bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic modification of
Streptococcus dysgalactiae
by natural transformation
Authors: Mårli Marita Torrissen , Oppegaard Oddvar , Porcellato Davide , Straume Daniel , Kjos Morten 
Published: June 2024

ABSTRACT

Streptococcus dysgalactiae
is an emerging human and animal pathogen. Functional studies of genes involved in virulence of
S. dysgalactiae
and other pyogenic group streptococci are often hampered by limited genetic tractability. It is known that pyogenic streptococci carry genes required for competence for natural transformation; however, in contrast to other streptococcal subgroups, there is limited evidence for gene transfer by natural transformation in these bacteria. In this study, we systematically assessed the genomes of 179
S
.
dysgalactiae
strains of both human and animal origins (subsp.
equisimilis
and
dysgalactiae,
respectively) for the presence of genes required for natural transformation. While a considerable fraction of the strains contained inactive genes, the majority (64.2%) of the strains had an intact gene set. In selected strains, we examined the dynamics of competence activation after addition of competence-inducing pheromones using transcriptional reporter assays and exploratory RNA-seq. Based on these findings, we were able to establish a protocol allowing us to utilize natural transformation to construct deletion mutants by allelic exchange in several
S. dysgalactiae
strains of both subspecies. As part of the work, we deleted putative lactose utilization genes to study their role in growth on lactose. The data presented here provide new knowledge on the potential of horizonal gene transfer by natural transformation in
S. dysgalactiae
and, importantly, demonstrates the possibility to exploit natural transformation for genetic engineering in these bacteria.

IMPORTANCE

Numerous
Streptococcus
spp. exchange genes horizontally through natural transformation, which also facilitates efficient genetic engineering in these organisms. However, for the pyogenic group of streptococci, including the emerging pathogen
Streptococcus dysgalactiae
, there is limited experimental evidence for natural transformation. In this study, we demonstrate that natural transformation
in vitro
indeed is possible in
S. dysgalactiae
strains under optimal conditions. We utilized this method to perform gene deletion through allelic exchange in several strains, thereby paving the way for more efficient gene engineering methods in pyogenic streptococci.
Gemykibivirus detection in acute encephalitis patients from Nepal
Authors: Tuladhar Eans Tara , Shrestha Smita , Vernon Susan , Droit Lindsay , Mihindukulasuriya Kathie A. , Tamang Mamta , Karki Lata , Elong Ngono Annie , Jha Bimlesh , Awal Bal Krishna , Chalise Bimal Sharma , Jha Runa , Shresta Sujan , Wang David , Manandhar Krishna Das 
Published: June 2024

ABSTRACT

Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the family
Genomoviridae
. The complete genome of 2,211 nucleotides was sequenced, which shared 98.69% nucleotide identity to its closest relative, Human associated gemykibivirus 2 isolate SAfia-449D. Two real-time PCR assays were designed, and screening of 337 cerebrospinal fluid (CSF) and 164 serum samples from AES patients in Nepal collected in 2020 and 2022 yielded 11 CSF and 1 serum sample that were positive in both PCR assays. Complete genomes of seven of the positives were sequenced. These results identify a potential candidate etiologic agent of encephalitis in Nepal.

IMPORTANCE
Viral encephalitis is a devastating disease, but unfortunately, worldwide, the causative virus in many cases is unknown. Therefore, it is important to identify viruses that could be responsible for cases of human encephalitis. Here, using metagenomic sequencing of CSF, we identified a gemykibivirus in a male child from Nepal with acute encephalitis syndrome (AES). We subsequently detected gemykibivirus DNA in CSF or serum of 12 more encephalitis patients by real-time PCR. The virus genomes we identified are highly similar to gemykibiviruses previously detected in CSF of three encephalitis patients from Sri Lanka. These results raise the possibility that gemykibivirus could be an underrecognized human pathogen.
The potential of
Pseudomonas fluorescens
SBW25 to produce viscosin enhances wheat root colonization and shapes root-associated microbial communities in a plant genotype-dependent manner in soil systems
Authors: Guan Ying , Bak Frederik , Hennessy Rosanna Catherine , Horn Herms Courtney , Elberg Christine Lorenzen , Dresbøll Dorte Bodin , Winding Anne , Sapkota Rumakanta , Nicolaisen Mette Haubjerg 
Published: June 2024

