bluuebunny/crossref_metadata_2025 huggingface dataset:
421 A Phase 1 and Randomized Phase 2 Clinical Trial of Selinexor and Temozolomide in Recurrent Glioblastoma Among Adults: The Product of a Successful Team Science Approach
Authors: Chow Frances , Berens Michael , Tamir Sharon , Landesman Yosef , Walker Christopher , Krailo Mark , Gore Steven , Portnow Jana
Published: April 2023

OBJECTIVES/GOALS: Selinexor is a novel XPO1 inhibitor that blocks nuclear export, thus impairing DNA repair and causing apoptosis. Our goal was to conduct preclinical and clinical studies to test our hypothesis that selinexor’s efficacy is boosted by priming with temozolomide and is associated with a tissue biomarker. METHODS/STUDY POPULATION: We leveraged a team science approach through the NCI Cancer Therapy Evaluation Program (CTEP) to design preclinical experiments, develop a novel RNAseq analysis pipeline, and use pre-existing clinical experience to open an early phase clinical trial for recurrent glioblastoma. Team members included a CTEP medical officer, cancer biologist, pharmacist, industry scientist, translational scientist, and early career clinician scientist mentored by an expert clinician scientist. Based on preclinical results, participants in the clinical trial experimental arm will receive sequential temozolomide 150mg/m2 on days 1-5 and a starting dose of selinexor 60mg on days 8 and 15 of a 28-day cycle. Participants in the control arm will receive monotherapy temozolomide. RESULTS/ANTICIPATED RESULTS: Sequential treatment of U87 cells and intracranial xenografts had superior DNA damage (É£H2A.X, cleaved PARP) and overall survival compared to combination or single-agent (HR 0.25 [95% CI, 0.07-0.84]; p=0.01, log-rank). We used the top-scoring gene pair method to identify an RNAseq signature associated with response to selinexor. We then designed a trial for first recurrent MGMT methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and validation of a molecular signature. Phase 1 dose finding (n=12) will be followed by a randomized phase 2 (n=72); using proportional hazards regression, RHR 0.5 with p DISCUSSION/SIGNIFICANCE: The NCI CTEP Project Team employs team science as a framework to successfully develop multidisciplinary collaborations, build investigator trial experience, and lead the way to future research opportunities. Our trial addresses a significant unmet need to offer novel therapies and molecular biomarkers in glioblastoma.
438 Platelets, Inflammation and Thrombosis in Chronic Kidney Disease
Authors: Jain Nishank , Karaduta Oleg , Ware Jerry , Mehta J L , Smyth Susan , Arthur J M
Published: April 2023

OBJECTIVES/GOALS: Platelets reside at the nexus of thrombosis and inflammation which make them an ideal target of investigation to understand mechanisms underlying chronic kidney disease (CKD)-related inflammatory and thrombotic dysregulation. Our objective is to determine whether a pro-inflammatory state in CKD is exacerbated by platelets. METHODS/STUDY POPULATION: Aim 1 will investigate effects of engineered reduction in the interaction of platelets with leukocytes [by disruption of one of the platelet surface receptor (GPIb-IX)] in the development of CKD in murine models. Aim 2 will investigate effects of platelet inhibitors on the development of CKD in murine models. RESULTS/ANTICIPATED RESULTS: We anticipate that the proposed studies in Aim 1 will demonstrate reduction in the interaction of platelets with leukocytes results in exacerbation of kidney injury upon CKD induction with cisplatin. We also anticipate that inhibition of platelets in Aim 2 with P2Y12 receptor inhibitors results in reduction in kidney injury upon CKD induction with cisplatin. DISCUSSION/SIGNIFICANCE: Upon successful completion of the proposed studies, we shall be able to better describe the role of platelets as modulators of inflammation in CKD. This will be a significant stride towards understanding the pathophysiology of a pro-inflammatory state in CKD and how platelets exacerbate inflammation and thrombosis in this population.
463 Childhood Emotional Neglect on Nucleus Accumbens Connectivity in Adult Survivors of Trauma
Authors: Liuzzi Michael T. , Harb Farah , Petranu Kevin , Larson Christine L.
Published: April 2023

OBJECTIVES/GOALS: Neuroimaging research has found that childhood maltreatment is related to reduced activation of the nucleus accumbens. The long-lasting impact of this relationship is not as well understood. This study aims to explore the association between childhood emotional neglect and reward-related functional connectivity in an adult trauma sample. METHODS/STUDY POPULATION: Participants (N=169, M age=, 32.2; SD=10.3; women=94) experienced a traumatic injury and were recruited from a Level I Trauma Center. Two-weeks post injury, participants completed the Childhood Trauma Questionnaire (emotional neglect M=10.6; SD=5.2), a self-reported, retrospective account of childhood maltreatment, and underwent a resting-state functional magnetic resonance imaging (fMRI) scan. Whole-brain resting-state left and right nucleus accumbens connectivity analyses were completed using the CONN Toolbox. RESULTS/ANTICIPATED RESULTS: Whole-brain left nucleus accumbens connectivity analyses revealed one significant region (angular gyrus (AG); p DISCUSSION/SIGNIFICANCE: Results suggest that childhood emotional neglect is related to nucleus accumbens connectivity and a brain region associated with memory, attention, and theory of mind in adult survivors of trauma. Early life emotional neglect may be contributing to heightened baseline reward sensitivity–particularly for social rewards (implicated by the AG).
498 Structural Determination of the CqsR CACHE Domain and its Autoinducer
Authors: Guarnaccia Andrew , Ng Wei-Lung , Steenhaut Anjali , Olenic Sandra , Perez Lark J. , Neiditch Matthew B.
Published: April 2023

