bluuebunny/crossref_metadata_2025 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

Chronic 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

Concomitant 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

Background

Personalized 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.

Objective

Characterize 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.

Methods

We 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.

Results

The 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.

Conclusions

Cognitive 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

Increasing 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

Bidirectional 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.

Highlight

Small 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

Recombination 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 summary

The 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

Carbapenemase-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.

Importance

The 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

ABSTRACT

Double 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

Transcription 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

Background

Although 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.

Results

This 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.

Conclusions

The 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

We 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.
Continue staying in online health platforms or not: the moderating role of threat appraisal
Authors: Li Ping , Wong Siew Fan , Wang Shan , Chang Younghoon
Published: December 2023

Purpose

This study aims to study the mechanisms and conditions of users' intention to continue to use online health platforms from an information technology (IT) affordance perspective.

Design/methodology/approach

b This research proposes that a critical affordance effect on an online health platform, users' intention to continue the use of the platform, is affected by five platform affordances via two actualized affordances (i.e. perceived benefits (PBs) and online engagement (OE)). Perceived health threat moderates the effect generated by affordance actualization. A dataset involving 409 users from the “Ping An Health” platform was collected through an online survey and analyzed to validate the research hypotheses.

Findings

The data analysis results confirm that the proposed online health platform affordances affect users' PBs and OE, which influence users' intentions to continue using the platform. Perceived threats (perceived vulnerability (PVU) and perceived severity (PSE)) moderate the relationship between PBs and continuance intention (CI) and between OE and CI.

Practical implications

The research provides important recommendations for online health platform designers to develop IT affordances that can support users' needs for healthcare services.

Originality/value

Limited studies investigated why users continue participating in online diagnosis and treatment. This study provides a new perspective to expand the affordance framework by combining technology features and user health behavior. The study also emphasizes the importance of perceived threats in IT use.
Financial accessibility and crime – Empirical study based on panel data from Chinese cities
Authors: Wang Zifeng , Ye Dezhu , Liang Tao
Published: December 2023

Purpose

This paper empirically investigates the relationship between financial availability and crime by measuring it across five dimensions: banking, securities, insurance, private lending and digital inclusive finance.

Design/methodology/approach

The study utilizes 2011–2017 data from prefecture-level cities as a representative sample. Moreover, these findings remain robust after addressing endogeneity through the use of the historical distance between cities and the railroad network as an instrumental variable.

Findings

The findings demonstrate a significant negative relationship between financial accessibility and crime rates. Heterogeneity exists in the inhibitory effect of different types of financial accessibility on crime, with banking finance exhibiting a stronger inhibitory effect compared to private lending. Areas affected by natural disasters and infectious diseases exhibit a stronger inhibitory effect of financial accessibility on crime rates, particularly in areas with severe shocks of natural disasters and epidemics. This effect is attributed to the low financing threshold and easy access to private lending, which plays a more effective role than bank finance when people face extreme risks.

Practical implications

There should be stricter regulations imposed on private lending markets and the introduction of more rational legislation aimed at guiding a healthy development within these markets; such measures serve as effective and complementary means for individuals from all walks of life to access credit financing.

Social implications

The regulation of financial resources by the government should always prioritize ensuring the accessibility of financial policies to cater to the needs of the majority population.

Originality/value

This study is for the first time in an emerging economy context, the causal relationship between financial accessibility and crime. To provide a more comprehensive measure of financial accessibility in a region, this paper proposes a five-dimensional methodology.
Celebrity endorsers and social media influencers for leveraging consumer advocacy and relationship intentions – a multivariate mediation analysis
Authors: Kalam Abul , Goi Chai Lee , Tiong Ying Ying
Published: December 2023

Purpose

The purpose of this study is to explore the comparative effects of mainstream celebrities and social media influencers on consumer advocacy and relationship intentions. The study also examines the direct and serial mediation effects on those relationships.

