bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fabry disease with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion
Authors: Zhou Shanshan , Wang Xiaocong , Xu Hui , Li Jing , Zhang Liping , Li Hang 
Published: May 2022

Abstract

Rationale:
Fabry disease (FD) is a rare, X-linked lysosomal deposition disease characterized by multi-system symptoms. The accumulation of globotriaosylceramide in various organs, such as the kidneys and heart, as well as the nervous system, has been speculated to be the mechanism involved in tissue damage, including vascular impairment with thrombotic events.

Patient concerns:
Here, we describe a 72-year-old male patient diagnosed with FD, who first presented with acute myocardial infarction, left ventricular thrombosis, and pericardial effusion, accompanied by cardiac hypertrophy.

Diagnoses:
A physical examination showed that he was hemodynamically stable and an electrocardiogram showed ventricular tachycardia (Fig. 1A). The single obvious abnormality was an ST segment depression with a preterminal negative T wave in leads I and aVL (Fig. 1B). Coronary angiography revealed regular findings (Fig. 2). Echocardiogram conducted at our hospital revealed hypertrophy, ejection fraction 40%, pericardial effusion (Fig. 3). Speckle tracking two-dimensional echocardiography strain analysis technology confirmed left ventricular thrombosis, and also revealed decreased movement of the inferior and posterior walls, the basal segment of the posterior wall was locally fibrotic (Fig. 4A and B). Further, myocardial contrast echocardiography confirmed left ventricular thrombosis (Fig. 4C). Cardiovascular magnetic resonance imaging indicated biventricular uneven hypertrophy, which was considered metabolic cardiomyopathy, with diffuse fibrosis of biventricular walls, apical thrombosis, and ischemic cardiomyopathy in the basal segment of the left ventricular lateral wall and left ventricular anterior wall (Fig. 5). Serum alpha-galactosidase concentration was 0.7 nmol/h/mgPr (normal range, 29.0–64.4 nmol/h/mgPr). Subsequent genetic testing revealed that he was hemizygous for a previously reported missense mutation (c.902G>A) inexon 6 of the GLA gene,
[1]
which induce p.R301Q (p.Arg301Gln), confirming a diagnosis of FD (Fig. 6).

Interventions:
Orally administered drugs included rivaroxaban, sacubitril valsartan, beta blockers, dapagliflozin, and mineralocorticoid receptor antagonist. Cardiac resynchronization therapy with an implanted defibrillator was implemented to prevent sudden death.

Outcomes:
At present, he is still in follow-up and there have been no adverse events.

Conclusion:
Our case suggests that clinicians should consider the possibility of FD in patients with acute myocardial infarction and cardiomyopathy. A detailed analysis of subtle historical clues would help promote earlier diagnosis of FD.
Prevalence of Functional Gastrointestinal Disorders in Brazilian Infants Seen in Private Pediatric Practices and Their Associated Factors
Authors: de Morais Mauro Batista , Toporovski Mauro Sergio , Tofoli Marise Helena Cardoso , Barros Karina Vieira , Silva Luciana Rodrigues , Ferreira Cristina Helena Targa 
Published: May 2022

Objectives:
To assess the prevalence of the most frequent functional gastrointestinal disorders (FGIDs) in Brazilian infants seen in private pediatric clinics and their relationship with cesarean delivery, breastfeeding, and history of prematurity.

Methods:
This cross-sectional study enrolled 5080 infants under 12 months old with routine visits in private pediatric clinics in Brazil. The mothers answered questions about the type of delivery, type of feeding (breast milk, infant formula, cow milk, mixed feeding), history of prematurity, and gastrointestinal symptoms. Rome IV criteria were used to diagnose FGIDs.

Results:
The prevalence of infant regurgitation was 10.7% (487/4560); infant colic, 6.1% (131/2162); infant dyschezia, 4.0% (157/3895); functional constipation, 7.6% (341/4506); and functional diarrhea, 0.09% (2/2186). Prematurity was associated (P < 0.05) with infant regurgitation (odds ratio [OR] = 1.41; 95% confidence interval [CI]: 1.05, 1.90), infant colic (OR = 1.97; 95% CI: 1.19, 3.24), infant dyschezia (OR = 1.64, 95% CI: 1.02, 2.64), and functional constipation (OR = 1.44; 95% CI: 1.02, 2.02). Prematurity was associated (P < 0.001) with two or more FGIDs between 21 days and 150 days of age (OR = 3.06; 95% CI: 1.74, 5.37).

