bluuebunny/crossref_metadata_2025 huggingface dataset:
Connexin 43 Regulates Intercellular Mitochondrial Transfer from Human Mesenchymal Stromal Cells to Chondrocytes
Authors: Irwin Rebecca M. , Thomas Matthew A. , Fahey Megan J. , Mayán María D. , Smyth James W. , Delco Michelle L.
Published: March 2024

Background

The phenomenon of intercellular mitochondrial transfer from mesenchymal stromal cells (MSCs) has shown promise for improving tissue healing after injury and has potential for treating degenerative diseases like osteoarthritis (OA). Recently MSC to chondrocyte mitochondrial transfer has been documented, but the mechanism of transfer is unknown. Full-length connexin43 (Cx43, encoded byGJA1) and the truncated internally translated isoform GJA1-20k have been implicated in mitochondrial transfer between highly oxidative cells, but have not been explored in orthopaedic tissues. Here, our goal was to investigate the role of Cx43 in MSC to chondrocyte mitochondrial transfer. In this study, we tested the hypotheses that (a) mitochondrial transfer from MSCs to chondrocytes is increased when chondrocytes are under oxidative stress and (b) MSC Cx43 expression mediates mitochondrial transfer to chondrocytes.

Methods

Oxidative stress was induced in immortalized human chondrocytes using tert-Butyl hydroperoxide (t-BHP) and cells were evaluated for mitochondrial membrane depolarization and reactive oxygen species (ROS) production. Human bone-marrow derived MSCs were transduced for mitochondrial fluorescence using lentiviral vectors. MSC Cx43 expression was knocked down using siRNA or overexpressed (GJA1+ and GJA1-20k+) using lentiviral transduction. Chondrocytes and MSCs were co-cultured for 24 hrs in direct contact or separated using transwells. Mitochondrial transfer was quantified using flow cytometry. Co-cultures were fixed and stained for actin and Cx43 to visualize cell-cell interactions during transfer.

Results

Mitochondrial transfer was significantly higher in t-BHP-stressed chondrocytes. Contact co-cultures had significantly higher mitochondrial transfer compared to transwell co-cultures. Confocal images showed direct cell contacts between MSCs and chondrocytes where Cx43 staining was enriched at the terminal ends of actin cellular extensions containing mitochondria in MSCs. MSC Cx43 expression was associated with the magnitude of mitochondrial transfer to chondrocytes; knocking down Cx43 significantly decreased transfer while Cx43 overexpression significantly increased transfer. Interestingly, GJA1-20k expression was highly correlated with incidence of mitochondrial transfer from MSCs to chondrocytes.

Conclusions

Overexpression of GJA1-20k in MSCs increases mitochondrial transfer to chondrocytes, highlighting GJA1-20k as a potential target for promoting mitochondrial transfer from MSCs as a regenerative therapy for cartilage tissue repair in OA.
Inhibitory Effect of Subthreshold TMS on the Long-Latency Response in the Flexor Carpi Radialis
Authors: Helm Cody A. , Sergi Fabrizio
Published: March 2024

The corticospinal pathway and several secondary motor pathways contribute to long-latency responses (LLRs). However, it is unknown if secondary pathways can produce LLRs independently from corticospinal input. Transcranial magnetic stimulation (TMS) can modulate corticospinal excitability during the LLR.SubthresholdTMS would be ideal for inhibition of corticospinal excitability as it would allow to study function of secondary motor pathways using functional imaging methods with low temporal resolution with minimal activation confound. However, thesubthresholdTMS parameters that maximally inhibit corticospinal activity are unknown.

In this study, thirty-six healthy participants performed a protocol combining surface electromyography(EMG), robot-evoked wrist perturbations, and single pulse TMS applied to the motor cortex to study the effect of TMS intensity and latency on the LLR amplitude in the flexor carpi radialis. In one experiment, we tested two TMS intensities of 90% and 95% of the active motor threshold and three latencies, defined such that the motor evoked potential (MEP) peak would arrive at 0 ms, 20 ms, or 50 ms prior to perturbation onset (T1, T2, T3, respectively). In a second experiment, we sought to determine whether the inhibitory effect ofsubthresholdTMS was specific to long-latency responses.

TMS significantly reduced the LLR amplitude when applied with T3latency, even when restricting the analysis to stimulation modes that did not induce a motor-evoked response (padj= 0.005). However, we found no evidence that TMS inhibition was specific to the LLR. Overall, our findings indicate that single-pulse,subthresholdTMS significantly reduces the corticospinal component of the LLR.

