bluuebunny/crossref_metadata_2025_split huggingface dataset:
biomapp::chip: large-scale motif analysis
Authors: Garbelini Jader M. Caldonazzo , Sanches Danilo S. , Pozo Aurora T. Ramirez 
Published: March 2024

Abstract
Background
Discovery biological motifs plays a fundamental role in understanding regulatory mechanisms. Computationally, they can be efficiently represented as kmers, making the counting of these elements a critical aspect for ensuring not only the accuracy but also the efficiency of the analytical process. This is particularly useful in scenarios involving large data volumes, such as those generated by the ChIP-seq protocol. Against this backdrop, we introduce biomapp::chip, a tool specifically designed to optimize the discovery of biological motifs in large data volumes.

Results
We conducted a comprehensive set of comparative tests with state-of-the-art algorithms. Our analyses revealed that biomapp::chip outperforms existing approaches in various metrics, excelling both in terms of performance and accuracy. The tests demonstrated a higher detection rate of significant motifs and also greater agility in the execution of the algorithm. Furthermore, the smt component played a vital role in the system’s efficiency, proving to be both agile and accurate in kmer counting, which in turn improved the overall efficacy of our tool.

Conclusion
biomapp::chip represent real advancements in the discovery of biological motifs, particularly in large data volume scenarios, offering a relevant alternative for the analysis of ChIP-seq data and have the potential to boost future research in the field. This software can be found at the following address: (https://github.com/jadermcg/biomapp-chip).
Structure predictions and functional insights into Amidase_3 domain containing N-acetylmuramyl-L-alanine amidases from Deinococcus indicus DR1
Authors: Modi Malvika , Thambiraja Menaka , Cherukat Archana , Yennamalli Ragothaman M , Priyadarshini Richa 
Published: March 2024

Abstract
Background
N-acetylmuramyl-L-alanine amidases are cell wall modifying enzymes that cleave the amide bond between the sugar residues and stem peptide in peptidoglycan. Amidases play a vital role in septal cell wall cleavage and help separate daughter cells during cell division. Most amidases are zinc metalloenzymes, and E. coli cells lacking amidases grow as chains with daughter cells attached to each other. In this study, we have characterized two amidase enzymes from Deinococcus indicus DR1. D. indicus DR1 is known for its high arsenic tolerance and unique cell envelope. However, details of their cell wall biogenesis remain largely unexplored.

Results
We have characterized two amidases Ami1Di and Ami2Di from D. indicus DR1. Both Ami1Di and Ami2Di suppress cell separation defects in E. coli amidase mutants, suggesting that these enzymes are able to cleave septal cell wall. Ami1Di and Ami2Di proteins possess the Amidase_3 catalytic domain with conserved –GHGG- motif and Zn2+ binding sites. Zn2+- binding in Ami1Di is crucial for amidase activity. AlphaFold2 structures of both Ami1Di and Ami2Di were predicted, and Ami1Di was a closer homolog to AmiA of E. coli.

Conclusion
Our results indicate that Ami1Di and Ami2Di enzymes can cleave peptidoglycan, and structural prediction studies revealed insights into the activity and regulation of these enzymes in D. indicus DR1.
Mathematical kinetic modelling followed by in vitro and in vivo assays reveal the bifunctional rice GTPCHII/DHBPS enzymes and demonstrate the key roles of OsRibA proteins in the vitamin B2 pathway
Authors: Faustino Maria , Lourenço Tiago , Strobbe Simon , Cao Da , Fonseca André , Rocha Isabel , Van Der Straeten Dominique , Oliveira M. Margarida 
Published: March 2024

Abstract
Background
Riboflavin is the precursor of several cofactors essential for normal physical and cognitive development, but only plants and some microorganisms can produce it. Humans thus rely on their dietary intake, which at a global level is mainly constituted by cereals (> 50%). Understanding the riboflavin biosynthesis players is key for advancing our knowledge on this essential pathway and can hold promise for biofortification strategies in major crop species. In some bacteria and in Arabidopsis, it is known that RibA1 is a bifunctional protein with distinct GTP cyclohydrolase II (GTPCHII) and 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) domains. Arabidopsis harbors three RibA isoforms, but only one retained its bifunctionality. In rice, however, the identification and characterization of RibA has not yet been described.

