bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Controlled Double-Blinded Split-Face Prospective Clinical Trial to Assess the Efficacy, Safety, and Tolerability of a Novel 3-Step Routine Compared to Benzyl Peroxide for the Treatment of Mild to Moderate Acne Vulgaris
Authors: Gern Alison , Walter Jessica , Xu Shuai , Vakharia Paras P.
Published: November 2023

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid and graduated retinol regimen (Geologie Clear System) versus a common OTC BPO-based regimen (Proactiv Solution) over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, Geologie outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. “I would use this in the future), performance (“my skin improved” and “helped my acne clear up faster”). Geologie users reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (Geologie) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability Geologie was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p=0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.
Analytical treatment interruption: detection of an increase in the latent, inducible HIV-1 reservoir more than a decade after viral resuppression
Authors: Lungu Cynthia , Hossain Tanvir , Prins Henrieke A.B. , Hensley Kathryn S. , Crespo Raquel , Rokx Casper , Rao Shringar , van Kampen Jeroen J. A. , van de Vijver David A.M.C. , Mesplède Thibault , Katsikis Peter D. , Mueller Yvonne M. , Gruters Rob A. , Mahmoudi Tokameh
Published: November 2023

Analytical treatment interruption (ATI) studies are increasingly being performed to evaluate the efficacy of putative strategies towards HIV-1 reservoir elimination or antiretroviral therapy (ART)-free viral control. A limited number of studies have evaluated the impact of ATI on the HIV-1 reservoir in individuals on suppressive ART. Available data suggests that ATIs have transient impact on the HIV-1 reservoir, mostly measured by levels of total or integrated HIV-1 DNA, in peripheral blood cells prior to ATI and shortly after ART-mediated viral re-suppression. The long-term impact of intervention ATI studies on the latent, inducible HIV-1 reservoir remains uncertain. We report the first clinical study demonstrating an increase in the latent, inducible HIV-1 reservoir, measured by expression of tat/rev multiply spliced RNA, in nine individuals, despite more than a decade of re-suppressive ART, after undergoing an immune intervention ATI conducted in 2006-2009. Our findings challenge the status quo on ATI risk of viral reservoir reseeding and the long-term outcomes thereof.
Wastewater monitoring of SARS-CoV-2 gene for COVID-19 epidemiological surveillance in Tucumán Argentina
Authors: D’Arpino María Cecilia , Sineli Pedro Eugenio , Goroso Gustavo , Watanabe William , Saavedra María Lucila , Hebert Elvira María , Martínez María Alejandra , Migliavaca Julieta , Gerstenfeld Silvina , Chahla Rossana Elena , Bellomio Augusto , Albarracín Virginia Helena
Published: November 2023

Epidemiology based on the detection of pathogens in wastewater is extremely useful in providing information about a population’s health status. This study aimed to analyze and report the epidemiological dynamics of SARS-CoV-2 in the province of Tucumán, Argentina during the second and third surges of COVID-19 between April 2021 and March 2022. The study aimed to quantify SARS-CoV-2 RNA in wastewater, correlating it with clinically reported COVID-19 cases. Wastewater samples (n=72) were collected from 16 sampling points located in 3 cities of Tucumán (San Miguel de Tucumán, Yerba Buena y Banda del Río Salí). Detection of viral nucleocapsid markers (N1 gene) was carried out using one-step RT-qPCR. Viral loads were determined for each positive sample using a standard curve. A positive correlation (p<0.05) was observed between viral load (copies/mL) and the clinically confirmed COVID-19 cases reported during the sampling period in San Miguel de Tucumán. Our research findings provided a crucial insight into the dynamics of SARS-CoV-2 infection during epidemic outbreaks. The implementation of wastewater monitoring has proven to be an invaluable epidemiological tool, facilitating early detection of potential surges in COVID-19 cases, and enabling a comprehensive tracking of the pandemic. Our study underscores the significance of incorporating SARS-CoV-2 genome-based surveillance as a standard practice which will contribute to anticipating any future spikes in infections.
Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial
Authors: Lentz Robert J. , Frederick-Dyer Katherine , Planz Virginia B. , Koyama Tatsuki , Aboudara Matthew C. , Swanner Briana , Roller Lance , Low See-Wei , Salmon Cristina , Avasarala Sameer K. , Hoopman Todd C. , Wahidi Momen M. , Mahmood Kamran , Cheng George Z. , Katsis James M. , Kurman Jonathan S. , D’Haese Pierre-François , Johnson Joyce , Grogan Eric L. , Walston Charla , Yarmus Lonny , Silvestri Gerard A. , Rickman Otis B. , Rahman Najib M. , Maldonado Fabien
Published: November 2023

Background

Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases.

