bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Z chromosomal inversion and lineage-specific sweeps reveal widespread local adaptation inHelicoverpa armigera
Authors: Ke Fushi
Published: October 2023

Efficient pest management requires comprehensive knowledge of its biology, ecology, and evolution, particularly adaptation that exacerbating pest damage.Helicoverpa armigera(Hübner) is a notorious pest that attacks more than 200 species, adapts to diverse environments, and has developed resistance to almost all applied insecticides. However, local adaptation of this species was less investigated. Here, we analyzed genomic variation ofHelicoverpa armigerain China and Oceania to identify adaptative loci in different lineages. Despite intensive gene flow, two differentiated Z chromosomal lineages in Central China (i.e., northern and southern lineages) were formed by chromosome inversion and local adaptation. Based on population genomic analysis, we identified genes related to circadian clock (period,cycle,cyr2anddaywake), insulin secretion (IGF2BP2) and energy metabolism (SLC25A25,CCG7766,D11DS,TSTPandCPQ) were under selection in northern lineage. These genes may have contributed to its adaptation to high latitudes. In the southern lineage however, the Z chromosome inversion harboring alien alleles of two clock genes (periodandcycle) and may have disrupted clock oscillator for adaptation. We further conducted selective sweep analysis in lineages from Northwestern China, Central China, and Oceania, and found several insecticide resistant genes that shared among different lineages were likely contributed by introgression. Nevertheless, many candidates, including a cadherin that involved in resistance toBacillus thuringiensisprotein in Oceanian populations, are lineage-specific. Our results highlight the importance of investigating local adaptation in effective pest control under globalization of agriculture.
COMPARISON OF HIGH-THROUGHPUT SINGLE-CELL RNA-SEQ METHODS FOR EX VIVO DRUG SCREENING
Authors: Gezelius Henrik , Enblad Anna Pia , Lundmark Anders , Åberg Martin , Blom Kristin , Rudfeldt Jakob , Raine Amanda , Harila Arja , Rendo Verónica , Heinäniemi Merja , Andersson Claes , Nordlund Jessica
Published: October 2023

Functional precision medicine (FPM) aims to optimize patient-specific drug selection based on the unique characteristics of their cancer cells. Recent advancements in high throughputex vivodrug profiling have accelerated interest in FPM. Here, we present a proof-of-concept study for an integrated experimental system that incorporatesex vivotreatment response with a single-cell gene expression output enabling barcoding of several drug conditions in one single-cell sequencing experiment. We demonstrate this through a proof-of-concept investigation focusing on the glucocorticoid-resistant acute lymphoblastic leukemia (ALL) E/R+ Reh cell line. Three different single-cell transcriptome sequencing (scRNA-seq) approaches were evaluated, each exhibiting high cell recovery and accurate tagging of distinct drug conditions. Notably, our comprehensive analysis revealed variations in library complexity, sensitivity (gene detection), and differential gene expression detection across the methods. Despite these differences, we identified a substantial transcriptional response to fludarabine, a highly relevant drug for treating high-risk ALL, which was consistently recapitulated by all three methods. These findings highlight the potential of our integrated approach for studying drug responses at the single-cell level and emphasize the importance of method selection in scRNA-seq studies. Finally, our data encompassing 27,327 cells are freely available to extend to future scRNA-seq methodological comparisons.
Knowledge-Driven Online Multimodal Automated Phenotyping System
Authors: Xiong Xin , Sweet Sara Morini , Liu Molei , Hong Chuan , Bonzel Clara-Lea , Panickan Vidul Ayakulangara , Zhou Doudou , Wang Linshanshan , Costa Lauren , Ho Yuk-Lam , Geva Alon , Mandl Kenneth D. , Cheng Suchun , Xia Zongqi , Cho Kelly , Gaziano J. Michael , Liao Katherine P. , Cai Tianxi , Cai Tianrun
Published: October 2023

Though electronic health record (EHR) systems are a rich repository of clinical information with large potential, the use of EHR-based phenotyping algorithms is often hindered by inaccurate diagnostic records, the presence of many irrelevant features, and the requirement for a human-labeled training set. In this paper, we describe a knowledge-driven online multimodal automated phenotyping (KOMAP) system that i) generates a list of informative features by an online narrative and codified feature search engine (ONCE) and ii) enables the training of a multimodal phenotyping algorithm based on summary data. Powered by composite knowledge from multiple EHR sources, online article corpora, and a large language model, features selected by ONCE show high concordance with the state-of-the-art AI models (GPT4 and ChatGPT) and encourage large-scale phenotyping by providing a smaller but highly relevant feature set. Validation of the KOMAP system across four healthcare centers suggests that it can generate efficient phenotyping algorithms with robust performance. Compared to other methods requiring patient-level inputs and gold-standard labels, the fully online KOMAP provides a significant opportunity to enable multi-center collaboration.
Cell-binding IgM in CSF is distinctive of multiple sclerosis and targets the iron transporter SCARA5
Authors: Callegari I. , Oechtering J. , Schneider M. , Perriot S. , Mathias A. , Voortman M.M. , Cagol A. , Lanner U. , Diebold M. , Holdermann S. , Kreiner V. , Becher B. , Granziera C. , Junker A. , Du Pasquier R. , Khalil M. , Kuhle J. , Kappos L. , Sanderson NSR , Derfuss T.
Published: October 2023

