bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal-specific Alms1 knockout in mice recapitulates key metabolic features of Alström Syndrome
Authors: McKay Eleanor J. , Luijten Ineke , Weng Xiong , Martinez de Morentin Pablo B. , De Frutos González Elvira , Gao Zhanguo , Kolonin Mikhail G. , Heisler Lora K. , Semple Robert K.
Published: October 2023

Background

Alström Syndrome (AS), a multi-system disease caused by mutations in theALMS1gene, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and hepatosteatosis. How loss of ALMS1 causes this phenotype is poorly understood, but prior studies have circumstancially implicated impaired adipose tissue expandability. We set out to test this by comparing the metabolic effects of selectiveAlms1knockout in mesenchymal cells including preadipocytes to those of globalAlms1knockout.

Methods

GlobalAlms1knockout (KO) mice were generated by crossing floxedAlms1and CAG-Cre mice. APdgfrα-Cre driver was used to abrogate Alms1 function selectively in mesenchymal stem cells (MSCs) and their descendants, including preadipocytes. We combined metabolic phenotyping of global andPdgfrα+Alms1-KO mice on a 45% fat diet with measurements of body composition and food intake, and histological analysis of metabolic tissues.

Results

GlobalAlms1KO caused hyperphagia, obesity, insulin resistance, dyslipidaemia, and fatty liver.Pdgfrα-credriven KO ofAlms1(MSC KO) recapitulated insulin resistance, fatty liver, and dyslipidaemia in both sexes. Other phenotypes were sexually dimorphic: increased fat mass was only present in femaleAlms1MSC KO mice. Hyperphagia was not evident in maleAlms1MSC KO mice, but was found in MSC KO females, despite no neuronal Pdgfrαexpression.

Conclusions

Mesenchymal deletion ofAlms1recapitulates the metabolic features of AS, including severe fatty liver. This confirms a key role forAlms1in the adipose lineage, where its loss is sufficient to cause systemic metabolic effects and damage to remote organs. AS should be regarded as aforme frusteof lipodystrophy. Therapies should prioritise targeting positive energy balance.
New purifications reveal yeast and human stress granule cores are discrete particles with complex transcriptomes and proteomes
Authors: Demeshkina Natalia A. , Ferré-D’Amaré Adrian R.
Published: October 2023

Stress granules are a conserved response of eukaryotic cells to environmental insults. These cytoplasmic ribonucleoprotein condensates have hitherto been primarily studied by microscopy, which showed previously that they comprise dense ≈200 nm cores embedded in a diffuse shell. We have developed new purifications of budding yeast and mammalian (HEK293T cell) stress granule cores that do not rely on immunoprecipitation of candidate protein constituents. These unbiased preparations reveal that stress granule cores are discrete particles with variable size (mean, 135 nm and 225 nm, yeast and human, respectively) and shape. Proteomics and transcriptomics demonstrate complex composition. The results of hybrid chain reaction FISH analyses in HEK293T cells are consistent with stress granule cores having heterogeneous composition,i.e., each stress granule core particle contains only a limited number of mRNA species. Biochemical purification now opens the way to mechanistic analysis of the heterogeneity and complexity of stress granules.
COST AND UTILIZATION TRENDS OF PERCUTANEOUS KIDNEY BIOPSY IN KIDNEY TRANSPLANT PATIENTS: A 4-YEAR CLAIMS DATA ANALYSIS
Authors: Vilalta Adrian
Published: October 2023

Objective

This study evaluated patterns of utilization and costs of percutaneous kidney biopsies in kidney transplant patients.

Methods

The IBMTreatment Pathwaystool was used to interrogate cohorts selected from the IBMMarketScandataset. Analyses were done for both adult and pediatric patients. Differences in biopsy paid amounts and utilization patterns were assessed for commercial payers, Medicare, and Medicaid. Claims data were collected for the years 2016 to 2019.

Results

A total of 15,337 records for percutaneous kidney biopsy events performed between 2016 and 2019 were identified in the database. Out of these, 840 corresponded to pediatric patients.

Discussion

Analysis showed that the paid amount for the procedure increased by 10% from 2016 to 2019 for commercial payers for adult patients, with US $4,137 being the median paid amount in 2019. Median paid amounts by both Medicare and Medicaid remained essentially flat for the same time at US $2,063 for Medicare and US $865 for Medicaid in 2019. Median cost of the procedure in pediatric patients increased 17% between 2016 and 2019 for commercial payers being US $6,068 in 2019. Medicaid payments for the pediatric patient population showed little change between 2016 and 2019, being US $1,666 in 2019.
Demonstrating the Utility of Instrumented Gait Analysis in the Treatment of Children with Cerebral Palsy
Authors: Schwartz Michael H. , Ries Andrew J. , Georgiadis Andrew G. , Kainz Hans
Published: October 2023

Background

Instrumented gait analysis (IGA) has been around for a long time but has never been shown to be useful for improving patient outcomes. In this study we demonstrate the potential utility of IGA by showing that machine learning models are better able to estimate treatment outcomes when they include both IGA and clinical (CLI) features compared to when they include CLI features alone.