Methods

The VERITAS trial (naVigationEndoscopy toReach Indeterminate lung nodules versusTransthoracic needleAspiration, a randomized controlledStudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure.

Discussion

The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility.

Trial registration

ClinicalTrials.govNCT04250194
Cardiomyopathy in patients with acute ischemic stroke and methamphetamine use: Relevance for cardioembolic stroke and outcome
Authors: Lee Sook Joung , Liu Shimeng , Blackwill Haley , Stradling Dana , Shafie Mohammad , Yu Wengui
Published: November 2023

Methamphetamine use has emerged as a major risk factor of cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate the relevance of methamphetamine use and cardiomyopathy in patients with acute ischemic stroke.

We performed a retrospective study of consecutive patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy defined as left ventricular ejection fraction ≤ 45%. Methamphetamine use was identified by self-reported history of use and/or positive urine drug screen. Logistic regression model was performed to analyze the relevance of methamphetamine-associated cardiomyopathy and cardioembolic stroke.

Among 973 consecutive patients screened for the study, 48 (4.9%) were identified to have methamphetamine use. Compared with Non-meth group (n=892), the patients in the Meth group were significantly younger (53.2 ± 10.0 vs. 69.7 ± 15.2, p <0.001), more likely male (76.6% vs. 50.0%, p <0.001), and associated with significantly higher rate of cardiomyopathy (30.4% vs. 14.0%, p <0.01). They were also less likely to have history of atrial fibrillation (8.7% vs. 33.4%, p<0.01) or hyperlipidemia (28.3% vs. 51.7%, p <0.01). Compared with patients with cardiomyopathy without methamphetamine use, those with methamphetamine use and cardiomyopathy had better functional outcome at 3 months, likely due to younger age and fewer comorbidities. In the logistic regression model, methamphetamine-associated cardiomyopathy was found to be a significant risk factor of cardioembolic stroke (OR 2.88, 95% CI 1.81-4.58, p < 0.0001).

Our results demonstrate that methamphetamine use increases the risk of cardiomyopathy and cardioembolic stroke in young adults.
Effect of outpatient cardiac rehabilitation following in-hospital stroke rehabilitation on motor function and health-related quality of life in stroke survivors
Authors: Yokota Chiaki , Kamada Masatoshi , Nakatsuka Kiyomasa , Takegami Misa , Miura Hiroyuki , Murata Makoto , Nishizono Hiroaki , Nishimura Kunihiro , Goto Yoichi
Published: November 2023

Background

Outpatient cardiac rehabilitation (CR) is a promising tool for improving functional outcome in stroke survivors, however, evidence for improving emotional health is limited. We aimed to clarify the effects of outpatient CR following in-hospital stroke rehabilitation on health-related quality of life (HRQOL) and motor function.

Methods

Patients with acute ischemic stroke or transient ischemic attack discharged directly home were recruited, and 128 patients (male, 92, mean age,73.5 years) who fulfilled criteria for insurance coverage of CR were divided into the CR (+) group (n=46) and CR (−) group (n=82). All patients underwent in-hospital stroke rehabilitation, and within 2 months after stroke onset, patients in the CR (+) group started a 3-month outpatient CR program of supervised outpatient sessions (1-3 times/week). Changes of motor function and HRQOL assessed by the short form-36 version 2 (SF-36) from discharge to 3 months post-discharge were compared between the two groups.

Results

Twenty-six patients in the CR (+) group completed the program and 66 patients in the CR (−) group were followed up at a 3-month examination. Least-square mean changes in 6-minute walk distance and isometric knee extension muscle strength were significantly higher in the CR (+) group than the CR (−) group (52.6 vs. 16.3 m; 10.1 vs. 3.50 kgf/kg). Improvement of HRQOL at 3 months was not observed in the CR (+) group.

Conclusions

Outpatient CR followed by in-hospital stroke rehabilitation within 2 months after stroke onset improved exercise tolerance and functional strength but not HRQOL after completion of CR.
Assessing Facioscapulohumeral Muscular Dystrophy through Comparative Analysis of Bulk and Single-Cell Transcriptomes
Authors: Sayad Saed , Hiatt Mark , Mustafa Hazem
Published: November 2023

Background

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by progressive weakening of the muscles. While the two types of FSHD (FSHD1 and FSHD2) have distinct genetic causes, they share similarities in their clinical presentations. Both result in muscle weakness, particularly in the face, shoulders, and upper arms. Genetic testing is essential for accurately diagnosing the specific type of FSHD and guiding treatment and management.

