bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Bingo’—a large language model- and graph neural network-based workflow for the prediction of essential genes from protein data
Authors: Ma Jiani , Song Jiangning , Young Neil D , Chang Bill C H , Korhonen Pasi K , Campos Tulio L , Liu Hui , Gasser Robin B
Published: December 2023

The identification and characterization of essential genes are central to our understanding of the core biological functions in eukaryotic organisms, and has important implications for the treatment of diseases caused by, for example, cancers and pathogens. Given the major constraints in testing the functions of genes of many organisms in the laboratory, due to the absence of in vitro cultures and/or gene perturbation assays for most metazoan species, there has been a need to develop in silico tools for the accurate prediction or inference of essential genes to underpin systems biological investigations. Major advances in machine learning approaches provide unprecedented opportunities to overcome these limitations and accelerate the discovery of essential genes on a genome-wide scale. Here, we developed and evaluated a large language model- and graph neural network (LLM–GNN)-based approach, called ‘Bingo’, to predict essential protein-coding genes in the metazoan model organisms Caenorhabditis elegans and Drosophila melanogaster as well as in Mus musculus and Homo sapiens (a HepG2 cell line) by integrating LLM and GNNs with adversarial training. Bingo predicts essential genes under two ‘zero-shot’ scenarios with transfer learning, showing promise to compensate for a lack of high-quality genomic and proteomic data for non-model organisms. In addition, the attention mechanisms and GNNExplainer were employed to manifest the functional sites and structural domain with most contribution to essentiality. In conclusion, Bingo provides the prospect of being able to accurately infer the essential genes of little- or under-studied organisms of interest, and provides a biological explanation for gene essentiality.
Interest Rate Pass-Through in Euro Area Mortgage Markets: The Long Shadow of the Great Financial Crisis
Authors: Egan Paul , McQuinn Kieran
Published: December 2023

The tightening of monetary policy in response to the recently observed surge in inflation has focussed attention on the potential impact of changes in policy rates on European mortgage holders. Central to this question is the pass-through of policy rates to the mortgage rate charged in residential markets across the Euro Area as housing costs have contributed significantly to recent inflationary pressures. In particular, how much and how quickly does the change in the Euro Area policy rate pass-through to the mortgage rate in a particular member country’s market? The effectiveness of the monetary policy transmission mechanism has been impaired in a number of ways by the continuing effects of the great financial crisis (GFC). In this article, we seek to examine the manner in which the pass-through relationship between Euro Area policy rates and representative mortgage market rates has been impacted by financial sector considerations such as the degree of concentration in the sector, banks’ holdings of impaired loans, and the overall level of financial stress in the economy. Overall, our empirical findings indicate the level of financial stress experienced during the GFC has had a major impact on the effectiveness of monetary policy transmission in the Euro area. This article suggests that the GFC still has implications for the efficacy of current monetary policy in the Euro Area through several different but related channels. (JEL codes: E52, F45, and G21)
Inhibition of a novel Dickkopf-1-LDL receptor–related proteins 5 and 6 axis prevents diabetic cardiomyopathy in mice
Authors: Ma En , Wo Da , Chen Jinxiao , Yan Hongwei , Zhou Xiaohui , He Jia , Wu Celiang , Wang Qing , Zuo Changjing , Li Xiao , Li Li , Meng Qingshu , Zheng Liang , Peng Luying , Chen Lidian , Peng Jun , Ren Dan-ni , Zhu Weidong
Published: December 2023

Background and Aims

Anti-hypertensive agents are one of the most frequently used drugs worldwide. However, no blood pressure–lowering strategy is superior to placebo with respect to survival in diabetic hypertensive patients. Previous findings show that Wnt co-receptors LDL receptor–related proteins 5 and 6 (LRP5/6) can directly bind to several G protein–coupled receptors (GPCRs). Because angiotensin II type 1 receptor (AT1R) is the most important GPCR in regulating hypertension, this study examines the possible mechanistic association between LRP5/6 and their binding protein Dickkopf-1 (DKK1) and activation of the AT1R and further hypothesizes that the LRP5/6-GPCR interaction may affect hypertension and potentiate cardiac impairment in the setting of diabetes.

Methods

The roles of serum DKK1 and DKK1-LRP5/6 signalling in diabetic injuries were investigated in human and diabetic mice.

Results

Blood pressure up-regulation positively correlated with serum DKK1 elevations in humans. Notably, LRP5/6 physically and functionally interacted with AT1R. The loss of membrane LRP5/6 caused by injection of a recombinant DKK1 protein or conditional LRP5/6 deletions resulted in AT1R activation and hypertension, as well as β-arrestin1 activation and cardiac impairment, possibly because of multiple GPCR alterations. Importantly, unlike commonly used anti-hypertensive agents, administration of the anti-DKK1 neutralizing antibody effectively prevented diabetic cardiac impairment in mice.

