bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary effects of aucubin on growth and flesh quality of grass carp (Ctenopharyngodon idellus) based on metabolomics
Authors: Xu Zhen , Yang Hang , Li Xiaoqin , Xu Xiaoying , Tan Hongxin , Leng Xiangjun
Published: August 2022

This aim of this study was to investigate the effects of dietary aucubin on the growth, flesh quality, and metabolomics of grass carp (Ctenopharyngodon idella). Five diets were designed with the aucubin inclusion of 0 (control diet), 0.2, 0.4, 0.6, and 0.8 g/kg (Auc-0.2, Auc-0.4, Auc-0.6, Auc-0.8) and were fed to grass carp with an initial body weight of 17.0 ± 0.2 g for 60 d. The results indicated that dietary aucubin did not significantly affect the growth performance of grass carp (P > 0.05). Compared to the control, dietary supplementation with 0.2 to 0.8 g/kg aucubin increased flesh hardness, chewiness, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the contents of total free amino acids (TFAA) and n-3 polyunsaturated fatty acids (n-3 PUFA) (P < 0.05). The contents of malondialdehyde (MDA) and lactic acid (LD) in the flesh were significantly decreased by the addition of 0.4 to 0.6 g/kg aucubin and by the addition of 0.6 to 0.8 g/kg aucubin (P < 0.05), respectively, while the content of delicious amino acids (DAA) was significantly enhanced by the addition of 0.4 to 0.8 g/kg aucubin (P < 0.05). Moreover, the contents of collagen and C22:6n3 (DHA) in the flesh of the Auc-0.8 group were significantly higher than those of the control (P < 0.05). In the metabolomics profiling of flesh, 133 and 135 named differential metabolites were identified in the Auc-0.4 and Auc-0.8 groups, respectively, compared to the control, and these metabolites were found to be involved in the second-grade pathways of “lipid metabolism” and “amino acid metabolism”. Regarding gene expression, the mRNA levels of CuZn-SOD, CAT, COL1A1, COL1A2, Smad4, and FAS in flesh were upregulated in the Auc-0.4 and Auc-0.8 groups, and the expression levels of GPx, Nrf2, and TGF-β1 mRNA were also upregulated in the Auc-0.8 group (P < 0.05). In summary, dietary aucubin did not promote growth, but improved the flesh quality of grass carp, which might be associated with the TGF-β/Smad and Nrf2 pathways. The recommended supplementation level of aucubin in the diet of grass carp was 0.6 to 0.8 g/kg.
A False-Positive Gamma-Hydroxy Butyric Acid Urine Screening in a Patient with High Anion Gap Metabolic Acidosis Due to Ethylene Glycol Poisoning
Authors: Steels Sophie , De Bont Erika , Verbinnen Margo , Van den Eede Nele , Pauwels Steven
Published: August 2022

A young woman with a history of several suicide attempts was admitted to the hospital after suspicion of a new intoxication without definite identification of the causing agent. The patient had a high anion gap metabolic acidosis (HAGMA) with respiratory compensation, a lactate gap and an osmolar gap at admission. Initial toxicological screening showed no abnormalities except for a weak positive gamma-hydroxy butyric acid (GHB) enzymatic screen in urine. This finding could not be confirmed using chromatographic analysis nor be explained by the presence of known cross-reacting substances like ethanol. In this case, falsely elevated urinary GHB screening was caused by the ingestion of ethylene glycol. To confirm that the interference was due to ethylene glycol or its metabolites, we performed a spiking experiment. Cross reactivity was linked to ethylene glycol and was low in our experiments (0.1–0.2%). Substantial amounts of ethylene glycol are required to slightly elevated GHB results, depending on the endogenous cutoff used. We can conclude that ethylene glycol can give rise to falsely elevated urinary GHB levels at ethylene glycol concentrations that are typically found in intoxications.
Unravelling of the Number 16 in Corporeality, Percussion, and the Bengali Hindu Cosmos: The Experience of the Body/Mṛdaṅga
Authors: Sarbadhikary Sukanya
Published: August 2022

This paper analyses how the body and sacred drum, mṛdaṅga—used as the rhythm-accompaniment of Bengal’s devotional music dedicated to deities, Rādhā–Kṛṣṇa (kīrtana)—are cultivated and experienced as homologous, mirror-reflections of a macrocosmic sonic buzz, Nāda-brahman. Dimensions of cosmic/acoustic transcendence and its materialising potential as the body and instrument are explored through the number 16. 16 is analysed as an unfolded, expanded expression of what Yoga texts describe as the unstruck drone, AUM̐, or Nāda-brahman, composed of 3½ (4-fold) parts, exactly like the Tantric kuṇḍalinī, spiralled as the feminine, sonic power at the spinal base. I argue that these Yogic, Tantric, and devotional ontologies come together in Bengal’s mahā-mantra: 16 nāma (names) 32 akṣara (syllables), or Hare Kṛṣṇa chant, which practitioners say, constitute both the body and mṛdaṅga. Based on decade-long ethnographic work with Bengal Vaiṣṇavas, and mṛdaṅga’s makers, players, and sound meditators, studying expert techniques, oral traditions of esoteric poems and myths relating the body–mṛdaṅga as mirroring agents, and through philosophy of sound readings in Yoga and Tantra, I argue that the meditative body’s transcendental potential is analogous with mṛdaṅga’s sounding. Both these vessels are constituted through various classifications of number 16: evident in the body’s/drum’s constructions, breathing, rhythming, tonality, and being. The body becomes the drum and vice-versa, and these resonant vessels throb with Nāda-brahman’s vibration, or AUM̐’s/16’s cosmic pulsations. In making the mṛdaṅga, the body externalises inner aural potential, and while playing it, fuses the body’s and drum’s constitutive buzzing hum, AUM̐, through their own immanent materialities.
Habitat Type Affects Elevational Patterns in Ground-dwelling Arthropod Communities
Authors: Uhey Derek A , Bowker Matthew A , Haubensak Karen A , Auty David , Vissa Sneha , Hofstetter Richard W
Published: August 2022