NEW & NOTEWORTHY

This study for the first time shows the capability of subthreshold TMS to reduce the long-latency response amplitude in a forearm muscle. We evaluate the effect of the latency between subthreshold TMS and onset of a wrist perturbation using precisely timed TMS pulses, and establish that the inhibition induced by subthreshold TMS is not specific to LLR, but likely resulting from aspecific intracortical inhibition. Insights from this work can be used to design neuroimaging protocols.
A unique and biocompatible approach for corneal collagen crosslinking in vivo
Authors: Gulzar Ayesha , Kaleli Humeyra N , Koseoglu Gulsum D , Hasanreisoglu Murat , Yildiz Ayşe , Sahin Afsun , Kizilel Seda
Published: March 2024

Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases by increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light in rat corneas and evaluated factors important for clinical application. To perform the CXL procedure, the corneal epithelium of rats was removed under anesthesia, followed by the application of a solution containing ruthenium and sodium persulfate (SPS). The corneas were then exposed to blue light at 430 nm at 3 mW/cm2for 5 minutes. Rat corneas were examined and evaluated for corneal opacity, corneal and limbal neovascularization, and corneal epithelial regeneration at days 0, 1, 3, 6, 8, and 14. On day 28, the corneas were isolated for subsequent tissue follow-up and analysis. CXL with ruthenium and blue light showed rapid epithelial healing, with 100% regeneration of the corneal epithelium and no corneal opacity by day 6. The ruthenium group also exhibited significantly reduced corneal (p<0.01) and limbal neovascularization (p<0.001). Histological analysis revealed no signs of cellular damage or apoptosis, which further confirms the biocompatibility and nontoxicity of our method. Confocal and scanning electron microscopy (SEM) images showed a greater density of collagen fibrils, indicating efficient crosslinking and enhanced structural integrity. This study confirmed the in vivo safety, biocompatibility, and functionality of ruthenium and blue light CXL. This method can prevent toxicity caused by UV-A light and can be a rapid alternative treatment to standard crosslinking procedures.

Graphical Abstract
Dedifferentiation of caudate functional organization is linked to reduced D1 dopamine receptor availability and poorer memory function in aging
Authors: Korkki Saana M. , Johansson Jarkko , Nordin Kristin , Pedersen Robin , Bäckman Lars , Rieckmann Anna , Salami Alireza
Published: March 2024

Age-related alterations in cortico-striatal function have been highlighted as an important determinant of declines in flexible, higher-order, cognition in older age. However, the mechanisms underlying such alterations remain poorly understood. Computational accounts propose age-related dopaminergic decreases to impoverish neural gain control, possibly contributing to reduced specificity of cortico-striatal circuits, that are modulated by dopamine, in older age. Using multi-modal neuroimaging data (fMRI, PET) from a large lifespan cohort (n= 180), we assessed the relationship between dopamine D1-like receptors (D1DRs) and cortico-striatal function during rest and an n-back working memory task. The results revealed gradual age-related decreases in the specificity of functional coupling between the centrolateral caudate and cortical association networks during both rest and working memory, which in turn was associated with poorer short and long-term memory performance with older age. Critically, reduced D1DR availability in the caudate and the prefrontal cortex predicted less differentiated caudate-cortical coupling across the lifespan, in part accounting for the age-related declines observed on this metric. These findings provide novel empirical evidence for a key role of dopamine in maintaining functional specialization of cortico-striatal circuits as individuals age, aligning with computational models that propose deficient catecholaminergic neuromodulation to underpin age-related dedifferentiation of brain function.
Viral diversity and phloem transcriptional changes in Grapevine Shiraz disease infected vines
Authors: Onetto Cristobal , Nagahatenna Dilrukshi S. K. , Wang Yeniu Mickey , Pagay Vinay , Borneman Anthony
Published: March 2024

Shiraz disease (SD) is a highly destructive disease of grapevines that is associated with Grapevine Virus A (GVA) infection of vineyards in Australia and South Africa. However, little is known about the transcriptional modifications in grapevine phloem tissues induced by SD. In this study, we explored the viral diversity and transcriptional changes linked to SD. Vines symptomatic for SD exhibited higher viral abundance and were also shown to be co-infected with both GVA and grapevine leafroll-associated virus (GLRaV-4) strain 9. Differential gene (DE) expression analysis revealed physiological responses ofVitis vinifera to the infection. Similar to other plant pathogen infections, SD upregulated genes associated with the systemic acquired resistance (SAR) mechanism and downregulated genes related to vine immunity. Additionally, upregulated genes suggests that callose deposition and the blocking of phloem sieve elements are likely employed byV. viniferaas a defence strategy to limit the internal spread of SD viruses.

Grapevine Shiraz disease, Grapevine Virus A, Grapevine Leafroll Associated virus, Systemic Acquired Resistance, Transcriptomics
Manipulating plant development by editing histone methylation with the dCas9 tool: theCUC3boundary gene as a case study
Authors: Fal Kateryna , Masson Marie Le , Berr Alexandre , Carles Cristel C.
Published: March 2024

Chromatin modifications are deemed to associate with gene expression patterns, yet their causal function on transcription and cell fate remains unestablished. Here, we demonstrate the direct impact of an epigenome editing tool designed to remove a key chromatin modification at a precise locus in living plants, with outcomes from the molecular to the developmental scale.

The manipulated mark, H3K27me3, deposited at Lysine 27 of Histone 3 by the methyltransferase Polycomb PRC2 complex, is associated with the repression of developmental genes. As a new approach to investigate this histone mark genuine function, we used a dCas9-derived tool to bring a specific demethylase function at theCUP SHAPED COTYLEDON 3(CUC3)organ frontier gene, aiming to remove the trimethyl mark at H3K27. We show that the removal of H3K27me3 at the locus causally induces activation ofCUC3expression within its regular territory, as well as ectopically. Our precise perturbation strategy reveals that alterations in a chromatin mark lead to changes in transcription and developmental gene expression patterning, with sharp consequences on plant morphogenesis and growth.

