bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond prescribed activities: examining passive postural sway and gait data in patients with multiple sclerosis
Authors: Meyer Brett M. , Agarwal Nishit , Gamboa Kevin Machado , O’Learly Aisling , Solomon Andrew J. , McGinnis Ryan S. , Ceruolo Melissa
Published: November 2024

Symptoms of multiple sclerosis (MS) are highly variable and include impaired senses, instability, and fatigue, making persons with MS (PwMS) ill-suited for the traditional six-month office visit paradigm. Instead, PwMS are well suited for remote monitoring to capture their true impairment. The objective of this work is to investigate the value of free-living data compared to prescribed walking tasks. Wearable sensor data were utilized from six-weeks of data from 25 PwMS. Participants completed a daily 1-minute walk, 30-second standing task, and patient reported outcomes of balance confidence (ABC), fatigue (MFIS) and walking impairment (MSWS). We compared gait and sway, as well as correlated them to patient reported outcomes (PRO). Lastly, we used a regression to determine the variance accounted for (VAF) in each PRO by different data sources. Temporal gait features were moderately correlated (r=0.6 – 0.81) between passive and prescribed walking, however, no postural sway features were correlated with each other. Passive data was found to have greater clinical relevance in our sample of PwMS compared to prescribe tasks for both gait and sway analyses. Passive sway features were found to be moderately related to ABC, MFIS, and MSWS (r=0.42-0.74, VAF=0.42-0.7), while prescribe sway was only correlated to MFIS (r = 0.41, VAF = 0.44). Both passive and prescribed measures of gait were related to ABC and MSWS; stronger relationships were found in the passive data (r = 0.42-0.78, VAF = 0.64-0.78). Additionally, we found the performance increased for passive monitoring with a shorter monitoring duration – highlighting the need to properly match the monitoring and analysis duration to the population. Overall, our findings highlight the importance of including passive free-living analysis in future studies.
An accurate genetic colocalization method for the HLA locus
Authors: Butler-Laporte Guillaume , Lu Tianyuan , Morris Sam , Zhang Wenmin , Band Gavin , Hamilton Fergus , Chong Amanda , Lin Kuang , Nanjala Ruth , Brent Richards J , Lee Mei-Hsuan , Yang Ling , Yao Pang , Li Liming , Chen Zhengming , Luo Yang , Milwood Iona Y , Walters Robin G , Mentzer Alexander J
Published: November 2024

Genetic colocalization analyses are frequently conducted to determine if causal signals at a genetic locus are shared between two phenotypes. However, colocalization is rarely undertaken at the HLA locus, due to its complex linkage disequilibrium (LD) and high polymorphism density. This lack of genetic causal inference method limits our ability to translate HLA associations into therapeutic targets. Here we present a method that uses HLA alleles, instead of nucleotide variants, to perform genetic colocalization of two traits at HLA genes. The method, which we call HLA-colocalization, works by controlling for LD using Bayesian variable selection, then performing Bayesian regression on the resulting posterior inclusion probabilities. We first show through simulation that the method correctly identifies truly colocalizing genes. We then test the method in two positive control scenarios, showing colocalization between hepatitis B and liver disease atHLA-DPB1, and between Epstein-Barr virus and multiple sclerosis atHLA-DRB1andHLA-DQB1. Lastly, we perform a large colocalization scan between multiple viruses and auto-immune diseases, demonstrating that the method is well calibrated, and uncovering multiple biologically plausible novel causal associations, such as cytomegalovirus and ulcerative colitis. To our knowledge, HLA-colocalization is the first accurate genetic colocalization method for the HLA locus (github:https://github.com/DrGBL/hlacoloc).
The impact of diabetes mellitus and HBV infection on major adverse cardiovascular events related to statin use for Chinese population with cardiovascular disease
Authors: Wu Qian , He Xiaoxuan , Tong Xiaoning , Li Ying , Wang Xiaoqin
Published: November 2024

BACKGROUND

The association between hepatitis B virus (HBV) infection, diabetes mellitus (DM) and cardiovascular disease (CVD) remains uncertain. This study was aimed to investigate the impact of HBV infection and DM on 13 major adverse cardiovascular events (MACEs) among CVD patients with or without statin use.

METHODS AND RESULTS

In total, 45,013 individuals participated in the baseline survey between June 2020 and August 2023. The patients were categorized into two groups according to their surface antigen status. Finally, a sample size of 496 participants was included in the study: patients with coexisting CVD and HBV (n = 225) and patients with CVD alone (n = 271).The implementation of statins has demonstrated the potential to reduce the incidence of coronary heart disease (CHD) and angina pectoris (AP) in individuals with CVD who are also affected by HBV infection. The analysis of stratification, taking into account the presence of DM, has demonstrated a significant increased vulnerability to myocardial infarction (MI), acute myocardial infarction (AMI), and heart failure (HF) among individuals with HBV infection combined with CVD. DM and hemoglobin A1c (HBA1c) level of ≥ 6 are identified as risk factors for the development of CHD, MI, AP, and hypertension. Our study also suggests that statin therapy led to a dose-dependent decrease in liver fibrosis, as well as improvement of the atherogenicity index and systemic inflammatory response in patients with CVD.

