bluuebunny/crossref_metadata_2025 huggingface dataset:
A Genome-Informed Functional Modeling Approach to Evaluate the Responses of Breast Cancer Patients to CDK4/6 Inhibitors-Based Therapies and Simulate Real-World Clinical Trials
Authors: Yang Mei , Liu Yuhan , Zhang Chunming , Hsueh Yi-Ching , Zhang Qiangzu , Fan Yanhui , Xu Juntao , Huang Min , Li Xu , Yang Jianfei , Tan Guangming , Niu Gang
Published: May 2023

PURPOSE

Varied therapeutic responses were observed among cancer patients receiving the same treatment regimen, highlighting the challenge of identifying patients most likely to benefit from a given therapy. Here, we present an artificial intelligence-based approach, called CDK4/6 inhibitor Response Model (CRM), to address the complexity of predicting patient responses to treatment by a certain clinical scene on CDK4/6 inhibitors (CDK4/6i).

PATIENTS AND METHODS

To train the CRM, we transformed the genomic data of 980 breast cancer patients from the TCGA database into activity profiles of signaling pathways (APSP) by utilizing the modified Damage Assessment of Genomic Mutations (DAGM) algorithm. A scoring model was then established by random forest algorithm to classify the HR+/HER2− and HR−/HER2− breast cancer molecular subtypes by the differential APSP features between the two, which reasonably reflected the potential role played by CDK4/6 molecules in HR+/HER2− breast cancer cells. The effectiveness of CRM was then tested in a separate local patient cohort (n = 343) in Guangdong, China. Twin in-silico clinical trials (ICT) of previously disclosed clinical trials (NCT02246621,NCT02079636,NCT03155997,NCT02513394,NCT02675231) were performed to demonstrate the potential of CRM in generating concerted results as the real-world clinical outcomes.

RESULTS

The CRM displayed high precision in classifying HR+/HER2− and HR−/HER2− breast cancer patients in both TCGA (AUC=0.9956) and local patient cohorts (AUC=0.9795). Significantly, the scores were distinct (p = 0.025) between CDK4/6i-treated patients with different responses. Breast cancer patients from different subtypes were grouped into five distinct populations based on the scores assigned by the CRM. From twin ICT, the CRM scores reflected the differential responses of patient groups to CDK4/6i-based therapies.

CONCLUSION

The CRM score showed not only a robust association to clinically observed CDK4/6i responses but also heterogenetic responses across subtypes. More than half of HR+/HER2+ patients may be benefited from CDK4/6i-based treatment. The CRM empowered us to conduct ICT on different types of cancer patients responding to CDK4/6i-based therapies. These findings showed the potential of CRM as the companioned ICT to guide CDK4/6i application in the clinical end. CRM-guided ICT could be a universal method to demonstrate drug sensitivity to various patients.
Cross-sectional associations between 24-hour time-use composition, grey matter volume and cognitive function in healthy older adults
Authors: Mellow Maddison L , Dumuid Dorothea , Olds Timothy , Stanford Ty , Dorrian Jillian , Wade Alexandra T , Fripp Jurgen , Xia Ying , Goldsworthy Mitchell R , Karayanidis Frini , Breakspear Michael J , Smith Ashleigh E
Published: May 2023

Background

Increasing physical activity (PA) is an effective strategy to slow reductions in cortical volume and maintain cognitive function in older adulthood. However, PA does not exist in isolation, but coexists with sleep and sedentary behaviour to make up the 24-hour day. We investigated how the balance of all three behaviours (24-hour time-use composition) is associated with grey matter volume in healthy older adults, and whether grey matter volume influences the relationship between 24-hour time-use composition and cognitive function.

Methods

This cross-sectional study included 378 older adults (65.6 ± 3.0 years old, 123 male) from the ACTIVate study across two Australian sites (Adelaide and Newcastle). Time-use composition was captured using 7-day accelerometry, and T1-weighted magnetic resonance imaging was used to measure grey matter volume both globally and across regions of interest (ROI: frontal lobe, temporal lobe, hippocampi, and lateral ventricles). Pairwise correlations were used to explore univariate associations between time-use variables, grey matter volumes and cognitive outcomes. Compositional data analysis linear regression models were used to quantify associations between ROI volumes and time-use composition, and explore potential associations between the interaction between ROI volumes and time-use composition with cognitive outcomes.