OBJECTIVES/GOALS: Our goal is to determine the structure of the CACHE domain of the Vibrio cholerae quorum sensing receptor CqsR as well as its autoinducer (AI). We are performing X-ray crystallography on the protein in its apo form, with the fractions containing the AI, and with known ligand ethanolamine (ETA). METHODS/STUDY POPULATION: We have transformed BL21(DE3) E. coli cells with a pTB146 vector to contain the gene for the CqsR CACHE domain. We grow these cells to high optical density and induce protein expression, at which point we harvest them and purify the protein. This entails lysing the cells, separating the protein with Ni-NTA resin, cleaving our protein tag, and column chromatography. With purified protein, high-throughput screens are set up to find crystallization conditions of apo CqsR, CqsR-ETA, and CqsR-AI. We then determine conditions that best lead to crystal formation and optimize them. Crystals are then diffracted with X-rays, process the data, and determine the structure of protein and AI. RESULTS/ANTICIPATED RESULTS: We anticipate finding the structure of the CqsR CACHE domain to a high resolution in addition to the identity of its autoinducer. Previous results found that the structure is homologous to another V. cholerae chemoreceptor, Mlp37, and we expect the results from this project to confirm this. In addition, we know that the autoinducer weighs approximately 62 daltons, the same as the known ligand, ethanolamine. Given that CACHE domains bind specifically to their ligands, we anticipate that the autoinducer will be structurally similar to ethanolamine. DISCUSSION/SIGNIFICANCE: The results will reveal the structure of the CqsR CACHE domain and its autoinducer. This knowledge will better allow researchers to treat cholera, as both autoinducer identity and receptor conformational changes will be uncovered, allowing for drug development to inhibit cell growth.
Racial disparities among candidemic patients at a Southern California teaching hospital
Authors: Grant Victoria C. , Zhou Anna Y. , Tan Karen K. , Abdul-Mutakabbir Jacinda C.
Published: April 2023

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.
Lower bound for the expected supremum of fractional brownian motion using coupling
Authors: Bisewski Krzysztof
Published: April 2023

We derive a new theoretical lower bound for the expected supremum of drifted fractional Brownian motion with Hurst index
$H\in(0,1)$
over a (in)finite time horizon. Extensive simulation experiments indicate that our lower bound outperforms the Monte Carlo estimates based on very dense grids for
$H\in(0,\tfrac{1}{2})$
. Additionally, we derive the Paley–Wiener–Zygmund representation of a linear fractional Brownian motion in the general case and give an explicit expression for the derivative of the expected supremum at
$H=\tfrac{1}{2}$
in the sense of Bisewski, Dȩbicki and Rolski (2021).
Large deviations of extremal eigenvalues of sample covariance matrices
Authors: Uwamariya Denise , Yang Xiangfeng
Published: April 2023

Large deviations of the largest and smallest eigenvalues of
$\mathbf{X}\mathbf{X}^\top/n$
are studied in this note, where
$\mathbf{X}_{p\times n}$
is a
$p\times n$
random matrix with independent and identically distributed (i.i.d.) sub-Gaussian entries. The assumption imposed on the dimension size p and the sample size n is
$p=p(n)\rightarrow\infty$
with
$p(n)={\mathrm{o}}(n)$
. This study generalizes one result obtained in [3].
Trends in measuring BMR and RMR after spinal cord injury: a comprehensive review
Authors: Alazzam Ahmad M. , Alrubaye Malak W. , Goldsmith Jacob A. , Gorgey Ashraf S.
Published: April 2023

Studying factors that contribute to our understanding of maintaining normal energy balance are of paramount significance following spinal cord injury (SCI). Accurate determination of energy needs is crucial for providing nutritional guidance and managing the increasing prevalence of malnutrition or obesity after SCI. BMR represents 75–80 % of the total energy expenditure in persons with SCI. Accurately measuring BMR is an important component for calculating total energetic needs in this population. Indirect calorimetry is considered the gold-standard technique for measuring BMR. However, technical challenges may limit its applications in large cohort studies and alternatively rely on prediction equations. Previous work has shown that BMR changes in response to disuse and exercise in the range of 15–120 %. Factors including sex, level of injury and type of assistive devices may influence BMR after SCI. RMR is erroneously used interchangeably for BMR, which may result in overestimation of energetic intake when developing nutritional plans. To address this concern, we comprehensively reviewed studies that conducted BMR (n=15) and RMR (n=22) in persons with SCI. The results indicated that RMR is 9 % greater than BMR in persons with SCI. Furthermore, the SCI-specific prediction equations that incorporated measures of fat-free mass appeared to accurately predict BMR. Overall, the current findings highlighted the significance of measuring BMR as well as encouraging the research and clinical community to effectively establish countermeasures to combat obesity after SCI.
A River Runs through It: The Elbe, Socialist Security, and East Germany's Borders
Authors: Ault Julia E.
Published: April 2023

