bluuebunny/crossref_metadata_2025 huggingface dataset:
Emulation-based adaptive differential evolution: fast and auto-tunable approach for moderately expensive optimization problems
Authors: Nishihara Kei , Nakata Masaya
Published: February 2024

In the field of expensive optimization, numerous papers have proposed surrogate-assisted evolutionary algorithms (SAEAs) for a few thousand or even hundreds of function evaluations. However, in reality, low-cost simulations suffice for a lot of real-world problems, in which the number of function evaluations is moderately restricted, e.g., to several thousands. In such moderately restricted scenario, SAEAs become unnecessarily time-consuming and tend to struggle with premature convergence. In addition, tuning the SAEA parameters becomes impractical under the restricted budgets of function evaluations—in some cases, inadequate configuration may degrade performance instead. In this context, this paper presents a fast and auto-tunable evolutionary algorithm for solving moderately restricted expensive optimization problems. The presented algorithm is a variant of adaptive differential evolution (DE) algorithms, and is called emulation-based adaptive DE or EBADE. The primary aim of EBADE is to emulate the principle of sample-efficient optimization, such as that in SAEAs, by adaptively tuning the DE parameter configurations. Specifically, similar to Expected Improvement-based sampling, EBADE identifies parameter configurations that may produce expected-to-improve solutions, without using function evaluations. Further, EBADE incepts a multi-population mechanism and assigns a parameter configuration to each subpopulation to estimate the effectiveness of parameter configurations with multiple samples carefully. This subpopulation-based adaptation can help improve the selection accuracy of promising parameter configurations, even when using an expected-to-improve indicator with high uncertainty, by validating with respect to multiple samples. The experimental results demonstrate that EBADE outperforms modern adaptive DEs and is highly competitive compared to SAEAs with a much shorter runtime.
The Market in the Kingdom of Ends
Authors: Santori Paolo
Published: February 2024

In the literature on the Moral Limits of the Markets, Kant’s moral philosophy is often employed to assess the amoral or immoral nature of the commercial sphere. Markets and morality are antipodes since the instrumentality of market transactions excludes or undermines moral values. The kingdom of ends, where everything has either a price or a dignity, closes the door to market logic. The present paper challenges this view, which is also endorsed by business ethics authors advocating for Moral Purism. I will show that Kant imagined a market within the Kingdom of Ends where everyone pursues their own aims while assisting others in pursuing theirs. This model, built on the universalization of the maxim of mutual assistance and the duty of honoring the spirit of mutually beneficial contracts, can be employed to judge the morality of real (empirical) market transactions.
The Contemporary International Committee of the Red Cross
Authors: Forsythe David P.
Published: February 2024

The International Committee of the Red Cross (ICRC) was founded in 1863 and is often considered the gold standard in humanitarian action. Despite its many positive achievements over more than 150 years, some former ICRC officials believe that the organization is now in decline because of a series of recent policy choices. Their view is that the organization has undermined its reputation for independent and neutral humanitarian action, while growing too fast and too large, which has weakened its reputation for quick, tightly focused, and effective action in the field.
David P. Forsythe revisits the ICRC policy decisions of recent decades and suggests that the organization is not in fatal decline, but that it does need to reconsider some of its policies at the margins. Though some errors have been made and some corrections are in order, Forsythe argues that its obituary is premature.
Regional Politics in Oceania
Authors: Lawson Stephanie
Published: February 2024

Stephanie Lawson's book is by far the most comprehensive study of regional politics in Oceania produced to date. Drawing on a range of interdisciplinary sources, she provides a systematic account of major issues facing the region and presents conceptual and theoretical issues in a sophisticated but accessible manner. She traces the trajectories of regional politics from the earliest human settlements to European exploration and colonization, the period of formal regionalization in the post-war period, decolonization, the Cold War, and key geopolitical developments in the post-Cold War period. She also focuses on identity politics, manifest at various levels from the local through to the national, subregional and regional, as well as broader configurations around the West/non-West divide. This book will be of interest to anyone engaged with the history and politics of Oceania or comparative regional studies, especially given the relevance of themes to Asian, African and Latin American contexts.
The Shiny Seventh
Authors: Holden Len
Published: February 2024

The Shiny Seventh was an ordinary Kitchener battalion, a body of men raised for the duration of the war, forming part of an ordinary county regiment.
The Diocese of Exeter in 1821
Authors: Cook Michael
Published: February 2024

