bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Anti-Adhesive Potential of Tetraspanin CD9 Peptides againstPseudomonas aeruginosain Human Keratinocytes
Authors: Murad Khairiyah , Ab-Rahim Sharaniza , Al-Talib Hassanain
Published: October 2023

Multidrug-resistantP. aeruginosastrains are becoming a public health problem worldwide, causing numerous nosocomial infections. Adhesion of bacteria to host cells is a crucial step in infection, hence interruption of this stage can reduce bacterial infection. Tetraspanin CD9 was chosen for this study as it has been implicated in the pathogenesis of bacterial infections in a previous study. The aim of this study is to investigate the adhesion inhibition of tetraspanin CD9 peptides againstP. aeruginosain human keratinocytes. HaCaT cells were infected withP. aeruginosa, prior to treatment with CD9 peptides. The CD9 peptides cytotoxicity testing was determined by MTT assay. Bacterial adhesion was also determined quantitatively by counting viable bacterial cells and qualitatively by Giemsa staining and transmission electron microscope. Inflammatory markers (IL-8 and IL-6) expression was measured by Elisa assay. CD9 peptides did not affect HaCaT cell viability and inflammatory markers release. This study successfully demonstrated that CD9 peptides reducedP. aeruginosaadherence. Colonies produced byP. aeruginosaisolates treated with CD9 peptides were significantly reduced. Giemsa staining and TEM showed that treated samples had lower bacterial density and were located farther from the cells. These data suggest that tetraspanin CD9 peptides as the potential therapeutic approach againstP. aeruginosadue to its property that inhibits bacterial adhesion without killing the bacteria, whereby at the same time does not adversely affect the nature of host cells.
Behavioral and genetic correlates of heterogeneity in learning performance in individual honeybees,Apis mellifera
Authors: Chakroborty Neloy Kumar , Leboulle Gérard , Einspanier Ralf , Menzel Randolf
Published: October 2023

Learning an olfactory discrimination task leads to heterogeneous results in honeybees with bees performing very well and others at low rates. Here we investigated this behavioral heterogeneity and asked whether it is associated with particular gene expression patterns. Bees were individually conditioned in a sequential conditioning protocol involving several phases of olfactory learning and retention tests. The rate of CS+ odor learning was found to correlate highest with a cumulative performance score extracted from all learning and retention tests. The cumulative score was used to sort the tested bees into high and low performers. Microarray analysis of gene expression in the mushroom body area of the brains of these bees disclosed a list of genes, which were differentially expressed between the high and low performers. These candidate genes are implicated in diverse biological functions, such as neurotransmission, memory formation, cargo trafficking and development.
Bacterial diversity and composition on the rinds of specific melon cultivars and hybrids from across different growing regions in the United States
Authors: Goforth Madison , Obergh Victoria , Park Richard , Porchas Martin , Crosby Kevin M. , Jifon John L. , Ravishankar Sadhana , Brierley Paul , Leskovar Daniel L. , Turini Thomas A. , Schultheis Jonathan , Coolong Timothy , Miller Rhonda , Koiwa Hisashi , Patil Bhimanagouda S. , Cooper Margarethe A. , Huynh Steven , Parker Craig T. , Guan Wenjing , Cooper Kerry K.
Published: October 2023

The goal of this study was to characterize the bacterial diversity on different melon varieties grown in different regions of the US, and determine the influence that region, rind netting, and variety of melon has on the composition of the melon microbiome. Assessing the bacterial diversity of the microbiome on the melon rind can identify antagonistic and protagonistic bacteria for foodborne pathogens and spoilage organisms to improve melon safety, prolong shelf-life, and/or improve overall plant health. Bacterial community composition of melons (n = 603) grown in seven locations over a four-year period were used for 16S rRNA gene amplicon sequencing and analysis to identify bacterial diversity and constituents. Statistically significant differences in alpha diversity based on the rind netting and growing region (p < 0.01) were found among the melon samples. Principal Coordinate Analysis based on the Bray-Curtis dissimilarity distance matrix found that the melon bacterial communities clustered more by region rather than melon variety (R2value: 0.09 & R2value: 0.02 respectively). Taxonomic profiling among the growing regions foundEnterobacteriaceae,Bacillaceae,Microbacteriaceae,andPseudomonadaceaepresent on the different melon rinds at an abundance of ≥ 0.1%, but no specific core microbiome was found for netted melons. However, a core ofPseudomonadaceae,Bacillaceae, andExiguobacteraceaewere found for non-netted melons. The results of this study indicate that bacterial diversity is driven more by the region that the melons were grown in compared to rind netting or melon type. Establishing the foundation for regional differences could improve melon safety, shelf-life, and quality as well as the consumers’ health.
Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1
Authors: Morrison Logan M. , Huang Haoran , Handler Hillary P. , Fu Min , Bushart David D. , Pappas Samuel S. , Orr Harry T. , Shakkottai Vikram G.
Published: October 2023

One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases inintrinsicmembrane excitability as the more likely mechanism underlying this novel SCA1 phenotype. Specifically, transcriptome analysis indicates that SCA1-KI IO hyperexcitability is associated with a reduced medullary expression of ion channels responsible for spike afterhyperpolarization (AHP) in IO neurons – a result that has a functional consequence, as SCA1-KI IO neuron spikes exhibit a diminished AHP. These results reveal membrane excitability as a potential link between disparate causes of IO degeneration, suggesting that HOD can result from any cause, intrinsic or extrinsic, that increases excitability of the IO neuron membrane.