This article traces the course of the Elbe River from Czechoslovakia through the German Democratic Republic (GDR) into the Federal Republic, where it flows into the North Sea. As the GDR's main water artery, the Elbe's border crossings became a site of security concern for the GDR. Traversing the GDR's border with fellow communist state Czechoslovakia as well as its rival West German state, the river linked the GDR to a larger ecological system as well as transnational sociopolitical dynamics. These connections illuminated the GDR's crucial position in central Europe and beyond. Yet the Elbe also presented challenges for the GDR in terms of controlling information, people, and pollution that streamed into—and out of—the country. The river thus was a precious and contested resource that revealed the communist dictatorship's limited ability to control nature, humans, or interactions between the two. Ultimately, the Elbe's border crossings were a site of transnational and global connection that called into question the GDR's domestic legitimacy and international standing.
TOWARDS A NEW EDITION OF JULIAN'SCONTRA GALILAEOS: ASSESSING THE MATERIAL FROM THE SYRIAC TRANSMISSION OF CYRIL'SCONTRA IVLIANVM
Authors: Crawford Matthew R.
Published: April 2023

Emperor Julian's three-book treatiseContra Galilaeossurvives solely in those Christian sources that quoted it in order to respond to its forceful attack on Christianity. The bulk of these survivals comes from Cyril of Alexandria's twenty-bookContra Iulianum. The recent publication of the first modern critical edition of Cyril's work creates the occasion for a fresh study of the remnants of Julian's text that can be recovered from it. This is especially true for Books 11–20 of Cyril's treatise that are themselves lost and survive only in quotations in later Greek and Syriac sources. The present article undertakes a reassessment of the Julianic material preserved via the Syriac transmission ofContra Iulianum, including several passages hitherto unknown or ignored in earlier studies of Julian's treatise. It provides the Syriac text and English translation of eight passages and contextualizes them in the wider argumentative aim ofContra Galilaeos.
Detecting and describing ramification for structured ring spectra
Authors: Höning Eva , Richter Birgit
Published: April 2023

John Rognes developed a notion of Galois extension of commutative ring spectra, and this includes a criterion for identifying an extension as unramified. Ramification for commutative ring spectra can be detected by relative topological Hochschild homology and by topological André–Quillen homology. In the classical algebraic context, it is important to distinguish between tame and wild ramification. Noether’s theorem characterizes tame ramification in terms of a normal basis, and tame ramification can also be detected via the surjectivity of the trace map. For commutative ring spectra, we suggest to study the Tate construction as a suitable analog. It tells us at which integral primes there is tame or wild ramification, and we determine its homotopy type in examples in the context of topological K-theory and topological modular forms.
Research status of seed improvement in underutilized crops: prospects for enhancing food security
Authors: Adelabu D. B. , Franke A. C.
Published: April 2023

Planning future directions and adapting approaches for seed improvement in underutilized crops requires the assessment of research activities. We have examined the trends and research activities conducted on seed improvement of underutilized crops. We identified research hotspots based on keywords and prolific research titles mapped across three decades (1990 to 2021). Data were compiled using Google Scholar, Web of Science and Scopus databases, loaded into the bibliometric R-package and viewed via VOSviewers software. In research on seed improvement among underutilized crops (SUC), we have observed 7.2% annual growth in publication and increase in the studies and citations. There were strong research publications with strong research links from studies conducted in USA, Canada, India, Nigeria and China, while South Africa and Egypt were among the African countries with high research studies in SUC. Among underutilized crops with improvement among their seed traits are sorghum, quinoa, Bambara groundnut, amaranth, barley, tef, cowpea and millet. Some of the trending research areas are genetic diversity, seed performance, seed domestication, yield, crop management, water use efficiency, nutritional properties, molecular strategies and genetic analysis tools for seed improvement. There is gradual increase for international collaborations and funding in SUC studies. The current research emphases are on qualitative studies, appropriate methodological procedures and advanced breeding resources to help understand and promote seed improvement among underutilized crops.
A New Standard Reference Work on Bibles in China
Authors: PFISTER LAUREN
Published: April 2023

As a relatively open academic atmosphere related to religious studies in general became manifest in the People's Republic of China in the early 1990s, new possibilities for studies of various forms of Christianity in greater China (the mainland and Chinese communities outside of the PRC) began to be realised both within China and overseas. Within the first decade of the twenty-first century, two major handbooks related to the study of Christianity in China were produced under the editorships of the Belgian Jesuit scholar, Nicolas Standaert (1959–)1 and the German Protestant scholar, R. G. Tiedemann (1941–2019),2 initiating what should be considered to be the most up-to-date and essentially new standard reference works regarding the study of all forms of Christianity that have had interactions with various Chinese persons over the period of time from the beginning of the Tang dynasty (seventh century) to the year 2000. Both volumes were large by any standard, the former being nearly a thousand pages in length, and the latter extending beyond a thousand pages. Both produced a state-of-the-art account of their particular historical coverage of varying forms of Christianity that came to or emerged within China during those periods. Notably, most of the supporting authors who contributed to those two massive volumes were foreign scholars of the history of Christianity in China and Chinese Christianity.3
Extra-cardiac and complex Fontan baffle fenestration using radio frequency current via surgical electrocautery
Authors: Khan Asra , Qureshi Athar M. , Bansal Manish , Stapleton Gary , Webb Melissa K. , Lam Wilson , Eilers Lindsay , Singh Harinder R. , Gowda Srinath T.
Published: April 2023

Background:

Fontan baffle punctures and creation of Fontan fenestration for cardiac catheterisation procedures remain challenging especially due to the heavy calcification of prosthetic material and complex anatomy.

