bluuebunny/crossref_metadata_2025 huggingface dataset:
Band gap and gate dielectric engineered novel Si0.9Ge0.1/InAs junctionless TFET for RFIC applications
Authors: Kumar Kaushal , Kumar Ajay , Kumar Vinay , Jain Aditya , Sharma Subhash Chander
Published: August 2024

In this study, we present a dual dielectric material gated novel Si0.9Ge0.1/InAs hetero-structure Junctionless TFET (DMG-HJLTFET), in which first time, a novel amalgamation of Si0.9Ge0.1/InAs along with HfO2 and SiO2 is used on the basis of band gap and gate dielectric engineering respectively. Our main goal is to examine the performance of the reported device in terms of radio frequency (RF), linearity, and intermodulation distortion parameters. The reported device’s (DMG-HJLTFET) result is compared with latest published articles and conventional Si-JLTFET to show the improvement. Our simulation results reveal that DMG-HJLTFET outperforms Si-JLTFET in several key metrics, such as parasitic capacitance (Cgg, 49% ↓), maximum oscillation frequency (fmax, 589 times ↑), gain bandwidth product (GBP, 238.5 times ↑), intrinsic gain (Av, 2.24 × 102 times ↑), peak transconductance (gm, 110 times ↑), and second-order voltage intercept point (VIP2, 330.2% ↑). Our findings lead us to the conclusion that DMG-HJLTFET might be a promising substitute for low-power and high-frequency applications.
What is a combinatorial interpretation?
Authors: Pak Igor
Published: August 2024

In this survey we discuss the notion ofcombinatorial interpretationin the context of Algebraic Combinatorics and related areas. We approach the subject from the Computational Complexity perspective. We review many examples, state a workable definition, discuss many open problems, and present recent results on the subject.
Castelnuovo-Mumford regularity and Schubert geometry
Authors: Yong Alexander
Published: August 2024

We study the Castelnuovo-Mumford regularity of tangent cones of Schubert varieties. Conjectures about this statistic are presented; these are proved for the covexillary case. This builds on work of L. Li and the author on these tangent cones, as well as that of J. Rajchgot-Y. Ren-C. Robichaux-A. St. Dizier-A. Weigandt and J. Rajchgot-C. Robichaux-A. Weigandt on tableau rules for computing regularity of some matrix Schubert varieties.
Some open problems on Coxeter groups and unimodality
Authors: Brenti Francesco
Published: August 2024

In this paper I present some open problems on Coxeter groups and unimodality, together with the main partial results, and computational evidence, that are known about them.
Racial Affect, Spectral Jewishness, and the Haunting of Racial Modernity
Authors: Nahme Paul E
Published: August 2024

This chapter outlines the emotional economy of nineteenth-century Europe and the spectral place of Jews and Jewishness therein. By analyzing key texts from the discourse of Enlightenment humanism to the early twentieth-century racialization of Jews in antisemitic thought, the chapter suggests that Jewishness is configured as a racial specter for European Enlightenment thought.
Gaston Crunelle and Flute Playing in Twentieth-Century France
Authors: Garrison Leonard
Published: August 2024

Gaston Crunelle and Flute Playing in Twentieth-Century France establishes Crunelle’s place in history as one of the most important flutists of the twentieth century. Crunelle (1898–1990), unjustly forgotten today, won a prix d’excellence as a student of Léopold Lafleurance and Philippe Gaubert at the Paris Conservatory. After performing in cinemas during the silent film era, he became principal flutist of the Opéra-Comique and the Pasdeloup Orchestra. When Marcel Moyse left Paris during the German Occupation, Crunelle was appointed professor of flute at the Paris Conservatory and from 1941 to 1969 taught an entire generation of the world’s leading flutists; oral history interviews document his pedagogy. He oversaw the commissioning of important contest pieces by Henri Dutilleux, Pierre Sancan, André Jolivet, Olivier Messiaen, and others. The book chronicles the four-decade history of the Quintette instrumental de Paris in which Crunelle developed a close collaboration with harpist Pierre Jamet. The ensemble, founded by flutist Rene Le Roy left a sumptuous legacy of about fifty commissioned works for flute, harp, and string trio. As an orchestral, chamber, and solo flutist, Crunelle’s recordings are among the best of the 78-rpm and early LP eras. His long career embodies the evolution of musical life in France from World War I through the tumult of May 1968.
Introduction
Authors: Garrison Leonard
Published: August 2024

This chapter explains the gulf between Gaston Crunelle’s renown as a flutist during his lifetime and his posthumous reputation. He was principal flutist in the Opéra-Comique and the Pasdeloup Orchestra, had the longest tenure of any professor of flute in the history of the Paris Conservatory, and taught more first-prize winners than any other flute professor, but his name is hardly known today. He died without family members to curate his legacy. Unlike René Le Roy, he was not an entrepreneur, and unlike Marcel Moyse, he published few pedagogical works and did not develop an international following. His style of playing was eclipsed by the meteoric rise of his student, Jean-Pierre Rampal. Yet an examination of Crunelle’s achievements confirms that he is essential to the history of the French flute school.
Early Years
Authors: Garrison Leonard
Published: August 2024