Understanding factors that drive biodiversity distributions is central in ecology and critical to conservation. Elevational gradients are useful for studying the effects of climate on biodiversity but it can be difficult to disentangle climate effects from resource differences among habitat types. Here we compare elevational patterns and influences of environmental variables on ground-dwelling arthropods in open- and forested-habitats. We examine these comparisons in three arthropod functional groups (detritivores, predators, and herbivores) and two taxonomic groups (beetles and arachnids). We sampled twelve sites spanning 1,132 m elevation and four life zones, collecting 4,834 individual ground arthropods identified to 123 taxa. Elevation was a strong predicator for arthropod composition, however, patterns differed among functional and taxonomic groups and individual species between open- and forested-habitats. Beetles, arachnids, and predators decreased with elevation in open habitats but increased in forests showing a significant interaction between habitat type and elevation. Detritivores and herbivores showed no elevational patterns. We found 11 arthropod taxa with linear elevational patterns, seven that peaked in abundance at high elevations, and four taxa at low elevations. We also found eight taxa with parabolic elevational patterns that peaked in abundance at mid-elevations. We found that vegetation composition and productivity had stronger explanatory power for arthropod composition in forested habitats, while ground cover was a stronger predictor in open habitats. Temperature and precipitation were important in both habitats. Our findings demonstrate that relationships between animal diversity and elevation can be mediated by habitat type, suggesting that physiological restraints and resource limitations work differently between habitat types.
Assessment of Caregivers’ Burden When Caring for Patients With Pancreatic and Periampullary Cancer
Authors: Fong Zhi Ven , Teinor Jonathan , Yeo Theresa P , Rinaldi Dee , Greer Jonathan B , Lavu Harish , Qadan Motaz , Johnston Fabian M , Ferrone Cristina R , Chang David C , Yeo Charles J , Wolfgang Christopher L , Warshaw Andrew L , Lillemoe Keith D , Fernandez-del Castillo Carlos , Weiss Matthew J , Wolff Jennifer L , Wu Albert W
Published: August 2022

Background

Family and other unpaid caregivers play an active role in the recovery of individuals with pancreatic and periampullary cancer after pancreatectomy. However, little is known about caregivers’ experiences and how to better support them.

Methods

Caregivers accompanying patients to 1-month postpancreatectomy visits at 3 hospitals completed an electronic survey between November 2018 and February 2020. We examine measures of absenteeism and work productivity loss among the subset of caregivers who reported working for pay and comparatively assess caregiver experiences by employment status. All analyses were performed as 2-sided tests.

Results

Of 265 caregivers approached for study participation, 240 (90.6%) enrolled. Caregivers were primarily female (70.8% female, 29.2% male) and spouses (58.3%) or adult children (25.8%) of patients, with a median age of 60 years. Of the 240 caregivers included in the study, 107 (44.6%) worked for pay. Nearly half (44.4%) of working caregivers reported being absent from work because of caregiving amounting to a 14% loss in work hours. While at work, 58.9% of working caregivers reported increased work difficulty as a result of caregiving. Taken together, an estimated 59.7% loss in work productivity was experienced because of caregiving in the month following pancreatectomy. After adjustment for sociodemographic factors, working (vs nonworking) caregivers reported increased financial (odds ratio [OR] = 2.32; P = .04) and emotional (OR = 1.93; P = .04) difficulties and daily activity restrictions (OR = 1.85; P = .048).

Conclusions

Working caregivers of patients with pancreatic and periampullary cancer experience negative impacts on work and productivity, and caregiving-related financial and emotional difficulties may be amplified. This study highlights the need for workplace policies to support unpaid cancer caregiving.
Immune Microenvironment and Lineage Tracing Help to Decipher Rosette-Forming Glioneuronal Tumors: A Multi-Omics Analysis
Authors: Lerond Julie , Morisse Mony Chenda , Letourneur Quentin , Gimonnet Coralie , Navarro Soledad , Gaspar Cassandra , Idbaih Ahmed , Bielle Franck
Published: August 2022

