bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of persistence: Genetic and behavioral population complexity of winter flounder amid population declines
Authors: Dolan Tara E. , Feldheim Kevin A. , O'Leary Shannon J. , Fede Catherine M. , McElroy Anne E. , Frisk Michael G.
Published: August 2024

Winter flounder Pseudopleuronectes americanus (Walbaum 1792) are a coastal flatfish species of economic and cultural importance that have dwindled to <15, % of their historic abundance in the southern New England/Mid‐Atlantic region of the United States, with evidence indicating near‐extirpation of certain local populations. This species exhibits intricate behaviors in spawning and migration that contribute to population complexity and resilience. These behaviors encompass full or partial philopatry to natal estuaries, the generation of multiple pulses of larval delivery, and partial migration. The patterns of genetic diversity within and among estuaries and cohorts presented here carry important implications in understanding the susceptibility to demographic shocks, even if the full extent of genetic diversity within and among winter flounder stocks on the US East Coast remains unresolved. Our findings reveal connectivity between estuaries in Long Island, New York, suggesting the potential for genetic rescue of depleted subpopulations. Family reconstruction and relatedness analysis indicate that split cohorts and migration contingents are not the result of genetically distinct lineages. We found no evidence for genetic structure separating these groups, and in some instances, we were able to detect closely related individuals that belonged to different migratory contingents or cohorts. Characterizing the spatial and behavioral organization of this species at the population level is crucial for comprehending its potential for recovery, not only in terms of biomass but also in reinstating the complex population structure that supports resilience. The search for generality in winter flounder spawning and migration behavior remains elusive, but perhaps the lack of generalities within this species is what has allowed it to persist in the face of decades of environmental and anthropogenic stressors.
‘My words would have more weight’: exploring weight stigma in UK dietetic practice and dietitian's lived experiences of weight stigma
Authors: Brown Adrian , Flint Stuart W.
Published: August 2024

Background

Weight stigma is pervasive within healthcare and negatively impacts both access to care and the patient‐practitioner relationship. There is limited evidence on weight stigma among registered dietitians, particularly in the United Kingdom, though data show weight‐related prejudice towards people living with obesity. The aim of this study was to examine both explicit and implicit weight stigma in practicing dietitians in the United Kingdom, as well as the lived experience of weight stigma among dietitians, both towards themselves and towards others.

Methods

An online cross‐sectional survey was disseminated between February and May 2022 using snowball sampling. Inclusion criteria were that participants were UK registered dietitians aged 20–70 years.

Results

Four hundred and two dietitians responded to the survey (female [94.1%], mean age 40.2 years [standard deviation (SD) 10.7]; White ethnicity [90%]; median 12 years [interquartile range (IQR) 6, 22] within dietetic practice). Mean self‐reported body mass index was 25.1 kg/m² (SD 8.7). Most dietitians reported experiencing weight stigma prior to (51%) and postregistration (59.7%), whereas nearly a quarter (21.1%) felt that weight influenced their ability as a dietitian. Weight stigma was experienced across the weight spectrum. Overall participants reported explicit weight bias attitudes, moderate beliefs that obesity is controllable and implicit antifat bias. Within open‐ended responses, dietitians reported three key themes related to their personal experiences of weight stigma: (1) experiences of stigma in dietetic practice, (2) impact of weight stigma and (3) perception of weight, appearance and job.

Conclusion

This study shows that UK dietitians exhibit both explicit and implicit weight bias towards people living with obesity. Dietitians reported experiencing weight stigma, which impacted their career‐related decisions and their perception of their own ability to perform as dietitians. The study highlights the need to address weight stigma and its implications within the dietetic profession.
Reverse and antegrade vector thread lifting techniques: Correcting nasolabial and marionette lines
Authors: Park Soo Yeon , Kim Soo‐Bin , Wan Jovian , Samin Kashif Ali , Lee Kar Wai Alvin , Chan Lisa Kwin Wah , Suwanchinda Atchima , Yi Kyu‐Ho
Published: August 2024

Background

This study evaluates the efficacy of reverse and antegrade thread lifting vectors in conjunction with thread selection for correcting nasolabial folds and marionette lines, aiming to enhance treatment precision and effectiveness.

Methods

Three female patients aged 43, 48, and 53, presenting with primary concerns regarding nasolabial folds, underwent distinct treatment regimens utilizing various types of threads and vectors. Additionally, video demonstrations were recorded to showcase the procedural techniques employed in each case.

Results

The outcomes of the thread lifting procedures demonstrated significant improvements in the correction of the nasolabial fold and marionette line.

