bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation DNA sequencing identifies mutated FANCD2 Gene as a novel Biomarker for monitoring early disease progression and timely therapeutic interventions in advanced phase Chronic Myeloid Leukemia patients
Authors: Alanazi Nawaf , Siyal Abdulaziz , Absar Muhammad , Shammas Masood , Al-Mukhaylid Sarah , Mahmood Amer , Iqbal Zafar 
Published: December 2023

AbstractChronic Myeloid Leukemia, resulting due to chromosomal aberration t(9;22) through formation of oncogenic BCR-ABL fusion oncogene. Modern BCR-ABL inhibitors, called TKIs, have revolutionized CML treatment. CML has three stages: chronic, accelerated, and blast crisis. TKIs work well in CP-CML, where patients survive as long as the normal population, but they don’t work in AP- and BC-CML. Even with advances in treatment, BC-CML has an average overall survival of less than a year, giving oncologists little time to clinically intervene. Oncologists can delay or prevent CML advancement by detecting patients at risk of disease progression early and making timely treatment decisions, especially with third and fourth generation TKIs. However, no universal molecular biomarkers exist to diagnose CML patient groups at risk of disease progression.A recent study found that all BC-CML patients have mutant FANCD2. Our study was designed to detect mutant FANCD2 in AP-CML (early progression phase) to investigate its potential as a novel biomarker of early CML progression from chronic phase to accelerated phase due to the urgent need for such a biomarker.Our study comprised of 123 CP-CML (control group) and 60 AP-CML patients (as experimental group) from Hayatabad Medical Complex, Peshawar, Pakistan, from Jan 2020 to July 2023. DNA was extracted from the patients and FANCD2 gene was sequenced using Illumina next generation sequencer (NGS) Illumina MiSeq sequencer. NGS analysis revealed a unique splice site mutation in FANCD2 gene (c. 2022-5C>T). This mutation was detected in all CP-CML patients but in none of CP-CML. The mutation was confirmed by Sanger sequencing.FANCD2 is member of Fanconi anemia (FA-) pathway gene involved in DNA repair and genomic instability. Therefore, our studies show that FANCD2 (c. 2022-5C>T) mutation as a very specific molecular biomarker for early CML progression. We recommend to clinical validate this biomarker is prospective clinical trials.
Antibiotic treatment modestly reduces protection against Mycobacterium tuberculosis reinfection in macaques
Authors: Ganchua Sharie Keanne , Maiello Pauline , Chao Michael , Hopkins Forrest , Mugahid Douaa , Lin Philana Ling , Fortune Sarah M. , Flynn JoAnne L. 
Published: December 2023

AbstractConcomitant immunity is generally defined as an ongoing infection providing protection against reinfection1. Its role in prevention of tuberculosis (TB) caused byMycobacterium tuberculosis(Mtb) is supported by epidemiological evidence in humans as well as experimental evidence in mice and non-human primates (NHPs). Whether the presence of live Mtb, rather than simply persistent antigen, is necessary for concomitant immunity in TB is still unclear. Here, we investigated whether live Mtb plays a measurable role in control of secondary Mtb infection. Using cynomolgus macaques, molecularly barcoded Mtb libraries, PET-CT imaging, flow cytometry and cytokine profiling we evaluated the effect of antibiotic treatment after primary infection on immunological response and bacterial establishment, dissemination, and burden post-secondary infection. Our data provide evidence that, in this experimental model, treatment with antibiotics after primary infection reduced inflammation in the lung but was not associated with a significant change in bacterial establishment, dissemination or burden in the lung or lymph nodes. Nonetheless, treatment of the prior infection with antibiotics did result in a modest reduction in protection against reinfection: none of the 7 antibiotic treated animals demonstrated sterilizing immunity against reinfection while 4 of the 7 non-treated macaques were completely protected against reinfection. These findings support that antibiotic-treated animals were still able to restrict bacterial establishment and dissemination after rechallenge compared to naïve macaques, but not to the full extent of non-antibiotic treated macaques.
Associations between music and dance relationships, rhythmic proficiency, and spatiotemporal movement modulation ability in adults with and without mild cognitive impairment
Authors: Slusarenko Alexandra , Rosenberg Michael C. , Kazanski Meghan E. , McKay J. Lucas , Emmery Laura , Kesar Trisha M. , Hackney Madeleine E. 
Published: December 2023