Rosette-forming glioneuronal tumors (RGNT) are rare low-grade primary central nervous system (CNS) tumors. The methylation class (MC) RGNT (MC-RGNT) delineates RGNT from other neurocytic CNS tumors with similar histological features. We performed a comprehensive molecular analysis including whole-exome sequencing, RNAseq, and methylome on 9 tumors with similar histology, focusing on the immune microenvironment and cell of origin of RGNT. Three RGNT in this cohort were plotted within the MC-RGNT and characterized by FGFR1 mutation plus PIK3CA or NF1 mutations. RNAseq analysis, validated by immunohistochemistry, identified 2 transcriptomic groups with distinct immune microenvironments. The “cold” group was distinguishable by a low immune infiltration and included the 3 MC-RGNT and 1 MC-pilocytic astrocytoma; the “hot” group included other tumors with a rich immune infiltration. Gene set enrichment analysis showed that the “cold” group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes, while the “hot” group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative cell of origin of RGNT. Our study identified distinct tumor biology and immune microenvironments as key features relevant to the pathogenesis and management of RGNT.
Change in Seizure Incidence in Febrile Children With COVID-19 in the Era of Omicron Variant of Concern
Authors: Iijima Hiroyuki , Kubota Mitsuru , Ogimi Chikara
Published: August 2022

In this single-center retrospective observational study, we report that the incidence of seizures in febrile children with COVID-19 was significantly higher in the Omicron era than in the pre-Omicron era (14.6% vs 1.7%, P < .001). One-third of the cases in the Omicron era were older than 5 years.
Excitation of vertical breathing motion in disc galaxies by tidally-induced spirals in fly-by interactions
Authors: Kumar Ankit , Ghosh Soumavo , Kataria Sandeep Kumar , Das Mousumi , Debattista Victor P
Published: August 2022

It is now clear that the stars in the Solar neighbourhood display large-scale coherent vertical breathing motions. At the same time, Milky Way-like galaxies experience tidal interactions with satellites/companions during their evolution. While these tidal interactions can excite vertical oscillations, it is still not clear whether vertical breathing motions are excited directly by the tidal encounters or are driven by the tidally-induced spirals. We test whether excitation of breathing motions are directly linked to tidal interactions by constructing a set of N-body models (with mass ratio 5:1) of unbound single fly-by interactions with varying orbital configurations. We first reproduce the well-known result that such fly-by interactions can excite strong transient spirals (lasting for ${\sim}2.9{-}4.2\,{\rm Gyr}$) in the outer disc of the host galaxy. The generation and strength of the spirals are shown to vary with the orbital parameters (the angle of interaction, and the orbital spin vector). Furthermore, we demonstrate that our fly-by models exhibit coherent breathing motions whose amplitude increases with height. The amplitudes of breathing motions show characteristic modulation along the azimuthal direction with compressing breathing motions coinciding with the peaks of the spirals and expanding breathing motions falling in the inter-arm regions – a signature of a spiral-driven breathing motion. These breathing motions in our models end when the strong tidally-induced spiral arms fade away. Thus, it is the tidally-induced spirals which drive the large-scale breathing motions in our fly-by models, and the dynamical role of the tidal interaction in this context is indirect.
Spectroscopic analysis of BPS CS 22940−0009: connecting evolved helium stars
Authors: Snowdon E J , Scott L J A , Jeffery C S , Woolf V M
Published: August 2022

BPS CS 22940−0009 is a helium-rich B-star that shares characteristics with both helium-rich B subdwarfs and extreme helium stars. The optical spectrum of BPS CS 22940−0009 has been analysed from SALT observations. The atmospheric parameters were found to be $T_{\rm eff} = 34\, 970 \pm 370$ K, $\log g/{\rm cm\, s^{-2}} = 4.79 \pm 0.17$, nH/nHe ≃ 0.007, nC/nHe ≃ 0.007, nN/nHe ≃ 0.002, although further improvement to the helium line fits would be desirable. This places the star as a link between the He-sdB and EHe populations in g-T space. The abundance profile shows enrichment of N from CNO-processing, and C from 3α burning. Depletion of Al, Si, S and a low upper limit for Fe show the star to be intrinsically metal-poor. The results are consistent with BPS CS 22940−0009 having formed from the merger of two helium white dwarfs and currently evolving towards the helium main sequence.
On the numerical modelling of astrospheres, including those of luminous blue variable stars, and the modulation of cosmic rays within
Authors: Light Juandré , Ferreira S E S , Engelbrecht N E , Scherer K , Herbst K
Published: August 2022

Luminous blue variable-type stars are massive O-type stars that show variable outflow parameters. These stars can also undergo eruptions where a large amount of mass is ejected in a very short duration. The astrospheres of these stars are modelled using a magnetohydrodynamic model including the effect of radiative cooling. The variation in outflow parameters is demonstrated to lead to a variation in number density up to the termination shock, after which there is no effect in the post-shocked regions. On the other hand, eruptions increase the size of the astrosphere and cause the termination shock to oscillate between the inner boundary and the astropause. Galactic cosmic ray modulation within these types of astrospheres is also studied using a 1D stochastic differential equation model. It is shown that, even though these astrospheres are considerably larger than the heliosphere, calculated cosmic ray differential intensities remain larger than what is observed in the heliosphere at Earth, implying lower levels of modulation related to larger cosmic ray diffusion coefficients. During eruptive events, modelled cosmic ray intensities fluctuate due to the oscillating termination shock, and varying plasma parameters. It is also shown that such behaviour, can in principle, lead to the acceleration of these particles, but the results of this study, due to the 1D approach taken to solving the Parker transport equation, are argued to represent an upper limit to this phenomenon.
OGLE-2019-BLG-1470LABc: Another microlensing giant planet in a binary system?
Authors: Kuang (匡仁昆) Renkun , Zang (臧伟呈) Weicheng , Jung Youn Kil , Udalski Andrzej , Yang (杨弘靖) Hongjing , Mao (毛淑德) Shude , Albrow Michael D , Chung Sun-Ju , Gould Andrew , Han Cheongho , Hwang Kyu-Ha , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Yee Jennifer C , Cha Sang-Mok , Kim Dong-Jin , Kim Hyoun-Woo , Kim Seung-Lee , Lee Chung-Uk , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W , Mróz Przemek , Skowron Jan , Poleski Radoslaw , Szymański Michał K , Soszyński Igor , Pietrukowicz Paweł , Kozłowski Szymon , Ulaczyk Krzysztof , Rybicki Krzysztof A , Iwanek Patryk , Wrona Marcin , Gromadzki Mariusz , Wang (王涵悦) Hanyue , Huang (黄硕) Shuo , Zhu (祝伟) Wei
Published: August 2022