Conclusion

Innovative thread insertion techniques involve entry points above the zygomatic arch and threading toward the temple hairline for lateral face lifting. These utilize barbs to pull skin and underlying tissues. The reversal technique involves inserting threads in a criss‐cross pattern, forming a fibrous structure that may prolong the duration of results. Various thread combinations, considering factors such as composition, thickness, and barb size, provide customized procedures. This research introduces clinical applications, including temple area hairline lifting for nasolabial fold and marionette line correction, reverse vectors targeting nasolabial folds and marionette lines, and antegrade approaches from the lateral side.
Prior Running, as Well as Swimming, Hinders Swimming‐Based Taste Aversion Learning in Rats
Authors: Nakajima Sadahiko
Published: August 2024

Running in an exercise wheel or swimming in a water pool endows rats with a conditioned aversion to a taste substance consumed before the activity. The present study explores the psychophysiological processes underlying these activity‐based taste aversions. Experiment 1 demonstrated that prior experience of running or swimming (i.e., familiarization) hinders subsequent taste aversion learning based on swimming in rats, implying a similar psychophysiological process between running and swimming in establishing taste aversion. Experiment 2 replicated the findings of Experiment 1 with rats obtained from another animal supplier. The running‐to‐swimming cross‐familiarization effect demonstrated in these experiments contrasts with a previous report in which prior swimming had no effect on subsequent running‐based taste aversion learning. Theoretical considerations regarding such asymmetrical cross‐familiarization effects extended to discussions on the similarities and differences in the psychophysiological states induced by running, swimming, and emetic lithium chloride injection.
Clinical Prevalence of Hepatitis D Virus Among Hepatitis B Patients in Sulaymaniyah Governorate, Northern Iraq
Authors: Hama Salih A. , Sirwan Raz , Abubakr Muhsin , Ahmed Gasha S. , Rahim Hawbash M.
Published: August 2024

Hepatitis D virus (HDV), which occurs as a co‐infection with the hepatitis B virus (HBV), is a significant public health burden. Currently, there is a scarcity of data regarding this co‐infection in the developing countries. This study aims to address the clinical prevalence of HDV among HBV‐infected patients in Sulaymaniyah Governorate, Iraq. This prospective cross‐sectional study, conducted from May to November 2022, screened HBV DNA‐positive patients visiting Sulaimani Teaching Hospital in Sulaymaniyah governorate, Iraq, for anti‐HDV antibodies and HDV RNA. The study included 150 confirmed HBV DNA‐positive patients. Of these, 54.7% were male. The mean age of the patients was 49.1 ± 10.1 (18–68). Serological assessment found that 23 (15.3%) of the patients had anti‐HDV IgG antibodies, suggesting past or chronic HDV infection, while 16 (10.7%) tested positive for anti‐HDV IgM, indicating recent/acute infection. Further molecular analysis confirmed HDV RNA in 15 (10%) of HBV patients, indicating real HDV prevalence. The prevalence of anti‐HDV and HDV RNA did not significantly differ by age, gender, marital status, residency, medical, family or medical history (p > 0.05). In conclusion, this study demonstrated a relatively high HDV prevalence among HBV patients in Sulaymaniyah Governorate, Iraq, at 10%, which stresses the need for better screening, health strategies and focused research to combat its impact.
Plant infection by the necrotrophic fungus Botrytis requires actin‐dependent generation of high invasive turgor pressure
Authors: Müller Tobias , Bronkhorst Jochem , Müller Jonas , Safari Nassim , Hahn Matthias , Sprakel Joris , Scheuring David
Published: August 2024

The devastating pathogen Botrytis cinerea infects a broad spectrum of host plants, causing great socio‐economic losses. The necrotrophic fungus rapidly kills plant cells, nourishing their wall and cellular contents. To this end, necrotrophs secrete a cocktail of cell wall degrading enzymes, phytotoxic proteins and metabolites. Additionally, many fungi produce specialized invasion organs that generate high invasive pressures to force their way into the plant cell. However, for most necrotrophs, including Botrytis, the biomechanics of penetration and its contribution to virulence are poorly understood.

Here, we use a combination of quantitative micromechanical imaging and CRISPR–Cas‐guided mutagenesis to show that Botrytis uses substantial invasive pressure, in combination with strong surface adherence, for penetration.

We found that the fungus establishes a unique mechanical geometry of penetration that develops over time during penetration events, and which is actin cytoskeleton dependent. Furthermore, interference of force generation by blocking actin polymerization was found to decrease Botrytis virulence, indicating that also for necrotrophs, mechanical pressure is important in host colonization.

Our results demonstrate for the first time mechanistically how a necrotrophic fungus such as Botrytis employs this ‘brute force’ approach, in addition to the secretion of lytic proteins and phytotoxic metabolites, to overcome plant host resistance.
The Optimal Variation Range of Posterior Condylar Offset Associated with Positive Clinical Outcomes of Primary Total Knee Arthroplasty: A Retrospective Analysis
Authors: Zhong Yanlin , Deng Zengfa , Gu Cheng , Li Ming , Kang Yan , Liao Weiming , Zhang Zhiqi
Published: August 2024

Objective

Posterior condylar offset (PCO) and anterior condylar offset (ACO) exert an influence on the sagittal alignment in total knee arthroplasty (TKA). However, there is no common consensus that the variation range of posterior condylar offset (PCO) is associated with patient‐reported outcome measures (PROMs) and the optimum variation range of PCO. This study aims to investigate the correlation between PCO and the PROMs of primary TKA for osteoarthritis (OA) and find out the optimal variation range of the PCO.