Results

After adjusting for covariates (age, sex, education), there were no significant associations between time-use composition and any volumetric outcomes. There were significant interactions between time-use composition and frontal lobe volume for long-term memory (p=0.018) and executive function (p=0.018), and between time-use composition and total grey matter volume for executive function (p=0.028). Spending more time in moderate-vigorous PA was associated with better long-term memory scores, but only for those with smaller frontal lobe volume (below the sample mean). Conversely, spending more time in sleep and less time in sedentary behaviour was associated with better executive function in those with smaller total grey matter volume.

Conclusions

Although 24-hour time use was not associated with total or regional grey matter independently, total grey matter and frontal lobe grey matter volume mediated the relationship between time-use composition and several cognitive outcomes. Future studies should investigate these relationships longitudinally to assess whether changes in time-use composition correspond to changes in grey matter volume and cognition.
What’s UPDOG? A novel tool for trans-ancestral polygenic score prediction
Authors: Howard David M. , Pain Oliver , Gillett Alexandra C. , Vassos Evangelos , Lewis Cathryn M.
Published: May 2023

Polygenic scores provide an indication of an individual’s genetic propensity for a trait within a test population. These scores are calculated using results from genetic analysis conducted in discovery populations. However, when the test and discovery populations have different ancestries, predictions are less accurate. As many genetic analyses are conducted using European populations, this hinders the potential for making predictions in many of the underrepresented populations in research. To address this, UP and Downstream Genetic scoring (UPDOG) was developed to consider the genetic architecture of both the discovery and test cohorts before calculating polygenic scores. UPDOG was tested across four ancestries and six phenotypes and benchmarked against five existing tools for polygenic scoring. In approximately two-thirds of cases UPDOG improved trans-ancestral prediction, although the increases were small. Maximising the efficacy of polygenic scores and extending it to the global population is crucial for delivering personalised medicine and universal healthcare equality.
Molecular logic for cellular specializations that initiate the auditory parallel processing pathways
Authors: Jing Junzhan , Hu Ming , Ngodup Tenzin , Ma Qianqian , Lau Shu-Ning Natalie , Ljungberg Cecilia , McGinley Matthew J. , Trussell Laurence O. , Jiang Xiaolong
Published: May 2023

The cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.
HIC1 interacts with FOXP3 multi protein complex: a novel mechanism to regulate human regulatory T cell differentiation and function
Authors: Ahmad Andrabi Syed Bilal , Batkulwar Kedar , Bhosale Santosh D. , Moulder Robert , Khan Meraj Hasan , Buchacher Tanja , Khan Mohd Moin , Arnkil Ilona , Rasool Omid , Marson Alexander , Kalim Ubaid Ullah , Lahesmaa Riitta
Published: May 2023

Transcriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 Interactome in human Treg cells. Altogether 61 high-confidence interactors were identified, including IKZF3, which is a key transcription factor in the development of Treg cells. The biological processes associated with these interacting proteins include protein transport, mRNA processing, non-coding (ncRNA) transcription and RNA metabolism. The results revealed that HIC1 is part of a FOXP3-RUNX1-CBFB protein complex that regulates Treg signature genes thus improving our understanding of HIC1 function during early Treg cell differentiation.

Highlights

Systematic characterization of HIC1 interactome in regulatory T cells by Affinity Purification-Mass Spectrometry

HIC1 binds to theRUNX1promoter and regulates its expression

HIC1-a part of FOXP3-RUNX1-CBFB transcriptional complex

Graphical abstract
Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint
Authors: Zhou Felix Y. , Waterman David P. , Ashton Marissa , Caban-Penix Suhaily , Memisoglu Gonen , Eapen Vinay V. , Haber James E.
Published: May 2023