AbstractBackgroundPersonalized dance-based movement therapies may improve cognitive and motor function in individuals with mild cognitive impairment (MCI), a precursor to Alzheimer’s disease. While age- and MCI-related deficits reduce individuals’ abilities to perform dance-like rhythmic movement sequences (RMS)—spatial and temporal modifications to movement—it remains unclear how individuals’ relationships to dance and music affect their ability to perform RMS.ObjectiveCharacterize associations between RMS performance and music or dance relationships, as well as the ability to perceive rhythm and meter (rhythmic proficiency) in adults with and without MCI.MethodsWe used wearable inertial sensors to evaluate the ability of 12 young adults (YA; age=23.9±4.2 yrs; 9F), 26 older adults without MCI (OA; age=68.1±8.5 yrs; 16F), and 18 adults with MCI (MCI; age=70.8±6.2 yrs; 10F) to accurately perform spatial, temporal, and spatiotemporal RMS. To quantify self-reported music and dance relationships and rhythmic proficiency, we developed Music (MRQ) and Dance Relationship Questionnaires (DRQ), and a rhythm assessment (RA), respectively. We correlated MRQ, DRQ, and RA scores against RMS performance for each group separately.ResultsThe OA and YA groups exhibited better MRQ and RA scores than the MCI group (p<0.006). Better MRQ and RA scores were associated with better temporal RMS performance for only the YA and OA groups (r2=0.18-0.41; p<0.045). DRQ scores were not associated with RMS performance in any group.ConclusionsCognitive deficits in adults with MCI likely limit the extent to which music relationships or rhythmic proficiency improve the ability to perform temporal aspects of movements performed during dance-based therapies.
Large pan-cancer cell screen coupled to (phospho-)proteomics underscores high-dose vitamin C as a potent anti-cancer agent
Authors: Vallés-Martí Andrea , Böttger Franziska , Yau Elysia , Tejjani Khadija , Meijs Loes , Sharma Sugandhi , Mumtaz Madiha , Le Large Tessa Y. S. , Erozenci Ayse , Dekker Daniëlle , Schelfhorst Tim , Medema Jan Paul , Bijnsdorp Irene V , Knol Jaco C , Piersma Sander R , Pham Thang V. , Giovannetti Elisa , Jiménez Connie R 
Published: December 2023

ABSTRACTIncreasing preclinical and clinical evidence has positioned high-dose vitamin C as a promising anti-cancer treatment that merits more clinical attention. Multiple cytotoxicity mechanisms have been described, including pro-oxidant effects. To contribute to the preclinical understanding of the broad pan-cancer effects of high-dose vitamin C in a global manner, we determined the IC50 of a large panel of cancer cell lines (n=51) representing 7 solid tumour types and generated proteome data. The majority of cell lines were highly sensitive (IC50 range 0.036-10mM, mean 1.7 ± 0.4 mM), well below a clinically achievable dose. The proteome data (>5000 proteins per sample), showed that high sensitivity is associated with proliferation, as indicated by functional enrichment of cell cycle, RNA splicing and chromatin organization, while lower sensitivity is linked to extracellular vesicles, glycolysis, fatty acid metabolism and mitochondria. Moreover, (phospho-)proteome analysis of on-treatment vitamin C effects on four pancreatic ductal adenocarcinoma (PDAC) cells dosed at a range of IC50 values (Hs766 T, 2 mM; Capan-2, 0.6 mM; PANC-1, 0.14 mM and Suit-2, 0.1 mM) revealed, next to cell line specific effects, down-modulation of AKT-MTOR signalling and immune suppressive signalling, while IFN-α response was enhanced upon vitamin C. Altogether, our comprehensive pharmacological and (phospho-)proteome analysis is the first to assess cancer vulnerabilities and effects of vitamin C on a large cancer cell line panel and underscores the potential of high-dose vitamin C as an anti-cancer agent.
A pipeline for validation of sRNA effectors suggests cross-kingdom communication in the symbiosis ofArabidopsiswithSerendipita indica
Authors: Nasfi Sabrine , Shahbazi Saba , Bitterlich Katharina , Šečić Ena , Kogel Karl-Heinz , Steinbrenner Jens 
Published: December 2023

