bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of HIV transmission bursts to future HIV infections, United States
Authors: Billock Rachael M. , France Anne Marie , Saduvala Neeraja , Panneer Nivedha , Hallmark Camden J. , Wertheim Joel O. , Oster Alexandra M.
Published: December 2024

Objective:

To estimate the influence of bursts of rapid HIV transmission on future transmission and describe populations affected by transmission bursts.

Design:

Phylogenetic analysis of US National HIV Surveillance System data.

Methods:

Time-scaled phylogenetic trees were inferred for six geographic regions using sequences from persons with HIV (PWH) with diagnoses of HIV infection 2014–2019. Transmission bursts were defined as ≥3 adjacent inferred transmission events in the phylogeny during a detection period. We calculated the relative contribution of transmission bursts 2015–2016 to transmission 2017–2019 compared with non-bursts. Then, we detected bursts within any sliding 2-year period 2014–2019 and assessed descriptive associations of characteristics of individuals involved with or descended from transmission bursts using univariate risk ratios.

Results:

The 5.6% of phylogenetic lineages involved in transmission bursts 2015–2016 contributed to 14.9% of inferred transmission events 2017–2019. The relative contribution of lineages involved in transmission bursts to future transmission was 2.94 times that of lineages not involved in bursts. Younger age at diagnosis, self-identification as transgender or an additional gender identity, or as a cisgender man, male-to-male sexual contact, injection drug use, or male-to-male sexual contact and injection drug use, and diagnosis during acute or early infection were most strongly associated with involvement in or descendance from transmission bursts.

Conclusions:

Transmission bursts contribute disproportionately to future HIV transmission, underscoring the value of detecting and responding to rapid transmission to reduce incidence. Bursts of rapid transmission may also contribute to enduring disparities in incidence among some key populations.
Comparison of Nasal Packing, Trans-septal Suturing, and Submucosal Trans-septal Suturing Techniques After Septal Extension Grafts With Autogenous Costicartilage
Authors: Gan Yufeng , Wu Jiacheng , Peng Su , Huang Xin , Chen Xiang , Wu Jie , Guo Zongke , Lin Jinde
Published: December 2024

Background:

Nasal packing (NP), trans-septal suturing (TSS), and submucosal trans-septal suturing (STSS) are common techniques to avoid dead space after the deviated septum is corrected. However, there is rare data about surgical complications and discomfort of these techniques after septal extension grafts (SEG) with autogenous costicartilage.

Objective:

To compare the complications and discomfort of NP, TSS, and STSS techniques after SEG with autogenous costicartilage.

Materials and Methods:

The authors randomly divided 90 patients into NP, TSS, and STSS groups. The discomfort (sleeping disturbance, nasal obstruction, and pain), complications, and extra surgical duration were recorded and compared among the 3 groups.

Results:

The difference in extra-surgical duration was statistically significant between the 3 groups. Compared with the other 2 groups, the NP group had obviously higher average scores of sleeping disturbance, nasal obstruction, and pain during 48 hours after surgery, while TSS had an obviously higher incidence of septal mucoperichondrial injury. There was no statistically significant difference in terms of foreign body sensation, bleeding, hematoma, septal perforation, and infection between the 3 groups.

Conclusion:

The TSS technique is preferable after SEG with autogenous costicartilage.
A Patient of Secondary Malignant Fibrous Histiocytoma of the Head Following Trauma and Review of the Literature
Authors: Li Sen , Han Bin , Fan Danjie , Ji Xiangyu , Li Dachuan , Wang Zengwu
Published: December 2024

Malignant fibrous histiocytoma (MFH) is a malignancy originating from soft tissues and ranks among the most prevalent soft tissue sarcomas in adults. The considerable complexity and heterogeneity of MFH contribute to an obscure pathogenesis, presenting with atypical clinical manifestations and pathologic features that complicate the clinical diagnostic process. Typically, MFH manifests in the extremities, trunk, and retroperitoneum, while occurrences in the head and neck regions are exceedingly rare. A thorough review of extant literature indicates that fewer than 5 cases of MFH secondary to a documented history of trauma have been reported globally. This article delineates an exceptionally rare instance of secondary MFH of the head subsequent to trauma, elaborating on the diagnostic and therapeutic procedures undertaken. It seeks to enrich the understanding of MFH treatment and pathogenesis and, by reviewing pertinent literature, aims to elucidate the clinical characteristics and prognostic outlook of MFH.
Comparative Neuroexcitation Patterns Using fNIRS in Women With Overactive Bladder
Authors: Burkett Linda S. , Ghatas Mina , Query Helen , Daniels Peter , Grob Gabrielle , Matthew Ashley , Rogers Devin , Stothers Lynn , Speich John E. , Klausner Adam P.
Published: December 2024

Importance

Functional near-infrared spectroscopy (fNIRS) is a noninvasive technique used to quantify prefrontal cortex (PFC) neuroexcitation. The PFC is involved in the decision to void, and dysfunction in the region has been associated with overactive bladder (OAB). This study demonstrates neuroexcitation differences in the brain region associated with the decision to void (prefrontal cortex) using noninvasive fNIRS.