Our work thus constitutes a proof of concept for the effective use of epigenome editing tools in unveiling the causal role of mark dynamics, supported by both molecular and developmental evidences.
The impact of wildtype SARS-CoV-2 on fatigue and quality of life: prevalence of post COVID-19 condition in a Dutch population-based serosurveillance cohort
Authors: Mutubuki Elizabeth N. , van Hagen Cheyenne C.E. , Vos Eric R.A. , den Hartog Gerco , van der Klis Fiona R.M. , van den Wijngaard Cees C. , de Melker Hester E. , van Hoek Albert Jan
Published: March 2024

Background

Our aim was to assess the relationship between (time since) wild-type SARS-CoV-2 infection and health-related quality of life (HRQoL) and fatigue as endpoints linked to Post COVID-19 condition (PCC).

Methods

Participants ≥15 years were selected from the February 2021 round of the population-based PIENTER Corona study. We investigated the association between (time since) SARS-COV-2 infection and health outcomes: HRQoL (health utility (SF-6D); physical health and mental health (both SF-12)) and fatigue (CIS-fatigue) using multivariable logistic regression analyses adjusted for age, sex, educational level, number of comorbidities, COVID-19 vaccination status, and the intensity of restrictions. For each outcome, multivariable logistic regression models were fitted at cut-off points selected based on the cumulative distribution of those uninfected.

Results

Results shown correspond to the cut-off point related to the worst off 15% of each outcome. Significant differences between those uninfected (n=4,614) and cases infected ≤4 months ago (n=368) were observed for health utility (OR [95%CI]: 1.6 [1.2-2.2]), physical health (OR [95%CI]: 1.7 [1.3-2.3]) and fatigue (OR [95%CI]: 1.6 [1.2-2.0]), but not for mental health. There were no significant differences between uninfected and cases infected >4 months ago (n=345) for all outcomes.

Conclusions

In a Dutch population-based cohort of seroconverted individuals, those infected with wild-type SARS-CoV-2 ≤4 months ago more often reported poor health utility and physical health and were more often severely fatigued compared to those uninfected (at the 15% cut-off). HRQoL and fatigue remained below the detection limit for those infected >4 months ago, suggesting a relatively low prevalence of PCC.
Synapse specific and plasticity-regulated AMPAR mobility tunes synaptic integration
Authors: Nowacka Agata , Getz Angela M. , Zieger Hanna L. , Bessa-Neto Diogo , Breillat Christelle , Daburon Sophie , Lemoigne Cécile , Marais Sébastien , Ducros Mathieu , Penn Andrew C. , Sainlos Matthieu , Choquet Daniel
Published: March 2024

Synaptic responses adapt to fast repetitive inputs during bursts of neuronal network activity over timescales of milliseconds to seconds, either transiently facilitating or depressing. This high-frequency stimulus-dependent short-term synaptic plasticity (HF-STP) relies on a number of molecular processes that collectively endow synapses with filtering properties for information processing, optimized for the transmission of certain input frequencies and patterns in distinct circuits1–3. Changes in HF-STP are traditionally thought to stem from changes in pre-synaptic transmitter release1,2, but post-synaptic modifications in receptor biophysical properties or surface diffusion also regulate HF-STP4–11. A major challenge in understanding synapse function is to decipher how pre- and post-synaptic mechanisms synergistically tune synaptic transmission efficacy during HF-STP, and to determine how neuronal activity modifies post-synaptic signal computation and integration to diversify neuronal circuit function. Here, taking advantage of new molecular tools to directly visualize glutamate release12and specifically manipulate the surface diffusion of endogenous AMPAR in intact circuits13, we define the respective contributions of pre-synaptic glutamate release, AMPAR desensitization and surface mobility to frequency-dependent synaptic adaptation. We demonstrate that post-synaptic gain control and signal integration capacity in synaptic networks is influenced by synapse-specific differences in AMPAR desensitization and diffusion-trapping characteristics that are shaped by molecular signaling events recruited during LTP.
Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma
Authors: Ghisai Santoesha A , van Hijfte Levi , Vallentgoed Wies R , Tesileanu C Mircea S , de Heer Iris , Kros Johan M , Sanson Marc , Gorlia Thierry , Wick Wolfgang , Vogelbaum Michael A , Brandes Alba A , Franceschi Enrico , Clement Paul M , Nowak Anna K , Golfinopoulos Vassilis , van den Bent Martin J , French Pim J , Hoogstrate Youri
Published: March 2024

Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological grading is however difficult and, apart from CDKN2A/B homozygous deletions in IDH-mutant astrocytomas, there are no other objective molecular markers used for grading. Experimental Design: RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n=138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide. We integrated the RNA sequencing data with matched DNA-methylation and NGS data. We also used multi-omics data from IDH-mutant astrocytomas included in the TCGA dataset and validated results on matched primary and recurrent samples from the GLASS-NL study. We used the DNA-methylation profiles to generate a Continuous Grading Coefficient (CGC) that is based on classification scores derived from a CNS-tumor classifier. We found that the CGC was an independent predictor of survival outperforming current WHO-CNS5 and methylation-based classification. Our RNA-sequencing analysis revealed four distinct transcription clusters that were associated with i) an upregulation of cell cycling genes; ii) a downregulation of glial differentiation genes; iii) an upregulation of embryonic development genes (e.g. HOX, PAX and TBX) and iv) an upregulation of extracellular matrix genes. The upregulation of embryonic development genes was associated with a specific increase of CpG island methylation near these genes.
Model-driven engineering ofCutaneotrichosporon oleaginosusATCC 20509 for improved microbial oil production
Authors: Duman-Özdamar Zeynep Efsun , Julsing Mattijs K. , Verbokkem Janine A.C. , Wolbert Emil , dos Santos Vitor A.P. Martins , Hugenholtz Jeroen , Suarez-Diez Maria
Published: March 2024

Consumption of plant-based oils, especially palm oil, is increasing at an alarming rate. This boosted demand for palm oil has drastic effects on the ecosystem as its production is not sustainable.C. oleaginosusis an oleaginous yeast with great potential as a source for microbial-based oil production which is a sustainable alternative to palm oil. However, microbial processes are not yet economically feasible to replace palm oil, unto a large extent due to limited lipid accumulation in the microbe, which limits titers and productivity. Therefore, obtaining enhanced lipid accumulation is essential to render this process commercially viable. Herein we deployed a systematic, iterative Design-Build-Test-Learn (DBTL) approach to establishC. oleaginosusas an efficient fatty acid production platform. In the design step, we identified genes and medium supplements that improved lipid content. To this end, we compared its transcriptional landscape in conditions with high and low amounts of lipid production. A metabolic map was reconstructed and integrated with the expression data. Finally, the genome-scale metabolic model ofC. oleaginosuswas used to explore metabolism under maximal growth and maximal production conditions. The combination of these four analyses led to the selection of four overexpression targets (ATP-citrate lyase (ACL1), acetyl-CoA carboxylase (ACC), threonine synthase (TS), and hydroxymethylglutaryl-CoA synthase (HMGS)) and five media supplements (biotin, thiamine, threonine, serine, and aspartate). We established an electroporation-based co-transformation method to implement selected genetic interventions. These findings were experimentally validated in the build and test steps of the DBTL approach by adding supplements into the medium and overexpressing the identified genes. Characterization of ACL, ACC, and TS at various C/N ratios, and the addition of medium supplements provided up to 56% (w/w) lipid content, and a 2.5-fold increase in total lipid in the glycerol and urea-based defined medium. In the learn step, quadratic models identified the optimum C/N ratios shifted towards around C/N240. These results firmly confirmC. oleaginousas a sustainable alternative to replace palm as an oil source.

Highlights

Transcriptional profile and metabolic model analyzed, predicting genetic targets and medium supplements.

Genetic targets and medium supplements for improved oil production.

The genetic toolbox forC. oleaginosuswas expanded (co-transformation method, promoters, genes, and terminators).

Experimental validations showed that biotin, and threonine increased lipid content.

Overexpression ofACL1, ACC,andTSinC. oleaginosusprovided higher oil content.

Graphical Abstract
The origin and evolution of cultivated rice and genomic signatures of heterosis for yield traits in super-hybrid rice
Authors: Liu Daliang , Yin Hao , Li Tao , Wang Liang , Lu Song , Yu Houlin , Sun Xinhao , Zhang Taikui , Zhao Quanzhi , Zhao Yiyong
Published: March 2024

Unraveling evolutionary history and genomic basis of heterosis is fundamental for advancing rice productivity. We developed a genome-scale phylogeny ofOryzeaeby coalescing 39,984 gene trees. Our analysis supports parallel, independent origins and nearly synchronous evolutionary trajectories leading to the subsequent domestication ofindicaandjaponica, evidenced by molecular dating and synonymous substitution rates for syntenic and domestication-associated genes. Our survey of 1,383 gene duplications in ancestor ofO. sativauncovers their roles in vital biological processes, highlighting the significance in environmental adaptability. Additionally, we confirm the lack of hybridization event among subspecies ancestors through gene tree topology and D-statistical analyses. We generated 71.67 GB whole-genome sequencing data for five super-hybrid rice varieties and their progenitors, revealing differential positive selection and genetic exchanges between subspecies, essential for heterosis formation. Crucially, our study underscores the role of non-additive gene expression in heterosis, particularly in genes associated with DNA repair and recombination, which may confer resistance traits. Furthermore, eQTL and de novo mutation analyses identify key developmental and stress response genes, offering targets for enhancing heterosis in rice. Overall, our research reveals crucial insights into the genetics of rice domestication and heterosis, offering a genomic resource to improve rice’s agricultural productivity.
BRD8 guards the pluripotent state by sensing and maintaining histone acetylation
Authors: Sun Li , Fu Xiuling , Xiao Zhen , Ma Gang , Zhou Yibin , Hu Haoqing , Shi Liyang , Li Dongwei , Jauch Ralf , Hutchins Andrew
Published: March 2024