Objectives:

We sought to evaluate our experience using radiofrequency current via surgical electrocautery needle for Fontan baffle puncture to facilitate diagnostic, electrophysiology, and interventional procedures.

Methods:

A retrospective chart review of all Fontan patients (pts) who underwent Fontan baffle puncture using radiofrequency energy via surgical electrocautery from three centres were performed from January 2011 to July 2021.

Results:

A total of 19 pts underwent 22 successful Fontan baffle puncture. The median age and weight were 17 (3–36 years) and 55 (14–88) kg, respectively. The procedural indications for Fontan fenestration creation included: diagnostic study (n = 1), atrial septostomy and stenting (n = 1), electrophysiology study and ablation procedures (n = 8), Fontan baffle stenting for Fontan failure including protein-losing enteropathy (n = 7), and occlusion of veno-venous collaterals (n = 2) for cyanosis. The type of Fontan baffles included: extra-cardiac conduits (n = 12), lateral tunnel (n = 5), classic atrio-pulmonary connection (n = 1), and intra-cardiac baffle (n = 1). A Fontan baffle puncture was initially attempted using traditional method in 6 pts and Baylis radiofrequency trans-septal system in 2 pts unsuccessfully. In all pts, Fontan baffle puncture using radiofrequency energy via electrocautery needle was successful. The radiofrequency energy utilised was (10–50 W) and required 1–5 attempts for 2–5 seconds. There were no vascular or neurological complications.

Conclusions:

Radiofrequency current delivery using surgical electrocautery facilitates Fontan baffle puncture in patients with complex and calcified Fontan baffles for diagnostic, interventional, and electrophysiology procedures.
Drop, Cover, and Hold On versus Fetal Position in the Triangle of Life to Survive in an Earthquake: A Delphi Study
Authors: Celikmen Mustafa Ferudun , Yilmaz Sarper , Tatliparmak Ali Cankut , Unal Colak Figen
Published: April 2023

Objective:

This study aims to determine and compare the effectiveness of Drop, Cover, and Hold On versus Fetal Position in the Triangle of Life regarding reducing casualties during earthquakes and establishing a consensus among medical search and rescue experts.

Methods:

In this study, the data collected from ten experienced medical search and rescue professionals were analyzed using a three-stage Delphi technique to compare Drop, Cover, and Hold On versus Fetal Position in the Triangle of Life.

Results:

At the end of the first round of Delphi, all of the experts mentioned the following factors: age, position, and surface area of the injured person. A victim’s time under rubble and the experience of search and rescue teams are two prominent factors related to search and rescue. After the earthquake simulation in the second round, mannequin damage rates were examined by opening rubble pavement and tunnels. Following the second round of ratings, a third round of questionnaires was administered. As part of this questionnaire, participants were asked to give a score from one to ten based on their level of agreement. Whether they agreed or disagreed with Fetal Position in the Triangle of Life and Drop, Cover, and Hold On using a ten-point Likert scale, and the agreement rates were measured and compared. Experts completed a comparison of the two positions in the third round.

Conclusion:

According to this expert consensus, the Fetal Position in the Triangle of Life has the following advantages over Drop, Cover, and Hold On: reduced surface area, less crush injuries, protection of a larger body part from injury, better protection from hypothermia, and better maintenance of basal metabolism.
Productive Learning Through Labs: Data Laboratories and Their Value in Undergraduate Education and Scholarly Research
Authors: Gade Emily K. , Wallace Geoffrey P. R.
Published: April 2023

Data Laboratories (Data Labs)—by which we mean a collaborative, group-based research program that can be conducted inside and/or outside of the classroom and is designed to generate observational datasets—have numerous advantages for undergraduate learning and scholarly research. Undergraduate researchers in Data Labs learn about the actual process of collecting and constructing research-quality data—a skillset that is relevant for both academic and workplace opportunities but otherwise under-covered in most undergraduate political science degrees. This article discusses our experiences in founding and running Data Labs, general guidelines for effective lab structure, positive impacts on undergraduate learning and research output, and challenges to consider.
Dairy food consumption is beneficially linked with iodine status in US children and adults: National Health and Nutrition Examination Surveys 2001–2018
Authors: Qin Yue , Cifelli Christopher J , Agarwal Sanjiv , Fugoni Victor L
Published: April 2023

Objectives:

The objective of this study was to determine the association between the consumption of dairy foods with urinary iodine concentration (UIC) and iodine deficiency risk in a nationally representative sample of the US population.

Design, Setting and Participants:

24-hour dietary recall data and laboratory data for UIC (μg/l) from subjects 2+ years old US population participating in National Health and Nutrition Examination Surveys 2001–2018 were used (n26 838) for analyses after adjusting for demographic covariates. Significant associations were assessed atP< 0·05.

Results:

Mean intakes of total dairy were 2·21, 2·17 and 1·70 cup equivalents (cup eq) among those 2–8, 9–18 and 19+ years, respectively. Of the dairy components, intake of milk was highest followed by cheese and yogurt for all age groups. Total dairy intakes were positively associated with UIC among those 2–8 years (β= 29·9 ± 9·9 μg/l urine/cup eq dairy) and 9–18 years (β= 26·0 ± 4·8 μg/l urine/cup eq dairy) but not associated among those 19+ years. Total dairy intakes were associated with lowered risks (30 %, 21 % and 20 % for among 2–8, 9–18 and 19+ years, respectively) of being classified as iodine insufficient (UIC < 100 μg/l) or lowered risk (47 %, 30 % and 26 % among 2–8, 9–18 and 19+ years, respectively) of being classified as iodine severely deficient (UIC < 20 μg/l).

