bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical presentations and pitfalls of achalasia
Authors: Müller M , Förschler S , Wehrmann T , Marini F , Gockel I , Eckardt A J 
Published: May 2023

Summary
Achalasia is a rare disease with significant diagnostic delay and association with false diagnoses and unnecessary interventions. It remains unclear, whether atypical presentations, misinterpreted symptoms or inconclusive diagnostics are the cause. The aim of this study was the characterization of typical and atypical features of achalasia and their impact on delays, misinterpretations or false diagnoses. A retrospective analysis of prospective database over a period of 30 years was performed. Data about symptoms, delays and false diagnoses were obtained and correlated with manometric, endoscopic and radiologic findings. Totally, 300 patients with achalasia were included. Typical symptoms (dysphagia, regurgitation, weight loss and retrosternal pain) were present in 98.7%, 88%, 58.4% and 52.4%. The mean diagnostic delay was 4.7 years. Atypical symptoms were found in 61.7% and led to a delay of 6 months. Atypical gastrointestinal symptoms were common (43%), mostly ‘heartburn’ (16.3%), ‘vomiting’ (15.3%) or belching (7.7%). A single false diagnosis occurred in 26%, multiple in 16%. Major gastrointestinal misdiagnoses were GERD in 16.7% and eosinophilic esophagitis in 4%. Other false diagnosis affected ENT-, psychiatric, neurologic, cardiologic or thyroid diseases. Pitfalls were the description of ‘heartburn’ or ‘nausea’. Tertiary contractions at barium swallows, hiatal hernias and ‘reflux-like’ changes at endoscopy or eosinophils in the biopsies were misleading. Atypical symptoms are common in achalasia, but they are not the sole source for diagnostic delays. Misleading descriptions of typical symptoms or misinterpretation of diagnostic studies contribute to false diagnoses and delays.
Refractory left atrial mural endocarditis secondary to a mitral valve jet lesion requiring thoracotomy: a case report
Authors: Matsumura Mikiko Nakahara , Horiuchi Kohei , Domae Keitaro , Higuchi Yoshiharu 
Published: May 2023

Abstract

Background
Infective endocarditis (IE) lesions rarely exist only in the endocardium, except on the valves. Such lesions are usually treated with the same strategy used to treat valvular IE. Depending on the causative organisms and degree of intracardiac structure destruction, it might be cured with conservative treatment consisting of antibiotics alone.

Case summary
A 38-year-old woman had a continuous high fever. Echocardiography revealed a vegetation located on the endocardial side of the posterior wall of the left atrium, from the valve ring on the side of the posteromedial scallop, which was exposed to a mitral regurgitation jet. Mural endocarditis caused by methicillin-sensitive Staphylococcus aureus (MSSA) was diagnosed based on blood cultures. Splenic infarction developed despite various types of appropriate antibiotics. The vegetations increased in size over time to &gt;10 mm. The patient underwent surgical resection and had an uneventful post-operative course. There was no evidence of exacerbation or recurrence during the post-operative outpatient follow-up visits.

Discussion
Even in cases of isolated mural endocarditis, infections caused by MSSA that are resistant to multiple antibiotics can be challenging to manage with antibiotics alone. Specifically, for cases of MSSA IE that show resistance to various antibiotics, early consideration should be given to surgical intervention as part of the treatment process.
Percutaneous rheolytic thrombectomy and cerebral embolic protection in a massive thrombosis of a fenestrated Fontan conduit: a case report
Authors: Marzullo Raffaella , Capestro Alessandro , Muçaj Andi , Piva Tommaso 
Published: May 2023

Abstract

Background
Clinical thromboembolism in Fontan patients is often a catastrophic event resulting in death and adverse long-term outcomes. The treatment of acute thromboembolic complications in these patients is very controversial.

Case summary
We describe the use of rheolytic thrombectomy in a Fontan patient with life-threatening pulmonary embolism, employing a cerebral protection system to reduce the risk of stroke through the fenestration.