Results
Through mathematical kinetic modeling, we identified RibA as the rate-limiting step of riboflavin pathway and by bioinformatic analysis we confirmed that rice RibA proteins carry both domains, DHBPS and GTPCHII. Phylogenetic analysis revealed that OsRibA isoforms 1 and 2 are similar to Arabidopsis bifunctional RibA1. Heterologous expression of OsRibA1 completely restored the growth of the rib3∆ yeast mutant, lacking DHBPS expression, while causing a 60% growth improvement of the rib1∆ mutant, lacking GTPCHII activity. Regarding OsRibA2, its heterologous expression fully complemented GTPCHII activity, and improved rib3∆ growth by 30%. In vitro activity assays confirmed that both OsRibA1 and OsRibA2 proteins carry GTPCHII/DHBPS activities, but that OsRibA1 has higher DHBPS activity. The overexpression of OsRibA1 in rice callus resulted in a 28% increase in riboflavin content.

Conclusions
Our study elucidates the critical role of RibA in rice riboflavin biosynthesis pathway, establishing it as the rate-limiting step in the pathway. By identifying and characterizing OsRibA1 and OsRibA2, showcasing their GTPCHII and DHBPS activities, we have advanced the understanding of riboflavin biosynthesis in this staple crop. We further demonstrated that OsRibA1 overexpression in rice callus increases its riboflavin content, providing supporting information for bioengineering efforts.
The activation of iron deficiency responses of grapevine rootstocks is dependent to the availability of the nitrogen forms
Authors: Khalil Sarhan , Strah Rebeka , Lodovici Arianna , Vojta Petr , Berardinis Federica De , Ziegler Jörg , Pompe Novak Maruša , Zanin Laura , Tomasi Nicola , Forneck Astrid , Griesser Michaela 
Published: March 2024

Abstract
Background
In viticulture, iron (Fe) chlorosis is a common abiotic stress that impairs plant development and leads to yield and quality losses. Under low availability of the metal, the applied N form (nitrate and ammonium) can play a role in promoting or mitigating Fe deficiency stresses. However, the processes involved are not clear in grapevine. Therefore, the aim of this study was to investigate the response of two grapevine rootstocks to the interaction between N forms and Fe uptake. This process was evaluated in a hydroponic experiment using two ungrafted grapevine rootstocks Fercal (Vitis berlandieri x V. vinifera) tolerant to deficiency induced Fe chlorosis and Couderc 3309 (V. riparia x V. rupestris) susceptible to deficiency induced Fe chlorosis.

Results
The results could differentiate Fe deficiency effects, N-forms effects, and rootstock effects. Interveinal chlorosis of young leaves appeared earlier on 3309 C from the second week of treatment with NO3−/NH4+ (1:0)/-Fe, while Fercal leaves showed less severe symptoms after four weeks of treatment, corresponding to decreased chlorophyll concentrations lowered by 75% in 3309 C and 57% in Fercal. Ferric chelate reductase (FCR) activity was by trend enhanced under Fe deficiency in Fercal with both N combinations, whereas 3309 C showed an increase in FCR activity under Fe deficiency only with NO3−/NH4+ (1:1) treatment. With the transcriptome analysis, Gene Ontology (GO) revealed multiple biological processes and molecular functions that were significantly regulated in grapevine rootstocks under Fe-deficient conditions, with more genes regulated in Fercal responses, especially when both forms of N were supplied. Furthermore, the expression of genes involved in the auxin and abscisic acid metabolic pathways was markedly increased by the equal supply of both forms of N under Fe deficiency conditions. In addition, changes in the expression of genes related to Fe uptake, regulation, and transport reflected the different responses of the two grapevine rootstocks to different N forms.

Conclusions
Results show a clear contribution of N forms to the response of the two grapevine rootstocks under Fe deficiency, highlighting the importance of providing both N forms (nitrate and ammonium) in an appropriate ratio in order to ease the rootstock responses to Fe deficiency.
A decrease in integrin α5β1/FAK is associated with increased apoptosis of aortic smooth muscle cells in acute type a aortic dissection
Authors: Xue Mingming , Xing Lingyu , Yang Yilin , Shao Mian , Liao Fengqing , Xu Feixiang , Chen Yumei , Wang Sheng , Chen Bin , Yao Chenling , Gu Guorong , Tong Chaoyang 
Published: March 2024

Abstract
Background
Acute type A aortic dissection (AAAD) is a devastating disease. Human aortic smooth muscle cells (HASMCs) exhibit decreased proliferation and increased apoptosis, and integrin α5β1 and FAK are important proangiogenic factors involved in regulating angiogenesis. The aim of this study was to investigate the role of integrin α5β1 and FAK in patients with AAAD and the potential underlying mechanisms.

