bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery room resuscitation intensity and associated neonatal outcomes of 24+0–31+6 weeks’ preterm infants in China: a retrospective cross-sectional study
Authors: Wang Si-Lu , Chen Chun , Gu Xin-Yue , Yin Zhao-Qing , Su Le , Jiang Si-Yuan , Cao Yun , Du Li-Zhong , Sun Jian-Hua , Liu Jiang-Qin , Yang Chuan-Zhong ,   Chinese Neonatal Network Investigators
Published: June 2023

Background

The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0–31+6 weeks’ gestation age (GA).

Methods

This was a retrospective cross-sectional study. The source population was infants born at 24+0–31+6 weeks’ GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O2/CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression.

Results

Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O2/CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation (P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation.

Conclusions

Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed.
Exploring the Binding Mechanism of NRG1–ERBB3 Complex and Discovery of Potent Natural Products to Reduce Diabetes-Assisted Breast Cancer Progression
Authors: Marafie Sulaiman K. , Alshawaf Eman , Abu-Farha Mohamed , Thanaraj Thangavel Alphonse , Wei Dong-Qing , Al-Mulla Fahd , Khan Abbas , Abubaker Jehad , Mohammad Anwar
Published: June 2023

Diabetes mellitus significantly contributes to breast cancer progression, where hyperglycemia upregulates specific genes, leading to more aggressive tumor growth. In patients with BC that develop diabetes, neuregulin 1 (NRG1) and epidermal growth factor receptor 3 (ERBB3) overexpression exacerbate tumor growth and progression. Since the interaction between NRG1 and ERBB3 is critical for tumor growth, understanding the molecular mechanisms underlying NRG1–ERBB3 complex formation is essential for elucidating diabetes-assisted breast cancer progression. However, the key residues forming the NRG1–ERBB3 complex remain unknown. Here, we substituted specific residues in NRG1 with alanine and studied its interactions with ERBB3 using computational structural biology tools. We further screened the South African natural compounds database to target the complex’s interface residues to discover potential inhibitors. The conformational stability and dynamic features of NRG1–WT, –H2A, –L3A, and –K35A complexed with ERBB3 were subjected to 400 ns molecular dynamics simulations. The free binding energies of all NRG1–ERBB3 complexes were calculated using the molecular mechanics-generalized Born surface area (MM/GBSA). The H2 and L3 alanine substitutions caused a loss of interaction with ERBB3 residue D73, weakening the interaction with ERBB3. Screening 1300 natural compounds identified four (SANC00643, SANC00824, SANC00975, and SANC00335) with the best potential to inhibit ERRB3-NRG1 coupling. The binding free energies for each complex were − 48.55 kcal/mol for SANC00643, − 47.68 kcal/mol for SANC00824, − 46.04 kcal/mol for SANC00975, and − 45.29 kcal/mol for SANC00335, showing their overall stronger binding with ERBB3 than NRG1 and their potential to act as ERBB3-NRG1 complex inhibitors. In conclusion, this complex may represent a residue-specific drug target to inhibit BC progression.

Graphical abstract
What is a fire resilient landscape? Towards an integrated definition
Authors: Thacker Fiona E. Newman , Ribau Marc Castellnou , Bartholomeus Harm , Stoof Cathelijne R.
Published: June 2023

The concept of fire resilience has become increasingly relevant as society looks to understand and respond to recent wildfire events. In particular, the idea of a ‘fire resilient landscape’ is one which has been utilised to explore how society can coexist with wildfires. However, the concept of fire resilient landscapes has often been approached in silos, either from an environmental or social perspective; no integrated definition exists. Based on a synthesis of literature and a survey of scientists and practitioners, we propose to define a fire resilient landscape as ‘a socio-ecological system that accepts the presence of fire, whilst preventing significant losses through landscape management, community engagement and effective recovery.’ This common definition could help guide policy surrounding fire resilient landscapes, and exemplify how such landscapes could be initiated in practice. We explore the applicability of the proposed definition in both Mediterranean and temperate Europe.
Co-production of high density biomass and high-value compounds via two-stage cultivation of Chlorella vulgaris using light intensity and a combination of salt stressors
Authors: El-fayoumy Eman A. , Ali Hamdy Elsayed Ahmed , Elsaid Khaled , Elkhatat Ahmed , Al-Meer Saeed , Rozaini Mohd Zul Helmi , Abdullah Mohd Azmuddin
Published: June 2023

