bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal-level genome assembly of golden birdwingTroides aeacus(Felder & Felder, 1860)
Authors:   Hong Kong Biodiversity Genomics Consortium, Hui Jerome H.L. , Chan Ting Fung , Chan Leo L. , Cheung Siu Gin , Cheang Chi Chiu , Fang James K.H. , Gaitan-Espitia Juan D. , Lau Stanley C.K. , Sung Yik Hei , Wong Chris K.C. , Yip Kevin Y.L. , Wei Yingying , So Wai Lok , Nong Wenyan , Pun Hydrogen S.F. , Yau Wing Kwong , Chiu Colleen Y.L. , Chan Sammi S.S. , Man Kacy K.L. , Yip Ho Yin
Published: January 2024

Troides aeacus, the golden birdwing (Lepidoptera, Papilionidae) is a large swallowtail butterfly widely distributed in Asia. Despite its occurrence,T. aeacushas been assigned as a major protective species in many places given the loss of their native habitats under urbanisation and anthropogenic activities. Nevertheless, the lack of its genomic resources hinders our understanding of their biology, diversity, as well as carrying out conservation measures based on genetic information or markers. Here, we report the first chromosomal-level genome assembly ofT. aeacususing a combination of PacBio SMRT and Omni-C scaffolding technologies. The assembled genome (351 Mb) contains 98.94% of the sequences anchored to 30 pseudo-molecules. The genome assembly also has high sequence continuity with scaffold length N50 = 12.2 Mb. A total of 28,749 protein-coding genes were predicted, and high BUSCO score completeness (98.9% of BUSCO metazoa_odb10 genes) was also revealed. This high-quality genome offers a new and significant resource for understanding the swallowtail butterfly biology, as well as carrying out conservation measures of this ecologically important lepidopteran species.
Rapid and label-free exosome analysis by surface-enhanced Raman spectroscopy using silver nanoparticle substrate based on selective laser ablation and melting of silver nanowire
Authors: Nam Hyeono , Park Jong-Eun , Hwang June Sik , Kim Seunggyu , Kim Seong Jae , Kim Sanha , Yang Minyang , Jeon Jessie S.
Published: January 2024

Early diagnostics of breast cancer is crucial to reduce the risk of cancer metastasis and late relapse. Exosome, which contains distinct information of its origin, can be the target object as a liquid biopsy. However, its low sensitivity and inadequate diagnostic tools interfere with the point-of-care testing (POCT) of the exosome. Recently, Surface-enhanced Raman spectroscopy (SERS), which enables the detection of Raman scattering, has been proved as a promising tool for exosome detection but the fabrication process of SERS probe or substrate is still inefficient and far from large-scale production. This study proposes rapid and label-free detection of breast cancer-derived exosomes by statistical analysis of Raman spectra using silver nanoparticle SERS substrate fabricated by selective laser ablation and melting. Employing silver nanowire and optimizing pulse repetition rate power enable rapid and energy-efficient fabrication of SERS substrate. The functionality including sensitivity, reproducibility, stability, and renewability was evaluated using rhodamine 6G as a probe molecule. Then, the feasibility of POCT was examined by the statistical analysis of Raman spectra of exosomes from malignant breast cancer cells and non-tumorigenic breast epithelial cells. The presented framework is anticipated to be utilized in other biomedical applications, facilitating cost-effective and large-scale production performance.
False discovery rate control: Moving beyond the Benjamini–Hochberg method
Authors: Laha Nilanjana , Koner Salil , De Sarkar Navonil
Published: January 2024

Modern bioinformatics studies often involve numerous simultaneous statistical tests, increasing the risk of false discoveries. To control the false discovery rate (FDR), these studies typically employ a statistical method called the Benjamini–Hochberg (BH) method. Often, the BH approach tends to be overly conservative and overlooks valuable biological insights associated with data structures, particularly those of groups. Group structures can manifest when closely located genomic coordinates are functionally active and closely related because of co-regulation. Recent statistical advancements have led to the development of updated BH methods tailored for datasets featuring pre-existing group structures. These methods can improve the statistical power and potentially enhance scientific discoveries. In this study, we elucidated the advantages of contemporary group-aware BH methods using a previously published microRNA (miRNA) dataset. For this dataset, group-aware BH methods identified a larger set of miRNAs with significantly deregulated expression (p-value <0.05) than the traditional BH method. These new findings are supported by existing literature on miRNAs and a related 2017 study. Our results underscore the potential of specialized BH methods for controlling the FDR in high throughput omics studies with pre-defined group structures.
Individual Differences in Belief Updating and Phasic Arousal Are Related to Psychosis Proneness
Authors: Murphy Peter R , Krkovic Katarina , Monov Gina , Kudlek Natalia , Lincoln Tania , Donner Tobias H
Published: January 2024