Conclusions:

The results indicate that dairy foods are beneficially associated with UIC and lowered iodine deficiency risk.
Kant on Mind-Dependence: Possible or Actual Experience?
Authors: Kohl Markus
Published: April 2023

In Kant’s idealism, all spatiotemporal objects depend on the human mind in a certain way. A central issue here is whether the existence of spatiotemporal things requires that these things are, at least at some point, objects of some actual experience or of a merely possible experience. In this essay, I argue (on textual and philosophical grounds) for the latter view: spatiotemporal things exist (or spatiotemporal events occur) if they are objects of a (suitably qualified) possible experience.
Manning Clark’s Repudiation of Anglicanism and the Appeal of ‘Sentimental Humanism’ in his Quest for Grace
Authors: Moses John A.
Published: April 2023

Manning Clark is regarded as a pioneer of Australian national history. His output has been unequalled but it has provoked a vigorous division of opinions concerning its accuracy and the all-pervading thesis that Australia, to achieve its true national self-perception, must throw off the British heritage that included the baleful influence of the Anglicanism in which Clark was raised by his priest father. Here the work of three key scholarly critics, namely Dr George Shaw, Professor Brian Fletcher and Professor Alan Atkinson is evaluated, all of whom are Anglican historians of Australia. They have made very different assessments of the evolution of Australian national identity and the permanence of the British heritage. Shaw, as a former student of Clark, has assessed his mentor’s work not as rigorous history but essentially as ‘sentimental humanism’. As well, the opportunity is taken to reflect on the two extensive biographies of Clark, namely by Brian Matthews and Mark McKenna. Both these men were educated as Roman Catholics at a time when Rome was decidedly allergic to the idea of ecumenical outreach. Consequently, it is argued here that an accurate assessment of Manning Clark’s oeuvre is yet to be accomplished.
Paternal and Maternal Problem Drinking and Lifetime Problem Drinking of Their Adult Children
Authors: Sipilä Pyry N. , Keski-Rahkonen Anna , Lindbohm Joni V. , Rose Richard J. , Kaprio Jaakko
Published: April 2023

Parents’ alcohol use is associated with alcohol use of their adolescent offspring, but does this association extend to the adulthood of the offspring? We examined associations of paternal and maternal problem drinking with lifetime problem drinking of their adult offspring prospectively assessed in a population-based Finnish twin-family cohort (FinnTwin16). Problem drinking (Malmö-modified Michigan Alcoholism Screening Test) was self-reported separately by mothers and fathers when their children were 16. The children reported on an extended lifetime version of the same measure during their mid-twenties (21-28 years) and mid-thirties (31-37 years). 1235 sons and 1461 daughters in mid-twenties and 991 sons and 1278 daughters in mid-thirties had complete data. Correlations between fathers’ and their adult children’s problem drinking ranged from .12 to .18. For mothers and their adult children, these correlations ranged from .09 to .14. In multivariate models, adjustment for potential confounders had little effect on the observed associations. In this study, parental problem drinking was modestly associated with lifetime problem drinking of their adult children. This association could be detected even when the children had reached the fourth decade of life.
Enlist™ corn tolerance to preemergence and postemergence applications of synthetic auxin and ACCase-inhibiting herbicides
Authors: Godar Amar S. , Norsworthy Jason K. , Barber Tom L.
Published: April 2023

Allowing the use of two additional modes of action (MOAs), Enlist™ corn is a novelty in the continuum of herbicide-resistant crop development efforts that have occurred since the 1990s. Knowledge of Enlist corn tolerance to labeled herbicides and other herbicides within the same MOA for various use and/or exposure scenarios is not well established. Four site-year field experiments for preemergence (PRE) and postemergence (POST) applications were conducted at sites in Fayetteville (2021 and 2022) and Tillar (2020 and 2021), Arkansas, to evaluate Enlist corn response following PRE or POST applications of synthetic auxin herbicides or those that inhibit acetyl-CoA carboxylase (ACCase). A non-Enlist and an Enlist corn hybrid were used for each herbicide treatment to establish differential tolerance. Injury response to PRE application varied among site-years; clethodim was the only herbicide that occasionally caused significant (7% to 17%) injury to Enlist corn. None of the PRE treatments affected plant height, stand, or yield of Enlist corn; these responses were generally similar or better for Enlist corn compared to non-Enlist corn. Enlist corn showed significant injury to POST applications of florpyrauxifen-benzyl (>10%), fluazifop-P-butyl and quizalofop-P-ethyl (>5%), and clethodim and sethoxydim (>75%) 1 wk after application (WAA). These initial injury responses to clethodim and sethoxydim were generally reflected in Enlist corn yield; however, the minimal injury from fluazifop-P-butyl and quizalofop-P-ethyl did not affect yield. Injury to non-Enlist corn with POST-applied ACCase-inhibiting herbicides 2 WAA was >80%, resulting in a proportionate yield reduction. Even though florpyrauxifen-benzyl caused more initial injury to non-Enlist corn, yield reduction in non-Enlist corn was occasionally less than of Enlist corn, with both hybrids experiencing >75% yield reduction. In summary, Enlist corn may occasionally show transient injury even to labeled herbicides when applied POST, and even though the injury from florpyrauxifen-benzyl is initially mild, it nonetheless results in substantial yield loss.
Small‐Scale Discharges Observed Near the Top of a Thunderstorm
Authors: Scholten O. , Hare B. M. , Dwyer J. , Liu N. , Sterpka C. , Assink J. , Leijnse H. , Veen S. ter
Published: April 2023