Cells evoke the DNA damage checkpoint (DDC) to inhibit mitosis in the presence of DNA double-strand breaks (DSBs) to allow more time for DNA repair. In budding yeast, a single irreparable DSB is sufficient to activate the DDC and induce cell cycle arrest prior to anaphase for about 12 to 15 hours, after which cells “adapt” to the damage by extinguishing the DDC and resuming the cell cycle. While activation of the DNA damage-dependent cell cycle arrest is well-understood, how it is maintained remains unclear. To address this, we conditionally depleted key DDC proteins after the DDC was fully activated and monitored changes in the maintenance of cell cycle arrest. Degradation of Ddc2ATRIP, Rad9, Rad24, or Rad53CHK2results in premature resumption of the cell cycle, indicating that these DDC factors are required both to establish and to maintain the arrest. Dun1 is required for establishment, but not maintenance of arrest, whereas Chk1 is required for prolonged maintenance but not for initial establishment of the mitotic arrest. When the cells are challenged with 2 persistent DSBs, they remain permanently arrested. This permanent arrest is initially dependent on the continuous presence of Ddc2, Rad9, and Rad53; however, after 15 hours these proteins become dispensable. Instead, the continued mitotic arrest is sustained by spindle-assembly checkpoint (SAC) proteins Mad1, Mad2, and Bub2 but not by Bub2’s binding partner Bfa1. These data suggest that prolonged cell cycle arrest in response to 2 DSBs is achieved by a handoff from the DDC to specific components of the SAC. Furthermore, the establishment and maintenance of DNA damage-induced cell cycle arrest requires overlapping but different sets of factors.
Phylogeographical evidence for historical long-distance dispersal in the flightless stick insectRamulus mikado
Authors: Suetsugu Kenji , Nozaki Tomonari , Hirota Shun K , Funaki Shoichi , Ito Katsura , Isagi Yuji , Suyama Yoshihisa , Kaneko Shingo
Published: May 2023

Exploring how organisms overcome geographical barriers to dispersal is a fundamental question in biology. Passive long-distance dispersal events, although infrequent and unpredictable, have a considerable impact on species range expansions. Despite limited active dispersal capabilities, many stick insect species have vast geographical ranges, indicating that passive long-distance dispersal is vital for their distribution. A potential mode of passive dispersal in stick insects is via the egg stage within avian digestive tracts, as suggested by experimental evidence. However, detecting such events under natural conditions is challenging due to their rarity. To indirectly assess the importance of historical avian-mediated dispersal, we examined the population genetic structure of the flightless stick insectRamulus mikadobased on a multifaceted molecular approach (COI haplotypes, nuclear SSR markers, and genome-wide SNPs). Subsequently, we identified unique phylogeographic patterns, including the discovery of identical COI genotypes spanning considerable distances, which substantiates the notion of passive long-distance genotypic dispersal. Overall, all the molecular data revealed low and mostly non-significant genetic differentiation among populations, with identical or very similar genotypes across distant populations. We propose that long-distance dispersal facilitated by birds is the most plausible explanation for the unique phylogeographic pattern observed in this flightless stick insect.
DNA methylation rates scale with maximum lifespan across mammals
Authors: Crofts Samuel. J. C. , Latorre-Crespo Eric , Chandra Tamir
Published: May 2023

DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are - or are linked to - an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.
The Prolonged Terminal Phase of Human Life Induces Survival Response in the Skin Transcriptome
Authors: Abouhashem Ahmed S , Singh Kanhaiya , Srivastava Rajneesh , Liu Sheng , Mathew-Steiner Shomita S , Gu Xiaoping , Kacar Sedat , Hagar Amit , Sandusky George E. , Roy Sashwati , Wan Jun , Sen Chandan K
Published: May 2023

Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression (GTEx) database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such asFOXO1,FOXO3,ATF4andCEBPD. Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. In addition, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix (collagen expression and metabolism). Efforts to understand the significance of death as a biological variable (DABV) in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.
Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states
Authors: Yao Junjun , Dai Shaoxing , Zhu Ran , Tan Ju , Zhao Qiancheng , Yin Yu , Sun Jiansen , Du Xuewei , Ge Longjiao , Xu Jianhua , Hou Chunli , Li Nan , Li Jun , Ji Weizhi , Zhu Chuhong , Zhang Runrui , Li Tianqing
Published: May 2023

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are re-activated following stroke injury. Together, our findings provide valuable insights into the development, aging, and re-activation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
Rad53 regulates the lifetime of Rdh54 at homologous recombination intermediates
Authors: Hu Jingyi , Ferlez Bryan , Dau Jennifer , Crickard J. Brooks
Published: May 2023