Design

We carried out a retrospective analysis of data from ambulatory children diagnosed with cerebral palsy who were seen at least twice at our gait analysis center. Individuals underwent a variety of treatments (including no treatment) between sequential gait analyses. We fit Bayesian Additive Regression Tree (BART) models that estimated outcomes for mean stance foot progression to demonstrate the approach. We built two models: one using CLI features only, and one using CLI and IGA features. We then compared the models’ performance in detail. We performed similar, but less detailed, analyses for a number of other outcomes. All results were based on independent test data from a 70%/30% training/testing split.

Results

The IGA model was more accurate than the CLI model for mean stance-phase foot progression outcomes (RMSEIGA= 11∘, RMSECLI= 13∘) and explained more than 1.5× as much of the variance (R2IGA= .45, R2CLI= .28). The IGA model outperformed the CLI model for every level of treatment complexity, as measured by number of simultaneous surgeries. The IGA model also exhibited superior performance for estimating outcomes of mean stance-phase knee flexion, mean stance-phase ankle dorsiflexion, maximum swing-phase knee flexion, gait deviation index (GDI), and dimensionless speed.

Interpretation

The results show that IGA has thepotentialto be useful in the treatment planning process for ambulatory children diagnosed with cerebral palsy. We propose that the results of machine learning outcome estimators — including estimates of uncertainty — become the primary IGA tool utilized in the clinical process, complementing the standard medical practice of conducting a through patient history and physical exam, eliciting patient goals, reviewing relevant imaging data, and so on.
PCBP2 as an intrinsic aging factor regulates the senescence of hBMSCs through the ROS-FGF2 signaling axis
Authors: Chen Pengbo , Li Bo , Lu Zeyu , Xu Qingyin , Zheng Huoliang , Jiang Shengdan , Jiang Leisheng , Zheng Xinfeng
Published: October 2023

Background

It has been reported that loss of PCBP2 led to increased reactive oxygen species (ROS) production and accelerated cell aging. Knockdown of PCBP2 in HCT116 cells leads to significant down-regulation of fibroblast growth factor 2 (FGF2). Here, we tried to elucidate the intrinsic factors and potential mechanisms of BMSCs aging from the interactions among PCBP2, ROS and FGF2.

Methods

Unlabeled quantitative proteomics were performed to show differentially expressed proteins in the replicative senescent human-derived bone marrow stromal cells (RS-hBMSCs). ROS and FGF2 were detected in the loss-and-gain cell function experiments of PCBP2. The function recovery experiments were performed to verify whether PCBP2 regulates cell function through ROS/FGF2-dependent ways.

Results

PCBP2 expression was significantly lower in P10-hBMSCs. Knocking down the expression of PCBP2 inhibited the proliferation while accentuated the apoptosis and cell arrest of RS-hBMSCs. PCBP2 silence could increase the production of ROS. On the contrary, overexpression of PCBP2 increased the viability of both P3-hBMSCs and P10-hBMSCs significantly. Meanwhile, over-expression of PCBP2 led to significantly reduced expression of FGF2. Overexpression of FGF2 significantly offset the effect of PCBP2 overexpression in P10-hBMSCs, leading to decreased cell proliferation, increased apoptosis and reduced G0/G1 phase ratio of the cells.

Conclusion

This study initially elucidates that PCBP2 as an intrinsic aging factor regulates the replicative senescence of hBMSCs through the ROS-FGF2 signaling axis.
Atrial functional substrates for the prediction of atrial fibrillation recurrence after pulmonary vein isolation
Authors: Masuda Masaharu , Matsuda Yasuhiro , Uematsu Hiroyuki , Asai Mitsutoshi , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Tsujimura Takuya , Hata Yosuke , Higashino Naoko , Nakao Sho , Mano Toshiaki
Published: October 2023

Background

Low-voltage areas have been used as atrial structural substrates in estimating fibrotic degeneration in patients with atrial fibrillation (AF). The high-resolution maps obtained by recently developed mapping catheters allow the visualization of several functional abnormalities.

Objectives

We investigated the association between left atrial (LA) functional abnormal findings on a high-resolution substrate map and AF recurrence in patients who underwent pulmonary vein isolation without any additional LA substrate ablation.

Methods

One hundred consecutive patients who underwent second ablation for AF (paroxysmal, 48%; persistent, 52%) were considered for enrollment. Patients with extra-pulmonary-vein LA substrate ablation during the initial and second ablation were excluded. LA mapping was performed using a 64-pole mini-basket catheter on the Rhythmia mapping system. Patients were followed for 2 years.

Results

AF recurrence developed in 39 (39%) patients. On the high-resolution substrate map, AF recurrence was associated with the presence of the following findings: low-voltage areas (<1.0 mV, >5cm2; hazard ratio [HR]=2.53; 95% confidence interval [CI]=1.30-4.93; p<0.006), fractionated-electrogram areas (≥5 peaks, >5cm2; HR=2.15, 95%CI=1.10-4.19; p=0.025), LA conduction time of >130 msec (HR=3.11, 95%CI=1.65-5.88, p<0.0001), deceleration zone (≥5 isochrones/cm2; HR=1.97, 95%CI=1.04-3.37, p=0.039), and multiple septal breakout points (HR=3.27, 95%CI=1.50-7.16, p=0.003). Accumulation of these risk factors increased AF recurrence in a stepwise manner, with an HR=1.90, 95%CI=1.44-2.52, p<0.00001 for each additional risk factor.