Gaston Crunelle was born in Douai and first studied at its conservatory. When the town was taken by German forces in 1914, Crunelle’s family moved to Paris, where Gaston studied at the Conservatory with Léopold Lafleurance and Philippe Gaubert, with service in the French Army interrupting his studies. This chapter details the traditions of the Paris Conservatory from its inception in 1795 through the reforms of Gabriel Fauré, who served as its director from 1905 to 1920. These traditions include solfège, the annual concours, and instrumental studies in classes rather than individual lessons. The chapter also covers the evolution of flute teaching from François Devienne through Gaubert, especially that of Paul Taffanel, who developed a style based on vocal models and brought a new seriousness to the solo flute repertoire by reviving Bach’s flute sonatas and Mozart’s flute concertos and by commissioning pieces by leading composers of the belle époque.
Crunelle’s Teaching
Authors: Garrison Leonard
Published: August 2024

This chapter documents Gaston Crunelle’s pedagogy as flute professor at the Paris Conservatory from 1941 to 1969 through oral histories. An unflattering portrait by James Galway does not align with the recollections of most of Crunelle’s students, who depict him as generous and warm but demanding. His teaching had a practical goal, focused exclusively on winning a first prize for each student in the annual concours. His system derived from daily practice of scales and arpeggios from the Taffanel–Gaubert flute method, an inordinate number of études, and repertoire largely limited to Paris Conservatory contest pieces. He was prescriptive—there was usually one correct interpretation of each work down to the details of where to breathe. His tenure coincided with increasing numbers of women in the flute class and the student protests of May 1968.
Crunelle’s Retirement and Legacy
Authors: Garrison Leonard
Published: August 2024

This chapter chronicles Gaston Crunelle’s later years and legacy. Remarkably, after retirement from the Paris Conservatory, he continued teaching at municipal conservatories in the Paris area. He was promoted to officier in the Légion d’Honneur and celebrated at a large funeral in the Église Saint-Roch de Paris, but his achievements are now little known. His students have become major international soloists, orchestral flutists, and flute professors throughout France and the world. Meanwhile, French musical life has been transformed. Cultural resources are now more decentralized, and the traditions of the Paris Conservatory have evolved in conformance with the international standardization of musical training in the European Union.
Properties of the ‘friend of a friend’ model for network generation
Authors: Lo Tiffany Y Y , Levens Watson , Sumpter David J T
Published: August 2024

The way in which a social network is generated, in terms of how individuals attach to each other, determines the properties of the resulting network. Here, we study an intuitively appealing ‘friend of a friend’ model, where a network is formed by each newly added individual attaching first to a randomly chosen target and then to nq ⩾ 1 randomly chosen friends of the target, each with probability 0<q⩽ 1. We revisit the master equation of the expected degree distribution for this model, providing an exact solution for the case when nq allows for attachment to all of the chosen target’s friends [a case previously studied by Bhat et al. (2016, Phys. Rev. E, 94, 062302)], and demonstrating why such a solution is hard to obtain when nq is fixed [a case previously studied by Levens et al. (2022, R. Soc. Open Sci., 9, 221200)]. In the case where attachment to all friends is allowed, we also show that when q<q*≈0.5671, the expected degree distribution of the model is stationary as the network size tends to infinity. We go on to look at the clustering behaviour and the triangle count, focusing on the cases where nq is fixed.
Current understanding and future prospects for ash dieback disease with a focus on Britain
Authors: Combes Matt , Webber Joan , Boddy Lynne
Published: August 2024

Hymenoscyphus fraxineus is an introduced ascomycete fungus which causes ash dieback and has resulted in widespread mortality of ash throughout Europe. Although H. fraxineus has been present on the continent for at least four decades, it was not identified until 2006. The first record of the pathogen in Britain came in 2012 although it was probably present a decade earlier. The most common host European ash (Fraxinus excelsior L.) is economically and ecologically important to Britain where the cost of ash dieback is estimated at billions of pounds. The impact of ash dieback has stimulated a major research response which we review with the aim of providing up-to-date information relevant to Britain and identifying knowledge gaps where research would contribute to improved disease mitigation. Hymenoscyphus fraxineus is an outcrossing fungus with high genotypic diversity; ascospores produced via sexual reproduction are critical to aerial dispersal and infection. Temperature, moisture, and ground cover influence pathogen fruit body development, the timing of ascospore release, and extent of ascospore germination; they also interact together to affect the likelihood of infection. In addition, stand characteristics, including tree density, tree height, and landscape fragmentation, affect disease dynamics with increased disease severity on moist sites with high ash density. Efforts at finding natural resistance in ash have identified genetic markers associated with disease tolerance, and gene expression analysis is providing insights into the basis of that resistance. Mainland European findings indicate that ash dieback makes trees more vulnerable to other pathogens, whilst endophytes in the ash phyllosphere can suppress infection by H. fraxineus. Possible tools for long-term control of ash dieback include (1) deployment of resistant ash, (2) quantitatively informed management practices based on microclimate models and better understanding of the pathogen life cycle, and (3) manipulation of biocontrol agents from the ash microbiome or pathogen mycoviruses.
Genomic diversity and evolution of the Hawaiian Islands endemic Kokia (Malvaceae)
Authors: Kayal Ehsan , Arick Mark A , Hsu Chuan-yu , Thrash Adam , Yorkston Mitsuko , Morden Clifford W , Wendel Jonathan F , Peterson Daniel G , Grover Corrinne E
Published: August 2024