Significance statement

Little is known about the factors that make inferior olive (IO) neurons susceptible to degeneration in the spinocerebellar ataxias (SCAs), a group of inherited neurodegenerative movement disorders. Another well-described form of IO degeneration, known as hypertrophic olivary degeneration (HOD), results from inhibitory denervation of the IO after brainstem injury. Here, we describe a novel finding of HOD in SCA1 without inhibitory denervation, in association with increased intrinsic membrane excitability and reduced potassium channel transcripts. This suggests that increased membrane excitability may be the underlying primary mechanism of HOD. Identifying hyperexcitability as the mechanistic driver of HOD would imply that reducing intrinsic IO excitability could be an effective strategy for treating diverse causes of both inherited and sporadic olivary degeneration.
Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs
Authors: Rahman Shafaqat M. , Buchholz David W. , Imbiakha Brian , Jager Mason C. , Leach Justin , Osborn Raven M. , Birmingham Ann O. , Dewhurst Stephen , Aguilar Hector C. , Luebke Anne E.
Published: October 2023

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. However, neurological signs of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion- related dizziness. We then evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS- CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. First, we determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic and/or endemic coronaviruses.

Importance

COVID-19 can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. Here, we first infected two commonly used wildtype mice lines (C57BL/6 and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including motion-related dizziness. Further, we showed that migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes of infection.
A Pipeline for a Primate Projectome: mapping every individual myelinated axon across the whole brain
Authors: Wildenberg Gregg , Boergens Kevin , Nikitin Viktor , Deriy Alex , De Carlo Francesco , De Andrade Vincent , Xiao Xianghui , Kasthuri Narayan
Published: October 2023

1

We developed a pipeline to detail the morphology and complete trajectory of every long distance projecting neuron in large volumes of the non-human primate brain - a projectome. A projectome would organize how the hundreds of brain regions in a primate brain communicate with each other and provide a comprehensive classification of long distance neurons. The reason such projectomes do not exist already is that there is no single imaging technique with the resolution and sampling depth capable of producing one in primates. Here we address that gap by combining new ways to cut brains with minimal tissue loss, nanoscale x-ray microscopy imaging that reveals every individual myelinated axon (MA) and the location, size, and morphology of every neuron, and algorithms for tracing individual myelinated axons for millimeters to centimeters, across tissue gaps.
Roles of SNORD115 and SNORD116 ncRNA clusters in neuronal differentiation
Authors: Helwak Aleksandra , Turowski Tomasz , Spanos Christos , Tollervey David
Published: October 2023

Prader-Willi syndrome shows features linked to brain development and hypothalamus-related endocrine abnormalities. The smallest clinical deletions fall within the large (∼650Kb) SNHG14 gene, removing 29 consecutive introns that each generate SNORD116. SNHG14 also includes 48 tandem introns encoding SNORD115 and generates multiple, extended snoRNA-related species. SNORD115 and SNORD116 resemble box C/D small nucleolar RNAs (snoRNAs) but lack known targets. Both snoRNAs strongly accumulated during neuronal differentiation. SNORD116 accumulation apparently reflected stabilization, potentially linked to the appearance of FBLL1, a homologue of the ubiquitous snoRNA-associated protein Fibrillarin (FBL). In contrast, SNORD115 was selectively transcribed, apparently due to regulated termination. For functional characterization we created cell lines lacking only the expressed, paternal, SNORD115 or SNORD116 cluster. Analyses during neuronal development indicated changes in RNA stability and protein synthesis. Altered mRNAs includedMAGEL2, mutation of which causes the PWS-like disorder Schaaf-Yang syndrome. Comparison of SNORD115 and SNORD116 mutants indicated overlapping or interacting functions. Most changes in mRNA and protein abundance appeared relatively late in development, with roles including cytoskeleton formation, extracellular matrix, neuronal arborization. Comparison with human embryonic midbrain development suggested enhanced progression in neuronal development in the snoRNA mutants. Subtle impairment of relative neuronal maturation during development, might generate the clinical phenotypes.
Synthesis and crystal structures of two solvates of 1-{[2,6-bis(hydroxymethyl)-4-methylphenoxy]methyl}-3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzene
Authors: Stapf Manuel , Schmidt Ute , Seichter Wilhelm , Mazik Monika
Published: October 2023