Design/methodology/approach

The survey questionnaire was used to collect data from 718 respondents throughout Malaysia, with convenience and snowball sampling techniques employed. The data were analyzed based on the structural equation modeling (SEM) approach through the AMOS version 24. The PROCESS MACRO v-4.20 was applied to evaluate mediating effects in the model.

Findings

The results reveal that celebrity endorsers' involvement in social media significantly influences the uses of social media, which also impacts the attitudes and, subsequently, consumer relationship and advocacy intentions. The study found that mainstream celebrities and social media influencers effectively promote brands, and it discovered insignificant differences in their effects on the analyzed relationships.

Research limitations/implications

This study has been conducted on consumers in Malaysia; it may have different effects on consumers in other countries.

Practical implications

Brand managers and policymakers may benefit from following the study's guidelines for making consumer relationship and advocacy intentions by celebrity endorsers and uses of social media.

Social implications

The brand community can benefit from tightening their social bondage by sharing and managing crucial information from celebrities and using social media.

Originality/value

The study explores the effects of mainstream celebrities on consumer relationship and advocacy intentions using social media networks and managing consumer attitudes.
Modeling the effect of processing parameters on temperature history in Directed Energy Deposition: an analytical and finite element approach
Authors: Ghasempour-Mouziraji Mehran , Afonso Daniel , Hosseinzadeh Saman , Goulas Constantinos , Najafizadeh Mojtaba , Hosseinzadeh Morteza , Ganji D.D. , Alves de Sousa Ricardo
Published: December 2023

Purpose

The purpose of this paper is to assess the feasibility of analytical models, specifically the radial basis function method, Akbari–Ganji method and Gaussian method, in conjunction with the finite element method. The aim is to examine the impact of processing parameters on temperature history.

Design/methodology/approach

Through analytical investigation and finite element simulation, this research examines the influence of processing parameters on temperature history. Simufact software with a thermomechanical approach was used for finite element simulation, while radial basis function, Akbari–Ganji and Gaussian methods were used for analytical modeling to solve the heat transfer differential equation.

Findings

The accuracy of both finite element and analytical methods was validated with about 90%. The findings revealed direct relationships between thermal conductivity (from 100 to 200), laser power (from 400 to 800 W), heat source depth (from 0.35 to 0.75) and power absorption coefficient (from 0.4 to 0.8). Increasing the values of these parameters led to higher temperature history. On the other hand, density (from 7,600 to 8,200), emission coefficient (from 0.5 to 0.7) and convective heat transfer (from 35 to 90) exhibited an inverse relationship with temperature history.

Originality/value

The application of analytical modeling, particularly the utilization of the Akbari–Ganji, radial basis functions and Gaussian methods, showcases an innovative approach to studying directed energy deposition. This analytical investigation offers an alternative to relying solely on experimental procedures, potentially saving time and resources in the optimization of DED processes.
Efficacy of oral JAK1 or JAK1/2 inhibitor for treating refractory pruritus in dystrophic epidermolysis bullosa: A retrospective case series
Authors: Kwon Il Joo , Kim Song‐Ee , Kim Soo‐Chan , Lee Sang Eun
Published: December 2023