ABSTRACT

Microorganisms interact with plant roots through colonization of the root surface, i.e., the rhizoplane or the surrounding soil, i.e., the rhizosphere. Beneficial rhizosphere bacteria such as
Pseudomonas
spp. can promote plant growth and protect against pathogens by producing a range of bioactive compounds, including specialized metabolites like cyclic lipopeptides (CLPs) known for their biosurfactant and antimicrobial activities. However, the role of CLPs in natural soil systems during bacteria-plant interactions is underexplored. Here,
Pseudomonas fluorescens
SBW25, producing the CLP viscosin, was used to study the impact of viscosin on bacterial root colonization and microbiome assembly in two cultivars of winter wheat (Heerup and Sheriff). We inoculated germinated wheat seeds with SBW25 wild type or a viscosin-deficient mutant and grew the plants in agricultural soil. After 2 weeks, enhanced root colonization of SBW25 wild type compared to the viscosin-deficient mutant was observed, while no differences were observed between wheat cultivars. In contrast, the impact on root-associated microbial community structure was plant-genotype-specific, and SBW25 wild type specifically reduced the relative abundance of an unclassified oomycete and
Phytophthora
in Sheriff and Heerup, respectively. This study provides new insights into the natural role of viscosin and specifically highlights the importance of viscosin in wheat root colonization under natural soil conditions and in shaping the root microbial communities associated with different wheat cultivars. Furthermore, it pinpoints the significance of microbial microdiversity, plant genotype, and microbe-microbe interactions when studying colonization of plant roots.

IMPORTANCE

Understanding parameters governing microbiome assembly on plant roots is critical for successfully exploiting beneficial plant-microbe interactions for improved plant growth under low-input conditions. While it is well-known from
in vitro
studies that specialized metabolites are important for plant-microbe interactions, e.g., root colonization, studies on the ecological role under natural soil conditions are limited. This might explain the often-low translational power from laboratory testing to field performance of microbial inoculants. Here, we showed that viscosin synthesis potential results in a differential impact on the microbiome assembly dependent on wheat cultivar, unlinked to colonization potential. Overall, our study provides novel insights into factors governing microbial assembly on plant roots, and how this has a derived but differential effect on the bacterial and protist communities.
Top 10 research priorities for congenital diaphragmatic hernia in Australia: James Lind Alliance Priority Setting Partnership
Authors: Chiletti Roberto , Vodopic Courtney , Hunt Emiko , Lawer Jess , Bertinetti Monique , Malarbi Stephanie , Kyritsis Valerie , Petersen Scott , Stewart David , Hellstern Jean , Stewart Michael , Hickey Leah , Tingay David G , Prentice Trisha M 
Published: June 2024

ObjectivesThe Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance (JLA) and the Murdoch Children’s Research Institute to identify research priorities for people with CDH, their families and healthcare workers in Australasia.DesignResearch PSP in accordance with the JLA standardised methodology.SettingAustralian community and institutions caring for patients with CDH and their families.PatientsCDH survivors, families of children born with CDH (including bereaved) and healthcare professionals including critical care physicians and nurses (neonatal and paediatric), obstetric, surgical, allied health professionals (physiotherapists, speech pathologists and speech therapists) and general practitioners.Main outcome measureTop 10 research priorities for CDH.Results377 questions, from a community-based online survey, were categorised and collated into 50 research questions. Through a further prioritisation process, 21 questions were then discussed at a prioritisation workshop where they were ranked by 21 participants (CDH survivors, parents of children born with CDH (bereaved and not) and 11 multidisciplinary healthcare professionals) into their top 10 research priorities.ConclusionStakeholders’ involvement identified the top 10 CDH-related research questions, spanning from antenatal care to long-term functional outcomes, that should be prioritised for future research to maximise meaningful outcomes for people with CDH and their families.
Reproducibility Report for the Paper: "Spatial/Temporal Locality-based Load-sharing in Speculative Discrete Event Simulation on Multi-core Machines"
Authors: Tan Wen Jun 
Published: June 2024