Intrathecal IgM production in multiple sclerosis (MS) is associated with a worse disease course. To investigate pathogenic relevance of autoreactive IgM in MS, CSF from two independent cohorts, including MS patients and controls, were screened for antibody binding to induced pluripotent stem cell-derived neurons and astrocytes, and a panel of CNS-related cell lines. IgM binding to a primitive neuro-ectodermal tumour cell line discriminated 10% of MS donors from controls. Transcriptomes of single IgM producing CSF B cells from patients with cell-binding IgM were sequenced and used to produce recombinant monoclonal antibodies for characterisation and antigen identification. We produced 5 cell-binding recombinant IgM antibodies, of which one, cloned from an HLA-DR+ plasma-like B cell, mediated antigen-dependent complement activation. Immunoprecipitation and mass spectrometry, and biochemical and transcriptome analysis of the target cells identified the iron transport scavenger protein SCARA5 as the antigen target of this antibody. Intrathecal injection of a SCARA5 antibody led to an increased T cell infiltration in an EAE model. CSF IgM might contribute to CNS inflammation in MS by binding to cell surface antigens like SCARA5 and activating complement, or by facilitating immune cell migration into the brain.
Normal Uterine Fibroblast Are Reprogramed into Ovarian Cancer-Associated Fibroblasts by Ovarian Tumor-derived Conditioned Media
Authors: Axemaker Hailey , Plesselova Simona , Calar Kristin , Jorgensen Megan , Wollman Jared , de la Puente Pilar
Published: October 2023

Cancer-associated fibroblasts (CAFs) are key contributors to ovarian cancer (OC) progression and therapeutic resistance through dysregulation of the extracellular matrix (ECM). CAFs are a heterogenous population derived from different cell types through activation and reprogramming. Current studies rely on uncharacterized heterogenous primary CAFs or normal fibroblasts that fail to recapitulate CAF-like tumor behavior. Here, we present a translatable-based approach for the reprogramming of normal uterine fibroblasts into ovarian CAFs using ovarian tumor-derived conditioned media to establish two well-characterized ovarian conditioned CAF lines. Phenotypic and functional characterization demonstrated that the conditioned CAFs expressed a CAF-like phenotype, strengthened proliferation, secretory, contractility, and ECM remodeling properties when compared to resting normal fibroblasts, consistent with an activated fibroblast status. Moreover, conditioned CAFs significantly enhanced drug resistance and tumor progression and resembled a CAF-like subtype associated with worse prognosis. The present study provides a reproducible, cost-effective, and clinically relevant protocol to reprogram normal fibroblasts into CAFs using tumor-derived conditioned media. Using these resources, further development of therapeutics that possess potentiality and specificity towards CAF-mediated chemoresistance in OC are further warranted.
Clay larvae do not accurately measure biogeographic patterns in predation
Authors: Rodriguez-Campbell Antonio , Rahn Olivia , Chiuffo Mariana , Hargreaves Anna
Published: October 2023

Aim

Spatial variation in predation can shape geographic patterns in ecology and evolution, but testing how predation varies across ecosystems is challenging as differing species compositions and defensive adaptations can mask underlying patterns. Recently, biogeography has borrowed a tool from ecology –clay prey models. But clay models have not been adequately tested for geographic comparisons, and a well-known problem –that clay prey only appeal to a subset of potential predators– could lead to inaccurate detection of geographic patterns whenever the relative importance of predator guilds varies among sites. Here, we test whether clay larvae accurately capture geographic differences in predation on real larvae.

Location

90° of latitude and >2000 m elevation across the Americas

Taxon

vertebrate and invertebrate predation on ‘superworms’ (Zophobaslarve)

Methods

Across six sites that vary dramatically in latitude, elevation, and biome, we quantified predation on live, dead, and clay larvae. We physically excluded vertebrate predators from some larvae to distinguish total predation and invertebrate-only predation.

Results

Predation on live superworms almost doubled from our high-elevation high-latitude site to out low-elevation tropical site. Geographic patterns were highly consistent among live and dead larvae, but clay larvae missed extremely high predation at some sites and therefore mismeasured true geographic patterns. Clay larvae did a particularly bad job at capturing geographic patterns in predation by invertebrates.