Many decisions entail the updating of beliefs about the state of the environment, a process that may go awry in psychosis. When environments are subject to hidden changes in their state, optimal belief updating requires non-linear modulation of sensory evidence, which may be subserved by pupil-linked, phasic arousal. Here, we analyzed behavior and pupil responses during evidence accumulation in a changing environment in a community sample of human participants and assessed their subclinical psychotic experiences (psychosis proneness). Subjects most prone to psychosis showed overall less flexible belief updating profiles, with diminished weighting of late evidence. These same subjects also exhibited overall smaller pupil responses and less reliable pupil encoding of computational variables governing the adaptive belief updating. The observed changes in belief updating and arousal dynamics may account for the emergence of cognitive biases in psychotic psychopathology. Our results open a new window on the pathophysiology of mental disorders.
Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice
Authors: Jangra Sonia , Lamoot Alexander , Singh Gagandeep , Laghlali Gabriel , Chen Yong , Yz Tingting , García-Sastre Adolfo , De Geest Bruno G. , Schotsaert Michael
Published: January 2024

Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), TLR7/8 adjuvant. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating the direct delivery of a RIG-I agonist to the cytosol. We have previously tested SDI and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated in a licensed vaccine setting (quadrivalent influenza vaccine or QIV) against H1N1 influenza virus, showing robust induction of antibody titres and T cell responses. Depending on the adjuvant combination and LNP lipid composition (K-Ac7-Dsa or S-Ac7-Dog lipids), humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with protection during viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was examined against challenge with the vaccine-matching strain of H1N1 influenza A virus. Groups that received either LNP formulated with SDI, IMDQ-PEG-Chol or both showed very low levels of viral replication in their lungs at five days post virus infection. LNP ionizable lipid composition as well as loading (empty versus SDI) also skewed host responses to infection, as reflected in the cytokine and chemokine levels in lungs of vaccinated animals upon infection. These studies show the potential of LNPs as adjuvant delivery vehicles for licensed vaccines and illustrate the importance of LNP composition for subsequent host responses to infection, an important point of consideration for vaccine safety.
Modeling the transmission of antibiotic-resistant Enterobacterales in the community: a systematic review
Authors: Rahbé Eve , Glaser Philippe , Opatowski Lulla
Published: January 2024

Background

Infections by antibiotic-resistant Enterobacterales are a public health threat worldwide. While dissemination of these opportunistic pathogens has been largely studied in hospitals, less is known about their acquisition and spread in the community. Here, we aim to characterize mechanistic hypotheses and scientific contributions of mathematical modeling studies focusing on antibiotic-resistant Enterobacterales in the community.

Methods

We conducted a systematic review of mathematical modeling studies indexed in PubMed and focusing on the transmission of antibiotic-resistant Enterobacterales in the community (i.e., excluding models only specific to hospitals). For each study, we extracted model features (host population, setting), formalism (compartmental, individual-based), biological hypotheses (transmission, infection, antibiotic use impact, resistant strain specificities) and main findings. We discussed additional mechanisms to be considered, open scientific questions, and most pressing data needs to further improve upon existing epidemiological modeling.

Results

We identified 18 modeling studies focusing on the human transmission of antibiotic-resistant Enterobacterales in the community (n=11) or in both community and hospital (n=7). Models aimed at: (i) understanding mechanisms driving resistance dynamics; (ii) identifying and quantifying transmission routes; or (iii) evaluating public health interventions to reduce resistance. Studies highlighted that community transmission, compared to hospital transmission, play a significant role in the overall acquisition of antibiotic-resistantEscherichia coli. Predictions across models regarding the success of public health interventions to reduce resistance rates depended on pathogens, settings, and antibiotic resistance mechanisms. ForE. coli, lowered person-to-person transmission led to greater reduction in antibiotic resistance rates compared to lowered antibiotic use in the community (n=2). ForKlebsiella pneumoniaelowered antibiotic use in the hospital led to greater reduction compared to lowered use in the community (n=2). Finally, we reported a moderate number of modeling studies inferring parameters from empirical data (n=9), probably due to a critical lack of available data for antibiotic resistance rates in the community.

Conclusions

We found a limited number of modeling studies addressing the transmission of antibiotic-resistant Enterobacterales in the community, highlighting a need for model development and extensive community-based data collection. Such modeling will be critical to better understand the spread of antibiotic-resistant Enterobacterales in the community and design public health interventions specific to this setting.
Establishment of a novel amyotrophic lateral sclerosis patient-derived blood-brain barrier model: Investigating barrier dysfunction and immune cell interaction
Authors: Matsuo Kinya , Nagata Kazuhiro , Umeda Ryusei , Shiota Takaya , Morimoto Satoru , Suzuki Naoki , Aoki Masashi , Okano Hideyuki , Nakamori Masayuki , Nishihara Hideaki
Published: January 2024