Methods

In this study, we performed a radiographic analysis of 106 patients (112 knees) with primary TKA. Patients were divided into two cohorts (A and B) according to the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC). Correlations between the sagittal parameter and WOMAC were investigated using univariate and multivariate analysis. The receiver operating characteristic (ROC) curve was used to establish the cut‐off value for the optimal variation range. We then further investigated how different variation range affects the WOMAC subscale score and forgotten‐joint‐score‐12 (FJS‐12).

Results

Univariate analysis revealed a correlation between the variation range of PCO (p < 0.01), ACO (p < 0.01) and PROMs. Multivariate analysis showed that only PCO was associated with PROMs. In the ROC graph, the cut‐off value of the variation range of PCO is 2.85 mm (AUC = 0.66, Youden index = 0.26). The WOMAC functional ability score of the group outside the PCO variation range of 2.85 mm significantly increased compared to the group within the range.

Conclusion

In this study, PCO variation was significantly associated with clinical outcomes in TKA and the optimal PCO variation range was within 2.85 mm. Maintaining the PCO variation within 2.85 mm could enhance functional recovery and patient satisfaction.
Integrative taxonomy reveals inflated biodiversity in the European Temnothorax unifasciatus complex (Hymenoptera: Formicidae)
Authors: Csősz Sándor , Alicata Antonio , Báthori Ferenc , Galkowski Christophe , Schifani Enrico , Yusupov Zalimkhan , Herczeg Gábor , Prebus Matthew M.
Published: August 2024

Temnothorax unifasciatus (Latreille, 1798) is a widely distributed pan‐European species from the Iberian Peninsula to the Caucasus. This taxon's relatively high morphological variability prompts the taxonomists of earlier times and today to mention the morphologically different elements at specific or subspecific ranks. This paper aims to understand the population structure and genetic diversity within this lineage via integrative taxonomy, incorporating molecular phylogenetics, species delimitation analyses and multivariate analyses of continuous morphometric data from across the geographic range of the T. unifasciatus complex. Phylogenetic analyses yielded incongruent trees. The genealogical diversity index (gdi) and the confirmatory analyses on morphological data found only weak, ambiguous delimitations within the unifasciatus complex. The most highly supported scenario splits T. brackoi from the remaining unifasciatus complex with ambiguous support (gdi = 0.56). This scenario is supported by multivariate morphometry with 100% accuracy in classification success. Instead, our results suggest complex morphological and genetic population structuring within the broad range of T. unifasciatus. Therefore, we confirm the validity of two species, T. brackoi Salata & Borowiec, 2019 and T. unifasciatus (Latreille, 1798), and propose five new junior synonymies, T. cordieri (Bondroit, 1918) syn. nov., T. tauricus (Ruzsky, 1902) syn. nov., T. berlandi (Bondroit, 1918) syn. nov., T. unifasciatus staegeri (Bondroit, 1918) syn. nov., T. tuberum ciscaucasicus (Arnol'di, 1977) syn. nov. with the latter. To achieve maximal taxonomic stability, we designated a lectotype for Temnothorax unifasciatus (Latreille, 1798).
Structural Analysis of Periodic Trusses and Lattice Materials: States of Self-Stress, Mechanisms, and Mechanical Properties
Authors: Ickin Oguz Aycan , Tekoglu Cihan
Published: August 2024

In the realm of low relative density, a rigid-jointed lattice material exhibits a mechanical response analogous to that of a pin-jointed periodic truss with an identical micro-architecture. This correspondence simplifies the evaluation of the lattice's structural performance. While established matrix methods in linear algebra are capable of determining the states of self-stress, infinitesimal mechanisms, and mechanical properties of pin-jointed periodic trusses, they lack a systematic approach to deriving closed-form expressions for these properties. This paper presents a straightforward approach to address this gap. Furthermore, we introduce an inventive finite element framework that directly yields self-stress states and infinitesimal mechanisms in periodic trusses subjected to specific uniform macroscopic loading conditions. This framework allows for the determination of mechanical properties for periodic trusses by solving straightforward boundary value problems, such as uniaxial tension/compression or simple shear. The developed finite element framework offers greater simplicity compared to the matrix methods, with its benefits becoming more pronounced for complex micro-architectures. To demonstrate the effectiveness of the two newly developed methods, we conduct structural analyses on five different lattice materials, achieving successful outcomes.
A new form of severe acute localized reactions following intra-articular hyaluronic acid injections in knee osteoarthritis. A case report
Authors: Fodor Daniela , Serban Oana , Macavei Sergiu Gabriel , Tudoran Lucian Barbu , Bora Paula , Badarinza Maria
Published: August 2024

Intra-articular hyaluronic acid (HA) injections are widely used for the treatment of symptomatic knee osteoarthritis. Adverse reactions were described in a limited number of patients and consist in local inflammatory reactions and severe acute inflammatory reactions (pseudosepsis). We present the case of a 71-year-old woman who experienced a severe acute adverse effect immediately (within minutes) following intraarticular HA administration, attributed to HA precipitation. The severe very early local manifestations were accompanied by important systemic reactions, necessitating treatment with systemic corticosteroids besides joint lavage.
High extinction risk in large foraminifera during past and future mass extinctions
Authors: Feng Yan , Song Haijun , Song Hanchen , Wu Yuyang , Li Xing , Tian Li , Dong Shuaishuai , Lei Yanli , Clapham Matthew E.
Published: August 2024