Objective

The objective of this study was to compare PFC neuroexcitation during natural filling in female participants with and without OAB.

Study Design

Female participants with OAB were cross-sectionally compared with controls without urinary urgency. The fNIRS signals were continuously recorded during an oral hydration protocol. Simultaneously, recordings of real-time bladder sensation of fullness were completed. A period of “high sensation” was defined as the time from first desire to 100% sensation. Signal analysis included removal of motion artifact, low pass filtering, and interpolated to standardize reporting bladder filling time.

Results

A total of 25 female participants were enrolled and had complete analyzable data, including 14 with OAB and 11 controls without OAB. Change in O2Hb during the high sensation period was significantly lower in all PFC regions in the OAB group compared with controls (P < 0.001). The majority of OAB participants had a constant or decreasing neuroexcitation pattern, which differenced in comparison to normal controls who displayed an increasing pattern.

Conclusions

This study demonstrates that fNIRS PFC excitation during a period of high sensation is consistently lower in women with OAB as compared with controls. These data support the hypothesis that the PFC plays an inhibitory role in voiding function and that there may be a lack of inhibitory control in women with OAB.
Vaginal Orthosis After Native Tissue Reconstructive Surgery: Design and Phase 0
Authors: Cadena Max C. , Hong Christopher X. , Blokker Alexandra , Sham Derek , Richter Holly E.
Published: December 2024

Importance

Pelvic organ prolapse recurrence following native tissue repair occurs with composite failure rates of 9–19% within 12 months, predominantly involving apical/anterior compartments. Objective The objective of this study was to develop a novel vaginal orthosis (NVO) device prototype through an iterative design process based on investigator and user feedback.

Study Design

The NVO was designed based on pelvic floor biomechanical principles to mitigate unopposed intra-abdominal pressure of the anterior vagina by absorbing and redirecting intra-abdominal forces to the levator ani and tailored to accommodate postoperative vaginal caliber and axis. Prototypes were fabricated by 3D-printing negative molds, cast, and cured with medical-grade biocompatible silicone. Ten healthy volunteers were recruited to provide qualitative feedback for iterative design refinement (phase 0).

Results

Through an iterative engineering design process, initial concepts were refined to align with the natural, resting H-shape of the vagina. Key features included a distal self-retaining feature, posterior curvature, proximal taper, and apical/anterior contact areas for support. A more rigid material to withstand intra-abdominal forces without folding was required; therefore, Shore A60 (medium soft) instead of A40 (soft) silicone was used. Based on participant feedback, the NVO retaining feature width range was reduced (47.5–63 mm to 45–50 mm) to decrease pressure on lateral vaginal walls and levator ani distally maintaining self-retaining function. Updates to the fitting and education process also provided increased descriptive instructions for insertion and removal.

Conclusions

A novel vaginal orthosis was designed specifically tailored to facilitate wound healing using an orthomedical model, improving the design through iterative feedback.
Evolving Enterococcus faecalis Biofilms and Urinary Tract Infection Relapse: Does Vaginal Estrogen Matter?
Authors: Abankwa Aileen , Squires Natalie , Sansone Stephanie , Asfaw Tirsit , Segal Saya
Published: December 2024

Importance

Enterococcus faecalis urinary tract infection (UTI) is common in postmenopausal females and these bacteria create biofilms that may reduce treatment efficacy. The role of local vaginal estrogen therapy in susceptibility to E. faecalis infection is unclear.

Objective

The aim of the study was to evaluate differences in the treatment of relapsing E. faecalis UTIs in postmenopausal women using vaginal estrogen compared to premenopausal women.

Study Design

This was a secondary analysis of a retrospective cohort study of 71 female ambulatory patients seen within the gynecology or urogynecology practices between 2011 and 2020. Patients included had symptomatic E. faecalis UTI and a diagnosis of recurrent UTI. Patients with asymptomatic bacteriuria and concurrent pregnancy were excluded. Data was retrieved by chart review, stored, and analyzed utilizing descriptive statistics. A 2-sided Fisher exact test was performed to compare outcomes between postmenopausal and premenopausal patients and the prescription of additional rounds of antibiotics for relapse.

Results

Within this cohort, 57.8% were postmenopausal and 42.2% were premenopausal. There was no statistically significant difference in the need for additional antibiotics between postmenopausal and premenopausal patients (10.8% vs 14.3%, P = 0.72), postmenopausal patients not using vaginal estrogen and premenopausal patients (0% vs 14.3%, P = 0.28), postmenopausal patients using vaginal estrogen and premenopausal patients (20% vs 14.3%, P = 0.70), and among postmenopausal vaginal estrogen users and nonusers (20% vs 0%, P = 0.11).