Amyotrophic lateral sclerosis (ALS) is a major neurodegenerative disease for which there is currently no effective treatment. The main feature of the disease is the loss of motor neurons in the central nervous system (CNS), but other CNS components and the immune system also appear to be involved in the pathogenesis of the disease. The blood-brain barrier (BBB) is formed by specialized brain microvascular endothelial cells (BMECs) and plays a crucial role in maintaining homeostasis within the central nervous system (CNS). Autopsy studies have reported BBB abnormalities in ALS patients, and studies in animal models suggest that BBB breakdown may precede neurodegeneration. However, the difficulty of obtaining patient samples has hampered further studies. We used the method of differentiating BMEC-like cells from human induced pluripotent stem cells (hiPSCs), which have robust barrier functions and express adhesion molecules necessary for immune cell adhesion, to investigate BBB functions in ALS patients. We also established a method using automated analysis techniques to analyze immune cell adhesion to the BBB in multiple samples simultaneously and with minimal bias. BMEC-like cells derived from ALS patients carryingTARDBPN345K/WTmutations exhibited increased permeability to small molecules due to loss of tight junction, as well as increased expression of cell surface adhesion molecules, leading to enhanced immune cell adhesion. BMEC-like cells derived from hiPSCs with other types ofTARDBPgene mutations (TARDBPK263E/K263EandTARDBPG295S/G295S) introduced by genome editing technology did not show such BBB dysfunction compared to the isogenic control. These results indicate that our model can recapitulate BBB abnormalities reported in ALS patients using patient (TARDBPN345K/WT) -derived hiPSCs and that two types of missense mutation,TARDBPK263E/K263EandTARDBPG295S/G295S, do not contribute to the BBB dysfunction. This novel ALS patient-derived BBB model is useful for the challenging analysis of the involvement of BBB dysfunction in the pathogenesis and to promote therapeutic drug discovery.
Global view of domain-specific O-linked mannose glycosylation in glycoengineered cells
Authors: Povolo Lorenzo , Tian Weihua , Vakhrushev Sergey Y. , Halim Adnan
Published: January 2024

Protein O-linked mannose (O-Man) glycosylation is an evolutionary conserved post-translational modification (PTM) that fulfills important biological roles during embryonic development. Three non-redundant enzyme families, POMT1/POMT2, TMTC1-4 and TMEM260, selectively coordinate the initiation of protein O-Man glycosylation on distinct classes of transmembrane proteins, including α-dystroglycan, cadherins and plexin receptors. However, a systematic investigation of their substrate specificities is lacking, in part due to the ubiquitous expression of O-Man glycosyltransferases in cells, which precludes analysis of pathway-specific O-Man glycosylation on a proteome-wide scale. Here, we apply a targeted workflow for membrane glycoproteomics across five human cell lines to extensively map O-Man substrates and genetically deconstruct O-Man initiation by individual and combinatorial knock-out (KO) of O-Man glycosyltransferase genes. We established a human cell library for analysis of substrate specificities of individual O-Man initiation pathways by quantitative glycoproteomics. Our results identify 180 O-Man glycoproteins, demonstrate new protein targets for the POMT1/POMT2 pathway and show that TMTC1-4 and TMEM260 pathways widely target distinct Ig-like protein domains of plasma membrane proteins involved in cell-cell and cell-extracellular matrix interactions. The identification of O-Man on Ig-like folds adds further knowledge on the emerging concept of domain-specific O-Man glycosylation which opens for functional studies of O-Man glycosylated adhesion molecules and receptors.
Direct Measurement of 8OGsyn-antiFlips in Mutagenic 8OG•A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using1H CEST NMR
Authors: Gu Stephanie , Al-Hashimi Hashim M.
Published: January 2024

Elucidating how damage impacts DNA dynamics is essential for understanding the mechanisms of damage recognition and repair. Many DNA lesions alter the propensities to form lowly-populated and short-lived conformational states. However, NMR methods to measure these dynamics require isotopic enrichment, which is difficult for damaged nucleotides. Here, we demonstrate the utility of the1H chemical exchange saturation transfer (CEST) NMR experiment in measuring the dynamics of oxidatively damaged 8-oxoguanine (8OG) in the mutagenic 8OGsyn•Aantimismatch. Using 8OG-H7 as an NMR probe of the damaged base, we directly measured 8OGsyn-antiflips to form a lowly-populated (pop. ∼ 5%) and short-lived (lifetime ∼ 50 ms) non-mutagenic 8OGanti•Aanti. These exchange parameters were in quantitative agreement with values from13C off-resonanceR1ρand CEST on a labeled partner adenine. The Watson-Crick-like 8OGsyn•Aantimismatch also rescued the kinetics of Hoogsteen motions at distance A-T base pairs, which the G•A mismatch had slowed down. The results lend further support for 8OGanti•Aantias a minor conformational state of 8OG•A, reveal that 8OG damage can impact Hoogsteen dynamics at a distance, and demonstrate the utility of1H CEST for measuring damage-dependent dynamics in unlabeled DNA.
Translational validation of shotgun proteomics findings in cerebrospinal fluid of sporadic cerebral amyloid angiopathy patients
Authors: Vervuurt Marc , de Kort Anna M. , Kersten Iris , Rens Astrid van , Klijn Catharina J. M. , Schreuder Floris H. B. M. , Lefeber Dirk J. , Kuiperij H. Bea , Verbeek Marcel M.
Published: January 2024

Background

Prior research conducted in model rats of CAA Type 1 (rTg-DI) identified a range of cerebrospinal fluid biomarker candidates associated with sCAA pathology. This list of potential biomarkers includes the lysosomal proteases cathepsins B and S (CTSB/CTSS) and hexosaminidase B (HEXB). It is yet unknown if these findings obtained in rTg-DI rats translate to differential protein levels and/or enzyme activities in cerebrospinal fluid (CSF) of sCAA patients. In this study, we attempted to validate CTSB, CTSS and HEXB in CSF as potential biomarkers for sCAA in a human population.