Method

We acquired bulk and single-cell gene expression data for FSHD2 from theNIH portal website. Our analysis involved an extensive array of differentially expressed genes, and pathway and gene ontology analysis. Using statistical tests, we identified the top up- and down-regulated genes, and the pathways and gene ontology terms characterizing those genes that exhibited substantial changes across both bulk and single-cell transcriptomes.

Results

The top 10 up-regulated genes identified in the bulk gene expression analysis represent a diverse range of biological functions, but all are associated with FSHD. In contrast to the bulk down-regulated genes, the single-cell top 10 down-regulated genes are primarily linked to muscle-related functions. These genes, such asACTC1, ACTA1, MYL11, MYH3, MYL6B, MYBPH, TPM2, MYL2, MYL1, andTNNI1are integral to muscle contraction and skeletal muscle function. Moreover, all the top 10 single-cell down-regulated pathways are implicated in the pathogenesis of muscle dystrophy. Finally, the top 10 down-regulated gene ontology terms are all relevant to the pathogenesis of muscular dystrophy.

Conclusions

This study unequivocally demonstrates that single-cell transcriptomics surpasses bulk transcriptomics in elucidating the genes, pathways, biological processes, molecular functions, and cellular components associated with FSHD2. While bulk transcriptomics offers a broader perspective on gene expression, single-cell transcriptomics shines in its capacity to unveil cell-specific gene regulation, especially in the realm of muscle-related functions.
Variability of mutational signatures is a footprint of carcinogens
Authors: Morrison Maike L. , Mangé Laurane , Senkin Sergey , Rosenberg Noah A. , Foll Matthieu , Fernandez-Cuesta Lynnette , Alcala Nicolas
Published: November 2023

Understanding the genomic impact of carcinogens is fundamental to cancer biology and prevention. However, recent coordinated efforts to detect such fingerprints have been largely unsuccessful, challenging the paradigm that carcinogens induce identifiable mutational signatures. Here we introduce a new method based on statistics from population genetics, signature variability analysis (SVA), that elucidates both the diversity of tumorcausing processes and the heterogeneity of population carcinogen exposure. When we use SVA to re-analyze four prominent studies commonly cited as evidence of nonmutagenic carcinogens, we find that tumors induced by environmental carcinogens do possess mutational signature patterns that distinguish them from spontaneous tumors, even if a specific mutational signature cannot be detected. We find that, across cancers, organs, and model organisms, carcinogen exposure generally increases both the diversity of mutational signatures within a tumor and the homogeneity of signature activity across subjects. Importantly, we show that this increase in signature diversity, far from being a background effect, is associated with the geographic incidence of cancer and can facilitate the acquisition of cancer driver mutations. Our results both encourage a re-examination of the genomic impact of numerous substances and introduce new tools for the analysis of the genomic effects of other substances, potentially influencing carcinogen classifications and cancer prevention policies.
Intra-cellular accumulation of amyloid is a marker of selective neuronal vulnerability in Alzheimer’s disease
Authors: Caramello Alessia , Fancy Nurun , Tournerie Clotilde , Eklund Maxine , Chau Vicky , Adair Emily , Papageorgopoulou Marianna , Jackson Johanna , Hardy John , Matthews Paul M.
Published: November 2023

Characterisation of vulnerable neurons that die earliest with Alzheimer’s disease (AD) could provide rationale treatment targets to slow or prevent neurodegeneration. We used imaging mass cytometry to identify the neuronal sub-types lost earliest in AD and explored associated mechanisms with paired single nuclear transcriptomics inpost-mortemmiddle temporal gyri from diseased donors. We found L5-6 RORB+and L3-6 GAD1+neurons show the greatest loss in AD. These neuronal subtypes also accumulated β-amyloids intracellularly. By contrast, pTau+tangles progressively formed in a distinct L3 RORB+GPC5+subtype that appeared resilient. Both astrocytes and microglia expressed reactive phenotype markers with AD and reactive microglia were spatially associated with vulnerable neurons. RORB+neuronal sub-types accumulating either amyloids or pTau showed increased expression of autophagy-related genes. In conclusion, we identified layer- and neuronal subtype-specific loss with AD that suggest intrinsic autophagy-related defects associated with intracellular accumulation of β-amyloids, rather than pTau, may initiate early neurodegeneration.
Care home’s resilience during the pandemic: changing to adapt
Authors: Da Silva Miguel Vasconcelos , Khan Zunera , Austbø Holteng Lise Birgitte , Gjestsen Martha Therese , Aarsland Dag , Testad Ingelin
Published: November 2023

Introduction

The unfolding of the pandemic in 2020 led to an unprecedented level of stress in care homes, including adjustments and changes within this pivotal service to the community in coping with the increased pressures on and need of support for the National Health Service (NHS). Care homes (CH) were crucial in providing healthcare services, but the support given to them was limited and lacked strategic information that enabled them to experience better outcomes. It was important to understand the CH’s views and strategies and how these endured during the pandemic.