In 1821 Bishop Carey conducted a visitation of the clergy of Devon and Cornwall, asking about the state of their parishes. This volume, along with DCRS New Series volume 4, presents the answers for Devon, and they tell us much about religious life in the county, including the state of parishes, the activities of the clergy, and the relationship between dissenters and the ordinary life of the parish.
Stakeholder Cues, National Origin, and Public Opinion Towards Firms: Evidence in the Context of the First Bank in an American Indian Nation
Authors: Wellhausen Rachel L. , Feir Donn L. , Thrall Calvin
Published: February 2024

When and how does stakeholder credibility matter in shaping public opinion? We explore this question in a real-world setting: in order to fight its citizens’ financial exclusion—a key barrier to development in Indian Country—American Indian Nation “A” negotiated the first entry of the first bank to its reservation. The bank is owned by American Indian Nation “B.” To the Federal Reserve, the bank branch is a potential proof-of-concept for the capacity of tribe-to-tribe investment to improve capital access in underserved Native communities. The bank’s success ultimately depends on whether Nation A’s citizens use its services; in the months before its opening, all three stakeholders independently attempted to influence public opinion toward the bank. We collaborated to conduct a first-of-its-kind survey of Nation A’s tribal members, finding high baseline buy-in especially given the bank’s nationality, but weak and even counterproductive treatment effects of pro-banking cues provided by Nation A and the Federal Reserve. Our results make clear the practical benefits of theory-building around stakeholder credibility, and the crucial role of individual attitudes in the political economy of development.
Business politics is usually about attempts to exert influence rather than power. Evidence from Australia
Authors: Bell Stephen , Hindmoor Andrew
Published: February 2024

We argue that the everyday language distinction drawn between power and influence is meaningful and significant. There is good reason to believe that much corporate lobbying activity which is currently described under the heading of business power is better understood as attempts to secure negotiated agreements based on exerting influence rather than power and that the latter is usually used only when attempts to use influence have failed. We develop an analytical distinction between influence, understood as successful efforts at persuasion, and power using Keith Dowding’s work on power. Drawing upon findings from interviews with corporate professionals operating at the coalface of business and government interaction in Australia, we show that lobbyists generally seek “quiet” behind-the-scenes accommodations with governments via attempts to exert influence rather than power.
Effects of dilatation and turbulence on tangential strain rates in premixed hydrogen and iso-octane flames
Authors: Chu Hongchao , Berger Lukas , Gauding Michael , Attili Antonio , Pitsch Heinz
Published: February 2024

The tangential strain rate in premixed flames impacts significantly the flame surface area generation and thus the combustion process. Studies on incompressible isotropic turbulence have revealed that the mean tangential strain rate at material and iso-scalar surfaces is positive and exhibits a universal value when normalized by the Kolmogorov time. This is associated with the preferential alignment of the surface normal with the most compressive principal strain rate. The present study investigates such effects in premixed hydrogen and iso-octane flame kernels using direct numerical simulations. It is shown that the normalized mean tangential strain rate of the investigated flames has a very similar value compared with the incompressible flows. However, in the reaction zone, the flame surface normal aligns preferentially with the most extensive principal strain rate. Furthermore, this alignment depends on the reaction progress variable and the Lewis number, while the tangential strain rate remains independent of these parameters. Such counter-intuitive behaviour is systematically investigated by decomposing the effects of dilatation and residual solenoidal turbulence. It is found that the solenoidal turbulence influences significantly the tangential strain rate. A general effect of turbulence on the tangential strain rate is identified, which is consistent with incompressible flows and independent of the Lewis number and the reaction progress variable. This is a remarkable finding indicating that models of the tangential strain rate developed based on incompressible flows apply also to premixed flames with different Lewis numbers, and, for the modelling, only the solenoidal turbulence should be considered.
The effects of word and beat priming on Mandarin lexical stress recognition: an event-related potential study
Authors: Yu Wenjing , Chien Yu-Fu , Wang Bing , Zhao Jianjun , Li Weijun
Published: February 2024

Music and language are unique communication tools in human society, where stress plays a crucial role. Many studies have examined the recognition of lexical stress in Indo-European languages using beat/rhythm priming, but few studies have examined the cross-domain relationship between musical and linguistic stress in tonal languages. The current study investigates how musical stress and lexical stress influence lexical stress recognition in Mandarin. In the auditory priming experiment, disyllabic Mandarin words with initial or final stress were primed by disyllabic words or beats with either congruent or incongruent stress patterns. Results showed that the incongruent condition elicited larger P2 and the late positive component (LPC) amplitudes than the congruent condition. Moreover, the Strong-Weak primes elicited larger N400 amplitudes than the Weak-Strong primes, and the Weak-Strong primes yielded larger LPC amplitudes than the Strong-Weak primes. The findings reveal the neural correlates of the cross-domain influence between music and language during lexical stress recognition in Mandarin.
The Eureka theorem of Gauss
Authors: Dolan Stan
Published: February 2024