In this study, the effects of combined stress factors involving light intensity and salinity (NaCl, MgCl2, CaCl2, and their combinations) on the two-stage cultivation of Chlorella vulgaris for simultaneous production of biomass and high-value products, were investigated. The two-stage strategies comprised a 25-day vegetative stage in BG11 medium, followed by a 15-day combined stress stage. During salt stress conditions, the addition of 15 g L−1 CaCl2 or 7.5 g L−1 MgCl2 / 7.5 g L−1 CaCl2 mixture with 140 µmol m−2 s−1 light intensity significantly promoted the growth of C. vulgaris achieving maximum biomass productivity of 50.50 ± 0.50 and 50.25 ± 3.25 mg L−1 d−1, respectively. Cultivation of C. vulgaris in a medium containing 7.5 g L−1 NaCl/ 7.5 g L−1 CaCl2 had remarkably increased the lipid content (31.15 ± 1.18%) and lipid productivity (14.55 ± 1.48 mg L−1 d−1). The saturated fatty acids (SFAs) at 39.52–59.29%, monounsaturated fatty acids (MUFAs) at 27.16–35.47%, and polyunsaturated fatty acids (PUFAs) at 7.18–29.97%, were obtained with palmitic (C16:0), oleic (C18:1), stearic (C18:0), and linolenic (C18:3) acids as predominant fatty acids. Cultures supplemented with 5 g L−1 NaCl / 5 g L−1 MgCl2 / 5 g L−1 CaCl2 and high light intensity exposure attained consistently high carbohydrate content (52.71 ± 2.50%). The combination of 7.5 g L−1 NaCl / 7.5 g L−1 MgCl2 also resulted in a marked increase in the protein content (35.32 ± 2.20%) and total carotenoids (0.31 ± 0.03 μg mL−1) as compared to the Controls. The highest antioxidant activity (86.16%) was achieved with a 7.5 g L−1 NaCl / 7.5 g L−1 CaCl2 combination in the growth stage. The antioxidant activities were attributed to the presence of phenolics, flavonoids, and tannins due to the stressed conditions. One of the key benefits of using a combined stress strategy in this study is that if one factor has a low impact on enhancing target metabolites, other factors can compensate.
Sicherheitsaspekte bei der Behandlung mit Clozapin
Authors: Berger Stefan J. , Hofer Alex
Published: June 2023

Hintergrund

Auf Grund seiner unvergleichbaren Wirksamkeit bei therapieresistenten schizophrenen Störungen ist der Abbruch einer Behandlung mit Clozapin häufig mit einer erheblichen Verschlechterung der Krankheitssymptomatik, aber auch mit einem erhöhten Suizidrisiko verbunden. Ziel der vorliegenden Übersichtsarbeit ist es, auf Basis aktueller Fachliteratur verschiedene Monitoring-Empfehlungen zusammen zu fassen, um diese Therapie gegebenenfalls trotz auftretender unerwünschter Arzneimittelwirkungen (UAW) fortsetzen zu können. Des Weiteren wird ausgearbeitet, wann eine unterbrochene Therapie mit Clozapin wieder aufgenommen werden kann (Rechallenge) und wann ein definitiver Behandlungsabbruch erfolgen muss.

Material und Methoden

Die Datenbank Medline sowie die Guideline for the use of clozapine 2013 der Netherlands Clozapine Collaboration Group und die S3-Behandlungsleitlinie Schizophrenie der Deutschen Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde e.V. wurden nach relevanter Literatur untersucht, die letzte Abfrage erfolgte am 28.04.2023.

Resultate

Bei Entwicklung einer Agranulozytose oder einer Kardiomyopathie muss die Behandlung mit Clozapin beendet werden und sollte auch im weiteren Verlauf nicht wieder aufgenommen werden. Dem gegenüber kann eine auf Grund einer Myokarditis bzw. einer unter der Behandlung auftretenden Verlängerung der QTc-Zeit abgebrochene Behandlung mit Clozapin bei regelrechter linksventrikulärer Funktion bzw. nach Normalisierung der QTc-Zeit gegebenenfalls fortgesetzt werden. Andere UAW stellen in der Regel keine absolute Kontraindikation für eine Rechallenge dar, erfordern jedoch häufig den adjuvanten Einsatz zusätzlicher pharmakologischer und nicht-pharmakologischer Maßnahmen.

Schlussfolgerung

Unter Berücksichtigung verschiedener Monitoring-Empfehlungen kann die Beendigung einer Behandlung mit Clozapin häufig verhindert bzw. eine auf Grund von UAW abgebrochene Behandlung mit Clozapin wieder aufgenommen werden.
The transcription factor HBF1 directly activates expression of multiple flowering time repressors to delay rice flowering
Authors: Li Cong , Zhang Liya , Wang Xin , Yu Chunsheng , Zhao Tao , Liu Bin , Li Hongyu , Liu Jun , Zhang Chunyu
Published: June 2023

