bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Genetic and Genomic Connection Underlying Neurodegeneration with Brain Iron Accumulation and the Risk for Parkinson’s Disease
Authors: Jerez Pilar Álvarez , Alcantud Jose Luis , los Reyes-Ramírez Lucia de , Moore Anni , Ruz Clara , Montero Francisco Vives , Rodriguez-Losada Noela , Saini Prabhjyot , Gan-Or Ziv , Alvarado Chelsea , Makarious Mary B. , Billingsley Kimberley J. , Blauwendraat Cornelis , Noyce Alastair J , Singleton Andrew , Duran Raquel , Bandres-Ciga Sara
Published: September 2022

Background

Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation and the presence of axonal spheroids in the brain. In Parkinson’s Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in mechanisms that precipitate cell death.

Objectives

The aim of this present study was to comprehensively explore the genetic and genomic connection between NBIA and PD etiology.

Methods

We screened the presence of known and rare pathogenic mutations in autosomal dominant and recessive genes linked to NBIA in a total of 4,481 PD cases and 10,253 controls from the Accelerating Medicines Partnership Parkinsons’ Disease Program and the UKBiobank. We further examined whether a genetic burden of NBIA variants contributes to PD risk through single-gene, gene-set, and single-variant association analyses. To investigate the potential effect of NBIA gene expression on PD, we assessed publicly available expression quantitative trait loci (eQTL) data through Summary-based Mendelian Randomization and conducted transcriptomic analyses in blood of 1,886 PD cases and 1,285 controls.

Results

Out of 28 previously reported NBIA screened coding variants, four missense were found to be associated with PD risk at a nominal p value < 0.05 (p.T402M-ATP13A2, p.T207M-FA2H, p.P60L-C19orf12, p.C422S-PANK2). No enrichment of heterozygous variants in NBIA-related genes risk was identified in PD cases versus controls. Burden analyses did not reveal a cumulative effect of rare NBIA genetic variation on PD risk. Transcriptomic analyses suggested thatDCAF17is differentially expressed in blood from PD cases and controls.

Conclusions

Taking into account the very low mutation occurrence in the datasets and the lack of replication, our analyses suggest that NBIA and PD may be separate molecular entities, supporting the notion that the mechanisms underpinning iron accumulation in PD are likely not shared with NBIA. Elevated nigral iron levels may not contribute to PD etiology and may vary with anti-parkinsonian drugs used for treatment, environmental factors, or iron sequestration in tissue as a response to PD pathological change.
Differences in COVID-19 cyclicity and predictability among U.S. counties and states reflect the effectiveness of protective measures
Authors: Bozzuto Claudio , Ives Anthony R.
Published: September 2022

Data available for COVID-19 in the USA make it possible to assess the dynamics of disease spread with 20:20 hindsight. Here, we analyze archived data to explain variation among counties and states in the cyclicity and predictability (that is, the extent to which predictions are possible) of disease dynamics, using a combination of statistical and simulation models. For the period after the initial outbreak but before widespread vaccination (May 2020 – February 2021), we show that for half the counties and states the spread rate of COVID-19, r(t), was predictable at most 9 weeks and 8 weeks ahead, respectively, corresponding to at most 40% and 35% of an average cycle length of 23 weeks and 26 weeks. However, there were large differences among counties and states, and high predictability was associated with high cyclicity of r(t). Furthermore, predictability was negatively associated with R0 values from the pandemic’s onset. This suggests that a severe initial outbreak induced strong and sustained protective measures to lower disease transmission, and these protective measures in turn reduced both cyclicity and predictability. Thus, decreased predictability of disease spread should be viewed as a by-product of positive and sustained steps that people take to protect themselves and others.

Significance statement

During the COVID-19 pandemic, many quantitative approaches were employed to predict the course of disease spread. However, forecasting faces the challenge of inherently unpredictable spread dynamics, setting a limit to the accuracy of all models. For counties and states in the USA, we document very high variation in predictability after the initial outbreak and before widespread vaccination. Jurisdictions with high predictability were those that showed pronounced cyclic re-emergences (‘waves’). The variation in predictability can be explained by differences in the human responses to disease: jurisdictions in which individuals and authorities took strong and sustained protective measures against COVID-19 successfully curbed subsequent waves of disease spread, but at the same time unintentionally decreased its predictability.
Global proteome metastability response in isogenic animals to missense mutations and polyglutamine expansions in aging
Authors: Sui Xiaojing , Prado Miguel A. , Paulo Joao A. , Gygi Steven P. , Finley Daniel , Morimoto Richard I.
Published: September 2022