AbstractBidirectional communication between pathogenic microbes and their plant hosts via small (s)RNA-mediated cross-kingdom RNA interference (ckRNAi) is one key element for successful host colonisation. However, whether mutualistic fungi from the Serendipitaceae family, known for their extremely broad host range, employ sRNAs to colonize plant roots is still under discussion. To address this question, we developed a pipeline to validate the accumulation, translocation, and activity of fungal sRNAs in post-transcriptional silencing ofArabidopsis thalianagenes. Using stem-loop PCR, we detected the expression of a specific set ofSerendipita indica(Si)sRNAs, targeting host genes involved in cell wall organization, hormonal signalling regulation, immunity, and gene regulation. To confirm the gene silencing activity of these sRNA in plant cells,SisRNAs were transiently expressed in protoplasts. Stem-loop PCR proved the expression of sRNAs, while qPCR validated post-transcriptional gene silencing of their predicted target genes. Furthermore, ARGONAUTE 1 immunoprecipitation (AtAGO1-IP) revealed the loading of fungalSisRNAs into the plant RNAi machinery, suggesting the translocation ofSisRNA from the fungus into root cells. In conclusion, this study provides a blueprint for rapid selection and analysis of sRNA effectors in plant-microbe interactions and further suggests cross-kingdom communication in the Sebacinoid symbiosis.HighlightSmall RNAs of the beneficial fungusSerendipita indicaare translocated and silence Arabidopsis genes at the onset of the interaction, revealing cross-kingdom communication in sebacinoid symbiosis.
Male-biased recombination at chromosome ends in a songbird revealed by precisely mapping crossover positions
Authors: Zhang Hongkai , Lundberg Max , Ponnikas Suvi , Hasselquist Dennis , Hansson Bengt 
Published: December 2023

AbstractRecombination plays a crucial role in evolution by generating novel haplotypes and disrupting linkage between genes, thereby enhancing the efficiency of selection. Here, we analyse the genomes of twelve great reed warblers (Acrocephalus arundinaceus) in a three-generation pedigree to identify precise crossover positions along the chromosomes. We located more than 200 crossovers and found that these were highly concentrated towards the telomeric ends of the chromosomes. While the number of recombination events was similar between the sexes, the crossovers were located significantly closer to the ends of paternal compared to maternal chromosomes. The frequency of crossovers was similar between intergenic and genic regions, but within genes, they occurred more frequently in exons than in introns. In conclusion, our study of the great reed warbler revealed substantial variation in crossover frequencies within chromosomes, with a distinct bias towards the sub-telomeric regions, particularly on the paternal side. These findings emphasise the importance of thoroughly screening the entire length of chromosomes to characterise the recombination landscape and uncover potential sex-biases in recombination.Article summaryThe genetic exchange between the paternal and maternal chromosomes during meiosis – recombination – plays a crucial role in evolution by generating new haplotypes that natural selection can act upon. By analysing genomic data of a three-generation family of great reed warblers, we detected precise locations of approximately 200 recombination events in the genome of these birds. This unveiled a prominent sex-bias with recombination occurring more often towards chromosome ends in males than in females.
Comparison of Multiple Carbapenemase Tests Based on an Unbiased Colony Selection Method
Authors: Wang Hsin-Yao , Tseng Yi-Ju , Lin Wan-Ying , Wang Yu-Chiang , Lin Ting-Wei , Hsu Jen-Fu , Wu Marie Yung-Chen , Wu Chiu-Hsiang , Kalpana Sriram , Lu Jang-Jih 
Published: December 2023