Conclusions

These findings establish a novel DKK1-LRP5/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects. Thus, monitoring and therapeutic elimination of blood DKK1 may be a promising strategy to attenuate diabetic injuries.
Variable antiviral activity of islatravir against M184I/V mutant HIV-1 selected during antiretroviral therapy
Authors: Aulicino Paula C , Sharma Suman , Truong Khanghy , Kukunoor Vindhya , Ghei Karm , Arazi-Caillaud Solange , Taicz Moira , Bologna Rosa , Mangano Andrea , Kimata Jason T
Published: December 2023

Background

Islatravir is a new antiretroviral drug that inhibits the reverse transcriptase (RT) of HIV-1 through multiple mechanisms. It is proposed to be used in combination with doravirine, a new NNRTI. M184V/I mutations have been shown to reduce the in vitro antiviral activity of islatravir, but their effect when pre-selected during ART has not been investigated.

Methods

HIV-1 rt sequences were obtained from four individuals of the Garrahan HIV cohort prior to, or during virological failure to ART. HIV-1 infectious molecular clones were constructed on an NL4-3 backbone, and infectious viruses were produced by transfection of 293T cells. Fold-changes in IC50 were calculated for each mutant versus the NL4-3 WT. HIV-1 phenotypic drug resistance was tested in vitro against NRTIs and NNRTIs.

Results

In all the cases, M184I/V, either alone or in the presence of other mutations, was associated with reduced susceptibility to islatravir, abacavir and lamivudine. Viruses carrying M184V/I showed variable levels of resistance to islatravir (4.8 to 33.8-fold). The greatest reduction in susceptibility was observed for viruses carrying the mutations M184V + V106I (33.8-fold resistance) or M184V + I142V (25.2-fold resistance). For NNRTIs, the presence of V106I alone did not affect susceptibility to doravirine or etravirine, but showed a modest reduction in susceptibility to efavirenz (6-fold). Susceptibility to doravirine was slightly reduced only for one of the mutants carrying V106I in combination with Y181C and M184V.

Conclusions

Mutations and polymorphisms selected in vivo together with M184V/I depend on the viral genetic context and on ART history, and could affect the efficacy of islatravir once available for use in the clinic.
Streptococcus suis serotype 9 in Italy: genomic insights into high-risk clones with emerging resistance to penicillin
Authors: Massacci Francesca Romana , Cucco Lucilla , Panicciá Marta , Luppi Andrea , Albini Elisa , Peruzzo Arianna , Ferroni Laura , Ustulin Martina , Orsini Massimiliano , Magistrali Chiara Francesca
Published: December 2023

Background

Streptococcus suis is an important pig pathogen and an emerging zoonotic agent. In a previous study, we described a high proportion of penicillin-resistant serotype 9 S. suis (SS9) isolates on pig farms in Italy.

Objectives

We hypothesized that resistance to penicillin emerged in some SS9 lineages characterized by substitutions at the PBPs, contributing to the successful spread of these lineages in the last 20 years.

Methods

Sixty-six SS9 isolates from cases of streptococcosis in pigs were investigated for susceptibility to penicillin, ceftiofur and ampicillin. The isolates were characterized for ST, virulence profile, and antimicrobial resistance genes through WGS. Multiple linear regression models were employed to investigate the associations between STs, year of isolation, substitutions at the PBPs and an increase in MIC values to β-lactams.

Results

MIC values to penicillin increased by 4% each year in the study period. Higher MIC values for penicillin were also positively associated with ST123, ST1540 and ST1953 compared with ST16. The PBP sequences presented a mosaic organization of blocks. Within the same ST, substitutions at the PBPs were generally more frequent in recent isolates. Resistance to penicillin was driven by substitutions at PBP2b, including K479T, D512E and K513E, and PBP2x, including T551S, while reduced susceptibility to ceftiofur and ampicillin were largely dependent on substitutions at PBP2x.

Conclusions

Here, we identify the STs and substitutions at the PBPs responsible for increased resistance of SS9 to penicillin on Italian pig farms. Our data highlight the need for monitoring the evolution of S. suis in the coming years.
Usefulness of inclusion of ertapenem and temocillin screening breakpoints in the EUCAST rapid antimicrobial susceptibility testing (RAST) for rapid detection of OXA-48-producing Klebsiella pneumoniae directly from positive blood cultures
Authors: Fernández-Caso Belén , Lumbreras-Iglesias Pilar , Rodicio M Rosario , Fernández Javier , Rodríguez-Lucas Carlos
Published: December 2023

Objectives

The aims of this study were: (i) to assess the ability of the meropenem screening breakpoint as part of the screening rapid antimicrobial susceptibility testing (sRAST) of EUCAST for the detection of OXA-48 carbapenemase-producing Klebsiella pneumoniae directly from positive blood cultures (BCs); and (ii) to evaluate the inclusion of ertapenem and temocillin discs into the sRAST to enhance the detection of OXA-48-producing isolates.

Methods

BC bottles were spiked with a total of 117 K. pneumoniae isolates, including 77 previously characterized OXA-48 producers and 40 non-OXA-48 producers. Disc diffusion assays were directly performed from positive BCs with meropenem (10 µg), ertapenem (10 µg) and temocillin (30 µg) discs, and inhibition zones were manually measured after 4, 6 and 8 h of incubation. The screening cut-off values of sRAST were applied to evaluate their capability in detecting OXA-48-producing isolates. Receiver operating characteristic curves were constructed to illustrate the performance efficacy of the disc diffusion assays to detect OXA-48 producers.