Materials and methods

We have included sCAA patients (n = 34) and control participants (n = 27) from our BIONIC/CAFE cohort. We analysed the CSF of these participants with ELISA for protein levels of CTSB and CTSS. Additionally, we used in-house enzyme assays to determine activity levels of total hexosaminidase and hexosaminidase A (HEXA) in CSF. The proportion of HEXA activity to total HEX activity was used as a proxy for HEXB activity.

Results

CSF CTSB and CTSS protein levels were not significantly different between sCAA and controls (p = 0.21 and p = 0.34). Total HEX activity was unaltered as well (p = 0.11), whereas a significant decrease was observed in HEXA activity levels (p = 0.05). HEXA / total HEX activity levels (as a proxy for HEXB activity) were unaltered between sCAA patients and controls (p = 0.19). Additionally, CTSB and CTSS protein levels positively associated with total HEX activity (rsp= 0.37, p = 0.005; rsp= 0.40, p = 0.003).

Conclusion

The contrasting results between biomarker discovery in rats and validation in human participants highlight the challenges and complexities of biomarker research. These findings offer valuable insights into the nuances of disease and the difficulties in translating laboratory findings using animal models to clinical practice. Understanding these discrepancies is essential for improving the precision of biomarker translation, ensuring clinical relevance, and developing comprehensive biomarker panels for CAA and related conditions.
Projection-Targeted Photopharmacology Reveals Distinct Anxiolytic Roles for Presynaptic mGluR2 in Prefrontal- and Insula-Amygdala Synapses
Authors: Munguba Hermany , Gutzeit Vanessa A. , Srivastava Ipsit , Kristt Melanie , Singh Ashna , Vijay Akshara , Arefin Anisul , Thukral Sonal , Broichhagen Johannes , Stujenske Joseph M. , Liston Conor , Levitz Joshua
Published: January 2024

Dissecting how membrane receptors regulate neural circuit function is critical for deciphering basic principles of neuromodulation and mechanisms of therapeutic drug action. Classical pharmacological and genetic approaches are not well-equipped to untangle the roles of specific receptor populations, especially in long-range projections which coordinate communication between brain regions. Here we use viral tracing, electrophysiological, optogenetic, and photopharmacological approaches to determine how presynaptic metabotropic glutamate receptor 2 (mGluR2) activation in the basolateral amygdala (BLA) alters anxiety-related behavior. We find that mGluR2-expressing neurons from the ventromedial prefrontal cortex (vmPFC) and posterior insular cortex (pIC) preferentially target distinct cell types and subregions of the BLA to regulate different forms of avoidant behavior. Using projection-specific photopharmacological activation, we find that mGluR2-mediated presynaptic inhibition of vmPFC-BLA, but not pIC-BLA, connections can produce long-lasting decreases in spatial avoidance. In contrast, presynaptic inhibition of pIC-BLA connections decreased social avoidance, novelty-induced hypophagia, and increased exploratory behavior without impairing working memory, establishing this projection as a novel target for the treatment of anxiety disorders. Overall, this work reveals new aspects of BLA neuromodulation with therapeutic implications while establishing a powerful approach for optical mapping of drug action via photopharmacology.

Highlights

- Basolateral amygdala is a key site for anxiolytic action of mGluR2 agonism

- BLA receives dense Grm2+inputs from ventromedial prefrontal cortex and posterior insular cortex

- Photoactivation of mGluR2 has distinct anxiolytic effects in vmPFC-BLA and pIC-BLA synapses

- Grm2+vmPFC and pIC projections target medial and lateral BLA subregions, respectively
Superiority of chromosomal compared to plasmid-encoded compensatory mutations
Authors: Wright Rosanna C.T. , Wood A. Jamie , Bottery Michael J. , Muddiman Katie J. , Paterson Steve , Harrison Ellie , Brockhurst Michael A. , Hall James P.J.
Published: January 2024