The conformational stability of the proteome has tremendous implications for the health of the cell and its capacity to determine longevity or susceptibility to age-associated degenerative diseases. For humans, this question of proteome conformational stability has the additional complexity from non-synonymous mutations in thousands of protein coding genes challenging the capacity of the proteostasis network to properly fold, transport, assemble and degrade proteins. Here, we quantify the proteome-wide capacity to such challenges using the isogenic organism Caenorhabditis elegans by examining the dynamics of global proteome conformational stability in animals expressing different temperature-sensitive (ts) proteins or short polyglutamine (polyQ) expansions in the context of biological aging. Using limited proteolysis of native extracts together with tandem mass tag-based quantitative proteomics, we identify proteins that become metastable under these conditions and monitor the effects on proteome solubility and abundance. Expression of different mutant proteins in the same tissue identifies hundreds to a thousand proteins that become metastable affecting multiple compartments and processes in a cell autonomous and non-autonomous manner. Comparison of the network of metastable proteins, however, reveals only a small number of common proteins. The most dramatic effects on global proteome dynamics occur in aging with one-third of the proteome undergoing conformational changes in early adulthood. These age-dependent metastable proteins overlap substantially with ts proteins and polyQ; moreover, expression of polyQ accelerates the aging phenotype. Together, these results reveal that the proteome responds to misfolding one-at-a-time to generate a metastable sub-proteome network with features of a fingerprint for which aging is the dominant determinant of proteome metastability.
Rapid response of fly populations to gene dosage across development and generations
Authors: Li Xueying C. , Gandara Lautaro , Ekelöf Måns , Richter Kerstin , Alexandrov Theodore , Crocker Justin
Published: September 2022

Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges at a systems level remains limited. Here, we have examined the phenotypic consequences of disturbing the classicbicoidnetwork inDrosophila, which is essential for anterior-posterior patterning in the early embryo. This network can be synthetically perturbed by increasing the dosage ofbicoid, which causes a posterior shift of the network’s regulatory outputs and a decrease in fitness. To directly monitor network changes across populations and time with extra copies ofbicoid, we performed genome-wide EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level. In the future, such synthetic evolution approaches using animal models could provide a generalizable platform for studying the propagation of genetic perturbations across the many layers of complex multicellular systems.
Exosome-derived lncRNA HOXA-AS3 promotes castration resistance and progression of prostate cancer via the miR-29b-3p/Mcl-1/STAT3 axis
Authors: Teng Jie , Zhao Yan , Shang Limin , Li Yang , Zhang Jian , Zhu Liang , Chen Yegang , Li Gang , Liu Zhifei , Jia Mingfei , Kang Shaosan , Niu Haitao , Niu Yuanjie , Cai Qiliang
Published: September 2022

Prostate cancer is one of the leading causes of cancer-related deaths in men. While endocrine therapy is effective in the early stage of metastasis, significantly inhibits the progression of metastatic prostate cancer, most patients eventually develop CRPC. Tumor microenvironment are involved in the progression of prostate cancer as an “accomplice”, cancer cell–secreted exosomes were identified as crucial messengers can carry lncRNAs to participate in intercellular communication. we revealed PC-3-derived exosomes promote androgen resistance in LNCaP cells. HOXA-AS3 as a ceRNA of miRNA-29b-3p affects the proliferation and invasion ability of prostate cancer cells. A series of molecular experiments, cell experiments and clinical tissue verification experiments confirmed that HOXA-AS3 participates in the castration resistance and progression of prostate cancer through regulating the miR-29b-3p/Mcl-1/STAT3/Cytochrome C/caspases-9 pathway. Dysregulation of HOXA-AS3 is observed in many cancer types, and this study shows the importance of this lncRNA in controlling prostate cancer cell progression, thus highlighting it as a potential biomarker for inhibiting prostate cancer progression and a target for immunotherapy.
TGFβ-induced long non-coding RNA LINC00313 activates Wnt signalling and promotes cholangiocarcinoma
Authors: Papoutsoglou Panagiotis , Louis Corentin , Pineau Raphaël , L’Haridon Anaïs , Banales Jesus M. , Gilot David , Aubry Marc , Coulouarn Cédric
Published: September 2022

Cholangiocarcinoma (CCA) is a poor prognosis liver cancer characterized by high aggressiveness and resistance to therapy. Long non-coding RNAs (lncRNAs) and signals imposed by oncogenic pathways, such as transforming growth factor β (TGFβ), contribute to cholangiocarcinogenesis. Here, we identified LINC00313 lncRNA as a novel target of TGFβ signalling in CCA cells. TGFβ induced LINC00313 expression in a TβRI/Smad-dependent manner. Gene expression and genome-wide chromatin accessibility profiling revealed that nuclear LINC00313 transcriptionally regulated genes involved in Wnt signalling, such as TCF7. LINC00313 gain-of-function enhanced TCF/LEF-dependent transcription, promoted colony formation in vitro and accelerated tumour growth in vivo. Genes associated with LINC00313 over-expression in human CCA were characterized by KRAS and TP53 mutations and reduced patient’s overall survival. Mechanistically, actin-like 6A (ACTL6A), a subunit of SWI/SNF chromatin remodelling complex, interacted with LINC00313 and impacted on TCF7 and SULF2 transcription. We propose a model whereby TGFβ induces LINC00313 in order to regulate expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and boosts cholangiocarcinogenesis.
DASH/Dam1 complex mutants stabilize ploidy by weakening kinetochore-microtubule attachments
Authors: Haase Max A. B. , Ólafsson Guðjón , Flores Rachel L. , Boakye-Ansah Emmanuel , Zelter Alex , Dickinson Miles Sasha , Lazar-Stefanita Luciana , Truong David M. , Asbury Charles L. , Davis Trisha N. , Boeke Jef D.
Published: September 2022