Flowering time (or heading date) is an important agronomic trait that determines the environmental adaptability and yield of many crops, including rice (Oryza sativa L.). Hd3a BINDING REPRESSOR FACTOR 1 (HBF1), a basic leucine zipper transcription factor, delays flowering by decreasing the expression of Early heading date 1 (Ehd1), Heading date 3a (Hd3a), and RICE FLOWERING LOCUS T 1 (RFT1), but the underlying molecular mechanisms have not been fully elucidated. Here, we employed the hybrid transcriptional factor (HTF) strategy to enhance the transcriptional activity of HBF1 by fusing it to four copies of the activation domain from Herpes simplex virus VP16. We discovered that transgenic rice lines overexpressing HBF1-VP64 (HBF1V) show significant delays in time to flower, compared to lines overexpressing HBF1-MYC or wild-type plants, via the Ehd1–Hd3a/RFT1 pathway, under both long-day and short-day conditions. Transcriptome deep sequencing analysis indicated that 19 WRKY family genes are upregulated in the HBF1V overexpression line. We demonstrate that the previously unknown gene, OsWRKY64, is a direct downstream target of HBF1 and represses flowering in rice, whereas three known flowering repressor genes, Days to heading 7 (DTH7), CONSTANS 3 (OsCO3), and OsWRKY104, are also direct target genes of HBF1 in flowering regulation. Taking these results together, we propose detailed molecular mechanisms by which HBF1 regulates the time to flower in rice.
Investigation of physico-chemical properties and evaluation of the biological potential of essential oil extracted from Artemisia pallens
Authors: Jha Vikas , Kadam Purvesh , Jain Tisha , Bhargava Agraj , Marick Arpita , Saiya Badal , Maiti Sathi , Pandya Siddhartha , Patel Reetikesh , Jadhav Namrata
Published: June 2023

Artemisia pallens, an aromatic and medicinal plant occasionally referred to as Davana is a member of the Asteraceae family. Understanding the physiochemical and therapeutic properties of Davana essential oil (DEO) is the major aim of this study. Essential oil from plant material was extracted using the hydro-distillation method. Examination of the phytochemical components and several plant constituents from the whole oil were detected using GC–MS analysis and some components were Isobutyl propionate, 4,5-Dimethyl-Thiazole, Ligustrazin, Endo-2-Norborneol, Tetradecanoic acid, and Octadecanoic acid. The thermal stability of the oil was tested using thermoanalytical studies such as TG–DTA and DSC. Moreover, to comprehend the biological potential of the oil antimicrobial, antituberculosis, antimalarial, antioxidant, anticancer, and antibiofilm activities were investigated essential oil was tested for antimicrobial activity against 10 bacterial and 7 fungal strains. The antimalarial potential was evaluated against Plasmodium falciparum. Cytotoxicity of the DEO was determined against MCF-7, HeLa, and CHO cell lines employing MTT assay. Meanwhile, the DPPH assay was adopted to assess antioxidant potential, and the ability to suppress biofilm formation was also assessed. The study’s findings reveal that Artemisia pallens is a reservoir of natural compounds and can be used against numerous ailments.
Ciprofloxacin analogues: drug likeness, biological and molecular docking studies
Authors: Asghar Basim H. , Arshad Mohammad
Published: June 2023

The search for new antimicrobial agents due to the development of antimicrobial resistance is one of the greatest points of concern among medicinal chemists. It has been observed that the infections due to the antimicrobial resistance pathogens are one of the reasons for the mortality. Therefore, it is really important to find out some new low molecular weight antimicrobial drugs with different mode of action. Despite of being a better antibiotic, ciprofloxacin represented resistance against many pathogens. Herein, this study reported the synthesis of novel analogues of ciprofloxacin (1) including 1,3,4-oxadiazole, thiazolidine-4-one, 1,3,4-oxazoline, 1,2,4-triazole, Schiff's base, hydrazide, and 1,3,4-thiadiazole (2–8), following their computational assessment. All analogues were then synthesized and characterized using FT-IR, NMR, Mass spectroscopy, etc. The prepared analogs were then assessed for antimicrobial properties against bacterial pathogens and fungal isolates using disc diffusion and serial dilution methodology. To observe the toxicity of the prepared analogs the MTT assay was performed against HepG2 cells. The receptor glucosamine-6-phosphatase (GlcN-6P) and lanosterol 14-alpha-demethylase (CYP51) were used for the molecular docking assay using Auto Dock Tools-1.5.6 to evaluate the degree of hydrogen bonding and binding affinities. It was observed that analogue (2) established strong hydrogen bonds with the both receptors, with great binding affinities.
Neuro-cognitive complications of nephropathic cystinosis
Authors: Trauner Doris A.
Published: June 2023

Purpose

To review the neuro-cognitive complications of nephropathic cystinosis.

Methods

Review of published information on neurological and cognitive complications of cystinosis.

Results

Nephropathic cystinosis is a rare disorder of cystine metabolism. Although renal failure is the earliest and most severe complication of this condition, all organs of the body eventually become involved. The brains of children with cystinosis demonstrate structural changes early in life. Neuro-cognitive differences, including motor incoordination and visual spatial dysfunction, are present from early life and may negatively impact learning. Executive functioning is also impaired and this may contribute to poor adherence to medication regimens.