Plasmids are important vectors of horizontal gene transfer in microbial communities but can impose a burden on the bacteria that carry them. Such plasmid fitness costs are thought to arise principally from conflicts between chromosomal- and plasmid-encoded molecular machineries, and thus can be ameliorated by compensatory mutations (CMs) that reduce or resolve the underlying causes. CMs can arise on plasmids (i.e. plaCM) or on chromosomes (i.e. chrCM), with contrasting predicted effects upon plasmid success and subsequent gene transfer because plaCM can also reduce fitness costs in plasmid recipients, whereas chrCM can potentially ameliorate multiple distinct plasmids. Here, we develop theory and a novel experimental system to directly compare the ecological effects of plaCM and chrCM that arose during evolution experiments betweenPseudomonas fluorescensSBW25 and its sympatric mercury resistance megaplasmid pQBR57. We show that while plaCM was predicted to succeed under a broader range of parameters in mathematical models, experimentally chrCM dominated under all conditions, including those with numerous recipients, due to a more efficacious mechanism of compensation, and advantages arising from transmission of costly plasmids to competitors (plasmid ‘weaponisation’). We show analytically the presence of a mixed Rock-Paper-Scissors regime for plaCM, driven by trade-offs with horizontal transmission, that explains the observed failure of plaCM to dominate even in competition against an uncompensated plasmid. Our results reveal broader implications of plasmid-bacterial evolution for plasmid ecology, demonstrating the importance of compensatory mutations for resistance gene spread. One consequence of the superiority of chrCM over plaCM is the likely emergence in microbial communities of compensated bacteria that can act as ‘hubs’ for plasmid accumulation and dissemination.
Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson’s disease
Authors: Khan Shahzad S. , Jaimon Ebsy , Lin Yu-En , Nikoloff Jonas , Tonelli Francesca , Alessi Dario R. , Pfeffer Suzanne R.
Published: January 2024

Activating LRRK2 mutations cause Parkinson’s disease. Previously, we showed that cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice. Single nucleus RNA sequencing shows that cilia loss in cholinergic interneurons correlates with higher LRRK2 expression and decreased glial derived neurotrophic factor transcription. Nevertheless, much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia in mice and humans. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. Human striatal tissue from LRRK2 pathway mutation carriers and idiopathic Parkinson’s disease show similar cilia loss in cholinergic interneurons and astrocytes and overall loss of such neurons. These data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson’s disease.

Teaser

Cilia loss in Parkinson’s disease decreases dopaminergic neuroprotection due to inability to sense Hedgehog signals
Gene editing of pigs to control influenza A virus infections
Authors: Kwon Taeyong , Artiaga Bianca L. , McDowell Chester D. , Whitworth Kristin M. , Wells Kevin D. , Prather Randall S. , Delhon Gustavo , Cigan Mark , White Stephen N. , Retallick Jamie , Gaudreault Natasha N. , Morozov Igor , Richt Juergen A.
Published: January 2024

Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA which is cleaved by ubiquitous proteases, such as furin; in contrast, the monobasic HA motif is recognized and activated by trypsin-like proteases, such as the transmembrane serine protease 2 (TMPRSS2). Here, we aimed to determine the effects of TMPRSS2 on the replication of pandemic H1N1 and H3N2 subtype IAVs in the natural host, the pig. The use of the CRISPR/Cas 9 system led to the establishment of homozygous gene edited (GE)TMPRSS2knockout (KO) pigs. Delayed IAV replication was demonstrated in primary respiratory cells of KO pigsin vitro. IAV infectionin vivoresulted in significant reduction of virus shedding in the upper respiratory tract, and lower virus titers and pathological lesions in the lower respiratory tract ofTMPRSS2KO pigs as compared to WT pigs. Our findings could support the commercial use of GE pigs to minimize (i) the economic losses caused by IAV infection in pigs, and (ii) the emergence of novel IAVs with pandemic potential through genetic reassortment in the “mixing vessel”, the pig.
Invariant neural representation of parts of speech in the human brain
Authors: Misra Pranav , Shih Yen-Cheng , Yu Hsiang-Yu , Weisholtz Daniel , Madsen Joseph R , Sceillig Stone , Kreiman Gabriel
Published: January 2024

Elucidating the internal representation of language in the brain has major implications for cognitive science, brain disorders, and artificial intelligence. A pillar of linguistic studies is the notion that words have defined functions, often referred to as parts of speech. Here we recorded invasive neurophysiological responses from 1,801 electrodes in 20 patients with epilepsy while they were presented with two-word phrases consisting of an adjective and a noun. We observed neural signals that distinguished between these two parts of speech. The selective signals were circumscribed within a small region in the left lateral orbitofrontal cortex. The representation of parts of speech showed invariance across visual and auditory presentation modalities, robustness to word properties like length, order, frequency, and semantics, and even generalized across different languages. This selective, invariant, and localized representation of parts of speech for nouns versus adjectives provides elements for the compositional processes of language.
“You’ve actually got two patients, you haven’t got one”: parent-informed criteria for evaluating the autism assessment process
Authors: Burden Daisy Grace
Published: January 2024

Purpose

Parents whose children have undergone an autism assessment often describe the process as extremely stressful. This affects how parents engage with services post-diagnosis, meaning less likelihood of using subsequent service support despite struggling to cope. Since parents already report many barriers to accessing services, e.g. long waiting lists, lack of co-ordination and limited resources (Sapiets et al. 2023), negative experiences during assessment should not pose another potential barrier to engagement. This study aimed to address how families’ needs can be better met during the assessment process.