AbstractCarbapenemase-producing organisms (CPOs) present a major threat to public health, demanding precise diagnostic techniques their detection. Discrepancies among CPO tests have raised concerns, partly due to limitations in detecting bacterial diversity within host/specimen. We explored the impact of unbiased colony selection on carbapenemase testing and assessed its relevance on various tests. Based on “FirstAll” for unbiased colony selection to reduce bias, we compared modified carbapenem inactivation method/EDTA-modified carbapenem inactivation method (mCIM/eCIM), Carba5, the CPO panel, and multiplex PCR (M-PCR). Initially, we compared FirstAll to conventional colony selection for mCIM. Second, we used M-PCR as a reference, to evaluate test performance across seven CPO species. The results revealed that FirstAll selection improved carbapenemase detection, revising false-negative in 10.5% ofK. pneumoniaeisolates. In addition, 12.4% of CPOs tested positive for multiple carbapenemase genes. Both the Carba5 test and CPO panel showed suboptimal performance (sensitivity/specificity: Carba5 75.5%/89.0%, CPO panel 78.1%/74.0%). Carba5 test provided specific carbapenemase class assignments but CPO panel failed in 20.3% of cases. Carba5 test and the CPO panel results correlated well with ceftazidime-avibactam minimal inhibitory concentrations (MICs). Concordance for class A/D with MICs was 88.3% for Carba5 and 92.0% for the CPO panel; whereas for class B, it was 86.5% for Carba5 and 76.2% for the CPO panel. In conclusion, FirstAll as the unbiased colony selection impacted carbapenemase testing. With FirstAll, the diagnostic performance of either Carba5 or the CPO panel was compromised. The utilization of ceftazidime-avibactam guided by either the CPO panel or Carba5 was appropriate.ImportanceThe increasing carbapenemase-producing organisms (CPO) is concerning due to high mortality rates and limited treatment options. Precise testing for CPO is crucial not only for antibiotic treatments but also for infection control. However, discrepant results for an individual overtime or even intra-specimen are found in either phenotypic or genetic testing, posing considerable challenge in clinical management. Based on the colonization-infection model of CPO infections, there would be strain heterogeneity in an individual. On top of the heterogeneity, the single colony selection method in conventional CPO testing would be the source of discrepancy and bias. To test the hypothesis, we proposed FirstAll method as the unbiased colony selection method. We demonstrated that FirstAll corrected around 10% false-negative cases. Lower diagnostic performances of CPO tests were also found in comparison to previous related studies. The study revealed that colony selection would have considerable impacts on CPO testing.
A rise in double-strand breaks sensitizes tumours to oxidative metabolism inhibitors
Authors: Medina-Jover Ferran , Figueras Agnès , Lahiguera Álvaro , Guillén Pau , Espín Roderic , Pardo Miguel Ángel , Pujana Miquel Angel , Berra Edurne , Villanueva Alberto , Bernat-Peguera Adrià , Romeo Margarita , Perales José Carlos , Viñals Francesc 
Published: December 2023

ABSTRACTDouble strand brakes (DSB) accumulate in cellular DNA as a result of deficiencies in homologous recombination repair systems, such as mutations inBRCAgenes, or upon antitumoral treatments. In the present study we show that the accumulation of DSB, regardless of its origins, leads to a shift towards oxidative metabolism. We have identified that DSB-induced reactive oxygen species (ROS) promote the activation of NRF2 which downregulates the glycolytic transcription factor HIF-1. HIF-1 inhibition is a key step in this metabolic shift, because leads to the reduction of PDHK1 levels and the consequential activation of pyruvate dehydrogenase, a mitochondrial gatekeeper of cellular metabolism, promoting this metabolic shift. Remarkably, after the induction of DSBs, the tumour is more sensitive to the inhibition of oxidative metabolism since both treatments synergize in vivo, resulting in reduced tumour growth. Therefore, we demonstrate a significant feedback between DSBs induction and cancer cell metabolism that ultimately limits the cell’s potential for metabolic plasticity, hence sensitizing it to the action of counteracting drugs.
Effectivein vivobinding energy landscape illustrates kinetic stability of RBPJ-DNA binding
Authors: Huynh Duyen , Hoffmeister Philipp , Friedrich Tobias , Zhang Kefan , Bartkuhn Marek , Ferrante Francesca , Giaimo Benedetto Daniele , Kovall Rhett , Borggrefe Tilman , Oswald Franz , Gebhardt J. Christof M. 
Published: December 2023

AbstractTranscription factors (TFs) such as the central DNA-binding hub in Notch signal transduction, RBPJ, bind to specific DNA sequences to regulate gene transcription. How the efficiency of gene regulation depends on the TF-DNA binding kinetics and cofactor interactions is mostly unknown. We determined the DNA binding kinetics and the transcriptional activity of RBPJ and several mutant variants by live-cell single-molecule tracking and reporter assays, and measured their genome-wide chromatin occupation by ChIP-Seq. We observed that cofactor binding, in addition to DNA binding, was required for target site specificity. Importantly, the target site search time of RBPJ was longer than its residence time, indicating kinetic rather than thermodynamic binding stability. Impaired DNA binding, e.g. by mutation K195E related to Adams-Oliver-Syndrome, modulated not only dissociation, but also association to target sites. Impaired cofactor binding mainly altered the rates of unspecific binding and target site association. For other TFs, we also observed longer search than residence times, indicating that kinetic rather than thermodynamic stability of DNA binding might be a general feature of TFsin vivo. We propose that an effectivein vivobinding energy landscape of TF-DNA interactions constitutes an instructive visualization of TF-DNA binding kinetics and the changes upon mutations.
FastProtein – An automated software forin silicoproteomic analysis
Authors: Moreira Renato Simões , Filho Vilmar Benetti , Maia Guilherme Augusto , Soratto Tatiany Aparecida Teixeira , Kawagoe Eric Kazuo , Russi Bruna Caroline , Miletti Luiz Claudio , Wagner Glauber 
Published: December 2023