Conclusions

Early recognition of these difficulties allows for intervention to minimize problems associated with the neurocognitive deficits in cystinosis.
A Monte Carlo algorithm for the extrema of tempered stable processes
Authors: González Cázares Jorge Ignacio , Mijatović Aleksandar
Published: June 2023

We develop a novel Monte Carlo algorithm for the vector consisting of the supremum, the time at which the supremum is attained, and the position at a given (constant) time of an exponentially tempered Lévy process. The algorithm, based on the increments of the process without tempering, converges geometrically fast (as a function of the computational cost) for discontinuous and locally Lipschitz functions of the vector. We prove that the corresponding multilevel Monte Carlo estimator has optimal computational complexity (i.e. of order
$\varepsilon^{-2}$
if the mean squared error is at most
$\varepsilon^2$
) and provide its central limit theorem (CLT). Using the CLT we construct confidence intervals for barrier option prices and various risk measures based on drawdown under the tempered stable (CGMY) model calibrated/estimated on real-world data. We provide non-asymptotic and asymptotic comparisons of our algorithm with existing approximations, leading to rule-of-thumb principles guiding users to the best method for a given set of parameters. We illustrate the performance of the algorithm with numerical examples.
Investing in Nutrition: A Global Best Investment Case
Authors: Larsen Bjorn , Hoddinott John , Razvi Saleema
Published: June 2023

Undernutrition and micronutrient deficiencies are key drivers of infant and child mortality and are causes of impaired human potential for hundreds of millions of children every year. Investing in nutrition in the first 1,000 days from conception not only supports individual lifetime health, education, and productivity, but is also key to breaking the intergenerational cycle of malnutrition and enhance equitable development pathways for low- and middle-income countries. This paper provides a cost–benefit analysis of three nutrition interventions: 1) provision of preventive small-quantity lipid-based nutrient supplements (SQ-LNS) to children 6−23 months of age; 2) Complementary Feeding Promotion (CFP) for children 6−23 months of age; 3) provision of multiple micronutrient (MMN) and calcium (Ca) supplements to pregnant women. The benefit–cost ratios (BCRs) for MMN supplementation for pregnant women replacing iron and folic acid (37.5), as well as MMN and Ca combined (19-24), are the highest. The BCRs for CFP for children in the two highest socio-economic status (SES) quintiles and SQ-LNS for children in the three lowest SES quintiles are fairly similar at 16 and 14, respectively. The lowest BCR is for CFP for children in the three lowest SES quintiles due to the high cost of accomplishing behavioral change for improved complementary feeding in resource-poor households.
A precipitation downscaling method using a super-resolution deconvolution neural network with step orography
Authors: Reddy P. Jyoteeshkumar , Matear Richard , Taylor John , Thatcher Marcus , Grose Michael
Published: June 2023

Coarse spatial resolution in gridded precipitation datasets, reanalysis, and climate model outputs restricts their ability to characterize the localized extreme rain events and limits the use of the coarse resolution information for local to regional scale climate management strategies. Deep learning models have recently been developed to rapidly downscale the coarse resolution precipitation to the high local scale resolution at a much lower cost than dynamic downscaling. However, these existing super-resolution deep learning modeling studies have not rigorously evaluated the model’s skill in producing fine-scale spatial variability, particularly over topographic features. These current deep-learning models also have difficulty predicting the complex spatial structure of extreme events. Here, we develop a model based on super-resolution deconvolution neural network (SRDN) to downscale the hourly precipitation and evaluate the predictions. We apply three versions of the SRDN model: (a) SRDN (no orography), (b) SRDN-O (orography only at final resolution enhancement), and (c) SRDN-SO (orography at each step of resolution enhancement). We assess the ability of SRDN-based models to reproduce the fine-scale spatial variability and compare it with the previously used deep learning model (DeepSD). All the models are trained and tested using the Conformal Cubic Atmospheric Model (CCAM) data to perform a 100 to 12.5 km of hourly precipitation downscaling over the Australian region. We found that SRDN-based models, including orography, deliver better fine-scale spatial structures of both climatology and extremes, and significantly improved the deep-learning downscaling. The SRDN-SO model performs well both qualitatively and quantitatively in reconstructing the fine-scale spatial variability of climatology and rainfall extremes over complex orographic regions.
Accelerated protons with energies up to 70 MeV based on the optimized SG-II Peta-watt laser facility
Authors: An H. H. , Wang W. , Xiong J. , Wang C. , Pan X. , Ouyang X. P. , Jiang S. , Xie Z. Y. , Wang P. P. , Yao Y. L. , Hua N. , Wang Y. , Jiang Z. C. , Xiao Q. , Ding F. C. , Wan Y. T. , Liu X. , Wang R. R. , Fang Z. H. , Yang P. Q. , Jiang Y. E. , Zhang P. Z. , Zhu B. Q. , Sun J. R. , Qiao B. , Lei A. L. , Zhu J. Q.
Published: June 2023

The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
A few or several? Construal, quantity, and argumentativity
Authors: Katzir Nicole , Ariel Mira
Published: June 2023