Methods
Aortic tissue samples were obtained from 8 patients with AAAD and 4 organ donors at Zhongshan Hospital of Fudan University. The level of apoptosis in the aortic tissues was assessed by immunohistochemical (IHC) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The expression of integrin α5β1 and FAK was determined. Integrin α5β1 was found to be significantly expressed in HASMCs, and its interaction with FAK was assessed via coimmunoprecipitation (Co-IP) analysis. Proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assays and flow cytometry after integrin α5β1 deficiency.

Results
The levels of integrin α5β1 and FAK were both significantly decreased in patients with AAAD. Downregulating the expression of integrin α5β1-FAK strongly increased apoptosis and decreased proliferation in HASMCs, indicating that integrin α5β1-FAK might play an important role in the development of AAAD.

Conclusions
Downregulation of integrin α5β1-FAK is associated with increased apoptosis and decreased proliferation in aortic smooth muscle cells and may be a potential therapeutic strategy for AAAD.
Psychometric evaluation of the Decision Support System (DSS) for municipal nurses encountering health deterioration among older adults
Authors: Kihlgren Annica , Lammgård Tomas , Pejner Margaretha Norell , Svensson Fredrik , Adolfsson Ann-Sofie , Lindner Helen 
Published: March 2024

Abstract
Background
A valid and reliable tool is crucial for municipal registered nurses (RNs) to make quick decisions in older adults who show rapid signs of health deterioration. The aim of this study was to investigate the psychometric properties of the Decision Support System (DSS) among older adults in the municipal healthcare system.

Methods
Firstly, we utilized the Rasch dichotomous model to analyze the DSS assessments (n=281) that were collected from municipal RNs working with older adults in the municipal healthcare system. We examined the properties of the DSS in terms of its unidimensionality, item fit, and separation indices. Secondly, to investigate inter-rater agreement in using the DSS, four experienced municipal RNs used the DSS to assess 60 health deterioration scenarios presented by one human patient simulators. The 60 DSS assessments were then analyzed using the ICC (2,1), percentage agreement, and Cohen κ statistics.

Results
The sample of older adults had a mean age of 82.8 (SD 11.7). The DSS met the criteria for unidimensionality, although two items did not meet the item fit statistics when all the DSS items were analyzed together. The person separation index was 0.47, indicating a limited level of separation among the sample. The item separation index was 11.43, suggesting that the DSS has good ability to discriminate between and separate the items. At the overall DSS level, inter-rater agreements were good according to the ICC. At the individual DSS item level, the percentage agreements were 75% or above, while the Cohen κ statistics ranged from 0.46 to 1.00.

Conclusions
The Rasch analysis revealed that the psychometric properties of the instrument were acceptable, although further research with a larger sample size and more items is needed. The DSS has the potential to assist municipal RNs in making clinical decisions regarding health deterioration in older adults, thereby avoiding unnecessary emergency admission and helping to alleviate emergency department overcrowding.
Comparison of metagenomic next-generation sequencing and conventional culture for the diagnostic performance in febrile patients with suspected infections
Authors: Yang Hui , Xu Nannan , Yan Meichen , Yang Lulu , Wen Sai , Wang Shanshan , Qu Chunmei , Xu Ke , Yang Xuying , Wang Gang 
Published: March 2024

Abstract
Background
Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration.

Methods
This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared.

Results
Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p < 0.001) and negative predictive value (54.67% vs. 42.9%) of mNGS were superior to those of culture. In contrast, the culture exhibited higher specificity (99.27% vs. 85.40%, p < 0.001) and positive predictive value (98.84% vs. 87.01%) than mNGS. Among infected patients with positive mNGS results, 64 received adjusted antibiotic therapy including treatment transitions, antibiotic downgrading, and combination therapy. Among them, 9 had additional antifungal drugs and 21 patients had a treatment turning point based on the mNGS results and these patients recovered and discharged due to timely antibiotic adjustment. Both positive rates of puncture fluid mNGS and tissue mNGS were higher than those of culture in the patients who had prior antibiotic use, and this difference was statistically significant (p = 0.000).