Main conclusions

Clay larvae are inappropriate for large-scale tests of predation, and should be abandoned for biogeographic studies. Biogeographic experiments should instead employ realistic baits, and clay prey should be reserved for comparisons within, rather than across, predator communities.
Inferring B cell phylogenies from paired heavy and light chain BCR sequences with Dowser
Authors: Jensen Cole G. , Sumner Jacob A. , Kleinstein Steven H. , Hoehn Kenneth B.
Published: October 2023

Antibodies are vital to human immune responses and are composed of genetically variable heavy and light chains. These structures are initially expressed as B cell receptors (BCRs). BCR diversity is shaped through somatic hypermutation and selection during immune responses. This evolutionary process produces B cell clones, cells that descend from a common ancestor but differ by mutations. Phylogenetic trees inferred from BCR sequences can reconstruct the history of mutations within a clone. Until recently, BCR sequencing technologies separated heavy and light chains, but advancements in single cell sequencing now pair heavy and light chains from individual cells. However, it is unclear how these separate genes should be combined to infer B cell phylogenies. In this study, we investigated strategies for using paired heavy and light chain sequences to build phylogenetic trees. We found incorporating light chains significantly improved tree accuracy and reproducibility across all methods tested. This improvement was greater than the difference between tree building methods and persisted even when mixing bulk and single cell sequencing data. However, we also found that many phylogenetic methods estimated significantly biased branch lengths when some light chains were missing, such as when mixing single cell and bulk BCR data. This bias was eliminated using maximum likelihood methods with separate branch lengths for heavy and light chain gene partitions. Thus, we recommend using maximum likelihood methods with separate heavy and light chain partitions, especially when mixing data types. We implemented these methods in the R package Dowser:https://dowser.readthedocs.io.
Psychological well-being modulates neural synchrony during naturalistic fMRI
Authors: Klamer K. , Craig J. , Sullivan K. , Haines C. , Ekstrand C.
Published: October 2023

Psychological well-being (PWB) is a combination of self-acceptance, life purpose, personal growth, positive relationships, and autonomy, and has a significant relationship with physical and mental health. Previous studies using resting-state functional magnetic resonance imaging (fMRI) and static picture stimuli have implicated the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), orbitofrontal cortex (OFC), insula and thalamus in PWB, however, the replication of associations across studies is scarce, both in strength and direction, resulting in the absence of a model of how PWB impacts neurological processing. Naturalistic stimuli better encapsulate everyday experiences and can elicit more “true-to-life” neurological responses, and therefore may be a more appropriate tool to study PWB. The current study seeks to identify how differing levels of PWB modulate neural synchrony in response to an audiovisual film. With consideration of the inherent variability of the literature, we aim to ascertain the validity of the regions previously mentioned and their association with PWB. We identified that higher levels of PWB were associated with heightened neural synchrony in the bilateral OFC and left PCC, and that lower levels of PWB were associated with heightened neural synchrony in the right temporal parietal junction (TPJ) and left superior parietal lobule (SPL), regions related to narrative processing. Taken together, this research confirms the validity of several regions in association with PWB and suggests that varying levels of PWB produce differences in the processing of a narrative during complex audiovisual processing.
Reviving collapsed networks from a single species: the importance of trait variation and network architecture
Authors: Baruah Gaurav , Wittmann Meike
Published: October 2023

Mutualistic ecological networks can suddenly transition to undesirable states, due to small changes in environmental conditions. Recovering from such a collapse can be difficult as reversing the original environmental conditions may be infeasible. Additionally, such networks can also exhibit hysteresis, implying that ecological networks may not recover. Here, using a dynamical eco-evolutionary framework, we try to resurrect mutualistic networks from an undesirable low-functional collapse state to a high-functioning state. We found that restoring the original environmental conditions rarely aided in recovering the original network due to the presence of hysteresis. By combining concepts from signal propagation theory and eco-evolutionary dynamical modeling, we show that network resurrection could be readily achieved by perturbing a single species that controls the response of the dynamical networks. We show that during the resurrection of collapsed networks, the historical network architecture, levels of trait variation, and eco-evolutionary dynamics could aid in the revival of the network even in undesirable environmental conditions. Our study argues that focus should be applied to a few species whose dynamics one could steer to resurrect the entire network from a collapsed state.
Synthesis, Insertion, and Characterization of SARS-CoV-2 Membrane Protein Within Lipid Bilayers
Authors: Zhang Yuanzhong , Anbir Sara , McTiernan Joseph , Li Siyu , Worcester Michael , Mishra Pratyasha , Colvin Michael E. , Gopinathan Ajay , Mohideen Umar , Zandi Roya , Kuhlman Thomas E.
Published: October 2023

SUMMARY/ABSTRACT

The membrane protein (M) is the most abundant structural protein in the SARS-CoV-2 virus and functions exclusively as a membrane-embedded homodimer. M protein is required for the formation of the SARS-CoV-2 virus particle and has been shown to interact with the Spike and Envelope proteins, as well as the RNA-packaging Nucleocapsid protein. Our knowledge of M protein is very limited due to its small size and challenges in expressing enough protein for use in structural and biophysical experiments. We report the successful development of a SUMO tag-based expression system to produce and purify significant quantities of M protein, and a method to insert the synthesized dimers into a suspended lipid membrane in a homogeneous orientation. We used AFM and Cryo-EM to image individual membrane-bound M protein dimers and characterize the configurations that they can assume. Our experimental results are in agreement with our molecular dynamics simulations which predict thinning of the membrane around the M protein and a propensity to induce local membrane curvature. Taken together, our results shed new light on M protein properties within the lipid bilayer and suggest mechanisms that could contribute to viral assembly and budding.
The near-normal viability of heterozygote for a lethal enhancer allele suggests a route forcis-regulatory evolution
Authors: Ludwig Michael Z.
Published: October 2023