Island species are highly vulnerable due to habitat destruction and their often small population sizes with reduced genetic diversity. The Hawaiian Islands constitute the most isolated archipelago on the planet, harboring many endemic species. Kokia is an endangered flowering plant genus endemic to these islands, encompassing 3 extant and 1 extinct species. Recent studies provided evidence of unexpected genetic diversity within Kokia. Here, we provide high-quality genome assemblies for all 3 extant Kokia species, including an improved genome for Kokia drynarioides. All 3 Kokia genomes contain 12 chromosomes exhibiting high synteny within and between Kokia and the sister taxon Gossypioides kirkii. Gene content analysis revealed a net loss of genes in K. cookei compared to other species, whereas the gene complement in K. drynarioides remains stable and that of Kokia kauaiensis displays a net gain. A dated phylogeny estimates the divergence time from the last common ancestor for the 3 Kokia species at ∼1.2 million years ago (mya), with the sister taxa (K. cookei + K. drynarioides) diverging ∼0.8 mya. Kokia appears to have followed a stepping-stone pattern of colonization and diversification of the Hawaiian archipelago, likely starting on low or now submerged older islands. The genetic resources provided may benefit conservation efforts of this endangered endemic genus.
Biogeography
Authors: Lomolino Mark V. , Riddle Brett R. , Whittaker Robert J.
Published: August 2024

Biogeography, which is in its fifth edition, provides an explanation of how geographic variation across terrestrial and marine environments has influenced the fundamental processes of immigration, extinction, and evolution to shape species distributions and nearly all patterns of biological diversity. This edition builds on the strengths of previous editions to illustrate general patterns and processes using examples from a broad diversity of life forms, time periods, and aquatic and terrestrial ecosystems.
Salicylic acid improves chilling tolerance via CsNPR1–CsICE1 interaction in grafted cucumbers
Authors: Fu Xin , Feng Yiqing , Zhang Yanyan , Bi Huangai , Ai Xizhen
Published: August 2024

Salicylic acid (SA) plays a role in the regulation of grafting-induced cold tolerance. However, the molecular mechanism behind it is still unknown. Here, we established that the phenylalanine ammonia-lyase (PAL) pathway-dependent elevate in SA content in grafted cucumber leaves was not only synthesized in the leaves but also transported from the roots under chilling stress. RNAi-CsPAL with low SA content as rootstock reduced SA accumulation in grafted seedling leaves while decreasing rootstock-induced cold tolerance, as evidenced by higher electrolyte leakage (EL), hydrogen peroxide (H2O2), and superoxide anion (O2·−) contents and lower expression of cold-responsive genes (CsICE1, CsDREB1A, CsDREB1B, and CsCOR47), whereas OE-CsPAL with high SA content as rootstock improved the cold tolerance of grafted plants in comparison with the wild type (WT). In addition, CsNPR1 was significantly upregulated in grafted cucumber under chilling stress, with exogenous and endogenous overexpressed SA inducing its transcriptional expression and protein stability, which exhibited higher expression in grafted plants than in self-root plants. While CsNPR1-overexpression (OE-CsNPR1) seedlings as scions were more tolerant to chilling stress than WT seedlings, CsNPR1-suppression (Anti-CsNPR1) seedlings as scions were more vulnerable to chilling stress. Notably, CsNPR1–CsICE1 interactions alleviated ROS accumulation and activated the expression of CsDREB1A, CsDREB1B, CsCOR47, CsCOR15, CsCOR413, and CsKIN1 to enhance SA-mediated chilling tolerance in grafted cucumber. Overall, our findings reveal that SA enhances chilling tolerance in grafted cucumbers via the model of the CsNPR1–CsICE1 transcriptional regulatory cascade.
Introduction to the 2024 Chordate Origins, Evolution, and Development SICB Symposium
Authors: Swalla Billie J
Published: August 2024

Synopsis

The evolution of the distinct chordate body plan has intrigued scientists for over 170 years. Modern genomics and transcriptomics have allowed the elucidation of the developmental gene regulatory networks (GRNs) underlying the developmental programs for particular tissues and body axes in invertebrates and vertebrates. This has been most revealing in the Deuterostomia, the superphylum in which chordates evolved. The time was ripe to gather those working on deuterostome developmental GRNs to revisit the development and evolution of chordates and discuss the evolution of this unique body plan at the SICB 2024 meetings in Seattle, WA, USA. It has been several years since the genomes of the major deuterostome clades have been sequenced—echinoderms, hemichordates, tunicates, lancelets, and vertebrates. Genomic analyses have shown that lancelets have a genome and body plan that closely resemble the vertebrates, although phylogenomic analyses suggest that the tunicates are the sister group of the vertebrates. The evolution of the sessile and sometimes colonial adult tunicates was likely from a motile, lancelet-like ancestor. Scientists from all over the world converged at the SICB meetings in Seattle to discuss the current ideas of how chordates evolved. Some common mechanisms and themes emerged and are captured in this ICB volume on Chordate Origins, Evolution, and Development.
Distinct microbial communities are linked to organic matter properties in millimetre-sized soil aggregates
Authors: Simon Eva , Guseva Ksenia , Darcy Sean , Alteio Lauren , Pjevac Petra , Schmidt Hannes , Jenab Kian , Ranits Christian , Kaiser Christina
Published: August 2024