There is a strong relationship between metazoan body size and extinction risk. However, the size selectivity and underlying mechanisms in foraminifera, a common marine protozoa, remain controversial. Here, we found that foraminifera exhibit size-dependent extinction selectivity, favoring larger groups (>7.4 log
10
cubic micrometer) over smaller ones. Foraminifera showed significant size selectivity in the Guadalupian-Lopingian, Permian-Triassic, and Cretaceous-Paleogene extinctions where the proportion of large genera exceeded 50%. Conversely, in extinctions where the proportion of large genera was <45%, foraminifera displayed no selectivity. As most of these extinctions coincided with oceanic anoxic events, we conducted simulations to assess the effects of ocean deoxygenation on foraminifera. Our results indicate that under suboxic conditions, oxygen fails to diffuse into the cell center of large foraminifera. Consequently, we propose a hypothesis to explain size distribution–related selectivity and Lilliput effect in animals relying on diffusion for oxygen during past and future ocean deoxygenation, i.e., oxygen diffusion distance in body.
Examining air pollution exposure dynamics in disadvantaged communities through high-resolution mapping
Authors: Su Jason G. , Aslebagh Shadi , Vuong Vy , Shahriary Eahsan , Yakutis Emma , Sage Emma , Haile Rebecca , Balmes John , Jerrett Michael , Barrett Meredith
Published: August 2024

This study bridges gaps in air pollution research by examining exposure dynamics in disadvantaged communities. Using cutting-edge machine learning and massive data processing, we produced high-resolution (100 meters) daily air pollution maps for nitrogen dioxide (NO
2
), fine particulate matter (PM
2.5
), and ozone (O
3
) across California for 2012–2019. Our findings revealed opposite spatial patterns of NO
2
and PM
2.5
to that of O
3
. We also identified consistent, higher pollutant exposure for disadvantaged communities from 2012 to 2019, although the most disadvantaged communities saw the largest NO
2
and PM
2.5
reductions and the advantaged neighborhoods experienced greatest rising O
3
concentrations. Further, day-to-day exposure variations decreased for NO
2
and O
3
. The disparity in NO
2
exposure decreased, while it persisted for O
3
. In addition, PM
2.5
showed increased day-to-day variations across all communities due to the increase in wildfire frequency and intensity, particularly affecting advantaged suburban and rural communities.
Feasibility of keeping Mars warm with nanoparticles
Authors: Ansari Samaneh , Kite Edwin S. , Ramirez Ramses , Steele Liam J. , Mohseni Hooman
Published: August 2024

One-third of Mars’ surface has shallow-buried H
2
O, but it is currently too cold for use by life. Proposals to warm Mars using greenhouse gases require a large mass of ingredients that are rare on Mars’ surface. However, we show here that artificial aerosols made from materials that are readily available at Mars—for example, conductive nanorods that are ~9 micrometers long—could warm Mars >5 × 10
3
time smore effectively than the best gases. Such nanoparticles forward-scatter sunlight and efficiently block upwelling thermal infrared. Like the natural dust of Mars, they are swept high into Mars’ atmosphere, allowing delivery from the near-surface. For a 10-year particle lifetime, two climate models indicate that sustained release at 30 liters per second would globally warm Mars by ≳30 kelvin and start to melt the ice. Therefore, if nanoparticles can be made at scale on (or delivered to) Mars, then the barrier to warming of Mars appears to be less high than previously thought.
Saponin nanoparticle adjuvants incorporating Toll-like receptor agonists drive distinct immune signatures and potent vaccine responses
Authors: Ou Ben S. , Baillet Julie , Filsinger Interrante Maria V. , Adamska Julia Z. , Zhou Xueting , Saouaf Olivia M. , Yan Jerry , Klich John H. , Jons Carolyn K. , Meany Emily L. , Valdez Adian S. , Carter Lauren , Pulendran Bali , King Neil P. , Appel Eric A.
Published: August 2024

Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus (HIV). Herein, we developed a highly modular saponin-based nanoparticle platform incorporating Toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, and TLR7/8a adjuvants and their mixtures. These various TLRa–saponin nanoparticle adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific T helper responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform that could improve the design of vaccines and affect modern vaccine development.
The making of a nucleic acid sensor at the dawn of jawed vertebrate evolution
Authors: Wu Zhiwei , Chu Lingyu , Gong Zhen , Han Guan-Zhu
Published: August 2024