In the crystal structures of the formamide monosolvate (1a) and the n-propanol/H2O solvate/hydrate (1b) of the title compound, C38H50N4O3 (1), the tripodal host molecule adopts a conformation in which the substituents attached to the central benzene ring are arranged in an alternating order above and below the ring plane. As a result of the different nature of the involved guest species, the crystal components in 1a create a three-dimensional supramolecular architecture, while the crystal structure of 1b consists of two-dimensional supramolecular aggregates extending parallel to the crystallographic ab plane.
Synthesis and crystal structure of bis(9-mesityl-9,10-dihydro-10-aza-9-borabenzo[h]quinolinato-κ2
N
1,N
10)zinc(II)
Authors: Appiarius Yannik , Puylaert Pim , Staubitz Anne
Published: October 2023

The title compound, [Zn(C20H18BN2)2] (Zn

L

2
), is an overall uncharged chelate that consists of two units of an NH-deprotonated 10-aza-9-borabenzo[h]quinoline ligand (L) per ZnII center. It was synthesized in two steps by treating the protonated ligand HL with lithium bis(trimethylsilyl)amide and further conversion with diethylzinc. Its asymmetric unit comprises one ZnL fragment; the molecule is completed by application of inversion symmetry at Zn. Due to the fourfold coordination with nitrogen atoms, the zinc(II) ion is located in a distorted tetrahedral environment. Besides the relatively short N—Zn bonds, Zn

L

2
is characterized by the significant protrusion of the central ion from the plane of the ligand backbone. The crystal structure is consolidated by intra- and intermolecular π–π stacking interactions, while the polarized B—N bond is barely involved in any close atom contacts.
What does the performance appraisal approach tell us about the organizational culture's basic assumptions?
Authors: Ben-Hador Batia
Published: October 2023

Purpose

Performance appraisal (PA) is an organizational practice whose ultimate goal is to improve employee performance. This goal can be achieved using two approaches: the administrative approach, which emphasizes materialistic incentives and rewards excellent performers, and the developmental approach, which focuses on employee personal and professional development. The literature points out that organizations cannot utilize both approaches at the same time, but the reason for this is vague. Therefore, the research purpose is to bridge this gap by exploring the basic assumptions behind the administrative and developmental PA approaches as part of the hidden layers of organizational culture.

Design/methodology/approach

A qualitative document analysis (QDA) was used to analyze 124 Israeli organizations' PA forms and employee reports.

Findings

The organization's PA approaches were diagnosed as a first step in revealing the reason for the inability to use both approaches simultaneously. In the next step, it was revealed that organizational culture assumptions are the reason for the contradiction of the PA approaches. Eventually, McGregor's theory X is the basic assumption behind the administrative approach, and theory Y is the assumption behind the developmental approach. Since these two approaches contradict each other, it explains the difficulty of using both approaches simultaneously.

Originality/value

This study dives into the hidden levels of organizational culture and attempts to bridge a long-standing but still current research gap, as well as extend and refine organizational culture and performance appraisal theories.
Hospital ownership and admission rates from the emergency department, evidence from Florida
Authors: Howard David H. , David Guy
Published: October 2023

Objective

In light of Department of Justice investigations of for‐profit chains for over‐admitting patients, we sought to evaluate whether for‐profit hospitals are more likely to admit patients from the emergency department.

Data Sources

We used statewide visit‐level inpatient and emergency department records from Florida's Agency for Healthcare Administration for 2007–2019.

Study Design

We calculated differences in admission rates between for‐profit and other hospitals, adjusting for patient and hospital characteristics. We also estimated instrumental variables models using differential distance to a for‐profit hospital as an instrument.

Data Collection/Extraction Methods

Our main analysis focuses on patients ages 65 and older treated in hospitals that primarily serve adults.

Principal Findings

Adjusted admission rates among patients ages 65 and older were 7.1 percentage points (95% CI: 5.1–9.1) higher at for‐profit hospitals in 2019 (or 18.8% of the sample mean of 37.8%). Differences in admission rates have remained constant since 2009.