This study examines two seemingly similar quantifiers, a few and several, and argues that the differences between them go beyond the (slightly) different quantities they each denote. Specifically, we argue that several construes its nominal complement as composed of individuated entities, which renders them more prominent, and thus a stronger basis in support of a conclusion the speaker is arguing for. We base our analysis on two experiments and a corpus study. The experiments show that there is indeed an argumentative difference between the quantifiers, and the corpus study points to the discourse factors behind it. In comparison with a few, several is associated with a higher discourse prominence for its complement (greater individuation, significance) and with greater argumentative strength. Based on this data, we characterize the quantifiers’ prototypical discourse profiles. A typical instance of several occurs in persuasive genres, refers to a not-so-small quantity, construes the plural entity as composed of individuated entities, and contributes to a strong argument. A typical instance of a few occurs in non-persuasive genres, denotes a small quantity, construes the entities composing the plural entity as un-individuated, and contributes to a weak or neutral argument.
Does fruit and vegetable consumption impact mental health? Systematic review and meta-analyses of published controlled intervention studies
Authors: Appleton Katherine M. , Boxall Lucy R. , Adenuga-Ajayi Olabimpe , Seyar Dilara F.
Published: June 2023

Associations between fruit and vegetable (FV) consumption and mental health are suggested, largely from observational studies. This systematic review aimed to identify and summarise all published controlled intervention studies investigating the effects of FV consumption on mental health in adults. Four academic databases (Medline, PsycINFO, PubMed, Web of Science) were searched on 16 September 2022, over all years, for studies that used an intervention design; included FV consumption; included an appropriate non-FV-consumption control; used a validated measure of mental health and were conducted in healthy adults or adults with solely a depressive or anxiety-related condition. Study details were tabulated and combined using meta-analyses. Risk of bias was assessed using the domains of the Cochrane Collaboration. Six studies, enrolling 691 healthy adults and reporting on one or more mental health outcomes, were found. Meta-analyses found small and imprecise effects of FV consumption for: psychological well-being (4 studies, 289 participants) standardised mean difference (SMD) = 0·07 (95 % CI −0·17, 0·30), P = 0·58, I2 = 0 %; depressive symptomology (3 studies, 271 participants) SMD = –0·15 (95 % CI −0·40, 0·10), P = 0·23, I2 = 47 % and anxiety-related symptomology (4 studies, 298 participants) SMD = –0·15 (95 % CI −0·39, 0·08), P = 0·20, I2 = 71 %. Some benefit for psychological well-being was found in change-from-baseline data: SMD = 0·28 (95 % CI 0·05, 0·52), P = 0·02, I2 = 0 %. Risk of bias was high in many studies. Limitations include the consideration only of published studies and stem from the studies found. Given the few, limited studies available and the small size of effects, stronger evidence is needed before recommending FV consumption for mental health.
Runes and Rye: Administration in Denmark and the Emergence of the Younger Futhark, 500–800
Authors: Cole Richard
Published: June 2023

In this article, I take up the case of runic writing to reflect upon James Scott’s view of the nexus between writing and various forms of domination in early states, especially the use of literacy for taxation in cereal-growing societies. Scott’s theses provide interesting matter “to think with,” even when his grasp of historical detail has been found wanting. It is not controversial to grant Scott that cuneiform writing was a remarkable tool for statecraft, and exploitation, in the first states of Mesopotamia, around 3500 BC. The same is true of writing in other early states. But in the first states of Scandinavia, particularly Denmark ca. AD 500–800, writing had a more troubled relationship with the state. No evidence survives that runic writing was used to administer taxation or much else, as it was in other agrarian civilisations. It is true that the runic script was used to commemorate kings, most famously by Haraldr Blátǫnn (r. ca. 958–ca. 986.). But, statistically speaking, it was more often used to aggrandize the sort of local big men who usually resisted centralized power. In this article, I survey the relationship between runic writing and administration. I consider what the Danish situation suggests about the relationship between states and writing and offer a tentative hypothesis of a short-lived attempt at runic bureaucracy around 800, which created—and quickly lost control of—a shortened variety of the runic script (the Younger Futhark).
A Delayed Revenge: “Yellow Journalism” and the Long Quest for Cuba, 1851–1898
Authors: Burge Daniel J.
Published: June 2023

Historians have long been intrigued by the role that the press played in McKinley’s decision to intervene in Cuba in 1898. Most, however, have focused their attention on the decade of the 1890s, ignoring the long history of interventionism aimed at Cuba. This essay uses the story of William L. Crittenden to explore the many instances where interventionists tried (and failed) to drum up support for Cuban intervention. Crittenden was executed by the Spanish in 1851 after a failed filibuster raid. Over the next four decades, interventionists wrote newspaper accounts, held boisterous public meetings, penned poems, and published novels that demanded revenge upon Spain. Yet Millard Fillmore, Franklin Pierce, James Buchanan, Ulysses Grant, and Grover Cleveland did not choose to intervene. By focusing on nearly five decades as opposed to a single year, this essay calls into question the idea that the press reflected public opinion and challenges the larger assertion that the “Yellow Press” propelled the United States into a war with Spain. Whether they shouted “Remember the Maine,” “Remember the Virginius,” or “Remember Crittenden,” writers, editors, poets, and journalists simply did not have the power to control public opinion and certainly did not prove to be successful at manipulating presidents to intervene.
International Arbitration and the Roots of Women’s Foreign Policy Activism
Authors: Threlkeld Megan
Published: June 2023