Soils provide essential ecosystem services and represent the most diverse habitat on Earth. It has been suggested that the presence of various physico-chemically heterogeneous microhabitats supports the enormous diversity of microbial communities in soil. However, little is known about the relationship between microbial communities and their immediate environment at the micro- to millimetre scale. In this study, we examined whether bacteria, archaea, and fungi organize into distinct communities in individual 2-mm-sized soil aggregates and compared them to communities of homogenized bulk soil samples. Furthermore, we investigated their relationship to their local environment by concomitantly determining microbial community structure and physico-chemical properties from the same individual aggregates. Aggregate communities displayed exceptionally high beta-diversity, with 3–4 aggregates collectively capturing more diversity than their homogenized parent soil core. Up to 20%–30% of ASVs (particularly rare ones) were unique to individual aggregates selected within a few centimetres. Aggregates and bulk soil samples showed partly different dominant phyla, indicating that taxa that are potentially driving biogeochemical processes at the small scale may not be recognized when analysing larger soil volumes. Microbial community composition and richness of individual aggregates were closely related to aggregate-specific carbon and nitrogen content, carbon stable-isotope composition, and soil moisture, indicating that aggregates provide a stable environment for sufficient time to allow co-development of communities and their environment. We conclude that the soil microbiome is a metacommunity of variable subcommunities. Our study highlights the necessity to study small, spatially coherent soil samples to better understand controls of community structure and community-mediated processes in soils.
Selection for greater dispersal in early life increases rate of age-dependent decline in locomotor activity and shortens lifespan
Authors: Ruchitha B G , Kumar Nishant , Sura Chand , Tung Sudipta
Published: August 2024

Locomotor activity is one of the major traits that is affected by age. Greater locomotor activity is also known to evolve in the course of dispersal evolution. However, the impact of dispersal evolution on the functional senescence of locomotor activity is largely unknown. We addressed this knowledge gap using large outbred populations of Drosophila melanogaster selected for increased dispersal. We tracked locomotor activity of these flies at regular intervals until a late age. The longevity of these flies was also recorded. We found that locomotor activity declines with age in general. However interestingly, the activity level of dispersal-selected populations never drops below the ancestry-matched controls, despite the rate of age-dependent decline in activity of the dispersal-selected populations being greater than their respective controls. The dispersal-selected population was also found to have a shorter lifespan as compared to its control, a potential cost of elevated level of activity throughout their life. These results are crucial in the context of invasion biology as contemporary climate change, habitat degradation, and destruction provide congenial conditions for dispersal evolution. Such controlled and tractable studies investigating the ageing pattern of important functional traits are important in the field of biogerontology as well.
The role of sexual partner in women’s seeking for labiaplasty: a systematic review and meta-analysis
Authors: Alavi-Arjas Fatemeh , Nahidi Fatemeh , Simbar Masoumeh , Majd Hamid Alavi , Rastegar Fereshteh
Published: August 2024

Background

The primary reasons for labiaplasty usually revolve around aesthetic, sexual, and functional concerns. Upon delving deeper into these issues, it becomes apparent that sexual partners play a controversial role in influencing women’s decisions to undergo surgery.

Aim

This study aimed to investigate the impact of sexual partners on women’s choices to pursue labiaplasty.

Methods

A comprehensive search was conducted across electronic databases covering the period from January 2000 to February 2024. After removing duplicates, a total of 931 articles were retrieved by searching keywords in titles and abstracts.

Outcomes

The meta-analysis revealed that 36.7% of women who sought labiaplasty cited their partners’ negative comments as a factor influencing their decision.

Results

After applying the eligibility criteria and excluding irrelevant articles, a total of 12 articles involving 962 participants were included in the analysis. With the exception of 2 articles, the majority of the studies suggested a discernible influence of male partners on women’s decisions to seek labiaplasty. Frequently, sexual partners are not the primary decision makers, nor do they exert significant pressure when it comes to seeking labiaplasty. In certain instances, women seeking labiaplasty acknowledged that their sexual partners did influence their decisions, either by making disparaging comments about their genitalia or by directly pressuring or requesting them to undergo labiaplasty. Additionally, women might opt for labiaplasty out of fear of their partner’s negative remarks or to enhance sexual pleasure for their partners. For a more accurate result, a meta-analysis was conducted noting a considerable heterogeneity.

Clinical Implications

The findings of this study can be applied in prelabiaplasty counseling sessions to acknowledge and explore the role of the sexual partner in women’s decision making.

Strengths and Limitations

This study stands as the inaugural systematic review examining the impact of sexual partners on women seeking labiaplasty, encompassing all original studies exploring the role of the sexual partner. However, a notable limitation lies in the varied interpretations of the sexual partner’s role, that the heterogeneous nature of these interpretations poses a challenge to providing a more precise answer through meta-analysis.

