bluuebunny/crossref_metadata_2025 huggingface dataset:
How U.S. Health Policy Embraced Markets and Helped Wall Street Gentrify Medicine
Authors: BRIDGMAN PERKINS BARBARA
Published: September 2022

This article examines the financial industry’s critical role in retargeting U.S. health policy goals of improving peoples’ health in the 1960s to those of expanding institutional wealth in the 1970s. Government collaborated with finance to support not-for-profit hospitals’ use of debt to build services that augmented capital and operated like for-profit businesses. Certificate of Need, hospital rate review, and national health planning programs came to assess hospital performance in terms of capital formation, returns on investment, and bond ratings. The regulatory programs helped gentrify medicine by reinforcing selective investment in lucrative, high-tech services that market specialty procedures to affluent populations in place of disease control, primary care, and general acute care for all. Their actions laid the groundwork for the 1980s finance industry coup, which employed market ideology to dominate health policy at the expense of equality, effectiveness, and public health governance.
TheCuriosCarnival
Authors: Tan Marcus Cheng Chye
Published: September 2022

Theatricality in music performances is often regarded as extraneous, but avantgarde toy pianist Margaret Leng Tan exploits the intermediality between theatricality and musicality to demonstrate how theatrimusicality is imperative to the creation and reception of her music.Curios(2015) is one example in which the work’s structure of meaning and the experience of the carnivalesque are evoked through such a theatrimusical dramaturgy.
Playing with Knowledge
Authors: Seita Sophie
Published: September 2022

Seated between art and academia, the lecture performance is a hybrid and playful genre that questions the norms and forms of lectures. Often highly reflexive, discursive, and pedagogical, it draws attention to the structures of how knowledge is produced, distributed, and received. It stages and costumes knowledge; makes it wearable or movable.
What’s the Crowd Got to Do with It?
Authors: Jack Max
Published: September 2022

For a group of antifascist fans who support Eis Hockey Club Dynamo Berlin, street protest and ice hockey games are both sites of left-wing political intervention. Despite the team’s reputation in Germany as “The Nazi Club,” the group aims to cultivate politically minded crowd action and uplift the atmosphere in the arena in hopes of ridding Germany of representations of its authoritarian past.
Security, Social Policy, Agency and Work of the Courts in Relation to Ukrainian Internally Displaced Persons
Authors: Krakhmalova Kateryna
Published: September 2022

The following article is dedicated to the empirical case study from Ukraine and focuses on the work of Ukrainian courts resolving the cases of internally displaced persons in the realm of social policy. Based on interviews and secondary sources in terms of data, it explains the problem area of the legal regulations and administrative practices applicable to internally displaced Ukrainians in the sphere of social rights, and it analyses selected decisions of the courts in the cases brought by them, including the courts’ approaches, motivations and limitations, all while doing so from the combined perspective of security, law and internal migrants’ agency.
Environmental Warfare Tactics in Irregular Conflicts
Authors: Feuer Anna
Published: September 2022

This article considers how, and under what conditions, actors in irregular conflicts weaponize nature. When do insurgents and counterinsurgents pursue environmental degradation—ranging from limited and short-term damage to ecocidal violence—as a tactic of war? To what extent do we see variation in the frequency and form of environmental warfare? And when do conflict actors exercise restraint in their use of violence against the natural environment? Often, the intentional destruction of the natural landscape is difficult to explain by reference to operational strategy or tactical logic alone. Deliberate attacks on the natural landscape, the frequency with which these tactics are deployed, and the diverse forms they take are conditioned by context-specific incentives, constraints, and intervening variables. I identify six categories of incentives and constraints that influence the decision to engage in environmental destruction: strategic, tactical, political, ideological, cultural, and technological. Using suggestive evidence from multiple case studies, I theorize some possible interactions between incentives and constraints that help to explain variation in the form and frequency of environmental warfare tactics.
What are farmers' perceptions about farmland landbirds? A Galapagos Islands perspective
Authors: Geladi Ilke , Henry Pierre-Yves , Couenberg Paulina , Welsh Rick , Fessl Birgit
Published: September 2022