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permissive differentiation. However, the epigenetic control mechanisms are not well understood. Here, we show that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive-specific genes. When Brd8 expression was reduced, chromatin accessibility was unchanged, but histone acetylation at primed-specific genes was reduced. Conversely, naive-specific genes had reduced repressive chromatin marks, and acquired accessible chromatin more rapidly during the cell type conversion. We show that this process requires active histone deacetylation to promote the conversion of primed to naive. Our data supports a model for BRD8 reading histone acetylation to accurately localize the genome-wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability.
Characteristics of school effectiveness at the level of colleges of education in Ghana
Authors: Alagbela Alaric Awingura , Bayuo Jonas
Published: March 2024

Purpose

School effectiveness has attracted some currency in educational research globally since the 1960s though such studies mostly point to the efforts of principal leadership as the basis for promoting effective schools. However, in the case of Ghana, there is a lack of research conducted in the area, and due to that, this study sought to explore internal public perspectives of what constitutes school effectiveness in the Colleges of Education in the Upper East Region of Ghana.

Design/methodology/approach

This study employed the convergent parallel mixed-method design otherwise called concurrent mixed-method design. The population for the study comprised second and third-year students, tutors and leadership of the colleges. In total, 308 respondents constituted the sample size. The breakdown is 257 students in all, 41 tutors and 10 leaders of the colleges. Two instruments, namely, an in-depth interview guide and a questionnaire were used to elicit responses to address the object of this study.

Findings

The study revealed that the characteristics of effective schools include the high academic performance of students and a good show of disciplined behavior by both students and staff in the colleges among others.

Originality/value

To the best of our knowledge, during the search for studies conducted on school effectiveness, there is no scientific study done in Ghana highlighting the attributes of effective educational institutions. Most of the studies conducted in the area of educational studies only focused on principal leadership, educational access, participation and equity at the level of pre-tertiary institutions.
Artificial intelligence applications implication for ESG performance: can digital transformation of enterprises promote sustainable development?
Authors: Chen Rongxin , Zhang Tianxing
Published: March 2024

Purpose

In the global context, artificial intelligence (AI) technology and environmental, social and governance (ESG) have emerged as central drivers facilitating corporate transformation and the business model revolution. This paper aims to investigate whether and how the application of AI enhances the ESG performance of enterprises.

Design/methodology/approach

This study uses panel data from Chinese A-share listed companies spanning the period from 2012 to 2022. Through a multivariate regression analysis, it examines the impact of AI on the ESG performance of enterprises.

Findings

The findings suggest that the application of AI in enterprises has a positive impact on ESG performance. Internal control systems within the organization and external information environments act as mediators in the relationship between AI and corporate ESG performance. Furthermore, corporate compliance plays a moderating role in the connection between AI and corporate ESG performance.

Originality/value

This paper underscores the pivotal role played by AI in enhancing corporate ESG performance. It explores the pathways to improving corporate ESG behavior from the perspectives of internal control and information environments. This discussion holds significant implications for advancing the application of AI in enterprises and enhancing their sustainable governance capabilities.
Digital market and its adequacy of merger assessment in Indonesian business competition law
Authors: Sukarmi Sukarmi , Tejomurti Kukuh , Silalahi Udin
Published: March 2024

Purpose

This study aims to analyze the development of digital market characteristics particularly focusing on how the strategic choices of platforms are not fully reflected in pricing. In addition, the implications for the development of theories of harm are investigated to explore the necessity of a relevant market definition in assessing infringement and evaluating the adequacy of Indonesian competition law.

Design/methodology/approach

This study is a legal analysis that uses statutory approaches, cases, comparative law and the development of theories of harm in digital mergers. The case approach is conducted by analyzing three cases decided by the Indonesia Business Competition Supervisory Commission. This approach provides insight into the response of Komisi Pengawas Persaingan Usaha concerning the merger and acquisition cases in the digital era as well as the provision of different analyses in conventional markets. However, competition can be potentially damaged in digital markets and a comparative law approach is taken by analyzing digital merger cases decided by authorities in other countries.

Findings

Results reveal that the digital market has created a “relevant market” that is challenging and blurred due to multi-sided network effects and consumer data usage characteristics. Platform-based enterprises’ prices fluctuate due to the digital market’s network effect and consumer data statistics. Smartphone prices depend on the number of apps and consumer data. Neoclassical theory focusing on product markets and location applied in Indonesia must be revised to establish a relevant digital economy market. To evaluate digital mergers, new harm theories are needed. The merger should also protect consumer data. Law Number 27 of 2022 on Personal Data Protection and Government Regulation on the Implementation of Electronic Systems and Transactions protects online consumers, a basic step in due diligence for digital mergers. The Indonesian Government should promptly strengthen the notion of “relevant markets” in the digital economy, which could lead to fair business competition violations like big data control. Notify partners or digital merger participants of the accessibility of sensitive data like transaction history and user location.