Refractory pruritus is the most distressing, disease‐related symptom in patients with dystrophic epidermolysis bullosa (DEB), inducing an itch‐scratch‐blister cycle. Chronic inflammation is a hallmark of DEB, thus upregulation of inflammatory cytokines and Janus kinase (JAK) signaling may play a role in DEB‐related pruritus. We retrospectively reviewed the medical records of DEB patients with refractory pruritus who were treated with either baricitinib, a JAK1/2 inhibitor, or upadacitinib, a selective JAK1 inhibitor. Patients received baricitinib (4 mg) or upadacitinib (15 mg) once a day for 2–32 weeks. A total of 12 DEB patients (six recessive DEB and six dominant DEB) were included in this study. The mean±SD baseline pruritus visual analog scale (VAS) score was 7.5 ± 1.7. Upadacitinib or baricitinib treatment resulted in a rapid and sustained decrease in itch. Four out of 12 patients (33.3%) and seven out of 10 patients (70%) showed a decrease of at least 3 points in the pruritus VAS score from baseline at weeks 2 and 4, respectively. The mean percentage changes from baseline in pruritus VAS scores at weeks 2 and 4 were −42.9% and −52.7%, respectively. Subgroup analysis showed greater reductions in the pruritus VAS score in the baricitinib group (n = 5) compared to the upadacitinib group (n = 7), and in patients with epidermolysis bullosa pruriginosa (n = 3) compared to other subtypes of DEB (n = 9); however, these differences did not reach statistical significance. Three out of 10 (33.3%) patients showed at least a 2‐point reduction in pain intensity from baseline at week 4. Eight out of 12 patients (66.7%) also showed a reduction in the number of new blisters, which correlated with a reduction in the pruritus score. No patient discontinued treatment because of serious adverse events. Our results suggest that JAK1 or JAK1/2 inhibitors could be a promising treatment option for DEB‐related pruritus. Long‐term safety should be assessed in future studies.
Ionotropic receptors mediate olfactory learning and memory in Drosophila
Authors: Ali Md Zeeshan , Anushree  , Ahsan Aarif , Ola Mohammad Shamsul , Haque Rizwanul , Ahsan Jawaid
Published: December 2023

Phenylacetaldehyde (PAH), an aromatic compound, is present in a diverse range of fruits including overripe bananas and prickly pear cactus, the two major host fruits for Drosophila melanogaster. PAH acts as a potent ligand for the ionotropic receptor 84a (IR84a) in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex. Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance. In D. melanogaster, two distinct kinds of olfactory receptors, that is, odorant receptors (ORs) and ionotropic receptors (IRs), perceive the odorant stimuli. They display unique structural, molecular, and functional characteristics in addition to having different evolutionary origins. Traditionally, olfactory cues detected by the ORs such as ethyl acetate, 1‐butanol, isoamyl acetate, 1‐octanol, 4‐methylcyclohexanol, etc. classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies. This underlines the participation of OR‐activated olfactory pathways in learning and memory formation. Our study elucidates that likewise ethyl acetate (EA) (an OR‐responsive odorant), PAH (an IR‐responsive aromatic compound) too can form learning and memory when associated with an appetitive gustatory reinforcer. The association of PAH with sucrose (PAH/SUC) led to learning and formation of the long‐term memory (LTM). Additionally, the Orco1, Ir84aMI00501, and Ir8a1 mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning. These results highlight the involvement of IRs via an IR‐activated pathway in facilitating robust olfactory behavior.
Microbial lag calculator: A shiny‐based application and an R package for calculating the duration of microbial lag phase
Authors: Smug Bogna J. , Opalek Monika , Necki Maks , Wloch‐Salamon Dominika
Published: December 2023

The duration of lag phase can be used as an organismal fitness marker; however, it is often underreported as its estimation may be challenging and method and parameters dependent. Moreover, there are no publicly available tools to calculate lag duration by different methods.

We developed a shiny‐based web application (https://microbialgrowth.shinyapps.io/lag_calulator/) where the lag duration can be calculated based on the user‐specified growth curve data, and for various explicitly specified methods, parameters and data preprocessing techniques. Additionally, we release an R package ‘miLAG’ that can be further customised and developed.

We also describe in short the assumptions, advantages and disadvantages of the most popular lag calculation methods and propose a decision tree to choose a method most suited to one's data.

Finally, we show some working examples of how to calculate lag duration using our shiny server.
Risk of malignancy in incidental oropharyngeal lesions exhibiting fluorodeoxyglucose uptake which proceed to tissue biopsy
Authors: Key Seraphina , Chia Clemente , Magarey Matthew , Dixon Benjamin
Published: December 2023

Background

Utilization of positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose is increasing in use for a variety of indications, including surveillance of cancer patients. There is a paucity of evidence pertaining to the significance of incidental PET‐avid oropharyngeal lesions. This study aims to examine the clinical and radiological features of these incidental oropharyngeal lesions in patients undergoing PET for indications other than head and neck cancer.