Self and nonself discrimination is fundamental to immunity. However, it remains largely enigmatic how the mechanisms of distinguishing nonself from self originated. As an intracellular nucleic acid sensor, protein kinase R (PKR) recognizes double-stranded RNA (dsRNA) and represents a crucial component of antiviral innate immunity. Here, we combine phylogenomic and functional analyses to show that PKR proteins probably originated from a preexisting kinase protein through acquiring dsRNA binding domains at least before the last common ancestor of jawed vertebrates during or before the Silurian period. The function of PKR appears to be conserved across jawed vertebrates. Moreover, we repurpose a protein closely related to PKR proteins into a putative dsRNA sensor, recapturing the making of PKR. Our study illustrates how a nucleic acid sensor might have originated via molecular tinkering with preexisting proteins and provides insights into the origins of innate immunity.
In vivo Bruton’s tyrosine kinase inhibition attenuates alcohol-associated liver disease by regulating CD84-mediated granulopoiesis
Authors: Nagesh Prashanth Thevkar , Cho Yeonhee , Zhuang Yuan , Babuta Mrigya , Ortega-Ribera Marti , Joshi Radhika , Brezani Veronika , Patel Arman , Datta Aditi Ashish , Brezani Viliam , Hsieh Yun-Cheng , Ramos Adriana , Mehta Jeeval , Copeland Christopher , Kanata Eleni , Jiang Zhenghui Gordon , Vlachos Ioannis , Asara John ,   AlcHepNet Consortium, Szabo Gyongyi , Bataller Ramon , McClain Craig J. , Sanya Arun , Mitchell Mack C. , Dasarathy Srinivasan , Shah Vijay H. , Chalasani Naga , Gawrieh Samer , Tu Wanzhu , Barton Bruce
Published: August 2024

Severe alcohol-associated hepatitis (AH) is a life-threatening form of alcohol-associated liver disease. Liver neutrophil infiltration is a hallmark of AH, yet the effects of alcohol on neutrophil functions remain elusive. Identifying therapeutic targets to reduce neutrophil-mediated liver damage is essential. Bruton’s tyrosine kinase (BTK) plays an important role in neutrophil development and function; however, the role of BTK in AH is unknown. Using RNA sequencing of circulating neutrophils, we found an increase in

Btk

expression (
P
= 0.05) and phosphorylated BTK (pBTK) in patients with AH compared with healthy controls. In vitro, physiologically relevant doses of alcohol resulted in a rapid, TLR4-mediated induction of pBTK in neutrophils. In a preclinical model of AH, administration of a small-molecule BTK inhibitor (evobrutinib) or myeloid-specific
Btk
knockout decreased proinflammatory cytokines and attenuated neutrophil-mediated liver damage. We found that pBTK was essential for alcohol-induced bone marrow granulopoiesis and liver neutrophil infiltration. In vivo, BTK inhibition or myeloid-specific
Btk
knockout reduced granulopoiesis, circulating neutrophils, liver neutrophil infiltration, and liver damage in a mouse model of AH. Mechanistically, using liquid chromatography–tandem mass spectrometry, we identified CD84 as a kinase target of BTK, which is involved in granulopoiesis. In vitro, CD84 promoted alcohol-induced interleukin-1β and tumor necrosis factor–α in primary human neutrophils, which was inhibited by CD84-blocking antibody treatment. Our findings define the role of BTK and CD84 in regulating neutrophil inflammation and granulopoiesis, with potential therapeutic implications in AH.
Metagenomes, metagenome-assembled genomes, and metatranscriptomes from a chlorinated ethene-dechlorinating culture amended with biochar pyrolyzed at different temperatures
Authors: Dang Hongyu , Zhao Weilun , Mattes Timothy E.
Published: August 2024

We investigated the effects of biochar and pyrolysis temperature on a chlorinated ethene-dechlorinating anaerobic consortium. Sequencing of nucleic acids from suspended and biochar-attached cells yielded 9 metagenomes, 122 metagenome-assembled genomes, and 18 metatranscriptomes that provide insights into the structure, function, activity, and interactions of the dehalogenating consortium with biochar.
Comprehensive contact tracing during an outbreak of alpha-variant SARS-CoV-2 in a rural community reveals less viral genomic diversity and higher household secondary attack rates than expected
Authors: Sivertsen Audun , Mortensen Nicolay , Solem Unni , Valen Eivind , Bullita Marie Francoise , Wensaas Knut-Arne , Litleskare Sverre , Rørtveit Guri , Grewal Harleen M. S. , Ulvestad Elling
Published: August 2024

Sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes throughout the COVID-19 pandemic has generated a wealth of data on viral evolution across populations, but only a few studies have so far explored SARS-CoV-2 evolution across large connected transmission networks. Here, we couple data from SARS-CoV-2 sequencing with contact tracing data from an outbreak with a single origin in a rural Norwegian community where samples from all exposed persons were collected prospectively. A total of 134 nasopharyngeal samples were positive by PCR. Among the 121 retrievable genomes, 81 were identical to the genome of the introductor, thus demonstrating that genomics beyond clustering genotypically similar viral genomes to confirm relatedness offers limited additional value to manual contact tracing. In the cases where mutations were discovered, five small genetic clusters were identified. We observed a household secondary attack rate of 77%, with 92% of household members infected among households with secondary transmission, suggesting that SARS-CoV-2 introduction into large families is likely to affect all household members.