Conclusion

Based on the findings of this systematic review, it is evident that sexual partners exert multifaceted influences on women’s decisions to seek labiaplasty. While not serving as the primary decision makers, women opt for labiaplasty with the aim of enhancing attractiveness in sexual relationships and mitigating potential negative comments from their partners.
Operando chemo-mechanical evolution in LiNi0.8Co0.1Mn0.1O2 cathodes
Authors: Zhang Yi , Hao Shuaipeng , Pei Fei , Xiao Xiangpeng , Lu Chang , Lin Xing , Li Zhe , Ji Haijin , Shen Yue , Yuan Lixia , Li Zhen , Huang Yunhui
Published: August 2024

Ni-rich LiNixCoyMnzO2 (NCMxyz, x + y + z = 1, x ≥ 0.8) layered oxide materials are considered the main cathode materials for high-energy-density Li-ion batteries. However, the endless cracking of polycrystalline NCM materials caused by stress accelerates the loss of active materials and electrolyte decomposition, limiting the cycle life. Hence, understanding the chemo-mechanical evolution during (de)lithiation of NCM materials is crucial to performance improvement. In this work, an optical fiber with με resolution is designed to in operando detect the stress evolution of a polycrystalline LiNi0.8Co0.1Mn0.1O2 (P-NCM811) cathode during cycling. By integrating the sensor inside the cathode, the stress variation of P-NCM811 is completely transferred to the optical fiber. We find that the anisotropy of primary particles leads to the appearance of structural stress, inducing the formation of microcracks in polycrystalline particles, which is the main reason for capacity decay. The isotropy of primary particles reduces the structural stress of polycrystalline particles, eliminating the generation of microcracks. Accordingly, the P-NCM811 with an ordered arrangement structure delivered high electrochemical performance with capacity retention of 82% over 500 cycles. This work provides a brand-new perspective with regard to understanding the operando chemo-mechanical evolution of NCM materials during battery operation, and guides the design of electrode materials for rechargeable batteries.
A seamless living biointerface for inflammation management
Authors: Yin Junyi , Wang Shaolei , Chen Guorui , Xiao Xiao , Chen Jun
Published: August 2024

A novel living biointerface that integrates living biological and hydrogel systems, can significantly improve monitoring and treatment through enhanced interaction with biological tissues, revolutionizing our chronic inflammation management.
Genotype-phenotype associations in Von-Hippel Lindau Syndrome: implications for screening
Authors: Murray Nicole
Published: August 2024

Background

Von Hippel-Lindau (VHL) is an autosomal dominant genetic disease with an estimated incidence of 1:36,000. The type of germline VHLI alteration has been shown to impact downstream VHL expression and clinical phenotype. However, current screening practices do not differ based on VHL genomic subtype. We aim to assess genotype-phenotype association among an institutional cohort of VHL patients.

Methods

We conducted a retrospective cohort study of 69 patients (27 families) at the University of Utah and Huntsman Cancer Institute from 1998- December 2023. 41 patients had documented germline testing in our system to define VHL type. VHL Type 1 was defined as those with nonsense mutations, deletions, and duplications and Type 2 as those with missense and splice mutations. Mean follow-up was 86- and 59-months for VHL type 1 and 2 respectively. We then evaluated the association of VHL type with risk of pheochromocytoma (Pheo), renal cancer (RCC), and hemangioblastoma (HB).

Results

We identified 24 unique VHL alterations among 41 patients. 83% (29/41) patients had missense mutations, 7.5% (3/41) had nonsense mutations, 17% (6/41) had splice mutations, and 3% (3/41) had a deletion. The median age at VHL diagnosis was 43 years old for type 1 (range 19-76) and 38 for VHL type 2 (range 4-67). VHL Type 2 was more common, 85% (35/41). All VHL Type 1 patients (6/6) developed RCC and HB. No patients with VHL Type 1 developed PheoPara. Of the 35 patients diagnosed with VHL Type 2, 20% (7/35) were diagnosed with PheoPara, 9% (3/35) with RCC, 31% (n = 11) with HB, and 37% (n = 13) were asymptomatic. No VHL Type 1 patients were asymptomatic.

Conclusions

VHL type 2 comprised the majority of VHL diagnoses in our cohort. Individuals diagnosed with VHL type 2 have the highest penetrance for: hemangioblastoma (hb), Pheo-Para, and renal cell carcinoma (RCC). In our study, 37% of VHL type 2 participants did not demonstrate any VHL manifestation. VHL type 1 had a high prevalence for RCC and HB, with a notable absence of PheoPara manifestation. However, majority of these patients (75%) were below the age of 20, and thus likely did not develop a manifestation yet. This cohort add to evidence supporting utilizing genetic VHL Types to personalize surveillance guidelines. Validation in larger cohorts with longer follow-up suggest that VHL type 1 patients could forgo pheo/para screening.
16 Linking VHL and SETD2 in a common oncogenic pathway that converges on the mitoticspindle
Authors: Dere Ruhee
Published: August 2024

Background

Loss of chromosome 3p is a landmark event in clear cell renal cell carcinoma (ccRCC) that results in mono-allelic loss of VHL (von Hippel Lindau) and SETD2 (Set-domain containing 2) (and other tumor suppressors co-located on 3p). Second hits in VHL inactivate this key tumor suppressor initiating tumor progression. SETD2, a histone methyltransferase, was previously shown to have a dual function in methylating both histones and microtubules, thereby contributing to both the histone and tubulin codes. Methylation by SETD2 on microtubules occurs at the mitotic spindle and is essential for normal mitosis and cytokinesis, with loss of SETD2 acting as a strong driver of apoptosis. This raises a conundrum of how cancer cells survive early mono-allelic loss of SETD2, escaping cell death.