Forcing budding yeast to chromatinize their DNA with human histones manifests an abrupt fitness cost. We previously proposed chromosomal aneuploidy and missense mutations as two potential modes of adaptation to histone humanization. Here we show that aneuploidy in histone-humanized yeasts is specific to a subset of chromosomes, defined by their centromeric evolutionary origins, however, they are not adaptive. Instead we show that a set of missense mutations in outer kineto-chore proteins drive adaptation to human histones. Further, we characterize the molecular mechanism of two mutants of the outer kinetochore DASH/Dam1 complex, which reduce aneuploidy by suppression of chromosome instability. Molecular modeling and biochemical experiments show that these two mutants likely disrupt a conserved oligomerization interface thereby weakening microtubule attachments. Lastly, we show that one mutant, DAD1E50D, while suppressing chromosome instability in mitosis, leads to gross defects in meiosis. In sum, our data show how a set of point mutations evolved in the histone-humanized yeasts to counterbalance human histone induced chromosomal instability through weakening microtubule interactions, eventually promoting a return to euploidy.
HSV-1 infection induces a downstream shift of promoter-proximal pausing for most host genes
Authors: Weiß Elena , Hennig Thomas , Graßl Pilar , Djakovic Lara , Whisnant Adam W. , Jürges Christopher S. , Koller Franziska , Kluge Michael , Erhard Florian , Dölken Lars , Friedel Caroline C.
Published: September 2022

Herpes simplex virus 1 (HSV-1) infection exerts a profound shut-off of host gene expression at multiple levels. Recently, HSV-1 infection was reported to also impact promoter-proximal RNA Polymerase II (Pol II) pausing, a key step in the eukaryotic transcription cycle, with decreased and increased Pol II pausing observed for activated and repressed genes, respectively. Here, we demonstrate that HSV-1 infection induces more complex alterations in promoter-proximal pausing than previously suspected for the vast majority of cellular genes. While pausing is generally retained, it is shifted to more downstream and less well-positioned sites for most host genes. We exclude that this is an artefact of alternativede novotranscription initiation at downstream sites or read-in transcription originating from disruption of transcription termination for upstream genes. Use of downstream 2ndpause sites associated with +1 nucleosomes was previously observed upon NELF depletion. However, downstream shifts of Pol II pausing upon HSV-1 infection are much more pronounced than observed upon NELF depletion. Thus, our study reveals a novel aspect in which HSV-1 infection fundamentally reshapes host transcriptional processes with implications for our understanding of maintenance of promoter-proximal Pol II pausing in eukaryotic cells.
Treatment of Hydrocephalus by Decreasing Inflammatory Cytokine Response Using GIT 27
Authors: Zaranek Mira , Harris Carolyn
Published: September 2022

Background

Surgical insertion of a ventricular shunt initiates a cytokine response shown to play a role in shunt failure caused by obstruction. These pro-inflammatory and anti-inflammatory cytokines cause astrocytes, amongst others, to enter an activated state which causes an increase in attachment. 4,5-Dihydro-3-phenyl-5-isoxazoleacetic acid (GIT 27) is a reagent with immunomodulatory properties which acts by blocking the main signaling protein on astrocytes and microglia called toll-like receptor 4 (TLR-4).

Methods

In this experiment, we tested the effect of GIT 27 on astrocytes when used as a pre-treatment, simultaneous treatment, and post-treatment relative to shunt insertion represented by the introduction of IL-1β or IL-10. Control, DMSO vehicle control, and GIT 27 treated sample groups were assayed for cell counts and cytokine concentration data.

Results

Exposure of astrocytes to suspended GIT 27 in a DMSO vehicle caused a decrease in cell attachment and a significant decrease in the concentration of the majority of cytokines. Comparisons of GIT 27 exposure times, represented by pre-, simultaneous, and post-treatment groups, showed that pre-treatment with GIT 27 is most effective at decreasing cellular attachment where post-treatment was generally the most effective at decreasing pro-inflammatory cytokine concentrations. In future practice, this could be embodied by pharmacologic dosing prior to shunting and/or slow release from the shunt surface.