We report the discovery and analysis of a candidate triple-lens single-source (3L1S) microlensing event, OGLE-2019-BLG-1470. This event was first classified as a normal binary-lens single-source (2L1S) event, but a careful 2L1S modelling showed that it needs an additional lens or source to fit the observed data. It is found that the 3L1S model provides the best fit, but the binary-lens binary-source (2L2S) model is only disfavoured by Δχ2 ≃ 18. All of the feasible models include a planet with planet-to-host mass-ratios 10−3 ≲ q ≲ 10−2. A Bayesian analysis based on a Galactic model indicates that the planet is super-Jovian, and the projected host-planet separation is about 3 au. Specifically, for the best-fitting 3L1S model, the two stars have masses of $M_1=0.57^{+0.43}_{-0.32}{\rm M}_{\odot}$, and $M_2=0.18^{+0.15}_{-0.10}\mathrm{M}_{\odot}$ with projected separation of $1.3^{+0.5}_{-0.5}$ au, and the planetary mass is $M_3=2.2^{+1.8}_{-1.3}M_{\rm {Jupiter}}$. For the 2L2S model, the masses of the host star and the planet are $0.55^{+0.44}_{-0.31}\mathrm{M}_{\odot }$ and $4.6^{+3.7}_{-2.6}M_{\rm {Jupiter}}$, respectively. By investigating the properties of all known microlensing planets in binary systems, we find that all planets in binary systems published by the KMTNet survey are located inside the resonant caustics range with q ≳ 2 × 10−3, indicating the incompleteness of the KMTNet sample for planets in binary systems. Thus, planets in binary systems cannot be included in the current study of the KMTNet mass-ratio function, and a systematic search for planetary anomalies in KMTNet microlensing light curves of binary systems is needed.
Unimodal productivity–biodiversity relationship along the gradient of multidimensional resources across Chinese grasslands
Authors: Wang Yanfen , Du Jianqing , Pang Zhe , Liu Yali , Xue Kai , Hautier Yann , Zhang Biao , Tang Li , Jiang Lili , Ji Baoming , Xu Xingliang , Zhang Jing , Hu Ronghai , Zhou Shutong , Wang Fang , Che Rongxiao , Wang Di , Zhou Chaoting , Cui Xiaoyong , Eisenhauer Nico , Hao Yanbin
Published: August 2022

Resources can affect plant productivity and biodiversity simultaneously and thus are key drivers of their relationships in addition to plant–plant interactions. However, most previous studies only focused on a single resource while neglecting the nature of resource multidimensionality. Here we integrated four essential resources for plant growth into a single metric of resource diversity (RD) to investigate its effects on the productivity–biodiversity relationship (PBR) across Chinese grasslands. Results showed that habitats differing in RD have different PBRs—positive in low-resource habitats, but neutral in medium- and high-resource ones—while collectively, a weak positive PBR was observed. However, when excluding direct effects of RD on productivity and biodiversity, the PBR in high-resource habitats became negative, which leads to a unimodal instead of a positive PBR along the RD gradient. By integrating resource effects and changing plant–plant interactions into a unified framework with the RD gradient, our work contributes to uncovering underlying mechanisms for inconsistent PBRs at large scales.
Highly crystalline and water-wettable benzobisthiazole-based covalent organic frameworks for enhanced photocatalytic hydrogen production
Authors: Huang Wei , Hu Yongpan , Qin Zhengyuan , Ji Yujin , Zhao Xuan , Wu Yunling , He Qing , Li Youyong , Zhang Chunfeng , Lu Jun , Li Yanguang
Published: August 2022

