bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Robotic Manipulation With Decision-RWKV: A Recurrent Sequence Modeling Approach for Lifelong Learning
Authors: Dong Yujian , Wu Tianyu , Song Chaoyang 
Published: December 2024

Abstract
Models based on the transformer architecture have seen widespread application across fields such as natural language processing (NLP), computer vision, and robotics, with large language models (LLMs) like ChatGPT revolutionizing machine understanding of human language and demonstrating impressive memory capacity and reproduction capabilities. Traditional machine learning algorithms struggle with catastrophic forgetting, detrimental to the diverse and generalized abilities required for robotic deployment. This article investigates the receptance weighted key value (RWKV) framework, known for its advanced capabilities in efficient and effective sequence modeling, integration with the decision transformer (DT), and experience replay architectures. It focuses on potential performance enhancements in sequence decision-making and lifelong robotic learning tasks. We introduce the decision-RWKV (DRWKV) model and conduct extensive experiments using the D4RL database within the OpenAI Gym environment and on the D’Claw platform to assess the DRWKV model’s performance in single-task tests and lifelong learning scenarios, showing its ability to handle multiple subtasks efficiently. The code for all algorithms, training, and image rendering in this study is available online (open source).
Genetic interaction analysis of
Candida glabrata
transcription factors
CST6
and
UPC2A
in the regulation of respiration and fluconazole susceptibility
Authors: Ollinger Tomye L. , Zarnowski Robert , Parker Josie E. , Kelly Steven L. , Andes David R. , Stamnes Mark A. , Krysan Damian J. 
Published: December 2024

ABSTRACT

Candida glabrata
is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other
Candida
spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an
in vitro
microevolution experiment, we found that loss-of-function mutants of the ATF/CREB transcription factor
CST6
suppresses the fluconazole hyper-susceptibility of the
upc2A
∆ mutant. Here, we confirm that the
cst6
∆
upc2A
∆ mutants are resistant to fluconazole but not to hypoxia relative to the
upc2A
∆ mutant. Sterol analysis of these mutants indicates that this suppression phenotype is not due to restoration of ergosterol levels in the
cst6
∆
upc2A
∆ mutant. Furthermore, increased expression of
CDR1
, the efflux pump implicated in the vast majority of azole-resistant
C. glabrata
strains, does not account for the suppression phenotype. Instead, our data suggest that this effect is due in part to increased expression of the adhesin
EPA3
, which has been shown by others to reduce fluconazole susceptibility in
C. glabrata
. In addition, we find that loss of both
UPC2A
and
CST6
reduces the expression of mitochondrial and respiratory genes and that this also contributes to the suppression phenotype as well as to the resistance of
cst6
∆ to fluconazole. These latter data further emphasize the connection between mitochondrial function and azole susceptibility.
A microaerobically induced small heat shock protein contributes to
Rhizobium leguminosarum
/
Pisum sativum
symbiosis and interacts with a wide range of bacteroid proteins
Authors: Domingo-Serrano Lucía , Sanchis-López Claudia , Alejandre Carla , Soldek Joanna , Palacios José Manuel , Albareda Marta 
Published: December 2024

ABSTRACT

During the establishment of the symbiosis with legume plants, rhizobia are exposed to hostile physical and chemical microenvironments to which adaptations are required. Stress response proteins including small heat shock proteins (sHSPs) were previously shown to be differentially regulated in bacteroids induced by
Rhizobium leguminosarum
bv. viciae UPM791 in different hosts. In this work, we undertook a functional analysis of the host-dependent sHSP RLV_1399. A
rlv_1399-
deleted mutant strain was impaired in the symbiotic performance with peas but not with lentil plants. Expression of
rlv_1399
gene was induced under microaerobic conditions in a FnrN-dependent manner consistent with the presence of an anaerobox in its regulatory region. Overexpression of this sHSP improves the viability of bacterial cultures following exposure to hydrogen peroxide and to cationic nodule-specific cysteine-rich (NCR) antimicrobial peptides. Co-purification experiments have identified proteins related to nitrogenase synthesis, stress response, carbon and nitrogen metabolism, and to other relevant cellular functions as potential substrates for RLV_1399 in pea bacteroids. These results, along with the presence of unusually high number of copies of
shsp
genes in rhizobial genomes, indicate that sHSPs might play a relevant role in the adaptation of the bacteria against stress conditions inside their host.