Conclusions

GIT 27 is most effective at decreasing cell counts and cytokines when in-suspension compared to when attached to the shunt surface. Our data show that GIT 27 has the potential to be used as an effective way to modulate the cytokine response associated with shunt insertion.
Parallel evolution and cryptic diversification in the common and widespread Amazonian tree, Protium subserratum
Authors: Misiewicz Tracy M. , Simmons Tracey , Carter Benjamin E. , Fine Paul V. A. , Moore Abigail J.
Published: September 2022

The lowland Amazon rainforest houses some of the greatest tree diversity on earth. While the vast majority of these species are rare, a small number are common and widespread and thus considered to play a disproportionate role in many of the global ecosystem services provided by the Amazon. However, the extent to which dominant Amazonian tree species actually include multiple clades, each on their own unique evolutionary trajectory, is unknown. Here we investigate the extent to which lineage divergence may be occurring within Protium subserratum (Burseraceae), a common and widespread tree species that is monophyletic with populations exhibiting genotypic and phenotypic differences associated with soil and geography. Utilizing a combination of phylogenomic and population genomic methods with sampling from across the range, we found that P. subserratum contains at least eight distinct clades. Specialization onto white-sand soils has evolved independently at least two times within the species; however, phenotype is not correlated with soil type. Finally, cryptic diversity at the base of the Andes is associated with elevational shifts. Together these results lend support to the hypothesis that common and widespread Amazon tree species may not represent evolutionary cohesive units. Instead, these dominant species may more commonly represent species complexes, undergoing evolutionary transitions on a trajectory to become multiple range restricted, specialist species.
Resolving inter-regional communication capacity in the human connectome
Authors: Milisav Filip , Bazinet Vincent , Iturria-Medina Yasser , Misic Bratislav
Published: September 2022

Applications of graph theory to the connectome have inspired several models of how neural signaling unfolds atop its structure. Analytic measures derived from these communication models have mainly been used to extract global characteristics of brain networks, obscuring potentially informative interregional relationships. Here we develop a simple standardization method to investigate polysynaptic communication pathways between pairs of cortical regions. This procedure allows us to determine which pairs of nodes are topologically closer and which are further than expected on the basis of their degree. We find that communication pathways delineate canonical functional systems. Relating nodal communication capacity to meta-analytic probabilistic patterns of functional specialization, we also show that areas that are most closely integrated within the network are associated with higher-order cognitive functions. We find that these regions’ proclivity towards functional integration could naturally arise from the brain’s anatomical configuration through evenly distributed connections among multiple specialized communities. Throughout, we consider two increasingly constrained null models to disentangle the effects of the network’s topology from those passively endowed by spatial embedding. Altogether, the present findings uncover relationships between polysynaptic communication pathways and the brain’s functional organization across multiple topological levels of analysis and demonstrate that network integration facilitates cognitive integration.
Achieving quantitative and accurate measurement of the human gut microbiome
Authors: Maghini Dylan , Dvorak Mai , Dahlen Alex , Roos Morgan , Kuersten Scott , Bhatt Ami S.
Published: September 2022

Robust benchmarking studies have highlighted how measured relative microbial abundances can vary dramatically depending on how DNA is extracted, made into libraries, sequenced, and analyzed. To build upon prior research, we investigated how sample preservation and storage choices impact observed absolute microbial load and relative metagenomic and metatranscriptomic measurements. Specifically, we studied how two common stool preservatives (OMNIgene GUT OMR200 and Zymo DNA/RNA PowerShield) perform across a range of storage temperatures (−80°C, 23°C and 40°C). For immediately frozen samples with no preservatives, we observed a mean colonic load of ∼100 trillion (1.2 × 1014) prokaryotes across ten donors, revising the gut prokaryote:human cell ratio of ∼1:1 to ∼4:1. We found that both preservatives introduce significant bias in the metagenomics results; and, while OMNIgene results were robust to storage temperature, samples stored in Zymo preservative had further bias with increasing storage temperatures. In terms of measured composition, we observed a ∼1.9x and ∼1.5x difference in the metagenomic Bacteroidetes:Firmicutes ratio in OMNIgene and Zymo preservatives, respectively. Absolute abundance measurements revealed that these differences are driven by higher measured Bacteroidetes in OMNIgene-preserved samples and lower measured Firmicutes in Zymo-preserved samples. For metatranscriptomic measurements, we also found that both preservatives introduced bias, but that RNA likely degraded in samples stored in OMNIgene preservative at high temperature. In summary, we recommend the OMNIgene preservative for studies that include significant field components. For metatranscriptomics studies, we recommend kits rated for RNA preservation such as the Zymo kit; however, existing samples collected in non-RNA rated kits might also be viable for limited metatranscriptomic studies. This study demonstrates how sample collection and storage choices can affect measured microbiome research outcomes, makes additional concrete suggestions for sample handling best practices, and demonstrates the importance of including absolute abundance measurements in microbiome studies.
De novo protein identification in mammalian sperm using high-resolution in situ cryo-electron tomography
Authors: Chen Zhen , Shiozaki Momoko , Haas Kelsey M. , Zhao Shumei , Guo Caiying , Polacco Benjamin J. , Yu Zhiheng , Krogan Nevan J. , Kaake Robyn M. , Vale Ronald D. , Agard David A.
Published: September 2022