Results

The meropenem cut-off values of sRAST only detected 90.91% of the OXA-48-producing isolates after 6 and 8 h of incubation. With the proposed cut-off points for ertapenem [<19 mm (4/6 h) and <20 mm (8 h)] and temocillin [<10 mm (4 h) and <11 mm (6/8 h)], all OXA-48-positive isolates were detected without any false-positive results at any reading time.

Conclusions

In healthcare settings with a high prevalence of OXA-48 producers, the inclusion of ertapenem and temocillin discs in the sRAST procedure may improve the detection of OXA-48-producing K. pneumoniae isolates directly from positive BCs, providing reliable results after only a 4 h incubation period.
Gene Regulatory Network that Shaped the Evolution of Larval Apical Organ in Cnidaria
Authors: Gilbert Eleanor , Craggs Jamie , Modepalli Vengamanaidu
Published: December 2023

Among non-bilaterian animals, a larval apical sensory organ with integrated neurons is only found in cnidarians. Within cnidarians, an apical organ with a ciliary tuft is mainly found in Actiniaria. Whether this apical tuft has evolved independently in Actiniaria or alternatively originated in the common ancestor of Cnidaria and Bilateria and was lost in specific groups is uncertain. To test this hypothesis, we generated transcriptomes of the apical domain during the planula stage of four species representing three key groups of cnidarians: Aurelia aurita (Scyphozoa), Nematostella vectensis (Actiniaria), and Acropora millepora and Acropora tenuis (Scleractinia). We showed that the canonical genes implicated in patterning the apical domain of N. vectensis are largely absent in A. aurita. In contrast, the apical domain of the scleractinian planula shares gene expression pattern with N. vectensis. By comparing the larval single-cell transcriptomes, we revealed the apical organ cell type of Scleractinia and confirmed its homology to Actiniaria. However, Fgfa2, a vital regulator of the regionalization of the N. vectensis apical organ, is absent in the scleractinian genome. Likewise, we found that FoxJ1 and 245 genes associated with cilia are exclusively expressed in the N. vectensis apical domain, which is in line with the presence of ciliary apical tuft in Actiniaria and its absence in Scleractinia and Scyphozoa. Our findings suggest that the common ancestor of cnidarians lacked a ciliary apical tuft, and it could have evolved independently in the Actiniaria.
Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites
Authors: Kumar Niranjan , Taneja Arushi , Ghosh Meenakshi , Rothweiler Ulli , Sundaresan Nagalingam Ravi , Singh Mahavir
Published: December 2023

The regulator of telomere elongation helicase 1 (RTEL1) plays roles in telomere DNA maintenance, DNA repair, and genome stability by dismantling D-loops and unwinding G-quadruplex structures. RTEL1 comprises a helicase domain, two tandem harmonin homology domains 1&2 (HHD1 and HHD2), and a Zn2+-binding RING domain. In vitro D-loop disassembly by RTEL1 is enhanced in the presence of replication protein A (RPA). However, the mechanism of RTEL1 recruitment at non-telomeric D-loops remains unknown. In this study, we have unravelled a direct physical interaction between RTEL1 and RPA. Under DNA damage conditions, we showed that RTEL1 and RPA colocalise in the cell. Coimmunoprecipitation showed that RTEL1 and RPA interact, and the deletion of HHDs of RTEL1 significantly reduced this interaction. NMR chemical shift perturbations (CSPs) showed that RPA uses its 32C domain to interact with the HHD2 of RTEL1. Interestingly, HHD2 also interacted with DNA in the in vitro experiments. HHD2 structure was determined using X-ray crystallography, and NMR CSPs mapping revealed that both RPA 32C and DNA competitively bind to HHD2 on an overlapping surface. These results establish novel roles of accessory HHDs in RTEL1’s functions and provide mechanistic insights into the RPA-mediated recruitment of RTEL1 to DNA repair sites.
Glycyrrhizin Production in Licorice Hairy Roots Based on Metabolic Redirection of Triterpenoid Biosynthetic Pathway by Genome Editing
Authors: Chiyo Naoki , Seki Hikaru , Kanamoto Takuya , Ueda Hiroshi , Kojoma Mareshige , Muranaka Toshiya
Published: December 2023