Conclusion:
FGIDs are common in infants seen in the private pediatric practice in Brazil. History of prematurity was associated with infant regurgitation, infant colic, functional dyschezia, and functional constipation.
Solitary Fibrous Tumor of the Bone Detected by FDG PET/CT
Authors: Li Jie , Kuang Anren , Shen Guohua 
Published: May 2022

Abstract
Solitary fibrous tumor as a rare mesenchymal tumor can occur in a wide variety of body sites, including serosal membranes, liver, lung, and deep soft tissues; however, primary tumor arising in bone is rarely documented. Herein, we reported the MRI, bone scan, and FDG PET/CT findings of a primary spinal solitary fibrous tumor in a 39-year-old woman.
Retrospective Evaluation of Rabbit Antithymocyte Globulin Induction in Heart Transplant Patients
Authors: Lee Grace Pui-Yun , Cheng Richard K. , Vasbinder Alexi , Wu Sixuan , Wong Beatrice , Farris Stephen D. , Fishbein Daniel , Wong Jenny Man-Ching 
Published: May 2022

Background.
The dosing intensity of antithymocyte globulin as induction therapy in heart transplantation remains controversial. We sought to evaluate the efficacy and safety of rabbit antithymocyte globulin at a total dose of 4.5 mg/kg compared with <4.5 mg/kg.

Methods.
This was a retrospective study of consecutive patients who underwent heart transplantation from January 2016 to December 2018 at a single quaternary care center. Exposure was defined as full antithymocyte globulin (4.5 mg/kg total) induction compared with partial (<4.5 mg/kg) induction. The primary outcome was the incidence of The International Society for Heart and Lung Transplantation 1990 acute cellular rejection grade 2 or above at 2 y. Secondary outcomes were all-cause mortality, number of infections, and time to therapeutic tacrolimus levels. Cox proportional hazard models were used to compare rejection rates and mortality.

Results.
Of 201 patients, 61 received partial and 140 received full induction. There was no difference in the cumulative incidence of cellular rejection grade 2 or above (18% versus 11.4%, P = 0.209) within 2 y. The adjusted hazard ratio was 1.45 (confidence interval: 0.62-3.37, P = 0.388) for partial compared with full induction for any grade rejection. Landmark survival analysis conditional on survival to 1 mo showed no difference in mortality (P = 0.239). There was no difference in the incidence of infection within 3 mo of transplant (partial 29.5% versus full 20.0%, P = 0.140). Both groups achieved therapeutic tacrolimus levels by day 7 after initiation.

Conclusions.
There was no difference in overall risk for any grade cellular rejection between partial or full dose induction therapy. Additionally, there was no difference in medium-term mortality from landmark survival analysis.
Profiling the effects of acne therapeutics, including the novel antibiotic sarecycline, on the human microbiota
Authors: Buckley Anthony , Moura Ines , Clark Emma , Altringham James , Spittal William , Bentley Karen , Wilcox Mark 
Published: May 2022

Many factors shape the human intestinal microbiota, some of which can confer a deleterious effect on the microbiota, e.g. antibiotic therapy. Disruption to the microbiota has been implicated in the progression of C. difficile infection (CDI), multiplication of multi-drug resistant organisms and many extra-intestinal diseases. Thus, determining the off-target effects of antibiotics is essential to determine a patient’s risk of these diseases, particularly for new therapies. Here we characterise the effect of sarecycline, a novel tetracycline antibiotic for the treatment of moderate to severe acne vulgaris; and compared its effect to the gut microbiota with other acne treatments. Using four independent in vitro gut models, we exposed the human microbiota to either sarecycline, minocycline, doxycycline, or clindamycin, and monitored the changes to the bacterial populations, and whether these changes were sufficient to induce CDI.
Sarecycline or doxycycline exposure caused a temporary reduction in the bacterial diversity upon initial exposure. Sarecycline exposure was characterised by a transient increase in Enterococcus spp. and Enterobacteriaceae, and a decrease in Bifidobacterium spp. Doxycycline exposure caused longer-term changes to the Lactobacillaceae and Ruminococcaceae populations. Minocycline exposure resulted in a dramatic reduction to the bacterial diversity, with extensive expansions to the Enterococcus spp. and Enterobacteriaceae populations, whilst the Lactobacillaceae and Ruminococcaceae populations contracted. Whilst clindamycin did induce simulated CDI, neither sarecycline, minocycline, nor doxycycline created a niche conducive for CDI.
These data show that long-term sarecycline use has a lower potential for disruption of the colonic microbiota, compared with the current treatments for acne vulgaris.
The ecology and antimicrobial resistance of Staphylococci colonising neonates
Authors: Felgate Heather , Sethi Dheeraj , Langridge Gemma , Crossman Lisa , Wain John , Clarke Paul , Page Andrew , Webber Mark A 
Published: May 2022