Conclusion
mNGS is more sensitive and accurate than traditional culture, making it ideal for identifying pathogens and screening infectious diseases, especially for those with uncultivated or difficult-to-cultivate species. Early diagnosis allows for prompt treatment with targeted antibiotics, and mNGS is recommended when samples are limited.
Modelling the impact of human behavior using a two-layer Watts-Strogatz network for transmission and control of Mpox
Authors: Jia Qiaojuan , Xue Ling , Sui Ran , Huo Junqi 
Published: March 2024

Abstract
Purpose
This study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023.

Methods
We develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size.

Results
Our results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749–6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one.

Conclusion
We need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.
SIRT5 promote malignant advancement of chordoma by regulating the desuccinylation of c-myc
Authors: Jiang Minghui , Huang Zheng , Chen Li , Deng Ting , Liu Junpeng , Wu Yue 
Published: March 2024

AbstractChordoma is a relatively rare and locally aggressive malignant tumor. Sirtuin (SIRT)5 plays pivotal roles in various tumors, but the role of SIRT5 in chordoma has not been found. This study was performed to investigate the regulatory effects of SIRT5 on cell proliferation, migration, and invasion and the underlying mechanism in chordoma. A xenograft tumor mouse model was established to assess tumor growth. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA levels of SIRT5 and c-myc. The effects of SIRT5 and c-myc on cell proliferation, migration, and invasion of chordoma cells were detected by cell counting kit-8, colony formation, and Transwell assays. The interaction between SIRT5 and c-myc was evaluated by co-immunoprecipitation (IP) assay. The succinylation of c-myc was analyzed by IP and Western blot. The results showed that SIRT5 expression was upregulated in chordoma tissues and cells. SIRT5 interacted with c-myc to inhibit the succinylation of c-myc at K369 site in human embryonic kidney (HEK)-293T cells. Silencing of SIRT5 suppressed the cell proliferation, migration, and invasion of chordoma cells, while the results were reversed after c-myc overexpression. Moreover, silencing SIRT5 suppressed tumor growth in mice. These findings suggested that SIRT5 promoted the malignant advancement of chordoma by regulating the desuccinylation of c-myc.
Epithelial ingrowth in descemet membrane endothelial keratoplasty associated with vitreous loss
Authors: Cheng Anny M.S. , Kubal Anup , Gupta Shailesh K. , Vedula Anil S. , Yang David T.Y. , Kubal Aarup A. 
Published: March 2024

Abstract
Background
Epithelial ingrowth is a rare but potentially sight-threatening complication caused by the invasion of corneal or conjunctival epithelial cells into the eye during ocular surgeries. DMEK is emerging as a widely used surgery for endothelial keratoplasty with its improved safety profile. We describe a case of epithelial ingrowth in the graft-host interface after uneventful DMEK associated with vitreous prolapse in the anterior chamber.

Case presentation
An 81-year-old female with Fuchs endothelial dystrophy underwent DMEK for corneal decompensation following cataract surgery. During the DMEK procedure, vitreous prolapse was observed around the intraocular lens (IOL). Her early postoperative course was unremarkable, but a dense paracentral interface opacity was observed during the 3-month follow-up. The area of epithelial ingrowth was imaged with optical coherence tomography (OCT) as a uniform nodule with a discrete increase in interface hyperreflectivity. A low-energy YAG laser was applied to remove the opacity. She maintained good vision and clear cornea without reoccurrence after treatment.

Conclusions
We propose that, in addition to the introduction of epithelial cells during surgery, vitreous retention in the anterior chamber may be a risk factor by providing a scaffold that potentially aggravates epithelial ingrowth in DMEK. Our case demonstrated that early YAG intervention may disrupt interface epithelial cell growth, and the transmitted laser energy may fragment the scaffold vitreous noninvasively.
The Mood and Resilience in Offspring (MARIO) project: a longitudinal cohort study among offspring of parents with and without a mood disorder
Authors: Vreeker Annabel , Horsfall Melany , Eikelenboom Merijn , Beerthuizen Annemerle , Bergink Veerle , Boks Marco P. M. , Hartman Catharina A. , de Koning Ricki , de Leeuw Max , Maciejewski Dominique F. , Penninx Brenda W. J. H. , Hillegers Manon H. J. 
Published: March 2024

BackgroundOne of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors.MethodsMARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected.DiscussionThe MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.