Glycyrrhizin, a type of the triterpenoid saponin, is a major active ingredient contained in the roots of the medicinal plant licorice (Glycyrrhiza uralensis, G. glabra and G. inflata), and is used worldwide in diverse applications, such as herbal medicines and sweeteners. The growing demand for licorice threatens wild resources and therefore a sustainable method of supplying glycyrrhizin is required. With the goal of establishing an alternative glycyrrhizin supply method not dependent on wild plants, we attempted to produce glycyrrhizin using hairy root culture. We tried to promote glycyrrhizin production by blocking competing pathways using CRISPR/Cas9-based gene editing. CYP93E3 CYP72A566 double-knockout (KO) and CYP93E3 CYP72A566 CYP716A179 LUS1 quadruple-KO variants were generated, and a substantial amount of glycyrrhizin accumulation was confirmed in both types of hairy root. Furthermore, we evaluated the potential for promoting further glycyrrhizin production by simultaneous CYP93E3 CYP72A566 double-KO and CYP88D6-overexpression. This strategy resulted in a 3-fold increase (∼1.4 mg/g) in glycyrrhizin accumulation in double-KO/CYP88D6-overexpression hairy roots, on average, compared with that of double-KO hairy roots. These findings demonstrate that the combination of blocking competing pathways and overexpression of the biosynthetic gene is important for enhancing glycyrrhizin production in G. uralensis hairy roots. Our findings provide the foundation for sustainable glycyrrhizin production using hairy root culture. Given the widespread use of genome editing technology in hairy roots, this combined with gene knockout and overexpression could be widely applied to the production of valuable substances contained in various plant roots.
Temperature-Regulated Flowering Locus T–Like Gene Coordinates the Spike Initiation in Phalaenopsis Orchid
Authors: Lu Hsiang-Chia , Huang Chiao-Wen , Mimura Tetsuro , Sukma Dewi , Chan Ming-Tsair
Published: December 2023

Phalaenopsis aphrodite can be induced to initiate spike growth and flowering by exposure to low ambient temperatures. However, the factors and mechanisms responsible for spike initiation in P. aphrodite remain largely unknown. In this study, we show that a repressor Flowing Locus T-like (FTL) gene, FTL, can act as a negative regulator of spike initiation in P. aphrodite. The mRNA transcripts of PaFTL are consistently high during high ambient temperature, thereby preventing premature spike initiation. However, during low ambient temperature, PaFTL expression falls while FT expression increases, allowing for spike initiation. Knock-down of PaFTL expression through virus-inducing gene silencing promoted spike initiation at 30/28°C. Moreover, PaFTL interacts with FLOWERING LOCUS D in a similar manner to FT to regulate downstream flowering initiation genes. Transgenic P. aphrodite plants exhibiting high expression of PaFTL do not undergo spike initiation, even when exposed to low ambient temperatures. These findings shed light on the flowering mechanisms in Phalaenopsis and provide new insights into how perennial plants govern spike initiation in response to temperature cues.
Resistance‐only and concurrent exercise induce similar myofibrillar protein synthesis rates and associated molecular responses in moderately active men before and after training
Authors: Lee Matthew J. , Caruana Nikeisha J. , Saner Nicholas J. , Kuang Jujiao , Stokes Tanner , McLeod Jonathan C. , Oikawa Sara Y. , Bishop David J. , Bartlett Jonathan D. , Phillips Stuart M.
Published: December 2023

Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free‐living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance‐only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance‐only exercise (RE, n = 8), RE plus high‐intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre‐ and post‐training, was used to determine MyoPS using orally administered deuterium oxide (D2O). In both weeks, MyoPS rates were comparable between groups. Post‐exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order‐dependent responses. In Week 10, exercise‐induced changes in MyoPS and some genes (PGC‐1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance‐only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.
Effect of Levodopa on Heat Hypersensitivity and Complex Motor Parkinsonism
Authors: Noyes Eric , Rajput Ali H. , Bocking Sarah , Rajput Alex
Published: December 2023

Objectives

The aim of the study is to report a case with heat intolerance, complex motor fluctuations, and parkinsonism.

Materials and Methods

A male with onset of heat intolerance at the age of 46 years developed left upper limb tremor at the age of 58 years. He was diagnosed with Parkinson disease at the age of 62 years and presented to Movement Disorders Clinic Saskatchewan at the age of 65 years. He reported motor response fluctuations, including WO and dyskinesias. There was no history of dizziness on standing, bladder, or sexual dysfunction. We recorded an asymptomatic drop of orthostatic blood pressure. He reported loss of smell sensation for 5 years and REM behavior disorder characterized by talking in his sleep. He was assessed at the age of 65 years over the course of a day with 4 video recordings of his evolving findings and symptoms with his informed consent.

Results

Initial assessment after levodopa was withheld more than 14 hours revealed him to be ‘off’ with severe dystonic neck flexion and with bradykinesia and rigidity in the limbs. He was anhidrotic, felt hot, and needed a wet towel over his neck. Over the course of 4 hours, he turns “on” with improvement in heat intolerance, neck hypertonicity, and parkinsonian findings and develops evolving dyskinetic movements before turning “off” again. His overall clinical picture was most consistent with multiple system atrophy.