At first glance, international arbitration—a legalistic method for the peaceful settlement of disputes among nations—may seem like a topic belonging only to the formal, male-dominated realms of diplomacy and international law. Most men in the late nineteenth century certainly thought so, and many historians since have treated it as such. But prominent women like May Wright Sewall and Belva Lockwood, and mass organizations like the Woman’s Christian Temperance Union, took a lively interest in the subject in the 1890s. In that interest lay the roots of women’s foreign policy activism that led to their participation in debates over the War of 1898 and their peace efforts during and after World War I. International arbitration appealed to women because it complemented their better-known campaigns for temperance, suffrage, and other causes. As a more “civilized” method of resolving conflicts, arbitration was both a symbol of and a prerequisite for a more advanced, temperate, and equal society. It thus became a key component of women’s arguments for inclusion in the public and political life of the nation.
Sound Citizenship: Hearing and Speech Disabilities in World War I
Authors: Sullivan Evan P.
Published: June 2023

This article discusses speech and hearing disabled Americans’ claims to citizenship during World War I, and the ways American policymakers sought to rehabilitate American soldiers treated in the U.S. Army Section of Defects of Hearing and Speech—or those classified after the Section’s closure as deaf, hard-of-hearing, or “speech defective.” Ultimately, I argue that one’s aural communication abilities were indicators of worthiness in American society and that this was especially the case during World War I, when tensions about speech and hearing heightened within and outside of the Deaf community due to significant pressures placed on Americans to show support for the war. Such pressures also shaped the experiences of American soldiers treated for speech and hearing disabilities after 1918, by suggesting that their service to the United States could not be complete until they were successfully rehabilitated through lip-reading training. To be able to aurally communicate signified the veterans’ sound citizenship in a literal and a metaphorical sense.
RELEVANT CONSEQUENCE RELATIONS: AN INVITATION
Authors: BADIA GUILLERMO , BĚHOUNEK LIBOR , CINTULA PETR , TEDDER ANDREW
Published: June 2023

We generalize the notion of consequence relation standard in abstract treatments of logic to accommodate intuitions of relevance. The guiding idea follows the use criterion, according to which in order for some premises to have some conclusion(s) as consequence(s), the premises must each be used in some way to obtain the conclusion(s). This relevance intuition turns out to require not just a failure of monotonicity, but also a move to considering consequence relations as obtaining between multisets. We motivate and state basic definitions of relevant consequence relations, both in single conclusion (asymmetric) and multiple conclusion (symmetric) settings, as well as derivations and theories, guided by the use intuitions, and prove a number of results indicating that the definitions capture the desired results (at least in many cases).
Visions of deliverance: Social scientization, functionalism, and the expansive purposiveness of state schooling in nineteenth-century British parliamentary politics
Authors: Smith Daniel Scott
Published: June 2023

Early in the nineteenth century, members in the UK Parliament (MPs) hardly ever debated education. When they did, it was nearly always in the context of aid for the religious instruction of the poor. Indeed, even by 1850, nearly two decades after the first Great Reform Act (1832), the Prime Minister Lord John Russell made the case that a system of compulsory state schooling would be immoral and un-British. Yet, by the ‘80s, MPs debating in Westminster routinely drew connections between schooling and the most critical social issues of the day: social-class mobility and equity, child welfare, national development, emigration, and the civil service, among others. What explains the expanding, and expansive, political uses that elite policymakers put to schooling? How did schooling and education take on such an aggrandized role in society for British statesmen? To address these questions, this paper combines natural language processing techniques, semantic network, discourse, and regression analyses to read and interpret the ∼1.1 million political speeches given in the UK Houses of Parliament during the long nineteenth century (1804–1913). In contrast to explanations emphasizing the direct role that economic, social, and political development as well as conflict played in the UK state’s historic expansion, this piece demonstrates how social scientization, the sweeping international epistemic movement that institutionalized and diffused functionalist social theory, created the context that made it possible for political elites to see and promote schooling as an effective policy instrument of greater cultural rationalization supporting the development of capitalist industrial society.
Insomnia in Cancer Survivors
Authors: Clara Maria Inês , Canavarro Maria Cristina , Miller-Mendes Mariana , Gomes Ana Allen
Published: June 2023