Design/methodology/approach

In this qualitative study, the author conducted semi-structured interviews with 11 parents whose child had undergone an autism assessment in the last five years. Thematic analysis determined key themes.

Findings

The six themes were: clarity and communication, access to support and resources, aftercare, recognition of parent concerns, personalisation of the assessment process and concerns around the use of personal protective equipment/online assessments. These themes led to criteria to assess the quality of autism assessment services in line with parent perspectives.

Practical implications

These parent-informed criteria could facilitate the consideration of parents’ views into service evaluations of autism assessment services across the UK.

Originality/value

Previous research indicates that the autism assessment experience is often extremely stressful and overwhelming for families (Crane et al., 2016). Despite this, guidance to improve autism services rarely prioritises the opinions and experiences of service-users and their families. The criteria presented here were derived from themes identified by interviewing parents on their experiences of the autism assessment process, thus shifting the focus onto service-users.
Ramification of work and life integration on exhaustion and work–life balance due to Covid-19 in IT and academic institutions
Authors: Tiwari Mansi , Mathur Garima , Narula Sumit
Published: January 2024

Purpose

The Covid-19 virus badly affected working patterns in almost every sector. The purpose of this paper is to analytically substantiate how work and life integration impacts the exhaustion and work–life balance among employees of academic institutions and IT companies.

Design/methodology/approach

Current study is empirical in nature based on the survey of 500 respondents taken from academic (250) and IT companies (250) from Ahmedabad and Gandhinagar, Gujarat. Structural equation modelling (SEM) was used to test the hypothesis with the application of the software Smart-PLS. Two surveys were conducted to collect the data separately for academic institutions and IT organizations.

Findings

Findings revealed the facts that during Covid-19, the employee’s work and life integration affected the work–life balance and exhaustion in academic institutions highly. The relationship was positively significant. But, for IT employees, it was identified as non-significant.

Practical implications

The current study highlighted the issues which employees faced during Covid-19 severe spread while managing work and family; how it varied due to the nature of work performed by the employees, for example, academics being more exposed to transformation from offline to complete online mode posed more challenges to teaching staff. This study also disclosed the scenario created and how it was handled in the deadly phase.

Social implications

This study presents the social contribution in understanding the importance of work and life balance and problems related to it, especially when everyone everywhere is scared of going out. The study provides insight into how it became difficult for employees to maintain their payroll successfully.

Originality/value

The current study contributes to the existing body of knowledge by testing statistically that the integration between work and life is important for work–life balance and prohibiting emotional exhaustion. The current paper extends the theoretical contribution by offering suggestions to companies on why to synchronize positive balance between work and life while keeping boundaries relatively strict between family and work to gain employee well-being and competitive advantages.
Cultural heritage beyond juridification: towards a place-first research agenda
Authors: Kanellopoulou Evgenia , Panayiotopoulos Aggelos , Pavlidis Savvas Alexandros
Published: January 2024

Purpose

This paper aims to propose a research agenda towards a holistic, grounded and flexible approach to cultural heritage that can address social challenges and transformations in the context of place. It critiques the dominant/hegemonic cultural heritage narratives, deriving from juridification and calls for a grounded approach in the way cultural heritage is framed and experienced.

Design/methodology/approach

The paper is conceptual, focusing on the need to open a line of enquiry into the relationship between legal texts, cultural heritage narratives and social challenges and transformations. It follows the letter of the international conventions on cultural heritage against the worked example of the medieval town of Rhodes in Greece.

Findings

The paper sets the relevant research priorities for the investigation of the effective relationship between cultural heritage and social challenges in the context of place, and further stretches the need to evaluate the role of legal and regulatory texts to that effect.

Originality/value

The paper identifies new priorities for thinking about the effects of juridification/the law, cultural heritage and social challenges/transformations in a place-specific context. It seeks to open new avenues of scientific explorations and new interdisciplinary dialogues between a variety of disciplines that are relevant to the way a place engages and addresses social challenges and transformations.
Impact of dynamic working capital management on operational efficiency: empirical evidence from Scandinavia
Authors: Yeboah Samuel , Kjærland Frode
Published: January 2024

Purpose

Consumer goods firms often tie up inventory and accounts receivable resources, creating cost and liquidity issues. Dynamic working capital management (DWCM) can mitigate these concerns and enhance operational profitability. The study investigates DWCM's impact on operational efficiency (OE).

Design/methodology/approach

The empirical estimation uses pooled ordinary least squares (OLS), random effect and system generalized method moments (GMM) regression analysis of consumer goods firms in Scandinavia from 2005 to 2022 to present the results.