CONCLUSION

Our study indicates that CVD patients who also have HBV infection or DM may experience a reduction in MACEs when treated with statins. Furthermore, our research indicates that focusing on long-term glycemic control is essential in this patient population in order to enhance cardiovascular outcomes. The observed improvements in hepatic function, atherosclerotic burden, and systemic inflammation associated with statin therapy may contribute to the favorable cardiovascular outcomes among individuals with CVD.

Clinical Perspective

What Is New?

This study investigates the association between statin therapy and major adverse cardiovascular events (MACEs) in Chinese patients with cardiovascular disease who have concurrent hepatitis B virus infection or diabetes mellitus.

The findings suggest potential cardiovascular benefits of statin therapy in this specific patient population.

The study explores the relationship between statin use and changes in hepatic function, atherosclerotic markers, and inflammatory parameters.

What Are the Clinical Implications?

The results provide evidence supporting statin use in cardiovascular disease patients with hepatitis B virus infection or diabetes mellitus.

Glycemic control appears to be an important factor in optimizing cardiovascular outcomes in these patients.

Regular monitoring of hepatic and inflammatory markers may be valuable in assessing treatment response.
Targeted H3K9 acetylation at lncSox1 promoter by cell type-specific epigenome editing promotes intermediate progenitor proliferation in developing mouse cortex
Authors: Sokpor Godwin , Ulmke Pauline Antonie , Nguyen Hoang Duy , Pham Linh , Kakani Princy , Chu Van Trung , Arnold Sebastian J. , Brand-Saberi Beate , Nguyen Huu Phuc , Tuoc Tran
Published: November 2024

The distribution and level of epigenetic (chromatin) marks have implications for differential regulatory effects at specific gene loci. Herein, we applied a protocol which combinesin vivoelectroporation and a CRISPR-dead (d)Cas9 system to probe and edit a specific chromatin mark in the epigenome of intermediate progenitor cells (IPCs) in developing mouse cortex. We found that the promoter oflncSox1, a long non-coding gene, is a key genomic locus for H3K9 acetylation (H3K9ac) during IPC amplification. CRISPR-dCas9–mediated addition of H3K9ac atlncSox1promoter resulted in lncSox1 upregulation, with attendant increase in IPC pool and augmented neurogenesis. Thus, we have identified dynamic regulation of lncSox1 as a major downstream target of H3 acetylation, and as part of an epigenetic mechanism involved in IPC proliferation during neocortex expansion. This finding is a proof-of-concept that our epigenome editing-based method can be used for manipulating specific epigenetic effectors to determine their (neuro)biological significance.

MOTIVATION

The abundance of basal progenitors is critical for cortical neurogenesis during brain development. There is growing interest in identifying how specific epigenetic factors regulate the genesis and expansion of basal progenitor cell sub-populations, including intermediate progenitor cells. We established a protocol that allowed us to identify the involvement of a long non-coding RNA (lncSox1) in regulating the proliferation of intermediate progenitor cells under the influence of H3K9 acetylation (H3K9ac). By enhancing H3K9ac at the promoter region oflncSox1using a CRISPR-dCas9–mediated gene-editing tool, we were able to determine that lncSox1 upregulation is a downstream effect of H3K9ac acetylation and is necessary for intermediate progenitor pool amplification during cortical development.

Highlights

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Identification of H3 acetylation-dependent expression of ncRNAs in developing cortex.

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Establishment of cell Cre/LoxP and CRISPR-dCas9-dependent H3K9ac epigenome editing.

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CRISPR-dCas9–mediated addition of H3K9ac at lncSox1 promoter resulted in lncSox1 upregulation.

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H3K9 acetylation at lncSox1 promoter enhances proliferation of TBR2-expressing IPCs.

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Targeted epigenome editing revealed lncSox1 as a key regulator of cortical development.
Development of an AAV Vector System for Highly Specific and Efficient Gene Expression in Microglia
Authors: Aoki Ryo , Konno Ayumu , Hosoi Nobutake , Kawabata Hayato , Hirai Hirokazu
Published: November 2024

Microglia play a critical role in diseases such as Alzheimer’s and stroke, making them a significant target for therapeutic intervention. However, due to their immune functions in detecting and combating viral invasion, efficient gene delivery to microglia remains challenging. We achieved specific and efficient gene delivery to microglia using an adeno- associated virus (AAV) vector designed for this purpose. This microglia-targeting AAV vector includes the mouse microglia/macrophage-specific ionized calcium-binding adaptor molecule 1 (mIba1) promoter, green fluorescent protein (GFP), microRNA target sequences (miR.Ts), woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), and polyadenylation (polyA) signal, positioned between inverted terminal repeats. When miR.Ts were placed downstream of WPRE (between WPRE and polyA), gene expression occurred not only in microglia but also in a substantial number of neurons. However, when miR.Ts were positioned upstream of WPRE (between GFP and WPRE) or on both sides of WPRE, neuronal expression was significantly suppressed, resulting in selective GFP expression in microglia. Notably, positioning miR.Ts on both sides of WPRE achieved over 90% specificity and more than 60% efficiency in transgene expression in microglia three weeks after viral administration. This vector also enabled GCaMP expression in microglia, facilitating real-time monitoring of calcium dynamics and microglial process activity in the cortex. Additionally, intravenous administration of this vector with the blood-brain barrier-penetrant AAV-9P31 capsid variant resulted in extensive GFP expression selectively in microglia throughout the brain. These findings establish this AAV vector system as a robust tool for long-term, specific, and efficient gene expression in microglia.
Unraveling eye movement-related eardrum oscillations (EMREOs): how saccade direction and tympanometric measurements relate to their amplitude and time course
Authors: Sotero Silva Nancy , Kayser Christoph , Bröhl Felix
Published: November 2024