Methods

Using biochemical kinase assays and mass spectrometry we have identified SETD2 as a substrate for AURKA. In addition, we have used immunoblotting and immunofluorescence assays to probe phosphorylation on SETD2 and the impact of phosphorylation of SETD2 both on its chromatin and cytoskeleton targets.

Results

We have identified the mitotic kinase, Aurora kinase A (AURKA), as a regulator of SETD2. Our data uncover SETD2 as a unique substrate for phosphorylation by AURKA, with mass spectrometry identifying serine 2080 (S2080) as the site of phosphorylation on SETD2. We found phosphorylation of SETD2 by AURKA at S2080 contributes to its methyltransferase (i.e. enzymatic) activity on microtubules but does not impact chromatin methylation on H3K36 which remains unaltered. We show that VHL regulates SETD2 via AURKA, and loss of phosphorylation on SETD2 results in mitotic defects and genomic instability. Importantly, we demonstrate that inhibition of AURKA is synthetic lethal in the setting of VHL and SETD2 deficiency.

Conclusions

AURKA expression levels are high in VHL-null cells resulting from an inability of VHL to target AURKA for degradation and our data now highlight a direct link between VHL and SETD2, two tumor suppressors believed to independently drive RCC pathogenesis. In summary, our data reveal a tumor-specific vulnerability linked to mitotic fragility that can be precisely targeted to ultimately drive mitotic catastrophe.

DOD CDMRP Funding: yes
68 Use of artificial intelligence to derive International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) elements from unstructured medical records
Authors: Jaime-Casas Salvador , Ebrahimi Hedyeh , Man Kingson , Mehdinia Sina , Lu Kun-Han , Barragan-Carrillo Regina , Castro Daniela , Mercier Benjamin , Gebrael Georges , Tripathi Nishita , Chehrazi-Raffle Alexander , Chawla Neal , Salgia Nicholas , Zugman Miguel , Hsu JoAnn , Yip Wesley , Tripathi Abhishek , Pal Sumanta
Published: August 2024

Background

Artificial intelligence technologies invoking large language models (LLMs) may be able to automate data collection for the IMDC registry, an otherwise labor-intensive process. We evaluate a proprietary tool (HopeLLM) in expediting data abstraction.

Methods

We utilized a City of Hope-managed IMDC data set that includes patients with metastatic renal cell carcinoma. From this data set, we randomly selected patients who initiated care after 2018 and had sufficient treatment-related information within the Epic electronic health record system to determine HopeLLM performance. Patient identification numbers were manually extracted to prompt HopeLLM for data abstraction. We compared treatment start and end dates between manually registered information and HopeLLM estimations. The difference ratio in months was compared between the two sources. Lin’s concordance correlation coefficient was performed to quantify the rate of agreement between both sources.

Results

Among 513 records, 91 patients were randomly selected. A total of 164 lines of treatment were recorded manually in the registry, and 146 were recorded by HopeLLM. A total of 75 lines of treatment were unique to the registry, while 42 were unique to HopeLLM. There were 117 unmatched lines of treatment between the registry and HopeLLM, which were not considered for concordance analysis. We recorded a difference (median (IQR)) of 0 mos (0-0.09 mos) for start dates between the registry and HopeLLM, with a concordance correlation coefficient of 0.99 (95%CI 0.99-0.99). We recorded a difference of 2.15 mos (0.46-5.54 mos) for end dates between the registry and HopeLLM, with a concordance correlation coefficient of 0.92 (95%CI 0.88-0.95).

Conclusions

HopeLLM can streamline data abstraction from unstructured medical records onto the IMDC database, as it accurately predicts treatment start and end dates for patients with metastatic renal cell carcinoma.
Distributions of Consecutive Level Spacings of Gaussian Unitary Ensemble and Their Ratio: ab initio Derivation
Authors: Nishigaki Shinsuke M
Published: August 2024

In recent studies of many-body localization in nonintegrable quantum systems, the distribution of the ratio of two consecutive energy level spacings, $r_n=(E_{n+1}-E_n)/(E_{n}-E_{n-1})$ or $\tilde{r}_n=\min (r_n,r_n^{-1})$, has been used as a measure to quantify the chaoticity, alternative to the more conventional distribution of the level spacings, $s_n=\bar{\rho }(E_n)(E_{n+1}-E_n)$, as the former makes unnecessary the unfolding required for the latter. Based on our previous work on the Tracy–Widom approach to the Jánossy densities, we present analytic expressions for the joint probability distribution of two consecutive eigenvalue spacings and the distribution of their ratio for the Gaussian unitary ensemble (GUE) of random Hermitian $N\times N$ matrices at $N\rightarrow \infty$, in terms of a system of differential equations. As a showcase of the efficacy of our results for characterizing an approach to quantum chaoticity, we contrast them to arguably the most ideal of all quantum-chaotic spectra: the zeroes of the Riemann $\zeta$ function on the critical line at increasing heights.
Investigation of the psychometric properties of the Toronto Alexithymia Scale in men with and without compulsive sexual behavior
Authors: do Espírito Santo Gonçalves Patrícia , de Tubino Scanavino Marco
Published: August 2024

Background

Previous studies have provided initial evidence supporting the association between compulsive sexual behavior (CSB) and alexithymia, but these studies did not investigate the psychometric property of a measure of alexithymia in individuals with CSB, which is necessary.