On 10th July 1796, when he was still a teenager, Gauss famously wrote EYPHKA! in his diary when recording the completion of a proof that every positive integer is the sum of at most three triangular numbers.
Singular matrices and pairwise-tangent circles
Authors: Beardon A. F.
Published: February 2024

The idea of using the generalised inverse of a singular matrix A to solve the matrix equation Ax = b has been discussed in the earlier papers [1, 2, 3, 4] in the Gazette. Here we discuss three simple geometric questions which are of interest in their own right, and which illustrate the use of the generalised inverse of a matrix. The three questions are about polygons and circles in the Euclidean plane. We need not assume that a polygon is a simple closed curve, nor that it is convex: indeed, abstractly, a polygon is just a finite sequence (v1, …, vn) of its distinct, consecutive, vertices. It is convenient to let vn + 1 = v1 and (later) Cn + 1 = C1.
Relating constructions and properties through duality
Authors: Kilner Steven J. , Farnsworth David L.
Published: February 2024

Our goal is to find new constructions and properties of parabolas. Our strategy is to display the steps in a known construction or property, and then to take the dual of the steps in order to create a new construction or property.
ARCHITECTURAL MEMORY AND TRIMALCHIO'S PORTICVS
Authors: Anguissola Anna
Published: February 2024

This paper seeks to respond to two questions posed by previous commentators concerning the arrangement of Trimalchio's porticus as described in Petronius’ Satyrica (Sat. 29): first, whether the freedman's house lacked an atrium; second, whether the cursores (runners) who are described as unconventionally exercising in the portico were pictorial representations or real-life athletes who would symbolize the social incompetence of the dominus. This paper argues that nothing in the text supports the interpretation of Trimalchio's house as having an unconventional architectural layout. Instead, as the narrative requires that Encolpius move quickly towards the triclinium, in his description the loca communia appear conflated, while he only sparsely notices a few relevant elements of the decor. The presentation of Trimalchio's porticus appears to have a functional rather than a simply descriptive purpose: it symbolizes both Roman contemporary practices (the loca communia as a distinctive unit within the domus) and the influence of Greek cultural habits (the characteristic association of colonnaded courtyards and athletics). The excerpt that describes the guests’ arrival at Trimalchio's house, therefore, serves an important narrative function, providing essential information about the character's origins, self-image and social life.
Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders
Authors: Guimond Synthia , Alftieh Ahmad , Devenyi Gabriel A. , Mike Luke , Chakravarty M. Mallar , Shah Jai L. , Parker David A. , Sweeney John A. , Pearlson Godfrey , Clementz Brett A. , Tamminga Carol A. , Keshavan Matcheri
Published: February 2024

Background

Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders.

Methods

The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration.

Results

Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006).

Conclusions

Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.
COINTEGRATING POLYNOMIAL REGRESSIONS: ROBUSTNESS OF FULLY MODIFIED OLS
Authors: Stypka Oliver , Wagner Martin , Grabarczyk Peter , Kawka Rafael
Published: February 2024

Cointegrating polynomial regressions (CPRs) include deterministic variables, integrated variables, and their powers as explanatory variables. Based on a novel kernel-weighted limit result and a novel functional central limit theorem, this paper shows that the fully modified ordinary least squares (FM-OLS) estimator of Phillips and Hansen (1990, Review of Economic Studies 57, 99–125) is robust to being used in CPRs. Being used in CPRs refers to a widespread empirical practice that treats the integrated variables and their powers, incorrectly, as a vector of integrated variables and uses textbook FM-OLS. Robustness means that this “formal” FM-OLS practice leads to a zero mean Gaussian mixture limiting distribution that coincides with the limiting distribution of the Wagner and Hong (2016, Econometric Theory 32, 1289–1315) application of the FM estimation principle to the CPR case. The only restriction for this result to hold is that all integrated variables to power one are included as regressors. Even though simulation results indicate performance advantages of the Wagner and Hong (2016, Econometric Theory 32, 1289–1315) estimator, partly even in large samples, the results of the paper give an asymptotic foundation to “formal” FM-OLS and thus enlarge the usability of the Phillips and Hansen (1990, Review of Economic Studies 57, 99–125) estimator implemented in many software packages.
Kṛṣṇa the Magician: metapoesis and ambivalence in Faiḍī's Mahābhārat
Authors: Smolin Justin N.
Published: February 2024