Rdh54 is a conserved DNA translocase that participates in homologous recombination (HR), DNA checkpoint adaptation, and chromosome segregation.Saccharomyces cerevisiaeRdh54 is a known target of the Mec1/Rad53 signaling axis, which globally protects genome integrity during DNA metabolism. While phosphorylation of DNA repair proteins by Mec1/Rad53 is critical for HR progression little is known about how specific post translational modifications alter HR reactions. Phosphorylation of Rdh54 is linked to protection of genomic integrity but the consequences of modification remain poorly understood. Here, we demonstrate that phosphorylation of the Rdh54 C-terminus by the effector kinase Rad53 regulates Rdh54 clustering activity as revealed by single molecule imaging. This stems from phosphorylation dependent and independent interactions between Rdh54 and Rad53. Genetic assays reveal that loss of phosphorylation leads to phenotypic changes resulting in loss-of-heterozygosity (LOH) outcomes. Our data highlight Rad53 as a key regulator of HR intermediates through activation and attenuation of Rdh54 motor function.
A Study of Microbial Diversity in a Biofertilizer Consortium
Authors: Hernández-Álvarez Cristóbal , Peimbert Mariana , Rodríguez-Martin Pedro , Trejo-Aguilar Dora , Alcaraz Luis D.
Published: May 2023

Biofertilizers supply living microorganisms to help plants grow and maintain their health. In this study, we examine the microbiome composition of a commercial biofertilizer that has been proven to promote plant growth. Using ITS and 16S rRNA gene sequence analyses, we describe the microbial communities of the biofertilizer, with 182 fungal species and 964 bacterial genera identified. The biofertilizer contains a variety of microorganisms that had been reported to enhance nutrient uptake, phytohormone production, stress tolerance, and pathogen resistance in plants. Plant roots created a microenvironment that boosted bacterial diversity but filtered fungal communities. We propose using plant roots as bioreactors to sustain dynamic environments that promote the proliferation of microorganisms with biofertilizer potential. However, preserving the fungal-inoculated substrate is crucial to maintain fungal diversity in the root fraction. The study suggests that bacteria grow close to plant roots, while root-associated fungi may be a subset of the substrate fungi. These findings indicate that the composition of the biofertilizer may be influenced by the selection of microorganisms associated with plant roots, which could have implications for the effectiveness of the biofertilizer in promoting plant growth.
TreeGOER: a database with globally observed environmental ranges for 48,129 tree species
Authors: Kindt Roeland
Published: May 2023

The BIOCLIM algorithm provides a straightforward method to estimate the effects of climate change on the distribution of species. Estimating the core ranges of species from 5% and 95% quantiles of bioclimatic variables, the algorithm remains widely used even when more sophisticated methods of species distribution modelling have become popular. Where sufficient representative observations are available, I expect that BIOCLIM correctly identifies locations that would not be suitable in a future climate. To accommodate climate change investigations based on BIOCLIM for 48,129 tree species (a substantial subset of known tree species), I developed theTreeGOER(Tree Globally Observed Environmental Ranges) database, providing information on environmental ranges for 38 bioclimatic, 8 soil and 3 topographic variables. The database can be accessed from:https://doi.org/10.5281/zenodo.7922928. Statistics that include 5% and 95% quantiles were estimated for a cleaned and taxonomically standardized occurrence data set with different methods of outlier detection, with estimates for roughly 45% of species being based on 20 or more observation records. Inferred core bioclimatic ranges of species along global temperature and moisture index gradients and across continents follow the known global distribution of tree diversity such as its highest levels in moist tropical forests and the ‘odd man out’ pattern of lower levels in Africa. To demonstrate how global analyses for large numbers of tree species can easily be done inRwithTreeGOER, here I present two case studies. The first case study investigated latitudinal trends of tree vulnerability and compared these with previous results obtained for urban trees. The second case study focused on tropical areas, compared trends in different longitudinal zones and investigated patterns for the moisture index.TreeGOERis expected to benefit researchers conducting biogeographical and climate change research for a wide range of tree species at a variety of spatial and temporal scales.
Differences in 5’untranslated regions highlight the importance of translational regulation of dosage sensitive genes
Authors: Wieder Nechama , D’Souza Elston N. , Martin-Geary Alexandra C. , Lassen Frederik H. , Talbot-Martin Jonathan , Fernandes Maria , Chothani Sonia P. , Rackham Owen J.L. , Schafer Sebastian , Aspden Julie L. , MacArthur Daniel G. , Davies Robert W. , Whiffin Nicola
Published: May 2023

Background

Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity.