Understanding molecular mechanisms of cellular pathways requires knowledge of the identities of participating proteins, their cellular localization and their 3D structures. Contemporary workflows typically require multiple techniques to identify target proteins, track their localization using fluorescence microscopy, followed by in vitro structure determination. To identify mammal-specific sperm proteins and understand their functions, we developed a visual proteomics workflow to directly address these challenges. Our in situ cryo-electron tomography and subtomogram averaging provided 6.0 Å resolution reconstructions of axonemal microtubules and their associated proteins. The well-resolved secondary and tertiary structures allowed us to computationally match, in an unbiased manner, novel densities in our 3D reconstruction maps with 21,615 AlphaFold2-predicted protein models of the mouse proteome. We identified Tektin 5, CCDC105 and SPACA9 as novel microtubule inner proteins that form an extensive network crosslinking the lumen of microtubule and existing proteins. Additional biochemical and mass spectrometry analyses helped validate potential candidates. The novel axonemal sperm structures identified by this approach form an extensive interaction network within the lumen of microtubules, suggesting they have a role in the mechanical and elastic properties of the microtubule filaments required for the vigorous beating motions of flagella.
USP22 overexpression fails to augment tumor formation in MMTV-ERBB2 mice but loss of function impacts MMTV promoter activity
Authors: Kuang Xianghong , Salinger Andrew , Benavides Fernando , Muller William J. , Dent Sharon Y. R. , Koutelou Evangelia
Published: September 2022

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously thatUsp22loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles ofUsp22into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting in mammary tumor formation. We found that USP22 overexpression in mammary glands did not further enhance primary tumorigenesis in MMTV-NIC female mice, but increased lung metastases were observed. However, deletion ofUsp22significantly decreased tumor burden and increased survival of MMTV-NIC mice. These effects were associated with markedly decreased levels of bothErbb2mRNA and protein, indicatingUsp22loss impacts MMTV promoter activity.Usp22loss had no impact on ERBB2 expression in other settings, including MCF10A cells bearing a Cytomegalovirus (CMV) - drivenERBB2transgene or in human epidermal growth factor receptor 2 (HER2)+ human SKBR3 and HCC1953 cells. Decreased activity of the MMTV promoter in MMTV-NIC mice correlated with decreased expression of known regulatory factors, including the glucocorticoid receptor (GR), the progesterone receptor (PR), and the chromatin remodeling factor Brahma-related gene-1 (BRG1). Together our findings indicate that increased expression of USP22 does not augment the activity of an activated ERBB2/NEU transgene but impacts of Usp22 loss on tumorigenesis cannot be assessed in this model due to unexpected effects on MMTV-driven Erbb2/Neu expression.
Cortical and subcortical connections change after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and predict clinical outcome
Authors: Rasgado-Toledo Jalil , Issa-Garcia Victor , Alcalá-Lozano Ruth , Garza-Villarreal Eduardo A. , González-Escamilla Gabriel
Published: September 2022

Background

Cocaine use disorder (CUD) is a worldwide public health condition which is suggested to induce pathological changes in macro- and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention to induce a reduction in CUD symptoms. Here, we sought to elucidate whether rTMS induces changes on white-matter (WM) microstructure in frontostriatal circuits after two weeks of therapy in patients with CUD, and to test whether baseline WM microstructure of the same circuits has an effect on clinical improvement. This study consisted of a 2-week, parallel group, double-blind, randomized controlled clinical trial (acute phase) (sham [n=23] and active [n=27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and HARDI-DWI at baseline and two weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared to sham rTMS in WM-tracts connecting left DLPFC with left and right vmPFC. Similarly, rTMS showed reduction in orientation dispersion in WM tracts connecting left DLPFC with left caudate nucleus, left thalamus and left vmPFC. Results also showed a greater reduction in craving VAS after rTMS when baseline ICVF was low in WM tracts connecting left caudate nucleus with substantia nigra, left pallidum, and left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in the treatment of CUD. Further, individual clinical improvement may rely on the patient’s individual structural connectivity integrity.

Highlights

White matter microstructural changes between fronto-striato-thalamic regions after 2 weeks of rTMS.

Whether rTMS would induce microstructural changes may depend on the baseline integrity of the connections between the striatum, thalamus, and the substantia nigra.