A variety of evolutionary processes shape the structure ofcis-regulatory elements such as enhancers. Functionally important regulatory sequences tend to be conserved as result of negative selection against deleterious mutations and positive selection for better-canalized performance. However, some forms of stabilizing selection can maintain functional conservation ofcis-regulatory elements for long periods of evolutionary time despite structural transcription binding sites turnover (Ludwig et al, 1998). In addition, compensatory evolution can even accelerate the substitution process in large populations to level greater than the neutral rate of substitution (Carter and Wagner, 2002). The effects of lethal mutations incis-regulatory regions on viability in heterozygotes and the impact of such mutations on evolutionary processes have not been substantially addressed.

We ask a fundamental biological question: How does a lethal mutant in an enhancer region affect viability when carried over a dominant “normal” allele?

Herecis-regulatory mutationeveΔMSEofeven-skippedgene (eve)inD. melanogaster, that is lethal in homozygote, has been tested for relative viability in heterozygous state. IneveΔMSEthe 480-bp fragment corresponding to MSE (Minimal Stipe Element) of theevestripe 2 enhancer was deleted and replaced with an unrelated DNA fragment (containingwhite+gene marker) by ends-out homologous recombination (Ludwig et al, 2011). We discovered that relative viability of flies carryingcis-regulatory mutationeveΔMSEin heterozygote was not reduced compared to the viability of wild-type flies. In contrast, the viability of heterozygotes carrying a homozygote-lethal nonsenseeveR13mutation (Fujioka et al, 1999) was significantly impacted. Our explanation to this surprising phenomenon relays on action ofevetranscriptional autoregulation. The transcription factor (TF) EVE regulates its own expression level through the autoregulatorycis-regulatory module. It could elevate the expression level from one dose to the level sufficient to restore up to 100% fitness in the heterozygote witheveΔMSElethal allele.

This example suggests that somecis-regulatory mutants (including the deleterious ones) may exist in populations as heterozygotes with high fitness for many generations, before possibly encountering an epistatic interaction with a compensatory mutation at a different site in the genome. Our study is consistent with the compensatory mechanisms of evolution for functionally importantcis-regulatory elements.
Cytomegalovirus promotes proliferation and survival of prostate cancer cells and constitutes a therapeutic target
Authors: Classon Johanna , Stenudd Moa , Zamboni Margherita , Alkass Kanar , Eriksson Carl-Johan , Pedersen Lars , Schörling Alrik , Thoss Anna , Bergh Anders , Wikström Pernilla , Adami Hans-Olov , Sørensen Henrik T , Druid Henrik , Frisén Jonas
Published: October 2023

Metastatic prostate cancer is incurable and new therapeutic targets and drugs are needed. Viruses are associated with several cancer types, but their connection to prostate cancer is unclear. Here we show that human herpes virus cytomegalovirus (CMV) infection is common in the healthy prostate epithelium as well as in prostate cancer, with 85% of tumors being infected to varying degrees. The CMV gene locusUL122-UL123upheld viral genome persistence in endogenously CMV infected prostate cancer cell lines. CMV promoted prostate cancer cell viability independently of androgen receptor status and anti-androgen resistance, partly through CMVUL97and the androgen signaling pathway. DNA intercalation mitigated CMV infection and reduced CMV-dependent tumor size in xenotransplantation experiments. The anti-herpes drug aciclovir showed modest effects, but the well tolerated CMV UL97 kinase inhibitor maribavir partly mimicked CMV loss by inducing apoptosis and attenuating proliferation, resulting in reduced tumor growthin vivo. We conclude that CMV infects prostate cellsin vivoand alters core prostate cancer cell properties, suggesting that it can be therapeutically targeted to improve prostate cancer outcomes.
Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks
Authors: Cheng Quen J. , Farrell Kylie , Fenn Jeffrey , Ma Zuchao , Makanani Sara K. , Siemsen Jonathan
Published: October 2023

Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. β-glucan, a Dectin-1 ligand purified from theCandida albicanscell wall, has been one of the most widely u:lized and well-characterized ligands for inducing innate immune memory. However, many Dectin-1 agonists exist, and it is not known whether all Dectin-1 ligands produce the same phenotype. Using a well-establishedin vitromodel of trained immunity, we compared two commercially available Dectin-1 agonists, zymosan and depleted zymosan, with the gold standard β-glucan in the literature. We found that depleted zymosan, a β-glucan purified fromSaccharomyces cerevisiaecell wall through alkali treatment, produced near identical training effects asC. albicansβ-glucan. However, untreated zymosan produced a distinct training effect from β-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of key cytokines such as TNF, IL-12, and IL-6. Zymosan activated NF𝓀B and AP-1 transcription factors more strongly than β-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of β-glucans to a phenotype resembling training with zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1. These findings bring clarity to the specific question of which Dectin-1 agonists produce prototypical training effects and provide broader insight into how signaling networks regulate innate immune training.
The I Ching as a Potential Jungian Application: History and Practice
Authors: Zeng Jingchao
Published: October 2023

Swiss psychiatrist Carl Jung had a lifelong interest in the I Ching after discovering it in 1919. Jung’s interest in the I Ching is arguably more practical than purely theoretical or intellectual, and references to I Ching divination appear frequently in his various publications, seminars, letters and clinical practice records. After a few observations on the history of the study of the I Ching in China, the author categorizes Jung’s three uses of the I Ching as physical use (to preview future potentials of outer reality), psychological use (to reveal one’s psychological state), and psychical approach (to engage with the divine through “神”[“shen”, spiritual agencies]). Finally, the author discusses the current Jungian engagement by demonstrating clinical cases in contemporary times. Some Jungian analysts practise I Ching divination to obtain insights into the physical and psychological state of therapeutic relationships and for personal development. This paper is a historical and critical engagement of the Jungian practice of I Ching divination.
Patents, foreign direct investment and economic growth in Australia, 1860–2010
Authors: Fleming Grant , Liu Zhangxin (Frank) , Merrett David , Ville Simon
Published: October 2023

We examine the long run relationship between innovation and economic development in Australia, using 150 years of data on patenting activity, and aggregate and sectoral economic indicators. Our initial results point to several important causal relationships, particularly the effects of patents on real GDP and of private capital formation on patents. We delve deeper at the sector level and find important causal relationships of patents with real foreign direct investment (FDI) since World War II. Australia's dependence on FDI for private capital formation served as an important stimulus for knowledge creation in key sectors including manufacturing, agriculture and mining.
A purebred South American breed showing high effective population size and independent breed ancestry: The Chilean Terrier
Authors: Mujica Paola C. , Martinez Víctor
Published: October 2023

The Chilean Terrier is a known breed in Chile that has not been genetically assessed despite its distinctive color patterns, agility, and hardiness across the diversity of climates encountered within the Chilean landscape. The population structure and its relatedness with other breeds, as well as the actual origin of the breed, remain unknown. We estimated several population parameters using samples from individuals representing the distribution of the Chilean Terrier across the country. By utilizing the Illumina HD canine genotyping array, we computed the effective population size (Ne), individual inbreeding, and relatedness to evaluate the genetic diversity of the breed. The results show that linkage disequilibrium was relatively low and decayed rapidly; in fact, Ne was very high when compared to other breeds, and similar to other American indigenous breeds (such as the Chihuahua with values of Ne near 500). These results are in line with the low estimates of genomic inbreeding and relatedness and the relatively large number of effective chromosome segments (Me = 2467) obtained using the properties of the genomic relationship matrix. Between population analysis (cross‐population extended haplotype homozygosity, di) with other breeds such as the Jack Russell Terrier, the Peruvian‐Inca Orchid, and the Chihuahua suggested that candidate regions harboring FGF5, PAX3, and ASIP, probably explained some morphological traits, such as the distinctive color pattern characteristic of the breed. When considering Admixture estimates and phylogenetic analysis, together with other breeds of American and European origin, the Chilean Terrier does not have a recent European ancestry. Overall, the results suggest that the breed has evolved independently in Chile from other terrier breeds, from an unknown European terrier ancestor.
Q&A
Authors: Maeda John , Heller Steven , Hoover Tim
Published: October 2023

John Maeda is a past president of Rhode Island School of Design and an internationally known designer. He's now involved in helping entrepreneurs build design into their company cultures.

Writer and educator Steven Heller pairs up with Tim Hoover, head of product and design at Canary, to talk about designer CEOs, start‐ups, and cutting out the middleman.
Q&A
Authors: Schwartz Bob , Lopez Natalia Zuluaga
Published: October 2023

As general manager for global design and user experience at GE Healthcare, and with experience at P&G and Motorola before that, Bob Schwartz has a few (!) thoughts about how to fertilize the relationship between design and business.

As design manager for the UK's Portland Communications, a high‐end public relations firm, Natalia Zuluagalo Lopez has more or less built her job from scratch.
Consumer Climate Change
Authors: Hendricks Nathan
Published: October 2023

If desires steer people, shape products, and define the zeitgeist, then why aren't designers taking them more seriously?

An exploration of the thermostat, the temperature of 2017, and a methodology that can make us better.
Connected by Design
Authors: Bethune Kevin
Published: October 2023

The digital trends of our time promise more changes for all of us, and more opportunities for startup companies. Large corporates have watched the audacity of startups, and they recognize they need to start deliberately reimagining themselves to play some offense. BCG Digital Ventures partners with the world's most important corporations to invent, launch and scale game‐changing businesses. Our strategic designers work on each new venture as a critical part of each multidisciplinary team.