Abstract: Insomnia is among the most prevailing and distressing iatrogenic complaints reported by cancer survivors. Untreated insomnia negatively impacts survivors’ functioning, quality of life and health, and may have implications for cancer progression. Cognitive behavioral therapy is recommended as the first-line treatment for cancer-related insomnia but remains largely unavailable in European oncology care. For cancer survivors, it may be prudent to expand the scope of insomnia treatment. In this paper, we analyze the etiopathogenesis of insomnia among cancer populations and review the latest developments in cognitive behavioral therapeutics for cancer-related insomnia. Pondering upon the distinctive nature and pathophysiology of cancer-related insomnia, we discuss opportunities to optimize insomnia treatment in cancer care. We suggest adapting the content and format delivery of standard cognitive behavioral therapy for insomnia to meet the needs of cancer survivors and surmount resource availability. Digital therapeutics may provide cancer survivors who would otherwise be limited to pharmacologic treatment options with the guideline treatment for insomnia. Internet-delivered cognitive behavioral interventions may be integrated into survivorship care programs within healthcare systems.
Dual Wave Energy Sources for the Atlantic Niño Events Identified by Wave Energy Flux in Case Studies
Authors: Song Qingyang , Tang Youmin , Aiki Hidenori
Published: June 2023

The evolution of equatorial sea surface temperature anomalies during Atlantic Niño events has demonstrated its diversity in both intensity and timing. To investigate the mechanism responsible for this diversity, this study focuses on ocean responses to atmospheric forcing, manipulating the wind forcing in both equatorial and off‐equatorial regions to excite linear ocean models for three types of events that occurred in 1999, 2019, and 2021 respectively. The results reveal the dual wave energy sources for the equatorial Kelvin waves (KWs): one is the local wind forcing in the western tropical basin; the other is the reflection due to the off‐equatorial Rossby waves in the western boundary. The reflected KWs can precondition the events when wind‐forced KWs insufficiently displace the thermocline (e.g., the boreal winter of 2019 and 2021). The participation of off‐equatorial wave energy hence leads to the diversity of the Atlantic Niños.
Understanding the Mechanisms for Tropical Surface Impacts of the Quasi‐Biennial Oscillation (QBO)
Authors: García‐Franco Jorge L. , Gray Lesley J. , Osprey Scott , Jaison Aleena M. , Chadwick Robin , Lin Jonathan
Published: June 2023

The impact of the quasi‐biennial oscillation (QBO) on tropical convection and precipitation is investigated through nudging experiments using the UK Met Office Hadley Center Unified Model. The model control simulations show robust links between the internally generated QBO and tropical precipitation and circulation. The model zonal wind in the tropical stratosphere was nudged above 90 hPa in atmosphere‐only and coupled ocean‐atmosphere configurations. The convection and precipitation in the atmosphere‐only simulations do not differ between the experiments with and without nudging, which may indicate that SST‐convection coupling is needed for any QBO influence on the tropical lower troposphere and surface. In the coupled experiments, the precipitation and sea‐surface temperature relationships with the QBO phase disappear when nudging is applied. Imposing a realistic QBO‐driven static stability anomaly in the upper‐troposphere lower‐stratosphere is not sufficient to simulate tropical surface impacts. The nudging reduced the influence of the lower troposphere on the upper branch of the Walker circulation, irrespective of the QBO, indicating that the upper tropospheric zonal circulation has been decoupled from the surface by the nudging. These results suggest that grid‐point nudging mutes relevant feedback processes occurring at the tropopause level, including high cloud radiative effects and wave mean flow interactions, which may play a key role in stratospheric‐tropospheric coupling.
Computational textural mapping harmonises sampling variation and reveals multidimensional histopathological fingerprints
Authors: Brummer Otso , Pölönen Petri , Mustjoki Satu , Brück Oscar
Published: June 2023

Background

Technical factors can bias H&E digital slides potentially compromising computational histopathology studies. Here, we hypothesised that sample quality and sampling variation can introduce even greater and undocumented technical fallacy.

Methods

Using The Cancer Genome Atlas (TCGA) clear-cell renal cell carcinoma (ccRCC) as a model disease, we annotated ~78,000 image tiles and trained deep learning models to detect histological textures and lymphocyte infiltration at the tumour core and its surrounding margin and correlated these with clinical, immunological, genomic, and transcriptomic profiles.

Results

The models reached 95% validation accuracy for classifying textures and 95% for lymphocyte infiltration enabling reliable profiling of ccRCC samples. We validated the lymphocyte-per-texture distributions in the Helsinki dataset (n = 64). Texture analysis indicated constitutive sampling bias by TCGA clinical centres and technically suboptimal samples. We demonstrate how computational texture mapping (CTM) can abrogate these issues by normalising textural variance. CTM-harmonised histopathological architecture resonated with both expected associations and novel molecular fingerprints. For instance, tumour fibrosis associated with histological grade, epithelial-to-mesenchymal transition, low mutation burden and metastasis.