Results

We investigated 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explored how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs (P<1×10−15), greater TSS diversity (P<1× 10−15), and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated.

Conclusions

Our results confirm the importance of post-transcriptional regulation through 5’UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR (https://vutr.rarediseasegenomics.org/), that supports exploration of the composition of individual 5’UTRs and the impact of genetic variation within them.
Lip movements and lexical features improve speech tracking differently for clear and multi-speaker speech
Authors: Haider Chandra Leon , Park Hyojin , Hauswald Anne , Weisz Nathan
Published: May 2023

Visual speech plays a powerful role in facilitating auditory speech processing and has been a publicly noticed topic with the wide usage of face masks during the Covid-19 pandemic. In a previous magnetoencephalography (MEG) study we showed that occluding the mouth area significantly impairs neural speech tracking. To rule out the possibility that this deterioration is due to degraded sound quality, in the present follow-up study, we presented participants with audiovisual (AV) and audio-only (A) speech. We further independently manipulated the trials by adding a face mask and a distractor speaker. Our results clearly show that face masks only affect speech tracking in AV conditions, not in A conditions. This shows that face masks indeed primarily impact speech processing by blocking visual speech and not by acoustic degradation. Furthermore, we observe differences in the speech features that are used for visual speech processing. On the one hand, processing in clear speech, but not in noisy speech, is profiting more from lexical unit features (phonemes and word onsets) hinting at improved phoneme discrimination. On the other hand, we observe an improvement in speech tracking driven by the modulations of the lip area in clear speech and conditions with a distractor speaker, which might aid by providing temporal cues for subsequent auditory processing. With this work, we highlight the effects of face masks in AV speech tracking and show two separate ways how visual speech might support successful speech processing.
The role of learned song in the evolution and speciation of Eastern and Spotted towhees
Authors: Du’Mottuchi Ximena León , Creanza Nicole
Published: May 2023

Oscine songbirds learn vocalizations that function in mate attraction and territory defense. Sexual selection pressures on these learned songs could accelerate speciation. The Eastern and Spotted towhees are sister species that diverged recently (0.28 Ma) but now have partially overlapping ranges with evidence of some hybridization; widespread community-science recordings of these species, including songs within their zone of overlap and from potential hybrids, enable us to investigate whether song differentiation might facilitate their reproductive isolation. Here, we quantify 16 song features to analyze geographic variation in Spotted and Eastern towhee songs and test for species-level differences. We then use random-forest models to measure how accurately their songs can be classified by species, both within and outside the zone of overlap. While no single song feature reliably distinguishes the two species, a random-forest model trained on 16 features accurately classified 89.5% of songs; interestingly, species classification was less accurate in the zone of overlap. Finally, our analysis of the limited publicly available genetic data from each species supports the hypothesis that they are reproductively isolated. Together, our results suggest that, in combination, small variations in song features may contribute to these sister species’ ability to recognize their species-specific songs.
A comprehensive catalog of 3D genome organization in diverse human genomes facilitates understanding of the impact of structural variation on chromatin structure
Authors: Li Chong , Bonder Marc Jan , Syed Sabriya ,   Human Genome Structural Variation Consortium (HGSVC),   HGSVC Functional Analysis Working Group, Zody Michael C. , Chaisson Mark J.P. , Talkowski Michael E , Marschall Tobias , Korbel Jan O , Eichler Evan E , Lee Charles , Shi Xinghua
Published: May 2023

The human genome is packaged into the three-dimensional (3D) nucleus and organized into functional units known as topologically associating domains (TADs) and chromatin loops. Recent studies show that the 3D genome can be modified by genome structural variants (SVs) through disrupting higher-order chromatin organizations such as TADs, which play an essential role in insulating genes from aberrant regulation by regulatory elements outside TADs. Here, we have developed an integrative Hi-C analysis pipeline to generate a comprehensive catalog of TADs, TAD boundaries, and loops in human genomes to fill the gap of limited resources. We identified 2,293 TADs and 6,810 sub-TADs missing in the previously released TADs of GM12878. We then quantified the impact of SVs overlapping with TAD boundaries and observed that two SVs could significantly alter chromatin architecture leading to abnormal expression and splicing of genes associated with human diseases.
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly
Authors: Braxton Julian R. , Shao Hao , Tse Eric , Gestwicki Jason E. , Southworth Daniel R.
Published: May 2023

The mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear. Here, we determined cryo-electron microscopy (cryo-EM) structures of a hyperstable disease-associated mtHsp60 mutant, V72I, at three stages in this cycle. Unexpectedly, client density is identified in all states, revealing interactions with mtHsp60’s apical domains and C-termini that coordinate client positioning in the folding chamber. We further identify a striking asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60/mtHsp10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify a new role for the apical domains in coordinating client capture and progression through the cycle, and suggest a conserved mechanism of group I chaperonin function.
Sustainable development and bank non-performing loans: are they correlated?
Authors: Ozili Peterson K.
Published: May 2023

Purpose

This paper aims to investigate the correlation between banking sector non-performing loans (NPLs) and the level of sustainable development.

Design/methodology/approach

Pearson correlation test statistic was used to assess the correlation between bank NPLs and sustainable development.

Findings

There is a significant positive correlation between banking sector NPLs and the level of sustainable development measured by the sustainable development index (SDI). The significant positive correlation is evident in European countries and in countries in the region of the Americas. There is a significant negative correlation between banking sector NPLs and achieving SDG3 and SDG7 in African countries and European countries. There is also a significant negative correlation between NPLs and achieving SDG10 in European countries. There is a significant positive correlation between banking sector NPLs and achieving SDG4 and SDG7 in the region of the Americas. There is also a significant positive correlation between NPLs and achieving SDG10 in African countries and in countries in the region of the Americas.

Originality/value

The present study is unique and different from other studies because it used a unique SDI to capture the level of sustainable development. The analysis is also unique because it covers several regions, which have not been covered in previous studies.
Cybersecurity effectiveness in UK construction firms: an extended McKinsey 7S model approach
Authors: Badi Sulafa , Nasaj Mohamed
Published: May 2023

Purpose

This study aims to assess the essential elements of internal organisational capability that influence the cybersecurity effectiveness of a construction firm. An extended McKinsey 7S model is used to analyse the relationship between a construction firm's cybersecurity effectiveness and nine internal capability elements: shared values, strategy, structure, systems, staff, style, skills, relationships with third parties and regulatory compliance.

Design/methodology/approach

Based on a quantitative research strategy, this study collected data through a cross-sectional survey of professionals working in the construction sector in the United Kingdom (UK). The collected data was analysed using descriptive and inferential statistical methods.

Findings

The findings underlined systems, regulatory compliance, staff and third-party relationships as the most significant elements of internal organisational capability influencing a construction firm's cybersecurity effectiveness, organised in order of importance.

Research limitations/implications

Future research possibilities are proposed including the extension of the proposed diagnostic model to consider additional external factors, examining it under varying industrial relationship conditions and developing a dynamic framework that helps improve cybersecurity capability levels while overseeing execution outcomes to ensure success.

Practical implications

The extended McKinsey 7S model can be used as a diagnostic tool to assess the organisation's internal capabilities and evaluate the effectiveness of implemented changes. This can provide specific ways for construction firms to enhance their cybersecurity effectiveness.

Originality/value

This study contributes to the field of cybersecurity in the construction industry by empirically assessing the effectiveness of cybersecurity in UK construction firms using an extended McKinsey 7S model. The study highlights the importance of two additional elements, third-party relationships and construction firm regulatory compliance, which were overlooked in the original McKinsey 7S model. By utilising this model, the study develops a concise research model of essential elements of internal organisational capability that influence cybersecurity effectiveness in construction firms.
Investigation and prediction of users' sentiment toward food delivery apps applying machine learning approaches
Authors: Hossain Md Shamim , Begum Humaira , Rouf Md. Abdur , Sabuj Md. Mehedul Islam
Published: May 2023

Purpose

The goal of the current research is to use different machine learning (ML) approaches to examine and predict customer reviews of food delivery apps (FDAs).