Methods

A total of 220 CH from the Care Home Research Network (CHRN) were invited to take part in an on-line survey, where 51 CH completed the survey. The survey comprised demographic- and open-ended questions concerning the service and adaptations/adjustments made within CH during the pandemic.

Results

CH staff reported an increase in the level of stress in their roles, including their workload, due to COVID-19, which made it difficult to cope with their tasks. CH also reported the fear of uncertainty, with some CH saying there was a lack of information. Loneliness and depression were reported as colossally increasing for residents. CH made changes to their working ways and spaces, adopting a more frequent use of technology platforms to meet residents’ needs.

Conclusion

CH were resilient and adaptable to highly stressful challenges, ensuring residents’ need were met. CH felt a huge pressure to support wider health services, whilst having to deal with uncertainty, staff and supply shortages as well as cope with the loss of residents. Nevertheless, CH reinvented themselves, promoted more teamwork and used supporting channels, including investment in technology to facilitate communication between residents’ and families but also with supporting services such as general practitioners (GPs). Despite these changes, loneliness and depression amongst residents was reported as high. Highlighting the need to assess the long-term impacts of this on residents includes the development of interventions or strategies that will reduce depression/loneliness.
South Asia’s unprotected poor: a systematic review of why social protection programs fail to reach their potential
Authors: Javed Warda , Mumtaz Zubia
Published: November 2023

The incongruity between South Asia’s economic growth and extreme poverty has led to a growing interest in social protection and the subsequent implementation of anti-poverty programs. These work to promote inclusive growth and ensure that the poor do not get left behind. However, many programs have systematically failed to achieve their full potential in reaching the poorest of the poor. We reviewed the literature to understand the determinants behind this inequity in South Asia.

A search of four databases, EconLit, Global Health Database, MEDLINE, SocINDEX, supplemented by citation tracking and an external search, yielded 42 papers evaluating 23 social protection programs. All articles were assessed for quality using the GRADE and GRADE CERQual criteria. Data were analyzed using Thomas & Harding’s thematic synthesis approach to generate new higher-order interpretations.

Our analysis identified five themes underscoring program processes that stop resources from reaching the poor. These include: (1) structurally flawed program theories that overlook the complexities of poverty and are instead rooted in simplistic cause-and-effect approaches overestimating the poor’s gain from participation; (2) elite capture of program resources through the direct appropriation of benefits, their powerful positioning in program implementation, and their ability to dictate the poor’s accessibility through relationships of patronage and withholding of information; (3) insufficient targeting strategies to reach the poorest and a subsequent redirection of resources toward the rich; (4) program designs that overlook gender-based restrictions, hidden costs, the poor’s lack of legal documentation, and their physical and social exclusion; (5) some of the poorest households actively choosing self-exclusion from social protection due to a desire to maintain dignity, a lack of capital, and a perception of programs as substandard.

The review highlights the disconnect between social protection program designs and the ground realities of their ‘ideal’ beneficiaries: the poorest of the poor. We propose the persistence of this well-documented disconnect may stem from three sources. First, there is an unclear understanding of who the poor are in South Asia, with definitions overlooking the historical influence of the caste system. Western perceptions of poverty continue to dominate the discourse. The second challenge is effective engagement and co-production of knowledge with the poor. Lastly, despite encouragement of international collaboration, fast-paced funding calls do not allocate sufficient time to build relationships with the poor primary stakeholders. We suggest the possibility that maintenance of this disconnect is intentional, reflecting a broader power dynamic in which the global and local elite dictate the lives of the poor based on geopolitical interests and national priorities.
LST-AI: a Deep Learning Ensemble for Accurate MS Lesion Segmentation
Authors: Wiltgen Tun , McGinnis Julian , Schlaeger Sarah , Kofler Florian , Voon CuiCi , Berthele Achim , Bischl Daria , Grundl Lioba , Will Nikolaus , Metz Marie , Schinz David , Sepp Dominik , Prucker Philipp , Schmitz-Koep Benita , Zimmer Claus , Menze Bjoern , Rueckert Daniel , Hemmer Bernhard , Kirschke Jan , Mühlau Mark , Wiestler Benedikt
Published: November 2023

Abstract

Automated segmentation of brain white matter lesions is crucial for both clinical assessment and scientific research in multiple sclerosis (MS). Over a decade ago, we introduced an engineered lesion segmentation tool, LST. While recent lesion segmentation approaches have leveraged artificial intelligence (AI), they often remain proprietary and difficult to adopt. As an open-source tool, we present LST-AI, an advanced deep learning-based extension of LST that consists of an ensemble of three 3D-UNets.