Two-dimensional covalent organic frameworks are promising for photocatalysis by virtue of their structural and functional diversity, but generally suffer from low activities relative to their inorganic competitors. To fulfill their full potential requires a rational tailoring of their structures at different scales as well as their surface properties. Herein, we demonstrate benzobisthiazole-based covalent organic frameworks as a superior photocatalyst for hydrogen production. The product features high crystallinity with ordered 2.5-nm-wide cylindrical mesopores and great water wettability. These structural advantages afford our polymeric photocatalyst with fast charge carrier dynamics as evidenced by a range of spectroscopic characterizations and excellent catalytic performances when suspended in solution or supported on melamine foams. Under visible-light irradiation, it enables efficient and stable hydrogen evolution with a production rate of 487 μmol h−1 (or a mass-specific rate of 48.7 mmol g−1 h−1)—far superior to the previous state of the art. We also demonstrate that hydrogen production can be stoichiometrically coupled with the oxidation conversion of biomass as exemplified by the conversion of furfuryl alcohol to 2-furaldehyde.
The safety and efficacy of probiotic supplementation for critically ill adult patients: a systematic review and meta-analysis
Authors: Alsuwaylihi Abdulaziz Sulaiman , McCullough Fiona
Published: August 2022

Context

The safety and efficacy of probiotics during severe illness has been a subject of ongoing interest. The impact of probiotics can worsen nutritional status, which could potentially result in a deterioration of the patient’s overall life-threatening status.

Objective

This systematic review and meta-analysis evaluated the safety and efficacy of probiotics in reducing intensive care unit (ICU)–acquired infections in adult critically ill patients.

Data Sources

PubMed and Cochrane library databases for the period 2011–2020 were searched.

Data Extraction

Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) methodology was used to search for randomized controlled trials that evaluated the use of probiotics among critically ill patients.

Data Analysis

No significant difference was observed between probiotics and control groups in terms of the mortality rate (risk ratio 1.13, 95% confidence interval .82 to 1.55, P = .46). Probiotics, however, provided a significant reduction in ICU-acquired infections (risk ratio .73, 95% confidence interval .58 to .93, P = .01).

Conclusion

The use of probiotics seems to play a role in decreasing the incidence of ICU-acquired infections. Also, a potential reduction in terms of the incidence of diarrhea has been reported, with no examples of adverse incidents, suggesting probiotics are safe.
Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials
Authors: Prokopidis Konstantinos , Giannos Panagiotis , Triantafyllidis Konstantinos K , Kechagias Konstantinos S , Forbes Scott C , Candow Darren G
Published: August 2022

Context

From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory.

Objective

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans.

Data Sources

The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021.

Data Extraction

Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis.

Data Analysis

Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04–0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66–76 years) (SMD = 0.88; 95%CI, 0.22–1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11–31 years) (SMD = 0.03; 95%CI, −0.14 to 0.20; I2 = 0%; P = 0.72). Creatine dose (≈ 2.2–20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings.

Conclusion

Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years).

Systematic Review Registration

PROSPERO registration no. 42021281027.
DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms
Authors: Yao James , Bergsland Emily , Aggarwal Rahul , Aparicio Ana , Beltran Himisha , Crabtree Judy S , Hann Christine L , Ibrahim Toni , Byers Lauren A , Sasano Hironobu , Umejiego John , Pavel Marianne
Published: August 2022

Introduction

Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis.

Methods

This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the potential for therapeutic targeting of DLL3, and ongoing studies of DLL3-targeting therapies. Classification, incidence, pathogenesis, and current management of NEN are reviewed to provide biological context and illustrate the unmet clinical needs.

Discussion

DLL3 is overexpressed in many NENs, implicated in tumor progression, and is typically associated with poor clinical outcomes, particularly in patients with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell engager molecules, CAR-Ts) have shown promising clinical activity in small-cell lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN.

Conclusions

Current treatment options for NEN do not provide sustained responses. DLL3 is expressed on the cell surface of many NEN types and is associated with poor clinical outcomes. Initial clinical studies targeting DLL3 therapeutically in SCLC have been promising, and additional studies are expanding this approach to the broader group of NEN.
Identification of growth regulators using cross-species network analysis in plants
Authors: Curci Pasquale Luca , Zhang Jie , Mähler Niklas , Seyfferth Carolin , Mannapperuma Chanaka , Diels Tim , Van Hautegem Tom , Jonsen David , Street Nathaniel , Hvidsten Torgeir R , Hertzberg Magnus , Nilsson Ove , Inzé Dirk , Nelissen Hilde , Vandepoele Klaas
Published: August 2022

With the need to increase plant productivity, one of the challenges plant scientists are facing is to identify genes that play a role in beneficial plant traits. Moreover, even when such genes are found, it is generally not trivial to transfer this knowledge about gene function across species to identify functional orthologs. Here, we focused on the leaf to study plant growth. First, we built leaf growth transcriptional networks in Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and aspen (Populus tremula). Next, known growth regulators, here defined as genes that when mutated or ectopically expressed alter plant growth, together with cross-species conserved networks, were used as guides to predict novel Arabidopsis growth regulators. Using an in-depth literature screening, 34 out of 100 top predicted growth regulators were confirmed to affect leaf phenotype when mutated or overexpressed and thus represent novel potential growth regulators. Globally, these growth regulators were involved in cell cycle, plant defense responses, gibberellin, auxin, and brassinosteroid signaling. Phenotypic characterization of loss-of-function lines confirmed two predicted growth regulators to be involved in leaf growth (NPF6.4 and LATE MERISTEM IDENTITY2). In conclusion, the presented network approach offers an integrative cross-species strategy to identify genes involved in plant growth and development.
SHOOT MERISTEMLESS participates in the heterophylly of Hygrophila difformis (Acanthaceae)
Authors: Li Gaojie , Yang Jingjing , Chen Yimeng , Zhao Xuyao , Chen Yan , Kimura Seisuke , Hu Shiqi , Hou Hongwei
Published: August 2022