Conclusions

A small percentage of premenopausal and postmenopausal patients with recurrent UTI required additional antibiotics for E. faecalis relapse. However, there are no statistically significant differences between our estrogen-deficient or estrogenized postmenopausal patients, and premenopausal patients.
Estimates of quantal synaptic parameters in light of more complex vesicle pool models
Authors: Bornschein Grit , Brachtendorf Simone , Schmidt Hartmut
Published: December 2024

The subdivision of synaptic vesicles (SVs) into discrete pools is a leading concept of synaptic physiology. To better explain specific properties of transmission and plasticity, it has been suggested initially that the readily releasable pool (RRP) of SVs is subdivided into two parallel pools differing in their release probability. More recently, evidence was provided that sequential pools with a single RRP and a series-connected finite-size replacement pool (RP) inserted between the reserve pool (RSP) and RRP equally well or even better account for most aspects of transmission and plasticity. It was further suggest that a fraction of the presynaptic release sites (N) are initially unoccupied by SVs, with vesicle recruitment occurring rapidly during activity, and furthermore that the number of release sites itself changes with rapid dynamics during activity. Here we propose a framework that identifies specific signs of the presence of the series-connected RP, using a combination of two experimental electrophysiological standard methods, cumulative analysis (CumAna) and multiple probability fluctuation analysis (MPFA). In particular we show that if the y-intercept (y(0)) of CumAna is larger thanNreported by MPFA (y(0) >NMPFA) this is a strong indication for a series-connected RP. This is due to the fact that y(0) reports the sum of RRP and RP. Our analysis further suggests that this result is not affected by unoccupied release sites, as such empty sites contribute to both estimates, y(0) andNMPFA. We discuss experimental findings and models in the recent literature in the light of our theoretical considerations.
Effectiveness of a single dose of oral cholera vaccine: findings from epidemiological and genomic surveillance ofVibrio Choleraein the Democratic Republic of the Congo (PICHA7 Program)
Authors: George Christine Marie , Namunesha Alves , Endres Kelly , Felicien Willy , Sanvura Presence , Bisimwa Jean-Claude , Perin Jamie , Bengehya Justin , Maheshe Ghislain , Cikomola Cirhuza , Bisimwa Lucien , Mwishingo Alain , Sack David A. , Domman Daryl
Published: December 2024

This study investigated whole-cell oral cholera vaccine (kOCV) single-dose effectiveness and transmission dynamics ofVibrio choleraethrough 4 years of epidemiological and genomic surveillance in Democratic Republic of the Congo (DRC). Whole genome sequencing was performed on clinical and waterV. choleraestrains from 200 patient households and found annual bimodal peaks ofV. choleraeclade AFR10e. 1154 diarrhea patients were enrolled with 342 culture confirmed cholera patients. A large clonal cholera outbreak occurred 18 months after a kOCV campaign of >1 million doses of Euvichol-Plus, likely because of low vaccine coverage in informal settlements (9%). Clinical and waterV. choleraestrains in the same household were more closely related than different households suggesting both person-to-person and water-to-person transmission. Single-dose kOCV vaccine effectiveness in the first 24 month after vaccination was 56.9% (95% CI: 18.6%-77.2%), suggesting a single-dose provided modest protection against medically attended cholera during the 24 months post-vaccination.
Crosslinking-mediated Interactome Analysis Identified PHD2-HIF1α Interaction Hotspots and the Role of PHD2 in Regulating Protein Neddylation
Authors: Ouyang Haiping , How Cindy Y. , Wang Xiaorong , Yu Clinton , Luo Ang , Huang Lan , Chen Yue
Published: December 2024

Prolyl Hydroxylase Domain protein 2 (PHD2) targets Hypoxia Inducible Factor alpha subunits (HIFα) for oxygen-dependent proline hydroxylation that leads to subsequent ubiquitination and degradation of HIFα. In addition to HIF proteins, growing evidence suggested that PHD2 may exert its multifaceted function through hydroxylase-dependent or independent activities. Given the critical role of PHD2 in diverse biological processes, it is important to comprehensively identify potential PHD2 interacting proteins. In this study, we engineered HeLa cells that stably express HTBH-tagged PHD2 to facilitate the identification of PHD2 interactome. Using DSSO-based cross-linking mass spectrometry (XL-MS) technology and LC-MSnanalysis, we mapped PHD2-HIF1α interaction hotspots and identified over 300 PHD2 interacting proteins. Furthermore, we validated the COP9 Signalosome (CSN) complex, a major deneddylase complex, as a novel PHD2 interactor. DMOG treatment promoted interaction between PHD2 and CSN complex and enhanced the deneddylase activity of the CSN complex, resulting in increased level of free Cullin and reduced target protein ubiquitination. This mechanism may serve as a negative feedback regulation of the HIF transcription pathway.
Deciphering the thiolactonization mechanism in thiolactomycin biosynthesis
Authors: Guo Jiawei , Zhang Qiaoyu , Cheng Fangyuan , Sang Moli , Wang Xuan , Liu Mingyu , Pan Yunjun , Yu Hao-Bing , Hu Bo , Wang Sheng , Zheng Liangzhen , Geng Ce , Yang Chaofan , Luo Lianzhong , Zhang Gang , Du Lei , Zhang Wei , Wang Binju , Li Shengying , Zhang Xingwang
Published: December 2024