LST-AI explicitly addresses the imbalance between white matter (WM) lesions and non-lesioned WM. It employs a composite loss function incorporating binary cross-entropy and Tversky loss to improve segmentation of the highly heterogeneous MS lesions. We train the network ensemble on 491 MS pairs of T1w and FLAIR images, collected in-house from a 3T MRI scanner, and expert neuroradiologists manually segmented the utilized lesion maps for training. LST-AI additionally includes a lesion location annotation tool, labeling lesion location according to the 2017 McDonald criteria (periventricular, infratentorial, juxtacortical, subcortical). We conduct evaluations on 103 test cases consisting of publicly available data using the Anima segmentation validation tools and compare LST-AI with several publicly available lesion segmentation models.

Our empirical analysis shows that LST-AI achieves superior performance compared to existing methods. Its Dice and F1 scores exceeded 0.62, outperforming LST, SAMSEG (Sequence Adaptive Multimodal SEGmentation), and the popular nnUNet framework, which all scored below 0.56. Notably, LST-AI demonstrated exceptional performance on the MSSEG-1 challenge dataset, an international WM lesion segmentation challenge, with a Dice score of 0.65 and an F1 score of 0.63—surpassing all other competing models at the time of the challenge. With increasing lesion volume, the lesion detection rate rapidly increased with a detection rate of >75% for lesions with a volume between 10mm3and 100mm3.

Given its higher segmentation performance, we recommend that research groups currently using LST transition to LST-AI. To facilitate broad adoption, we are releasing LST-AI as an open-source model, available as a command-line tool, dockerized container, or Python script, enabling diverse applications across multiple platforms.
Local reflects global: Life-stage dependent changes in the phenology of coastal habitat use by North Sea herring
Authors: Rademaker Mark , Peck Myron A. , van Leeuwen Anieke
Published: November 2023

Climate warming is affecting the suitability and utilisation of coastal habitats by marine fishes around the world. Phenological changes are an important indicator of population responses to climate-induced changes but remain difficult to detect in marine fish populations. The design of large-scale monitoring surveys does not allow fine-grained temporal inference of population responses, while the responses of ecologically and economically important species groups such as small pelagic fish are particularly sensitive to temporal resolution. Here, we use the longest, highest-resolution time series of species composition and abundance of marine fishes in northern Europe to detect possible phenological shifts in the small pelagic North Sea herring. We detect a clear forward temporal shift in the phenology of nearshore habitat use by small juvenile North Sea herring. This forward shift can best be explained by changes in water temperatures in the North Sea. We find that reducing the temporal resolution of our data to reflect the resolution typical of larger surveys makes it difficult to detect phenological shifts and drastically reduces the effect sizes of environmental covariates such as seawater temperature. Our study therefore shows how local, long-term, high-resolution time series of fish catches are essential to understand the general phenological responses of marine fishes to climate warming and to define ecological indicators of system-level changes.
Cryptococcus neoformansSlu7 ensures nuclear positioning during mitotic progression through RNA splicing
Authors: Krishnan Vishnu Priya , Negi Manendra Singh , Peesapati Raghavaram , Vijayraghavan Usha
Published: November 2023

The position of the nucleus before it divides during mitosis is variable in different budding yeasts. Studies in the pathogenic intron-rich fungusCryptococcus neoformansreveal that the nucleus moves entirely into the daughter bud before its division. Here, we report functions of a zinc finger motif containing spliceosome proteinC. neoformansSlu7 (CnSlu7) in cell cycle progression. The budding yeast and fission yeast homologs of Slu7 have predominant roles for intron 3’ splice site definition during pre-mRNA splicing. Using a conditional knockdown strategy, we show CnSlu7 is an essential factor for viability and is required for efficient cell cycle progression with major role during mitosis. Aberrant nuclear migration, including improper positioning of the nucleus as well as the spindle, were frequently observed in cells depleted of CnSlu7. However, cell cycle delays observed due to Slu7 depletion did not activate the Mad2-dependent spindle assembly checkpoint (SAC). Mining of the global transcriptome changes in the Slu7 knockdown strain identified downregulation of transcripts encoding several cell cycle regulators and cytoskeletal factors for nuclear migration, and the splicing of specific introns of these genes was CnSlu7 dependent. To test the importance of splicing activity of CnSlu7 on nuclear migration, we complemented Slu7 knockdown cells with an intron lessPAC1minigene and demonstrated that the nuclear migration defects were significantly rescued. These findings show that CnSlu7 regulates the functions of diverse cell cycle regulators and cytoskeletal components, ensuring timely cell cycle transitions and nuclear division during mitosis.
Synthesis and characterization of novel intrinsically fluorescent analogs of cholesterol with improved photophysical properties
Authors: Lehmann Max , Reinholdt Peter , Bashawat Mohammad , Scheidt Holger A. , Halder Senjuti , di Prima Duccio , Kongsted Jacob , Müller Peter , Wessig Pablo , Wüstner Daniel
Published: November 2023