In this article, I discuss the vilification of Kṛṣṇa as a deceitful sorcerer in the Mughal poet-laureate Shaikh Abū'l Faiḍ bin Mubārak, or ‘Faiḍī's Mahābhārat and his correspondent apotheosis as the ‘essence of the True God' in the Shāriq al-maʿrifat, a treatise also ascribed to Faiḍī. As I argue, this inconsistency, or ambivalence, is a common and overlooked facet of the elite Islamicate engagement with religious diversity and difference in early modern Hindustan. In the case of the Mahābhārat, however, Faiḍī's portrayal of Kṛṣṇa as a deceitful illusionist reflects not only an Islamic discomfort with Vaishnavite theology, but Faiḍī's own performative insecurities as a Hindustani writer of Persian poetry and literary prose. Kṛṣṇa's so-called ‘magic’ lies in large part in his way with words: the verbal and social manipulation he uses to stoke the flames of conflict. The character thus becomes a kind of shadow or double of Faiḍī himself-a demiurgic author of the Mahābhārat upon which the poet can displace the classical Islamicate association of poetry with sorcery and deceit.
The United States Has an Updated Map of Earthquake Hazards
Authors: Hasler Caroline
Published: February 2024

The new National Seismic Hazard Model shows where damaging earthquakes are likely to occur, informing public safety and infrastructure policies.
A pilot study of chlormequat in food and urine from adults in the United States from 2017 to 2023
Authors: Temkin Alexis M. , Evans Sydney , Spyropoulos Demetri D. , Naidenko Olga V.
Published: February 2024

Chlormequat chloride is a plant growth regulator whose use on grain crops is on the rise in North America. Toxicological studies suggest that exposure to chlormequat can reduce fertility and harm the developing fetus at doses lower than those used by regulatory agencies to set allowable daily intake levels. Here we report, the presence of chlormequat in urine samples collected from people in the U.S., with detection frequencies of 69%, 74%, and 90% for samples collected in 2017, 2018–2022, and 2023, respectively. Chlormequat was detected at low concentrations in samples from 2017 through 2022, with a significant increase in concentrations for samples from 2023. We also observed high detection frequencies of chlormequat in oat-based foods. These findings and chlormequat toxicity data raise concerns about current exposure levels, and warrant more expansive toxicity testing, food monitoring, and epidemiological studies to assess health effects of chlormequat exposures in humans.

Impact

This study reports the detection of chlormequat, an agricultural chemical with developmental and reproductive toxicity, in the U.S. population and U.S. food supplies for the first time. While similar levels of the chemical were found in urine sampled from 2017 to 2022, markedly increased levels were found in samples from 2023. This work highlights the need for more expansive monitoring of chlormequat in U.S. foods and in human specimens, as well as toxicological and epidemiological study on chlormequat, as this chemical is an emerging contaminant with documented evidence of low-dose adverse health effects in animal studies.
Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia
Authors: Boncompagni Gioia , Tatangelo Vanessa , Lopresti Ludovica , Ulivieri Cristina , Capitani Nagaja , Tangredi Carmela , Finetti Francesca , Marotta Giuseppe , Frezzato Federica , Visentin Andrea , Ciofini Sara , Gozzetti Alessandro , Bocchia Monica , Calzada-Fraile Diego , Martin Cofreces Noa B. , Trentin Livio , Patrussi Laura , Baldari Cosima T.
Published: February 2024