Thiolactomycin (1), which features a uniqueγ-thiolactone ring, is a promising antibiotic candidate that specifically targets bacterial type II fatty acid synthase. Despite extensive studies on its pharmacological activities, modes of action, and chemical synthesis, the enzymatic processes responsible for forming the activity-determiningγ-thiolactone ring have remained largely unknown. Here, we resolve this problem by revealing that the condensation and heterocyclization (Cy) domain of the nonribosomal peptide synthetase (NRPS) TlnC (TlnCCy), along with the cytochrome P450 enzyme TlnA, cooperatively enable theγ-thiolactone assembly. TlnCCymediates an unusual sulfurtransfer reaction to sulfurate the polyketide intermediate, generating a thiocarboxyl intermediate. Subsequently, TlnA acts as aγ-thiolactone synthase, converting the linear thiocarboxyl intermediate into1via a distal radical-based cyclization mechanism. These findings not only expand the functional and catalytic repertoires of NRPS Cy domains and P450 enzymes, but also highlight a special enzymatic strategy forγ-thiolactone biosynthesis in nature.
Bispecific antibody targeting of lipid nanoparticles
Authors: Amabile Angelo , Phelan Matthew , Yu Zhixin , Silva Pedro , Marks Adam , Morla-Folch Judit , Sohn Moah , Mollaoglu Gurkan , Falcomata Chiara , Teunissen Abraham J P , Brody Joshua D , Dong Yizhou , Brown Brian D.
Published: December 2024

Lipid nanoparticles (LNP) are the most clinically advanced non-viral gene delivery system. While progress has been made for enhancing delivery, cell specific targeting remains a challenge. Targeting moieties such as antibodies can be chemically-conjugated to LNPs however, this approach is complex and has challenges for scaling up. Here, we developed an approach to generate antibody-conjugated LNPs that utilizes a bispecific antibody (bsAb) as the targeting bridge. As a docking site for the bsAb, we generated LNPs with a short epitope, derived from hemagglutinin antigen (HA), embedded in the PEG component of the particle (LNPHA). We generated bsAb in which one domain binds HA and the other binds different cell surface proteins, including PD-L1, CD4, CD5, and SunTag. Non-chemical conjugation of the bsAb and LNP resulted in a major increase in the efficiency and specificity of transfecting cells expressing the cognate target. LNP/bsAb mediated a 4-fold increase inin vivotransfection of PD-L1 expressing cancer cells, and a 26-fold increase in ex vivo transfection of quiescent primary human T cells. Additionally, we created a universal bsAb recognizing HA and anti-rat IgG2, enabling LNP tethering to off-the-shelf antibodies such as CD4, CD8, CD20, CD45, and CD3. By utilizing a molecular dock and bsAb technology, these studies demonstrate a simple and effective strategy to generate antibody-conjugated LNPs, enabling precise and efficient mRNA delivery.
Structural and genetic determinants of zebrafish functional brain networks
Authors: Legare Antoine , Lemieux Mado , Boily Vincent , Poulin Sandrine , Legare Arthur , Desrosiers Patrick , De Koninck Paul
Published: December 2024

Network science has significantly advanced our understanding of brain networks across species, revealing universal connectivity principles. While human studies based on magnetic resonance imaging (MRI) have established several network principles at macroscopic scales, recent breakthroughs, including high-amplitude regional co-activation patterns and spatially contiguous functional gradients, remain unexplored at cellular resolution in animal models. Here, we employ whole-brain functional imaging at cellular resolution in larval zebrafish, combined with anatomical and spatial genetic expression profile databases, to investigate the structural and genetic basis of functional brain networks. We show that mesoscopic functional connectivity (FC) is a robust measure of brain activity that captures the individuality of larvae. Using a public dataset of thousands of single-neuron reconstructions, we reveal a strong coupling between FC and structural connectivity (SC). Numerous properties of the connectome that account for indirect pathways and diffusion mechanisms individually and collectively predict interregional correlations. The hierarchical modular structure of SC and FC significantly overlaps in space, and modules identified within the connectome constrain the shape of both spontaneous and stimulus-driven activity patterns. Using visual stimuli and tail monitoring, we identify a functional network gradient that maps onto the sensorimotor function of brain regions. Finally, we identify a set of genes whose co-expression in brain regions significantly predicts regional FC. Our findings reproduce several key features of mammalian brain networks in zebrafish, demonstrating the potential for studying large-scale network phenomena in smaller, optically accessible vertebrate brains.
Identifying the Brain Circuits that Regulate Pain-Induced Sleep Disturbances
Authors: Lynch Nicole , De Luca Roberto , Spinieli Richard L , Rillosi Enrico , Thomas Renner C , Sailesh Samuel , Gangeddula Nishta , Lima Janayna D , Bandaru Sathyajit , Arrigoni Elda , Burstein Rami , Thankachan Stephen , Kaur Satvinder
Published: December 2024

Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP(parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRPin pain-induced sleep disturbances. Inactivating the PBelCGRPneurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRPterminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics.