Findings

The findings indicate that DWCM has an inverse relationship with operating cost, while positively impacting operating profit. The final outcome demonstrates that DWCM enhances OE. Furthermore, the working capital ratio (WCR) consistently exceeds the cash conversion cycle (CCC) in all models, indicating that prudent management of cash in accounts receivable, inventory and accounts payable leads to higher cost savings and superior performance.

Practical implications

The results suggest that organizations that prioritize the management of the absolute cash committed to inventory, receivables and payables as much as the CCC experience improved OE.

Originality/value

This paper adds to the literature on how DWCM affects OE in the consumer goods sector. It also highlights the impact of time management and cash management in WCM on OE. Additionally, it analyzes how DWCM variables affect operating costs and profits, shedding light on their efficiency impact.
Early-career employees sensemaking strategies in organizationally constrained workplaces: a longitudinal multiple-case study
Authors: Tessema Kedir Assefa
Published: January 2024

Purpose

This study aimed to investigate the sensemaking strategies employed by early-career employees working within organizationally constrained environments.

Design/methodology/approach

Grounded in the sensemaking-as-accomplishment framework, a longitudinal multi-case study was conducted, involving three early-career employees. These participants were interviewed multiple times concerning tasks they themselves identified as anomalous and ambiguous.

Findings

The study's findings illuminate how early-career employees utilize sensemaking strategies to accomplish anomalous-ambiguous tasks. These strategies are interwoven with deliberate efforts to mitigate organizational constraints that exist in the organization or arise during the execution of complex tasks.

Research limitations/implications

Notable limitation pertains to the time gap between task completion and the interviews. Conducting real-time interviews concurrently with task execution or immediately afterward was not feasible due to constraints in participant availability. This research has implications for organizational learning initiatives, particularly those encompassing employee-driven self-learning components. Insights derived from studies like this can inform the development of effective self-learning schemes within organizations.

Originality/value

Previous sensemaking research focused on what takes place in high-reliability organizations. This study explored sensemaking strategies in workplaces that are organizationally constrained.
What could be considered as effective support for autistic females in high school? A systematic literature review
Authors: Ayirebi Katie , Thomas George
Published: January 2024

It could be argued that autistic females, attending high school, have a distinct set of needs when compared to their male counterparts. The purpose of this review is to synthesise reported findings on what could be considered as effective for supporting the needs of autistic females in high school settings. The review adhered to PRISMA guidelines. Searches identified 12 papers that included direct perspectives of autistic females, their families and the professionals supporting them. Data were analysed using thematic synthesis. The findings indicate seven main themes for support related to: mental health; identification of specific needs and post‐diagnostic support; friendship interventions and skills development; tiered support; relationships between home and school; transitions between levels of education; self, peer and staff advocacy, and sense of belonging. Social and emotional experiences of autistic females in high school are key areas to target in ensuring successful education. Findings are discussed in relation to integrated, inclusive practices that high schools may adopt to support this cohort of students. Implications for professional practice, policy and research are discussed, which will be of interest to educators and helping professionals alike.
Greening wallets or worsening landscapes: Exploring carbon footprints of renewable energy, tourism, and financial development indices
Authors: Mehmood Saqib , Kaewsaeng‐on Rudsada
Published: January 2024

Sustainable development goals (SDGs) 7 and 13 of the United Nation's 2030 Agenda for Sustainable Development emphasize cheap and clean energy and climate action, respectively. The relentless pursuit of sustainable development has spurred a growing interest in understanding the intricate relationships between carbon footprints, renewable energy practices, tourism, and financial development indices. This research embarks on a comprehensive exploration of the interplay among these critical factors, aiming to unravel the nuanced dynamics that shape our environmental and economic landscape of the top 10 tourist countries from 1991 to 2021. This investigation was conducted through quantile‐based modeling, where the long‐run estimates are achieved through lower, middle, and higher quantiles. Nevertheless, findings suggest that a 1% increase in tourism development will approximately result in a 0.109% to 0.298% increase in carbon footprint in the lower quantile quantiles, that is, the 10th to 30th quantile. In the middle and higher quantiles (40th to 60th and 70th to 90th), 0.313% to 0.565% and 0.721% to 1.369%, respectively. However, renewable energy and financial development index are the significant sources of reducing carbon footprints from the 10th to the 90th quantiles. Still, the intensity of their impacts is heterogeneous among different quantiles. Empirical findings demonstrate that financial development stimulates a growing demand for environmentally sustainable energy sources. Utilizing renewable energy decreases the presence of greenhouse gases in the environment in contrast to the use of fossil fuels. However, renewable energy, tourism, and financial development indices are concluded to be the cornerstones concerning carbon footprints through their distinct impacts. This study's quantile slope equality and symmetric quantile tests further corroborated the findings. Upon the conclusion of the current study, this research has offered policy implications for regulatory bodies and has deliberated on potential avenues for future investigation.
Avian influenza virus cross‐infections as test case for pandemic preparedness: From epidemiological hazard models to sequence‐based early viral warning systems
Authors: Brüssow Harald
Published: January 2024