IMPORTANCE

The identification and analysis of the mechanisms involved in host-dependent bacterial stress response is important to develop optimal
Rhizobium
/legume combinations to maximize nitrogen fixation for inoculant development and might have also applications to extend nitrogen fixation to other crops. The data presented in this work indicate that sHSP RLV_1399 is part of the bacterial stress response to face specific stress conditions offered by each legume host. The identification of a wide diversity of sHSP potential targets reveals the potential of this protein to protect essential bacteroid functions. The finding that nitrogenase is the most abundant RLV_1399 substrate suggests that this protein is required to obtain an optimal nitrogen-fixing symbiosis.
Positive regulation of a LuxR family protein, MilO, in mildiomycin biosynthesis
Authors: Li Zhiyu , Wang Yuli , Lin Chen , Wen Yu , Deng Zixin , Jiang Ming , He Xinyi 
Published: December 2024

ABSTRACT

Mildiomycin is a representative peptidyl nucleoside antibiotic and was first isolated from
Streptoverticillium rimofaciens
, which has been used as an important biological agent to control powdery mildew in plants. Despite its importance, the biosynthetic pathways and regulatory mechanisms remain to be fully elucidated. In this study, we identified MilO as a positive pathway-specific regulator of mildiomycin biosynthesis in the heterologous host
Streptomyces avermitilis
. Gene disruption of
milO
resulted in almost loss of mildiomycin production, and it was restored to the level comparable to that in the wild-type strain in complemented strain. Overexpression of
milO
using host native promoter
rpsJ
p, engineered promotor
SP44,
and
kasO
p* led to a 50%, 6.5-fold, and 9.2-fold increase in mildiomycin production compared with the wild-type strain, respectively. Quantitative real-time PCR and electrophoretic mobility shift assay (EMSA) experiments revealed that MilO directly enhances the transcription of the
milA
gene by 20 folds after 48 h fermentation and indirectly regulates the transcription levels of other genes from
milB
to
milM
. Using DNase I footprinting assays,
milO
was revealed to bind to a 44 bp DNA sequence of the
milA
promoter region. The binding region consists of three imperfect direct repeats of TGTC(N)
3
CGGT separated by two-nucleotide spacers and each repeat is important to efficient binding to MilO. In addition, we identified two related compounds by overexpressing
milO
in a structural gene
milN
-deficient mutant. Taken together, this study indicates that pathway-specific regulator MilO is essential for mildiomycin biosynthesis and provides an effective strategy to improve the production of mildiomycin and its intermediates.

IMPORTANCE

As an important biological agent to control powdery mildew on plants, mildiomycin has been commercialized and used in various plants. However, its regulatory mechanisms and biosynthetic pathways remain unknown. This study provides new insights into the regulation of mildiomycin biosynthesis through MilO, a LuxR family protein that modulates mildiomycin production by directly enhancing the transcription of
milA
. The yield of mildiomycin was significantly improved by overexpressing
milO
in a heterologous host. In addition, the positive regulatory effect of
milO
helped to discover two related compounds, which provide important clues for the timing of uploading of two amino acid side chains during mildiomycin biosynthesis for the first time. In brief, our findings on transcriptional regulation of mildiomycin biosynthesis by
milO
will be valuable to further increase the yield of mildiomycin and explore its biosynthetic pathways.
Single-chain antibody gene therapy strategy based on high-throughput screening triggers sustained antiviral activity in the body
Authors: Zhao Liang , Wei Xue-Feng , Xu Kun , Zhao Zhao , Chen Guo , Wang Hou-Peng , Zhu Bin 
Published: December 2024

ABSTRACT

The occurrence of viral diseases poses a huge threat and impact on human public health safety and the development of the animal and fishery industry. Here, a strain of single-chain antibody fragment, scFv-1, was isolated from the phage antibody display library construct by immunizing New Zealand white rabbits with rhabdovirus.
In vitro
analysis showed that the single-chain antibody could inhibit the infection of the virus in multiple pathways, including adsorption, fusion, and release.
In vivo
analysis revealed scFv-1 had a preventive and protective effect against the infection of virus. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, avoiding the need for lifelong, repeated passive immunization for treatment. In sum, high-throughput screening of neutralization genes based on phage display technology and transposon vector-based gene transfer provides effective methods for treating and preventing diseases and avoiding repetitive passive immunotherapy. This study also provides a reference for the prevention and treatment of unknown pathogens.