Coagulase Negative Staphylococci (CoNS) are common commensals of human skin, account for nearly 20% of the microbiota in infants and are thought to promote early immune responses in healthy babies. However, CoNS are opportunistic pathogens and in the UK between 2005 and 2014 were responsible for 57% of episodes of Late Onset Sepsis (LOS). In neonatal intensive care units (NICUs) this is a major concern and antiseptics are used to prevent vascular catheter infections. Chlorhexidine (CHX) and Octenidine (OCT) are the most common agents used for skin antisepsis, but evidence is emerging of antiseptic tolerance amongst CoNS.
We undertook a longitudinal survey of CoNS from skin and rectal swabs isolated from babies in two NICUs from countries with different antiseptic regimens (UK and Germany). Over 1000 isolates were characterised for antimicrobial susceptibility and sequenced. The most frequent species isolated were S. epidermidis and S. haemolyticus with similar strain types present in both units. Reduced susceptibility to CHX and OCT was observed in UK isolates (where CHX is used), compared to German isolates (where OCT is used).
Analysis of genome data using GWAS and clustering techniques has identified loci associated with antimicrobial susceptibility. Comparison of isolates taken on admission and thereafter, demonstrated that babies acquired isolates with decreased antiseptic tolerance after admission. This data provides new information about the phylogeny of CoNS in NICUs and suggest different potentials for selection of resistance between antiseptics commonly used in neonatal care.
Inactivation of antibiotic-resistant microorganisms by physical plasma
Authors: Hahn Veronika , Balazinski Martina , Schulz Tilo , Schmidt Michael , Zühlke Daniela , Woedtke Thomas von , Kolb Jürgen , Weltmann Klaus-Dieter , Riedel Katharina 
Published: May 2022

Wastewater treatment plants are “hotspots” for the dissemination of antibiotic-resistant microorganisms (ARM).1 General treatment methods only insuffiently reduce the load.2 Conversely, physical plasma methods have proven to be promising to inactivate microorganisms.3

Different plasma sources were tested according to their efficacy to inactivate ARM. Synthetic wastewater containing Escherichia coli GW-AmxH19 (isolate from hospital wastewater, Greifswald, Germany)4 was treated with the respective plasma source for 30min. The viable count was determined before and after plasma treatment.
In dependence of the source a reduction of the viable count of 1-7 log 10 was achieved.
Thus, physical plasma can be utilized as additional treatment stage in wastewater remediation and may also support the effort of “one health”.

1Rizzo, L.; Manaia, C.; Merlin, C.; Schwartz, T.; Dagot, C.; Ploy, M. C.; Michael, I.; Fatta-Kassinos, D. Science of the Total Environment 2013, 447, 345-360.

2Prado, T.; Pereira, W. C.; Silva, D. M.; Seki, L. M.; Carvalho, A. P. D.; Asensi, M. D. Letters in Applied Microbiology 2008, 46 (1), 136-141.

3Hahn, V.; Dikyol, C.; Altrock, B.; Schmidt, M.; Wende, K.; Ercan, U. K.; Weltmann, K. D.; von Woedtke, T. Plasma Processes and Polymers 2019, 16 (5).

4Schneider, D.; Zühlke, D.; Petscheleit, T.; Poehlein, A.; Riedel, K.; Daniel, R. Germany. Microbiology Resource Announcements 2020, 9 (21), e00279-20 (2pp).
In silico Approaches for Targeting an Essential Mycobacterial Protein, PrsA
Authors: Kingdon Alexander , Alderwick Luke 
Published: May 2022