IMPORTANCE

In outbreak investigations, obtaining a full overview of infected individuals within a population is seldom achieved. We here present an example where a single introduction of B1.1.7 SARS-CoV-2 within a rural community allowed for tracing of the virus from an introductor via dissemination through larger gatherings into households. The outbreak occurred before widespread vaccination, allowing for a “natural” outbreak development with community lockdown. We show through sequencing that the virus can infect up to five consecutive persons without gaining mutations, thereby showing that contact tracing seems more important than sequencing for local outbreak investigations in settings with few alternative introductory transmission pathways. We also show how larger households where a child introduced transmission appeared more likely to promote further spread of the virus compared to households with an adult as the primary introductor.
The Drosophila Zinc Finger Protein CG9609 Interacts with the Deubiquitinating (DUB) Module of the SAGA Complex and Participates in the Regulation of Transcription
Authors: Nikolenko J. V. , Kurshakova M. M. , Kopytova D. V. , Vdovina Y. A. , Vorobyova N. E. , Krasnov A. N.
Published: August 2024

In previous studies, we found that the zinc finger proteins Su(Hw) and CG9890 interact with the Drosophila SAGA complex and participate in the formation of the active chromatin structure and transcription regulation. In this research, we discovered the interaction of the DUB module of the SAGA complex with another zinc finger protein, CG9609. ChIP-Seq analysis was performed, and CG9609 binding sites in the Drosophila genome were identified. Analysis of binding sites showed that they are localized predominantly at gene promoters. The CG9609 protein has been shown to be involved in the regulation of gene expression.
Human eRF1 Translation Regulation
Authors: Shuvalov A. V. , Klishin A. A. , Biziaev N. S. , Shuvalova E. Y. , Alkalaeva E. Z.
Published: August 2024

Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied. Using reporter constructs, we studied the effect of eRF1 mRNA elements on its translation in cell-free translation systems and HEK293 cell culture. Our data indicate the absence of an NMD-dependent autoregulatory circuit for human eRF1 expression. We found that the translation of the eRF1 coding sequence is most strongly influenced by the 5′ untranslated region of eRF1 mRNA and the start codon of the upstream open reading frame. According to the transcription start database, eRF1 mRNA is characterized by high heterogeneity of the transcription start and a variable 5' untranslated region in length. In addition, the start codon of the CDS in eRF1 mRNA is located within the known translational regulator of short 5' untranslated regions (TISU), which also stimulates mRNA transcription of genes with high transcription start heterogeneity. We hypothesize that regulation of human eRF1 synthesis occurs at both the transcriptional and translational levels. At the transcription level, the length of the eRF1 5' untranslated region and the number of the upstream open reading frames in it are regulated. This regulation in turn, regulates the production of eRF1 at the translation level.
Computation of the Fundamental Limits of Data Compression for Certain Nonstationary ARMA Vector Sources
Authors: Gutiérrez-Gutiérrez J. , Barasoain-Echepare Í. , Zárraga-Rodríguez M. , Insausti X.
Published: August 2024

In the present article, the differential entropy rate and the rate distortion function (RDF) are computed for certain nonstationary real Gaussian autoregressive moving average (ARMA) vector sources.
Recurrent Cutaneous Manifestation in Multiple Myeloma
Authors: Hina Mariam , Naviwala Saad Salim , Shabbir-Moosajee Munira , Ali Nasir
Published: August 2024

Cutaneous involvement is an uncommonly encountered manifestation in multiple myeloma (MM), more commonly observed in patients with aggressive subtypes, and often resistant to conventional therapies. Due to its infrequency, reported clinical characteristics have been diverse and relatively non-specific. Particularly uncommon is lower extremity involvement. In this case report, we present a unique case of a patient with refractory immunoglobulin G lambda MM, who subsequently developed recurrence in the lower leg, while being on systemic therapy. Initially, the lesion resembled squamous cell carcinoma, posing a diagnostic challenge. Through meticulous histopathological and immunohistochemical evaluation, cutaneous involvement by MM was confirmed. This case highlights the importance of maintaining a high clinical suspicion for cutaneous involvement in patients with MM who present with new skin lesions, as early diagnosis is crucial for appropriate management.
Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination
Authors: Horswell Ronald , Chu San , Stone Addison E , Fort Daniel , Uwaifo Gabriel , Fonseca Vivian A , Norton Elizabeth B
Published: August 2024

Introduction

The objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of seasonal vaccination.

Research design and methods

We performed a retrospective cohort study using electronic medical records totaling 1,117,263 from two Louisiana healthcare providers spanning January 2012 through December 2017. Adults 18 years or older with two or more records within the study period were included. The primary outcome quantified was influenza-related diagnosis during inpatient (IP) or emergency room (ER) visits and risk reduction with the timing of immunization.

Results

Influenza-related IP or ER visits totaled 0.0122–0.0169 events per person within the 2013–2016 influenza seasons. Subjects with diabetes had a 5.6-fold more frequent influenza diagnosis for IP or ER visits than in subjects without diabetes or 3.7-fold more frequent when adjusted for demographics. Early immunization reduced the risk of influenza healthcare utilization by 66% for subjects with diabetes or 67% for subjects without diabetes when compared with later vaccination for the 2013–2016 influenza seasons. Older age and female sex were associated with a higher incidence of influenza, but not a significant change in risk reduction from vaccination.