Conclusion

A high-resolution map revealed new LA functional substrates associated with AF recurrence. Implementation of functional substrates may improve the prediction of AF recurrence after ablation, and possibly aid the development of tailored AF ablation strategies.

Graphical abstract

Abnormal LA substrates and accumulation of risk factors

Study design, representative maps demonstrating abnormal substrates, and AF recurrence rates stratified by the number of risk factors are shown. Accumulation of these risk factors increased AF recurrence rates in a stepwise manner with an HR = 1.90, 95% CI = 1.44 - 2.52, p<0.00001, for 1 risk increase. AF indicates atrial fibrillation; HR, hazard ratio; CI, confidence interval.
Characterization ofRalstonia pseudosolanacearumdiversity and screening host resistance to manage bacterial wilt in South Asia
Authors: Subedi Nagendra , Cowell Tabitha , Cope-Arguello Matthew , Paul Pierce , Cellier Gilles , Bkayrat Hashem , Bonagura Nicolas , Cadatal Angela , Chen Rachel , Enriquez Ariana , Parasar Rama , Repetto Lisa , Hernandez Rivas Aracely , Shahbaz Mahnoor , White Kaitlin , Lowe-Power Tiffany M. , Miller Sally A.
Published: October 2023

In South Asia, bacterial wilt pathogens in theRalstonia solanacearumspecies complex (RSSC) impose major constraints on eggplant, tomato, and pepper production. To improve the efficacy of bacterial wilt management, the goals of this study were to (1) conduct a survey of RSSC pathogens in Bangladesh and Nepal, (2) characterize the genetic diversity of these isolates, and (3) screen 37 tomato, eggplant, and pepper accessions for resistance to six representative isolates from South Asia. We isolated 99 isolates from Bangladesh and 20 isolates from Nepal and determined that all are phylotype I isolates of theRalstonia pseudosolanacearumspecies. We sequenced and assembled draft genomes for 25 isolates. Phylogenomic analyses suggest that there is a wide diversity of endemic phylotype I isolates in South Asia, and possible introductions of two clonal phylotype I lineages into Bangladesh and Nepal. We contextualize our newly described isolates based on prior reports of RSSC diversity in South Asia and global reports of RSSC pathogens on eggplant and pepper. Greenhouse trials revealed multiple tomato, eggplant, and pepper accessions that exhibit promising levels of resistance to six phylotype I isolates from South Asia.
Super-resolution imaging of potassium channels with genetically encoded EGFP
Authors: Call Isabelle M. , Bois Julian L. , Hansen Scott B.
Published: October 2023

The plasma membrane is a well-organized structure of lipids and proteins, segmented into lipid compartments under 200 nm in size. This specific spatial patterning is crucial for the function of proteins and necessitates super-resolution imaging for its elucidation. Here, we establish that the genetically encoded enhanced green fluorescent protein (EGFP), when combined with direct optical reconstruction microscopy (dSTORM), tracks shear- and cholesterol-induced nanoscopic patterning of potassium channels overexpressed in HEK293T cells. Leveraging EGFP in dSTORM (EGFP-STORM), our findings indicate that cholesterol directs the C-terminus of TWIK-related potassium channel (TREK-1) to ceramide-enriched lipid ganglioside (GM1) clusters. In the absence of the C-terminus, the channel associates with phosphatidylinositol 4,5-bisphosphate (PIP2) cluster. Similarly, cholesterol derived from astrocytes repositions EGFP-tagged inward-rectifying potassium (Kir) channels into GM1 clusters. Without cholesterol, the channel aligns with PIP2lipids. We deduce that cholesterol’s interaction with Kir sequesters the channel, separating it from its activating lipid PIP2. Fundamentally, a genetically encoded EGFP tag should make any protein amenable to dSTORM analysis.
Itaconic acid production by co-feeding ofUstilago maydis: a combined approach of experimental data, design of experiments and metabolic modeling
Authors: Ziegler A.L. , Ullmann L. , Boßmann M. , Stein K.L. , Liebal U.W. , Mitsos A. , Blank L.M.
Published: October 2023

Itaconic acid is a platform chemical with a range of applications in polymer synthesis and is also discussed for biofuel production. While produced in industry from glucose or sucrose, co-feeding of glucose and acetate was recently discussed to increase itaconic acid production by the smut fungusUstilago maydis. In this study, we investigate the optimal co-feeding conditions by interlocking experimental and computational methods. Flux balance analysis indicates that acetate improves the itaconic acid yield up to a share of 40 % acetate on a carbon molar basis. A design of experiment results in the maximum yield of 0.14 itaconic acid per carbon source from 100 g L−1glucose and 12 g L−1acetate. The yield is improved by around 22 % when compared to feeding of glucose as sole carbon source. To further improve the yield, gene deletion targets are discussed that were identified using the metabolic optimization tool OptKnock. The study contributes ideas to reduce land use for biotechnology, by incorporating acetate as co-substrate, a C2-carbon source that is potentially derived from carbon dioxide.
Biosynthesis of the azoxy compound azodyrecin fromStreptomyces mirabilisP8-A2
Authors: Maleckis Matiss , Wibowo Mario , Gren Tetiana , Jarmusch Scott A. , Sterndorff Eva B. , Booth Thomas , Henriksen Nathalie N. S. E. , Whitford Christopher M. , Jiang Xinglin , Jørgensen Tue S. , Ding Ling , Weber Tilmann
Published: October 2023