Originality/value

The development of digital market characteristics has implications for developing theories of harm in digital markets. Indonesian competition law needs to develop such theories of harm to analyze the potential for anticompetitive digital mergers in the digital economy era.
Six sigma project generation and selection: an action research study
Authors: Condé Giovanni Cláudio Pinto , Toledo José Carlos , Martens Mauro Luiz
Published: March 2024

Purpose

The purpose of this paper is to test and develop a method for generation and selection of six sigma projects. This is done by testing the use of the generation and selection method for six sigma projects (GSM_SSP) in a Brazilian manufacturing industry with the participation of managers, aiming to gather the user’s perspective and improvement opportunities for the approach itself.

Design/methodology/approach

The work adopts the action research (AR) approach once the researchers were busily involved in the training, implementation and use of the GSM_SSP. The intervention was performed in on a series of 15 workshops, with a group of managers, during six months.

Findings

The application of the eight steps of the GSM_SSP approach assisted the company’s management team to generate nine project candidates and also to select three six sigma projects. This study also finds and discusses barriers and lessons learned used to improve the GSM_SSP.

Research limitations/implications

This study presents an example of how six sigma project generation and selection has been applied to a manufacturing industry by adapting AR to the process using the eight steps of GSM_SSP, demonstrating how the management team was involved. This study should be replicated in different companies because AR is limited in its generalization.

Originality/value

To the best of the authors’ knowledge, this study represents the first use of AR methodology in six sigma project selection. This study contributes a method that can generate and select six sigma projects. In doing so, the research offers a simple approach that can be used by managers. In addition, the steps of the approach before selection were explored.
Are women satisfied with childbirth services provided in public health facilities? Evidence from two districts in Bihar, India
Authors: Youkta Kumari , Paramanik Rajendra Narayan
Published: March 2024

Purpose

This study aims to measure the level of satisfaction among women with childbirth services provided at public health facilities. Further, to analyse the impact of their socio-economic and obstetric characteristics on their level of satisfaction.

Design/methodology/approach

To accomplish these objectives a cross-sectional survey was conducted in two districts of an Indian state, Bihar. Structured questionnaire was developed based on the scale proposed by Okumu and Oyugi (2018) both for vaginal and caesarean birth patients. For empirical analysis multiple linear regression model was employed.

Findings

Results suggest that majority of mothers are satisfied with the care they received during childbirth, regardless of whether they chose a caesarean (55%) or vaginal delivery (53%). Women report the lowest levels of satisfaction with postpartum care and the privacy that was preserved by healthcare personnel at health facility. Further the study also confirms the association between patient’s socio-economic characteristics and their satisfaction level.

Originality/value

This is the first study of its kind to highlight the situation of public healthcare system in Bihar, which is the third most populated state in India with poor social and health indicators.
Self-organization, networks and sustainable innovations in microfinance institutions: Does organizational resilience matter?
Authors: Wakibi Aziz , Ntayi Joseph , Nkote Isaac , Tumwine Sulait , Nsereko Isa , Ngoma Muhammad
Published: March 2024

Purpose

The purpose of this study is to explore the interplay among self-organization, networks and sustainable innovations within microfinance institutions (MFIs) and to examine the extent to which organizational resilience plays a significant role in shaping these dynamics as a mediator.

Design/methodology/approach

This paper adopted a cross-sectional research design combined with analytical and descriptive approach to collect the data. Smart partial least squares structural equation modeling (PLS-SEM) was used to construct the measurement model and structural equation model to test the mediating effect under this study.

Findings

The results revealed that organizational resilience is a significant mediator in the relationship between self-organization, networks and sustainable innovations among microfinance institutions in Uganda.

Research limitations/implications

The data for this study were collected only from microfinance institutions in Uganda. Future studies may collect data from other formal financial institutions like commercial banks and credit institutions to test the mediating effect of organizational resilience. More still, the study adopted only a single approach of using a questionnaire. However, future research through interviews may be desirable. Likewise this study was cross-sectional in nature. Therefore, a longitudinal study may be useful in future while investigating the mediating role of organizational resilience traversing over a long time frame.

Practical implications

A possible implication is that microfinance institutions which desire to have sustainable innovative solutions for their business operations in disruptive circumstances may need to scrutinize their capacity to be resilient and self-organize.

Social implications

Microfinance institutions play a great role to the underserved clients. Thus, for each to re-organize to be able to provide services that meet users’ needs, without physical products so as to ensure long-term financial and social welfare combined with the ability to bounce back and adapt in times of economic downturn to avoid mission adrift.

Originality/value

While most studies have been carried out on organizational resilience, this paper takes center stage and is the first to test the mediating role of organizational resilience in the relationship between self-organization, networks and sustainable innovations, especially in microfinance institutions in Uganda. This paper generates strong evidence and contributes to the powerful influence of organizational resilience in enhancing the level of sustainable innovations based on self-organization and networks.
PDMSC: privacy-preserving decentralized multi-skill spatial crowdsourcing
Authors: Meng Zhaobin , Lu Yueheng , Duan Hongyue
Published: March 2024

Purpose

The purpose of this paper is to study the following two issues regarding blockchain crowdsourcing. First, to design smart contracts with lower consumption to meet the needs of blockchain crowdsourcing services and also need to design better interaction modes to further reduce the cost of blockchain crowdsourcing services. Second, to design an effective privacy protection mechanism to protect user privacy while still providing high-quality crowdsourcing services for location-sensitive multiskilled mobile space crowdsourcing scenarios and blockchain exposure issues.