Conclusions

Heat intolerance can precede onset of motor symptoms of parkinsonism by several years and supports a diagnosis of multiple system atrophy. To our knowledge, this is the first documented case of improvement in heat intolerance with levodopa.
The 8C model of vaccination readiness: A common framework to facilitate cross-study comparisons
Authors: Howe Piers , Dearnley Ferron
Published: December 2023

Several factors can potentially influence an individual’s vaccination readiness. To facilitate cross-study comparisons, it is essential that researchers use a shared framework to measure these factors. This would not only help determine their relative importance cross different contexts but also would aid in tailoring interventions to enhance vaccine uptake. Historically, five psychological antecedents of vaccination were identified: confidence, complacency, constraints, calculation, and collective responsibility. This 5C scale was later expanded to a 7C model by incorporating two additional components: compliance and conspiracy. Building upon this framework, we propose an eighth component, certification, defined as the person’s self-report that, in the past, they have had to provide evidence of vaccination. This component addresses a significant gap in the 7C model, as some individuals reported taking the COVID-19 vaccine primarily to obtain proof of vaccination, a motivation not captured by the 7C model. Our confirmatory factor analysis (N = 406) of a bifactor model of US citizens’ self-reported COVID-19 vaccination status showed that this eighth component had good psychometric properties and the 8C model had slightly higher criterion validity than the 7C model. We present the 8C model as a framework that provides a richer and more complete descriptions of the factors that determine vaccination readiness and encourage future studies of vaccination readiness to utilise it.
Improvements in cardiovascular health over the perinatal period predicts lower postpartum psychological distress
Authors: Donofry Shannon D. , Jouppi Riley J. , Call Christine C. , Conlon Rachel P. Kolko , Levine Michele D.
Published: December 2023

Background

Adverse cardiovascular events during pregnancy (e.g., pre-eclampsia) occur at higher rates among individuals with pre-pregnancy overweight or obesity (body mass index [BMI]≥25kg/m2) and have been associated with postpartum depression. However, it is unclear whether cardiovascular health (CVH), defined more holistically than the absence of cardiovascular conditions in pregnancy, relates to postpartum psychological functioning. The present study examined whether changes in CVH during the perinatal period predicted postpartum psychological functioning among individuals with pre-pregnancy BMI≥25kg/m2.

Methods

Individuals (N=226; Mage=28.43±5.4 years; MBMI=34.17±7.15kg/m2) were recruited when their pregnancies were 12-20 weeks gestation (M=15.64±2.45 weeks) for a longitudinal study of health and well-being. Participants completed the Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS) and reported on CVH behaviors (dietary intake, physical activity, nicotine exposure, and sleep) at baseline and at 6-months postpartum. BMI and CVH behaviors were coded according to the American Heart Association’s Life’s Essential 8 to create a CVH score at both timepoints. Linear regression analyses were performed to examine whether change in CVH related to postpartum CES-D and PSS scores. Because sleep was only measured in a subset of participants (n=114), analyses were conducted with and without sleep included. Baseline CVH, CES-D and PSS scores, and demographic factors were included as covariates in all models.

Results

Improved CVH was associated with lower postpartum CES-D (β=-0.18,p<0.01) and PSS (β=-0.13,p=0.02) scores when excluding sleep. Compared to those whose CVH improved by >1SD from pregnancy to 6-months postpartum, individuals whose CVH worsened by >1SD scored 6.42 points higher on the CESD (MCESD=15.25±10.92 vs. 8.52±6.90) and 6.12 points higher on the PSS (MPSS=24.45±8.29 vs. 17.83±8.70). However, when including sleep, these relationships were no longer significant (ps>0.4).

Conclusions

Improvements in CVH from early pregnancy to 6-months postpartum were associated with lower postpartum depressive symptoms and perceived stress. However, these relationships were no longer significant when including sleep in the CVH metric, potentially due to the large reduction in sample size. These data suggest that intervening during pregnancy to promote CVH may improve postpartum psychological functioning among high-risk individuals.
Gene prioritization in GWAS loci using multimodal evidence
Authors: Schipper Marijn , de Leeuw Christiaan A. , Maciel Bernardo A.P.C. , Wightman Douglas P. , Hubers Nikki , Boomsma Dorret I. , O’Donovan Michael C. , Posthuma Danielle
Published: December 2023

Genome-wide association studies (GWAS) yield large numbers of genetic loci associated with traits and diseases. Predicting the effector genes that mediate these locus associations remains challenging. Here we present the FLAMES framework, which predicts the most likely effector gene in a locus. FLAMES integrates machine learning predictions from biological data linking single nucleotide polymorphisms (SNPs) to genes with GWAS-wide convergence of gene interactions. We benchmark FLAMES on gene-locus pairs derived by expert curation, rare variant implication, and domain knowledge of molecular traits. We demonstrate that combining SNP-based and convergence-based modalities outperforms prioritization strategies using a single line of evidence. Applying FLAMES, we resolve theFSHBlocus in the GWAS for dizygotic twinning and further leverage this framework to find novel schizophrenia risk genes that converge with rare coding evidence and are relevant in different stages of life.
Assessing the contribution of rare variants to congenital heart disease through a large-scale case-control exome study
Authors: Audain Enrique , Wilsdon Anna , Dombrowsky Gregor , Sifrim Alejandro , Breckpot Jeroen , Perez-Riverol Yasset , Loughna Siobhan , Daly Allan , Antoniou Pavlos , Hofmann Philipp , Perez-Riverol Amilcar , Kahlert Anne-Karin , Bauer Ulrike , Pickardt Thomas , Klaassen Sabine , Berger Felix , Daehnert Ingo , Dittrich Sven , Stiller Brigitte , Abdul-Khaliq Hashim , Bu’lock Frances , Uebing Anselm , Kramer Hans-Heiner , Iyer Vivek , Larsen Lars Allan , Brook J David , Hitz Marc-Phillip
Published: December 2023