Conclusions

This study highlights texture-based standardisation to resolve technical bias in computational histopathology and understand the molecular basis of tissue architecture. All code, data and models are released as a community resource.
CAR T cells as micropharmacies against solid cancers: Combining effector T-cell mediated cell death with vascular targeting in a one-step engineering process
Authors: Altvater Bianca , Kailayangiri Sareetha , Spurny Christian , Flügge Maike , Meltzer Jutta , Greune Lea , Urban Katja , Schwöppe Christian , Brand Caroline , Schliemann Christoph , Hintelmann Heike , Harrach Saliha , Hartmann Wolfgang , Abken Hinrich , Kuehle Johannes , Schambach Axel , Görlich Dennis , Berdel Wolfgang E. , Rossig Claudia
Published: June 2023

To enhance the potency of chimeric antigen receptor (CAR) engineered T cells in solid cancers, we designed a novel cell-based combination strategy with an additional therapeutic mode of action. CAR T cells are used as micropharmacies to produce a targeted pro-coagulatory fusion protein, truncated tissue factor (tTF)-NGR, which exerts pro-coagulatory activity and hypoxia upon relocalization to the vascular endothelial cells that invade tumor tissues. Delivery by CAR T cells aimed to induce locoregional tumor vascular infarction for combined immune-mediated and hypoxic tumor cell death. Human T cells that were one-vector gene-modified to express a GD2-specific CAR along with CAR-inducible tTF-NGR exerted potent GD2-specific effector functions while secreting tTF-NGR that activates the extrinsic coagulation pathway in a strictly GD2-dependent manner. In murine models, the CAR T cells infiltrated GD2-positive tumor xenografts, secreted tTF-NGR into the tumor microenvironment and showed a trend towards superior therapeutic activity compared with control cells producing functionally inactive tTF-NGR. In vitro evidence supports a mechanism of hypoxia-mediated enhancement of T cell cytolytic activity. We conclude that combined CAR T cell targeting with an additional mechanism of antitumor action in a one-vector engineering strategy is a promising approach to be further developed for targeted treatment of solid cancers.
AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-β signaling in mice
Authors: Zhang Shijie , Tong Xiang , Liu Sitong , Huang Jizhen , Zhang Li , Zhang Tianli , Wang Dongguang , Fan Hong
Published: June 2023

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-β)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF‐β1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-β signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-β/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.
Octahedron distortion-triggered dipole–spin interaction in multiferroic magnetoelectric perovskites
Authors: Lu Xiangqian , Hu Renjie , Zhu Yabin , Song Kepeng , Qin Wei
Published: June 2023

The design of perovskite structures with multiferroic magnetoelectric coupling effects opens up new opportunities in fields such as the creation of next-generation spin-dependent multistate information storage technologies. In this work, we prepared a transition metal-implanted perovskite with multiferroic magnetoelectric coupling, in which both magnetoelectric coupling and a blueshift of photoluminescence were observed. The introduction of transition metal-generated polarized spin interacts with the electronic orbit through spin–orbital coupling to lead to a pronounced octahedron distortion, where the temperature dependence of the dielectric constant undergoes a ferroelectric polarization transition. An external magnetic field could enhance the strength of spin polarization to further affect the magnitude of electric polarization. Moreover, applying an electric field tunes the distortion of the octahedron dependence of electric polarization to feed back to the change in spin polarization. Overall, the spin polarization-induced electric polarization in perovskites provides a unique approach to realizing the room-temperature magnetoelectric coupling of multiferroic materials.
Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome
Authors: Flerlage Tim , Crawford Jeremy Chase , Allen E. Kaitlynn , Severns Danielle , Tan Shaoyuan , Surman Sherri , Ridout Granger , Novak Tanya , Randolph Adrienne , West Alina N. , Thomas Paul G.
Published: June 2023

Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.
Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity
Authors: Wang Chaoyu , Zhang Ruoshi , He Jia , Yu Lvshan , Li Xinyan , Zhang Junxia , Li Sai , Zhang Conggang , Kagan Jonathan C. , Karp Jeffrey M. , Kuai Rui
Published: June 2023

DNA derived from chemotherapeutics-killed tumor cells is one of the most important damage-associated molecular patterns that can activate the cGAS-STING (cyclic GMP-AMP synthase—stimulator of interferon genes) pathway in antigen-presenting cells (APCs) and promote antitumor immunity. However, conventional chemotherapy displays limited tumor cell killing and ineffective transfer of stable tumor DNA to APCs. Here we show that liposomes loaded with an optimized ratio of indocyanine green and doxorubicin, denoted as LID, efficiently generate reactive oxygen species upon exposure to ultrasound. LID plus ultrasound enhance the nuclear delivery of doxorubicin, induce tumor mitochondrial DNA oxidation, and promote oxidized tumor mitochondrial DNA transfer to APCs for effective activation of cGAS-STING signaling. Depleting tumor mitochondrial DNA or knocking out STING in APCs compromises the activation of APCs. Furthermore, systemic injection of LID plus ultrasound over the tumor lead to targeted cytotoxicity and STING activation, eliciting potent antitumor T cell immunity, which upon the combination with immune checkpoint blockade leads to regression of bilateral MC38, CT26, and orthotopic 4T1 tumors in female mice. Our study sheds light on the importance of oxidized tumor mitochondrial DNA in STING-mediated antitumor immunity and may inspire the development of more effective strategies for cancer immunotherapy.