Eye movement-related eardrum oscillations (EMREOs) reflect movements of the tympanic membrane that scale with the magnitude and direction of saccades. EMREOs have been consistently described in humans and non-human primates, yet many questions regarding this phenomenon remain unresolved. Based on bilateral in-ear recordings in human participants we here explore several properties of these EMREOs in order to improve our understanding of this signal’s origin and functional significance. Our data support that the EMREO time course is comparable between the left and right ears, and between paradigms guiding saccades by visual and auditory target stimuli. However, the precise amplitude time course differs significantly between ipsi-and contralateral saccades in addition to the previously known phase-inversion described for saccades in opposing directions. Finally, our data suggest that the EMREO amplitude is negatively related to the compliance of the tympanic membrane as established by tympanometry. Collectively, these results support the notion that EMREOs reflect motor-related top-down signals relayed to the ear from yet-to-be-resolved sources, and fuel the speculation that EMREOs may be generated by the middle ear muscles in a differential operation similar to the execution of ipsi-and contralateral saccades.
The phosphatase PP2C12 is a negative player in LRX-RALF-FER-mediated cell wall integrity sensing
Authors: Hou Xiaoyu , Bender Kyle W. , Kadler Gabor , Gupta Shibu , Häfliger Mona , Guérin Amandine , Diet Anouck , Roffler Stefan , Campanini Daniela , Wicker Thomas , Zipfel Cyril , Ringli Christoph
Published: November 2024

Plants have evolved an elaborate cell wall integrity (CWI) sensing system to monitor and modify cell wall formation. LRR-extensins (LRXs) are cell wall-anchored proteins that bind RAPID ALKALINIZATION FACTOR (RALF) peptide hormones and induce compaction of cell wall structures. At the same time, LRXs form a signaling platform with RALFs and the transmembrane receptor kinase FERONIA (FER) as a means to relay changes in CWI to the protoplast.LRX1ofArabidopsis thalianais predominantly expressed in root hairs andlrx1mutants develop defective root hairs. Here, we identify a regulator of LRX1-RALF-FER signaling as a suppressor of thelrx1root hair phenotype. Therepressor of lrx1_23(rol23) gene encodes PP2C12, a type 2C phosphatase of clade H that interacts with FER and dephosphorylates Thr696 in the FER activation loopin vitro. The LRX1-related function of PP2Cs appears clade H-specific and was not observed for other PP2Cs investigated. Collectively, our data suggest that LRX1 acts upstream of the RALF1-FER signaling module and PP2C12 has an inhibitory activity via modulating FER activity to fine-tune CWI signaling.
Microglia modulate cerebral blood flow and neurovascular coupling through ectonucleotidase CD39
Authors: Fu Zhongxiao , Ganesana Mallikarjunarao , Hwang Philip , Tan Xiao , Kinkaid Melissa Marie , Sun Yu-Yo , Bian Emily , Weybright Aden , Sol-Church Katia , Eyo Ukpong B. , Pridans Clare , Quintana Francisco J. , Robson Simon C. , Kumar Pankaj , Venton B. Jill , Schaefer Anne , Kuan Chia-Yi
Published: November 2024

Microglia and the border-associated macrophages (BAMs) contribute to the modulation of cerebral blood flow (CBF), but the mechanisms have remained ill-defined. Here, we show that microglia regulate the CBF baseline and upsurges after whisker stimulation or intracisternal magna injection of adenosine triphosphate (ATP). Genetic or pharmacological depletion of microglia reduces the activity-dependent hyperemia but not the cerebrovascular responses to adenosine stimulation. Notably, microglia repopulation corrects these CBF reactivity deficits. The microglial-dependent regulation of CBF requires the ATP-sensing P2ry12 receptor and the ectonucleotidase CD39 that initiates the breakdown of extracellular ATP. Pharmacological inhibition or microglia-specific deletion of CD39 simulates the CBF anomalies detected in microglia-deficient mice and reduces the rise of extracellular adenosine after whisker stimulation. Together, these results suggest that the microglial CD39-initiated conversion of extracellular ATP to adenosine is an important step in neurovascular coupling and the regulation of cerebrovascular reactivity.
Oral Boldine Administration Attenuates Glia Activation and Prevents Neuropathic Pain in a Murine Spared Nerve Injury Model
Authors: Pan Jiangping , Duarte Yorley , Chow Christine , Toro Carlos A. , Sáez Juan C. , Cardozo Christopher P. , Zhao Wei
Published: November 2024