Our results highlight rTMS as a potential therapeutic tool in the treatment of CUD, due to its ability to modulate altered brain microstructure.
Fronto-Striatal Dynamic Connectivity is linked to Dopaminergic Motor Response in Parkinson’s Disease
Authors: Hensel Lukas , Seger Aline , Farrher Ezequiel , Bonkhoff Anna K. , Shah N. Jon , Fink Gereon R. , Grefkes Christian , Sommerauer Michael , Doppler Christopher E. J.
Published: September 2022

Background

Differences in dopaminergic motor response in Parkinson’s disease (PD) patients are related to specific PD subtypes. An important factor driving dopaminergic response might lie in the temporal dynamics in corticostriatal connections.

Objectives

The aim of this study is to determine if altered resting-state dynamic functional network connectivity (dFNC) is associated with dopaminergic motor response.

Methods

We assessed static and dFNC in 32 PD patients and 18 healthy controls (HC). Patients were subgrouped according to their dopaminergic motor response as low and high responders using a median split.

Results

Patients featuring high dopaminergic responses spent more time in a regionally more integrated state 1 compared to HC. Furthermore, dFNC between aMCC/dACC (anterior midcingulate cortex/dorsal anterior cingulate cortex) and putamen was lower in low responders during a more segregated state 2 and correlated with dopaminergic motor response.

Conclusions

Alterations in temporal dynamics of fronto-striatal connectivity might underlie treatment response in PD.
Food values influencing consumers' decisions in a sub-Saharan African country
Authors: Femi-Oladunni Opeyemi Afolabi , Martínez-Ruiz María Pilar , Ruiz-Palomino Pablo , Muro-Rodríguez Ana Isabel
Published: September 2022

Purpose

Given food industry manufacturers and retailers' growing economic interest in sub-Saharan Africa (SSA), this research aims to contribute to the understanding of consumer food decisions in this specific geographical area. Thus, the intention is to analyze whether there are significant differences in the appreciation of food values according to certain key demographics of consumers (related to the individual and the context) in one of the largest SSA economies: Nigeria.

Design/methodology/approach

The review of the relevant literature enabled us to propose a series of hypotheses regarding potential significant differences in the appreciation of a series of food values (in particular, price, safety, environmental impact, nutrition and weight and measures) according to variables related to the individual and the economic and social context. In order to test the hypotheses, a structured questionnaire was personally administered to 500 Lagos residents between June and July 2020. The questionnaire contained, as well as diverse questions related to the appreciation of food values selected for this study, a group of questions about the consumers' sociodemographic characteristics – at both the individual and context level. The database was analyzed using descriptive statistics and Kruskal–Wallis tests.

Findings

The results show that nutrition and weight and measurement values are the most and least appreciated food values, respectively. However, these values differ across segments determined by the chosen sociodemographic variables.

Research limitations/implications

The results of this study are preliminary and not a complete representation of the Lagos State population, and, consequently, of the Nigerian population. Additional studies in the same and other countries in SSA are needed to confirm the authors’ findings. The results, however, provide an insight into what the most likely outcomes are. A field survey was used as respondents tend not to answer online surveys spontaneously.

Practical implications

Food manufacturers and retailers should encourage consumer-operator feedback mechanisms to improve product characteristics and development. The variations found across each segment can be capitalized upon for advertising and branding food products.

Originality/value

Having selected a country in SSA for the study is an important contribution, given that few studies have focused on this geographical area.
Islamic mobile banking smart services adoption and use in Jordan
Authors: Yaseen Saad G. , El Qirem Ihab Ali , Dajani Dima
Published: September 2022

Purpose

The research identifies the predictors of Islamic mobile banking (IMB) smart services adoption and usage in Jordan.

Design/methodology/approach

Based on the Unified Theory of the Acceptance and Use of Technology (UTAUT) and the Unified Theory of the Acceptance and Use of Technology 2 (UTAUT2), an extended and modified model that encompasses perceived trust was developed. The sample comprised 358 customers from Islamic banks (IBs) in Jordan, and structural equation modelling was applied to examine data drawn from the sample.

Findings

The research framework presented 0.728% of the behavioural intention variance and 0.455% of the use behaviour. Results discovered that performance expectancy, perceived trust and hedonic motivation have significant relations with behavioural intention. The finding that effort expectancy has an insignificant effect and that social influence has a significant negative influence on behavioural intention was unexpected.

Research limitations/implications

The research has successfully verified the effect of performance expectancy, perceived trust and hedonic motivation on the customer's intention to use IMB smart services. However, the research data findings are based on the cross-sectional design.

Practical implications

The outcomes hold implications for marketing strategy makers who are responsible for promoting IMB smart services in IBs.