Conservation practices in agricultural landscapes can greatly mitigate biodiversity loss. However, agricultural landscapes are embedded in complex, social-ecological systems and therefore require a strong social-ecological approach for effective conservation measures. The Galapagos Islands are globally recognized for their high levels of biodiversity. Nevertheless, in recent years, Galapagos landbirds have suffered rapid declines, specifically in the agricultural zone. Our study is the first to examine the farmers’ perception of landbirds in the agricultural zone of Santa Cruz, Galapagos Islands. We conducted semi-structured interviews with 38 farmers to characterize the relationship between farmers and landbirds including how landbirds affect farmers and farmers’ perceptions of landbirds. The interviewed farmers managed a diverse array of farm types including coffee in agroforestry settings (23.7%), small-scale fruit and vegetable (60.5%) and livestock production (15.8%). We found that 86.9% of farmers had a positive or neutral perception of birds despite 52.6% of farmers finding finches bothersome. The most common techniques farmers employed to deter birds were putting out food and water, using nets to protect seedbeds and crops and using protective tubes around young plants. Our results suggest a positive potential for future conservation work targeted on farmland biodiversity. Future conservation projects should also address disservices and the mitigation of crop raiding by landbirds, the uninformed use of pesticides and other pest issues such as ants and rats.
Case‐Control Study on a Decade of Ground‐Based Magnetometers in California Reveals Modest Signal 24–72 hr Prior to Earthquakes
Authors: Heavlin William D. , Kappler Karl , Yang Lusann , Fan Minjie , Hickey Jason , Lemon James , MacLean Laura , Bleier Thomas , Riley Patrick , Schneider Daniel
Published: September 2022

Magnetic field changes as earthquake precursors have been the subject of numerous studies and some controversy. Infrequent large earthquakes and sparse magnetometer coverage along fault zones complicate statistical analysis. We present an analysis of ground‐based magnetic time‐series measurements before 19 earthquakes ≥M4.5 in California drawing from over 330,000 site‐days of measurement spanning a decade. To perform a fair existential test for electromagnetic antecedents we applied a pre‐specified statistical analysis with two key ideas. First, we combine signals from nearby (≤40 km) sites via spectral cross‐power, and then look for large spikes in frequency domain (0.016–25 Hz). The former is only possible with a dense set of sites running over a long period of time. In this statistical case‐control study we used the machine learning concept of rigorously separated train and test sets of earthquakes which were generated via a rule‐based query of the USGS earthquake catalog. Before each declustered earthquake, we constructed one period 24–72 hr before (the “precursor” or “p‐period”) and a series of seven equally‐sized preceding periods (“quiescent” or “q‐periods”). We distilled the data in each period to a frequency‐dependent feature—the 98th percentile of spectral cross power. We trained a model based on Linear Discriminant Analysis and applied the discriminator to the test set revealing a modest effect in the days leading up to an earthquake. While the observed effect size is not directly useful for earthquake prediction (long a scientific goal), it suggests a relationship which should be further investigated for a physical link.
Recent advances in acoustofluidic separation technology in biology
Authors: Fan Yanping , Wang Xuan , Ren Jiaqi , Lin Francis , Wu Jiandong
Published: September 2022

Acoustofluidic separation of cells and particles is an emerging technology that integrates acoustics and microfluidics. In the last decade, this technology has attracted significant attention due to its biocompatible, contactless, and label-free nature. It has been widely validated in the separation of cells and submicron bioparticles and shows great potential in different biological and biomedical applications. This review first introduces the theories and mechanisms of acoustofluidic separation. Then, various applications of this technology in the separation of biological particles such as cells, viruses, biomolecules, and exosomes are summarized. Finally, we discuss the challenges and future prospects of this field.
Effects of acute and chronic administration of trace amine-associated receptor 1 (TAAR1) ligands on in vivo excitability of central monoamine-secreting neurons in rats
Authors: Grinchii Daniil , Hoener Marius C. , Khoury Talah , Dekhtiarenko Roman , Nejati Bervanlou Reyhaneh , Jezova Daniela , Dremencov Eliyahu
Published: September 2022