Design/methodology/approach

Using Google Play Scraper, data from five food delivery service providers were collected from the Google Play store. Following cleaning the reviews, the filtered texts were classified as having negative, positive, or neutral sentiments, which were then scored using two unsupervised sentiment algorithms (AFINN and Valence Aware Dictionary for sentiment Reasoning (VADER)). Furthermore, the authors employed four ML approaches to categorize each review of FDAs into the respective sentiment class.

Findings

According to the study's findings, the majority of customer reviews of FDAs were positive. This research also revealed that, while all of the methods (decision tree, linear support vector machine, random forest classifier and logistic regression) can appropriately classify the reviews into a sentiment category, support vector machines (SVM) beats the others in terms of model accuracy. The authors' study also showed that logistic regression provided the highest recall, F1 score and lowest Root Mean Square Error (RMSE) among the four ML models.

Practical implications

The findings aid FDAs in determining customer review behavior. The study's findings could help food apps developers better understand how customers feel about the developers' products and services. The food apps developer can learn how to use ML techniques to better understand the users' behavior.

Originality/value

The current study uses ML methodologies to investigate and predict consumer attitude regarding FDAs.
Reawakening criminology: the importance of scientific method and inquiry in policing practice
Authors: Birch Philip , Kruger Erin , Porter Glenn , Bizo Lewis A. , Kennedy Michael
Published: May 2023

Purpose

Criminology both as a field of study and as a practice draws on a broad range of disciplines from the social, behavioural, human, natural and medical sciences. However, over recent times, the natural and medical sciences have been dismissed, overlooked and even ridiculed, largely since the rise of critical criminology and related contemporary conflict and social harm approaches from the 1960s onwards. This has led to a chasm emerging between the study of criminology and the practice of criminology such as within a policing context. This paper aims to provide a review of an emerging forensic biological method, that of neuroscience, within a criminological context, to illustrate the importance of criminology embracing and reawakening its natural and medical science roots.

Design/methodology/approach

The paper draws on a conceptual design to realign criminology with the full range of disciplines used to inform its theory and application.

Findings

Through illustrating the role of forensic neuroscience, the paper reawakens the scientific method and inquiry of criminology reflecting the importance of the discipline being, and remaining, multi- and trans-disciplinary in nature. The paper, while reflecting on the limitations of scientific method and inquiry, outlines the strengths this approach to criminology engenders, promoting and delivering a scientific-based research agenda that aims to support industry partners in the prevention, disruption and reduction of crime, disorder and threats to public security.

Practical implications

Firstly, it is important for criminology as a field of study to (re)engage with its scientific method and inquiry. Secondly, criminology, by engaging in robust scientific method and inquiry, has a significant contribution to make to professional practice and the work of industry professionals. Thirdly, while there are limitations to such scientific method and inquiry, it should not lead to this component of criminology being discarded. Fourthly, there is a need for contemporary research in the area of scientific method and inquiry and its application to criminological contexts, including that of police practice. Finally, by engaging in scientific method and inquiry that is evidence based, a chasm between the field of study and the practice associated with criminology can be addressed.

Originality/value

This paper addresses the gap between criminology as a field of study and as a practice by reengaging with scientific method and inquiry, illustrating the need and value of criminology being and remaining multi- and trans-disciplinary, ensuring professions underpinned by criminology are supported in their practice.
Evaluating the quality of the organisational learning capability measurement model
Authors: Sanhokwe Hamfrey , Chinyamurindi Willie , Muzurura Joe
Published: May 2023

Purpose

This study aims to answer pertinent questions related to the quality of the organisational learning capability measurement model.

Design/methodology/approach

A time-separated design informed data collection. The organisational learning capability was exposed to classical higher-order and bifactor confirmatory factor analyses. Multigroup confirmatory factor analysis facilitated measurement invariance testing. This study assessed the predictive validity of the organisational learning capability subscales using hierarchical regression analysis.

Findings

This study replicated the second-order organisational learning capability model with four subscales. Bifactor modelling confirmed the multidimensionality of the organisational learning capability. The organisational learning capability was invariant between gender groups. The organisational learning capability subscales accounted for a significant variance in innovative work behaviour.

Practical implications

The organisational learning capability exhibits robust properties, making it a plausible option for monitoring the quality of organisational learning. Organisations must appreciate the quality of this dynamic capability and leverage it to generate new sources of value.