Live-cell imaging of cholesterol trafficking depends on suitable cholesterol analogs. However, existing fluorescent analogs of cholesterol either show very different physico-chemical properties compared to cholesterol or demand excitation in the ultraviolet spectral region. We present novel intrinsically fluorescent sterols containing four conjugated double bonds in the ring system and either a hydroxy or a keto group in the C3 position. Synthesis of these probes involves dehydrogenation of 7-dehydrocholesterol using mercury(II) acetate, Swern oxidation/dehydrogenation, and stereoselective Luche reduction. Molecular dynamics simulations and nuclear magnetic resonance spectroscopy reveal that the analog with a 3’-hydroxy-group like cholesterol can condense fatty acyl chains and form hydrogen bonds to water molecules at the bilayer interface. The emission of both probes is red-shifted by 80-120 nm compared to the widely used sterol analogs dehydroergosterol or cholestatrienol. This allows for their imaging on conventional microscopes, as we here show in giant unilamellar vesicles. These experiments reveal a preferred partitioning of both sterol probes into the biologically relevant liquid-ordered phase. In conclusion, we present a synthesis strategy leading to novel intrinsically fluorescent sterol probes with close resemblance of cholesterol. Their improved photophysical properties will allow for live-cell imaging of sterol transport in the future.
Disentangling the mechanisms by which nitrogen enrichment affects consumer damage at different organisational levels
Authors: Mannall Tosca , Daniel Caroline , Alessandrello Vera , Kempel Anne , Allan Eric
Published: November 2023

Nitrogen enrichment could affect primary consumers by increasing foliar N content (nitrogen-disease hypothesis), by increasing dominance of palatable, fast-growing plants (growth-defence trade-off) or by reducing plant diversity (resource concentration effect). These mechanisms might operate differently at different organizational levels. We tested this in a grassland experiment (PaNDiv), manipulating nitrogen enrichment, plant species richness, fast-slow functional composition, and foliar pathogens. We assessed herbivory and pathogen damage, on focal plant individuals, species, and communities. Plant community characteristics were more important drivers of consumer damage than nitrogen enrichment. Host concentration effects strongly affected pathogens but mostly at the species level. Growth-defence trade-off effects were widespread but frequently emerged from interactions between species (associational effects) or with resource concentration effects, leading to different patterns at species and community levels. Our findings suggest that key mechanisms may operate differently at different organisational levels calling for better understanding of how consumer effects scale across levels.
Improved workflow for untargeted metabolomics and NMR analysis of intracellular and extracellular metabolites isolated from Gram positive and Gram negative bacteria
Authors: Frawley Dean , Velasco-Torrijos Trinidad , Walsh Fiona
Published: November 2023

Metabolomics and Nuclear Magnetic Resonance (NMR) spectroscopy have proven to be useful for characterising key metabolome fluctuations in bacteria during stress responses to various environmental agents and antibiotics. However, a number of impediments to current workflows have led to the reduced use of these techniques in microbial research. In this study, we address these limitations and in response have developed a novel1H NMR-based untargeted metabolomics workflow. This method is suitable for use with various bacterial species, reducing the workload in comparison to previously established workflows. Our protocol is simple and reproducible and allows for the isolation of both intracellular (IC) and extracellular (EC) metabolites simultaneously from both Gram (+) and Gram (-) species. This method has been shown to produce consistent results for the ESKAPE pathogensEscherichia coli, Klebsiella pneumoniae, Enterococcus faeciumandStaphylococcus aureus. By using these data as a baseline, future studies involving a myriad of stress conditions can be compared to identify key metabolome differences in each species and to determine the mechanisms utilised by bacteria to respond to stress.
Benchmarking active learning protocols for ligand binding affinity prediction
Authors: Gorantla Rohan , Kubincová Alžbeta , Suutari Benjamin , Cossins Benjamin P. , Mey Antonia S. J. S.
Published: November 2023