Trace amine-associated receptor 1 (TAAR1) has been recently identified as a target for the future antidepressant, antipsychotic, and anti-addiction drugs. Full (e.g. RO5256390) and partial (e.g. RO5263397) TAAR1 agonists showed antidepressant-, antipsychotic- and anti-addiction-like behavioral effects in rodents and primates. Acute RO5256390 suppressed, and RO5263397 stimulated serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) and dopamine neurons of the ventral tegmental area (VTA) in brain slices, suggesting that the behavioral effects of TAAR1 ligands involve 5-HT and dopamine. For more comprehensive testing of this hypothesis, we examined acute and chronic effects of RO5256390 and RO5263397 on monoamine neurons in in vivo conditions. Excitability of 5-HT neurons of the DRN, noradrenaline neurons of the locus coeruleus (LC), and dopamine neurons of the VTA was assessed using single-unit electrophysiology in anesthetized rats. For acute experiments, RO5256390 and RO5263397 were administered intravenously; neuronal excitability after RO5256390 and RO5263397 administration was compared to the basal activity of the same neuron. For chronic experiments, RO5256390 was administered orally for fourteen days prior to electrophysiological assessments. The neuronal excitability in RO5256390-treated rats was compared to vehicle-treated controls. We found that acute RO5256390 inhibited 5-HT and dopamine neurons. This effect of RO5256390 was reversed by the subsequent and prevented by the earlier administration of RO5263397. Acute RO5256390 and RO5263397 did not alter the excitability of LC noradrenaline neurons in a statistically significant way. Chronic RO5256390 increased excitability of 5-HT neurons of the DRN and dopamine neurons of the VTA. In conclusion, the putative antidepressant and antipsychotic effects of TAAR1 ligands might be mediated, at least in part, via the modulation of excitability of central 5-HT and dopamine neurons.
Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: optimizing definition and management
Authors: Molloy Eleanor J. , Nakra Natasha , Gale Chris , Dimitriades Victoria R. , Lakshminrusimha Satyan
Published: September 2022

During the SARS-CoV-2-associated infection (COVID-19), pandemic initial reports suggested relative sparing of children inversely related to their age. Children and neonates have a decreased incidence of SARS-CoV-2 infection, and if infected they manifested a less severe phenotype, in part due to enhanced innate immune response. However, a multisystem inflammatory syndrome in children (MIS-C) or paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 emerged involving coronary artery aneurysms, cardiac dysfunction, and multiorgan inflammatory manifestations. MIS-C has many similarities to Kawasaki disease and other inflammatory conditions and may fit within a spectrum of inflammatory conditions based on immunological results. More recently neonates born to mothers with SARS-CoV-2 infection during pregnancy demonstrated evidence of a multisystem inflammatory syndrome with raised inflammatory markers and multiorgan, especially cardiac dysfunction that has been described as multisystem inflammatory syndrome in neonates (MIS-N). However, there is a variation in definitions and management algorithms for MIS-C and MIS-N. Further understanding of baseline immunological responses to allow stratification of patient groups and accurate diagnosis will aid prognostication, and inform optimal immunomodulatory therapies.

Impact

Multisystem inflammatory system in children and neonates (MIS-C and MIS-N) post COVID require an internationally recognized consensus definition and international datasets to improve management and plan future clinical trials.

This review incorporates the latest review of pathophysiology, clinical information, and management of MIS-C and MIS-N.