Originality/value

This research presents a deeper insight into IMB adoption and use. The research employed UTAUT and UTAUT2 as the baseline model and incorporates perceived trust to estimate behavioural intention. To the best of the authors' knowledge, this could be the first inquiry that examines IMB smart services adoption and use in Jordan.
Promoting collaborative learning in virtual worlds: the power of “we”
Authors: Li Yang-Jun , Cheung Christy M.K. , Shen Xiao-Liang , Lee Matthew K.O.
Published: September 2022

Purpose

As digital spaces for team collaboration, virtual worlds bring considerable verisimilitude to technology-mediated social interaction and change the process of traditional team learning. The purpose of this study is to understand how to promote collaborative learning in virtual worlds by leveraging the power of we-intention to participate in virtual worlds. The authors further use the valence–instrumentality–self-efficacy–trust model (VIST) model as a means of understanding the formation of we-intention to participate in virtual worlds, during which behavioral desire serves a bridging role.

Design/methodology/approach

The authors tested the research model using the data gathered from 298 users of a prominent form of virtual world, i.e. massively multiplayer online role-playing games. The authors used the structural equation modeling approach and the partial least squares technique for data analysis.

Findings

Results show that the four factors of the VIST model (i.e. valence on team goals, instrumentality of contribution, self-efficacy in team tasks and trust in team members) all positively influence we-intention to participate in virtual worlds through behavioral desire for team actions. We-intention to participate in virtual worlds further exerts a stronger positive effect on collaborative learning in virtual worlds, compared with I-intention to participate in virtual worlds.

Originality/value

This work advances the information systems literature by introducing a relevant and important concept, i.e. we-intention, to explain collaborative learning in virtual worlds. This study especially compared the effect of we-intention and I-intention on collaborative learning in virtual worlds. The results of this work also provide practitioners with insights into the role of we-intention in promoting collective actions in virtual worlds.
Women entrepreneurs’ success factors of Northern Indian community: a person–environment fit theory perspective
Authors: Chhabra Meghna , Singh Lata Bajpai , Mehdi Syed Asif
Published: September 2022

Purpose

Women entrepreneurs contribute significantly to Asian economies. However, women in this region face an alarming array of barriers to entrepreneurship. This research study aims to examine the factors, i.e. government support, family social support, financial literacy and managerial skills, in building the entrepreneurial capacity of women entrepreneurs under the lens of the person–environment (P-E) fit theory. Furthermore, the study also examines the moderating effect of socio-cultural barriers in the said relationships.

Design/methodology/approach

For the study, the data was collected from the owners of 311 women-owned manufacturing and services sector enterprises from the northern Indian community.

Findings

Findings suggest that all the factors significantly affect the entrepreneurial capacity of women entrepreneurs, and the barriers work as a moderator between the relationships.

Originality/value

Based on P-E fit theory, this unique research study proposes a model to test the role of factors such as government support, family social support, financial literacy and managerial skills in developing women entrepreneurs’ entrepreneurial capacity along with examining the moderating role of socio-cultural factors contributing to the entrepreneurial capacity of women.
The primary mental health care nurse specialist practice experience in primary care centers in Saudi Arabia: a qualitative study
Authors: Alhamidi Sami Abdullrahman , Alyousef Seham Mansour
Published: September 2022

Purpose

This paper aims to explore the value that care from a primary mental health care nurse (PMHCN) can bring to people with mental health (MH) problems in health-care delivery.

Design/methodology/approach

This study used a focus group of 20 PMHCNs working in primary care (PC) health settings in Saudi Arabia before using thematic content analysis to describe and explore their views and experiences of the integration of MH care into PC units. The researchers used a semi-structured interview format, which began with open-ended probes and proceeded to use of theoretical sampling based on emerging data related to their experiences and perceptions in the integration process.

Findings

Four main themes were derived from the thematic analysis of interviews: collaboration, knowledge and experience, awareness and orientation care and influential role.

Research limitations/implications

This study’s use of qualitative research methods has certain limitations, including the small sample size of 20 participants, which means that it may not be representative of all primary MH nurses in primary health-care centers in Saudi Arabia. To make the results applicable to a broader audience, the researcher sought to moderate this limitation by including participants with extensive experience in multiple settings and nurses of different ages.

Practical implications

The cost implications of the PMHCN service are not yet comprehensively understood, but it is apparent that this model is not only regarded extremely positively by MH practitioners but may also have significant benefits in terms of patient outcomes. The configuration of local services and relevant patient demographics will affect the extent to which this study’s findings are transferable. Meanwhile, further research in this area could seek to provide further evidence about the aspects of the PMHCN service model, such as secondary care referrals and waiting times, accident and emergency attendances and patient recovery rates and the impact of providing such a service on health-care practitioners as well as its cost-effectiveness.