Kevin Bethune spends a lot of time thinking about what digital connection will mean in the future. That's because his company, BCGDV, creates digital start‐ups for Fortune 500 companies.
Effect of Piascledine‐bacterial nanocellulose combination on experimental cutaneous wound healing in rat: Histopathological, biochemical and molecular studies
Authors: Panahi Nastaran , Hashemnia Mohammad , Rezaei Farid , Cheraghi Hadi
Published: October 2023

The study investigated the wound healing potential of Piascledine (an avocado/soybean mixture) alone and in combination with bacterial nanocellulose on rat cutaneous wounds. Full‐thickness excisional wounds (2 cm in diameter) were induced on the backs of 60 Sprague–Dawley rats, divided into four groups, treated with daily topical application of bacterial nanocellulose (BNC), Piascledine 10% (PSD 10%) and Piascledine+bacterial nanocellulose (PSD + BNC) (10 mg/disk) and normal saline (control) for 20 days. Wounds were monitored daily, and at 10, 20 and 30 days post‐injury (DPI), tissue samples were collected for biochemical, histopathological and molecular analyses. Treated rats with PSD and PSD + BNC showed a significant decrease in the wound area compared with other groups. PSD and particularly PSD + BNC modulated inflammation, improved fibroplasia and angiogenesis and scar tissue formation at short term. At the long term, they reduced the scar tissue size and improved collagen fibres alignment, tissue organization and remodelling as well as re‐epithelialization. PSD enhanced matrix metalloproteinase‐3 (MMP‐3) gene expression, collagen and glycosaminoglycans (GAGs) synthesis and decreased tissue inhibitor of metalloproteinase‐1 (TIMP‐1) gene expression at various stages of wound healing. The study concluded that topical application of Piascledine, particularly in combination with bacterial nanocellulose, promotes wound healing activity by modulating inflammation, regulating MMP‐3 expression and enhancing collagen and GAGs synthesis.
Peeling with retinoic acid in microemulsion for treatment of melasma: A double‐blind randomized controlled clinical study
Authors: de Andrade Ana Carolina Dias Viana , Coqueiro Raildo da Silva , Pithon Matheus Melo , Leite Mateus Freire
Published: October 2023

Objective

To evaluate the clinical efficacy of peeling with a microemulsion formulation containing 1% retinoic acid.

Materials and Methods

After development of the product, 60 patients with melasma were randomly divided into three groups (n = 20): Group 1–application of conventional 1% retinoic acid peeling (RA 1%). Group 2–application of 1% retinoic acid peeling in microemulsion (RA 1%M). Group 3–Application of placebo. The groups were submitted to four peeling sessions, fortnightly on Days 0, 15, 30, and 45, and analyzed at the time intervals of 0, 15, 30, 45, and 60 days. Evaluation was made by using the Melasma Area and Severity Index (MASI) and Melasma Quality of Life (MelasquoL) instrument. Hemato‐biochemical parameters were also evaluated at Days 0 and 60. After obtaining the results, normality was evaluated by means of the Kolmogorov–Smirnov test and afterwards, the following tests were applied: Friedman statistical (to test the effect of the treatments on the MASI index); Wilcoxon, (for comparison between pairs to test the effect of treatments on the MelasQoL index); Kruskal–Wallis, (to test the differences between the groups); and Mann–Whitney, (comparisons between treatments). The level of significance adopted was 5% (α = 0.05).

Results

The three groups presented a significant reduction in the MASI index, indicating the effect of all the treatments on reducing the melasma (p < 0.001). A significant reduction in the stains was observed with the use of retinoic acid peeling delivered in microemulsion (62%) when compared with the conventional peeling with 1% retinoic acid in a conventional vehicle (26%) and the placebo (12%). There was also a significant reduction in the MelasQoL index (sum of all the aspects) in the three groups, indicating the effect of all the treatments, including the placebo, on the overall quality of life of those with melasma. However, RA 1%M the treatment that promoted the greatest effect on the quality of life of individuals. In percentage terms, the RA 1%M provided a mean reduction of 30% in the MelasQoL index, against 13% of the conventional treatment and only 4% of the placebo. When the hemato‐biochemical parameters were compared on Days 0 and 60, there were no significant changes in the results.