Azoxy compounds are a distinctive group of bioactive secondary metabolites, characterized by a unique RN=N+(O-)R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins are cytotoxic azoxy metabolites produced byStreptomyces mirabilisP8-A2. Here we cloned and confirmed the putativeazdbiosynthetic gene cluster through CATCH cloning followed by expression and production of azodyrecins in two heterologous hosts,S. albidoflavusJ1074 andS. coelicolorM1146, respectively. We explored the function of 14 enzymes in azodyrecin biosynthesis through gene knock-out using CRISPR-Cas9 base editing in the native producer,S. mirabilisP8-A2. The key intermediates were analyzed in the mutants through MS/MS fragmentation studies, revealing azoxy bond formation via the conversion of hydrazine to azo compound; followed by further oxygenation. Additionally,N-oxygenase and dehydrogenase activities were confirmed among 8 core biosynthetic genes and five helper genes. Moreover, the distribution of the azoxy biosynthetic gene clusters acrossStreptomycesspp. genomes is explored, highlighting the presence of these clusters in over 20% of theStreptomycesspp. genomes and revealing that azoxymycin and valanimycin are scarce, while azodyrecin and KA57A like clusters are widely distributed across the phylogenetic tree.
The effects of genome size on cell size and the functional composition and morphology of leaves: a case study inRhododendron(Ericaceae)
Authors: Dastpak Arezoo , Williams Monica , Perkins Sally , Perkins John A. , Horn Charles , Thompson Patrick , Ryan Connor , Medeiros Juliana , An Yi-Dong , Jiang Guo-Feng , Simonin Kevin A. , Roddy Adam B.
Published: October 2023

Background and Aims

Despite the predominance of scaling photosynthetic metabolism by two-dimensional leaf surface area, leaves are three-dimensional structures composed of multiple tissues that directly and indirectly influence photosynthetic metabolism. The structure of leaf surfaces for CO2diffusion and light transmission and the internal volume of tissues that process energy and matter work together to control rates of resource acquisition and turnover. Here we investigate the influence of cell size and packing density on resource acquisition as measured by surface conductance to CO2and water vapor and on resource turnover as measured by leaf water turnover time.

Methods

We sampled wild and cultivated congeneric species in the genusRhododendron(Ericaceae) and measured genome size, anatomical traits related to cell sizes and packing densities, and morphological traits related to water content and dry mass allocation.

Results

AmongRhododendron, anatomical traits related to cell size and morphological traits related to water content and dry mass investment varied largely orthogonally to each other, allowing for many combinations of leaf traits to exist. However, there was a strong, negative relationship between the leaf water residence time (τ) and the maximum leaf surface conductance per leaf volume (gmax,vol), both of which are influenced by cell size and cell packing densities.

Conclusions

Despite leaf function being controlled by many potential combinations of leaf cell- and tissue-level traits, cell size has a pervasive effect on leaf function. Small cells allow for higher diffusion of CO2and water vapor per unit leaf volume (gmax,vol) even at constant leaf thickness, but small cells also result in shorter leaf water residence times (τ). The strong tradeoff betweengmax,voland (τ) illuminates how genome size-cell size allometry influences the fast-slow continuum of plant carbon and water economy.
EEG spectral attractors identify a geometric core of resting brain activity
Authors: Pourdavood Parham , Jacob Michael S.
Published: October 2023

Spectral analysis of electroencephalographic (EEG) data simplifies the characterization of periodic band parameters but can obscure underlying dynamics. By contrast, reconstruction of neural activity in state-space preserves geometric complexity in the form of a multidimensional, global attractor. Here we combine these perspectives, inferring complexity and shared dynamics from eigen-time-delay embedding of periodic and aperiodic spectral parameters to yield unique dynamical attractors for each EEG parameter. We find that resting-state alpha and aperiodic attractors show low geometric complexity and shared dynamics with all other frequency bands, what we refer to as geometric cross-parameter coupling. Further, the geometric signatures of alpha and aperiodic attractors dominate spectral dynamics, identifying a geometric core of brain activity. Non-core attractors demonstrate higher complexity but retain traces of this low-dimensional signal, supporting a hypothesis that frequency specific information differentiates out of an integrative, dynamic core. Older adults show lower geometric complexity but greater geometric coupling, resulting from dedifferentiation of gamma band activity. The form and content of resting-state thoughts were further associated with the complexity of core dynamics. Thus, the hallmarks of resting-state EEG in the frequency domain, the alpha peak and the aperiodic backbone, reflect a dynamic, geometric core of resting-state brain activity. This evidence for a geometric core in EEG complements evidence for a regionally defined dynamic core from fMRI-based neuroimaging, further supporting the utility of geometric approaches to the analysis of neural data.
Unlocking cellular plasticity: Enhancing human iPSC reprogramming through bromodomain inhibition and extracellular matrix gene expression regulation
Authors: Yang Jun , Karimi Kinyamu H. , Ward James M. , Scappini Erica , Archer Trevor K.
Published: October 2023