Mycobacterium tuberculosis is a leading cause of death worldwide and with increasing cases of drug-resistance, new treatments options are required. PrsA is an essential protein in mycobacteria and is necessary for arabinogalactan production and nucleotide biosynthesis. This protein is not currently targeted by any drugs in clinical development and represents a potential drug development avenue.
Currently, no crystal structure of M. tuberculosis PrsA (MtPrsA) is available, hence the SWISS-MODEL structure, based on M. smegmatis (93% similarity) was utilised. Molecular Dynamic simulations were performed on the modelled structure, to gain information on the protein’s predicted flexibility. The output trajectory was clustered, and representatives of each major cluster were used in downstream analysis. Ensemble docking, molecular docking on the ensemble of MtPrsA structures, of the GSK-177 prioritised compounds was undertaken. The docking predictions were also re-evaluated using machine learning based programmes, including NNScore.
This approach yielded several compounds which could be taken forward for further computational analysis. The compound rankings were also retroactively compared to experimental data studying the GSK-177 compounds’ interactions with mycobacteria.
This research represents a potential workflow for future in silico drug development efforts against M. tuberculosis and further work may allow the identified compounds to be used for the treatment of TB.
Shiga toxin-producing E. coli (STEC) isolated from wild mammals in Portugal
Authors: Dias Diana , Costa Sávio , Baraúna Rafael , Fonseca Carlos , Caetano Tânia , Mendo Sónia 
Published: May 2022

Background
Zoonoses are diseases common to humans and animals (livestock, wildlife, and pets). In 2018 about 360 000 zoonoses were reported in European Union. Shiga toxin-producing Escherichia coli (STEC) infections were among the most reported causes of these zoonotic diseases.

Methods
Faecal samples of mammal species (n=286) with distinct phenology (wild boar, red deer, otter, and red fox) were collected in Portugal. After the initial processing, the presence of STEC was screened by PCR, and suspicious samples were platted on CHROMagar STEC. STEC positive isolates were tested for antibiotic susceptibility. Thephylogenetic relationship of STEC strains was evaluated by PFGE. Of these, 20 representative strains were selected for whole genome sequencing with the Illumina NovaSeq 6000 system. For the assembly, annotation and genome characterization, multiple web-based bioinformatic tools were employed.

Results
Cultivable STEC (n=52) were recovered from 17% (n=49) of the samples collected from the four mammals. All the isolates were non-O157:H7 STEC encoding stx1 (n=2; 4%) and/or stx2 genes (n=51; 98%). Only one strain (2%) of red fox was resistant to ceftazidime, aztreonam and nalidixic acid. The 20 strains that were sequenced belong mainly to serotype O27:H30 (n=15), followed by O146:H28 (n=2), O146:H21 (n=1), O178:H19 (n=1) and O103:H2 (n=1). In addition to stx, all strains encode several virulence factors, mainly toxins, adhesins, fimbrae, secretion systems, among others. Additionally, several pathogenicity islands have been predicted for these strains.

Conclusions
Our results show that wild animals are reservoirs of STEC, potentially pathogenic to humans.
Intraspecies-Resolution Metabarcoding: automated primer design and a plant pathology case study
Authors: Pritchard Leighton , Humphris Sonia , Campbell Emma , Watts Lauren , Haynes Ed , Pufal Hollie , Cahill Greig , Davey Triona , Elphinstone John , Toth Ian 
Published: May 2022

We present results demonstrating species-specificity and sub-species resolution by novel, automatically-designed metabarcoding primers for environmental DNA analysis.
Conventional metabarcoding remains a cornerstone of rapid, high-throughput environmental DNA (eDNA) community analysis and biodiversity assessment. Standard barcodes such as 16S (prokaryotes) and ITS1 (fungi/oomycetes) have been instrumental in identifying the complex composition of communities using total eDNA. However, standard barcodes have limitations in terms of resolution and quantitation and, though genus-level identification can be reliable, species-level identification is often not possible.
To overcome the limitations of resolution, we implemented extensions to the diagnostic primer design tool pdp (https://github.com/widdowquinn/find_differential_primers [https://github.com/widdowquinn/find_differential_primers]) that enable automated design of metabarcoding markers and corresponding primers that are (i) specific to a prescribed taxon at species level and (ii) capable of discriminating between members of the same species. This allows for rapid, high-throughput measurement of diversity below species level for a target organism.
We aimed to survey geographical distribution and pathogen transfer of the widespread plant pathogenic bacterium Pectobacterium atrosepticum (Pba). This organism has considerable sub-species taxonomic structure identifiable using MLST and with whole-genome methods, but which is not accessible using standard barcodes. We designed metabarcoding primers (202bp) specific to Pba using `pdp`, and established that these have resolution comparable to eight-gene MLST, revealing sub species-level diversity within single fields, and on the same individual plant host.
Epigenetic Modification Impacts on Gene Regulation in Streptococcus pneumoniae
Authors: Althari Yasmeen , Chen Yongkui , Haigh Richard , Oggioni Marco 
Published: May 2022