We have used the LOw‐Frequency ARray (LOFAR) to image a few lightning flashes during a particularly severe thunderstorm. The images show an exceptional amount of VHF activity at altitudes above 10 km. Much of this is in the form of small‐scale discharges, not exceeding a few hundred meter, occurring seemingly randomly around the centers of active storm cells. To emphasize the incidental nature of these small‐scale discharges or sparks we refer to them as “sparkles.” A detailed investigation shows evidence that these sparkles are indicative of positive leader channels and that they are equivalent to the needle activity seen around positive leader tracks at lower altitudes.
The Flux‐Differencing Discontinuous Galerkin Method Applied to an Idealized Fully Compressible Nonhydrostatic Dry Atmosphere
Authors: Souza A. N. , He J. , Bischoff T. , Waruszewski M. , Novak L. , Barra V. , Gibson T. , Sridhar A. , Kandala S. , Byrne S. , Wilcox L. C. , Kozdon J. , Giraldo F. X. , Knoth O. , Marshall J. , Ferrari R. , Schneider T.
Published: April 2023

Dynamical cores used to study the circulation of the atmosphere employ various numerical methods ranging from finite‐volume, spectral element, global spectral, and hybrid methods. In this work, we explore the use of Flux‐Differencing Discontinuous Galerkin (FDDG) methods to simulate a fully compressible dry atmosphere at various resolutions. We show that the method offers a judicious compromise between high‐order accuracy and stability for large‐eddy simulations and simulations of the atmospheric general circulation. In particular, filters, divergence damping, diffusion, hyperdiffusion, or sponge‐layers are not required to ensure stability; only the numerical dissipation naturally afforded by FDDG is necessary. We apply the method to the simulation of dry convection in an atmospheric boundary layer and in a global atmospheric dynamical core in the standard benchmark of Held and Suarez (1994, https://doi.org/10.1175/1520-0477(1994)075〈1825:apftio〉2.0.co;2).
Post-transcriptional modification of m6A methylase METTL3 regulates ERK-induced androgen-deprived treatment resistance prostate cancer
Authors: Li Yang , Zhu Shimiao , Chen Yutong , Ma Qianwang , Kan Duo , Yu Wenyue , Zhang Boya , Chen Xuanrong , Wei Wanqing , Shao Yi , Wang Keruo , Zhang Mingpeng , Deng Shu , Niu Yuanjie , Shang Zhiqun
Published: April 2023

As the most common modification of RNA, N6-methyladenosin (m6A) has been confirmed to be involved in the occurrence and development of various cancers. However, the relationship between m6A and castration resistance prostate cancer (CRPC), has not been fully studied. By m6A-sequencing of patient cancer tissues, we identified that the overall level of m6A in CRPC was up-regulated than castration sensitive prostate cancer (CSPC). Based on the analysis of m6A-sequencing data, we found m6A modification level of HRas proto-oncogene, GTPase (HRAS) and mitogen-activated protein kinase kinase 2 (MEK2 or MAP2K2) were enhanced in CRPC. Specifically, tissue microarray analysis and molecular biology experiments confirmed that METTL3, an m6A “writer” up-regulated after castration, activated the ERK pathway to contribute to malignant phenotype including ADT resistance, cell proliferation and invasion. We revealed that METTL3-mediated ERK phosphorylation by stabilizing the transcription of HRAS and positively regulating the translation of MEK2. In the Enzalutamide-resistant (Enz-R) C4-2 and LNCap cell line (C4-2R, LNCapR) established in the current study, the ERK pathway was confirmed to be regulated by METTL3. We also found that applying antisense oligonucleotides (ASOs) to target the METTL3/ERK axis can restore Enzalutamide resistance in vitro and in vivo. In conclusion, METTL3 activated the ERK pathway and induced the resistance to Enzalutamide by regulating the m6A level of critical gene transcription in the ERK pathway.
Durability of neutralizing RSV antibodies following nirsevimab administration and elicitation of the natural immune response to RSV infection in infants
Authors: Wilkins Deidre , Yuan Yuan , Chang Yue , Aksyuk Anastasia A. , Núñez Beatriz Seoane , Wählby-Hamrén Ulrika , Zhang Tianhui , Abram Michael E. , Leach Amanda , Villafana Tonya , Esser Mark T.
Published: April 2023