Chronic pain is present in about 20% of the population and is a major burden to the health care system. About 30-40% of these patients report neuropathic pain. Neuropathic pain is defined as pain caused by injury or disease of the somatosensory nervous system. Current available treatments for neuropathic pain have limited efficacy and substantial side effects. To address the need for more effective and safer treatments for neuropathic pain, this study aimed to test whether boldine, a naturally occurring alkaloid, could attenuate neuropathic pain in a murine model of spared nerve injury (SNI). We found that oral administration of boldine at 50 mg/kg body weight/day resulted in significant reduction of SNI-induced mechanical and thermal hypersensitivity. Boldine also corrected SNI-induced weight bearing deficits, which are an indication of spontaneous pain. Boldine significantly inhibited SNI-induced peripheral inflammation as indicated by reduced levels of inflammatory cytokines/chemokines in the serum. Immunofluorescence studies revealed that boldine reduced the number of reactive astrocytes and inhibited microglia activation in the dorsal horn of lumbar spinal cord. Boldine also reduced the mRNA level of pro-inflammatory markers including IL-1β and TNF-α in the lumbar spinal cord after SNI. Quantitative PCR showed that boldine inhibited the lipopolysaccharide-induced overexpression of inflammatory markers in primary mouse astrocytes and in BV-2 microglial cells. Our findings suggest that boldine may be a promising therapeutic candidate for the treatment of neuropathic pain, possibly through inhibition of glia activation and neuroinflammation.
PgtE protease enables virulentSalmonellato evade C3-mediated serum and neutrophil killing
Authors: Lee Michael H. , Perez-Lopez Araceli , Knodler Leigh A. , Nguyen Grace , Walker Gregory T. , Behnsen Judith , Silva Steven , Celli Jean , Tamin Melissa A. , Liang Michael H. , Melchior Karine , Argueta Felix A. , Nuccio Sean-Paul , Raffatellu Manuela
Published: November 2024

Non-typhoidalSalmonellaserovars, such asSalmonella entericaserovar Typhimurium (STm), are a leading cause of inflammatory diarrhea in otherwise healthy individuals. Among children, the elderly, and immunocompromised individuals, STm can spread to systemic sites and cause potentially lethal bacteremia. Phagocytic cells and the immune complement system are pivotal to preventing the dissemination of STm. PgtE, an STm outer membrane protease, has been previously described to cleave over a dozen mammalian protein substratesin vitro, including complement protein C3. However, these activities have mostly been observed with mutant, avirulent strains with a truncated O-antigen that renders bacteria sensitive to complement killing. Here, we report that virulent STm utilizes PgtE to evade complement-mediated killingin vivo. The wild-type pathogen increasespgtEexpression and PgtE proteolytic function within macrophages and in macrophage-likein vitrogrowth conditions, concomitant with physiologic O-antigen shortening in these environments. Furthermore, we found that wild-type STm’s resistance to complement-mediated serum and neutrophil killing is PgtE-dependent. We propose that PgtE promotes the systemic spread of STm by acting as a second line of defense against complement when STm escapes from a macrophage.
In vivo cell-type and brain region classification via multimodal contrastive learning
Authors: Yu Han , Lyu Hanrui , Xu Ethan YiXun , Windolf Charlie , Lee Eric Kenji , Yang Fan , Shelton Andrew M , Olsen Shawn , Minavi Sahar , Winter Olivier ,   The International Brain Laboratory, Dyer Eva L , Chandrasekaran Chandramouli , Steinmetz Nicholas A , Paninski Liam , Hurwitz Cole
Published: November 2024

Current electrophysiological approaches can track the activity of many neurons, yet it is usually unknown which cell-types or brain areas are being recorded without further molecular or histological analysis. Developing accurate and scalable algorithms for identifying the cell-type and brain region of recorded neurons is thus crucial for improving our understanding of neural computation. In this work, we develop a multimodal contrastive learning approach for neural data that can be fine-tuned for different downstream tasks, including inference of cell-type and brain location. We utilize this approach to jointly embed the activity autocorrelations and extracellular waveforms of individual neurons. We demonstrate that our embedding approach, Neuronal Embeddings via MultimOdal contrastive learning (NEMO), paired with supervised fine-tuning, achieves state-of-the-art cell-type classification for an opto-tagged visual cortex dataset and brain region classification for the public International Brain Laboratory brain-wide map dataset. Our method represents a promising step towards accurate cell-type and brain region classification from electrophysiological recordings.
Ecological Determinants of Altruism in Prokaryote Antivirus Defense
Authors: Biba Dmitry A. , Makarova Kira S. , Wolf Yuri I. , Waldron Levi , Koonin Eugene V. , Rochman Nash D.
Published: November 2024

Prokaryote evolution is driven in large part by the incessant arms race with viruses. Genomic investments in antivirus defense can be coarsely classified into two categories, immune systems that abrogate virus reproduction resulting in clearance, and altruistic programmed cell death (PCD) systems. Prokaryotic defense systems are enormously diverse, as revealed by an avalanche of recent discoveries, but the basic ecological determinants of defense strategy remain poorly understood. Through mathematical modeling of defense against lytic virus infection, we identify two principal determinants of optimal defense strategy and, through comparative genomics, we test this model by measuring the genomic investment into immunity vs PCD among diverse bacteria and archaea. First, as viral pressure grows, immunity becomes the preferred defense strategy. Second, as host population size grows, PCD becomes the preferred strategy. We additionally predict that, although optimal strategy typically involves investment in both PCD and immunity, overinvestment in immunity can result in system antagonism, increasing the probability a PCD-competent cell will lyse due to infection. Together these findings indicate that, generally, PCD is preferred at low multiplicity of infection (MOI) and immunity is preferred at high MOI, and that the landscape of prokaryotic antivirus defense is substantially more complex than previously suspected.
Relationships between measures of neurovascular integrity and fluid transport in aging: a multi-modal neuroimaging study
Authors: Rowsthorn Ella , Cribb Lachlan , Sinclair Benjamin , Pham William , Chong Trevor , Yiallourou Stephanie , Cavuoto Marina , Vivash Lucy , O’Brien Terence J. , Shao Xingfeng , Wang Danny J.J. , Law Meng , Pase Matthew P. , Harding Ian H.
Published: November 2024