Originality/value

This study fills a critical gap in organisational learning-related capabilities in sub-Saharan African contexts, providing a base to influence innovation-related trajectories positively.
Robust framework to prioritize blockchain-based supply chain challenges: the fuzzy best-worst approach for multiple criteria decision-making
Authors: Shoaib Muhammad , Zhang Shengzhong , Ali Hassan , Akbar Muhammad Azeem , Hamza Muhammad , Rehman Waheed Ur
Published: May 2023

Purpose

This study aims to identify and prioritize the challenges to adopting blockchain in supply chain management and to make its taxonomic model. Moreover, validate whether these challenging factors exist in the real world and, if they exist, then in what percentage.

Design/methodology/approach

This research adopted the fuzzy best-worst method (F-BWM), which integrates fuzzy set theory with the best-worst method to identify and prioritize the prominent challenges of the blockchain-based supply chain by developing a weighted multi-criteria model.

Findings

A total of 20 challenges (CH's) were identified. Lack of storage capacity/scalability and lack of data privacy challenges were found as key challenges. The findings of this study will provide a robust framework of the challenges that will assist academic researchers and industry practitioners in considering the most significant category concerning their working area.

Practical implications

Blockchain provides the best solution for tracing and tracking where RFID has not succeeded. It can improve quality management in a supply chain network by improving standards and speeding up operations. For inventory management, blockchain provides transparency of documentation for both parties within no time.

Originality/value

To the best of the authors' knowledge, no previous research has adopted the fuzzy best-worst method to prioritize the identified challenges of blockchain implementation in the supply chain. Moreover, no study provides a taxonomic model for the challenges of implementing a blockchain-based supply chain.
The impact of the Russia–Ukraine war on the United States natural gas futures prices
Authors: Saad Ghadi
Published: May 2023

Purpose

This paper attempts to investigate the impact of the Russia–Ukraine war on the returns and volatility of the United States (US) natural gas futures market.

Design/methodology/approach

The study uses secondary data of 996 trading day provided by the US Department of Energy and investing.com websites and applies the event study methodology in addition to the generalized autoregressive conditional heteroscedastic (GARCH) family models.

Findings

The findings from the exponential EGARCH (1,1) estimate are the best indication of a significant positive effects of the Ukraine–Russia war on the returns and volatility of the US natural gas futures prices. The cumulative abnormal returns (CARs) of the event study show that the natural gas futures prices reacted negatively but not significantly to the Russian–Ukraine war at the event date window [−1,1] and the [−15, −4] event window. CARs for the longer pre and post-event window display significant positive values and coincides with the standard finance theory for the case of the US natural gas futures over the Russia–Ukraine conflict.

Originality/value

This is the first study to examine the impact of the Russia–Ukraine war on natural gas futures prices in the United States. Thus, it provides indications on the behavior of investors in this market and proposes new empirical evidence that help in investment analyses and decisions.
Investigating the impact of power outages on sustainable community development: exploring the local community’s perception in Pakistan
Authors: Ali Zaigham , Hussain Ammar , Hussain Shahid
Published: May 2023

Purpose

The purpose of the present study is to investigate the community’s view of power outages and their effect on sustainable community development. This research has three aims. This project will first investigate how a blackout affects a community’s ability to live sustainably.

Design/methodology/approach

A survey questionnaire was developed that included 22 factors from the literature. The questionnaire was distributed to diversified segments of society from different regions of Pakistan and examined critical factors affecting sustainable community development. A total of 349 (77%) responses were received.

Findings

The study results confirm that power failure negatively affects the sustainable life of a community. This study found that the reduced production of large manufacturing, decrease leisure and comfort, reduced public administrative efficiency, loss of educational opportunities and increased use of traditional energy sources are the most important factors for sustainable community development. Findings also suggest that policymakers and practitioners in public organizations need to ensure that projects are completed in a timely manner to meet growing community needs.

Originality/value

The purpose of this research is to address knowledge gaps related to power outages and sustainable community development. The major impact of power disruptions on communities was previously disregarded in development discourse. Participants in these discussions recognize communities as genuine stakeholders and acknowledge that power outages can have a substantial impact on their economic and social development. However, previous studies have neglected to address this phenomenon.