IMPORTANCE
Livestock and fisheries play an important role in economic development and food security. The frequent outbreaks of viral diseases have caused great losses to the livestock industry, while the increase in drug resistance caused by the use of antibiotics as well as the potential risks to human health have raised serious concerns. Here, we constructed a phage display antibody library by immunizing New Zealand white rabbits with purified rhabdovirus and selected a single-chain antibody, scFv-1, with good neutralizing activity, which was validated and found to be able to block multiple phases of the virus and thus play a neutralizing role. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, reducing the need for lifelong, repeated passive immunization for treatment. Our work not only provides methods for the prevention and treatment of viral diseases but also provides the body with long-lasting and even permanent protection against repeated passive immunization.
Complete genome of the mutualistic symbiont
Buchnera aphidicola
AIST from a Japanese strain of the pea aphid
Acyrthosiphon pisum
Authors: Mizutani Masaki , Koga Ryuichi , Fukatsu Takema , Kakizawa Shigeyuki 
Published: December 2024

ABSTRACT

The genome of
Buchnera aphidicola
National Institute of Advanced Industrial Science and Technology (AIST), an obligate bacterial endosymbiont from a Japanese strain of the pea aphid
Acyrthosiphon pisum
, was determined. The genome sequence provides valuable information for comparative and evolutionary aspects of the intimate insect-microbe mutualism.
Response of the gut microbiome and metabolome to dietary fiber in healthy dogs
Authors: Bhosle Amrisha , Jackson Matthew I. , Walsh Aaron M. , Franzosa Eric A. , Badri Dayakar V. , Huttenhower Curtis 
Published: December 2024

ABSTRACT

Dietary fiber confers multiple health benefits originating from the expansion of beneficial gut microbial activity. However, very few studies have established the metabolic consequences of interactions among specific fibers, microbiome composition, and function in either human or representative animal models. In a study design reflective of realistic population dietary variation, fecal metagenomic and metabolomic profiles were analyzed from healthy dogs fed 12 test foods containing different fiber sources and quantities (5–13% as-fed basis). Taxa and functions were identified whose abundances were associated either with overall fiber intake or with specific fiber compositions. Fourteen microbial species were significantly enriched in response to ≥1 specific fiber source; enrichment of fiber-derived metabolites was more pronounced in response to these fiber sources. Positively associated fecal metabolites, including short-chain fatty acids, acylglycerols, fiber bound sugars, and polyphenols, co-occurred with microbes enriched in specific food groups. Critically, the specific metabolite pools responsive to differential fiber intake were dependent on differences both in individual microbial community membership and in overall ecological configuration. This helps to explain, for the first time, differences in microbiome-diet associations observed in companion animal epidemiology. Thus, our study corroborates findings in human cohorts and reinforces the role of personalized microbiomes even in seemingly phenotypically homogeneous subjects.

IMPORTANCE
Consumption of dietary fiber changes the composition of the gut microbiome and, to a larger extent, the associated metabolites. Production of health-relevant metabolites such as short-chain fatty acids from fiber depends both on the consumption of a specific fiber and on the enrichment of beneficial metabolite-producing species in response to it. Even in a seemingly homogeneous population, the benefit received from fiber consumption is personalized and emphasizes specific fiber-microbe-host interactions. These observations are relevant for both population-wide and personalized nutrition applications.
Comparison of positive BioFire FilmArray meningitis/encephalitis (ME) panels, CSF cultures, CSF parameters, clinical presentation and in-patient mortality among patients with bacterial and fungal meningitis
Authors: Myint Thein , Soria Jaime , Gao Yuanzheng , Conejo Castillo Marice Ruiz , Arora Vaneet , Ribes Julie A. 
Published: December 2024

ABSTRACT

The BioFire FilmArray meningitis/encephalitis panel (MEP) was brought to the University of Kentucky in 2016 to aid in the identification of community-acquired meningitis and encephalitis (ME). This panel has shown variable performance with some institutions showing high sensitivity and specificity for many pathogens but others seeing false positives during clinical use. We evaluated the panel’s performance using retrospective chart review of patients at the University of Kentucky from October 2016 to September 2022, including 7,551 MEP results. Cerebrospinal fluid (CSF) samples with positive results for bacterial and fungal pathogens were compared with CSF and blood cultures, other laboratory parameters, and clinical presentations, to classify MEP results as true positive (TP), likely TP, or false positive (FP). Of 132 patients with positive bacterial or fungal MEP results, 48.9% of bacterial and 88.9% of cryptococcal analytes were classified as TP. The positive predictive value (PPV) varied by organism, with the highest being
Listeria monocytogenes
and
Neisseria meningitidis
. One-third of the FP results were
Streptococcus agalactiae
. Among patients with likely TP, 75.7% (28 out of 37) received oral or IV antibiotics before blood or CSF culture. MEP was 100% specific compared to culture. The PPV based on pathogen ranged from 78.6% to 100%. Interestingly, 27.4% (29 out of 106) cases (excluding FPs) would have no pathogen definitively identified if MEP had not been used. This study highlights the utility of MEP in rapidly diagnosing ME, particularly in patients pretreated with antibiotics. It also emphasizes the importance of correlating MEP results with clinical assessments and other diagnostic tests to assure accuracy.