Pandemic preparedness starts with an early warning system of viruses with a pandemic potential. Based on information collected in a multitude of surveys, hazard models were developed identifying influenza viruses presenting a pandemic threat. Scores are attributed for 10 viral traits by expert panels which identified avian influenza viruses (AIV) belonging to subtypes H7N9 and H5N1 as representing the greatest pandemic risk. In 2013, more than 100 human cases infected with AIV H7N9 were observed in China. Case fatality rate (CFR) was high (27%), but the human‐to‐human transmission rate was low and by serological evidence H7N9 did not spread widely. Nevertheless, until 2019 more than 1500 H7N9 patients were identified characterized by a high CFR of 39%. Serology demonstrated that mild infections with H7N9 were widespread. In 2003, more than 400 people experienced AIV H7N7 cross‐infection causing mainly conjunctivitis during a large poultry epidemic in The Netherlands. Between 1996 and 2019, a total of 881 human infections with avian H5N1 viruses were documented showing a CFR of 52%. Outbreaks were centred on South East Asia and showed close associations with epizootics in poultry. Mutations predisposing to human cross‐infections were identified in the haemagglutinin (HA) and the RNA polymerase subunit PB2 of human H7N9 isolates. Human H5N1 isolates showed mutations in the receptor binding domain of HA and transmission in mammals could be obtained by as few as four additional aa changes introduced experimentally. Researchers have defined viral point mutations in HA, PB2 and the nucleoprotein NP that allowed AIV to cross the species barrier to mammals with respect to receptor recognition, RNA replication and escape from innate immunity respectively. Based on this insight a sequence‐based early warning system for AIV preadapted to human transmission could be envisioned. Mink farms and live poultry markets are prime targets for such sequencing efforts.
Gut microbiota composition may be an indicator of erectile dysfunction
Authors: Qiao Yu , Chen Jianhuai , Jiang Yongsheng , Zhang Ziheng , Wang Heng , Liu Tao , Yang Zhaoxu , Fu Guangbo , Chen Yun
Published: January 2024

Erectile Dysfunction (ED) is considered a physical and mental illness. A variety of potential associations between gut microbiota and health or disease have been found. By comparing the gut microbiota of healthy controls and ED patients, our study investigated the relationship between ED and gut microbiota. The results revealed that the ED group exhibited a significantly higher relative abundance of Bacteroides, Fusobacterium, Lachnoclostridium, Escherichia‐Shigella and Megamonas, while showing a significantly lower relative abundance of Bifidobacterium compared to the control group. The dysbiosis of gut microbiota played a role in the onset and progression of ED by influencing the gut barrier, cardiovascular system and mental health, which provided a novel perspective on understanding the pathophysiology of ED. What is more, we had identified several key gut microbiota. By combining 16S rRNA sequencing with machine learning techniques, we were able to uncover the significant value and impact of gut microbiota in the early detection of ED.
Efficacy of osimertinib in patients with EGFR‐mutation positive non‐small cell lung cancer with malignant pleural effusion
Authors: Kiritani Ayu , Amino Yoshiaki , Uchibori Ken , Akita Takahiro , Harutani Yuhei , Ogusu Shinsuke , Tsugitomi Ryosuke , Manabe Ryo , Ariyasu Ryo , Kitazono Satoru , Yanagitani Noriko , Nishio Makoto
Published: January 2024

Background

As an epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI), osimertinib has emerged as a standard EGFR‐mutation positive treatment for non‐small cell lung cancer (NSCLC). However, the efficacy of osimertinib for malignant pleural effusion (MPE) remains understudied. This study aimed to evaluate the impact of osimertinib on time to treatment failure (TTF) and overall survival (OS) in patients with EGFR‐mutation positive NSCLC, comparing those with and without MPE.

Methods

This retrospective analysis included patients with advanced or recurrent NSCLC treated with osimertinib at our hospital between April 2016 and June 2021. TTF was defined as the duration from osimertinib initiation to discontinuation, and OS as the duration until death, irrespective of the reason.

Results

Among 229 patients receiving osimertinib, 84 had MPE before administration, 39 acquired EGFR exon20 T790M mutation following previous EGFR‐TKI therapy, and 45 were EGFR‐TKI‐naive. Among EGFR‐TKI‐naive patients, median TTF was 14.8 and 19.8 months for those with and without MPE, respectively (hazard ratio [HR] 1.40; 95% confidence interval [CI]: 0.90–2.18; p = 0.12). Median OS was 32.0 and 42.0 months for patients with and without MPE, respectively (HR 1.43; 95% CI: 0.86–2.38; p = 0.16). Among patients with T790M mutation, median TTF was 12.3 and 13.1 months for patients with and without MPE, respectively (HR 1.03; 95% CI: 0.69–1.55; p = 0.88). Median OS for patients with and without MPE was 23.2 and 24.7 months, respectively (HR 1.09; 95% CI: 0.72–1.67; p = 0.68).

Conclusion

Among patients with EGFR‐mutation positive NSCLC, the evidence of MPE has little effect on survival with osimertinib.