The tumor microenvironment (TME) plays a central role in the pathogenesis of chronic lymphocytic leukemia (CLL), contributing to disease progression and chemoresistance. Leukemic cells shape the TME into a pro-survival and immunosuppressive niche through contact-dependent and contact-independent interactions with the cellular components of the TME. Immune synapse (IS) formation is defective in CLL. Here we asked whether soluble factors released by CLL cells contribute to their protection from cytotoxic T cell (CTL)-mediated killing by interfering with this process. We found that healthy CTLs cultured in media conditioned by leukemic cells from CLL patients or Eμ-TCL1 mice upregulate the exhaustion marker PD-1 and become unable to form functional ISs and kill target cells. These defects were more pronounced when media were conditioned by leukemic cells lacking p66Shc, a proapoptotic adapter whose deficiency has been implicated in disease aggressiveness both in CLL and in the Eμ-TCL1 mouse model. Multiplex ELISA assays showed that leukemic cells from Eμ-TCL1 mice secrete abnormally elevated amounts of CCL22, CCL24, IL-9 and IL-10, which are further upregulated in the absence of p66Shc. Among these, IL-9 and IL-10 were also overexpressed in leukemic cells from CLL patients, where they inversely correlated with residual p66Shc. Using neutralizing antibodies or the recombinant cytokines we show that IL-9, but not IL-10, mediates both the enhancement in PD-1 expression and the suppression of effector functions in healthy CTLs. Our results demonstrate that IL-9 secreted by leukemic cells negatively modulates the anti-tumor immune abilities of CTLs, highlighting a new suppressive mechanism and a novel potential therapeutical target in CLL.
A novel bystander effect in tamoxifen treatment: PPIB derived from ER+ cells attenuates ER− cells via endoplasmic reticulum stress-induced apoptosis
Authors: Yang Tinglin , Li Wenhui , Zhou Jun , Xu Ming , Huang Ziwei , Ming Jie , Huang Tao
Published: February 2024

Tamoxifen (TAM) is the frontline therapy for estrogen receptor-positive (ER+) breast cancer in premenopausal women that interrupts ER signaling. As tumors with elevated heterogeneity, amounts of ER-negative (ER−) cells are present in ER+ breast cancer that cannot be directly killed by TAM. Despite complete remissions have been achieved in clinical practice, the mechanism underlying the elimination of ER− cells during TAM treatment remains an open issue. Herein, we deciphered the elimination of ER− cells in TAM treatment from the perspective of the bystander effect. Markable reductions were observed in tumorigenesis of ER− breast cancer cells by applying both supernatants from TAM-treated ER+ cells and a transwell co-culture system, validating the presence of a TAM-induced bystander effect. The major antitumor protein derived from ER+ cells, peptidyl-prolyl cis-trans isomerase B (PPIB), is the mediator of the TAM-induced bystander effect identified by quantitative proteomics. The attenuation of ER− cells was attributed to activated BiP/eIF2α/CHOP axis and promoted endoplasmic reticulum stress (ERS)-induced apoptosis, which can also be triggered by PPIB independently. Altogether, our study revealed a novel TAM-induced bystander effect in TAM treatment of ER+ breast cancer, raising the possibility of developing PPIB as a synergistic antitumor agent or even substitute endocrine therapy.
Identification of structural and regulatory cell-shape determinants in Haloferax volcanii
Authors: Schiller Heather , Hong Yirui , Kouassi Joshua , Rados Theopi , Kwak Jasmin , DiLucido Anthony , Safer Daniel , Marchfelder Anita , Pfeiffer Friedhelm , Bisson Alexandre , Schulze Stefan , Pohlschroder Mechthild
Published: February 2024

Archaea play indispensable roles in global biogeochemical cycles, yet many crucial cellular processes, including cell-shape determination, are poorly understood. Haloferax volcanii, a model haloarchaeon, forms rods and disks, depending on growth conditions. Here, we used a combination of iterative proteomics, genetics, and live-cell imaging to identify mutants that only form rods or disks. We compared the proteomes of the mutants with wild-type cells across growth phases, thereby distinguishing between protein abundance changes specific to cell shape and those related to growth phases. The results identified a diverse set of proteins, including predicted transporters, transducers, signaling components, and transcriptional regulators, as important for cell-shape determination. Through phenotypic characterization of deletion strains, we established that rod-determining factor A (RdfA) and disk-determining factor A (DdfA) are required for the formation of rods and disks, respectively. We also identified structural proteins, including an actin homolog that plays a role in disk-shape morphogenesis, which we named volactin. Using live-cell imaging, we determined volactin’s cellular localization and showed its dynamic polymerization and depolymerization. Our results provide insights into archaeal cell-shape determination, with possible implications for understanding the evolution of cell morphology regulation across domains.
A landscape of gene expression regulation for synovium in arthritis
Authors: Jiang Feng , Hu Shou-Ye , Tian Wen , Wang Nai-Ning , Yang Ning , Dong Shan-Shan , Song Hui-Miao , Zhang Da-Jin , Gao Hui-Wu , Wang Chen , Wu Hao , He Chang-Yi , Zhu Dong-Li , Chen Xiao-Feng , Guo Yan , Yang Zhi , Yang Tie-Lin
Published: February 2024