Methods

Retrospective cohort study of three Australian tertiary hospitals, from 2015 to 2021, on adult patients undergoing biopsy of incidental PET‐avid oropharyngeal lesions. Primary outcome of interest was the incidence of malignancy. Patients with a previous history of, or undergoing investigations for, head and neck cancer were excluded.

Results

Thirty‐one patients were included, wherein 21 patients had tonsillar uptake, and 13 patients had base of tongue uptake. Tonsillar disease was mostly asymmetrical (n = 15/21), bilateral (n = 11/21), and had median SUVmax9.35 (n = 12, IQR 7.4–11.15). Base of tongue was mostly asymmetrical (n = 7/13, 54%), bilateral (n = 8/13, 62%), and had median SUVmax8.2 (n = 10, IQR 6.9–12.65). Seven patients had malignancy confirmed on tissue biopsy: five biopsies confirmed the tissue diagnosis of suspected lymphoma, and two incidental findings of unexpected malignancies: one p16 positive tonsillar squamous cell carcinoma, and one metastatic breast cancer.

Conclusion

In 31 patients undergoing tissue biopsy for incidental PET‐avid oropharyngeal lesions, there were two unexpected malignancies. Our study results indicate that although unexpected malignancies are uncommon, a malignant diagnosis cannot be excluded from clinical features alone.
Infant gastroesophageal reflux disease management consensus
Authors: Vandenplas Yvan , Orsi Marina , Benninga Marc , Gatcheco Felizardo , Rosen Rachel , Thomson Mike
Published: December 2023

Aim

Infant gastroesophageal reflux is mostly benign; however, when associated with complications like failure to thrive, it may be indicative of gastroesophageal reflux disease. There are currently several unmet needs pertaining to the management of infant gastroesophageal reflux (disease). Reflux in infants is mostly composed of breast milk or formula, so this population is significantly different to older children and adults. The objective of this Delphi consensus was to establish recommendations based on published literature and the experience of clinical experts in paediatric gastroenterology in the context of infant gastroesophageal reflux (disease).

Methods

The Delphi methodology was used to obtain a consensus on 18 statements relating to clinical aspects of infant gastroesophageal reflux (disease).

Results

The expert panel comprising paediatric gastroenterology clinical specialists reached a consensus for all statements by means of an online, anonymised voting system.

Conclusion

It was highlighted that there is generally low awareness of or adherence to guidelines in clinical practice and that acid suppression therapy should not be indicated for non‐acid reflux, which constitutes a significant proportion of total gastroesophageal reflux episodes among infants. Furthermore, it was emphasised that there is an unmet medical need for therapy for some symptomatic infants with non‐acid reflux disease.
Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases
Authors: Akkus Erman , Tuncalı Timur , Akın Hasan Yalım , Aydın Yıldız , Beşışık Sevgi Kalayoğlu , Gürkan Emel , Ratip Siret , Salihoğlu Ayşe , Sargın Deniz , Ünal Ali , Turcan Ayşegül , Sevindik Ömür Gökmen , Demir Muzaffer , Beksac Meral
Published: December 2023

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM‐affected families, comprising 77 individuals, were included. Targeted next‐generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease‐causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease‐causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.
Distribution of ubiquilin 2 and TDP‐43 aggregates throughout the CNS in UBQLN2 p.T487I‐linked amyotrophic lateral sclerosis and frontotemporal dementia
Authors: Nementzik Laura R. , Thumbadoo Kyrah M. , Murray Helen C. , Gordon David , Yang Shu , Blair Ian P. , Turner Clinton , Faull Richard L. M. , Curtis Maurice A. , McLean Catriona , Nicholson Garth A. , Swanson Molly E. V. , Scotter Emma L.
Published: December 2023