Further understanding of the pathophysiology of MIS-C and MIS-N will allow future targeted therapies to prevent and limit clinical sequelae.
JMJD family proteins in cancer and inflammation
Authors: Manni Wang , Jianxin Xue , Weiqi Hong , Siyuan Chen , Huashan Shi
Published: September 2022

The occurrence of cancer entails a series of genetic mutations that favor uncontrollable tumor growth. It is believed that various factors collectively contribute to cancer, and there is no one single explanation for tumorigenesis. Epigenetic changes such as the dysregulation of enzymes modifying DNA or histones are actively involved in oncogenesis and inflammatory response. The methylation of lysine residues on histone proteins represents a class of post-translational modifications. The human Jumonji C domain-containing (JMJD) protein family consists of more than 30 members. The JMJD proteins have long been identified with histone lysine demethylases (KDM) and histone arginine demethylases activities and thus could function as epigenetic modulators in physiological processes and diseases. Importantly, growing evidence has demonstrated the aberrant expression of JMJD proteins in cancer and inflammatory diseases, which might serve as an underlying mechanism for the initiation and progression of such diseases. Here, we discuss the role of key JMJD proteins in cancer and inflammation, including the intensively studied histone lysine demethylases, as well as the understudied group of JMJD members. In particular, we focused on epigenetic changes induced by each JMJD member and summarized recent research progress evaluating their therapeutic potential for the treatment of cancer and inflammatory diseases.
Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data
Authors: Wallert John , Boberg Julia , Kaldo Viktor , Mataix-Cols David , Flygare Oskar , Crowley James J. , Halvorsen Matthew , Ben Abdesslem Fehmi , Boman Magnus , Andersson Evelyn , Hentati Isacsson Nils , Ivanova Ekaterina , Rück Christian
Published: September 2022

This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (n = 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730,P = 0.084) but not vs XGBoost (D = 0.463,P = 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.
Exosomal protein angiopoietin-like 4 mediated radioresistance of lung cancer by inhibiting ferroptosis under hypoxic microenvironment
Authors: Zhang Yuhong , Liu Xinglong , Zeng Liang , Zhao Xinrui , Chen Qianping , Pan Yan , Bai Yang , Shao Chunlin , Zhang Jianghong
Published: September 2022

Background

Hypoxia-mediated radioresistance is a major reason for the adverse radiotherapy outcome of non-small cell lung cancer (NSCLC) in clinical, but the underlying molecular mechanisms are still obscure.

Methods

Cellular and exosomal ANGPTL4 proteins under different oxygen status were examined. Colony survival, lipid peroxidation and hallmark proteins were employed to determine the correlation between ferroptosis and radioresistance. Gene regulations, western blot and xenograft models were used to explore the underlying mechanisms of the role of ANGPTL4 in radioresistance.

Results

ANGPTL4 had a much higher level in hypoxic NSCLC cells compared to normoxic cells. Up- or down- regulation of ANGPTL4 positively interrelated to the radioresistance of NSCLC cells and xenograft tumours. GPX4-elicited ferroptosis suppression and lipid peroxidation decrease were authenticated to be involved in the hypoxia-induced radioresistance. ANGPTL4 encapsulated in the exosomes from hypoxic cells was absorbed by neighbouring normoxic cells, resulting in radioresistance of these bystander cells in a GPX4-dependent manner, which was diminished when ANGPTL4 was downregulated in the donor exosomes.

Conclusion

Hypoxia-induced ANGPTL4 rendered radioresistance of NSCLC through at least two parallel pathways of intracellular ANGPTL4 and exosomal ANGPTL4, suggesting that ANGPTL4 might applicable as a therapeutic target to improve the therapeutic efficacy of NSCLC.
GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL
Authors: De Falco Filomena , Rompietti Chiara , Sorcini Daniele , Esposito Angela , Scialdone Annarita , Baldoni Stefano , Del Papa Beatrice , Adamo Francesco Maria , Silva Barcelos Estevão Carlos , Dorillo Erica , Stella Arianna , Di Ianni Mauro , Screpanti Isabella , Sportoletti Paolo , Rosati Emanuela
Published: September 2022