In heterophyllous plants, leaf shape shows remarkable plasticity in response to environmental conditions. However, transgenic studies of heterophylly are lacking and the molecular mechanism remains unclear. Here, we cloned the KNOTTED1-LIKE HOMEOBOX family gene SHOOT MERISTEMLESS (STM) from the heterophyllous plant Hygrophila difformis (Acanthaceae). We used molecular, morphogenetic, and biochemical tools to explore its functions in heterophylly. HdSTM was detected in different organs of H. difformis, and its expression changed with environmental conditions. Heterologous, ectopic expression of HdSTM in Arabidopsis (Arabidopsis thaliana) increased leaf complexity and CUP-SHAPED COTYLEDON (CUC) transcript levels. However, overexpression of HdSTM in H. difformis did not induce the drastic leaf change in the terrestrial condition. Overexpression of HdSTM in H. difformis induced quick leaf variations in submergence, while knockdown of HdSTM led to disturbed leaf development and weakened heterophylly in H. difformis. HdCUC3 had the same spatiotemporal expression pattern as HdSTM. Biochemical analysis revealed a physical interaction between HdSTM and HdCUC3. Our results provide genetic evidence that HdSTM is involved in regulating heterophylly in H. difformis.
Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography
Authors: Maker Allison , Bolejack Madison , Schecterson Leslayann , Hammerson Brad , Abendroth Jan , Edwards Thomas E , Staker Bart , Myler Peter J , Gumbiner Barry M
Published: August 2022

E-cadherin adhesion is regulated at the cell surface, a process that can be replicated by activating antibodies. We use cryo-electron microscopy (EM) and X-ray crystallography to examine functional states of the cadherin adhesive dimer. This dimer is mediated by N-terminal beta strand-swapping involving Trp2, and forms via a different transient X-dimer intermediate. X-dimers are observed in cryo-EM along with monomers and strand-swap dimers, indicating that X-dimers form stable interactions. A novel EC4-mediated dimer was also observed. Activating Fab binding caused no gross structural changes in E-cadherin monomers, but can facilitate strand swapping. Moreover, activating Fab binding is incompatible with the formation of the X-dimer. Both cryo-EM and X-ray crystallography reveal a distinctive twisted strand-swap dimer conformation caused by an outward shift in the N-terminal beta strand that may represent a strengthened state. Thus, regulation of adhesion involves changes in cadherin dimer configurations.
Totally disconnected semigroup compactifications of topological groups
Authors: Stephens Alexander , Stokke Ross
Published: August 2022

We introduce the notion of an introverted Boolean algebra $\mathcal{B}$ of closed-and-open subsets of a topological group G, show that the associated Stone space $(\nu_{\mathcal{B}} G, \nu_{\mathcal{B}})$ is a totally disconnected semigroup compactification of G and show that every totally disconnected semigroup compactification of G takes this form. We identify and study the universal totally disconnected semigroup compactification, the universal totally disconnected semitopological semigroup compactification and the universal totally disconnected group compactification of G. Our main results are obtained independently of Gelfand theory and well-known properties of the (typically non-totally disconnected) universal compactifications GLUC, GW AP and GAP, although we do employ Gelfand theory to clarify the relationship between these familiar universal compactifications and their totally disconnected counterparts.
Managerial Entrenchment and the Market for Talent
Authors: Feriozzi Fabio
Published: August 2022

This paper studies how the nature of managerial skills affects firms’ governance decisions. As required skills shift from firm specific toward more general abilities, replacing an underperforming CEO with an outside hire becomes more profitable for shareholders. Therefore, firms adopt stronger governance arrangements to limit the entrenchment of incumbent CEOs and exploit the improved opportunities offered by the market for talent. The analysis rationalizes the observed trend toward stronger corporate governance and offers novel empirical predictions concerning the relationship between managerial entrenchment, firm size, and the nature of managerial skills. (JEL D83, D86, G34)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Sleep spindle alterations relate to working memory deficits in individuals at clinical high-risk for psychosis
Authors: Mayeli Ahmad , Wilson James D , Donati Francesco L , LaGoy Alice D , Ferrarelli Fabio
Published: August 2022

Study Objectives

Sleep spindles are waxing and waning EEG waves exemplifying the main fast oscillatory activity occurring during NREM sleep. Several recent studies have established that sleep spindle abnormalities are present in schizophrenia spectrum disorders, including in early-course and first-episode patients, and those spindle deficits are associated with some of the cognitive impairments commonly observed in these patients. Cognitive deficits are often observed before the onset of psychosis and seem to predict poor functional outcomes in individuals at clinical high-risk for psychosis (CHR). Yet, the presence of spindle abnormalities and their relationship with cognitive dysfunction has not been investigated in CHR.

Methods

In this study, overnight high-density (hd)-EEG recordings were collected in 24 CHR and 24 healthy control (HC) subjects. Spindle density, duration, amplitude, and frequency were computed and compared between CHR and HC. Furthermore, WM was assessed for both HC and CHR, and its relationship with spindle parameters was examined.

Results

CHR had reduced spindle duration in centro-parietal and prefrontal regions, with the largest decrease in the right prefrontal area. Moderation analysis showed that the relation between spindle duration and spindle frequency was altered in CHR relative to HC. Furthermore, CHR had reduced WM performance compared to HC, which was predicted by spindle frequency, whereas in HC spindle frequency, duration, and density all predicted working memory performance.

Conclusion

Altogether, these findings indicate that sleep spindles are altered in CHR individuals, and spindle alterations are associated with their cognitive deficits, thus representing a sleep-specific putative neurophysiological biomarker of cognitive dysfunction in psychosis risk.
Cytokine Mixtures Mimicking the Local Milieu in Patients with Inflammatory Bowel Disease Impact Phenotype and Function of Mesenchymal Stromal Cells
Authors: Barnhoorn Marieke C , van der Meulen-de Jong Andrea E , Schrama Ellen C L M , Plug Leonie G , Verspaget Hein W , Fibbe Willem E , van Pel Melissa , Hawinkels Lukas J A C , Schepers Koen
Published: August 2022

Locally applied mesenchymal stromal cells (MSCs) have the capacity to promote the healing of perianal fistulas in Crohn’s disease (CD) and are under clinical development for the treatment of proctitis in ulcerative colitis (UC). Despite these clinical advances, the mechanism of action of local MSC therapy in inflammatory bowel disease (IBD) is largely unknown. We hypothesized that the local cytokine environment in IBD patients affects the immunomodulatory properties of MSCs. To evaluate this, 11 cytokines were analyzed in inflamed tissues obtained from CD and UC patients. Based on the identified cytokine profiles 4 distinct cytokine mixtures that mimic various inflammatory IBD environments were established. Next, MSCs were cultured in the presence of either of these 4 cytokine mixtures after which the expression of immunomodulatory and tissue regenerative molecules and the capacity of MSCs to modulate T-cell proliferation and dendritic cell (DC) differentiation were assessed. Our data show that MSCs respond, in a cytokine-specific manner, by upregulation of immunomodulatory and tissue regenerative molecules, including cyclooxygenase-2, indoleamine 2,3-dioxygenase, and transforming growth factor-β1. Functional studies indicate that MSCs exposed to a cytokine profile mimicking one of the 2 UC cytokine milieus were less effective in inhibition of DC differentiation. In conclusion, our data indicate that cytokine mixes mimicking the local cytokine milieus of inflamed UC colonic or CD fistulas tissues can differentially affect the immunomodulatory and tissue regenerative characteristics of MSCs. These data support the hypothesis that the local intestinal cytokine milieu serves as a critical factor in the efficacy of local MSC treatment.
Nebulized Salbutamol with or without Magnesium Sulphate in the Management of Acute Asthma in Children in India: A Randomized Controlled Trial
Authors: Siddiqui Harun , Siddiqui Shahid Akhtar , Yadav Rajesh Kumar , Singh Mukesh Vir , Kumar Dinesh , Kumar Durgesh , Singh Dinesh Kumar
Published: August 2022

Background

There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population.

Objectives

Whether the use of nebulized salbutamol with or without MgSO4 in the management of acute asthma results in clinically significant improvement in lung function in Indian children? The primary outcome measure was to assess improvements in peak expiratory flow rate (PEFR), heart rate, respiratory rate and SpO2.

Methods

This was a single centre; prospective double-blind randomized control trial conducted in paediatric intensive care unit of a tertiary care centre. Ninety children of 6–14 years with acute exacerbations of bronchial asthma were enrolled to receive either inhaled magnesium sulphate (95 mg) with salbutamol (5 mg) or inhaled salbutamol (5 mg) alone. All patients got three nebulizations done during the first hour at 20 min intervals, two nebulizations during the second hour at 30 min intervals, hourly for the next 2 h and then at 24 and 48 h.

Results

Eighty-five patients were finally analysed as per protocol analysis. The trial showed that PEFR increased gradually in both groups over the study duration, but it was statistically not significant. Heart rate decreased significantly in both groups over the study duration. Respiratory rate decreased significantly between the groups at 24 and 48 h only. SpO2 improved too in both groups but was not significant statistically.

Conclusion

The addition of nebulized MgSO4 to salbutamol does not seem to result in improvement in lung function in the management of acute asthma in Indian children.
Physicochemical Space of Synthetic and Natural Pesticides – A Meta-Analysis
Authors: Dubey Sylvain , Guignard Florian , Gaume Alain , Gindro Katia , Schnee Sylvain , Joz-Roland Mathis , Broennimann Olivier , Dubey Olga
Published: August 2022