The transformation of fibroblasts into epithelial cells is critical for iPSC reprogramming. In this report, we describe studies with PFI-3, a small molecule inhibitor that specifically targets the bromodomains of SMARCA2/4 and PBRM1 subunit of SWI/SNF complex, as an enhancer of iPSC reprogramming efficiency. Our findings revealed that PFI-3 induces cellular plasticity in multiple human dermal fibroblasts, leading to a mesenchymal-epithelial transition (MET) during iPSC formation. This transition was characterized by the upregulation of E-cadherin expression, a key protein involved in epithelial cell adhesion. Additionally, we identified COL11A1 as a reprogramming barrier and demonstrated COL11A1 knockdown increased reprogramming efficiency. Notably, we found that PFI-3 significantly reduced the expression of numerous extracellular matrix (ECM) genes, particularly those involved in collagen assembly. Our research provides key insights into the early stages of iPSC reprogramming, highlighting the crucial role of ECM changes and cellular plasticity in this process.
Non-verbal skills in auditory word processing: Implications for typical and dyslexic readers
Authors: Jhilal Soufiane , Molinaro Nicola , Klimovich-Gray Anastasia
Published: October 2023

Dyslexia is characterized by poor phonological skills and atypical neural responses to text and speech stimuli, while non-verbal intelligence remains unaffected. However, the impact of non-verbal intelligence on language-evoked neural responses in dyslexia is underexplored. This study examines non-verbal intelligence’s effects on neural responses to auditory words in typical and dyslexic readers. Participants completed IQ tests, reading and phonological assessments, and underwent magnetoencephalography recordings while listening to words. Event-related brain field responses at different stages of auditory word processing (100ms, 200ms, 400ms) were analyzed in relation to non-verbal IQ scores and reading performance. Higher non-verbal IQ in typical readers yielded earlier right hemisphere perceptual responses (100ms). Dyslexic readers showed no IQ-related latency effects but those with lower non-verbal IQ displayed amplified left hemisphere response amplitudes at 100ms. These findings confirm the link between non-verbal cognitive abilities and early auditory word processing in adults, highlighting distinct effects in dyslexia and controls.
The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics
Authors: Sherman David J. , Liu Lei , Mamrosh Jennifer L. , Xie Jiansong , Ferbas John , Lomenick Brett , Ladinsky Mark S. , Verma Rati , Rulifson Ingrid C. , Deshaies Raymond J.
Published: October 2023

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the genePNPLA3, encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD to date. Despite its discovery twenty years ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear. In this study, we sought to dissect the biogenesis of PNPLA3 and PNPLA3-I148M and characterize changes induced by endogenous expression of the disease-causing variant. Contrary to bioinformatic predictions and prior studies with overexpressed proteins, we demonstrate here that PNPLA3 and PNPLA3-I148M are not endoplasmic reticulum-resident transmembrane proteins. To identify their intracellular associations, we generated a paired set of isogenic human hepatoma cells expressing PNPLA3 and PNPLA3-I148M at endogenous levels. Both proteins were enriched in lipid droplet, Golgi, and endosomal fractions. Purified PNPLA3 and PNPLA3-I148M proteins associated with phosphoinositides commonly found in these compartments. Despite a similar fractionation pattern as the wild-type variant, PNPLA3-I148M induced morphological changes in the Golgi apparatus, including increased lipid droplet-Golgi contact sites, which were also observed in I148M-expressing primary human patient hepatocytes. In addition to lipid droplet accumulation, PNPLA3-I148M expression caused significant proteomic and transcriptomic changes that resembled all stages of liver disease. Cumulatively, we validate an endogenous human cellular system for investigating PNPLA3-I148M biology and identify the Golgi apparatus as a central hub of PNPLA3-I148M-driven cellular change.

Significance Statement

Fatty liver disease affects nearly a quarter of the world’s population and has both environmental and genetic risk factors. A mutation in the genePNPLA3that converts Ile 148 to Met is the strongest known genetic risk factor for developing fatty liver disease. Using a series of techniques to track endogenous PNPLA3 and PNPLA3-I148M biogenesis and localization, we reveal new insights into how the mutation changes cellular dynamics. Although previous reports focus on its role on lipid droplets, we reveal that PNPLA3-I148M also functions at the Golgi apparatus, an organelle critical for protein transport into and out of the cell and lipid signaling. PNPLA3-I148M causes altered Golgi morphology and drives changes reminiscent of liver disease.
Concentration-effect relationships of plasma caffeine on EEG delta power and cardiac autonomic activity during human sleep
Authors: Baur Diego M. , Dornbierer Dario A. , Landolt Hans-Peter
Published: October 2023