Conclusion

Our results are consistent with allegations that for‐profit hospitals maintain lower admission thresholds to increase occupancy levels.
LP309 a new strain of Lactiplantibacillus pentosus that improves the lactic fermentation of Spanish‐style table olives
Authors: Rodríguez‐Gómez Francisco , Valero Antonio , Vives Lara Elena , Marín Ana , Ramírez Eva María
Published: October 2023

Different varieties of table olives have suitable morphological characteristics that allow them to be processed as Spanish‐style green table olives. However, the Campiñesa cultivar presents difficulties when submitted to a lactic fermentation, in spite of being inoculated with dedicated starter cultures such as OleicaStarter. The strategy followed in this study to facilitate the start of lactic fermentation was to reinforce the OleicaStarter culture with the use of the Lactoplantibacillus pentosus Lp309 a strain that enhanced the survival of lactic acid bacteria (LAB) at the beginning of fermentation, reaching final pH values (4.08 ± 0.01), free acidity (1.00 ± 0.01 g/100 mL of brine), LAB population (6.17 ± 0.09 log CFU/mL), nutrient depletion (0.80 ± 0.09 g/kg of pulp), and lactic acid production (11.85 ± 0.72 g/L). These values allowed stabilization of the final product, thus complying with the quality and food safety standards established by the Codex Alimentarius for table olives.
Journeying towards best practice data management in biodiversity genomics
Authors: Forsdick Natalie J. , Wold Jana , Angelo Anton , Bissey François , Hart Jamie , Head Mitchell , Liggins Libby , Senanayake Dinindu , Steeves Tammy E.
Published: October 2023

Advances in sequencing technologies and declining costs are increasing the accessibility of large‐scale biodiversity genomic datasets. To maximize the impact of these data, a careful, considered approach to data management is essential. However, challenges associated with the management of such datasets remain, exacerbated by uncertainty among the research community as to what constitutes best practices. As an interdisciplinary team with diverse data management experience, we recognize the growing need for guidance on comprehensive data management practices that minimize the risks of data loss, maximize efficiency for stand‐alone projects, enhance opportunities for data reuse, facilitate Indigenous data sovereignty and uphold the FAIR and CARE Guiding Principles. Here, we describe four fictional personas reflecting differing user experiences with data management to identify data management challenges across the biodiversity genomics research ecosystem. We then use these personas to demonstrate realistic considerations, compromises and actions for biodiversity genomic data management. We also launch the Biodiversity Genomics Data Management Hub (https://genomicsaotearoa.github.io/data‐management‐resources/), containing tips, tricks and resources to support biodiversity genomics researchers, especially those new to data management, in their journey towards best practice. The Hub also provides an opportunity for those biodiversity researchers whose expertise lies beyond genomics and are keen to advance their data management journey. We aim to support the biodiversity genomics community in embedding data management throughout the research lifecycle to maximize research impact and outcomes.
Holistic care in healthy aging: Caring for the wholly and holy human
Authors: Acosta Lealani Mae Y. , Ely E. Wesley
Published: October 2023

Health care should address the holistic gap between health outcomes, spirituality, religion, and humanistic care to optimize patient care. Treating the whole person encompasses both physical and metaphysical elements. Patients want health care professionals to recognize their spiritual and religious preferences, because these matter in their approach to illness, coping, and long‐term outcomes.
Prevalence and experience of dental caries among Singaporean schoolchildren: A time‐trend analysis from 2007 to 2019
Authors: Peres Karen Glazer , Li Huihua , Tan Melissa , Lim Wanyi , Wong Yim Heng , Lai Bien , Eu Oy Chu , Peres Marco Aurelio
Published: October 2023

Objectives

This study aimed to describe caries prevalence and experience trends of permanent teeth among Singapore schoolchildren between 2007 and 2019.

Methods

Anonymized records of all 6‐year‐old Primary 1 (P1), 11‐year‐old Primary 6 (P6) and 14‐year‐old Secondary 3 (S3) before the start of each school year were extracted from the Integrated Dental Electronic Assessment System (IDEAS) by school level, ethnicity and sex. Prais–Winsten regression was used to assess trends of mean decayed, missing and filled teeth (DMFT) and caries prevalence (% DMFT > 0) among the schoolchildren by school level, with reported Average Annual Percentage Change (AAPC) together with respective 95% confidence interval (CI).

Results

In total, 519 471 P1, 566 573 P6 and 548 138 S3 were included during the above period, and the majority were comprised of Chinese children (P1: 67.2%, P6: 68.8% and S3: 71.0%, respectively). Overall, the prevalence of caries dropped from 6.9% in 2007 to 3.5% in 2019 among P1, from 34.5% in 2009 to 20.3% in 2019 among P6 and from 41.5% in 2007 to 33.5% in 2019 among S3 schoolchildren. The mean DMFT reduced from 0.11 to 0.05 among P1, 0.72 to 0.35 among P6 and 1.05 to 0.76 among S3 schoolchildren during the same period. Caries prevalence and mean DMFT were consistently higher among girls. On average, caries prevalence decreased 5% per year in P1 (AAPC −5.0 [95% CI: −6.1, −3.9]) and P6 (AAPC −4.9 [95% CI: −5.7, −4.1]) and 2% among S3 (AAPC −2.0 [95% CI: −3.5, −0.4]) schoolchildren. Caries prevalence decreased approximately 4% ~ 5% annually among P1 and P6 schoolchildren regardless of ethnicity. The average decrease in caries prevalence was lower (about 2%) among all ethnicities at S3 school level.