Nirsevimab is an extended half-life monoclonal antibody specific for the prefusion conformation of the respiratory syncytial virus (RSV) F protein, which has been studied in preterm and full-term infants in the phase 2b and phase 3 MELODY trials. We analyzed serum samples collected from 2,143 infants during these studies to characterize baseline levels of RSV-specific immunoglobulin G antibodies and neutralizing antibodies (NAbs), duration of RSV NAb levels following nirsevimab administration, the risk of RSV exposure during the first year of life and the infant’s adaptive immune response to RSV following nirsevimab administration. Baseline RSV antibody levels varied widely; consistent with reports that maternal antibodies are transferred late in the third trimester, preterm infants had lower baseline RSV antibody levels than full-term infants. Nirsevimab recipients had RSV NAb levels >140-fold higher than baseline at day 31 and remained >50-fold higher at day 151 and >7-fold higher at day 361. Similar seroresponse rates to the postfusion form of RSV F protein in nirsevimab recipients (68–69%) compared with placebo recipients (63–70%; not statistically significant) suggest that while nirsevimab protects from RSV disease, it still allows an active immune response. In summary, nirsevimab provided sustained, high levels of NAb throughout an infant’s first RSV season and prevented RSV disease while allowing the development of an immune response to RSV.
Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin
Authors: Li Xiaofei , Andrusivova Zaneta , Czarnewski Paulo , Langseth Christoffer Mattsson , Andersson Alma , Liu Yang , Gyllborg Daniel , Braun Emelie , Larsson Ludvig , Hu Lijuan , Alekseenko Zhanna , Lee Hower , Avenel Christophe , Kallner Helena Kopp , Åkesson Elisabet , Adameyko Igor , Nilsson Mats , Linnarsson Sten , Lundeberg Joakim , Sundström Erik
Published: April 2023

The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5–12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
Validation of subjective manual palpation using objective physiological recordings of the cranial rhythmic impulse during osteopathic manipulative intervention
Authors: Pelz Holger , Müller Gero , Keller Micha , Mathiak Klaus , Mayer Johannes , Borik Stefan , Perlitz Volker
Published: April 2023

Intermediate (IM) band physiology in skin blood flow exhibits parallels with the primary respiratory mechanism (PRM) or cranial rhythmic impulse (CRI), controversial concepts of osteopathy in the cranial field (OCF). Owing to inconsistent manual palpation results, validity of evidence of PRM/CRI activity has been questionable. We therefore tried to validate manual palpation combining instrumented tracking and algorithmic objectivation of frequencies, amplitudes, and phases. Using a standard OCF intervention, cranial vault hold (CVH), two OCF experts palpated and digitally marked CRI frequencies in 25 healthy adults. Autonomic nervous system (ANS) activity in low frequency (LF) and IM band in photoplethysmographic (PPG) forehead skin recordings was probed with momentary frequency of highest amplitude (MFHA) and wavelet amplitude spectra (WAS) in examiners and participants. Palpation errors and frequency expectation bias during CVH were analyzed for phases of MFHA and CRI. Palpated CRI frequencies (0.05–0.08 Hz) correlated highly with mean MFHA frequencies with 1:1 ratio in 77% of participants (LF-responders; 0.072 Hz) and with 2:1 ratio in 23% of participants (IM-responders; 0.147 Hz). WAS analysis in both groups revealed integer number (harmonic) waves in (very) low and IM bands in > 98% of palpated intervals. Phase analyses in participants and examiners suggested synchronization between MFHA and CRI in a subset of LF-responders. IM band physiology in forehead PPG may offer a sensible physiological correlate of palpated CRI activity. Possible coordination or synchronization effects with additional physiological signals and between examiners and participants should be investigated in future studies.
iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation
Authors: Otsuka Satoshi , Qin Xian-Yang , Wang Wenlong , Ito Tomohiro , Nansai Hiroko , Abe Kuniya , Fujibuchi Wataru , Nakao Yoichi , Sone Hideko
Published: April 2023

Chemical-induced dysregulation of DNA methylation during the fetal period is known to contribute to developmental disorders or increase the risk of certain diseases later in life. In this study, we developed an iGEM (iPS cell-based global epigenetic modulation) detection assay using human induced pluripotent stem (hiPS) cells that express a fluorescently labeled methyl-CpG-binding domain (MBD), which enables a high-throughput screening of epigenetic teratogens/mutagens. 135 chemicals with known cardiotoxicity and carcinogenicity were categorized according to the MBD signal intensity, which reflects the degree of nuclear spatial distribution/concentration of DNA methylation. Further biological characterization through machine-learning analysis that integrated genome-wide DNA methylation, gene expression profiling, and knowledge-based pathway analysis revealed that chemicals with hyperactive MBD signals strongly associated their effects on DNA methylation and expression of genes involved in cell cycle and development. These results demonstrated that our MBD-based integrated analytical system is a powerful framework for detecting epigenetic compounds and providing mechanism insights of pharmaceutical development for sustainable human health.
The seven phases of match status differentiate the running performance of soccer players in UEFA Champions League
Authors: Konefał Marek , Radzimiński Łukasz , Chmura Jan , Modrić Toni , Zacharko Michał , Padrón-Cabo Alexis , Sekulic Damir , Versic Sime , Chmura Paweł
Published: April 2023