Acute caffeine intake affects brain and cardiovascular physiology, yet the concentration-effect relationships on the electroencephalogram (EEG) and cardiac autonomic activity during sleep are poorly understood. To tackle this question, we simultaneously quantified the plasma caffeine concentration with ultra-high-performance liquid chromatography, as well as the EEG, heart rate and high-frequency (0.15-0.4 Hz) spectral power in heart rate variability (HR-HRV), representing parasympathetic activity, with standard polysomnography during undisturbed human sleep. Twenty-one healthy young men ingested in randomized, double-blind, cross-over fashion, 160 mg caffeine or placebo in a delayed, pulsatile-release caffeine formula at their habitual bedtime, and initiated a four-hour sleep opportunity 4.5 hours later. The mean caffeine levels during sleep exhibited high individual variability between 0.2 and 18.4 µmol/l. Across the first two NREM-REM sleep cycles, EEG delta (0.75-2.5 Hz) activity and heart rate were reliably modulated by waking and sleep states. Caffeine dose-dependently reduced delta activity and heart rate, and increased HR-HRV in NREM sleep when compared to placebo. The average reduction in heart rate equaled 3.24 ± 0.77 beats per minute. Non-linear statistical models suggest that caffeine levels above ∼ 7.4 µmol/l decreased EEG delta activity, whereas concentrations above ∼ 4.3 µmol/l and ∼ 4.9 µmol/l, respectively, reduced heart rate and increased HR-HRV. The findings provide quantitative concentration-effect relationships of caffeine, EEG delta power and cardiac autonomic activity and suggest increased parasympathetic activity during sleep after intake of caffeine.
Evaluation of fresh vegetable microbiological contamination in fast-food restaurants
Authors: Saleh Farag Ali , Al-Otaibi Mutlag Mohammad
Published: October 2023

Purpose

Fresh vegetables contain advantageous phytochemical components, making them one of the most significant sources of nutrition. The threat of harmful bacteria still exists because these vegetables are not heated in restaurants before being consumed. Therefore, this study aimed to evaluate the microbial quality of fresh vegetables in restaurants of different levels.

Design/methodology/approach

A total of 499 fresh vegetable samples (from sandwiches and fresh-cut vegetable salads) were collected from 3 different types of food service establishment: 201 from international restaurants (IRs), 210 from national restaurants (NRs), and 88 from cafeterias (CAs). The samples were prepared and inoculated on specific growth media. The aerobic mesophilic bacteria (AMB) Campylobacter spp., Staphylococcus aureus (S. aureus), Enterobacteriaceae, Escherichia coli (E. coli) and yeast and molds were counted, and Listeria monocytogenes, Salmonella spp. and Escherichia coli O157 were detected using specialized medium.

Findings

High counts of S. aureus, above 3 log cfu/g, suggested that 71.5% of samples collected from NRs and 77.3% from CA were not accepted, whereas 81.6% of samples collected from IRs were accepted. The low population of E. coli, less than 2 log cfu/g, suggested that 99.0, 97 and 92.0 % of samples collected from IRs, NRs and CA, respectively, were accepted. Listeria monocytogenes and Escherichia coli O157 were absent from every sample. One sample was positive for Salmonella spp. in each of the NR and CA sample groups.

Originality/value

RIs adhere to health and hygiene standards better than NRs and CAs, according to the findings of vegetable contamination tests.
What drives the effectual entrepreneurship: combinative effects of environmental uncertainty and entrepreneurs’ means
Authors: Bao Shuqin , An Wenwen , Wang Aihuan , Luo Shunjun
Published: October 2023

Purpose

Effectuation, which articulates the process of entrepreneurial action based on nonpredictive control logic, is receiving extensive scholarly attention. What drives the effectual entrepreneurship is featured with high complexity. However, existing studies ignored the complex driving forces underlying entrepreneurial decision-making. Building on a configurational perspective, the purpose of this study was to examine the combinative effects of environmental uncertainty and entrepreneurs’ means on effectual entrepreneurship.

Design/methodology/approach

Drawing on 54 entrepreneurs who are launching new ventures in China, this study adopts a fuzzy-set Qualitative Comparative Analysis (fsQCA) to investigate two sets of antecedent conditions and how they form different combinations for a highly effectual entrepreneurship.

Findings

Our findings disclose four highly effectual entrepreneurship paths involving novice–specialist effectual entrepreneurship in a highly uncertain environment, socialite–specialist effectual entrepreneurship in a highly uncertain environment, pure-specialist effectual entrepreneurship and resourceful effectual entrepreneurship, and one path of barefoot noneffectual entrepreneurship in a highly uncertain environment, which reveals the complex nature of environmental uncertainty and entrepreneurs’ means in driving entrepreneurs to adopt effectuation.

Originality/value

Our study makes the following contributions. First, by taking a configurational perspective, we are able to obtain an elaborate view of the combined effects of environmental uncertainty and entrepreneurs’ means on effectual entrepreneurship. Second, we expand prior thinking on the relationship between environmental uncertainty and effectuation. Third, our study offers a more delicate understanding of entrepreneurs’ means in driving effectuation by splitting means into three separate factors.
An artificial bee colony based-hyper heuristic algorithm with local search for the assembly line balancing problems
Authors: Deliktaş Derya , Aydin Dogan
Published: October 2023

Purpose

Assembly lines are widely employed in manufacturing processes to produce final products in a flow efficiently. The simple assembly line balancing problem is a basic version of the general problem and has still attracted the attention of researchers. The type-I simple assembly line balancing problems (SALBP-I) aim to minimise the number of workstations on an assembly line by keeping the cycle time constant.