Active learning (AL) has become a powerful tool in computational drug discovery, enabling the identification of top binders from vast molecular libraries with reduced costs for relative binding free energy calculations and experiments. To design a robust AL protocol, it is important to understand the influence of AL parameters, as well as the features of the datasets on the outcomes. We use four affinity datasets for different targets (TYK2, USP7, D2R, Mpro) to systematically evaluate the performance of machine learning models (Gaussian Process model, Chemprop), sample selection protocols, as well as the batch size based on metrics describing the overall predictive power of the model (R2, Spearman rank, RMSE) as well as the accurate identification of top 2% / 5% binders (Recall, F1 score). Both models have a comparable Recall of top binders on large datasets, but the GP models surpass Chemprop when training data is sparse. A larger initial batch size, especially on diverse datasets, increased the Recall of both models as well as overall correlation metrics. However, for subsequent cycles, smaller batch sizes of 20 or 30 compounds proved to be desirable. Furthermore, the presence of Gaussian noise to the data, up to a certain threshold, still allowed the model to identify clusters with top-scoring compounds. However, excessive noise (<1σ) did impact the model’s predictive and exploitative capabilities.

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rsofun v5.0: A model-data integration framework for simulating ecosystem processes
Authors: Arán Paredes Josefa , Hufkens Koen , Marcadella Mayeul , Bernhard Fabian , Stocker Benjamin D.
Published: November 2023

Mechanistic vegetation models serve to estimate terrestrial carbon fluxes and climate impacts on ecosystems across diverse biotic and abiotic conditions. Systematically informing them with data is key for enhancing their predictive accuracy and estimating uncertainty. Here we present the Simulating Optimal FUNctioning {rsofun} R package, providing a computationally efficient and parallelizable implementation of the P-model for site-scale simulations of ecosystem photosynthesis, complemented with functionalities for Bayesian model-data integration and estimation of parameters and uncertainty. We describe a use case to demonstrate the package functionalities for modelling ecosystem gross CO2uptake at one flux measurement site, including model sensitivity analysis, Bayesian parameter calibration, and prediction uncertainty estimation. {rsofun} lowers the bar of entry to ecosystem modelling and model-data integration and serves as an open-access resource for model development and dissemination.
Upgrade of the small-angle neutron scattering diffractometer SANS-J at JRR-3
Authors: Kumada Takayuki , Motokawa Ryuhei , Oba Yojiro , Nakagawa Hiroshi , Sekine Yurina , Micheau Cyril , Ueda Yuki , Sugita Tsuyoshi , Birumachi Atsushi , Sasaki Miki , Hiroi Kosuke , Iwase Hiroki
Published: November 2023

The small-angle neutron scattering diffractometer SANS-J at the research reactor JRR-3, Tokai, Japan has been upgraded. A 3He front detector was installed adjacent to the direct beam just behind the sample position to cover scattering in the range 1.3–6 nm−1 for the magnitude of the scattering vector Q. Additionally, the maximum Q covered by the existing main 3He detector was extended to 1.8 nm−1 by decreasing the minimum sample-to-detector distance. These modifications enabled gapless measurements of the scattering curve in the Q range 0.002–6 nm−1 with three standard device layouts that can be changed within 10 min. A new graphical user interface simplifies the operation of the device layouts and data acquisition.
The role of female executives in capital structure decisions: evidence from a Southeast Asian country
Authors: Siregar Muhammad Edo Suryawan , Suherman Suherman , Mahfirah Titis Fatarina , Usman Berto , Zairin Gentiga Muhammad , Kurniawati Herni
Published: November 2023

Purpose

This study aims to investigate how the presence of female executives on the board affects a company’s capital structure decisions. The critical mass of female executives on the board was also considered to observe their impact on capital structure.

Design/methodology/approach

Samples were taken from nonfinancial sector companies listed on the Indonesia Stock Exchange between 2012 and 2021 (3,707 firm-year observations). Capital structure was measured using four approaches, namely, debt-to-total asset ratio (DAR), debt-to-equity ratio (DER), short-term debt-to-total assets (STD) and long-term debt-to-total assets (LTD). The data were analyzed using panel data regression analysis, including a fixed effects model with clustered standard errors.

Findings

The presence of female executives on the board is significantly negatively related to capital structure as measured by DER and STD. The critical mass of women provided no evidence of a relationship with a firm’s capital structure. Robustness checks were performed, and the results were consistent with those in the main analysis.