One sentence summary

Parabrachial CGRP neurons regulate awakenings to pain.
A cytochrome P450 involved in apocarotenoid signaling enhances plant photosynthetic capacity and photooxidative stress tolerance
Authors: Tiwari Madhu , Ksas Brigitte , Légeret Betrand , Caffarri Stefano , Havaux Michel
Published: December 2024

β-cyclocitric acid and its precursor β-cyclocitral are signaling apocarotenoids which trigger defense and detoxification mechanisms enhancing plant tolerance to abiotic stresses. From a transcriptomic analysis of Arabidopsis plants exposed to each apocarotenoid over several exposure times, we identified a gene (CYP81D11) encoding a cytochrome P450 that is strongly induced under all conditions and is under the control of the TGAII-SCL14 transcription regulator. Overexpressing theCYP81D11gene in Arabidopsis led to a very tolerant phenotype to high light stress while aCYP81D11- deficient mutant was photosensitive. The transcriptomic profile of theCYP81D11overexpressor revealed a selective upregulation of genes related to photosynthesis and the response to high light stress. Photosynthetic electron transport, CO2fixation and biomass production were noticeably improved by high expression levels ofCYP81D11. These effects occurred in high light, not in low light, and were associated with a noticeable reduction of singlet oxygen photoproduction. These findings indicate that CYP81D11 is a key component of β-cyclocitral-induced stress tolerance, acting through enhancement of the photosynthetic capacity of leaves. This gene could be a new target for improving photosynthesis, particularly in sunny environments.
Long-Term Colonization Dynamics of ProbioticAliivibriospp. in Atlantic Salmon (Salmo salar) Following Bath Administration
Authors: Steen Dobloug Marius , Iakhno Stanislav , Foyn Nørstebø Simen , Evensen Øystein , Sørum Henning
Published: December 2024

Ulcerative conditions present a major challenge in Norwegian salmon farming. Probiotic Aliivibrio species have previously been demonstrated to provide health benefits in both Atlantic salmon and lumpfish, although the underlying mechanisms and the host-bacteria interactions remain unclear. This study aimed to investigate whether these bacteria could colonize Atlantic salmon following bath administration, determine the tissue tropism, and assess the duration of colonization. We examined the host microbiota using culture-based methods, qPCR and immunohistochemistry techniques specifically designed to target the applied Aliivibrio strains. Our findings reveal that the probiotic bacteria can successfully colonize Atlantic salmon and persist for at least nine months post-administration. We identified the administered strains in the skin and underlying tissue with all three methods. The probiotics were also identified in the distal intestine and the visceral organs. Additionally, we isolated the probiotic Aliivibrio species from mixed cultures in ulcerated areas. While viable bacteria were recoverable from recently euthanized fish, tissue decay promoted bacterial recovery of the administered species across all experiments. Given prior evidence on ulcer reduction associated with these probiotics, competitive exclusion appears to be a plausible mechanism of action, though further investigation is warranted.
The IQGAP1-Claudin Cell Junction Axis in Cisplatin-induced Kidney Damage
Authors: Barudi Yusuf , Fan Xiuzhen , Jenkins Kenneth W. , Dey Shubhra Kanti , Yakirevich Evgeny , Osman Mahasin A
Published: December 2024

Kidney damage resulting from nephrotoxicity is a major side effect of chemotherapy. Cisplatin is an effective antineoplastic agent broadly used in oncology where it interferes with DNA replication in dividing cells, however, its mechanism in kidney damage remains unclear. We tested the hypothesis that cisplatin displaces cell-contact proteins such as IQGAP1-claudin complex in the kidney tubules, causing epithelial cell dissociation and kidney damage. Employing a multifaceted approach, using mutant analyses and optimal cisplatin dose, this hypothesis was tested in cell culture andiqgap1−/-mouse models. Cisplatin inhibited cell proliferation and migration in an IQGAP1-dependent manner, displaced IQGAP1 from cell junctions and altered the expression level of key junctional markers, including claudins 2/4/8 and nephrin. Similar effects were observed in animal models where cisplatin treatment and loss of IQGAP1 had additive effects. These functional outcomes are accounted for by suppression of Akt1/PKB survival and ERK1/2 proliferation signals and activation of JNK-GSK3αβ stress and inflammatory signal, widely implicated in kidney injury. These findings present IQGAP1-claudin axis as biomarkers and therapeutic targets in kidney damage and pave the way for formulating new analogs that eliminate cisplatin adverse side effects while preserving its antineoplastic efficacy.
Shape-constrained, changepoint additive models for time series omics data with cpam
Authors: Yates Luke A. , Humphreys Jazmine L. , Charleston Michael A. , Smith Steven M.
Published: December 2024