The first commercial use of synthetic pesticides for crop protection dates back to the 1940s, followed by a fast spread of their use and the development of a large number of compounds. In contrast to synthetic pesticides that are now designed with the help of artificial intelligence, which includes computational science and combinatorial chemistry, natural pesticides are the results of long evolutionary processes involving specific host-pathogen, predator-prey, and competitor interactions. For these reasons, natural pesticides are often more specific and less harmful to the environment. Natural pesticides are very diverse and can be found in various living organisms. In the present study, we investigated differences in the physicochemical space occupied by synthetic and natural pesticides. In this respect, we measured the mean and breadth of synthetic and natural pesticides, as well as the overlap between these groups in a reduced physicochemical space derived from a set of 44 physicochemical variables. We showed that physicochemical space strongly differs between synthetic and natural pesticides and could be determined with 93 to 100% certainty, a result comparable to differences observed in drugs. Importantly, the physicochemical space occupied by synthetic pesticides was 2.6-fold smaller than that of natural pesticides, and toxicity potential was lower in the latter. In conclusion, our work showed that the design of commercialized synthetic pesticides is underexploiting the possible physicochemical space of known natural pesticides, likely due to specific constraints. Such limitations should trigger the development of efficient natural pesticides, avoiding as much as possible detrimental effects on nontarget organisms.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Potential role of ghrelin in the regulation of inflammation
Authors: Ma Yunxiao , Zhang Haifeng , Guo Weiying , Yu Lu
Published: August 2022

Several diseases are caused or progress due to inflammation. In the past few years, accumulating evidence suggests that ghrelin, a gastric hormone of 28‐amino acid residue length, exerts protective effects against inflammation by modulating the related pathways. This review focuses on ghrelin's anti‐inflammatory and potential therapeutic effects in neurological, cardiovascular, respiratory, hepatic, gastrointestinal, and kidney disorders. Ghrelin significantly alleviates excessive inflammation and reduces damage to different target organs mainly by reducing the secretion of inflammatory cytokines, including interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α), and inhibiting the nuclear factor kappa‐B (NF‐κB) and NLRP3 inflammasome signaling pathways. Ghrelin also regulates inflammation and apoptosis through the p38 MAPK/c‐Jun N‐terminal kinase (JNK) signaling pathway; restores cerebral microvascular integrity, and attenuates vascular leakage. Ghrelin activates the phosphoInositide‐3 kinase (PI3K)/protein kinase B (Akt) pathway and inhibits inflammatory responses in cardiovascular diseases and acute kidney injury. Some studies show that ghrelin exacerbates colonic and intestinal manifestations of colitis. Interestingly, some inflammatory states, such as non‐alcoholic steatohepatitis, inflammatory bowel diseases, and chronic kidney disease, are often associated with high ghrelin levels. Thus, ghrelin may be a potential new therapeutic target for inflammation‐related diseases.
Performance of the Hypotension Prediction Index May Be Overestimated Due to Selection Bias
Authors: Enevoldsen Johannes , Vistisen Simon T.
Published: August 2022

The Hypotension Prediction Index is a proprietary prediction model incorporated into a commercially available intraoperative hemodynamic monitoring system. The Hypotension Prediction Index uses multiple features of the arterial blood pressure waveform to predict hypotension. The index publication introducing the Hypotension Prediction Index describes the selection of training and validation data. Although precise details of the Hypotension Prediction Index algorithm are proprietary, the authors describe a selection process whereby a mean arterial pressure (MAP) less than 75 mmHg will always predict hypotension. We hypothesize that the data selection process introduced a systematic bias that resulted in an overestimation of the current MAP value’s ability to predict future hypotension. Since current MAP is a predictive variable contributing to Hypotension Prediction Index, this exaggerated predictive performance likely also applies to the corresponding Hypotension Prediction Index value. Other existing validation studies appear similarly problematic, suggesting that additional validation work and, potentially, updates to the Hypotension Prediction Index model may be necessary.
“Ally Theater Is a Problem”
Authors: Haghiri-Vijeh Roya
Published: August 2022

In a 2021 research study, exploring the experiences of lesbian, gay, bisexual, two-spirit, trans, queer, intersex, and the “+” (LGBTQI+) migrants in health care in Canada, participants referred to the term “ally theater” in relation to their encounters with nurses. That is, the participants asserted that some nurses publicly demonstrate performative, or superficial, allyship regarding their identities. Using participants' experiences in health care as a metaphorical theater, this article presents a theoretical exploration of ally theater, and raises questions about professional practice claims of inclusivity and antiracism. The participants felt like deviant performers for not abiding by institutionalized centering of White hetero-cis-normative norms and thereby positioning racialized, LGBTQI+, and migrant as other.
Teenagers and Young Adults Who Are Deaf or Hard of Hearing: a Snapshot of Acculturation in High School and Post-Secondary Life
Authors: Moog Jean Sachar , Grantham Heather , Rudge Amanda M. , Reimer Casey K.
Published: August 2022

Objectives:

The current study investigates acculturation in a group of teenagers and young adults who are deaf or hard of hearing (DHH) and who were raised in an age of early identification, early intervention, advanced audiologic technology, and inclusive education.

Design:

The Deaf Acculturation Scale (Maxwell-McCaw & Zea 2011) was administered via online survey to 106 teenagers and young adults (mean ages = 16.87 and 24.65 years, respectively). All participants were alumni of an early childhood program for children who are DHH in the United States learning listening and spoken language skills.

Results:

The majority of the participants scored as hearing acculturated (79%), with 1% scoring as deaf acculturated, and 20% as bicultural. Teenagers and adults did not differ significantly on acculturation. Participants who identified as hearing acculturated were less likely to use sign language with their friends, at work, or with their families than those who identified as bicultural.

Conclusions:

These results are in contrast to acculturation patterns reported in other populations of young DHH adults, indicating the need to continue investigating the diversity in cultural values, beliefs, and practices of people who are DHH.