Conclusion

The chemical peeling performed with RA 1%M was effective for the treatment of melasma, and was shown to be superior to the peeling performed with retinoic acid in a conventional vehicle, in reducing the stains and improving the quality of life of patients.
The American Founders Entrusted Elites to Save Democracy from Itself
Authors: Gardels Nathan
Published: October 2023

The word “democracy” does not appear in the US Constitution. Nor in the Bill of Rights or the Declaration of Independence. That is because, as most Americans today would likely be surprised to discover, America's Founding Fathers not only distrusted democracy but, based on their close reading of Greek and Roman history, were actually hostile to the notion that it was the best system for governing society.
President Trump, There Is A Deal To Be Made With North Korea
Authors: Perry William J.
Published: October 2023

North Korea might agree to a nuclear deal in return for economic concessions from South Korea and security assurances from the US
Transparency and Truth
Authors: Dennett Daniel C.
Published: October 2023

President Trump could learn a thing or two about keeping secrets.
Association of metabolic syndrome and chronic kidney disease
Authors: Scurt Florian G. , Ganz Maximilian J. , Herzog Carolin , Bose Katrin , Mertens Peter R. , Chatzikyrkou Christos
Published: October 2023

The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter‐2 (SGLT‐2) inhibitors or glucagon‐like peptide‐1 (GLP‐1) receptor agonists, a significant risk of progression to end‐stage renal disease remains in the high‐risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin‐to‐creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS‐associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity‐related kidney injury; (ii) the clinicopathological characteristics of obesity‐related kidney injury, primarily focusing on obesity‐associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.
Do reputational threats influence the rigidity of US agencies? A dynamic panel data approach
Authors: Boon Jan , Wynen Jan , Verhoest Koen
Published: October 2023

What happens to organizational rigidity when public organizations faced reputational threats over time? Do they take external criticism as incentives to become less rigid and more innovative and flexible through employee involvement and empowerment? Or do reputational threats paradoxically contribute to the very rigidity that is often stereotyped as inherent parts of government? Building on threat‐rigidity theory, we test the temporal relation between reputational threats (both in terms of the direction of reputation and its turbulence) and organizational rigidity. We apply a dynamic panel data approach combining different data sources on 34 US agencies over a period of 13 years. The results show that organizational rigidity increased, both when reputations evolved negatively over time and when reputations evolved more turbulently. No combined effect of negative reputations and reputational turbulence was observed. Both sources of reputational threats independently precluded organizations from creating a climate of employee empowerment, involvement, flexibility, and innovation.
Keep My Teeth: An evaluation of multi‐disciplinary training in mouth care for people with intellectual developmental disorders
Authors: Nowghani Fargol , Lisiecka Dominika , Phelan Seán , Horan Paul , O'Reilly Louise , Howell Yvonne , Mac Giolla Phadraig Caoimhin
Published: October 2023

Aim

To evaluate a modular didactic training intervention called Keep My Teeth designed by special care dentists, for a range of healthcare students to provide oral homecare for people with intellectual developmental disorders (PwIDD).

Methods

To evaluate the intervention a one‐group pre‐test post‐test pre‐experimental research design was utilized. The intervention was delivered by virtual platforms or face‐to‐face, with a sub‐sample of participants also receiving practical training. Healthcare students included Speech and Language Therapy (SLT), Registered Nurse Intellectual Disability (RNID), Dental Science (DS), Dental Nursing (DN), and Dental Hygiene (DH).

Results

Sixty‐three of the 147 trainees completed all surveys. A significant change in perspective on barriers was seen for most groups post‐training, with an increase in confidence in delivering oral care to PwIDD across disciplines; 67% of DH/DN students who took part in the practical training felt that the didactic training was just as effective without the practical training, while 42% of the DS students felt that was true.

Conclusions

The training interventions provided seem to have increased the awareness of study participants in relation to barriers to care, and increased their self‐efficacy towards, and intention to perform, oral homecare behaviors.
Science as a “Special”: Navigating the role of science specialist in urban elementary schools
Authors: Ronan Darcy M.
Published: October 2023

This ethnography explores the locally defined and culturally negotiated roles and responsibilities of elementary science specialists (ESS) in three New York City schools. Drawing upon interviews with ESS, classroom teachers, and building administrators, this study examines the roles and interactions of ESS with regards to instruction, support, and leadership as analyzed through a distributed leadership lens. The implementation pattern matched the characteristics of the science as a special model of elementary content specialization. While lacking specific qualifications or clearly defined roles, ESS were primary, exclusive, or supplementary providers of science instruction. Urban ESS leveraged relationships with various classroom generalists and faced challenges in navigating science leadership responsibilities such as curriculum coordination, communication, and support of classroom teachers.
The novel HLA‐A*11:448 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Lou Can , Wang Jing , An Lin , Hu Xiao‐zhuang , Li Jia‐ming
Published: October 2023

HLA‐A*11:448 differs from HLA‐A*11:01:01:01 by one nucleotide in exon 5.
Definability and decidability for rings of integers in totally imaginary fields
Authors: Springer Caleb
Published: October 2023