Time series omics experiments are critical for the study of a wide range of biological processes such as cell differentiation and developmental programs or responses to pathogens and environmental cues. While statistical tools for differential analysis across static conditions have matured, comparable comprehensive methodology is lacking for time series data. Here, we introducecpam, a novel time series method and user-friendly software that performs temporal differential analysis of omics data for case-only or case-control time series, incorporating quantification uncertainty. Powerful features ofcpaminclude changepoint detection and shape-constrained temporal trend estimation to allocate omics data into similar clusters. Performance evaluation shows thatcpamoutperforms existing time series methods in terms of control of the false discovery rate versus power to detect temporal changes and accurate changepoint estimation. In particular, we find that trend-based models provide superior performance compared to pairwise comparisons, even with as few as six time points. The software provides an interactive interface with modern customizable visualisations, offering both graphical and statistical insight into complex molecular processes. Application to published transcriptome data illustrates RNA isoform-level modelling together with high resolution clustering during human embryogenesis and the identification of 910 novel genes differentially expressed in response to excess light in Arabidopsis. This method has the potential for application to a range of omics data, including single-cell analyses via pseudobulked data, providing the analytical power to reveal complex temporal patterns of gene expression in any biological system.
Leveraging metaverse knowledge in the gig economy: a social cognitive perspective on freelancer engagement and performance
Authors: Akhtar Maria , Abbas Khan Naseer , Khan Azmat Yar , Khan Asfand Yar
Published: December 2024

Purpose

This study explores the impact of metaverse knowledge on freelancer engagement and performance within the gig economy, drawing upon the theoretical framework of social cognitive theory. The authors investigate the mediating role of freelancer engagement in the relationship between metaverse knowledge and performance, further examining the moderating influence of freelancer experience on these relationships.

Design/methodology/approach

Using a convenient sampling technique, data was collected through questionnaire from 301 freelancers working on various virtual platforms in Pakistan using a five-point Likert scale. Smart PLS 4.0 was used to analyze the data.

Findings

The findings reveal positive direct effect of metaverse knowledge on both freelancer engagement and performance. In addition, freelancer engagement significantly mediates the relationship between metaverse knowledge and performance. Furthermore, the findings affirm that the freelancers experience serves as a moderating factor in the relationship between metaverse knowledge, engagement and performance by indicating positive impact.

Originality/value

This study contributes a novel perspective to the gig economy literature by elucidating the underlying mechanisms through which metaverse knowledge drives freelancer performance via engagement. By examining the unique role of the metaverse in the gig context, the study offers valuable theoretical and practical implications for both scholars and practitioners seeking to understand and enhance freelancer engagement and performance in this evolving digital landscape.
Barriers to the adoption of sustainable construction materials in Zimbabwe
Authors: Moyo Tirivavi , Mudombo Mable Vongai , Omer Mazen M. , Moyo Cynthia
Published: December 2024

Purpose

The built environment contributes to environmental concerns, including carbon emissions, with traditional construction materials being problematic. Adopting sustainable construction materials (SCMs) is envisaged; however, barriers exist. Hence, this study sought to determine significant barriers to adopting SCMs in Zimbabwe.

Design/methodology/approach

An online questionnaire survey of construction professionals in consultancy firms and semi-structured interviews with key informants in Zimbabwe and Africa were instituted. Mean score analysis, normalisation values and exploratory factor analysis were quantitatively used to determine significant barriers. Content analysis of qualitative data from key informants was used to triangulate the findings.

Findings

From the normalisation (with values > 0.90) and thematic analysis, a lack of incentives, training and government support were exposed as the most critical barriers. The factor analysis revealed seven significant components: governmental policy, finance and research support-related; sustainable construction material supply chain-related; green building policy and capacitation-related; change and trust-related; cost and complexity-related; project execution and investment-related and awareness and demand-related.

Research limitations/implications

The insights of construction professionals from construction companies were not solicited. However, construction consultancy professionals who have a more significant influence on adopting SCMs were included. The government and clients are most critical in promoting the adoption of SCMs through enacting relevant policies and establishing buy-in.

Originality/value

According to the authors’ knowledge, this is the first study to determine barriers to adopting SCMs through the contribution of key informants from various countries within the African continent.
The role of work engagement and psychological safety in how socially responsible human resources management affects employee voice behaviour
Authors: Silva Vítor Hugo , Duarte Ana Patrícia
Published: December 2024

Purpose

This study aims to explore the role of socially responsible human resource management (SRHRM) as a key driver of employee voice behaviour. The hypotheses included that these human resources management (HRM) practices strengthen employees’ motivation to voice their opinions by increasing their work engagement (WE), thereby encouraging them to share their ideas and concerns about their organization more actively. The hypotheses also proposed that this effect is especially pronounced when employees experience a heightened sense of psychological safety.

Design/methodology/approach

A survey-based correlational study was conducted with a sample of 289 participants to analyse the proposed relationships between the selected variables.

Findings

The results indicate that SRHRM and WE are significantly associated with both promotive and prohibitive voice behaviour among employees. In addition, the moderated mediation model revealed that employees who perceive their organization as adopting SRHRM practices display higher levels of WE, which in turn increases these individuals’ likelihood of engaging in both types of voice behaviour. This relationship is particularly strong for promotive voice when employees experience high levels of organizational psychological safety.

Research limitations/implications

The findings are limited by the cross-sectional research design, which restricts causal inference.