Design/methodology/approach

This paper proposes a blockchain-based privacy-preserving crowdsourcing model for multiskill mobile spaces. The model in this paper uses the zero-knowledge proof method to make the requester believe that the user is within a certain location without the user providing specific location information, thereby protecting the user’s location information and other privacy. In addition, through off-chain calculation and on-chain verification methods, gas consumption is also optimized.

Findings

This study deployed the model on Ethereum for testing. This study found that the privacy protection is feasible and the gas optimization is obvious.

Originality/value

This study designed a mobile space crowdsourcing based on a zero-knowledge proof privacy protection mechanism and optimized gas consumption.
Innovative applications of whey protein for sustainable dairy industry: Environmental and technological perspectives—A comprehensive review
Authors: El‐Aidie Safaa A. M. , Khalifa Gamal S. A.
Published: March 2024

Industrial waste management is critical to maintaining environmental sustainability. The dairy industry (DI), as one of the major consumers of freshwater, generates substantial whey dairy effluent, which is notably rich in organic matter and thus a significant pollutant. The effluent represents environmental risks due to its high biological and chemical oxygen demands. Today, stringent government regulations, environmental laws, and heightened consumer health awareness are compelling industries to responsibly manage and reuse whey waste. Therefore, this study investigates sustainable solutions for efficiently utilizing DI waste. Employing a systematic review approach, the research reveals that innovative technologies enable the creation of renewable, high‐quality, value‐added food products from dairy byproducts. These innovations offer promising sustainable waste management strategies for the dairy sector, aligning with economic interests. The main objectives of the study deal with, (a) assessing the environmental impact of dairy sector waste, (b) exploring the multifaceted nutritional and health benefits inherent in cheese whey, and (c) investigating diverse biotechnological approaches to fashion value‐added, eco‐friendly dairy whey‐based products for potential integration into various food products, and thus fostering economic sustainability. Finally, the implications of this work span theoretical considerations, practical applications, and outline future research pathways crucial for advancing the sustainable management of dairy waste.
Ablation of secreted phosphoprotein‐1 in hepatocytes increases fatty acid oxidation and ameliorates alcohol‐associated liver disease
Authors: Das Sukanta , Subramaniyam Nithyananthan , Alén Rosa , Komakula Sai Santosh Babu , Song Zhuolun , Ge Xiaodong , Han Hui , Desert Romain , Athavale Dipti , Magdaleno Fernando , Chen Wei , Barahona Ines , Lantvit Daniel , Guzman Grace , Nieto Natalia
Published: March 2024

Background

Previously, we demonstrated that Spp1−/− mice exhibit a greater susceptibility to alcohol‐induced liver injury than wild‐type (WT) mice. Notably, alcohol triggers the expression of osteopontin (encoded by SPP1) in hepatocytes. However, the specific role of hepatocyte‐derived SPP1 in either mitigating or exacerbating alcohol‐associated liver disease (AALD) has yet to be elucidated. We hypothesized that hepatocyte‐derived SPP1 plays a role in AALD by modulating the regulation of steatosis.

Methods

We analyzed hepatic SPP1 expression using four publicly available datasets from patients with alcoholic hepatitis (AH). Additionally, we examined SPP1 expression in the livers of WT mice subjected to either a control or ethanol Lieber‐DeCarli (LDC) diet for 6 weeks. We compared the relationship between SPP1 expression and significantly dysregulated genes in AH with controls using correlation and enrichment analyses. To investigate the specific impact of hepatocyte‐derived SPP1, we generated hepatocyte‐specific Spp1 knock‐out (Spp1ΔHep) mice and subjected them to either a control or ethanol Lieber‐DeCarli diet for 6 weeks.

Results

Alcohol induced hepatic SPP1 expression in both humans and mice. Our analysis, focusing on genes correlated with SPP1, revealed an enrichment of fatty acid oxidation (FAO) in three datasets, and peroxisome proliferator‐activated receptor signaling in one dataset. Notably, FAO genes correlating with SPP1 were downregulated in patients with AH. Ethanol‐fed WT mice exhibited higher serum‐free fatty acids (FFAs), adipose tissue lipolysis, and hepatic fatty acid (FA) transporters. In contrast, ethanol‐fed Spp1ΔHep mice displayed lower liver triglycerides, FFAs, and serum alanine transaminase and greater FAO gene expression than WT mice, indicating a protective effect against AALD. Primary hepatocytes from Spp1∆Hep mice exhibited heightened expression of genes encoding proteins involved in FAO.