Fluid transport in the neurovascular unit (NVU) is essential for maintaining brain health through nutrient delivery and waste clearance. NVU integrity and fluid regulation can be assessed through MRI measures, including water exchange rate through the NVU (BBB kw), enlarged perivascular spaces (ePVS), cerebral blood flow (CBF), free water (FW), and white matter hyperintensities (WMH). This study investigated relationships between these MRI measures using Bayesian mixed models, and their variation with chronological age or biological brain age (brainageR) using linear regression in 132 non-clinical older adults (mean age=67 years; 68% female). BBB kwpositively associated with CBF (β^=0.08, 95% credible interval (CI)=[0.02,0.15]). FW positively associated with both ePVS (β^=0.44, CI=[0.30,0.63]) and WMH (β^=0.13, CI=[0.04,0.21]). BBB kw, CBF and ePVS decreased with age, while FW and WMH increased (allp<.05). There were no associations with brain age (allp>.05). Relationships between FW, ePVS and WMH likely reflect interconnectivity of fluid regulation within different compartments, while the relationship between BBB kwand CBF indicates a link between NVU fluid flow and vessel function. While individual metrics of NVU integrity are associated with age, their inter-relationships appear stable, providing a baseline for future research in fluid transport and vascular health in neurodegenerative disease.

Abstract Figure

Graphical Abstract:

Neurovascular function and the fluid transport system.

The brain’s fluid transport system comprises the neurovascular unit, interstitial fluid exchange in the parenchyma and venous outflow.a.The flow of water molecules from the vessel to the perivascular space through the blood-brain barrier, and subsequently into the brain (facilitated by aquaporin-4 (AQP4) channels) in quantified by BBB kw.b.Greater cerebral blood flow rate (CBF) is associated with greater BBB kw, possibly due to vessel pulsations increasing osmotic pressure.c.Enlarged perivascular spaces (ePVS) may indicate reduced fluid flow within the NVU and are associated with (d.) increased extracellular free water (FW) in the parenchyma, suggesting a link between fluid regulation within the vasculature and the surrounding brain tissue. Greater white matter hyperintensity (WMH) volume also occurs alongside increase FW, in line with WMH reflecting more severe fluid flow stagnation occurring in concert with neuroinflammation and/or neuronal demyelination.
Gapless assembly of complete human and plant chromosomes using only nanopore sequencing
Authors: Koren Sergey , Bao Zhigui , Guarracino Andrea , Ou Shujun , Goodwin Sara , Jenike Katharine M. , Lucas Julian , McNulty Brandy , Park Jimin , Rautiainen Mikko , Rhie Arang , Roelofs Dick , Schneiders Harrie , Vrijenhoek Ilse , Nijbroek Koen , Nordesjo Olle , Nurk Sergey , Vella Mike , Lawrence Katherine R. , Ware Doreen , Schatz Michael C. , Garrison Erik , Huang Sanwen , McCombie William Richard , Miga Karen H. , Wittenberg Alexander H.J. , Phillippy Adam M.
Published: November 2024

The combination of ultra-long (UL) Oxford Nanopore Technologies (ONT) sequencing reads with long, accurate Pacific Bioscience (PacBio) High Fidelity (HiFi) reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, “telomere-to-telomere” genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT “Duplex” sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy. To evaluate this new data type, we generated ONT Duplex data for three widely studied genomes: human HG002,Solanum lycopersicumHeinz 1706 (tomato), andZea maysB73 (maize). For the diploid, heterozygous HG002 genome, we also used “Pore-C” chromatin contact mapping to completely phase the haplotypes. We found the accuracy of Duplex data to be similar to HiFi sequencing, but with read lengths tens of kilobases longer, and the Pore-C data to be compatible with existing diploid assembly algorithms. This combination of read length and accuracy enables the construction of a high-quality initial assembly, which can then be further resolved using the UL reads, and finally phased into chromosome-scale haplotypes with Pore-C. The resulting assemblies have a base accuracy exceeding 99.999% (Q50) and near-perfect continuity, with most chromosomes assembled as single contigs. We conclude that ONT sequencing is a viable alternative to HiFi sequencing for de novo genome assembly, and provides a multirun single-instrument solution for the reconstruction of complete genomes.
Phase diagrams and topological mixed edge states in silicene with intrinsic and extrinsic Rashba effects
Authors: Lü Xiao-Long , Zhang Yan-Chao , Fu Pei-Hao , Liu Jun-Feng
Published: November 2024

We investigate the topological phases and corresponding edge states in silicene with fixed intrinsic and extrinsic Rashba spin-orbit couplings. The results show that silicene can exhibit four distinct topological phases, such as two types of valley-polarized quantum anomalous Hall effect (QAHE) and two types of QAHE that can be effectively controlled by the exchange field and electric field. In addition, these topological phases only correspond to the valley edge states distributed at the boundary of silicene. In particular, when the off-resonant circularly polarized (ORCP) light is further considered, silicene can host richer topological phases that are characterized by the Chern numbers from C=−3 to C=3, where the corresponding mixed edge states—where the valley and nonvalley edge states could coexist—can remarkably appear. More interestingly, the special higher Chern numbers C=±3 determine two valley edge states and one nonvalley edge state, with the right-moving or left-moving direction. These peculiar edge states are attributed to the ORCP light destroying the collapse of the Dirac cones that the valley edge states bridge. Additionally, silicene can experience multiple edge-state transitions for identical Chern numbers C=±2 between the valley edge state, nonvalley edge state, and two types of mixed edge state, under the ORCP light. This work may provide a platform and point of view for investigating other forms of topological edge state and is beneficial for designing multifunctional topological devices.

Published by the American Physical Society
2024
Implementing the Grover algorithm in homomorphic encryption schemes
Authors: Fernández Pablo , Martin-Delgado Miguel A.
Published: November 2024

We apply quantum homomorphic encryption (QHE) schemes suitable for circuits with a polynomial number of T+T† gates to Grover's algorithm, performing a simulation in Qiskit of a Grover circuit that contains three qubits. The T+T†-gate complexity of Grover's algorithm is also analyzed in order to show that any Grover circuit can be evaluated homomorphically in an efficient manner. We discuss how to apply these QHE schemes to allow for the efficient homomorphic evaluation of any Grover circuit composed of n qubits using n−2 extra ancilla qubits. We also show how the homomorphic evaluation of the special case where there is only one marked item can be implemented using an algorithm that makes the decryption process more efficient compared with the standard Grover algorithm.

Published by the American Physical Society
2024
Refueling intellectual capital toward innovation performance of SMEs in Saudi Arabia: mediating the role of entrepreneurial opportunity recognition
Authors: AlMulhim Abdullah Fahad , Mohammed Sanaa Mostafa , Benlaria Houcine , Gheraia Zouheyr
Published: November 2024

Purpose

The objectives of this research were to inspect the relationship of intellectual capital (IC), along with its dimensions (human, structural and internal and external relational capital) with innovation performance (IP), to explore entrepreneurial opportunity recognition (EOR) as a mediator between the IC and IP of small and medium-sized enterprises (SMEs) in Saudi Arabia.

Design/methodology/approach

This research used data collected via a well-structured questionnaire. The sample size was comprised of 457 participants who were owners and/or managers of SMEs in Saudi Arabia. Further, the findings were extracted from data using partial least squares (PLS) techniques.

Findings

The results indicated that all dimensions of IC, including human capital (HC), structural capital (SC), internal relational capital (IRC) and external relational capital (ERC), had a significant relation with both IP and EOR. It was also shown that EOR positively influenced IP. Furthermore, the results showed that EOR played an important role as a mediator between IC (HC, SC, IRC and ERC) and IP.

Practical implications

The present research offered a beneficial and novel managerial and theoretical strategy for improving a given firm’s IP with the support of IC and EOR. This finding offered a vision to the management teams of SMEs for full utilization of IC and IP. The present study also provided policymakers, administration and future studies with a path to improving the production and services of SMEs to secure market advantages.

Originality/value

According to the author’s best knowledge, the present research represented the first attempt to expose the mediating role of the EOR relationship between IC and IP. Furthermore, the present study also developed the relationship between dynamic capabilities (DC) theory, intellectual capital-based view (ICV) theory and resource-based view (RBV) theory, with variables that reveal the theoretical foundation of the study. Finally, the results of this study were verified by the existing literature.
Empathetic concern and social entrepreneurial intention: a moderated mediation model of social entrepreneurial self-efficacy and perceived cultural support
Authors: Nguyen Thuy Thi , Nguyen Tuan-Duong , Mustafa Michael James
Published: November 2024

Purpose

This study aims to explore whether social entrepreneurial self-efficacy (SESE) mediates the empathetic concern (EC)–social entrepreneurial intentions (SEIs) relationship. In addition, drawing on institutional theory, the authors propose that the EC–SESE–SEI relationship is contingent upon perceptions of cultural support (PCS) towards social entrepreneurship in a society.

Design/methodology/approach

Data from 232 Taiwanese business and management undergraduates were used to test the proposed relationships.

Findings

SESE was found to mediate the relationship between EC and SEI. However, cultural support towards social entrepreneurship in society had a negative moderating effect on the EC–SESE–SEI relationship, suggesting that the EC–SESE–SEI relationship was stronger under conditions of low, rather than high PCS.

Originality/value

This paper provides further insights into not only the link between EC and SEI but also the conditions under which EC is translated into SEI. It also enhances the recent limited knowledge about how context and cultural attitudes and values towards social entrepreneurship shapes SEI.
Managerial interlocking networks and firm risk spillover: evidence from China
Authors: Chen Lin , Niu Ruiyang , Yang Yajie , Zhao Longfeng , Xie Guanghua , Khan Inayat
Published: November 2024

Purpose

This paper examines the effect of managerial interlocking networks (MINs) on firm risk spillover by using a sample of Chinese A-share listed firms.

Design/methodology/approach

Applying the complex network approach, we build managerial interlocking networks (MINs) and leverage degree centrality to quantify a manager’s network position. To gauge firm risk spillover, we utilize the conditional autoregressive value at risk (CAViaR) model to compute the value-at-risk. Subsequently, we employ ordinary least squares to investigate the influence of MINs on firm risk spillover.

Findings

Our research uncovers a direct correlation between a firm risk spillover and the status of network positions within managerial interlocking networks; namely, the more central the position, the greater the risk spillover. This increase is believed to be due to central firms in MINs having greater connectedness and influence. This fosters a similarity in decision-making across different firms through interfirm managerial communication, thus amplifying the risk spillover. Economic policy uncertainty (EPU) and Guanxi culture furtherly intensify the effects of MINs. Additional analysis reveals that the impact of MINs on the firm risk spillover is significantly noticeable in non-state-owned enterprises, while good corporate governance diminishes the risk spillover prompted by MINs.

Originality/value

Our findings offer fresh insights into the interfirm risk outcome associated with MINs and extend practical guidelines for attenuating firm risk spillover with a view toward mitigating systemic risk.
Networks for healthcare delivery: a systematic literature review
Authors: Gremyr Ida , Colldén Christian , Hjalmarsson Yommine , Schirone Marco , Hellström Andreas
Published: November 2024

Purpose

Network configurations have been proposed as an efficient form of organisation and a promising area of research; however, a lack of conceptual clarity can be noted. The purpose of this review is to allow for a broad appreciation of network configurations and provide guidance for future studies of the concept.

Design/methodology/approach

A systematic literature review was conducted based on the PRISMA method; Scopus, Web of Science, PubMed and the Cochrane Library were searched for conference proceedings and journal articles describing organisational networks to integrate resources aimed at care delivery. Around 80 articles were included in the final review and analysed thematically and by use of bibliographic coupling.

Findings

The last decades have seen an increase in the frequency of articles describing networks for healthcare delivery. The most common contexts are care for multiple and/or long-term conditions. Three clusters of articles were found, corresponding to different conceptualisations of networks in healthcare: efficiency-enhancing cooperation, efficiency-enhancing integration and involvement for cocreation.

Research limitations/implications

To increase conceptual clarity and allow the research on network configurations in healthcare to produce meta-learnings and guidance to practice, scholars are advised to provide ample descriptions of studied networks and relate them to established network classifications.

Originality/value

The current review has only included articles including networks as a key concept, which provides a focused overview of the use of network configurations but limits the insights into similar approaches not described explicitly as networks.
Enabling crowdfunding platforms in Qatar: a regulatory framework for growth and sustainable innovation based on network analysis and Monte Carlo simulation
Authors: Syarif Muhammad Fazlurrahman , Aysan Ahmet Faruk
Published: November 2024

Purpose

This study aims to explore the structure and dynamics of Qatar’s crowdfunding ecosystem to support economic diversification and enhance entrepreneurial activities. This research focuses on analyzing the development of the industry, its regulatory environment and the collaborative dynamics among stakeholders.

Design/methodology/approach

This study used network analysis and Monte Carlo simulations to examine the interplay between various stakeholders, including entrepreneurs, to understand their roles and interconnections. This study also simulated different economic scenarios to evaluate the potential impact of crowdfunding under various market conditions and regulatory frameworks.

Findings

The analysis reveals a moderate level of crowdfunding activity characterized by conservative fundraising outcomes. The key factors identified include the pivotal role of a supportive regulatory framework and the necessity of robust stakeholder collaboration and infrastructure to ensure the industry’s resilience and growth.

Research limitations/implications

The findings are constrained by the simulated scenarios and the current state of the crowdfunding market in Qatar, suggesting that further research could explore emerging trends as the market evolves.

Practical implications

This study provides actionable recommendations for policymakers and regulatory authorities to boost a conducive environment for crowdfunding platforms. This includes enhancing connectivity among stakeholders and building robust infrastructure to support industry growth.

Social implications

This study underlines the significant social benefits of crowdfunding, including promoting innovation, supporting economic growth and facilitating entrepreneurship. These elements are vital to Qatar’s broader economic diversification strategy.

Originality/value

This study provides original insights into the crowdfunding landscape in Qatar, particularly in terms of strategic planning and risk management, using advanced simulation techniques to predict the outcomes of different regulatory and economic scenarios.
Mechanism for developing brand equity of higher education institutes using intangible resources: a serial-multiple mediation analysis
Authors: Khanna Kritika , Singh Jagwinder , Bedi Sarbjit Singh
Published: November 2024

Purpose

This study aims to build a comprehensive model for developing higher education institutes (HEIs) brand equity by examining the impact of HEIs intangible resources, brand management aspects, attachment strength and student’s contemporary citizenship behavior (CCB).

Design/methodology/approach

Data were gathered through a self-administered questionnaire from Indian students and alumni (n = 703). The study examines the proposed comprehensive model through serial and multiple mediation analysis.

Findings

The study unfolded “service quality? brand image? attachment strength? word-of-mouth? brand equity” as the most significant path to develop HEI’s brand equity.

Research limitations/implications

This study pioneers an empirically validated mechanism for developing brand equity in HEIs, addressing gaps identified by previous studies and offering a theoretical framework that elucidates how HEIs can leverage intangible resources through strategic brand management to foster attachment and influence positive student behaviors, thereby contributing to the development of HEI brand equity.

Practical implications

HEIs need to understand that relying solely on tangible aspects leads to short-lived effects. To maintain a lasting competitive advantage, HEIs should focus on crafting a rich historical narrative, retaining talented faculty and staff and earning respect from the public to build a lasting reputation.

Originality/value

This study develops the mechanism for developing brand equity of HEIs using its valuable, rare and inimitable intangible resources. Along with the introduction of novel constructs like competence, heritage and word-of-mouth to existing study, the proposed conceptual model is premised on the theory of self-congruence, social-exchange theory and CCB.
Green performance appraisal impact on organizational sustainability: exploring the role of green knowledge and behavior in Lebanese firms
Authors: Sadek Karim , Karkoulian Silva
Published: November 2024

Purpose

This research aims to reveal the impact of Green Performance Appraisal (GPA) on Organizational Sustainability (OS) and to explore the effect of GPA on Employee Green Behavior (EGB). Moreover, it investigates the factors underlying the relationship between GPA, EGB and OS. Further, it intends to examine the role of Green Knowledge Usage (GKU) in the relationship between EGB and OS.

Design/methodology/approach

Partial Least Squares Structural Equation Modelling technique, SPSS and the Smart PLS 4 Software were used to test the hypotheses and the data collected via a cross sectional online survey conducted among Lebanese firms registered in the local chamber of commerce.

Findings

The results show that GPA plays a significant role in enhancing EGB and in promoting OS. It proves also that EGB partially mediates the relationship between GPA and OS. Further, it reveals the moderating role of GKU in reinforcing the relationship between EGB and OS.

Research limitations/implications

Although the study has some limitations related to the limited sample targeted and the cross-sectional data used, the findings provide various managerial implications and help in enhancing OS. It also advances green human resources management practices theoretically and practically.

Originality/value

This research aims to fill the gaps observed in the literature and explores the impact of GPA on OS examining the mediating role of EGB and the moderating effect of GKU.
Temporal dynamics of stream algae under the combined impacts of climate and land‐use stressors
Authors: Penk Marcin R. , Kelly Ann‐Marie , Kelly‐Quinn Mary , Piggott Jeremy J.
Published: November 2024

Ecosystems are increasingly challenged by the multiple facets of climate change, coupled with intensifying land‐use pressures. These co‐occurring stressors can interact in complex ways, but we lack an empirical understanding of the impact of higher‐order interactions on temporal patterns.

Using 128 flow‐through circular stream mesocosms, we investigated the individual and combined effects of two climatic stressors (CO2 enrichment, flow variability) and two land‐use‐related stressors (siltation, light—as lack of shading) on algal communities and net ecosystem productivity (NPP) in a full‐factorial design. The sediment pulses coincided with high flow to mimic erosion events, whereas CO2 and light disturbances were applied continuously, as they would in nature.

Sediment emerged as a key stressor for algal biomass. Land‐use stressors had more pervasive individual effects, whereas climate‐change‐related stressors were more important in up to three‐way interactions with other stressors. However, CO2 was a key driver of NPP, followed by sediment and light, whereas flow variability was only important in interactions with other stressors. The effects of sediment and flow on algal biomass depended strongly on their temporal patterns. The combined effect of an increasing number of stressors on algal biomass appeared to reach saturation with three active stressors, with no apparent additional effect caused by the fourth stressor.

Synthesis. Sediment emerged as a key stressor in streams. Despite the mounting evidence and the multitude of available mitigation strategies, this problem persists worldwide. The complex interactions uncovered in our study illustrate context‐dependency that can be masked in two‐factor experiments. Our findings also highlighted that temporal patterns of individual and co‐occurring stressors can determine the ecological outcome.
Influence of (ultra‐)processing methods on aquatic proteins and product quality
Authors: Chen Jingjing , Ma Huawei , Guo Ailing , Lv Min , Pan Qingyan , Ya Shiya , Wang Hui , Pan Chuanyan , Jiang Linyuan
Published: November 2024

Aquatic products are a high‐quality source of protein for humans, and the changes in protein during aquatic product processing are crucial for nutritional value, product performance, and consumer health. With the advancement of science and technology, aquatic product processing methods have become increasingly diverse. In addition to traditional methods such as thermal processing (steaming, roasting, and frying) and pickling, emerging non‐thermal processing technologies, such as high pressure, ultrasound, and irradiation, are also being applied. During (ultra‐)processing, aquatic products undergo complex biochemical reactions, among which protein oxidation significantly affects the quality of aquatic products. Protein oxidation can alter the molecular structure of proteins, thereby changing their functional properties and ultimately impacting product quality. This paper primarily explored the effects of protein changes under different processing methods on aquatic product quality and human health, as well as techniques for controlling protein oxidation. It aims to provide a theoretical basis for selecting appropriate processing methods, improving aquatic product quality, and controlling protein oxidation in aquatic products, and to offer scientific guidance for practical production.