Conclusion

Dental caries in permanent dentition of Singaporean schoolchildren had decreased from 2007 to 2019. However, the decrease observed among primary school students was more than double that among secondary schoolchildren.
Banking concentration, financial openness, and financial development
Authors: Ghossoub Edgar A. , Harrison Andre , Reed Robert R.
Published: October 2023

We examine how financial development in the banking sector depends on the degree of capital account openness and the degree of bank concentration across countries. Using data on 136 countries, we find that the relationship of openness to credit market activity depends on the level of economic development. In high income countries, openness is only associated with higher credit market activity in concentrated banking systems. However, in developing countries, there is evidence that openness is associated with higher credit market activity regardless of concentration. Moreover, in contrast to previous work we examine how the impact of concentration depends on openness.
Efficacy of the novel guide sheath system for removing a migrated pancreatic duct stent after pancreaticoduodenectomy
Authors: Asada Shohei , Kitagawa Koh , Yoshiji Hitoshi
Published: October 2023

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Measuring auditory event‐related potentials at the external ear canal: A demonstrative study using a new electrode and error‐feedback paradigm
Authors: Arao Hiroshi , Suwazono Shugo , Kimura Akio , Asano Hirotoshi , Suzuki Hiroaki
Published: October 2023

Although ear canal electroencephalogram (EEG) recording has received interest from basic and applied research communities, evidence on how it can be implemented in practice is limited. The present study involving eight male participants including the authors presents the utility of our ear canal electrode and method by demonstrating both comparability of ear canal EEG to those at nearby sites and distinctiveness that ear canal event‐related potentials (ERPs) could have. For this purpose, we used the balanced noncephalic electrode reference and an experimental paradigm with an error‐feedback sound. Clear auditory ERPs were detected at the ear canal sites with a sufficiently low noise level comparable with those at conventional sites. The N1c, a temporal maximum subcomponent, spread over the bilateral temporal sites, including the ear canals and earlobes. While consecutive signals are generally highly similar between the ear canal and the earlobe, the N1c was larger at the ear canal than the earlobe, as demonstrated by the conventional frequentist and the hierarchical Bayesian modelling approaches. Although an evident caveat is that our sample was limited in terms of size and sex, the general capability indicates that the structure of our ear canal electrode provides EEG measurement that can be used in basic and applied settings. Our experimental method can also be an ERP‐based test that conveniently assesses the capability of existing and future ear canal electrodes. The distinctive nature of the ERPs to the error‐feedback sound may be utilized to examine the basic aspects of auditory ERPs and to test the processes involved in feedback‐guided behaviour of participants.
Epilepsy with generalized tonic–clonic seizures alone: Electroclinical features and prognostic patterns
Authors: Cerulli Irelli Emanuele , Gesche Joanna , Schlabitz Sophie , Fortunato Francesco , Catania Cecilia , Morano Alessandra , Labate Angelo , Vorderwülbecke Bernd J. , Gambardella Antonio , Baykan Betül , Holtkamp Martin , Di Bonaventura Carlo , Beier Christoph P.
Published: October 2023

Objective

Epilepsy with generalized tonic–clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients.

Methods

In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors.

Results

We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13–22) and a median follow‐up duration of 10 years (IQR = 5–20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2‐year remission was 24 months (IQR = 24–46.5) with a median number of 1 (IQR = 1–2) ASM. During the long‐term follow‐up (i.e., 202 patients followed ≥5‐years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no‐remission and relapsing–remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic–clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12‐month follow‐up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression.

Significance

GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.
Magnetic resonance imaging features to evaluate the neonatal hypoglycemia brain injury and investigation of related risk factors under the fuzzy C‐means clustering intelligent algorithm
Authors: Jin Dongmei , Zhang Zhongxu , Ma Yanru , Dai Zhushan , Zhao Lili , Ma Tongyao , Chen Guoping
Published: October 2023