Practical implications

By adopting people-centred HRM practices, organizations can foster psychologically safe environments that enhance employees’ willingness to engage in behaviour beneficial to their organization, such as WE and voice behaviours.

Originality/value

The results highlight the critical role of SRHRM and offer evidence-based insights into how interventions can foster positive employee behaviours and attitudes, including WE and voice behaviour.
Two secretory T2 RNases from a fungal pathogen target distinct insect cell transmembrane proteins to cause cytotoxicity
Authors: Yue Yong , Zhao Xin , Lu Zhuoyue , Dou Wei , Luo Zhibing , Lei Kangmin , Xu Dan , Zhang Yongjun
Published: December 2024

Fungal pathogens produce secretory ribonuclease (RNase) T2 proteins during infection, which contribute to fungal virulence via their enzyme functions in degradation of host cell RNA. However, the details of those proteins entering the host cells are unclear. Our previous study demonstrated that the two secretory RNase T2 members, BbRNT2 and BbTrv, produced by the insect fungal pathogen Beauveria bassiana, caused cytotoxic damage to insect cells and contributed to fungal virulence. Here, the Spodoptera frugiperda ovarian epithelial cells (sf9 cells) were used as models to investigate the interactions of the two fungus‐produced RNase T2 proteins with the insect cells. Two transmembrane proteins, an ABC transporter (SfABCG) and an Innexin 7‐like protein (Sfinx), were identified from the sf9 cells as interacting with BbRNT2 and BbTrv, respectively, through protein immunoprecipitation, yeast‐two hybrid tests and protein pull‐down assays. Although a slight decrease in the sf9 cell viability was examined by transfection of RNA interference of SfABCG or Sfinx, the transfected cells displayed a dramatically decreased sensitivity to BbRNT2 or BbTrv, suggesting the requirement of the two transmembrane proteins for BbRNT2 and BbTrv to enter the insect cells. These results reveal a mechanism of the cytotoxic molecules, T2 RNases, produced by the fungal pathogen, entering the insect cells via interaction with specific insect cell transmembrane proteins and causing cytotoxic damage.
The Future of China‐Gulf Solar and Wind Supply Chains
Authors: Sim Li‐Chen , Griffiths Steven
Published: December 2024

This paper examines the medium‐term trajectory of China‐Gulf renewable energy supply chains amid growing global trade restrictions on China. The research explores how the Arab Gulf states, key collaborators in China's renewable energy sector, navigate these challenges, focusing on the dominance of China in global supply chains for solar and wind components. Using a demand‐pull, supply‐push framework, qualitative analysis assesses two potential scenarios: ‘Blue Sky’, where China‐Gulf supply chains grow stronger through ambitious renewable energy targets and expanded foreign direct investment, and ‘Sand Storm’, where geopolitical tensions and export restrictions could weaken these ties. The findings indicate that while supply chain engagement with China has risks, on balance China‐Gulf supply solar and wind technology supply chains are currently robust and projected to remain so in the future. The study concludes with policy recommendations for strengthening China's engagement with the broader Global South, highlighting opportunities for countries as they scale up domestic renewable energy deployment.
Identification and characterisation of Zucchini yellow fleck virus and a novel Nepovirus from next‐generation sequencing of mixed virus infections in cucumbers (Cucumis sativus) from Crete
Authors: James Anthony , Kryovrysanaki Nikoleta , Andronis Christos , Pappi Polyxeni G. , Kalantidis Kriton , Katsarou Konstantina
Published: December 2024

Cucumbers are susceptible to infections with many characterised virus species. In some cases, mixed virus infections occur and produce novel symptoms. In Greece, routine screening is carried out when virus infection is suspected, or novel symptoms are observed in the field. To identify the viruses associated with distinct symptoms observed in samples from commercial cucumber production areas on the island of Crete, Greece, we carried out high‐throughput sequencing (HTS) from a pool of six samples. Following assembly and BLAST analysis, we identified at least seven viruses based on similarity to published sequences. Two of these sequences represented novel, near‐complete genomes of a putative new nepovirus and of zucchini yellow fleck virus (ZYFV). To confirm the HTS results, the six samples were screened for all identified viruses, and their presence was confirmed through Sanger sequencing of PCR products. The full‐length genomes of both the nepovirus and ZYFV were amplified by PCR and confirmed by Sanger sequencing. We have generated the complete genome of a novel nepovirus from cucumber as well as the first complete genome sequence of a cucumber‐infecting ZYFV isolate from Crete. The nepovirus was mechanically transmissible to Nicotiana benthamiana and induced typical cytopathological modifications consistent with virus infection, as revealed by TEM studies. We propose to name this new virus Cucumber nepovirus A (CuNVA).
Rare but relevant: Nitrous oxide and peripheral neurotoxicity, what do we know?
Authors: Brunt Tibor M. , van den Brink Wim , van Amsterdam Jan
Published: December 2024