Methylation by the type I restriction modification system (RMS) SpnIII in Streptococcus pneumoniae is hypothesised to regulate gene expression via epigenetic changes (Manos). The phase variable SpnIII generates six host specificity determinants (hsdS) alleles through site-specific recombination (DeSteCroix), each allele correspond with different methylation pattern.
In addition to known functions of the RMS in restricting phage infection (Furi) and transformation (Kwun), we have now tested impact on gene expression. RNAseq was used to analyse S. pneumoniae strains expressing a single spnIII allele (spnIIIA, spnIIIB or spnIIIE) to determine differences in gene expression profiles. The data have identified six genes which show differential expression and have a methylation site mapping to their predicted promoter region. Three synthetic promoters with the wild type and altered methylation target site were cloned in front of a luciferase gene in strains expressing a single spnIII alleles. For the first three sets of constructs analysed, data indicate that the methylated promoters show a three- to twenty-fold higher activity compared to non-methylated promoters. Results obtained were further confirmed by qPCR analysis. Preliminary data using drugs targeting DNA topoisomerases indicate that the mechanism by which methylation impact gene expression could be related to DNA topology. These data demonstrate for the first-time RMS dependent variations in gene expression and propose an alternative mechanism for this epigenetic regulation.
References:
* Manso, Nature Communication, 2014; 5:5055.
* De Ste Croix, J. Bacteriol. 2019; 201(15). pii: e00233-19.
* Furi, J. Bacteriol. 2019; 201(19). pii: e00370-19.
* Kwun, Nucleic Acids Res. 2018; 46(21):11438-11453.
Environment and the Evolutionary Trajectory of Horizontal Gene Transfer
Authors: Bhatia Rama , Kirit Hande , Bollback Jonathan 
Published: May 2022

Gene acquisition through horizontal gene transfer (HGT) may either exert a beneficial, neutral, or deleterious fitness effect on the recipient cell thereby determining the evolutionary fate of the newly transferred gene. The distribution of fitness effects (DFE) thus is a fundamental predictor of the outcome of an HGT event.
The environment plays a considerable role in altering the fitness of a horizontally transferred gene. We have studied the DFE of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability, with some genes becoming deleterious in one environment, while becoming neutral or even beneficial in another, suggesting that fluctuating environments may increase the likelihood of HGT.
The present study focuses on the DFE of genes transferred from Escherichia coli to macrophage-associated Salmonella Typhimurium strain 4/74 in four environments, that mimic the conditions inside a macrophage cell. In addition to the external environment, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. Functional similarity of the horizontally transferred gene to the endogenous copy can cause an imbalance due to increased protein dosage, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the ‘wild type’, in the four environments, we can elucidate when gene dosage acts as a barrier to HGT, helping us to understand the relationship of environmental quality and HGT, which is of evolutionary importance. We have identified 12 genes showing dosage dependent effects across the four environments, with some genes showing environment specificity, indicating an increased intolerance of the recipient to high protein dosage, making it a significant barrier to HGT.
A preprint is available on bioRxiv https://doi.org/10.1101/2022.04.01.486712
Automated pseudogene detection reveals insights into historical gene sharing dynamics in prokaryotes
Authors: Dimonaco Nicholas J , Aubrey Wayne , Clare Amanda , Kenobi Kim , Creevey Chris 
Published: May 2022

In recent years it has become apparent that prokaryotic genomes contain large numbers of pseudogenised genes which may provide valuable insights into the recent functional history of an organism. However, pseudogenes are difficult to detectab initioand are not routinely reported by gene prediction tools.
We present StORF-R(Stop-ORF-Reporter), a tool that takes as input an annotated genome and returns putative missed genes (functional and/or pseudogenised) from the intergenic regions. We show that this methodology can recover gene-families that the state-of-the-art methods continue to misreport or completely omit.
We applied StORF-R to the intergenic regions of2,665E. coligenomes and found on average 244 previously missed pseudogenised genes (with in-frame stop codons) per genome, many of which had high scoring similarity to known Swiss-Prot proteins. Many of these pseudogenised genes form widespread gene families across E. coli strains.
To investigate if this phenomenon exists in other taxa we further applied the methodology to 44,048 bacterial genomes representing 8,244 species from Ensembl. This revealed manygene-families spanning multiple species with large (>10,000) numbers of copies of both intact and pseudogenised versions. Many of these families had only previously been reported in a single or few genomes, though we detected many hundred pseudogenised versions with StORF-R, changing our understanding of how widespread these genes truly are.
These pseudogenised genes represent a pangenomic ‘graveyard’ which may alter our understanding of the definition of core and accessory genes for many species.