This research was aimed to analyse the application value of magnetic resonance imaging based on Fuzzy C‐means (FCM) algorithm in neonatal hypoglycemia brain injury (HBI), and explore the risk factors related to the occurrence of brain injury in children, to provide guidance for clinical diagnosis and treatment. 114 children with hypoglycemia were divided into brain injury group (58 cases) and no brain injury group (56 cases) according to whether they had brain injury or not. The MRI image signal performance, general data, average minimum blood glucose value, duration of hypoglycemia, first feeding time, age of onset of hypoglycemia, and algorithm segmentation performance of the two groups of patients were observed and compared. Furthermore, the Logistic factor analysis was carried out to summarize the MRI characteristics and related risk factors of neonatal hypoglycemic brain injury. The results showed that the average minimum blood glucose (1.09 ± 0.53 mmoL/L) in the brain injury group was lower than that in the non‐brain injury group (1.75 ± 0.49 mmoL/L), and the duration of hypoglycemia (43.1 ± 21.07 h) was higher than that in the non‐brain injury group (13.79 ± 6.81 h), p < 0.05. The first feeding time and age of hypoglycemia in the brain injury group were higher than those in the non‐brain injury group, showing a difference with p < 0.05. In the brain injury group, all 58 cases showed high DWI (diffusion weighted imaging) signal at the damaged site at the early stage of MRI (magnetic resonance imaging), and 23 cases (39.66%) were involved in parieto‐occipital lobe. Image segmentation coefficient of Vpc increased significantly under FCM clustering algorithm (p < 0.05). Late first feeding time, low blood sugar level, and long duration were high risk factors for hypoglycemic brain injury. In conclusion, MRI images based on FCM clustering algorithm had higher image quality. Late first feeding time, low blood sugar level, and long duration of hypoglycemia were high risk factors for hypoglycemic brain injury.
Effects of senescence on the tumour microenvironment and response to therapy
Authors: Reynolds Louise E. , Maallin Seynab , Haston Scott , Martinez‐Barbera Juan Pedro , Hodivala‐Dilke Kairbaan M. , Pedrosa Ana‐Rita
Published: October 2023

Cellular senescence is a state of durable cell arrest that has been identified both in vitro and in vivo. It is associated with profound changes in gene expression and a specific secretory profile that includes pro‐inflammatory cytokines, growth factors and matrix‐remodelling enzymes, referred to as the senescence‐associated secretory phenotype (SASP). In cancer, senescence can have anti‐ or pro‐tumour effects. On one hand, it can inhibit tumour progression in a cell autonomous manner. On the other hand, senescence can also promote tumour initiation, progression, metastatic dissemination and resistance to therapy in a paracrine manner. Therefore, despite efforts to target senescence as a potential strategy to inhibit tumour growth, senescent cancer and microenvironmental cells can eventually lead to uncontrolled proliferation and aggressive tumour phenotypes. This can happen either through overcoming senescence growth arrest or through SASP‐mediated effects in adjacent tumour cells. This review will discuss how senescence affects the tumour microenvironment, including extracellular matrix remodelling, the immune system and the vascular compartment, to promote tumourigenesis, metastasis and resistance to DNA‐damaging therapies. It will also discuss current approaches used in the field to target senescence: senolytics, improving the immune clearance of senescent cells and targeting the SASP.
Hypoxic microenvironment promotes dermal fibroblast migration and proliferation via a BNIP3‐autophagy pathway
Authors: Zhang Can , Li Hongmei , Jiang Min , Zhang Qiong , Chen Jigang , Jia Jiezhi , Zhang Ze , Yu Huiqing , Zhang Jiaping , Zhang Junhui
Published: October 2023

Upon injury, nearby cells, including fibroblasts at the wound edge, are often found in a hypoxic microenvironment. Nevertheless, the influence of hypoxia on skin fibroblasts is poorly understood. Using previously established mouse full‐thickness wounds, we show that Bcl‐2 and adenovirus E1B 19‐kDa interacting protein 3 (BNIP3) expression was significantly elevated at the wound edge, and hypoxia treatment enhanced BNIP3 expression in fibroblasts. Interestingly, BNIP3 promoted the migration and proliferation, as well as the activation of autophagy, in fibroblasts under hypoxia. The hypoxia‐induced autophagy was found to induce the migration and proliferation of fibroblasts, a process that could be reversed by knocking down the autophagy‐related gene for autophagy protein 5, ATG5. Furthermore, hypoxia‐inducible factor 1 subunit alpha (HIF‐1α) was significantly upregulated in fibroblasts under hypoxia treatment, and HIF‐1α knockdown attenuated the hypoxia‐induced expression of BNIP3 and the migration and proliferation of fibroblasts. Altogether, our results establish the hypoxia‐BNIP3‐autophagy signaling axis as a newly identified regulatory mechanism of skin fibroblast migration and proliferation upon wounding. Autophagy intervening might thus represent a promising therapeutic strategy for patients with chronic refractory wounds.
NUT carcinoma and thoracic SMARCA4‐deficient undifferentiated tumour: facts and controversies
Authors: Yoshida Akihiko
Published: October 2023

NUT carcinoma and thoracic SMARCA4‐deficient undifferentiated tumour are unique entities in the 5th edition of the World Health Organisation (WHO) Classification of Thoracic Tumours, whose definitions include molecular genetic abnormalities. These aggressive tumours require rapid work‐ups on biopsies, but a broad list of differential diagnoses poses challenges for practising pathologists. This review provides an update on their key clinicopathological and molecular characteristics, as well as controversies regarding tumour classification and diagnostic strategy. Phenotypical assessment plays a substantial role in diagnosis because recurrent and predictable clinicopathological findings exist, including robust immunohistochemical phenotypes. Accurate diagnosis is crucial for appropriate management and a clearer understanding of the disease.
Immobilization of beta‐galactosidase on metal‐chelate‐substituted gels
Authors: BM Brena , LG Ryden , Porath J.
Published: October 2023