Nitrous oxide (N2O), used medically as an anaesthetic, has gained popularity as a recreational drug, with rising prevalence particularly among young adults. While its reinforcing and addictive potential remains debated, N2O is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying N2O‐induced neurotoxicity involves inactivation of vitamin B12 (cobalamin), which disrupts methionine synthesis, essential for maintaining the myelin sheath. This can result in demyelinating diseases, including generalized demyelinating polyneuropathy (GDP). Clinical incidence of N2O‐induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of N2O use and vitamin B12 supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B12 deficiency, may heighten individual vulnerability for N2O's detrimental effects.
Non‐daily contraception: Reinforcing the choice of users and addressing unmet needs of reproductive health
Authors: Kopp Kallner Helena , Lindh Ingela , Gemzell‐Danielsson Kristina
Published: December 2024

Despite great societal efforts promoting female autonomy, Sweden still faces unmet contraceptive needs, with abortion rates being the highest in the Nordic countries. In this commentary, we discuss using non‐daily contraception options to combat these unmet needs. Non‐daily methods include transdermal (i.e., patch), ring, injectables, and long‐acting reversible contraception (LARC). Numerous studies have revealed that users prefer non‐daily methods, and studies implementing structured counseling have revealed an increase in non‐daily methods. Relative to LARC, the patch and the ring are non‐daily parenteral methods that offer the possibility for self‐management. Ultimately, client‐centered counseling and shared decision‐making are crucial for increasing awareness of all methods and enhancing method utilization and adherence. Finally, dispelling myths surrounding reversible hormonal contraception is essential for empowering women to make informed choices and improving overall reproductive health outcomes.
Early Albumin Administration in Veno‐Arterial Extracorporeal Membrane Oxygenation
Authors: Wengenmayer Tobias , Hirth Marvin L. , Jäckel Markus , Bemtgen Xavier , Kaier Klaus , Biever Paul M. , Supady Alexander , Maulhardt Thomas , Westermann Dirk , Staudacher Dawid L. , Rilinger Jonathan
Published: December 2024

Background

The clinical outcome and fluid balance of patients with veno‐arterial extracorporeal membrane oxygenation (VA ECMO) or after extracorporeal cardiopulmonary resuscitation (eCPR) may be improved by addressing the high fluid demand with an early albumin administration.

Methods

In this prospective observational study, patients supported with VA ECMO or eCPR received early albumin administration (25 g/L) to prime the VA ECMO system. These patients were compared to patients who received a regimen based solely on balanced crystalloids (crystalloid group) or a regimen based on a 1:4 volume mixture of albumin (10 g/L) and balanced crystalloids (albumin group).

Results

660 VA ECMO patients (66.4% eCPR) treated between January 2017 and June 2021 were analyzed, whereby 265 patients received crystalloid fluid therapy, 269 patients received albumin therapy, and 126 patients received early albumin therapy.

When compared to the albumin and crystalloid groups, patients in the early albumin treatment group had significantly lower cumulative fluid balances (p < 0.05). However, this effect was only observed in the group of eCPR patients and not in patients with cardiogenic shock. Logistic regression revealed albumin administration as an independent predictor of increased survival (Odds ratio 1.66 (1.11–2.47) [95%‐CI], p = 0.013). Yet, only eCPR patients showed a survival benefit from albumin administration compared to the crystalloid group (survival of 29.4% vs. 18.8%, p = 0.024).

Conclusion

Early albumin administration in eCPR patients was linked to a significant decline in fluid balance. Moreover, volume therapy with albumin application was an independent predictor for improved survival in eCPR patients.
Trauma in the courtroom: The role of prior trauma exposure and mental health on stress and emotional responses in jurors
Authors: Brooks Matthew , Glynn Jessica , Fawcett Hannah , Barnes Aminah , Carew Rachael , Errickson David , Livanou Maria
Published: December 2024

Objectives

Prior research indicates that jury duty can be distressing for some jurors. This study examined: (1) the influence of prior trauma characteristics (type, exposure, time since trauma), medical fear and mental health difficulties on stress and emotional responses during a mock trial and 1 week later; and (2) associations between early stress reactions during a trial on subsequent stress and emotional reactivity after exposure to skeletal evidence and 1 week later.

Methods

Mock jurors (n = 180) completed baseline self‐report mental health measures, read a summary of a murder case and were then exposed to graphic skeletal evidence. Stress and/or emotional responses were collected at baseline, after reading the case summary, before and after viewing the skeletal evidence and 7 days post‐trial.

Results

Participants reported a wide range of prior traumatic experiences, with nearly half reporting pre‐existing mental health difficulties. Average traumatic stress symptoms tripled from baseline to follow‐up, with 44% of participants meeting PTSD‐type criteria 7 days later. Medical fear and mental health difficulties were positively associated with some stress and/or emotional responses throughout the trial, with mixed findings concerning trauma characteristics, stress and emotional reactivity. Initial stress and emotional responses to case evidence were linked to later stress and emotional reactions, after accounting for pre‐existing trauma and mental health characteristics.

Conclusions

Past trauma experiences, mental health difficulties and immediate stress responses during a trial can exacerbate emotional and stress reactions. Addressing the psychological impacts of pre‐existing trauma symptoms could improve juror well‐being during this important civic duty.