Design/methodology/approach

This paper focuses on solving multi-objective SALBP-I problems by utilising an artificial bee colony based-hyper heuristic (ABC-HH) algorithm. The algorithm optimises the efficiency and idleness percentage of the assembly line and concurrently minimises the number of workstations. The proposed ABC-HH algorithm is improved by adding new modifications to each phase of the artificial bee colony framework. Parameter control and calibration are also achieved using the irace method. The proposed model has undergone testing on benchmark problems, and the results obtained have been compared with state-of-the-art algorithms.

Findings

The experimental results of the computational study on the benchmark dataset unequivocally establish the superior performance of the ABC-HH algorithm across 61 problem instances, outperforming the state-of-the-art approach.

Originality/value

This research proposes the ABC-HH algorithm with local search to solve the SALBP-I problems more efficiently.
Unstable propagation of hydraulic fractures under varying well spacing and initiation sequence of multiple horizontal wells considering shear stress shadows
Authors: Wang Yongliang , Liu Nana
Published: October 2023

Purpose

Multi-well hydrofracturing is an important technology to create new fractures and expand existing fractures to increase reservoir permeability. The propagation morphology of the fracture network is affected by the disturbance between the fractures initiation sequences and spacings between adjacent wells. However, it remains unclear how well spacing and initiation sequences lead to fracture propagation, deflection and connection.

Design/methodology/approach

In this study, the thermal-hydro-mechanical coupling effect in the hydrofracturing process was considered, to establish a finite element-discrete element model of multistage hydrofracturing in a horizontal well. Using typical cases, the unstable propagation of hydraulic fractures in multiple horizontal wells was investigated under varying well spacing and initiation sequences. Combined with the shear stress shadow caused by in situ stress disturbed by fracture tip propagation, the quantitative indexes of fracture propagation such as length, volume, displacement vector, deflection and unstable propagation behavior of the hydrofracturing fracture network were analyzed.

Findings

The results show that the shear stress disturbance caused by multiple hydraulic fractures is a significant factor in multi-well hydrofracturing. Reducing the spacing between multiple wells increases the stress shadow area and aggravates the mutual disturbance and deflection between the fractures. The quantitative analysis results show that a decrease of well spacing reduces the total length of hydraulic fractures but increases the total volume of the fracture; compared with sequential and simultaneous fracturing, alternate fracturing can effectively reduce stress shadow area, alleviate fracture disturbance and generate larger fracture propagation length and volume.

Originality/value

The numerical models and results of the unstable propagation and stress evolution of the hydraulic fracture network under thermal-hydro-mechanical coupling obtained in this study can provide useful guidance for the evaluation and design of rock mass fracture networks in deep unconventional oil and gas reservoirs.
Advantages and challenges of extra care housing in the UK for people living with dementia: a scoping review
Authors: Atkinson Teresa June , Oatley Rebecca , Evans Simon
Published: October 2023

Purpose

The purpose of this paper is to report on a scoping review of the advantages and challenges of extra care housing (ECH) provision in the UK for people living with dementia. Access to suitable housing is a fundamental right for people living with dementia and can enable people to live as well as possible (Twyford and Porteus, 2021). Understanding the advantages and disadvantages of different models of housing with care has been identified as a research priority by people living with dementia (Barrett et al., 2016) but “there is no current consensus on the best model of specialist housing for people with dementia” (Twyford and Porteus, 2021, p. 29).

Design/methodology/approach

This scoping review identifies the advantages and disadvantages of living in ECH for people with dementia. It is the preliminary stage of a study that seeks to develop knowledge about different models of ECH for people living with dementia (Atkinson et al., 2021).

Findings

Advantages include the promotion of independence, flexible staffing, safety and security, social inclusion, physical design and integrated service provision. Disadvantages include barriers to entry, tensions between independence and support, managing advanced dementia, resourcing flexible care, managing social exclusion, loneliness and stigma and a disabling environment.

Research limitations/implications

The scoping review reinforces the need for further research into different models of ECH provision in the UK for people living with dementia. The review provides insight that is of benefit to all stakeholders involved in ECH and contributes to the development of evidence-based provision called for in the recent All Party Parliamentary Group inquiry (Twyford and Porteus, 2021).

Originality/value

This scoping review summarises the current position for people living with dementia in ECH.
An early childhood teacher experience in lesson study: the case of Sara
Authors: Ramos Fonseca Maria Gorete , da Ponte João Pedro
Published: October 2023

Purpose

This research aims to understand the learning with regard to didactic knowledge of an early childhood teacher who participated in a Lesson Study (LS) on the topic of patterns, as well as her perspective about LS as a teacher education process.

Design/methodology/approach

This is a qualitative case study of an early childhood teacher who participated in a LS alongside three other colleagues and a facilitator. Data collection was made by participant observation with elaboration of a research journal, audio recording of sessions and a collective interview. Data analysis was made by content analysis based on the conceptual framework.