All Badges available in this process are awarded to the paper “Spatial/Temporal Locality-based Load-sharing in Speculative Discrete Event Simulation on Multi-core Machines”. The authors have uploaded their artifacts to Zenodo, which ensures a long-term retention of the artifact. This paper can thus receive the
Artifacts Available
badge. The artifact allows for easy re-running of experiments for 14 Figures and 4 tables. All of the dependencies are documented. The software in the artifact runs correctly with minimal intervention, and is relevant to the paper, earning the
Artifacts Evaluated–Functional
badge. The experimental results are reproduced in 9 experiments, which gains the
Results Reproduced
badge. Furthermore, since the artifact is also available on GitHub, the paper is assigned the
Artifacts Evaluated–Reusable
badge.
Folate Metabolism and Risk of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis from the Childhood Cancer and Leukemia International Consortium
Authors: Metayer Catherine , Spector Logan G. , Scheurer Michael E. , Jeon Soyoung , Scott Rodney J. , Takagi Masatoshi , Clavel Jacqueline , Manabe Atsushi , Ma Xiaomei , Hailu Elleni M. , Lupo Philip J. , Urayama Kevin Y. , Bonaventure Audrey , Kato Motohiro , Meirhaeghe Aline , Chiang Charleston W.K. , Morimoto Libby M. , Wiemels Joseph L. 
Published: June 2024

Abstract

Background:
Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

Methods:
We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.

Results:
None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10−6 and less-stringent P-value of 3.5 × 10−5 accounting for the number of “independent” SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.

Conclusions:
This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.

Impact:
Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene–folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.
Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis
Authors: Tabariès Sébastien , Robert Alma , Marcil Anne , Ling Binbing , Acchione Mauro , Lippens Julie , Pagé Martine , Fortin Annie , Meury Luc , Coutu Mathieu , Annis Matthew G. , Girondel Charlotte , Navarre Julie , Jaramillo Maria , Moraitis Anna N. , Siegel Peter M. 
Published: June 2024

Abstract
We have previously demonstrated that Claudin-2 is required for colorectal cancer (CRC) liver metastasis. The expression of Claudin-2 in primary CRC is associated with poor survival and highly expressed in liver metastases. Claudin-2 also promotes breast cancer liver metastasis by enabling seeding and cancer cell survival. These observations support Claudin-2 as a potential therapeutic target for managing patients with liver metastases. Antibody–drug conjugates (ADC) are promising antitumor therapeutics, which combine the specific targeting ability of monoclonal antibodies with the potent cell killing activity of cytotoxic drugs. Herein, we report the generation of 28 anti-Claudin-2 antibodies for which the binding specificities, cross-reactivity with claudin family members, and cross-species reactivity were assessed by flow cytometry analysis. Multiple drug conjugates were tested, and PNU was selected for conjugation with anti-Claudin-2 antibodies binding either extracellular loop 1 or 2. Anti-Claudin-2 ADCs were efficiently internalized and were effective at killing Claudin-2-expressing CRC cancer cells in vitro. Importantly, PNU-conjugated-anti-Claudin-2 ADCs impaired the development of replacement-type CRC liver metastases in vivo, using established CRC cell lines and patient-derived xenograft (PDX) models of CRC liver metastases. Results suggest that the development of ADCs targeting Claudin-2 is a promising therapeutic strategy for managing patients with CRC liver-metastatic disease who present replacement-type liver metastases.
Level of Perivascular Inflammation Is Significantly Lower Around the Left Internal Mammary Artery Than Around Native Coronary Arteries
Authors: Yuki Haruhito , Sundt Thoralf M. , Niida Takayuki , Suzuki Keishi , Kinoshita Daisuke , Fujimoto Daichi , Dey Damini , Lee Hang , McNulty Iris , Naganuma Toru , Nakamura Sunao , Usui Eisuke , Kakuta Tsunekazu , Jang Ik‐Kyung 
Published: June 2024

Background
The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease.

Methods and Results

A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (−82.9 [−87.3 to −78.0] versus −70.8 [−75.9 to −65.9];
P
<0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16–7.59];
P
=0.017).

Conclusions
The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA.

Registration

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT04523194.
Age‐Related Risk of Stroke Following Ocular Motor Cranial Nerve Palsy
Authors: Choi Daye Diana , Cheon Dae Young , Park Kyung‐Ah , Han Kyung‐Do , Jung Jin‐Hyung , Oh Sei Yeul 
Published: June 2024

Background
This cohort study aims to examine the relationship between the occurrence of cranial nerve palsy (CNP) affecting the third, fourth, or sixth cranial nerve and the subsequent risk of stroke, with a particular focus on the modulating effect of age on this association.