Discussion
Rheolytic thrombectomy may be a successful alternative to systemic thrombolytic therapy and open surgical resection for the treatment of acute high-risk pulmonary embolism in the Fontan population. Embolic protection device to capture and remove thrombus/debris may be an innovative tool to reduce the risk of stroke through the fenestration while performing a percutaneous procedure in fenestrated Fontan patient.
Systemism and International Relations: How a Graphic Method Can Enhance Communication
Authors: Canbolat Sercan , Gansen Sarah , James Patrick 
Published: May 2023

AbstractThis article brings a broad array of works, which pertain to different research areas of international relations (IR), into contact with each other via a graphic method, systemism, to obtain insights that otherwise might prove elusive. Completion of these tasks is anticipated to exemplify how the systemist approach can enhance communication throughout IR. Systemism is introduced as a graphic technique for communicating arguments. Systemist graphics are used to convey the contents of (a) two studies that focus on theory per se and (b) a range of topics—foreign policy analysis, forecasting, and conflict processes. Systematic synthesis focusing on the two works about theory and bricolagic bridging that is based on all five studies reveal the contributions of a systemist approach, respectively, to the logics of confirmation and discovery. Value added from the systemist approach is confirmed for both IR research and pedagogy.
The chickpeaWIP2gene underlying a major QTL contributes to lateral root development
Authors: Dwivedi Vikas , Pal Lalita , Singh Shilpi , Singh Nagendra Pratap , Parida Swarup Kumar , Chattopadhyay Debasis 
Published: May 2023

AbstractLateral roots are a major component of root system architecture, and lateral root count (LRC) positively contributes to yield under drought in chickpea. To understand the genetic regulation of LRC, a biparental mapping population derived from two chickpea accessions having contrasting LRCs was genotyped by sequencing, and phenotyped to map four major quantitative trait loci (QTLs) contributing to 13–32% of the LRC trait variation. A single- nucleotide polymorphism tightly linked to the locus contributing to highest trait variation was located on the coding region of a gene (CaWIP2), orthologous to NO TRANSMITTING TRACT/WIP domain protein 2 (NTT/WIP2) gene of Arabidopsis thaliana. A polymorphic simple sequence repeat (SSR) in the CaWIP2 promoter showed differentiation between low versus high LRC parents and mapping individuals, suggesting its utility for marker-assisted selection. CaWIP2 promoter showed strong expression in chickpea apical root meristem and lateral root primordia. Expression of CaWIP2 under its native promoter in the Arabidopsis wip2wip4wip5 mutant rescued its rootless phenotype to produce more lateral roots than the wild-type plants, and led to formation of amyloplasts in the columella. CaWIP2 expression also induced the expression of genes that regulate lateral root emergence. Our study identified a gene-based marker for LRC which will be useful for developing drought-tolerant, high-yielding chickpea varieties.
vissE.cloud: a webserver to visualise higher order molecular phenotypes from enrichment analysis
Authors: Mohamed Ahmed , Bhuva Dharmesh D , Lee Sam , Liu Ning , Tan Chin Wee , Davis Melissa J 
Published: May 2023

Abstract
Gene-set analysis (GSA) dominates the functional interpretation of omics data and downstream hypothesis generation. Despite its ability to summarise thousands of measurements into semantically interpretable components, GSA often results in hundreds of significantly enriched gene-sets. However, summarisation and effective visualisation of GSA results to facilitate hypothesis generation is still lacking. While some webservers provide gene-set visualization tools, there is still a need for tools that can effectively summarize and guide exploration of GSA results. To enable versatility, webservers accept gene lists as input, however, none provide end-to-end solutions for emerging data types such as single-cell and spatial omics. Here, we present vissE.Cloud, a webserver for end-to-end gene-set analysis, offering gene-set summarisation and highly interactive visualisation. vissE.Cloud uses algorithms from our earlier R package vissE to summarise GSA results by identifying biological themes. We maintain versatility by allowing analysis of gene lists, as well as, analysis of raw single-cell and spatial omics data, including CosMx and Xenium data, making vissE.Cloud the first webserver to provide end-to-end gene-set analysis of sub-cellular localised spatial data. Structuring the results hierarchically allows swift interactive investigations of results at the gene, gene-set, and clusters level. vissE.Cloud is freely available at https://www.vissE.Cloud.
DksA is a conserved master regulator of stress response in Acinetobacter baumannii
Authors: Maharjan Ram P , Sullivan Geraldine J , Adams Felise G , Shah Bhumika S , Hawkey Jane , Delgado Natasha , Semenec Lucie , Dinh Hue , Li Liping , Short Francesca L , Parkhill Julian , Paulsen Ian T , Barquist Lars , Eijkelkamp Bart A , Cain Amy K 
Published: May 2023

Abstract
Coordination of bacterial stress response mechanisms is critical for long-term survival in harsh environments for successful host infection. The general and specific stress responses of well-studied Gram-negative pathogens like Escherichia coli are controlled by alternative sigma factors, archetypically RpoS. The deadly hospital pathogen Acinetobacter baumannii is notoriously resistant to environmental stresses, yet it lacks RpoS, and the molecular mechanisms driving this incredible stress tolerance remain poorly defined. Here, using functional genomics, we identified the transcriptional regulator DksA as a master regulator for broad stress protection and virulence in A. baumannii. Transcriptomics, phenomics and in vivo animal studies revealed that DksA controls ribosomal protein expression, metabolism, mutation rates, desiccation, antibiotic resistance, and host colonization in a niche-specific manner. Phylogenetically, DksA was highly conserved and well-distributed across Gammaproteobacteria, with 96.6% containing DksA, spanning 88 families. This study lays the groundwork for understanding DksA as a major regulator of general stress response and virulence in this important pathogen.
WebTetrado: a webserver to explore quadruplexes in nucleic acid 3D structures
Authors: Adamczyk Bartosz , Zurkowski Michal , Szachniuk Marta , Zok Tomasz 
Published: May 2023

Abstract
Quadruplexes are four-stranded DNA/RNA motifs of high functional significance that fold into complex shapes. They are widely recognized as important regulators of genomic processes and are among the most frequently investigated potential drug targets. Despite interest in quadruplexes, few studies focus on automatic tools that help to understand the many unique features of their 3D folds. In this paper, we introduce WebTetrado, a web server for analyzing 3D structures of quadruplex structures. It has a user-friendly interface and offers many advanced features, including automatic identification, annotation, classification, and visualization of the motif. The program applies to the experimental or in silico generated 3D models provided in the PDB and PDBx/mmCIF files. It supports canonical G-quadruplexes as well as non-G-based quartets. It can process unimolecular, bimolecular, and tetramolecular quadruplexes. WebTetrado is implemented as a publicly available web server with an intuitive interface and can be freely accessed at https://webtetrado.cs.put.poznan.pl/.
ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy
Authors: Shi Xing-Xing , Wang Zhi-Zheng , Wang Fan , Hao Ge-Fei , Yang Guang-Fu 
Published: May 2023

Abstract
Drug discovery, which plays a vital role in maintaining human health, is a persistent challenge. Fragment-based drug discovery (FBDD) is one of the strategies for the discovery of novel candidate compounds. Computational tools in FBDD could help to identify potential drug leads in a cost-efficient and time-saving manner. The Auto Core Fragment in silico Screening (ACFIS) server is a well-established and effective online tool for FBDD. However, the accurate prediction of protein-fragment binding mode and affinity is still a major challenge for FBDD due to weak binding affinity. Here, we present an updated version (ACFIS 2.0), that incorporates a dynamic fragment growing strategy to consider protein flexibility. The major improvements of ACFIS 2.0 include (i) increased accuracy of hit compound identification (from 75.4% to 88.5% using the same test set), (ii) improved rationality of the protein-fragment binding mode, (iii) increased structural diversity due to expanded fragment libraries and (iv) inclusion of more comprehensive functionality for predicting molecular properties. Three successful cases of drug lead discovery using ACFIS 2.0 are described, including drugs leads to treat Parkinson's disease, cancer, and major depressive disorder. These cases demonstrate the utility of this web-based server. ACFIS 2.0 is freely available at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS2/.
αCharges: partial atomic charges for AlphaFold structures in high quality
Authors: Schindler Ondřej , Berka Karel , Cantara Alessio , Křenek Aleš , Tichý Dominik , Raček Tomáš , Svobodová Radka 
Published: May 2023

Abstract
The AlphaFold2 prediction algorithm opened up the possibility of exploring proteins’ structural space at an unprecedented scale. Currently, &gt;200 million protein structures predicted by this approach are deposited in AlphaFoldDB, covering entire proteomes of multiple organisms, including humans. Predicted structures are, however, stored without detailed functional annotations describing their chemical behaviour. Partial atomic charges, which map electron distribution over a molecule and provide a clue to its chemical reactivity, are an important example of such data. We introduce the web application αCharges: a tool for the quick calculation of partial atomic charges for protein structures from AlphaFoldDB. The charges are calculated by the recent empirical method SQE+qp, parameterised for this class of molecules using robust quantum mechanics charges (B3LYP/6-31G*/NPA) on PROPKA3 protonated structures. The computed partial atomic charges can be downloaded in common data formats or visualised via the powerful Mol* viewer. The αCharges application is freely available at https://alphacharges.ncbr.muni.cz with no login requirement.
TransCRISPR–sgRNA design tool for CRISPR/Cas9 experiments targeting specific sequence motifs
Authors: Woźniak Tomasz , Sura Weronika , Kazimierska Marta , Kasprzyk Marta Elżbieta , Podralska Marta , Dzikiewicz-Krawczyk Agnieszka 
Published: May 2023