Aim

This study investigated the factor analysis, reliability, and construct validity of the Toronto Alexithymia Scale (TAS) in men with CSB and control individuals.

Methods

This cross-sectional study included 418 participants (304 individuals with CSB and 114 control individuals) who underwent a semi-structured psychiatric interview and completed the following instruments: the Sexual Compulsivity Scale, Hypersexual Disorder Screening Inventory, Beck Anxiety Inventory, Beck Depression Inventory, TAS, and Barratt Impulsiveness Scale. The eligible participants were men 18 years of age or older who were literate and residing in Brazil. Individuals who met the diagnostic criteria for Goodman’s criteria for sex addiction were subsequently assessed for the excessive sexual drive (International Classification of Diseases–Tenth Revision F52.7) criteria. Those who met this second criteria were considered individuals with CSB. Participants who did not reach this point were considered control individuals. We conducted factor analysis, reliability analysis (internal consistency and temporal stability), and discriminant and construct validity analyses.

Outcomes

The outcomes included the TAS total score and scores on TAS factors 1, 2, 3, and 4.

Results

The extracted factors explained 44% of the variance in the TAS. Factor 1 explained 21%, but 3 items (items 2, 9, and 21) did not load onto this factor. The Cronbach’s alpha was 0.83, and the reproducibility (intraclass correlation coefficient) was 0.70. The TAS can differentiate between individuals with CSB and control individuals. The different forms of validity were demonstrated through correlations between factors 1 to 4 and the total score, as well as with impulsivity, hypersexuality, sexual compulsivity, and depression. Surprisingly, anxiety was only weakly correlated with factors 1 and 2. Moreover, the TAS-4 score was not correlated with impulsivity.

Clinical Implications

The TAS can be used in clinical practice to identify men with difficulties in recognizing subjective experiences, and proper interventions can subsequently be provided to these patients to increase their treatment efficacy.

Strengths and Limitations

Various dimensions of alexithymia covary with other key psychopathological symptoms of CSB. This study examined a convenience sample. The results cannot be generalized to the broader population. Factors 3 and 4 presented low internal consistency (0.50).

Conclusion

In general, TAS presented good psychometric properties in a sample mainly composed of individuals with CSB.
The underlying mechanisms by which boron mitigates copper toxicity in Citrus sinensis leaves revealed by integrated analysis of transcriptome, metabolome and physiology
Authors: Chen Xu-Feng , Wu Bi-Sha , Yang Hui , Shen Qian , Lu Fei , Huang Wei-Lin , Guo Jiuxin , Ye Xin , Yang Lin-Tong , Chen Li-Song
Published: August 2024

Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) μM CuCl2 and 2.5 (B2.5) or 25 (B25) μM HBO3 for 24 wk. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 μM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 μM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars and increased the concentrations of starch, glucose, fructose and total nonstructural carbohydrates in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350, and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites and genes that might lead to Cu tolerance in leaves.
Role of sentinel lymph node biopsy with indocyanine green and site of injection in endometrial cancer
Authors: Raimondo Diego , Raffone Antonio , Aguzzi Alberto , Bertoldo Linda , Seracchioli Renato
Published: August 2024

Purpose of review

The aim of the present narrative review is to summarize the state of art on sentinel lymph node biopsy (SLNB) in endometrial cancer, with a special focus on indocyanine green (ICG) as adopted tracer.

Recent findings

Over the years, the surgical nodal staging in patients with endometrial cancer has been intensively investigated. Traditionally, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess nodal involvement of the tumor. Through the last two decades, SLNB has gradually replaced lymphadenectomy as a more targeted procedure. A great heterogeneity of tracers and injection techniques have been proposed to perform SLNB. However, no universally accepted recommendations are still available.

SLNB has nowadays almost replaced pelvic lymphadenectomy in low-risk endometrial cancers, offering a better safety profile while being related to a comparable nodal involvement sensitivity. Currently, ICG is considered to be the most used tracer among others. Different injection sites have been proposed, with different detection features. While ICG cervical injection is nowadays the suggested technique for SLNB, noncervical injection techniques, such as hysteroscopic and combined procedures, seem to have a better accuracy in para-aortic nodal assessment, which have a role in high-risk endometrial cancers.
A Retrospective Review Comparing Renuvion Helium Plasma Radiofrequency with BodyTite Bipolar Radiofrequency after Liposuction or Body Contouring
Authors: Kluska Michael , Deal R. Chad , Summers Kyle , Chang Steven
Published: August 2024

Background:

Driven by demand for nonexcisional alternatives to address lax skin following liposuction, various energy-based technologies have become available. Helium plasma radiofrequency (RF) and bipolar RF have gained prominence. These technologies have distinctly different methods of action and indications, potentially influencing procedural safety and duration.