The use of copper, zinc, iron, nickel and calcium in three different chelating gels was investigated for preparing immobilized beta‐galactosidase. The chelated ligands [Cu(2+)‐iminodiacetate (IDA), Cu(2+)‐Tris(carboxymethyl)ethylenediamine (TED), Ni(2+)‐IDA and Fe(3+)‐IDA] absorbed the protein so strongly that it can be considered a true immobilization. The obtained enzyme derivatives were investigated with regard to activity and stability. Enzymic activity was highly preserved in general for the TED derivates (90% when compared with that for Cu(2+)‐TED). The immobilized Ni2+ derivatives were more stable to high temperature and to storage than the Cu2+ derivatives. Temperature‐stability of the immobilized enzyme was very much improved by adding a strong metal‐chelating gel such as carboxymethylated tetraethylenepentamine‐agarose. The gel could be re‐used and reloaded after elution with chelator. beta‐Galactosidase from Escherichia coli was purified using immobilized‐metal‐ion‐chelate chromatography (i.m.a.c.). The potential use of beta‐galactosidase immobilized on i.m.a.c. gels for technical purposes is discussed.
Isolation of intergeneric hybrids between Bacillus subtilis and Zymomonas mobilis and the production of thermostable amylase by hybrids
Authors: Christiansen C. , Kryvi H. , Sontum P. , Skotland T.
Published: October 2023

Stable hybrids were obtained by protoplast fusion between Bacillus subtilis and Zymomonas mobilis. All the hybrids were able to hydrolyse starch and possessed ampicillin‐ and tetracycline‐resistant phenotypes. Two of the hybrids, BZ‐1 and BZ‐2, were hyperproducers of alpha‐amylase. The enzyme produced by these hybrids exhibited increased thermostability. The results show that stable intergeneric gene transfer can be achieved through poly(ethylene glycol)‐mediated protoplast fusion between two industrially important genera of bacteria.
Purification and characterization of the endocellular beta‐glucosidase of a new strain of Candida entomophila isolated from fermenting agave (Agave sp.) juice
Authors: Gueguen Y. , Chemardin P. , Arnaud A. , Galzy P.
Published: October 2023

A yeast strain isolated in the laboratory from fermenting agave (Agave sp.) juice was studied and classified as Candida entomophila. The beta‐glucosidase of this yeast was purified by ion‐exchange chromatography and gel filtration. Its molecular mass estimated by gel filtration was 400 kDa. The oligomeric structure was determined following treatment of the purified enzyme with SDS. Its optimum pH was between 5 and 6, and its optimum temperature was 60 degrees C. The enzyme was active against soluble glucosides with (1–>3)‐beta, (1–>4)‐beta and (1–>4)‐alpha linkage configuration, and it possesses (1–>6)‐alpha‐arabinofuranosidase activity. It is competitively inhibited by glucose and by D‐gluconic acid lactone. The enzyme was constitutive and a glucosyltransferase activity is observed in the presence of ethanol. Since the glycosides present in wines and fruit juices represent a potential source of aromatic flavour, the possible use of the yeast glucosidase for the liberation of the bound aroma is discussed.
Phase evolution during conventional and reactive flash sintering of (Mg,Ni,Co,Cu,Zn)O via in situ X‐ray diffraction
Authors: Yoon Bola , Campos João V , Lavagnini Isabela R , Avila Viviana , Gardner James M , Ghose Sanjit K. , Jesus Lílian M.
Published: October 2023

Reactive flash sintering (RFS) enables the simultaneous synthesis and sintering of ceramics and has been shown to affect the reaction pathway of different materials. Herein, in situ synchrotron X‐ray diffraction (XRD) is used to investigate the (Mg,Ni,Co,Cu,Zn)O entropy‐stabilized oxide formation during: (i) conventional heating and (ii) RFS under current rate‐controlled mode. The same reaction pathway is verified in both instances: the starting rock‐salt (RS), spinel (Co3O4), tenorite (CuO), and wurtzite (ZnO) phases transform into a single RS phase with a (1 1 1) to (2 0 0) intensity ratio of 0.67, consistent with a random distribution of the cations into the structure. Pt lattice peak shift from the XRD patterns is used as standard to monitor the sample surface temperature, revealing a strong endothermic reaction during the RS single‐phase formation (Pt peaks shift toward higher angles while increasing sample temperature/current density). In RFS, the single‐phase RS structure is formed in just 60 s at a furnace temperature of 600°C and a current rate of 220 mA mm−2/min. Therefore, RFS greatly accelerates the synthesis of (Mg,Ni,Co,Cu,Zn)O, however, it does not play a role in the reaction pathway for this material formation.
Measurement invariance of the group climate inventory across adults with and without mild intellectual disability in secure residential facilities
Authors: Turhan Abdullah , Roest Jesse J. , Delforterie Monique J. , Van der Helm G. H. Peer , Neimeijer Elien G. , Didden Robert
Published: October 2023

Background

The Group Climate Inventory (GCI) was tested for measurement invariance across 332 adults with and 225 adults without mild intellectual disabilities in Dutch forensic treatment, and for latent mean differences on its Support, Growth, Repression, and Atmosphere subscales.