Several studies have demonstrated the value of large-scale human exome and genome data analysis, to maximise gene discovery in rare diseases. Using this approach, we have analysed the exomes of 4,747 cases and 52,881 controls, to identify single genes and digenic interactions which confer a substantial risk of congenital heart disease (CHD). We identified both rare loss-of-function and missense coding variants in ten genes which reached genome-wide significance (Bonferroni adjustedP< 0.05) and an additional four genes with a significant association at a false discovery rate (FDR)threshold of 5%. We highlight distinct genetic contributions to syndromic and non-syndromic CHD at both single gene and digenic level, by independently analysing probands from these two groups. In addition, by integrative analysis of exome data with single-cell transcriptomics data from human embryonic hearts, we identified cardiac-specific cells as well as putative biological processes underlying the pathogenesis of CHD. In summary, our findings strengthen the association of known CHD genes, and have identified additional novel disease genes and digenic interactions contributing to the aetiology of CHD.
A Bibliometric Approach to Scientific Production on Familial Hypophosphatemic Rickets in Scopus (2000-2022)
Authors: Hernández-García Frank , Gil-Peña Helena , Rodríguez Suárez Julián , López García José Manuel , Fuente Pérez Rocío , Carbajosa Patricia Oro , Corrales-Reyes Ibrain Enrique
Published: December 2023

Background

Hypophosphatemic rickets are disabling conditions that negatively impact physical functioning, activities of daily living, mental health, social life, and leisure activities. The most common cause of Hypophosphatemic rickets is genetic factors, such as X-linked hypophosphatemia. The evaluation of the scientific application of familial hypophosphatemic rickets aids in understanding the research landscape, identifying opportunities for improvement, and promoting significant advancements in the understanding and treatment of this medical condition.

Methods

An observational, descriptive, and cross-sectional study was conducted through a bibliometric analysis of the scientific output of the Familial Hypophosphatemic Rickets published in journals indexed in Scopus during 2020-2022. To retrieve the publications, Scopus was accessed on April 4, 2023, and an advanced search was performed using a filter by title, abstract and key words, source (journals), publication year, and type of article (article and review). The search terms used were extracted from the PubMed Medical Subject Headings (MeSH) related to the disease included in the MeSH catalog. Additionally, an analysis of co-occurrence between countries and keywords was carried out with VOSviewer software.

Results

This study identified 1,269 articles on hypophosphatemic rickets (938 articles and 331 reviews). In total, 39,548 citations were received, with an H index of 95. The majority of the articles (76.9%) were published in high-impact journals (Q1 and Q2 journals). Scientific production has shown a growing trend in recent years. The countries with the highest scientific production are the U.Ss, Japan, and the United Kingdom, considering that middle- and low-income countries contribute less to international scientific production.

Conclusions

Scientific production has shown sustained growth in recent years. The U.Ss solidifies itself as the country leading scientific production on hypophosphatemic rickets.
DNA Methylation-Based High-Resolution Mapping of Long-Distance Chromosomal Interactions in Nucleosome-Depleted Regions
Authors: Li Yi , Lee James , Bai Lu
Published: December 2023

3C-based methods have significantly advanced our understanding of 3D genome organization. However, it remains a formidable task to precisely capture long-range chromosomal interactions between individual loci, such as those between promoters and distal enhancers. Here, we presentMethyltransferaseTargeting-based chromosomeArchitectureCapture (MTAC), a method that maps the contacts between a target site (viewpoint) and the rest of the genome in budding yeast with high resolution and sensitivity. MTAC detects hundreds of intra-and inter-chromosomal interactions within nucleosome-depleted regions (NDRs) that cannot be captured by 4C, Hi-C, or Micro-C. By applying MTAC to various viewpoints, we find that 1) tethering to the nuclear pore complex (NPC) is a major mechanism that mediates long-distance chromosomal interactions in yeast, 2) genes co-regulated by methionine assemble into inter-chromosomal clusters near NPCs upon activation, 3) mediated by condensin, the mating locus forms a highly specific interaction with the recombination enhancer (RE) in a mating-type specific manner, and 4) correlation of MTAC signals among NDRs reveal spatial mixing and segregation of the genome. Overall, these results demonstrate MTAC as a powerful tool to resolve fine-scale long-distance chromosomal interactions and provide insights into the 3D genome organization.
Assessing the effect of baby schema cuteness on emotions, perceptions and attitudes towards insect-based packaged foods
Authors: Marquis Didier , Reinoso Carvalho Felipe , Pantin-Sohier Gaëlle
Published: December 2023

Purpose

Aversion linked to disgust and neophobia is the primary reason for human reluctance towards edible insects as a sustainable food source. Stimulating positive emotions may overcome these mental barriers. Cute visuals and claims on product packaging can trigger positive affective responses in consumers whilst modulating taste expectations. This study investigated how these elements influence emotions, perceptions and attitudes towards insect-based foods.

Design/methodology/approach

An online cross-cultural study involving French (n = 747) and Colombian (n = 695) consumers was conducted using two insect-based products: chips (hedonic) and bread (functional). Ten visual packaging variations were created per product, emphasising palatability, sustainability, nutrition and popularity (plus a control: no claim) affixed to the image of a cute anthropomorphic cricket or its silhouette. Visual appreciation and associations were assessed along with the participants' degree of food variety seeking, familiarity with entomophagy and openness to consuming edible insects.

Findings

Differences were reported in emotions, perceptions and attitudes based on the combination of packaging elements, product type and consumer segments. The findings suggest that food marketers should use cute insect depictions linked to palatability-focussed claims to alleviate young French adults' reluctance towards insect-based foods (IFs). Colombians responded better to pro-social claims and neutrally to cuteness.

Practical implications

The results should be valuable to stakeholders seeking to enhance food marketing strategies related to IFs amongst target consumer segments.

Originality/value

This study is the first to assess how baby schema cuteness induces emotional changes towards IFs and how it affects perceptions and attitudes amongst distinct populations and age segments.
The value of psychological ownership: how buy-online-and-pick-up-in-store enhances consumer loyalty
Authors: Li You , Chang Yaping , Li Zhen , Geng Lixiao
Published: December 2023

Purpose

Although buy-online-and-pick-up-in-store (BOPS) has been widely implemented by companies, scant attention has been paid to its effect on consumer experience and the concomitant outcomes. Using the psychological ownership theory, this study aims to examine whether and how the BOPS experience (vs online experience) can enhance consumer loyalty.

Design/methodology/approach

Study 1 investigated the consumer loyalty of shopping experience (self-pickup vs delivery) on actual consumer behavior through secondary data. Studies 2, 3 and 4 were controlled experiments to further investigate the mediating effect of product psychological ownership, and the moderating effects of product type and postdecision experience valence.

Findings

The authors found that BOPS shopping led to higher consumer loyalty (i.e. repeat purchase and repeat purchase frequency) compared with online shopping. Furthermore, the authors examined that this effect was mediated by product psychological ownership and moderated by product type and postdecision experience valence.

Research limitations/implications

Theoretical speculations about how BOPS shopping affects consumer experience should be probed in future research.

Practical implications

Retailers with physical stores can offer in-store pickup options for their online consumers to increase their product psychological ownership and consumer loyalty. And the positive effects of the BOPS strategy relied on product type and postdecision experience valence.

Originality/value

This research offers theoretical contributions to research on the BOPS strategy, psychological ownership theory and consumer loyalty.
Continuous professional development of LIS professionals in academic libraries: channels, challenges and motivation
Authors: Rehman Ikhlaq ur , Majeed Uzma , Ganaie Shabir Ahmad
Published: December 2023

Purpose

Continuous professional development (CPD) plays a crucial role in the library workplace by equipping library and information science (LIS) professionals with the skills and technical knowledge to bridge the theory-praxis gap, assuring that library practitioners and their organisations continue to innovate and stay successful and tailored to the requirement of their users. The aim of the study was to investigate the channels of CPD for LIS professionals working in the university libraries of Northern India. Also, it explored the motivations and barriers related to the LIS professionals’ CPD.

Design/methodology/approach

The study adopted a quantitative research design followed by the survey research method. The study population included LIS professionals working in the university libraries of Northern India. Data was gathered from 177 respondents via the census sampling method.

Findings

LIS professionals engaged in CPD activities through multiple channels. Intrinsic factors primarily governed the motivation for CPD. Similarly, time and finance were significant challenges for LIS CPD. Lastly, most libraries were headed by in-charge librarians (non-professionals). De-professionalisation, or the deliberate de-skilling of professional roles, threatens the basis upon which librarians establish their credibility as professionals.

Originality/value

To the best of the authors’ knowledge, the study is the first of its kind from the perspective of a developing country, adding to the CPD literature in academic libraries.
Progress and trends in healthcare marketing strategy (2018–2022): A descriptive and bibliometric analysis of the Web of Science (WOS) dataset
Authors: Kar Rohan , Wasnik Anurag
Published: December 2023

Purpose

Health-care marketing typically entails a coordinated set of outreach and communications designed to attract consumers (patients in the health-care context) who require services for a better health outcome and guide them throughout their health-care journey to achieve a higher quality of life. The purpose of this study is to understand the progress and trends in healthcare marketing strategy (HMS) literature between 2018 and 2022, with a special emphasis on the pre- and post-Covid-19 periods.

Design/methodology/approach

The authors examine 885 HMS-related documents from the WOS database between 2018 and 2022 that were extracted using a keyword-based search strategy. After that, the authors present the descriptive statistics related to the corpus. Finally, the authors use author co-citation analysis (ACA) and bibliographic coupling (BC) techniques to examine the corpus.

Findings

The authors present the descriptive statistics as research themes, emerging sub-research areas, leading journals, organisations, funding agencies and nations. Further, the bibliometric analysis reveals the existence of five thematic clusters: Cluster 1: macroeconomic and demographic determinants of healthcare service delivery; Cluster 2: strategies in healthcare marketing; Cluster 3: socioeconomics in healthcare service delivery; Cluster 4: data analytics and healthcare service delivery; Cluster 5: healthcare product and process innovations.

Research limitations/implications

This study provides an in-depth analysis of the advancements made in HMS-related research between 2018 and 2022. In addition, this study describes the evolution of research in this field from before to after the Covid-19 pandemic. The findings of this study have both research and practical significance.

Originality/value

To the best of the authors’ knowledge, this is the first study of its kind to use bibliometric analysis to identify advancements and trends in HMS-related research and to examine the pattern before and after Covid-19 pandemic.
Stability analysis of partial journal bearings lubricated with micropolar fluid
Authors: Sharma Sanyam , Verma Rajiv
Published: December 2023

Purpose

This study aims to investigate the stability performance of partial journal bearings of 120° and 180° partial angles with micropolar lubricant.

Design/methodology/approach

To investigate the stability characteristics of partial journal bearing, a MATLAB source code is written. To solve the Reynolds’ equation, the finite element method is used. Stability performances of 120° and 180° partial journal bearings are computed for a wide range of non-dimensional micropolar fluid parameters and working eccentricities.

Findings

The presented results provide design data for stability parameters in terms of equivalent stiffness, whirl frequency ratio, critical mass and threshold speed of the rotor with respect to eccentricities and material size of the lubricant. The stability of 180° partial journal bearing is found to be higher than 120° partial journal bearing.

Originality/value

In open literature, it is rare to find the stability of a partial journal bearing lubricated with micropolar fluid. Very few researchers have studied the combined effect of eccentricities and micropolar lubricant parameters on the dynamic performance of such bearings. Hence, it is important to study the dynamic stability to explore the complete investigation of the performance of partial journal bearings with micropolar fluid.
Fiber reinforced additive manufacturing: structurally motivated print orientation and sequential topology optimization of anisotropic material
Authors: Ray Noah , Kim Il Yong
Published: December 2023

Purpose

Fiber reinforced additive manufacturing (FRAM) is an emerging technology that combines additive manufacturing and composite materials. As a result, design freedom offered by the manufacturing process can be leveraged in design optimization. The purpose of the study is to propose a novel method that improves structural performance by optimizing 3D print orientation of FRAM components.

Design/methodology/approach

This work proposes a two-part design optimization method that optimizes 3D global print orientation and topology of a component to improve a structural objective function. The method considers two classes of design variables: (1) print orientation design variables and (2) density-based topology design variables. Print orientation design variables determine a unique 3D print orientation to influence anisotropic material properties. Topology optimization determines an optimal distribution of material within the optimized print orientation.

Findings

Two academic examples are used to demonstrate basic behavior of the method in tension and shear. Print orientation and sequential topology optimization improve structural compliance by 90% and 58%, respectively. An industry-level example, an aerospace component, is optimized. The proposed method is used to achieve an 11% and 15% reduction of structural compliance compared to alternative FRAM designs. In addition, compliance is reduced by 43% compared to an equal-mass aluminum design.

Originality/value

Current research surrounding FRAM focuses on the manufacturing process and neglects opportunities to leverage design freedom provided by FRAM. Previous FRAM optimization methods only optimize fiber orientation within a 2D plane and do not establish an optimized 3D print orientation, neglecting exploration of the entire orientation design space.
A CRISPR‐based strategy for targeted sequencing in biodiversity science
Authors: Littleford‐Colquhoun Bethan , Kartzinel Tyler R.
Published: December 2023

Many applications in molecular ecology require the ability to match specific DNA sequences from single‐ or mixed‐species samples with a diagnostic reference library. Widely used methods for DNA barcoding and metabarcoding employ PCR and amplicon sequencing to identify taxa based on target sequences, but the target‐specific enrichment capabilities of CRISPR‐Cas systems may offer advantages in some applications. We identified 54,837 CRISPR‐Cas guide RNAs that may be useful for enriching chloroplast DNA across phylogenetically diverse plant species. We tested a subset of 17 guide RNAs in vitro to enrich plant DNA strands ranging in size from diagnostic DNA barcodes of 1,428 bp to entire chloroplast genomes of 121,284 bp. We used an Oxford Nanopore sequencer to evaluate sequencing success based on both single‐ and mixed‐species samples, which yielded mean chloroplast sequence lengths of 2,530–11,367 bp, depending on the experiment. In comparison to mixed‐species experiments, single‐species experiments yielded more on‐target sequence reads and greater mean pairwise identity between contigs and the plant species' reference genomes. But nevertheless, these mixed‐species experiments yielded sufficient data to provide ≥48‐fold increase in sequence length and better estimates of relative abundance for a commercially prepared mixture of plant species compared to DNA metabarcoding based on the chloroplast trnL‐P6 marker. Prior work developed CRISPR‐based enrichment protocols for long‐read sequencing and our experiments pioneered its use for plant DNA barcoding and chloroplast assemblies that may have advantages over workflows that require PCR and short‐read sequencing. Future work would benefit from continuing to develop in vitro and in silico methods for CRISPR‐based analyses of mixed‐species samples, especially when the appropriate reference genomes for contig assembly cannot be known a priori.