Methods:

Conducted to collect and evaluate real-world procedure and safety data, this retrospective, single-center, contiguous series study included patients who underwent either helium plasma RF or bipolar RF following a liposuction or body contouring procedure.

Results:

The helium plasma RF group (N = 229) averaged 4.9 concurrent procedures, whereas the bipolar RF group (N = 236) averaged 4.4 concurrent procedures. The total treatment time, including concurrent procedures, was 182 minutes for the helium plasma RF group and 196 minutes for the bipolar RF group. The findings from the subanalysis group (n = 9) indicated that the treatment time for the helium plasma RF side of the body was 50% shorter than the bipolar RF side. A statistically significant difference in adverse events by group was observed. There were 45 events in 34 patients for helium plasma RF and 93 events in 62 patients for bipolar RF. Notably, fewer occurrences of burns, hematoma, hypertrophic scar, and seroma were reported for helium plasma RF compared with bipolar RF.

Conclusions:

The analysis reveals a notable difference in the occurrence of adverse events, with statistically significantly fewer incidents observed for helium plasma RF compared with bipolar RF. Data suggests that helium plasma RF exhibits shorter durations in the operating room compared with bipolar RF, suggesting increased procedural efficiency.
Customized Negative Pressure Wound Therapy: Innovative Design in Polyurethane Foam for Complex Burn Reconstruction
Authors: Amaris-Acuña Juan Sebastián , Mendoza-Toro Bibiana , Camacho-Obando David , Gómez-Ortega Viviana
Published: August 2024

The use of negative pressure wound therapy (NPWT) throughout the entire treatment of a burn patient boosts wound healing and recovery. Hand burns require specialized management that enhances wound healing and facilitates early physical rehabilitation. Thus, this article showcases a novel idea of NPWT foam customization that boosts recovery and rehabilitation in patients with hand burns. We present two patients with hand burns treated with NPWT using a customized foam design that allowed for early rehabilitation while providing and optimized recovery. In the two cases presented, the patients required two surgical stages; in the first surgery, debridement of the burns was performed and customized NPWT with instillation was applied, and in the second surgical stage, the bed was reconstructed with partial-thickness skin grafts, which were bolstered with customized conventional NPWT. The management, reconstruction, and rehabilitation were accomplished in under 2 weeks, achieving a remarkable 100% success rate in graft integration during the acute phase on the first attempt. This highlights the effectiveness of incorporating NPWT across all burn treatment phases, expediting recovery and ensuring optimal functional outcomes for patients. Surgeons can customize different NPWT foam shapes that facilitate its use on difficult-to-treat areas, allowing for a faster recovery and better rehabilitation outcomes.
Suitability and Early Clinical Outcomes of Corneal Donor Tissue in the 76–80-Year-Old Age Group
Authors: Greenwald Miles F. , Sawant Onkar B. , Titus Michael S. , Ballouz Dena , Hood Christopher T. , Mian Shahzad I.
Published: August 2024

Purpose:

There is a significant global shortage of corneal donor tissue suitable for keratoplasty. One simple strategy for addressing this shortage is to increase the upper age limit for acceptable tissue over the current customary upper limit of age 75. We describe a pilot study completed at one eye bank procuring, processing, and distributing keratoplasty tissue from donors aged 76 to 80 years.

Methods:

This is a retrospective case series of donor tissues aged 76 to 80 years in comparison with donor tissues aged 71 to 75 years. Standard tissue parameters were evaluated for all tissues, including tissue suitability, mean endothelial cell density (ECD), death-to-procurement time, and cause of death. For the older tissues, clinical outcomes through 3 months were obtained from each surgeon, including intraoperative and postoperative complications.

Results:

Corneal tissues from donors aged 76 to 80 years had a similar suitability rate (57%) when compared with donors aged 71 to 75 years (59%) (P = 0.635). Both groups had comparable ECDs (P = 0.097). Early clinical outcomes of corneal grafts from donors older than 76 years were favorable, with no early graft failure or significant concerns for clinical safety or efficacy.

Conclusions:

Our findings suggest that corneal tissues aged 76 to 80 years can be safely and efficiently transplanted in the United States. While additional study is needed, our results strengthen the case that expanding the upper age limit for donor age has the potential to help meet the global shortage for suitable keratoplasty tissue.
Mortality Among Children Under Five Years of Age Living With HIV on Antiretroviral Treatment From HIV Case Surveillance Data, Malawi, 2022
Authors: Chapman Kelly S. , Luhanga Misheck , Mtonga George , Agathis Nickolas , Kayira Dumbani , Hrapcak Susan , Patel Monita , Kress Howard , Arons Melissa
Published: August 2024

From Malawi’s HIV case surveillance, we report clinical characteristics and outcomes of 4461 children living with HIV on antiretroviral treatment <5 years old from January to December, 2022. Among the 4% of children living with HIV who died, 43% were asymptomatic, 35% had advanced or severe symptoms at the time of HIV diagnosis and 50% died within 6 months of receiving an HIV diagnosis.