Methods and Results
We established a cohort of individuals diagnosed with third, fourth, or sixth CNP who underwent national health screening within 2 years of diagnosis from 2010 to 2017. A control group was matched by sex and age at a ratio of 1:5. Participants were followed until December 31, 2019. We use multivariable Cox proportional hazards regression analyses to assess the association between ocular motor CNP and subsequent stroke stratified by age. Covariates including lifestyle, health behavior, underlying comorbidities, and Charlson comorbidity index score were also adjusted. Compared with the control group, the ocular motor CNP group had a higher risk of stroke after adjusting for potential confounders (hazard ratio [HR], 1.23 [95% CI,, 1.08–1.39]). The risk of stroke increased by 8.91 times in individuals with ocular motor CNP who were in their 30s (HR, 8.91 [95% CI, 1.63–48.66]). The risk increased by 2.49 times in those who were in their 40s, 1.78 times in those who were in their 50s, and 1.32 times in those who were in their 60s (HRs, 2.49, 1.78, and 1.32 [95% CI, 1.39–4.45, 1.31–2.42, and 1.08–1.62], respectively). However, for those who were in their 20s, 70s, or 80s, the incidence of stroke did not significantly increase.

Conclusions
Our study establishes an association between ocular motor CNP and an increased risk of stroke, particularly in young adults.
Heart Size Difference Drives Sex‐Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE‐MPP CRT Trial
Authors: Wijesuriya Nadeev , Mehta Vishal , De Vere Felicity , Howell Sandra , Niederer Steven A. , Burri Haran , Sperzel Johannes , Calo Leonardo , Thibault Bernard , Lin Wenjiao , Lee Kwangdeok , Grammatico Andrea , Varma Niraj , Gwechenberger Marianne , Leclercq Christophe , Rinaldi Christopher A. 
Published: June 2024

Background
Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex‐specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics.

Methods and Results

This is a post hoc analysis of the MORE‐CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing) trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle‐branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end‐diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%,
P
<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle‐branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (
P
<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708,
P
<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (
P
=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms.

Conclusions
In the nonischemic cardiomyopathy left bundle‐branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex‐specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex‐specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.
Prognostic Utility of Pericardial Effusion in the General Population: Findings From the STAAB Cohort Study
Authors: Sahiti Floran , Cejka Vladimir , Schmidbauer Lena , Albert Judith , Kerwagen Fabian , Frantz Stefan , Gelbrich Götz , Heuschmann Peter U. , Störk Stefan , Morbach Caroline , Maack Christoph , Ertl Georg , Wanner Christoph , Leyh Rainer , Volkmann Jens , Deckert Jürgen , Faller Hermann , Jahns Roland 
Published: June 2024

Background
The incidental finding of a pericardial effusion (PE) poses a challenge in clinical care. PE is associated with malignant conditions or severe cardiac disease but may also be observed in healthy individuals. This study explored the prevalence, determinants, course, and prognostic relevance of PE in a population‐based cohort.

Methods and Results
The STAAB (Characteristics and Course of Heart Failure Stages A/B and Determinants of Progression) cohort study recruited a representative sample of the population of Würzburg, aged 30 to 79 years. Participants underwent quality‐controlled transthoracic echocardiography including the dedicated evaluation of the pericardial space. Of 4965 individuals included at baseline (mean age, 55±12 years; 52% women), 134 (2.7%) exhibited an incidentally diagnosed PE (median diameter, 2.7 mm; quartiles, 2.0–4.1 mm). In multivariable logistic regression, lower body mass index and higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels were associated with PE at baseline, whereas inflammation, malignancy, and rheumatoid disease were not. Among the 3901 participants attending the follow‐up examination after a median time of 34 (30–41) months, PE was found in 60 individuals (1.5%; n=18 new PE, n=42 persistent PE). Within the follow‐up period, 37 participants died and 93 participants reported a newly diagnosed malignancy. The presence of PE did not predict all‐cause death or the development of new malignancy.

Conclusions
Incidental PE was detected in about 3% of individuals, with the vast majority measuring <10 mm and completely resolving. PE was not associated with inflammation markers, death, incident heart failure, or malignancy. Our findings corroborate the view of current guidelines that a small PE in asymptomatic individuals can be considered an innocent phenomenon and does not require extensive short‐term monitoring.