Research limitations/implications

Female executives can be appointed to management boards when determining a strategy to achieve the capital structure desired by a company.

Originality/value

This study increases the diversity of research in corporate governance by synthesizing various indicators from female executives into a single study to determine their relationships with companies’ capital structures. In addition, this study stands out by incorporating four distinct indicators for assessing capital structure and diverging from the norm observed in many other studies, many of which rely on just two indicators: DAR and DER. Moreover, it strongly emphasizes the unique economic, legal, social and cultural landscapes of developing countries like Indonesia in comparison to their developed counterparts, particularly Western nations.
Service recovery strategies: mitigating negative word-of-mouth in the hotel industry through enhanced customer engagement
Authors: Sukhu Anupama , Bilgihan Anil
Published: November 2023

Purpose

The purpose of this research is to investigate the effects of service recovery experiences on customer engagement in negative word-of-mouth (WOM) in the hotel industry and explore the psychological motives and mediating mechanisms driving consumer behavior.

Design/methodology/approach

A scenario-based experimental design on Qualtrics was used, with a pre-test (N = 200). The main study data were collected using Amazon's Mechanical Turk platform.

Findings

Findings reveal that negative service experiences lead to higher engagement in negative WOM compared to positive and satisfactory recovery service experiences. Even well-executed recovery efforts may not completely eliminate negative WOM. The mediating role of emotional responses is substantiated, as heightened negative service experiences result in more intense negative emotional responses, leading to increased engagement in negative WOM.

Originality/value

The study emphasizes the importance of service recovery strategies and the need for businesses to consistently strive for exceptional service quality. It also highlights the complexity of customer reactions to service experiences, suggesting that further research is needed to explore the factors that minimize negative WOM across various service contexts.
Potential applications and benefits of humanoids in the construction industry: a South African perspective
Authors: Ikuabe Matthew , Aigbavboa Clinton , Kissi Ernest
Published: November 2023

Purpose

In most developing countries, the delivery of construction project is still characterised by inefficiencies resulting from the use of outdated methods and techniques, which retards project performance. Hence, the call for the implementation of innovative technologies such as humanoids in the execution of construction projects as it has been proven to be very effective in other sectors while improving productivity and quality of work. Consequently, this study looks at how humanoids can be used in the construction industry and what benefits they can bring.

Design/methodology/approach

The study employed a quantitative approach underpinned in post-positivist philosophical view using questionnaire as the instrument for data collection. The target respondents were construction professionals, and purposive sampling was used, while a response rate of 62.5% was gotten. The methods of data analysis were mean item score, standard deviation and one-sample t-test.

Findings

The findings revealed that humanoids can be used in progress tracking, auto-documentation and inspection and surveillance of tasks in construction activities. Also, the most important benefits of using humanoids in construction work were found to be shorter delivery times, fewer injuries and more accurate work.

Practical implications

The outcome of the study gives professionals and relevant stakeholders in construction and other interested parties' information about the areas where humanoids can be used and their benefits in construction.

Originality/value

The novelty of this study is that it is a pioneering study in South Africa on humanoids' usage in the construction industry. Also, it expands the existing borderline of the conservation of construction digitalisation for enhanced project execution.
Festival personality, satisfaction and loyalty: the moderating effect of involvement
Authors: Karagöz Deniz , Ramkissoon Haywantee
Published: November 2023

Purpose

The objective of this study was to examine the relationships among festival personality, satisfaction and loyalty. Also, the study further analyzed the moderation effect of involvement on the relationships between festival personality, satisfaction and loyalty.

Design/methodology/approach

The authors adopt a two-stage mixed-method approach. Through a list of brand personality traits from previous research and in-depth interviews with participants of a film festival, festival personality constructs were identified: exceptional, competent, reliable and cozy. The authors then analyzed an integrative model of festival personality, satisfaction, involvement and loyalty from the qualitative findings. A survey with a convenience sample of 279 film festival participants was conducted.

Findings

The findings suggest that festival personality influence satisfaction and loyalty. Furthermore, this study confirms the significant impact of involvement on the relationships between festival personality, satisfaction and loyalty.

Originality/value

This study enables authors to understand the festival personality from the perspective of the visitors and expands the theoretical understanding of how the personality of the festival affects the visitors. The findings of this study suggest that the festival personality can be predictors and determinants of participants' satisfaction and loyalty. Also, this is one of the first attempts to identify the effects of involvement on festival personality and its outcomes. Current research findings demonstrated involvement as a moderator variable in the relationships between festival personality and festival satisfaction and loyalty.