IMPORTANCE
This study compares the performance of the meningitis/encephalitis panel (MEP) in detecting bacterial and fungal pathogens with cerebrospinal fluid cultures and other parameters. Almost half of bacterial analytes of MEP had positive cerebrospinal fluid (CSF) or blood cultures; the remaining 42% of bacterial analytes were correlated with clinical presentation and other CSF parameters. 27.4% (29 out of 106) cases would not have had a pathogen definitively identified if the MEP had not been used. This study highlights the importance of using MEP as a diagnostic tool, especially in patients who have already received antibiotics, where traditional culture-based methods may not be diagnostic. This research underscores the use of MEP in improving the speed of diagnosing meningitis. However, it emphasizes that MEP can produce false positive results in some patients. It is therefore necessary to interpret MEP results together with clinical assessments and other diagnostic tests to ensure the most accurate diagnosis.
Effectiveness of nutritional education intervention during pregnancy on birth outcomes in sub-Saharan Africa: a protocol for a systematic review and meta-analysis
Authors: Shibiru Shitaye , Jerene Degu , Mersha Abera , Ayele Gistane , Belachew Tefera 
Published: December 2024

IntroductionNutritional education intervention during pregnancy is the process of teaching pregnant women about the importance of a healthy diet and how to make healthy food choices. It is an important part of public health and vital to preventing adverse birth outcomes. Therefore, synthesising available evidence on the effect of nutritional education intervention on birth outcomes is essential for decision-making by policymakers and for identifying needed gaps for future research.ObjectiveTo systematically collect, review and summarise available evidence on the pooled effect of the nutrition education to pregnant women on birth outcomes in sub-Saharan Africa.Primary and secondary outcome measuresThe primary outcome measures will be birth outcomes, while maternal outcomes will be treated as secondary.Methods and analysisThis systematic review will systematically search and collect data from a variety of databases, including the MEDLINE, CINAHL, EMBASE, Joanna Briggs Institute Database, Cochrane Database, PEDro, POPLINE, ProQuest, OpenGrey (SIGLE), Google Scholar, Google, APA PsycINFO, Web of Science, Scopus and HINARI. In addition, the systematic review will also search for unpublished studies and grey literature from a variety of sources. The review will only include experimental and quasi-experimental studies published in English from 1 January 2013 to 31 December 2023. Two independent reviewers will critically appraise all eligible studies for methodological quality using the standard Joanna Briggs Institute (JBI) Critical Appraisal Checklist for randomised controlled trials. Any disagreements between the reviewers will resolve through discussion. Either a random effects or fixed effects model will be used to pool the data, depending on the appropriateness of the model. The heterogeneity will be assessed statistically using the standard χ² and I2tests. Publication bias will be examined graphically using funnel plots and statistically using Egger’s regression test. In the case when funnel plot is asymmetric and/or Egger’s test is statistically significant, the trim and fill (Duval and Tweedie’s) analysis will be performed. Statistical association between independent and dependent variables will be declared at p<0.05. The meta-analysis will be conducted using the statistical software STATA V.17.Ethics and disseminationBy synthesising existing research without ethical concerns, this impactful review will be published and presented across academic and relevant institutions.PROSPERO registration numberCRD42023473371.
Contextual factors influencing the use of digital health by patients and physicians in primary care: a scoping review protocol
Authors: Luchowska Katarzyna , Chmielewska Małgorzata , Byszek Katarzyna , Olearczyk Agata , Gawrońska Anna , Więckowska Barbara 
Published: December 2024

IntroductionIntegrating digital health technologies to improve the overall performance of healthcare systems counts among the top priorities of the WHO. As evidenced in recent research, there are specific factors that may decisively determine the effective implementation and development of innovative digital health solutions. This review attempts to recognise and map the existing body of research and evidence to identify the determinants that either favour or hinder the deployment and use of digital health technologies by patients and physicians in primary care.Methods and analysisThe scoping review will be conducted in accordance with the JBI Manual for Evidence Synthesis (2024 edition introducing nine stages) and with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Search strategy will be conducted in PubMed, Embase, Cochrane Database of Systematic Reviews and Scopus in November 2024. The review will include quantitative, qualitative, mixed-methods studies, systematic, scoping or umbrella reviews, as well as text and opinion papers. The study selection process will be conducted by two researchers using Rayyan. The data will be analysed using MAXQDA and extracted into a tool prepared by the researchers. This review will summarise the existing data and will help create a list of potential and determinant barriers and facilitators that may be useful in conducting empirical research on embedding new digital health solutions and sustaining their use.Ethics and disseminationAs no primary data will be collected for the purposes of this study, no formal ethical approval is required. Results will be published in a peer-reviewed journal. The findings will be used to conduct further research (HORIZON.2.1;grant:101095424) on the determinants of digital health implementation in primary care at the national level and to prepare recommendations for key stakeholders, as well as to develop recommendations on health policy in the European Union.