We show that the ring of integers of is existentially definable in the ring of integers of , where denotes the field of all totally real numbers. This implies that the ring of integers of is undecidable and first‐order nondefinable in . More generally, when is a totally imaginary quadratic extension of a totally real field , we use the unit groups of orders to produce existentially definable totally real subsets . Under certain conditions on , including the so‐called ‐number of being the minimal value , we deduce the undecidability of . This extends previous work that proved an analogous result in the opposite case . In particular, unlike prior work, we do not require that contains only finitely many roots of unity.
¿Son relevantes los cambios voluntarios de auditores para el mercado brasileño? Un análisis basado en el rendimiento y el volumen de negociación de acciones
Authors: Henrique Coutinho e Silva Adolfo , Sancovschi Moacir , Monteiro de Andrade Anderson
Published: October 2023

Este artigo explora a reação do mercado e dos investidores ao anúncio de mudanças de voluntárias de auditores (MVAs) de companhias abertas brasileiras entre 2012 e 2019. Para isso, foi aplicado o método de estudo de eventos sobre retorno e volume de negociação de ações, diante de uma amostra de 80 MVAs realizadas por 66 empresas. A amostra principal também foi segregada em subamostras de acordo com o porte da auditoria e a opinião emitida pelo auditor substituído. Os resultados indicam que, em geral, não há reação do mercado nem dos investidores ao anúncio das MVAs. Além disso, identificamos que muitas empresas brasileiras não divulgaram os motivos das MVAs ou deram motivos genéricos. Esse achado é importante porque mostra que ambientes institucionais que possuem mudanças obrigatórias de auditor em períodos curtos, como do Brasil, podem reduzir o efeito surpresa da divulgação das MVAs. Este fato, somado à opacidade dos motivos de mudança do auditor, consequentemente minimizaria a relevância das MVAs para o mercado.
Propuesta de distribución de costos indirectos de fabricación por el método algebraico para complementar las metodologías de costeo tradicional y ABC en empresas manufactureras
Authors: Sierra Vargas José , Londoño Osorio José Iván
Published: October 2023

En la actualidad, es cada vez mayor la exigencia de los mercados en cuanto al nivel de competitividad. Uno de los criterios de evaluación de esta son los costos de producción.

Se sabe que existen diversidad de sistemas de registro y clasificación de costos, y se es consciente de la problemática que se presenta a la hora de asignar los costos a los objetos de costo (productos, servicios, cliente, proyecto, pedido, etc.). Hasta el momento, muchas empresas utilizan el sistema tradicional de asignación, basado en establecer una tasa predeterminada para aplicarla a los objetos de costo, ya sea por horas de mano de obra, horas máquina o, simplemente, por el valor de las ventas de cada objeto de costo.

La necesidad actual de afinar esta distribución y asignación de costos indirectos sustenta el uso del método algebraico y se convierte en una solución complementaria cuando se presenta reciprocidad. Es decir que los centros de costos de servicios se prestan servicio entre ellos, así como a los departamentos productivos. La aplicación del método algebraico mejora la razonabilidad de los costos a obtener en cualquier metodología de costos.

Se propone el uso de los conceptos de álgebra lineal referentes al planteamiento y solución de ecuaciones y la aplicación práctica de las herramientas de Excel, las cuales facilitan su solución y complementan los métodos de costeo tradicional y ABC, previo a la distribución de los CIF por actividades.
Cross-listing, capital structure and firm performance: A simultaneous equation estimation
Authors: Ghadhab Imen , Jouida Sameh , Bouzgarrou Houssam
Published: October 2023

This paper investigates the relationship between cross-listing, capital structure and performance jointly for non-US firms cross-listed in the US. Using a sample of 703 companies over the period ranging from 1980 to 2019, we show a simultaneous significant effect of cross-listing on capital structure and performance and find bi-directional causality between the two later variables. Cross-listed firms issue more equity and exhibit better valuation. The legal bonding associated with the reasons for cross-listing finds its support. Firms that originated from a poor legal environment issue more equity and exhibit better performance when they cross-list their shares in the US, given that they better protect minority shareholders’ interests. Our results were robust to the use of several control variables.
On Ultra-Sharp Queueing Bounds
Authors: Ciucu Florin , Mehri Sima , Rizk Amr
Published: October 2023

Martingale-based techniques render sharp bounds in several queueing scenarios, but mainly in heavy-traffic and subject to the degree of burstiness. We present a related technique to render ultra-sharp bounds across all utilization levels and for various degrees of burstiness.
The Role of Advanced Math in Teaching Performance Modeling
Authors: Scully Ziv
Published: October 2023

How should we teach performance modeling without assuming a deep mathematical background? One approach is to focus on rigorously studying relatively simple stochastic models that do not require too much math background. But this may leave students underprepared to reason about systems in practice. They have multiple servers, bursty arrivals, heavy tails, and other features that demand more complex stochastic models. Reasoning about these phenomena calls for advanced tools from performance modeling theory, but rigorously learning such tools requires more math background than many computer science and engineering students have.
The First Workshop on Quantum Systems and Computations (2023)
Authors: Elkouss David , Lui John C.S. , Tassiulas Leandros
Published: October 2023

It is of great pleasure to host the first Workshop on Quantum Systems and Computation, which was held on June 19, 2023 at Orlando, Florida.