Conclusions

The risk for influenza-related healthcare utilization was 3.7-fold higher if patients had diabetes during 2013–2016 influenza seasons. Early immunization provides a significant benefit to adults irrespective of a diabetes diagnosis. All adults, but particularly patients with diabetes, should be encouraged to get the influenza vaccine at the start of the influenza season.
Role of remediation in cases of serious misconduct before UK healthcare regulators: a qualitative study
Authors: Price Tristan , Reynolds Ellie , O’Brien Tim , Gale Thomas , Quick Oliver , Bryce Marie
Published: August 2024

Background

The raison d’etre of healthcare profession regulators across the globe is to protect patients and the public from the risk of harm. In cases of serious misconduct, remediation is deemed to be an important factor when considering the risk of harm from a practitioner under investigation. Yet, we know very little about how regulators account for remediation in their decision-making, and whether it is consistent with the aim of risk reduction. This paper explores the role of remediation in decision-making in cases of serious misconduct before UK healthcare regulators.

Methods

We conducted interviews with 21 participants from across eight of the nine UK healthcare profession regulators, covering a range of roles in the decision-making process in misconduct cases. Interviews were conducted remotely by video call and digitally transcribed. Data were analysed using the framework analysis method. The initial framework was developed from existing literature and guidance documents from the regulators, and was subsequently refined through the various rounds of coding.

Results

Remediation influenced decision-making in three ways: (1) Some types of misconduct were deemed more inherently remediable than others. In cases involving dishonesty or sexual misconduct, remediation was less likely to serve as a mitigating factor. (2) Decision-makers often view remediation as a proxy indicator of practitioner insight. (3) Whether a practitioner had demonstrated their commitment to change through undergoing remediation was more likely to feed into decision-making at the point where current impairment was under consideration.

Conclusions

Remediation plays a key role in decision-makers’ judgements in cases of misconduct, particularly when these cases relate to clinical misconduct. In such cases, remediation informs judgements on the levels of practitioner insight and the risk of such misconduct being repeated. Our results suggest a need to develop remediation interventions that are explicitly geared towards the regulatory function of developing practitioner insight. Regulators should also consider the structure of their fitness to practise processes and whether there are appropriate opportunities for judgements on remediation to feed into decisions and to facilitate balanced and proportionate outcomes.
EphA3 CAR T cells are effective against glioblastoma in preclinical models
Authors: Martins Paulo , D’Souza Rochelle C J , Skarne Niclas , Lekieffre Lea , Horsefield Shane , Ranjankumar Madusha , Li Xiang , Le Thuy T , Smith Fiona , Smith Corey , Burrows Jacqueline , Day Bryan W , Khanna Rajiv
Published: August 2024

Background

Adoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin receptor A3 (EphA3), which is highly expressed in glioblastoma; in particular, on the tumor vasculature and brain cancer stem cells, is an ideal target for immune-based therapies.

Methods

We have designed an EphA3-targeted chimeric antigen receptor (CAR) using the single chain variable fragment of a novel monoclonal antibody, and assessed its therapeutic potential against EphA3-expressing patient-derived glioblastoma neurospheres, organoids and xenografted glioblastoma tumors in immunodeficient mice.

Results

In vitro expanded EphA3 CAR T cells from healthy individuals efficiently recognize and kill EphA3-positive glioblastoma cells in vitro. Furthermore, these effector cells demonstrated curative efficacy in an orthotopic xenograft model of glioblastoma. EphA3 CAR T cells were equally effective in targeting patient-derived neurospheres and infiltrate, disaggregate, and induce apoptosis in glioblastoma-derived organoids.

Conclusions

This study provides compelling evidence supporting the therapeutic potential of EphA3 CAR T-cell therapy against glioblastoma by targeting EphA3 associated with brain cancer stem cells and the tumor vasculature. The ability to target patient-derived glioblastoma underscores the translational significance of this EphA3 CAR T-cell therapy in the pursuit of effective and targeted glioblastoma treatment strategies.
EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses
Authors: Lertsumitkul Leesa , Iliopoulos Melinda , Wang Stacie S , McArthur Sarah J , Ebert Lisa M , Davenport Alexander J , Endersby Raelene , Hansford Jordan R , Drummond Katharine J , Cross Ryan , Jenkins Misty R
Published: August 2024

Background

High-grade gliomas including glioblastoma (GBM) and diffuse midline gliomas (DMG) represent the most lethal and aggressive brain cancers where current treatment modalities offer limited efficacy. Chimeric antigen receptor (CAR) T cell therapies have emerged as a promising strategy, boasting tumor-specific targeting and the unique ability to penetrate the blood-brain barrier. However, the effective clinical application hinges on the optimal choice of antigen, with a limited number, currently under investigation.

Methods

We employed cell surface proteomic analysis of primary human high-grade glioma samples from both adult and pediatric patients. This led to the identification of Ephrin type-A receptor 3 (EphA3) as a prevalently expressed target. We engineered a second-generation EphA3-targeted CAR T cell and assessed function using in vitro and in vivo models of GBM and DMG.

Results

EphA3-targeted CAR T cells demonstrated robust antigen-specific killing of human GBM and DMG cell lines in vitro. In an orthotopic xenograft NSG mouse model, EphA3-targeted CAR T cells not only effectively eradicated tumors but also established a functional T cell population protective on rechallenge. Remarkably, mice rechallenged with a second contralateral orthotopic tumor implantation achieved complete tumor clearance and maintained a sustained complete response 6 months following initial treatment.