Method

Multigroup confirmatory factor analysis was used to evaluate the configural, threshold, and loading and threshold invariance of the GCI across both groups, and to compare group latent means on each subscale.

Results

Measurement invariance was found across groups. Latent mean group comparisons showed small but significant differences reflected in lower scores on Support and Atmosphere in the group with mild intellectual disabilities.

Conclusion

The GCI allows meaningful comparisons between clients with and without mild intellectual disabilities in secure facilities. Results from the between‐group comparisons suggest that consideration should be given as to whether, and why, the support and atmosphere perceptions of clients with mild intellectual disabilities might be less good.
Market impacts of the 2020 short selling bans
Authors: Spolaore Alessandro , Le Moign Caroline
Published: October 2023

At the height of the COVID‐19 related market stress in March 2020, six European countries implemented market‐wide short selling bans. Based on a difference‐in‐difference approach using regulatory data, our estimation finds that the bans are associated with a deterioration in liquidity and trading volumes, and a decrease in volatility, without evidence of price impact. Remarkably, the negative impact persisted after the bans' lift. Liquidity deterioration appears stronger for liquid shares‐ large‐cap, highly fragmented stocks, and stocks with listed derivatives. Sectoral effects are noticed for the stocks most affected by the market stress. Finally, no displacement effect was observed.
The Effects of Fiscal Policy When Planning Horizons are Finite
Authors: LUSTENHOUWER JOEP , MAVROMATIS KOSTAS
Published: October 2023

We study the importance of planning horizons for fiscal multipliers in a New‐Keynesian model with bounded rationality. We show that, when agents have shorter planning horizons, government spending multipliers are smaller, whereas labor tax cut multipliers are larger. Furthermore, Ricardian equivalence breaks down, and transfer shocks feature a negative multiplier. Results are driven by the cognitive limitations of finite planning horizons that lead agent's expectations to deviate from the fully rational benchmark. We find larger investment responses, which are more in line with empirical findings than those of models with longer planning horizons, rule‐of‐thumb households, or a Blanchard–Yaari structure.
Police officers' perceptions and experiences of promoting honesty in child victims and witnesses
Authors: Salhab Gadda , Akehurst Lucy , Cassidy Hannah , Talwar Victoria
Published: October 2023

Purpose

This two‐phase study employed a mixed‐methods design to explore UK police officers' perceptions and experiences of promoting honesty in child witnesses with a special focus on the recommended inclusion of Truth‐Lies Discussions (TLDs) at the start of interviews with children.

Method

In Phase 1, police officers completed an online survey designed to cover their experiences and perceptions regarding truth‐promotion with child witnesses. In Phase 2, police officers were individually interviewed to elicit an in‐depth understanding of current practice relating to this aspect of investigative interviews with children.

Results

Around half of the survey respondents believed that TLDs promote honesty in children. The majority reported always using TLDs during interviews to ensure compliance with UK best‐practice guidance. There was evidence of a misconception among some police officers that children's performance on TLDs was related to their subsequent truth‐telling behaviour. Following analysis of the interview transcripts, we found a main theme of police officers' uses of TLDs, which included (i) gauging children's conceptual understanding of truths/lies, (ii) ensuring no deviation from guidance and (iii) communicating children's credibility to the court. A second main theme revealed the challenges and obstacles police officers perceived when embarking on TLDs. These were that (i) one type of TLD is not suitable for all children, (ii) the training is insignificant and the application is inappropriate and (iii) participants sometimes use alternative strategies to promote honesty with children.

Conclusion

Police officers reported following guidance because a failure to do so would jeopordise children's testimony and provided recommendations for future practice‐informed research designs to test techniques for the promotion of honesty in child witnesses.
Interspecies transcriptomic comparison identifies a potential porto‐sinusoidal vascular disorder rat model suitable for in vivo drug testing
Authors: Campreciós Genís , Vilaseca Marina , Tripathi Dinesh M. , Montironi Carla , Díaz Alba , Aguilar Daniel , García‐Calderó Héctor , Montañés Rosa , Anton Aina , Hernández‐Gea Virginia , García‐Pagán Joan Carles
Published: October 2023

Background

Porto‐sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life‐threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease.

Methods

We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium‐enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data.

Results

All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD‐specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model.

Conclusions

The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition.