bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-Driven Business Model Innovation: Pioneering New Frontiers in Value Creation
Authors: Aagaard Annabeth , Tucci Christopher
Published: July 2024

This chapter delves into the transformative impact of AI on business model innovation, exploring how it redefines value creation and how it impacts nine common components of business models. It offers an in-depth examination of AI's role as a dynamic catalyst, reshaping strategic thinking and operational approaches within contemporary business landscapes. By presenting an archetype model, it delineates the strategic pathways through which companies evolve as they embed AI into their business modeling, underscoring AI’s significant role in crafting novel value propositions, value creation, and redefining traditional business models. The analysis ventures beyond mere technological integration to highlight the imperative of adapting business strategies in the face of AI advancements, offering insights into leveraging AI for enduring competitive advantage. This discourse aims to equip scholars and practitioners with the acumen to navigate the complexities of AI in business, fostering innovation that resonates with the modern digital economy's demands, while fostering sustainable growth and innovation.
New Venues for Collaborative Business Model Innovation Through Ecosystems
Authors: Miehé Lucas , Gassmann Oliver
Published: July 2024

Digital transformation enables novel opportunities for incumbents and new entries to collaborate and jointly create value in ecosystems. Ecosystems can be considered as aligned and integrated business models along the customer journey. Using two illustrative examples from financial services, we explain what ecosystems are and which factors must be considered for success. We highlight three use cases that underline the significance of ecosystems for the financial service industry today and explain why ecosystems are game changers for future research on business model innovation.
Platformizers, Orchestrators, and Guardians: Three Types of B2B Platform Business Models
Authors: Ritala Paavo , Jovanovic Marin
Published: July 2024

This chapter develops a typology of B2B platform business models. B2B platforms can be divided into three types depending on the nature of the platform market structures they enable. (1) The product-service platformizer business model creates a platform-like interface on top of a product or service and helps bring in externally-provided production-side complements to join the focal firm’s value proposition. (2) The platform ecosystem orchestrator opens a multi-sided market on top of a B2B product-service value proposition and enables customers to select complements from an ecosystem. (3) The platform market guardian creates an open or semi-open platform marketplace for other B2B firms to transact products or services. For each type, we discuss and illustrate the B2B firm’s value creation and capture logic, platform governance, and platform architecture characteristics.
Effective Mission Integration: A Triple Bottom Line Canvas for Impact Business Model Innovation
Authors: Autio Erkko , Thomas Llewellyn D. W.
Published: July 2024

While there is a growing consensus that firms should consider their social and environmental impact in addition to their financial performance, many find it difficult to integrate social and environmental impact missions with their profit mission. The mission integration challenge is particularly acute when the beneficiaries of the impact missions are not the same as the firm’s customers and when additional activities and resources are required for the intended impact to materialize. Yet, there are few business model design tools specifically designed to facilitate mission integration in impact business models. In this chapter we introduce a new tool developed for to support impact business model integration, the ‘Triple Bottom Line Canvas’ (TBLC). By supporting mission integration, the TBLC should help converting impact missions from profit drags (impact mission comes at a cost to profit) to profit drivers (impact mission drives profit).
Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2
Authors: Chen Zhaoyuan , Zhang Jie , Gao Shenjia , Jiang Yi , Qu Mengdi , Gu Jiahui , Wu Han , Nan Ke , Zhang Hao , Wang Jun , Chen Wankun , Miao Changhong
Published: July 2024

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The inflammatory cytokine storm causes systemic organ damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased in sepsis-induced acute lung injury (ALI). Sepsis activated the MEK/ERK pathway and inhibited Skp2 expression in the pulmonary epithelium, resulting in a reduction of K48 ubiquitination of solute carrier family 3 member 2 (SLC3A2), thereby impairing its membrane localization and cystine/glutamate exchange function. Consequently, the dysregulated intracellular redox reactions induced ferroptosis in pulmonary epithelial cells, leading to lung injury. Finally, we demonstrated that intravenous administration of Skp2 mRNA-encapsulating lipid nanoparticles (LNPs) inhibited ferroptosis in the pulmonary epithelium and alleviated lung injury in septic mice. Taken together, these data provide an innovative understanding of the underlying mechanisms of sepsis-induced ALI and a promising therapeutic strategy for sepsis.
On Proper Direct Image in o-Minimal Expansions of Groups
Authors: Edmundo Mário J. , Prelli Luca
Published: July 2024

We show that the formalism of the six Grothendieck operations holds in the sub-category of definably locally closed definable subsets equipped with the o-minimal site in o-minimal expansions of ordered groups.
Penetrating trauma on the rise– nine-year trends of severe trauma in Sweden
Authors: Holmberg Lina , Mani Kevin , Linder Fredrik , Wanhainen Anders , Wahlgren Carl Magnus , Andréasson Håkan
Published: July 2024

Purpose

Sweden has an established trauma system involving national trauma criteria and the Swedish trauma registry (SweTrau), since over a decade. Meanwhile, the injury panorama has evolved, with an increase in gang-related violence in the Swedish community. In this study, we aimed to investigate long-term trends in mortality, management and trauma type in two major Swedish trauma centers over a nine-year period.

Methods

All trauma patients with a New Injury Score (NISS) > 15 or a Trauma Alert (TA) call during 2013–2021 were identified in the participating centers’ SweTrau registries. Data were analysed regarding mortality, proportion of emergency interventions, intensive care unit (ICU) admissions, mechanism of injury and type of trauma (penetrating or blunt). To assess trends, Chi-Squared test for trend and JoinPoint regression method were used.

Results

A total of 10,587 patients were included in the study. Mortality remained unchanged over time in patients with NISS > 15 (10.0-10.9%, p = 0.963) but increased in patients with a TA and NISS < 15 (1.3-2.7%, p = 0.005). For NISS > 15, the proportion undergoing emergency interventions was stable (53.9%-48.8%, p = 0.297) while ICU admissions declined (62.1%-45.7%, p < 0.001). Penetrating trauma increased (12.4-19.6%, p < 0.001), including knife (10.0-15.7%, p < 0.001) and gunshot wounds (2.3-3.8%, p < 0.001), whereas accidents involving motorcycles (8.8%-7.0%, p = 0.004) and pedestrians (5.3%-2.2%, p < 0.001) decreased. Assaults (both penetrating and blunt) increased from 14.7 to 21.4% (p < 0.001).

Conclusions

In this trend analysis at two major Swedish trauma centers during 2013–2021, penetrating trauma increased with over 50% while traffic injuries decreased. The rise in mortality in patients with a TA and NISS < 15 is concerning and requires further evaluation, as do the reduction in ICU admissions.
Ant-following behavior is correlated with plumage traits in African understory birds
Authors: Waltert Matthias , Klug Janina , Motombi Francis Njie , Cejp Benjamin , Bobo Kadiri Serge , Soofi Mahmood , Peters Marcell K.
Published: July 2024

Ant-following behavior is a common phenomenon in birds of Neotropical and Afrotropical rainforests but yet little is known from Central Africa. We here report on the phenomenon in lowland rainforest in Cameroon, quantifying the strength of the interaction of different ant-following bird species with driver ants and test the hypothesis that higher levels of specialization in ant-following behavior are associated with dominance or aggression-dependent plumage and other morphological traits. Flock size varied between 1 and 11 individuals with a mean size of 5.34 ± 2.68 (mean ± SD) individuals occurring at the same time. The maximum number of species present during one raid observed was ten, whereas the minimum number was four with an overall species richness of 6.89 ± 2.1 species. The 21 attending bird species strongly varied in the degree of ant-following behavior. In an interspecific comparison, plumage traits such as the presence of a colored crown, eyespots, and bare skin around the eye, in combination with metatarsus length and weight, were significantly correlated with ant-following behavior. These results suggest that—in size and identity of species—ant-following bird assemblages in Central Africa are similar to those reported from East Africa. They also suggest that ant following favors the selection of traits that signal dominance in interactions between individuals struggling for valuable food resources in the forest understory.
Entzündliche Ursachen von Schlaganfällen – Diagnostik und Therapie
Authors: Schmidt-Pogoda Antje , Straeten Frederike A. , Beuker Carolin , Werring Nils , Minnerup Jens
Published: July 2024

Entzündliche Schlaganfallursachen sind häufig und stellen oft eine diagnostische und therapeutische Herausforderung dar, da es hierzu kaum randomisierte Studien gibt und für viele Konstellationen keine klaren Leitlinienempfehlungen existieren. Nach Veröffentlichung der Empfehlungen der Europäischen Schlaganfallgesellschaft zur primären Angiitis des zentralen Nervensystems (PACNS) im letzten Jahr hat die Deutsche Gesellschaft für Neurologie (DGN) in diesem Jahr eine sehr klare Leitlinie zur Diagnostik und Therapie der PACNS herausgegeben und die Empfehlungen für die systemischen Vaskulitiden aktualisiert. Häufig treten Schlaganfälle jedoch nicht nur infolge einer primären Gefäßentzündung auf, sondern auch als Komplikation einer anderen Organinfektion. So erleiden ca. 5 % aller PatientInnen mit einer Sepsis, ca. 20 % der PatientInnen mit bakterieller Meningitis und bis zu 40 % der PatientInnen mit bakterieller Endokarditis als Komplikation einen Schlaganfall. Unser Artikel fasst die wichtigsten Charakteristika dieser entzündlichen Ursachen von Schlaganfällen zusammen und fokussiert hierbei insbesondere auch auf aktuelle Empfehlungen zum diagnostischen und therapeutischen Management.
Longitudinal metabolite and protein trajectories prior to diabetes mellitus diagnosis in Danish blood donors: a nested case–control study
Authors: Lundgaard Agnete T. , Westergaard David , Röder Timo , Burgdorf Kristoffer S. , Larsen Margit H. , Schwinn Michael , Thørner Lise W. , Sørensen Erik ,   DBDS Genomic Consortium, Nielsen Kaspar R. , Hjalgrim Henrik , Erikstrup Christian , Kjerulff Bertram D. , Hindhede Lotte , Hansen Thomas F. , Nyegaard Mette , Birney Ewan , Stefansson Hreinn , Stefánsson Kári , Pedersen Ole B. V. , Ostrowski Sisse R. , Rossing Peter , Ullum Henrik , Mortensen Laust H. , Vistisen Dorte , Banasik Karina , Brunak Søren
Published: July 2024

Aims/hypothesis

Metabolic risk factors and plasma biomarkers for diabetes have previously been shown to change prior to a clinical diabetes diagnosis. However, these markers only cover a small subset of molecular biomarkers linked to the disease. In this study, we aimed to profile a more comprehensive set of molecular biomarkers and explore their temporal association with incident diabetes.

Methods

We performed a targeted analysis of 54 proteins and 171 metabolites and lipoprotein particles measured in three sequential samples spanning up to 11 years of follow-up in 324 individuals with incident diabetes and 359 individuals without diabetes in the Danish Blood Donor Study (DBDS) matched for sex and birth year distribution. We used linear mixed-effects models to identify temporal changes before a diabetes diagnosis, either for any incident diabetes diagnosis or for type 1 and type 2 diabetes mellitus diagnoses specifically. We further performed linear and non-linear feature selection, adding 28 polygenic risk scores to the biomarker pool. We tested the time-to-event prediction gain of the biomarkers with the highest variable importance, compared with selected clinical covariates and plasma glucose.

Results

We identified two proteins and 16 metabolites and lipoprotein particles whose levels changed temporally before diabetes diagnosis and for which the estimated marginal means were significant after FDR adjustment. Sixteen of these have not previously been described. Additionally, 75 biomarkers were consistently higher or lower in the years before a diabetes diagnosis. We identified a single temporal biomarker for type 1 diabetes, IL-17A/F, a cytokine that is associated with multiple other autoimmune diseases. Inclusion of 12 biomarkers improved the 10-year prediction of a diabetes diagnosis (i.e. the area under the receiver operating curve increased from 0.79 to 0.84), compared with clinical information and plasma glucose alone.

Conclusions/interpretation

Systemic molecular changes manifest in plasma several years before a diabetes diagnosis. A particular subset of biomarkers shows distinct, time-dependent patterns, offering potential as predictive markers for diabetes onset. Notably, these biomarkers show shared and distinct patterns between type 1 diabetes and type 2 diabetes. After independent replication, our findings may be used to develop new clinical prediction models.

Graphical Abstract
Deletion of RFX6 impairs iPSC-derived islet organoid development and survival, with no impact on PDX1+/NKX6.1+ progenitors
Authors: Aldous Noura , Elsayed Ahmed K. , Memon Bushra , Ijaz Sadaf , Hayat Sikander , Abdelalim Essam M.
Published: July 2024

Aims/hypothesis

Homozygous mutations in RFX6 lead to neonatal diabetes accompanied by a hypoplastic pancreas, whereas heterozygous mutations cause MODY. Recent studies have also shown RFX6 variants to be linked with type 2 diabetes. Despite RFX6’s known function in islet development, its specific role in diabetes pathogenesis remains unclear. Here, we aimed to understand the mechanisms underlying the impairment of pancreatic islet development and subsequent hypoplasia due to loss-of-function mutations in RFX6.

Methods

We examined regulatory factor X6 (RFX6) expression during human embryonic stem cell (hESC) differentiation into pancreatic islets and re-analysed a single-cell RNA-seq dataset to identify RFX6-specific cell populations during islet development. Furthermore, induced pluripotent stem cell (iPSC) lines lacking RFX6 were generated using CRISPR/Cas9. Various approaches were then employed to explore the consequences of RFX6 loss across different developmental stages. Subsequently, we evaluated transcriptional changes resulting from RFX6 loss through RNA-seq of pancreatic progenitors (PPs) and endocrine progenitors (EPs).

Results

RFX6 expression was detected in PDX1+ cells in the hESC-derived posterior foregut (PF). However, in the PPs, RFX6 did not co-localise with pancreatic and duodenal homeobox 1 (PDX1) or NK homeobox 1 (NKX6.1) but instead co-localised with neurogenin 3, NK2 homeobox 2 and islet hormones in the EPs and islets. Single-cell analysis revealed high RFX6 expression levels in endocrine clusters across various hESC-derived pancreatic differentiation stages. Upon differentiating iPSCs lacking RFX6 into pancreatic islets, a significant decrease in PDX1 expression at the PF stage was observed, although this did not affect PPs co-expressing PDX1 and NKX6.1. RNA-seq analysis showed the downregulation of essential genes involved in pancreatic endocrine differentiation, insulin secretion and ion transport due to RFX6 deficiency. Furthermore, RFX6 deficiency resulted in the formation of smaller islet organoids due to increased cellular apoptosis, linked to reduced catalase expression, implying a protective role for RFX6. Overexpression of RFX6 reversed defective phenotypes in RFX6-knockout PPs, EPs and islets.

Conclusions/interpretation

These findings suggest that pancreatic hypoplasia and reduced islet cell formation associated with RFX6 mutations are not due to alterations in PDX1+/NKX6.1+ PPs but instead result from cellular apoptosis and downregulation of pancreatic endocrine genes.

Data availability

RNA-seq datasets have been deposited in the Zenodo repository with accession link (DOI: https://doi.org/10.5281/zenodo.10656891).

Graphical Abstract
Societal recovery trajectories in people with a psychotic disorder in long term care: a latent class growth analysis
Authors: Crutzen Stijn , Burger Simone R. , Visser Ellen , Ising Helga K. ,   PHAMOUS investigators, Arends Johan , Jörg Frederike , Pijnenborg Gerdina Hendrika Maria , Veling Wim , van der Gaag Mark , Castelein Stynke
Published: July 2024

Purpose

For many individuals with a psychotic disorder societal recovery is not accomplished. Research on societal recovery trajectories is mostly focussed on patients with a first episode psychosis. The present study aims to identify distinct societal trajectories in those with long duration of illness, through the identification of patient subgroups that are characterized by homogeneous trajectories.

Methods

Longitudinal data were used from an ongoing dynamic cohort in which people with a psychotic disorder receive yearly measurements to perform a latent class growth analysis. Societal functioning was assessed with the Functional Recovery tool, consisting of three items (1) daily living and self-care, (2) work, study and housekeeping, and (3) social contacts. Furthermore, logistic regression was used to compare subgroups with similar societal recovery at baseline, but distinct trajectories.

Results

A total of 1476 people were included with a mean treatment time of 19 years (SD 10.1). Five trajectories of functioning were identified, a high stable (24.5%), a medium stable (28.3%), a low stable (12.7%), a high declining (11.2%) and a medium increasing subgroup (23.3%). Predictors for not deteriorating included happiness, recent hospitalisation, being physically active, middle or higher education and fewer negative symptoms. Predictors for improving included fewer positive and negative symptoms, fewer behavioural problems and fewer physical and cognitive impairments.

Conclusion

While the majority of individuals show a stable trajectory over four years, there were more patients achieving societal recovery than patients deteriorating. Predictors for improvement are mainly related to symptoms and behavioural problems, while predictors for deteriorating are related to non-symptomatic aspects such as physical activity, happiness and level of education.
Additively manufactured conformal cooling channels through topology optimization
Authors: Lamarche-Gagnon Marc-Étienne , Molavi-Zarandi Marjan , Raymond Vincent , Ilinca Florin
Published: July 2024

Cooling channels play a critical role in various casting and molding processes, impacting both the cycle time and quality of the product. As additive manufacturing technologies become increasingly prevalent, conventional straight-drilled channels are being progressively substituted by intricate cooling lines that conform to the contours of the fabricated part. This transition can lead to a significant reduction of the solidification time and temperature gradients, consequently lowering the occurrence of part defects. However, designing such channels becomes challenging as geometric complexity and manufacturing constraints increase. In this work, we present a density-based topology optimization approach to generate conformal cooling channels in molds and dies inserts. To mitigate temperature variations, the objective function is penalized using the temperature standard deviation of the insert cavity surface. A density-gradient-based constraint is further utilized to reduce the generation of overhanging structures and promote manufacturability. In particular, the use of this constraint leads to the generation of channels characterized by a teardrop-shaped cross section. The cooling efficiency of a selected optimized design is confirmed through computations using a body-fitted solver. The geometry is subsequently manufactured by Laser Powder Bed Fusion (LPBF) and experiments are conducted to compare its performance in comparison to a design featuring straight-drilled channels. The results demonstrate that the optimized geometry significantly enhances the heat extraction rate and further leads to a 43% reduction of the cavity temperature standard deviation.
Effects of isolation on invertebrate biodiversity among the bladderwrack Fucus vesiculosus
Authors: Blanc Jean-François , Rinne Henna , Salovius-Laurén Sonja
Published: July 2024

Geographic isolation is a factor that is known to affect species composition and diversity in marine systems. In this study, we tested the effects of geographic isolation on invertebrate fauna living among the belt-forming foundation species Fucus vesiculosus in the northern Baltic Sea. Sampling was carried out on reefs with varying levels of isolation (0.5, 1 and 2 km) in July 2021 in the Åland islands (between 59.96°N 20.24°E and 59.75°N 20.84°E). The total number of taxa, abundance, Shannon-Wiener index, Pielou’s evenness and biomass were calculated and the effects of isolation were tested using generalised linear models. Multivariate methods were used to analyse differences in the invertebrate community composition. Although the number of taxa and Shannon´s diversity index did not vary along the isolation gradient, the total abundance of fauna decreased with increasing isolation. In addition, some taxa-specific patterns were observed, e.g. the abundance of insect larvae decreased with isolation while isopods were more numerous in the most isolated locations. As diversity and the number of taxa were similar regardless of isolation, shallow Fucus vesiculosus belts likely act as important biodiversity refuges and potential stepping-stones for invertebrates in remote outer archipelago areas. In a changing climate, these kinds of refuges aiding species dispersal are likely to be even more important, and should be considered in conservation planning.
Distinct Communities and Differing Dispersal Routes in Bacteria and Fungi of Honey Bees, Honey, and Flowers
Authors: Tiusanen Mikko , Becker-Scarpitta Antoine , Wirta Helena
Published: July 2024

Microbiota, the communities of microbes on and in organisms or organic matter, are essential for the functioning of ecosystems. How microbes are shared and transmitted delineates the formation of a microbiota. As pollinators forage, they offer a route to transfer microbes among the flowering plants, themselves, and their nests. To assess how the two components of the microbiota, bacteria and fungi, in pollination communities are shared and transferred, we focused on the honey bee Apis mellifera and collected honey bee, honey (representing the hive microbiota), and flower samples three times during the summer in Finland. We identified the bacteria and fungi by DNA metabarcoding. To determine the impact of honey bees’ flower choices on the honey bee and hive microbiota, we identified also plant DNA in honey. The bacterial communities of honey bees, honey, and flowers all differ greatly from each other, while the fungal communities of honey bees and honey are very similar, yet different from flowers. The time of the summer and the sampling area influence all these microbiota. For flowers, the plant identity impacts both bacterial and fungal communities’ composition the most. For the dispersal pathways of bacteria to honey bees, they are acquired directly from the honey and indirectly from flowers through the honey, while fungi are directly transmitted to honey bees from flowers. Overall, the distinctiveness of the microbiota of honey bees, honey, and the surrounding flowers suggests the sharing of microbes among them occurs but plays a minor role for the established microbiota.
Intravertebral collateral enhancement resembling sclerotic metastatic disease in a case of cervical epidural abscess
Authors: Schneider Daniel K. , Ok Ahmet Hakan , Simpfendorfer Claus S. , Forney Michael C. , Subhas Naveen
Published: July 2024

Vertebral body enhancement is occasionally seen on postcontrast CT imaging in the absence of osseous pathology. This enhancement can mimic sclerotic osseous metastatic disease, leading to a diagnostic dilemma for radiologists and increasing the chance of misinterpretation. Existing literature has focused on the association between this enhancement and concomitant central venous system obstruction. We report a 61-year-old woman with a history of nasopharyngeal carcinoma presenting with an epidural abscess who exhibited vertebral body enhancement resembling sclerotic metastatic disease without imaging evidence of central venous obstruction or vertebral osseous metastatic disease. Awareness of this unique presentation may prevent the incorrect diagnostic errors and their associated negative effects on patients.
Yield and clinical impact of image-guided bone biopsy in osteomyelitis of the appendicular skeleton: a systematic review and meta-analysis
Authors: Smayra Karen , Miangul Shahid , Witkowiak Maria M. , Persson Linn K. M. , Lugard Emily E. , Adra Maamoun , Yap Nathanael Q. E. , Ball Jake , Nakanishi Hayato , Than Christian A. , Khoo Michael
Published: July 2024

Objective

To assess the yield and clinical impact of image-guided bone biopsy for osteomyelitis of the appendicular skeleton.

Materials and methods

A literature search of several databases was conducted from inception to August 2023. Eligible studies reported patients who underwent image-guided bone biopsy for investigation of osteomyelitis of the appendicular skeleton. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023466419).

Results

From 370 initial studies screened, eight met the eligibility criteria, with a total of 700 patients. The pooled technical success rate was 99.6% (95% CI: 0.992, 1.001; I

2
 = 0%). Positive bone cultures were pooled at 31.9% (95% CI: 0.222, 0.416; I

2
 = 87.83%) and negative cultures at 68.1% (95% CI: 0.584, 0.778; I

2
 = 87.83%). Methicillin-Sensitive Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus yield was 24.5% (95% CI: 0.096, 0.394; I

2
 = 90.98%) and 7.6% (95% CI: 0.031, 0.121; I

2
 = 34.42%) respectively. Group A Streptococcus yield was 7.0% (95% CI: 0.014, 0.127; I

2
 = 70.94%). Polymicrobial culture yield was 15.7% (95% CI: 0.018, 0.297; I

2
 = 88.90%). Post-procedural management change rate was 36.5% (95% CI: 0.225, 0.504; I

2
 = 92.39%). No complications were reported across studies.

Conclusion

For patients under investigation of osteomyelitis of the appendicular skeleton, image-guided bone biopsy demonstrates a good rate of technical success. Additional studies may provide further support for the use of image-guided bone biopsy in this population. Image-guided bone biopsy results lead to change in antibiotics therapy in a portion of patients with suspected osteomyelitis suggesting its potential utility in select patients.
Significance of targeting DNMT3A mutations in AML
Authors: Huang Guiqin , Cai Xiaoya , Li Dengju
Published: July 2024

Acute myeloid leukemia (AML) is the most prevalent form of leukemia among adults, characterized by aggressive behavior and significant genetic diversity. Despite decades of reliance on conventional chemotherapy as the mainstay treatment, patients often struggle with achieving remission, experience rapid relapses, and have limited survival prospects. While intensified induction chemotherapy and allogeneic stem cell transplantation have enhanced patient outcomes, these benefits are largely confined to younger AML patients capable of tolerating intensive treatments. DNMT3A, a crucial enzyme responsible for establishing de novo DNA methylation, plays a pivotal role in maintaining the delicate balance between hematopoietic stem cell differentiation and self-renewal, thereby influencing gene expression programs through epigenetic regulation. DNMT3A mutations are the most frequently observed genetic abnormalities in AML, predominantly in older patients, occurring in approximately 20–30% of adult AML cases and over 30% of AML with a normal karyotype. Consequently, the molecular underpinnings and potential therapeutic targets of DNMT3A mutations in AML are currently being thoroughly investigated. This article provides a comprehensive summary and the latest insights into the structure and function of DNMT3A, examines the impact of DNMT3A mutations on the progression and prognosis of AML, and explores potential therapeutic approaches for AML patients harboring DNMT3A mutations.
Follow-up of non-palpable testicular incidentalomas under 1 cm: does growth rate differentiate malignant and non-malignant lesions?
Authors: Bertolotto Michele , Campo Irene , Freeman Simon , Lotti Francesco , Huang Dean Y. , Rocher Laurence , Dell’Atti Lucio , Valentino Massimo , Pavlica Pietro , Sidhu Paul S. , Derchi Lorenzo E.
Published: July 2024

Objective

To determine whether small, incidentally detected testicular lesions can be safely followed up, by assessing growth rate and volume threshold for benign vs. malignant lesions.

Methods

This retrospective observational study includes a consecutive series of 130 testicular incidentalomas < 1 cm and with negative tumour markers identified from October 2001 to November 2022, which were initially followed up with ultrasound. A total of 39 cases proceeded to surgery during the study period, either due to lesion growth (n = 28) or patient preference/recommendation by the referring urologist (n = 11). For the lesions that were growing, specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential growth pattern. In addition, the velocity of increase of the average diameter (∆Dav) and of the maximum diameter (∆Dmax) were calculated.

Results

Of the 130 nodules that were initially followed up, six disappeared, eight were reduced in size, eighty-eight were stable, and twenty-eight increased in size. For operated nodules all 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47 × 10−3%volume/day, ≤ 179 days, > 10 × 10−3 mm/day, and > 5 × 10−3 mm/day for SGR, DT, ∆Dmax, ∆Dav, respectively.

Conclusions

Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though overlap exists. An increase of the maximum diameter of about 1 mm and 2 mm in three months and in six months, respectively, suggests malignancy.

Clinical relevance statement

Growing parameters allow an educated assessment of benign and malignant small testicular incidentalomas. Non-aggressive management is justified and safe when follow-up includes self-examination and tumour marker assessment to reduce the risk of interval tumour growth.

Key Points

Small, non-palpable and asymptomatic testicular nodules < 1 cm are unexpectedly discovered during scrotal ultrasound.

Growth indicators estimate the potential malignancy, even though overlap with non-malignant lesions exists.

Non-growing incidentalomas can be safely followed up.
Effective lifetime of Ni laser induced fluorescence excited at 336.9 nm during spark plug discharge
Authors: Bi Ruike , Zhang Kailun , Ehn Andreas , Richter Mattias
Published: July 2024

In this study, the laser induced fluorescence lifetime of Ni atoms in ambient air with presence of a plasma discharge was measured for the first time. Free Ni atoms were generated in air at a pressure of 1 bar by spark plug discharges driven by an inductive coil. The Ni atoms were excited at the 336.957 nm absorption line by a 336.96 nm, 90 ps laser pulse and the resulting temporally resolved decaying fluorescence signals were captured by a PMT. An effective fluorescence lifetime of about 1.1 ns was observed for the fluorescence signal within a 7.4 nm detection window centered at 345 nm. Further analysis also revealed that the lifetime of the transition showed statistically insignificant change throughout the duration of the discharge. The peak intensity of the fluorescence signal was found to be proportional to the integrated signal intensities. This in turn suggests that the integrated fluorescence signals in the aforementioned spectral region are proportional to the population density of ground state Ni atoms in the detection volume. The number density of free Ni atoms in the spark gap was measured over time during the plasma discharge, showing an accumulating trend in the beginning phase of the discharge followed by a slow decrease until the termination.
Practical object and flow structure segmentation using artificial intelligence
Authors: Khojasteh Ali R. , van de Water Willem , Westerweel Jerry
Published: July 2024

This paper explores integrating artificial intelligence (AI) segmentation models, particularly the Segment Anything Model (SAM), into fluid mechanics experiments. SAM’s architecture, comprising an image encoder, prompt encoder, and mask decoder, is investigated for its application in detecting and segmenting objects and flow structures. Additionally, we explore the integration of natural language prompts, such as BERT, to enhance SAM’s performance in segmenting specific objects. Through case studies, we found that SAM is robust in object detection in fluid experiments. However, segmentations related to flow properties, such as scalar turbulence and bubbly flows, require fine-tuning. To facilitate the application, we have established a repository (https://github.com/AliRKhojasteh/Flow_segmentation) where models and usage examples can be accessed.
Subseasonal variability of sea level pressure and its influence on snowpack over mid-high-latitude Eurasia during boreal winter
Authors: Ru Yalu , Ren Xuejuan
Published: July 2024

The atmospheric circulation significantly influences the snowpack over mid-high-latitude Eurasia. This study examines the characteristics of the leading subseasonal variability mode of boreal winter sea level pressure (SLP) with 20-80-day period and its relationship with snowpack over mid-high-latitude Eurasia, using the fifth generation of European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis (ERA5) data and different snowpack datasets. The SLP leading mode, characterized by a monopole pattern with a strong surface anomalous high centered near the Ural Mountains, exhibits a barotropic structure and extends from the surface to the tropopause. Above SLP and geopotential height anomalies propagate southeastward from the Barents-Kara Sea to East Asia. This leading SLP mode contributes to surface air temperature (SAT) and snowfall circulation anomalies over mid-high-latitude Eurasia. The latter two both directly influence on snowpack anomalies in situ. Over high latitude region, snowfall circulation anomaly is the dominant factor to control the snow depth anomaly. Over middle latitude region, both SAT and snowfall circulation anomalies lead to the snowpack anomaly. Furthermore, the response of snow depth to the leading subseaonal SLP mode occurs 2–5 days earlier than the response of snow cover to the same mode over middle latitude region. In addition, it is suggested that the Arctic Oscillation (AO), East Atlantic/West Russia (EAWR) and Polar/Eurasia (PEU) pattern may contribute to the development of the leading SLP mode and subsequently influence snowpack anomalies.
Inhibition of cued but not executed task sets depends on cue-task compatibility and practice
Authors: Berger Alexander , Koch Iring , Kiefer Markus
Published: July 2024

In task switching, processing a task cue is thought to activate the corresponding task representation (“task set”), thereby allowing for advance task preparation. However, the contribution of preparatory processes to the emergence of n−2 repetition costs as index of task set inhibition processes is debated. The present study investigated whether merely preparing for a task activates a corresponding task set, which needs to be inhibited in order to switch to a different task. To this end, we presented so-called task cue-only trials in trial n−2 and assessed subsequent n−2 repetition costs. The results revealed n−2 repetition costs following a task cue-only, but only for compatible cues with a transparent cue-task relation and only at the beginning of the experiment. In contrast, n−2 repetition costs following task execution in trial n−2 were absent. In a second experiment, we sought to rule out that the presence of n−2 repetition costs following a task cue-only and the corresponding absence following task execution were the consequence of a decay of task sets. This second experiment replicated the result pattern of the first experiment, with n−2 repetition costs following a task cue-only being present only at the beginning of the experiment and only for compatible cues. Hence, cue-induced task set inhibition effects depended on cue-task compatibility and practice. Furthermore, merely prepared task sets were more likely inhibited than executed task sets.
Evaluation of the diagnostic sensitivity and specificity of two pen-side tests for detecting African swine fever virus in experimentally infected pigs
Authors: Vu Hanh D. , Luong Hung Q. , Lai Huong T.L. , Nguyen Hoa T. , Pham Trang H. , Truong Lam Q. , Nguyen Giap V. , Vu Hiep L.X.
Published: July 2024

African swine fever virus (ASFV) has spread through many countries and regions worldwide, causing significant losses. Timely detection of ASFV-infected pigs is crucial for disease control. In this study, we assessed the performance of two pen-side tests: a portable real-time PCR (qPCR) test for detecting viral genomic DNA and a lateral flow immunoassay (LFIA) for detecting viral antigens. To determine the time from infection to the earliest detection, 10 ASFV-seronegative pigs were inoculated intramuscularly with 104.0 hemadsorption dose 50 of a highly virulent ASFV strain. Whole blood and oral swab samples were alternately collected from each group of five pigs daily until all succumbed to the infection. Samples were promptly subjected to the two pen-side tests upon collection, and a subset was transported to a veterinary diagnostic laboratory for analysis using a reference qPCR assay. Viral genomic DNA was consistently detected by the reference qPCR assay in all blood samples from 2 days postinfection (dpi), preceding the onset of clinical signs, and in oral swabs from 4 dpi onwards. The portable qPCR test demonstrated comparable performance to the reference qPCR assay for both whole blood and oral swab samples. The LFIA exhibited 100% specificity when testing with whole blood samples but showed reduced sensitivity, particularly for blood samples collected early or late after infection. The antigen test did not perform well with oral swabs.
Qualitative properties for a Moore–Gibson–Thompson thermoelastic problem with heat radiation
Authors: Fernández José R. , Quintanilla Ramón
Published: July 2024

In this work, we study some qualitative properties arising in the solution of a thermoelastic problem with heat radiation. The so-called Moore–Gibson–Thompson equation is used to model the heat conduction. By using the logarithmic convexity argument, the uniqueness and instability of solutions are proved without imposing any condition on the elasticity tensor. Then, the existence of solutions is obtained assuming that the elastic tensor is positive definite applying the theory of linear semigroups, and the exponential energy decay is shown in the one-dimensional case. Finally, we consider the one-dimensional quasi-static version and we assume that the elastic coefficient is negative. The existence and decay of solutions are proved, and a justification of the quasi-static approach is also provided.
Increased cardiovascular disease risk among adolescents and young adults with gastric cancer
Authors: Choi Hea Lim , Kang Danbee , Kim Hyunsoo , Cho Juhee , Jeon Keun Hye , Jung Wonyoung , Shin Dong Wook , Jeong Su-Min
Published: July 2024

Background

Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer.

Objectives

This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors.

Methods

We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression.

Results

During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05–1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06–14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06–14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10–2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06–2.20) emerged as risk factors for CVD development.

Conclusion

This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.
The formal care costs of dementia: a longitudinal study using Swedish register data
Authors: Zilling Jennifer , Gerdtham Ulf-G. , Jarl Johan , Saha Sanjib , Persson Sofie
Published: July 2024

Background

This study investigates the excess costs of dementia from healthcare, social care services, and prescription drugs 3 years before to 6 years after diagnosis. Further, sociodemographic cost differences are explored.

Methods

Using Swedish register data from 2013 to 2016 to compare individuals diagnosed with dementia (n = 15,339) with population controls, the excess formal care costs for people with a dementia diagnosis are obtained with longitudinal regression analysis.

Results

People with dementia incur higher formal care costs for all years studied compared to people without dementia. The excess costs vary from €3400 3 years before diagnosis to €49,700 6 years after diagnosis. The costs are mainly driven by institutional care, and solitary living is a strong predictor of high excess costs.

Conclusion

The results show that the formal care costs of individuals with dementia are substantial, and that the economic burden of dementia in Sweden is larger than previously estimated.
Dynamics of the Polar Front in the southwestern area of Svalbard, Norway
Authors: Shulman Igor , Jarosz Ewa , Cayula Stephanie , Metzger E. Joseph
Published: July 2024

We have investigated the dynamics of the Polar Front (PF) in the southwestern area of Svalbard, where the dynamics are defined by the interaction between the Sørkapp Current (transporting cold and fresh Arctic-type water) and the West Spitsbergen Current (carrying the warmer and more saline Atlantic Water from the Norwegian Sea). Our approach was based on the global circulation model predictions. In accord with the model, the cold and fresher Arctic water masses originated from the eastern side of Svalbard and were flowing along the southern-most point of Svalbard into the southwestern area of Svalbard. This cold and fresher water was spreading and pushing warmer and more saline Atlantic water offshore. The model currents indicated that cold and fresher water masses were mostly transported northward along the south-western coast of Svalbard. In accord with the model and observed density profiles, the PF is a density compensated front with the density gradient mostly in the top 50-75 m. Presence of strong density gradients in the upper 50-75 m of the PF leads to the development of the submesoscale processes as surface frontogenesis and nonlinear Ekman transport. We found strong presence of surface frontogenesis at the PF in the model. The second submesoscale process, the nonlinear Ekman transport, is due to the forcing interaction. During the considered time frame, the winds were blowing mostly from the north-east to south-west across the PF, and therefore, the along-front wind component was very small, resulting in weak non-linear Ekman transport at the PF front.
Targeting sphingolipid metabolism in chronic lymphocytic leukemia
Authors: Nguyen Van Long Flora , Le Trang , Caron Patrick , Valcourt-Gendron Délya , Sergerie Roxanne , Laverdière Isabelle , Vanura Katrina , Guillemette Chantal
Published: July 2024

Elevated levels of circulating C16:0 glucosylceramides (GluCer) and increased mRNA expression of UDP-glucose ceramide glycosyltransferase (UGCG), the enzyme responsible for converting ceramides (Cer) to GluCer, represent unfavorable prognostic markers in chronic lymphocytic leukemia (CLL) patients. To evaluate the therapeutic potential of inhibiting GluCer synthesis, we genetically repressed the UGCG pathway using in vitro models of leukemic B cells, in addition to UGCG pharmacological inhibition with approved drugs such as eliglustat and ibiglustat, both individually and in combination with ibrutinib, assessed in cell models and primary CLL patient cells. Cell viability, apoptosis, and proliferation were evaluated in vitro, and survival and apoptosis were examined ex vivo. UGCG inhibition efficacy was confirmed by quantifying intracellular sphingolipid levels through targeted lipidomics using mass spectrometry. Other inhibitors of sphingolipid biosynthesis pathways were similarly assessed. Blocking UGCG significantly decreased cell viability and proliferation, highlighting the oncogenic role of UGCG in CLL. The efficient inhibition of UGCG was confirmed by a significant reduction in GluCer intracellular levels. The combination of UGCG inhibitors with ibrutinib demonstrated synergistic effect. Inhibitors that target alternative pathways within sphingolipid metabolism, like sphingosine kinases inhibitor SKI-II, also demonstrated promising therapeutic effects both alone and when used in combination with ibrutinib, reinforcing the oncogenic impact of sphingolipids in CLL cells. Targeting sphingolipid metabolism, especially the UGCG pathway, represents a promising therapeutic strategy and as a combination therapy for potential treatment of CLL patients, warranting further investigation.
Trade, productivity, and services input intensity
Authors: Hoekman Bernard , Sanfilippo Marco , Santi Filippo , Ticku Rohit
Published: July 2024

Using rich administrative microdata on Ugandan firms, we investigate the response of productivity to trade participation for firms in all sectors of the economy, and the moderating role of services input intensity. We find that companies that participate in trade, especially through importing, display a productivity premium. Firms that export are more productive only for a sub-sample spanning the manufacturing sector. We do not find evidence that using service inputs more intensively enhances the relationship between trade participation and firm productivity. Rather, we find some evidence that a higher share of spending on services inputs attenuates the positive relationship between trade status and productivity. This suggests that the quality of available services may not be up to the standard required to be internationally competitive.