AbstractBackgroundAlthough various tools provide proteomic information, each has its limitations regarding execution platforms, libraries, versions, and data output format. Therefore, integrating data analyses generated using different software programs is a manual process that can prolong the analysis time.ResultsThis paper presents FastProtein, a protein analysis pipeline tool developed in Java. This tool is user-friendly, easily installable, and provides important information regarding the subcellular location, transmembrane domains, signal peptide, molecular weight, isoelectric point, hydropathy, aromaticity, gene ontology, endoplasmic reticulum retention domains, and N- glycosylation domains of a protein. Furthermore, it helps determine the presence of glycosylphosphatidylinositol and obtain annotation information using InterProScan, PANTHER, PFam, and alignment-based annotation searches. Additionally, the software outputs a protein dataset with evidence of membrane localization.ConclusionsThe proposed tool provides the scientific community with an easy and user-friendly computational tool for proteomics data analysis. The tool is applicable to both small datasets and proteome-wide studies. It can be used in either the command line interface mode or through a web interface installed on a local server or via the BioLib web interface (http://biolib.com/UFSC/FastProtein). FastProtein also accelerates proteomics analysis routines by generating multiple results in a one-step run. The software is open-source and freely available. Installation and execution instructions, as well as the source code and test files generated for tool validation, are provided athttps://github.com/bioinformatics-ufsc/FastProtein.
Adapting Nanopore Sequencing Basecalling Models for Modification Detection via Incremental Learning and Anomaly Detection
Authors: Wang Ziyuan , Fang Yinshan , Liu Ziyang , Hao Ning , Zhang Hao Helen , Sun Xiaoxiao , Que Jianwen , Ding Hongxu 
Published: December 2023

ABSTRACTWe leverage machine learning approaches to adapt nanopore sequencing basecallers for nucleotide modification detection. We first apply the incremental learning technique to improve the basecalling of modification-rich sequences, which are usually of high biological interests. With sequence backbones resolved, we further run anomaly detection on individual nucleotides to determine their modification status. By this means, our pipeline promises the single-molecule, single-nucleotide and sequence context-free detection of modifications. We benchmark the pipeline using control oligos, further apply it in the basecalling of densely-modified yeast tRNAs andE.coligenomic DNAs, the cross-species detection of N6-methyladenosine (m6A) in mammalian mRNAs, and the simultaneous detection of N1-methyladenosine (m1A) and m6A in human mRNAs. Our IL-AD workflow is available at:https://github.com/wangziyuan66/IL-AD.
Where is the expertise? Investigating the drivers of top-down versus bottom-up approaches to cross-cultural conflict resolution training
Authors: Phan Lan H. , Coleman Peter T. 
Published: December 2023

Purpose
For decades, conflict resolution (CR) educators working cross-culturally have struggled with a fundamental dilemma – whether to offer western, evidence-based approaches through a top-down (prescriptive) training process or to use a bottom-up (elicitive) strategy that builds on local cultural knowledge of effective in situ conflict management. This study aims to explore which conditions that prompted experienced CR instructors to use more prescriptive or elicitive approaches to such training in a foreign culture and the implications for training outcomes.

Design/methodology/approach
There are two parts to this study. First, the authors conducted a literature review to identify basic conditions that might be conducive to conducting prescriptive or elicitive cross-cultural CR training. The authors then tested the identified conditions in a survey with experienced CR instructors to identify different conditions that afforded prescriptive or elicitive approaches. Exploratory factor analysis and regression were used to assess which conditions determined whether a prescriptive or elicitive approach produced better outcomes.

Findings
In general, although prescriptive methods were found to be more efficient, elicitive methods produced more effective, culturally appropriate, sustainable and culturally sensitive training. Results revealed a variety of instructor, participant and contextual factors that influenced whether a prescriptive or elicitive approach was applied and found to be more suitable.

Originality/value
This study used empirical survey data with practicing experts to provide insight and guidance into when to use different approaches to CC-CR training effectively.