Abstract
Eukaryotic genomes contain several types of recurrent sequence motifs, e.g. transcription factor motifs, miRNA binding sites, repetitive elements. CRISPR/Cas9 can facilitate identification and study of crucial motifs. We present transCRISPR, the first online tool dedicated to search for sequence motifs in the user-provided genomic regions and design optimal sgRNAs targeting them. Users can obtain sgRNAs for chosen motifs, for up to tens of thousands of target regions in 30 genomes, either for the Cas9 or dCas9 system. TransCRISPR provides user-friendly tables and visualizations, summarizing features of identified motifs and designed sgRNAs such as genomic localization, quality scores, closest transcription start sites and others. Experimental validation of sgRNAs for MYC binding sites designed with transCRISPR confirmed efficient disruption of the targeted motifs and effect on expression of MYC-regulated genes. TransCRISPR is available from https://transcrispr.igcz.poznan.pl/transcrispr/.
CAVE: a cloud-based platform for analysis and visualization of metabolic pathways
Authors: Mao Zhitao , Yuan Qianqian , Li Haoran , Zhang Yue , Huang Yuanyuan , Yang Chunhe , Wang Ruoyu , Yang Yongfu , Wu Yalun , Yang Shihui , Liao Xiaoping , Ma Hongwu 
Published: May 2023

Abstract
Flux balance analysis (FBA) is an important method for calculating optimal pathways to produce industrially important chemicals in genome-scale metabolic models (GEMs). However, for biologists, the requirement of coding skills poses a significant obstacle to using FBA for pathway analysis and engineering target identification. Additionally, a time-consuming manual drawing process is often needed to illustrate the mass flow in an FBA-calculated pathway, making it challenging to detect errors or discover interesting metabolic features. To solve this problem, we developed CAVE, a cloud-based platform for the integrated calculation, visualization, examination and correction of metabolic pathways. CAVE can analyze and visualize pathways for over 100 published GEMs or user-uploaded GEMs, allowing for quicker examination and identification of special metabolic features in a particular GEM. Additionally, CAVE offers model modification functions, such as gene/reaction removal or addition, making it easy for users to correct errors found in pathway analysis and obtain more reliable pathways. With a focus on the design and analysis of optimal pathways for biochemicals, CAVE complements existing visualization tools based on manually drawn global maps and can be applied to a broader range of organisms for rational metabolic engineering. CAVE is available at https://cave.biodesign.ac.cn/.
Forkhead box protein D2 suppresses colorectal cancer by reprogramming enhancer interactions
Authors: Kim Hyo-Min , Kang Byunghee , Park Sohyun , Park Hyorim , Kim Chan Johng , Lee Hyeonji , Yoo Mijoung , Kweon Mi-Na , Im Sin-Hyeog , Kim Tae Il , Roh Tae-Young 
Published: May 2023

AbstractSomatic stem cells contribute to normal tissue homeostasis, and their epigenomic features play an important role in regulating tissue identities or developing disease states. Enhancers are one of the key players controlling chromatin context-specific gene expression in a spatial and temporal manner while maintaining tissue homeostasis, and their dysregulation leads to tumorigenesis. Here, epigenomic and transcriptomic analyses reveal that forkhead box protein D2 (FOXD2) is a hub for the gene regulatory network exclusive to large intestinal stem cells, and its overexpression plays a significant role in colon cancer regression. FOXD2 is positioned at the closed chromatin and facilitates mixed-lineage leukemia protein-4 (MLL4/KMT2D) binding to deposit H3K4 monomethylation. De novo FOXD2-mediated chromatin interactions rewire the regulation of p53-responsive genes and induction of apoptosis. Taken together, our findings illustrate the novel mechanistic details of FOXD2 in suppressing colorectal cancer growth and suggest its function as a chromatin-tuning factor and a potential therapeutic target for colorectal cancer.
Attenuation of a DNA cruciform by a conserved regulator directs T3SS1 mediated virulence in Vibrio parahaemolyticus
Authors: Getz Landon J , Brown Justin M , Sobot Lauren , Chow Alexandra , Mahendrarajah Jastina , Thomas Nikhil A 
Published: May 2023