Mutations in the UBQLN2 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The neuropathology of such UBQLN2‐linked cases of ALS/FTD is characterised by aggregates of the ubiquilin 2 protein in addition to aggregates of the transactive response DNA‐binding protein of 43 kDa (TDP‐43). ALS and FTD without UBQLN2 mutations are also characterised by TDP‐43 aggregates, that may or may not colocalise with wildtype ubiquilin 2. Despite this, the relative contributions of TDP‐43 and ubiquilin 2 to disease pathogenesis remain largely under‐characterised, as does their relative deposition as aggregates across the central nervous system (CNS). Here we conducted multiplex immunohistochemistry of three UBQLN2 p.T487I‐linked ALS/FTD cases, three non‐UBQLN2‐linked (sporadic) ALS cases, and 8 non‐neurodegenerative disease controls, covering 40 CNS regions. We then quantified ubiquilin 2 aggregates, TDP‐43 aggregates and aggregates containing both proteins in regions of interest to determine how UBQLN2‐linked and non‐UBQLN2‐linked proteinopathy differ. We find that ubiquilin 2 aggregates that are negative for TDP‐43 are predominantly small and punctate and are abundant in the hippocampal formation, spinal cord, all tested regions of neocortex, medulla and substantia nigra in UBQLN2‐linked ALS/FTD but not sporadic ALS. Curiously, the striatum harboured small punctate ubiquilin 2 aggregates in all cases examined, while large diffuse striatal ubiquilin 2 aggregates were specific to UBQLN2‐linked ALS/FTD. Overall, ubiquilin 2 is mainly deposited in clinically unaffected regions throughout the CNS such that symptomology in UBQLN2‐linked cases maps best to the aggregation of TDP‐43.
Pollinator‐mediated effects of landscape‐scale land use on grassland plant community composition and ecosystem functioning – seven hypotheses
Authors: Hederström Veronica , Ekroos Johan , Friberg Magne , Krausl Theresia , Opedal Øystein H. , Persson Anna S. , Petrén Hampus , Quan Yuanyuan , Smith Henrik G. , Clough Yann
Published: December 2023

Environmental change is disrupting mutualisms between organisms worldwide. Reported declines in insect populations and changes in pollinator community compositions in response to land use and other environmental drivers have put the spotlight on the need to conserve pollinators. While this is often motivated by their role in supporting crop yields, the role of pollinators for reproduction and resulting taxonomic and functional assembly in wild plant communities has received less attention. Recent findings suggest that observed and experimental gradients in pollinator availability can affect plant community composition, but we know little about when such shifts are to be expected, or the impact they have on ecosystem functioning. Correlations between plant traits related to pollination and plant traits related to other important ecosystem functions, such as productivity, nitrogen uptake or palatability to herbivores, lead us to expect non‐random shifts in ecosystem functioning in response to changes in pollinator communities. At the same time, ecological and evolutionary processes may counteract these effects of pollinator declines, limiting changes in plant community composition, and in ecosystem functioning. Despite calls to investigate community‐ and ecosystem‐level impacts of reduced pollination, the study of pollinator effects on plants has largely been confined to impacts on plant individuals or single‐species populations.

With this review we aim to break new ground by bringing together aspects of landscape ecology, ecological and evolutionary plant–insect interactions, and biodiversity–ecosystem functioning research, to generate new ideas and hypotheses about the ecosystem‐level consequences of pollinator declines in response to land‐use change, using grasslands as a focal system. Based on an integrated set of seven hypotheses, we call for more research investigating the putative pollinator‐mediated links between landscape‐scale land use and ecosystem functioning. In particular, future research should use combinations of experimental and observational approaches to assess the effects of changes in pollinator communities over multiple years and across species on plant communities and on trait distributions both within and among species.