Conclusions

Alcohol induces the expression of SPP1 in hepatocytes, leading to impaired FAO and contributing to the development of AALD.
Girls with idiopathic central precocious puberty did not display substatial changes in body mass index after treatment with gonadotropin‐releasing hormone analogues
Authors: Uldbjerg Cecilie Skaarup , Lim Youn‐Hee , Renault Christoffer Højrup , Hansen Dorte , Juul Anders , Bräuner Elvira Vaclavik , Jensen Rikke Beck
Published: March 2024

Aim

To evaluate changes in body mass index (BMI) in girls during and after treatment for idiopathic central precocious puberty (iCPP).

Methods

We studied 123 girls receiving gonadotropin‐releasing hormone analogue (GnRHa)treatment for iCPP from 2009 to 2019. Pubertal and anthropometric measurements were monitored at routine clinical visits. BMI standard deviation scores (SDS) were estimated at baseline and followed in two stages from baseline to end of treatment (median 18.9 months) and from end of treatment to end of follow‐up (median 18.2 months). The influence of baseline BMI SDS and the frequency and dose of treatment was evaluated using BMI trajectories and latent class mixed models.

Results

The median age at treatment initiation was 8.5 years. The median BMI SDS at baseline was 0.7, corresponding to a median BMI of 17.4 kg/m2. Overall, no changes in BMI SDS were observed during treatment. According to baseline BMI subgroups, an increasing trend in BMI trajectories during treatment was observed for girls in the lowest BMI group. After treatment, most girls maintained stable BMI levels.

Conclusion

Our retrospective study did not provide evidence that GnRHa treatment for iCPP had a significant impact on BMI trajectories in girls.
Glucagon‐like peptide‐1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta‐analysis and meta‐regression
Authors: Rivera Frederick Berro , Lumbang Grace Nooriza O. , Gaid Danielle Rose Magno , Cruz Linnaeus Louisse A. , Magalong John Vincent , Bantayan Nathan Ross B. , Lara‐Breitinger Kyla M. , Gulati Martha , Bakris George
Published: March 2024

Aim

The cardiovascular benefits provided by glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) extend beyond weight reduction and glycaemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP‐lowering effects of GLP1‐RAs.

Methods

A comprehensive database search for placebo‐controlled randomized controlled trials on GLP‐1RA treatment was conducted until December 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with a mean difference (MD) in mmHg and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic BP (SBP) and diastolic BP. Subgroup analyses and meta‐regressions were done to account for covariates.

Results

Compared with placebo, GLP‐1RAs modestly reduced SBP [semaglutide: MD −3.40 (95% CI −4.22 to −2.59, p < .001); liraglutide: MD −2.61 (95% CI −3.48 to −1.74, p < .001); dulaglutide: MD −1.46 (95% CI −2.20 to −0.72, p < .001); and exenatide: MD −3.36 (95% CI −3.63 to −3.10, p < .001)]. This benefit consistently increased with longer treatment durations. Diastolic BP reduction was only significant in the exenatide group [MD −0.94 (95% CI −1.78 to −0.1), p = .03]. Among semaglutide cohorts, mean changes in glycated haemoglobin and mean changes in body mass index were directly associated with SBP reduction.

Conclusion

Patients on GLP‐1RA experienced modest SBP lowering compared with placebo. This observed effect was associated with weight/body mass index reduction and better glycaemic control, which suggests that BP‐lowering is an indirect effect of GLP‐1RA and unlikely to be responsible for the benefits.
Dipeptidyl peptidase‐4 inhibitor and sodium‐glucose cotransporter 2 inhibitor additively ameliorate hepatic steatosis through different mechanisms of action in high‐fat diet‐fed mice
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Dan Kazunori , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Shimoda Masashi , Nogami Yuka , Shirakiya Yoshiko , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: March 2024

Aim

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors suppress the inactivation of incretin hormones and lower blood glucose levels by inhibiting DPP‐4 function. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels in an insulin‐independent manner by inhibiting renal reabsorption of glucose. DPP‐4 and SGLT2 inhibitors each have the potential to improve hepatic steatosis; however, their combined effects remain unclear. In this study, we examined the effects of the combination of these drugs on hepatic steatosis using high‐fat diet‐fed mice.

Method

C57BL/6J male mice were fed a 60% high‐fat diet for 2 months to induce hepatic steatosis. Mice were divided into four groups (control; DPP‐4 inhibitor anagliptin; SGLT2 inhibitor luseogliflozin; anagliptin and luseogliflozin combination), and the effects of each drug and their combination on hepatic steatosis after a 4‐week intervention were evaluated.

Results

There were no differences in blood glucose levels among the four groups. Anagliptin suppresses inflammation‐ and chemokine‐related gene expression. It also improved macrophage fractionation in the liver. Luseogliflozin reduced body weight, hepatic gluconeogenesis and blood glucose levels in the oral glucose tolerance test. The combination treatment improved hepatic steatosis without interfering with the effects of anagliptin and luseogliflozin, respectively, and fat content and inflammatory gene expression in the liver were significantly improved in the combination group compared with the other groups.

Conclusion

The combination therapy with the DPP‐4 inhibitor anagliptin and the SGLT2 inhibitor luseogliflozin inhibits fat deposition in the liver via anti‐inflammatory effects during the early phase of diet‐induced liver steatosis.