Abstract
Pathogenic Vibrio species account for 3–5 million annual life-threatening human infections. Virulence is driven by bacterial hemolysin and toxin gene expression often positively regulated by the winged helix-turn-helix (wHTH) HlyU transcriptional regulator family and silenced by histone-like nucleoid structural protein (H-NS). In the case of Vibrio parahaemolyticus, HlyU is required for virulence gene expression associated with type 3 Secretion System-1 (T3SS1) although its mechanism of action is not understood. Here, we provide evidence for DNA cruciform attenuation mediated by HlyU binding to support concomitant virulence gene expression. Genetic and biochemical experiments revealed that upon HlyU mediated DNA cruciform attenuation, an intergenic cryptic promoter became accessible allowing for exsA mRNA expression and initiation of an ExsA autoactivation feedback loop at a separate ExsA-dependent promoter. Using a heterologous E. coli expression system, we reconstituted the dual promoter elements which revealed that HlyU binding and DNA cruciform attenuation were strictly required to initiate the ExsA autoactivation loop. The data indicate that HlyU acts to attenuate a transcriptional repressive DNA cruciform to support T3SS1 virulence gene expression and reveals a non-canonical extricating gene regulation mechanism in pathogenic Vibrio species.
IRSOM2: a web server for predicting bifunctional RNAs
Authors: Postic Guillaume , Tav Christophe , Platon Ludovic , Zehraoui Farida , Tahi Fariza 
Published: May 2023

Abstract
Recent advances have shown that some biologically active non-coding RNAs (ncRNAs) are actually translated into polypeptides that have a physiological function as well. This paradigm shift requires adapted computational methods to predict this new class of ‘bifunctional RNAs’. Previously, we developed IRSOM, an open-source algorithm to classify non-coding and coding RNAs. Here, we use the binary statistical model of IRSOM as a ternary classifier, called IRSOM2, to identify bifunctional RNAs as a rejection of the two other classes. We present its easy-to-use web interface, which allows users to perform predictions on large datasets of RNA sequences in a short time, to re-train the model with their own data, and to visualize and analyze the classification results thanks to the implementation of self-organizing maps (SOM). We also propose a new benchmark of experimentally validated RNAs that play both protein-coding and non-coding roles, in different organisms. Thus, IRSOM2 showed promising performance in detecting these bifunctional transcripts among ncRNAs of different types, such as circRNAs and lncRNAs (in particular those of shorter lengths). The web server is freely available on the EvryRNA platform: https://evryrna.ibisc.univ-evry.fr.
svCapture: efficient and specific detection of very low frequency structural variant junctions by error-minimized capture sequencing
Authors: Wilson Thomas E , Ahmed Samreen , Higgins Jake , Salk Jesse J , Glover Thomas W 
Published: May 2023

Abstract
Error-corrected sequencing of genomic targets enriched by probe-based capture has become a standard approach for detecting single-nucleotide variants (SNVs) and small insertion/deletions (indels) present at very low variant allele frequencies. Less attention has been given to comparable strategies for rare structural variant (SV) junctions, where different error mechanisms must be addressed. Working from samples with known SV properties, we demonstrate that duplex sequencing (DuplexSeq), which demands confirmation of variants on both strands of a source DNA molecule, eliminates false SV junctions arising from chimeric PCR. DuplexSeq could not address frequent intermolecular ligation artifacts that arise during Y-adapter addition prior to strand denaturation without requiring multiple source molecules. In contrast, tagmentation libraries coupled with data filtering based on strand family size greatly reduced both artifact classes and enabled efficient and specific detection of single-molecule SV junctions. The throughput of SV capture sequencing (svCapture) and base-level accuracy of DuplexSeq provided detailed views of the microhomology profile and limited occurrence of de novo SNVs near the junctions of hundreds of newly created SVs, suggesting end joining as a possible formation mechanism. The open source svCapture pipeline enables rare SV detection as a routine addition to SNVs/indels in properly prepared capture sequencing libraries.