Conclusion

Building on the proven safety profile of EphA3 antibodies in clinical settings, our study provides compelling preclinical evidence supporting the efficacy of EphA3-targeted CAR T cells against high-grade gliomas. These findings underscore the potential for transitioning this innovative therapy into clinical trials, aiming to revolutionize the treatment landscape for patients afflicted with these formidable brain cancers.
Assessment of piles’ resistance driven sequentially in fine-grained soils using pile load tests
Authors: Bilgin Ömer , Alzahrani Saeed , Narsavage Peter , Nusairat Jamal , Dettloff Alexander , Merklin Christopher
Published: August 2024

This paper presents a field pile load test program conducted on four 0.36 m closed-end steel pipe piles with lengths ranging between 11 and 13 m installed in fine-grained soils. Subsurface investigations with standard penetration tests and cone penetration tests with pore pressure measurements were performed at the site. Three pushed-in piezometers at incremental offsets from the piles were also installed to monitor pore water pressure changes during and after the installation of piles. Several dynamic load tests were performed at different times to observe the change in pile resistance. A static load test was also performed on one of the piles. Some load test results showed an unexpected decrease in the resistances of some piles with time. The study showed that construction activities, e.g., installation of other piles, disturbs the soil and groundwater conditions which can significantly affect the pile resistance measured during load tests. This investigation revealed that pile driving and restrikes should be scheduled such that the effect of construction activities on load tests results will be avoided or minimized.
Oscillations in the elastic high energy amplitude
Authors: Grafström P. , Martin A. D. , Ryskin M. G.
Published: August 2024

We discuss the oscillations in the elastic pp differential cross section seen in the TOTEM data at $$\sqrt{s}=13$$

s

=
13

TeV on the top of the usual smooth behaviour.
A Clebsch portrait for Schrödinger’s theory
Authors: Barbieri Gabriele , Spera Mauro
Published: August 2024

In this note we pursue the investigation initiated in Spera M (in: Nielsen, Barbaresco, (eds) Geometric Science of Information. GSI 2023. Lecture Notes in Computer Science, Springer, Cham, 2023) by addressing geometric and topological issues concerning the zero set of the wave function, provided it is a knot in 3-space. Since, the standard Madelung velocity breaks down thereat, it is necessary to resort to the Clebsch geometry of the probability current shown in the above paper. This leads to considering several tightly interknit symplectic manifolds.
Surface Roughness Prediction in Additive Manufacturing: Presenting the Power of Neural Networks Compared to Linear Regression
Authors: Abdulshahed A. M. , Wafa Fatma
Published: August 2024

This paper investigates surface roughness prediction in additive manufacturing through a comprehensive comparative analysis of linear regression (LR) and neural network (NN) models. Employing [Formula: see text]-means clustering, we identify four distinct clusters within the experimental data, each closely associated with specific 3D printing parameters. Within each cluster, we explore the optimal combination of factors that contribute to surface roughness and power efficiency. The main objective focuses on predicting a target variable, with an emphasis on evaluating model performance via key metrics such as [Formula: see text]-squared ([Formula: see text]2), adjusted [Formula: see text]-squared, predicted [Formula: see text]-squared, mean squared error (MSE), and correlation coefficient ([Formula: see text]). Our study’s results illuminate the robust predictive capabilities of both LR and NN models. However, it becomes evident that the Neural Network model outperforms Linear Regression. It exhibits excellent performance metrics, characterized by higher [Formula: see text]2 and correlation values, reduced MSE, and greater resilience to outliers. This pronounced disparity underscores the Neural Network model’s exceptional suitability for tasks requiring precise predictions and the identification of nonlinear patterns, particularly in the field of surface roughness prediction in additive manufacturing. These findings emphasize the key role of advanced machine learning techniques, illustrated by neural networks, in achieving precision within similar domains.
BUILDING A BRIDGE BETWEEN “EQUITY AND INGENUITY”: A SYSTEMATIC REVIEW OF ORGANISATIONAL JUSTICE AND INNOVATION AND FUTURE RESEARCH DIRECTIONS
Authors: RBIAA OUSSAMA , DEXTRAS-GAUTHIER JULIE
Published: August 2024

Innovation is a pivotal driver of competitive advantage and overall organisational success. Despite an extensive body of literature exploring the link between organisational justice (OJ) and innovation, a comprehensive synthesis regarding whether fair treatment within the workplace fosters innovation is notably lacking. This systematic review elucidates a predominantly positive correlation between OJ and various dimensions of innovation, although in some instances suggesting a neutral relationship between the two constructs. Furthermore, the research highlights knowledge sharing as a prominent intermediary variable among scholars. The study contributes significantly by demystifying the nuances of the relationship between OJ and innovation. Second, it introduces a categorisation of OJ and innovation subconstructs and identifies emergent concepts based on cluster analysis. Third, it presents a comprehensive conceptual model linking OJ, innovation, and several variables. Finally, the study offers seven theoretical research directions aimed at deepening our understanding of this topic.