The purpose of this research was to investigate the running performance of professional soccer players in relation to seven phases which resulted in the changing or maintaining the match status in the UEFA Champion League games during season 2020/2021. Moreover, we aimed to define which match status phases occur at the earliest stage of regular game time. This study involved professional soccer players from 24 teams participating in the group stage of UEFA Champions League in season 2020/21. The match status was divided into seven phases that result in changing or maintaining the match outcome: DW (Drawing to Winning); LD (Losing to Drawing); WW (Winning to Winning); DD (Drawing to Drawing); LL (Losing to Losing); DL (Drawing to Losing); WD (Winning to Drawing). Such running performance variables as: total distance covered (TDC) and distance covered in high-intensity running (HIR) were analyzed. Players participating in the UEFA Champions League matches cover the longest TDC in DW, DL and DD phases. TDC in these stages was between 111 and 123 m min−1. The highest HIR was recorded during phases: DW, DL and LL (range between 9.91 and 10.82 m min−1). In contrast, the lowest total distance and distance in HIR is covered during WD phase (only 105.57 ± 1.89 m min−1 and 7.34 m min−1 respectively). On average, phases resulting in the change of the match status occur during the first half, while all phases maintaining the result in the second half. Coaching staffs should consider registering and analysing the physical match performance in relation to described seven match status phases. Such information allows to prepare team-specific training drills, that players should perform more often in order to change or maintain the status of the game.
Ultrasound-guided lateral branch radiofrequency neurotomy for sacroiliac joint pain after lumbosacral spinal fusion surgery
Authors: Le Viet-Thang , Nguyen Anh Minh , Do Phuoc Trong
Published: April 2023

Our study evaluated the clinical feasibility of ultrasound-guided lateral branch radiofrequency neurotomy for sacroiliac joint (SIJ) pain after lumbosacral spinal fusion surgery (LSFS). This prospective study included a total of 46 patients who were diagnosed with SIJ pain after LSFS, did not respond to conservative treatment and therefore underwent ultrasound-guided SIJ radiofrequency neurotomy (RFN) from January 2019 to January 2022. These patients were followed up for twelve months after the procedure. Patients were assessed with the Numeric Rating Scale (NRS) and the Oswestry Disability Index (ODI) preprocedural and postprocedural for 1 month, 6 months and 12 months follow-ups. There was a significant improvement in postprocedural NRS and ODI scores (p < 0.001). Thirty-eight patients (82.6%) had a satisfactory response and good global perceived effect (GPE) after twelve months. No significant complications were observed during the 12-month follow-up. The ultrasound-guided radiofrequency device designed as a safe, easily applied and encouraging method could avoid revision surgery. It is a promising technique and has shown good results in providing intermediate pain relief. In addition to the limited series reported in the literature, future studies will add meaning to this topic by including it in routine practice.
Prolonged infusion of bivalirudin after elective percutaneous coronary intervention protects against procedural myocardial injury (a COBER study)—a randomized trial
Authors: Wu Zhiming , Meng Peina , Guo Yajie , You Wei , Wu Xiangqi , Ye Fei
Published: April 2023

Procedural myocardial injury (PMI), which is the most common complication of elective percutaneous coronary intervention (ePCI), is associated with future adverse cardiac events. In this randomized pilot trial, we assessed the effects of prolonged use of the anti-coagulant bivalirudin on PMI after ePCI. Patients undergoing ePCI were randomized into the following two groups: the bivalirudin use during operation group (BUDO, 0.75 mg/kg bolus plus 1.75 mg/kg/h) and the bivalirudin use during and after operation for 4 h (BUDAO, 0.75 mg/kg bolus plus 1.75 mg/kg/h). Blood samples were collected before and 24 h after ePCI (per 8 h). The primary outcome, PMI, was defined as an increase in post-ePCI cardiac troponin I (cTnI) levels of > 1 × 99th% upper reference limit (URL) when the pre-PCI cTnI was normal or a rise in cTnI of > 20% of the baseline value when it was above the 99th percentile URL, but it was stable or falling. Major PMI (MPMI) was defined as a post-ePCI cTnI increase of > 5 × 99th% URL. A total of 330 patients were included (n = 165 per group). The incidences of PMI and MPMI were not significantly higher in the BUDO group than in the BUDAO group (PMI: 115 [69.70%] vs. 102 [61.82%],P = 0.164; MPMI: 81 [49.09%] vs. 70 [42.42%],P = 0.269). However, the absolute change in cTnI levels (calculated as the peak value 24 h post-PCI minus the pre-PCI value) was notably larger in the BUDO group (0.13 [0.03, 1.95]) than in the BUDAO group (0.07 [0.01, 0.61]) (P = 0.045). Moreover, the incidence of bleeding events was similar between the two groups (BUDO: 0 [0.00%]; BUDAO: 2 [1.21%],P = 0.498). Prolonged infusion of bivalirudin for 4 h after ePCI reduces PMI severity without increasing the risk of bleeding.

ClinicalTrials.gov.Number: NCT04120961, 09/10/2019.
Comparison of the biological effects of gadodiamide (Omniscan) and gadoteridol (ProHance) by means of multi-organ and plasma metabolomics
Authors: Romano Francesca , Di Gregorio Enza , Riccardi Gelsomina , Furlan Chiara , Cavallini Nicola , Savorani Francesco , Di Porzio Anna , De Tito Stefano , Randazzo Antonio , Gianolio Eliana , Iaccarino Nunzia
Published: April 2023

Multi-organ and plasma metabolomics reveals marked metabolic changes induced in brain, cerebellum and liver of mice treated with a linear gadolinium-based contrast agent.
Synthesis of a trinuclear zinc(ii) cluster composed of [4.4.3.01,5]tridecane cages: a rapid detection and degradation probe for the chemical warfare agent simulant diethyl cyanophosphonate in protein-rich food products
Authors: Thakur Sahil , Rohilla Jyoti , Kumar Keshav , Kumar Harender , Singh Raghubir , Kaur Varinder , Kamboj Raman , Kaur Ravneet
Published: April 2023

Detection and degradation of diethyl cyanophosphonate in protein rich food products using trinuclear zinc(ii) cluster.