Originality/value

This study’s findings suggest that PMHCNs believe that their care improves the quality of PC for patients in PC settings. Elements of the PC placement that professionals particularly valued include their ability to assist patients in their own community and the inclusion of volunteer stakeholders who act as preceptors. The participants expressed a need for improvement of policy related to referrals within the clinics.
Qualitative and quantitative interdependence of mechanical properties of industrially extruded AA6063 alloy on process parameters and profile characteristics
Authors: Abdul Jawwad Abdul Kareem , Al-Bashir Adnan , Saleem Muhammad , Hasanain Bassam
Published: September 2022

Purpose

This study aims to investigate and model interrelationships between process parameters, geometrical profile characteristics and mechanical properties of industrially extruded aluminum alloys.

Design/methodology/approach

Statistical design of experiments (DOE) was applied to investigate and model the effects of eight factors including extrusion ratio, stem speed, billet-preheat temperature, number of die cavities, quenching media (water/air), time and temperature of artificial aging treatment and profile nominal thickness on four mechanical properties (yield strength, ultimate tensile strength, percent elongation and hardness). Experiments were carried out at an actual extrusion plant using 8-in. diameter billets on an extrusion press with 2,200 ton capacity.

Findings

Main factors and factor interactions controlling mechanical properties were identified and discussed qualitatively. Quantitative models with high prediction accuracy (in excess of 95%) were also obtained and discussed.

Practical implications

The obtained results are believed to be of great importance to researchers and industrial practitioners in the aluminum extrusion industry.

Originality/value

All practical and relevant parameters have been used to model all important mechanical properties in a collective manner in one study and within actual industrial setup. This is in contrast to all previous studies where either a partial set of parameters and/or mechanical properties are discussed and mostly under limited laboratory setup.
Compressive behavior of hollow triply periodic minimal surface cellular structures manufactured by selective laser melting
Authors: Zhang Mingkang , Xu Meizhen , Li Jinwei , Shi Wenqing , Chen Yangzhi
Published: September 2022

Purpose

This study aims to explore the compressive behavior of hollow triply periodic minimal surface (HTPMS) cellular structures by selective laser melting (SLM).

Design/methodology/approach

This study presents a design method for gyroid hollow triply periodic minimal surfaces (G-HTPMS) and primitive hollow triply periodic minimal surfaces (P-HTPMS) cellular structures, and SLM technology was applied to manufacture these cellular structures. Compressive behaviors and energy absorption behaviors of hollow cellular structures were researched in this study.

Findings

Compared with normal gyroid triply periodic minimal surfaces (G-TPMS) and normal primitive triply periodic minimal surfaces (P-TPMS), the G-HTPMS and P-HTPMS have higher elastic modulus, plateau stress and effective energy absorption under uniaxial compression. The hollow design in HTPMS can enhance the mechanical properties and energy absorption of the cellular structure. Finite element analysis also demonstrates that the hollow design can reduce stress concentration, which improved the compressive curves from a severely fluctuating state to a relatively flat state and reduces fracture. According to compressive behaviors, G-TPMS and G-HTPMS are the bending-dominated cellular structures with strain hardening characteristics, and P-TPMS and P-HTPMS are the stretching-dominated cellular structures with strain softening characteristics.

Originality/value

This research provided a design method for HTPMS, and it was proved that the mechanical properties increased by hollow design inspired by bamboo.
Exchange rate volatility and trade flows in Indonesia and ten main trade partners: asymmetric effects
Authors: Heriqbaldi Unggul , Esquivias Miguel Angel , Handoyo Rossanto Dwi , Rifami Alfira Cahyaning , Rohmawati Hilda
Published: September 2022

Purpose

This paper aims to examine whether Indonesian cross-border trade responds asymmetrically to exchange rate volatility (ERV).

Design/methodology/approach

An exponential generalized autorgressive conditional heteroscedasticity model is applied to estimate the ERV of Indonesia and ten main trade partners using quarterly data from 2006 to 2020. A nonlinear autoregressive distributed lag estimation is applied to estimate the impact of ERV on cross-border trade. Impacts from the global financial crisis (GFC) of 2008 and the COVID-19 pandemic are covered. Dynamic panel data is used for the robustness test.

Findings

In the short-run, ERV significantly affects exports to most of the top partners (positively, negatively or both). In the long run, asymmetric effects occur in Indonesia’s exports to five top destinations. The weakening of the Indonesian Rupiah mainly supports exports in the short term. Imports from top partners are also affected by ERV in both the short run and, to a lesser extent, in the long run. Both the GFC and the COVID-19 pandemic reduced trade: for most cases, in the short run. The dynamic panel model suggests that ERV has asymmetric impact on cross-border trade in the long run.

Practical implications

Exchange rate strategies need to avoid a single-side policy approach and, instead, account for exporter and importer differences in risk behaviour and an asymmetric response to ERV in trade. Policymakers need to consider policies that stabilise the currency.

Originality/value

This study provides evidence that cross-border trade can react asymmetrically to the exchange rate uncertainty and that the impacts of real ERV are asymmetric as well. The authors also apply a dynamic panel that signals that ERV matters in the long run for Indonesian trade with top partners.