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.
TFvelo: gene regulation inspired RNA velocity estimation
Authors: Li Jiachen , Pan Xiaoyong , Yuan Ye , Shen Hong-Bin
Published: February 2024

RNA velocity is closely related with cell fate and is an important indicator for the prediction of cell states with elegant physical explanation derived from single-cell RNA-seq data. Most existing RNA velocity models aim to extract dynamics from the phase delay between unspliced and spliced mRNA for each individual gene. However, unspliced/spliced mRNA abundance may not provide sufficient signal for dynamic modeling, leading to poor fit in phase portraits. Motivated by the idea that RNA velocity could be driven by the transcriptional regulation, we propose TFvelo, which expands RNA velocity concept to various single-cell datasets without relying on splicing information, by introducing gene regulatory information. Our experiments on synthetic data and multiple scRNA-Seq datasets show that TFvelo can accurately fit genes dynamics on phase portraits, and effectively infer cell pseudo-time and trajectory from RNA abundance data. TFvelo opens a robust and accurate avenue for modeling RNA velocity for single cell data.
Ca-dimers, solvent layering, and dominant electrochemically active species in Ca(BH4)2 in THF
Authors: Sanz Matias Ana , Roncoroni Fabrice , Sundararaman Siddharth , Prendergast David
Published: February 2024

Divalent ions (Mg, Ca, and Zn) are being considered as competitive, safe, and earth-abundant alternatives to Li-ion electrochemistry, but present challenges for stable cycling due to undesirable interfacial phenomena. We explore the formation of electroactive species in the electrolyte Ca(BH4)2∣THF using molecular dynamics coupled with a continuum model of bulk and interfacial speciation. Free-energy analysis and unsupervised learning indicate a majority population of neutral Ca dimers and monomers with diverse molecular conformations and an order of magnitude lower concentration of the primary electroactive charged species – the monocation, $${\rm{CaBH}}_{4}^{+}$$

CaBH

4

+

– produced via disproportionation of neutral complexes. Dense layering of THF molecules within ~1 nm of the electrode surface strongly modulates local electrolyte species populations. A dramatic increase in monocation population in this interfacial zone is induced at negative bias. We see no evidence for electrochemical activity of fully-solvated Ca2+. The consequences for performance are discussed in light of this molecular-scale insight.
Flexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing
Authors: de Cesare Mariateresa , Mwenda Mulenga , Jeffreys Anna E. , Chirwa Jacob , Drakeley Chris , Schneider Kammerle , Mambwe Brenda , Glanz Karolina , Ntalla Christina , Carrasquilla Manuela , Portugal Silvia , Verity Robert J. , Bailey Jeffrey A. , Ghinai Isaac , Busby George B. , Hamainza Busiku , Hawela Moonga , Bridges Daniel J. , Hendry Jason A.
Published: February 2024

Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum complicates the development of genomic methods, while resource constraints in malaria endemic regions can limit their deployment. Here, we demonstrate an approach for targeted nanopore sequencing of P. falciparum from dried blood spots (DBS) that enables cost-effective genomic surveillance of malaria in low-resource settings. We release software that facilitates flexible design of amplicon sequencing panels and use this software to design two target panels for P. falciparum. The panels generate 3–4 kbp reads for eight and sixteen targets respectively, covering key drug-resistance associated genes, diagnostic test antigens, polymorphic markers and the vaccine target csp. We validate our approach on mock and field samples, demonstrating robust sequencing coverage, accurate variant calls within coding sequences, the ability to explore P. falciparum within-sample diversity and to detect deletions underlying rapid diagnostic test failure.
Integrated microcavity electric field sensors using Pound-Drever-Hall detection
Authors: Ma Xinyu , Cai Zhaoyu , Zhuang Chijie , Liu Xiangdong , Zhang Zhecheng , Liu Kewei , Cao Bo , He Jinliang , Yang Changxi , Bao Chengying , Zeng Rong
Published: February 2024

Discerning weak electric fields has important implications for cosmology, quantum technology, and identifying power system failures. Photonic integration of electric field sensors is highly desired for practical considerations and offers opportunities to improve performance by enhancing microwave and lightwave interactions. Here, we demonstrate a high-Q microcavity electric field sensor (MEFS) by leveraging the silicon chip-based thin film lithium niobate photonic integrated circuits. Using the Pound-Drever-Hall detection scheme, our MEFS achieves a detection sensitivity of 5.2 μV/(m$$\sqrt{{{{{{{{\rm{Hz}}}}}}}}}$$

Hz

), which surpasses previous lithium niobate electro-optical electric field sensors by nearly two orders of magnitude, and is comparable to atom-based quantum sensing approaches. Furthermore, our MEFS has a bandwidth that can be up to three orders of magnitude broader than quantum sensing approaches and measures fast electric field amplitude and phase variations in real-time. The ultra-sensitive MEFSs represent a significant step towards building electric field sensing networks and broaden the application spectrum of integrated microcavities.
Assessing the impact of mRNA vaccination in chronic inflammatory murine model
Authors: Lee Seonghyun , Lee Jisun , Cho Sun-Hee , Roh Gahyun , Park Hyo-Jung , Lee You-Jeung , Jeon Ha-Eun , Lee Yu-Sun , Bae Seo-Hyeon , Youn Sue Bean , Cho Youngran , Oh Ayoung , Ha Dahyeon , Lee Soo-Yeon , Choi Eun-Jin , Cho Seongje , Lee Sowon , Kim Do-Hyung , Kang Min-Ho , Yoon Mee-Sup , Lim Byung-Kwan , Nam Jae-Hwan
Published: February 2024

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.
Effectiveness and safety of telehealth medication abortion in the USA
Authors: Upadhyay Ushma D. , Koenig Leah R. , Meckstroth Karen , Ko Jennifer , Valladares Ena Suseth , Biggs M. Antonia
Published: February 2024

Telehealth abortion has become critical to addressing surges in demand in states where abortion remains legal but evidence on its effectiveness and safety is limited. California Home Abortion by Telehealth (CHAT) is a prospective study that follows pregnant people who obtained medication abortion via telehealth from three virtual clinics operating in 20 states and Washington, DC between April 2021 and January 2022. Individuals were screened using a standardized no-test protocol, primarily relying on their medical history to assess medical eligibility. We assessed effectiveness, defined as complete abortion after 200 mg mifepristone and 1,600 μg misoprostol (or lower) without additional intervention; safety was measured by the absence of serious adverse events. We estimated rates using multivariable logistic regression and multiple imputation to account for missing data. Among 6,034 abortions, 97.7% (95% confidence interval (CI) = 97.2–98.1%) were complete without subsequent known intervention or ongoing pregnancy after the initial treatment. Overall, 99.8% (99.6–99.9%) of abortions were not followed by serious adverse events. In total, 0.25% of patients experienced a serious abortion-related adverse event, 0.16% were treated for an ectopic pregnancy and 1.3% abortions were followed by emergency department visits. There were no differences in effectiveness or safety between synchronous and asynchronous models of care. Telehealth medication abortion is effective, safe and comparable to published rates of in-person medication abortion care.
A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis
Authors: Haynes Paula R. , Pyfrom Elana S. , Li Yongjun , Stein Carly , Cuddapah Vishnu Anand , Jacobs Jack A. , Yue Zhifeng , Sehgal Amita
Published: February 2024

Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron–glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.
Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial
Authors: Hadanny Amir , Zilberman-Itskovich Shani , Catalogna Merav , Elman-Shina Karin , Lang Erez , Finci Shachar , Polak Nir , Shorer Ran , Parag Yoav , Efrati Shai
Published: February 2024

In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47–0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.
The effect of minimizing central line days for very low birth weight infants through quality improvement
Authors: Shin Jeongmin , Kang Hyun Mi , Kim Sae Yun , Youn Young-Ah , Choi Chang Won , Chang Yun Sil
Published: February 2024

Blood culture proven sepsis is associated with increased mortality and morbidity. Given the extended hospitalization of very preterm infants, catheter-related blood stream infections (CRBSIs) play a substantial role in sepsis. The reported incidence of CRBSIs in neonates varies from 3.2 to 21.8 CRBSIs per 1000 catheter line days. Moreover, discrepancies in neonatal practices and potential neglect may lead to the unwarranted prolongation of central lines. This study aims to compare two distinct periods (Pre-QI vs. Post-QI) in relation to the central line insertion rate and duration, as well as blood culture proven sepsis, duration of total parenteral nutrition (TPN), and the progression of feeding. These factors are known to be associated with prolonged hospitalization and increased morbidities. A total of 210 very low birth weight infants (VLBWIs), defined as either less than 32 weeks of gestational age (GA) or weighing less than 1500 g, were admitted to the Neonatal Intensive Care Unit (NICU) at Seoul St. Mary’s Hospital, The Catholic University of Korea, between January 2020 and June 2023. Fourteen infants were excluded from the study as they did not survive beyond 1 month of life, and one was excluded due to a congenital anomaly. Consequently, the analysis included 195 VLBWIs. The Quality Improvement (QI) initiative began in January 2022, marking the division into two distinct epochs: the Pre-QI period, encompassing the years 2020 to 2021, and the Post-QI period, spanning from 2022 to 2023. The primary outcome measures included PICC insertion rates, duration, and feeding advancement or feeding-related complications. The hospital outcome measures were also compared between the two periods. A total of 195 VLBWI were included in the analysis. The birth weight was significantly lower in the pre-QI period, with an average of 1023 g compared to 1218 g (P < 0.001). Severe BPD ≥ moderate was significantly lower in the post-QI period (36.2% vs. 53.9%) (P < 0.001) along with shorter mechanical ventilation days (12 ± 29 vs. 22 ± 27) (P = 0.046). The PICC insertion rate was significantly decreased from 95.6% in pre-QI period compared to 55.2% in post-QI period (P < 0.001) along with a notable reduction in blood culture-proven sepsis (25.6% vs. 10.5%, P = 0.008). CRBSI rate was reduced from 1.3 to 1.1 per 1000 catheter days in the post-QI period. Moreover, the time required to achieve full enteral feeding of 100 mL/kg/day was significantly shorter in the post-QI (24 ± 23 vs. 33 ± 25) (P = 0.006). Multivariable logistic regression analysis for sepsis revealed that both birth weight and pre/post QI consistently demonstrated an association with lower sepsis rates in the Post-QI period. QI has the potential to reduce the burden of unnecessary interventions and blood culture proven sepsis rate along with CRBSI rate, thereby, optimizing the better care of very preterm babies.
Neonatal lupus erythematosus as a rare trigger of gastrointestinal involvement in neonates
Authors: Fu Changchang , Sun Wenqiang , Peng Hanghang , Zhu Xueping
Published: February 2024

Cutaneous and cardiac involvement in neonatal lupus erythematosus (NLE) has been extensively studied; however, gastrointestinal system involvement (GSI) remains unexplored. This study aimed to investigate the clinical features of GSI in patients with NLE with a particular focus on feeding intolerance (FI) and diarrhea. We conducted a retrospective analysis of the clinical data of patients diagnosed with NLE at the Children’s Hospital of Soochow University between 2011 and 2022. In this study, of 39 patients diagnosed with NLE, 27 presented with GSI. 9 patients who presented with FI or diarrhea as the primary manifestation were positive for anti-SSA antibody, and 5 were dual positive for anti-SSA and anti-SSB antibodies. Among the mothers of the NLE patients with GSI, 18 had systemic lupus erythematosus, 3 had Sjogren’s syndrome, 2 had mixed connective tissue disease, and one each had autoantibody abnormalities and photosensitivity symptoms; 4 mothers denied having any autoimmune disease. In this study, 69.23% of patients with NLE exhibited GSI, which was linked to hypocomplementemia and anti-SSA antibodies. Thus, clinicians should remain vigilant for NLE in neonates, particularly when accompanied with rash and other organ dysfunction and when the high-risk factors of FI and diarrhea have been excluded.
The use of blackcurrant pomace and erythritol to optimise the functional properties of shortbread cookies
Authors: Raczkowska Ewa , Wojdyło Aneta , Nowicka Paulina
Published: February 2024

As a result of the production of blackcurrant juice, pomace is produced, which is a cheap, easy to further process raw material with high health benefits. The aim of the research was to develop a recipe for shortbread cookies based on blackcurrant pomace (0, 10, 30, 50%) and erythritol, and to assess their nutritional value (content of proteins, fats, sugars, dietary fibre, selected minerals and energy value), pro-health properties (antioxidant and anti-diabetic capacity) and sensory evaluation. The energy value of products with 50% of pomace sweetened with erythritol was nearly 30% lower compared to traditional cookies, while the content of dietary fibre was 10 times higher in products with the highest percentage of pomace. The antioxidant capacity and the total content of polyphenolic compounds increased with the increase in pomace content. The ability to inhibit α-amylase by shortbread cookies without pomace was about 400 times lower than those with 50% pomace. The results of the sensory evaluation showed that erythritol-sweetened cookies have more desirable characteristics compared to sucrose-sweetened cookies. Finally, it was proved that the proposed products are an excellent proposal for people struggling with food-dependent diseases, as well as being an opportunity to manage waste from the fruit industry.