Findings

This case study shows that early childhood teachers may become aware of the importance of working with their children mathematical ideas. It also shows that they may develop their didactic knowledge in several dimensions such as school mathematics, curriculum, children and their learning, and teaching practice and that they may appreciate LS as a means of professional development.

Originality/value

This study shows the potential of LS for the professional development of early childhood teachers, a scarcely researched area. It also shows that their learning may include dimensions related to specific curricular areas such as mathematics.
Why do and why don't consumers use fashion rental services? A consumption value perspective
Authors: Noe Heeju , Hyun Jonghan
Published: October 2023

Purpose

The study utilized the consumption value theory to explore the motivational factors that define and differentiate the users and nonusers of fashion rental services

Design/methodology/approach

A focus group was conducted to generate an initial list of measurement items. These items were refined through a pretest and then used in a self-administered online questionnaire to collect data from a total of 300 users and 300 nonusers. The collected data were analyzed using factor analysis to identify the factors that define users and nonusers. A MANOVA was then conducted to explore the differences in the identified factors between users and nonusers.

Findings

Using factor analysis, nine factors were extracted across the five consumption values (functional, social, emotional, conditional and epistemic). MANOVA revealed a significant difference between users and nonusers across all factors. Further analyses suggested that the most differentiating factors are two emotional value factors and one social value factor.

Originality

Despite existing studies of fashion rental services, it is debatable whether the phenomenon is fully understood since previous studies primarily focus on consumers who engage in fashion renting services – there is a lack of focus on nonusers. This study provides unique contributions by exploring the phenomenon from both the user's and the nonuser's perspective.
Developing internal marketing strategies for measuring and managing employee-based brand equity
Authors: Baca Granit , Reshidi Nail
Published: October 2023

Purpose

The purpose of this study is to propose a conceptual framework for measuring and managing employee-based brand equity. Drawing upon existing research, the authors argue that internal brand management should be approached from professional and socio-emotional perspectives.

Design/methodology/approach

The study establishes a comprehensive conceptual framework by thoroughly reviewing existing literature on employee-based brand equity and internal marketing. It builds upon existing research while adding unique insights to deepen the understanding of the subject.

Findings

The proposed conceptual framework highlights the importance of both professional and socio-emotional factors in building and managing employee-based brand equity. The framework emphasises the role of employees’ emotions, values and relationships in shaping their brand-related behaviours and their functional role in delivering brand promises.

Research limitations/implications

This paper offers a theoretical foundation for future research in internal branding. However, the framework is not empirically tested, and further research is needed to validate and refine the framework. Organisations can develop more effective internal branding strategies that enhance brand equity by recognising the importance of both professional and socio-emotional factors in shaping employees’ brand-related behaviours.

Practical implications

Organisations can develop more effective internal branding strategies that enhance brand equity by recognising the importance of both professional and socio-emotional factors in shaping employees’ brand-related behaviours.

Originality/value

This study presents a novel approach to internal brand management, introducing a unique, dual-perspective model. This enriches the current body of literature and provides fresh insights for academics and practitioners in the field of marketing and brand management.
This deserves a Huh?
Authors: Franz Diana
Published: October 2023

Research methodology

To complete this case, students will need to access financial statements from the Securities and Exchange Commission’s webpage. The links are provided. Students will also need to review the conceptual framework that is typically covered in Intermediate 1 to respond to question 5.

Case overview/synopsis

This case is based on the three financial statement restatements that Weatherford International Ltd. made over an approximately 18-month period. The restatements were due to a fraud committed by manipulating the income tax accrual in the financial statements. The manipulation used was to overstate the amount of income used to calculate the dividend exclusion and then use a relatively high tax rate to calculate the resulting tax benefit. The tax rate used for the fraud was substantially more than Weatherford’s effective tax rate (ETR), which was a prominent part of the company’s strategic growth plan. The tax senior with the external auditors who reviewed the entry made for the dividend exclusion captured the inconsistency with the comment that “This [the entry] deserves a huh?” The case is intended for students in Intermediate 2, where financial statement restatements and their effect on the company’s financial statements are typically covered. During the years covered in this case, Weatherford was also under investigation for violations of the Foreign Corrupt Practices Act (FCPA). Weatherford’s FCPA violations included multiple instances of bribery, the inappropriate use of volume discounts, improper payments and kickbacks in the United Nation’s Oil for Food program. Weatherford received the eighth-largest fine in the history of FCPA violations (at that time) of $152m. Weatherford’s FCPA investigation expanded, and the company paid another $100m in fines for violations of sanctions law and export control law. This case focuses only on the fraudulent manipulation of the financial statements through the tax accrual and does not delve into the other investigations. However, the linkage between those investigations and the fraud in this case is Weatherford’s nonexistent internal controls.

Complexity academic level

This case was designed to be used in Intermediate 2 financial accounting classes to highlight financial statement restatements and review the conceptual framework and materiality. The students who used the case did not have difficulty with the tax aspect of the case. However, most of the students had taken one tax class previously or concurrently. If students have not had any exposure to tax, the instructor might want to walk students through the tax aspects of the case.