24 are released from the CaN-MLL3 complex leading to the activation of CaN, dephosphorylation of MLL3, and in turn, histone H3 lysine 4 monomethylation. Selective cardiac MLL3 knockdown mitigates hypertrophy, and chromatin immunoprecipitation and DNA sequencing analysis demonstrates that MLL3 is de novo recruited at the transcriptional start site of genes implicated in cardiomyopathy in stress conditions. We also show that CaN and MLL3 colocalize at chromatin and that CaN activates MLL3 histone methyl transferase activity at distal intergenic regions under hypertrophic conditions.

CONCLUSIONS:
Our study reveals an unsuspected epigenetic mechanism of CaN that directly regulates MLL3 histone methyl transferase activity to promote cardiac remodeling.
Hemodynamic Failure Staging With Blood Oxygenation Level–Dependent Cerebrovascular Reactivity and Acetazolamide‐Challenged (
15
O‐)H
2
O‐Positron Emission Tomography Across Individual Cerebrovascular Territories
Authors: Sebök Martina , van der Wouden Frank , Mader Cäcilia , Pangalu Athina , Treyer Valerie , Fisher Joseph Arnold , Mikulis David John , Hüllner Martin , Regli Luca , Fierstra Jorn , van Niftrik Christiaan Hendrik Bas 
Published: December 2023

Background

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno‐occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography‐based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level–dependent cerebrovascular reactivity (BOLD‐CVR) with CO
2
is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD‐CVR to classify the extent of HF.

Methods and Results

Patients with symptomatic unilateral cerebrovascular steno‐occlusive disease, who underwent both an acetazolamide challenge (
15
O‐)H
2
O‐positron emission tomography and BOLD‐CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD‐CVR cutoff points between HF stages 0–1–2 were determined by comparing the quantitative BOLD‐CVR data to the qualitative (
15
O‐)H
2
O‐positron emission tomography classification using the 3‐dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2‐case scenario, classifying data points as HF 0 or 1–2 and HF 0–1 or 2, BOLD‐CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2.

Conclusions
Standardized and clinically accessible BOLD‐CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno‐occlusive disease.
“I Will Not Stand Aside and Watch. I Will Not be Silent”
Authors: Hanna Amy , Martinez Sainz Gabriela 
Published: December 2023

Abstract
Children are not typically considered as being “political”, but they do possess the right to freedom of association and peaceful assembly under international human rights instruments such as the International Covenant on Civil and Political Rights, and the UN Convention on the Rights of the Child. Nonetheless, a lack of commentary and jurisprudence on this right of children and young people has left it largely unexplored. This article presents the findings from a digital ethnography during the #FridaysForFuture and #ClimateStrikeOnline strikes in 2020 during which young people claimed their right to freedom of assembly both in person and online. Focusing on the right to freedom of assembly, we apply Bennett and Segerberg’s (2012) concept of “connective action” to conceptualise these rights for children and young people under the uncrc, and present a four-part model that captures young people’s exercise of their rights as “connect”, “express”, “collect” and “enact”.
Enhancing Children’s Participation Through Direct Reporting to the Public Authorities
Authors: Long Joëlle 
Published: December 2023

Abstract
Powerful tools for promoting children’s rights include direct reporting, which refers to communicative acts performed by individuals below the age of 18 to draw the attention of public authorities to rights’ violations experienced by themselves or their peers. However, for various reasons, children rarely reach out to public authorities to report offences or abuse. Drawing on data collected from focus groups with children, field visits to children’s ombudspersons, and two surveys conducted as part of the Children Digi-core project, we argue that while direct reporting can empower young people by giving them a voice, it can also result in secondary victimisation if not properly managed. Therefore, it is crucial to establish clear guidelines and procedures to ensure the well-being and protection of children. In light of this, the article offers recommendations to public authorities, particularly local ombudspersons for children, on how to collect and handle children’s reports.
Resolving the phylogeny of Thladiantha (Cucurbitaceae) with three different target capture pipelines
Authors: Raza Mustafa , Ortiz Edgardo M. , Schwung Lea , Shigita Gentaro , Schaefer Hanno 
Published: December 2023

Abstract
Background
Despite recent advances, reliable tools to simultaneously handle different types of sequencing data (e.g., target capture, genome skimming) for phylogenomics are still scarce. Here, we evaluate the performance of the recently developed pipeline Captus in comparison with the well-known target capture pipelines HybPiper and SECAPR. As test data, we analyzed newly generated sequences for the genus Thladiantha (Cucurbitaceae) for which no well-resolved phylogeny estimate has been available so far, as well as simulated reads derived from the genome of Arabidopsis thaliana.

Results
Our pipeline comparisons are based on (1) the time needed for data assembly and locus extraction, (2) locus recovery per sample, (3) the number of informative sites in nucleotide alignments, and (4) the topology of the nuclear and plastid phylogenies. Additionally, the simulated reads derived from the genome of Arabidopsis thaliana were used to evaluate the accuracy and completeness of the recovered loci. In terms of computation time, locus recovery per sample, and informative sites, Captus outperforms HybPiper and SECAPR. The resulting topologies of Captus and SECAPR are identical for coalescent trees but differ when trees are inferred from concatenated alignments. The HybPiper phylogeny is similar to Captus in both methods. The nuclear genes recover a deep split of Thladiantha in two clades, but this is not supported by the plastid data.

Conclusions
Captus is the best choice among the three pipelines in terms of computation time and locus recovery. Even though there is no significant topological difference between the Thladiantha species trees produced by the three pipelines, Captus yields a higher number of gene trees in agreement with the topology of the species tree (i.e., fewer genes in conflict with the species tree topology).