NOTCH1 alterations have been associated with chronic lymphocytic leukemia (CLL), but the molecular mechanisms underlying NOTCH1 activation in CLL cells are not completely understood. Here, we show that GSK3β downregulates the constitutive levels of the active NOTCH1 intracellular domain (N1-ICD) in CLL cells. Indeed, GSK3β silencing by small interfering RNA increases N1-ICD levels, whereas expression of an active GSK3β mutant reduces them. Additionally, the GSK3β inhibitor SB216763 enhances N1-ICD stability at a concentration at which it also increases CLL cell viability. We also show that N1-ICD is physically associated with GSK3β in CLL cells. SB216763 reduces GSK3β/N1-ICD interactions and the levels of ubiquitinated N1-ICD, indicating a reduction in N1-ICD proteasomal degradation when GSK3β is less active. We then modulated the activity of two upstream regulators of GSK3β and examined the impact on N1-ICD levels and CLL cell viability. Specifically, we inhibited AKT that is a negative regulator of GSK3β and is constitutively active in CLL cells. Furthermore, we activated the protein phosphatase 2 A (PP2A) that is a positive regulator of GSK3β, and has an impaired activity in CLL. Results show that either AKT inhibition or PP2A activation reduce N1-ICD expression and CLL cell viability in vitro, through mechanisms mediated by GSK3β activity. Notably, for PP2A activation, we used the highly specific activator DT-061, that also reduces leukemic burden in peripheral blood, spleen and bone marrow in the Eµ-TCL1 adoptive transfer model of CLL, with a concomitant decrease in N1-ICD expression. Overall, we identify in GSK3β a key component of the network regulating N1-ICD stability in CLL, and in AKT and PP2A new druggable targets for disrupting NOTCH1 signaling with therapeutic potential.
Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis
Authors: Lau Poyee , Zhang Guanxiong , Zhao Shuang , Liang Long , Zhang Hailun , Zhou Guowei , Hung Mien-Chie , Chen Xiang , Liu Hong
Published: September 2022

Immune checkpoint blockade (ICB) exhibits considerable benefits in malignancies, but its overall response rate is limited. Previous studies have shown that sphingosine kinases (SPHKs) are critical in the tumor microenvironment (TME), but their role in immunotherapy is unclear. We performed integrative analyses including bioinformatics analysis, functional study, and clinical validation to investigate the role of SPHK1 in tumor immunity. Functionally, we demonstrated that the inhibition of SPHK1 significantly suppressed tumor growth by promoting antitumor immunity in immunocompetent melanoma mouse models and tumor T-cell cocultures. A mechanistic analysis revealed that MTA3 functions as the downstream target of SPHK1 in transcriptionally regulating tumor PD-L1. Preclinically, we found that anti-PD-1 monoclonal antibody (mAb) treatment significantly rescued tumor SPHK1 overexpression or tumor MTA3 overexpression-mediated immune evasion. Significantly, we identified SPHK1 and MTA3 as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients. Our findings revealed a novel role for SPHK1 in tumor evasion mediated by regulating the MTA3-PD-L1 axis, identified SPHK1 and MTA3 as predictors for assessing the efficacy of PD-1 mAb treatment, and provided a therapeutic possibility for the treatment of melanoma patients.
Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia
Authors: Isobe Tomoya , Takagi Masatoshi , Sato-Otsubo Aiko , Nishimura Akira , Nagae Genta , Yamagishi Chika , Tamura Moe , Tanaka Yosuke , Asada Shuhei , Takeda Reina , Tsuchiya Akiho , Wang Xiaonan , Yoshida Kenichi , Nannya Yasuhito , Ueno Hiroo , Akazawa Ryo , Kato Itaru , Mikami Takashi , Watanabe Kentaro , Sekiguchi Masahiro , Seki Masafumi , Kimura Shunsuke , Hiwatari Mitsuteru , Kato Motohiro , Fukuda Shiro , Tatsuno Kenji , Tsutsumi Shuichi , Kanai Akinori , Inaba Toshiya , Shiozawa Yusuke , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Kotecha Rishi S. , Cruickshank Mark N. , Ishikawa Fumihiko , Morio Tomohiro , Eguchi Mariko , Deguchi Takao , Kiyokawa Nobutaka , Arakawa Yuki , Koh Katsuyoshi , Aoki Yuki , Ishihara Takashi , Tomizawa Daisuke , Miyamura Takako , Ishii Eiichi , Mizutani Shuki , Wilson Nicola K. , Göttgens Berthold , Miyano Satoru , Kitamura Toshio , Goyama Susumu , Yokoyama Akihiko , Aburatani Hiroyuki , Ogawa Seishi , Takita Junko
Published: September 2022

KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.
Deep learning for twelve hour precipitation forecasts
Authors: Espeholt Lasse , Agrawal Shreya , Sønderby Casper , Kumar Manoj , Heek Jonathan , Bromberg Carla , Gazen Cenk , Carver Rob , Andrychowicz Marcin , Hickey Jason , Bell Aaron , Kalchbrenner Nal
Published: September 2022

Existing weather forecasting models are based on physics and use supercomputers to evolve the atmosphere into the future. Better physics-based forecasts require improved atmospheric models, which can be difficult to discover and develop, or increasing the resolution underlying the simulation, which can be computationally prohibitive. An emerging class of weather models based on neural networks overcome these limitations by learning the required transformations from data instead of relying on hand-coded physics and by running efficiently in parallel. Here we present a neural network capable of predicting precipitation at a high resolution up to 12 h ahead. The model predicts raw precipitation targets and outperforms for up to 12 h of lead time state-of-the-art physics-based models currently operating in the Continental United States. The results represent a substantial step towards validating the new class of neural weather models.
A compendium of 32,277 metagenome-assembled genomes and over 80 million genes from the early-life human gut microbiome
Authors: Zeng Shuqin , Patangia Dhrati , Almeida Alexandre , Zhou Zhemin , Mu Dezhi , Paul Ross R. , Stanton Catherine , Wang Shaopu
Published: September 2022

Age-specific reference genomes of the human gut microbiome can provide higher resolution for metagenomic analyses including taxonomic classification, strain-level genomic investigation and functional characterization. We present the Early-Life Gut Genomes (ELGG) catalog with 32,277 genomes representing 2172 species from 6122 fecal metagenomes collected from children under 3 years old spanning delivery mode, gestational age, feeding pattern, and geography. The ELGG substantially expanded the phylogenetic diversity by 38% over the isolate microbial genomes, and the genomic landscape of the early-life microbiome by increasing recruitment of metagenomic reads to 82.8%. More than 60% of the ELGG species lack an isolate representative. The conspecific genomes of the most abundant species from children differed in gene diversity and functions compared to adults. The ELGG genomes encode over 80 million protein sequences, forming the Early-Life Gut Proteins (ELGP) catalog with over four million protein clusters, 29.5% of which lacked functional annotations. The ELGG and ELGP references provided new insights into the early-life human gut microbiome and will facilitate studies to understand the development and mechanisms of disturbances of the human gut microbiome in early life.
Critical ionic transport across an oxygen-vacancy ordering transition
Authors: Lim Ji Soo , Nahm Ho-Hyun , Campanini Marco , Lee Jounghee , Kim Yong-Jin , Park Heung-Sik , Suh Jeonghun , Jung Jun , Yang Yongsoo , Koo Tae Yeong , Rossell Marta D. , Kim Yong-Hyun , Yang Chan-Ho
Published: September 2022

Phase transition points can be used to critically reduce the ionic migration activation energy, which is important for realizing high-performance electrolytes at low temperatures. Here, we demonstrate a route toward low-temperature thermionic conduction in solids, by exploiting the critically lowered activation energy associated with oxygen transport in Ca-substituted bismuth ferrite (Bi1-xCaxFeO3-δ) films. Our demonstration relies on the finding that a compositional phase transition occurs by varying Ca doping ratio across xCa ≃ 0.45 between two structural phases with oxygen-vacancy channel ordering along <100> or <110> crystal axis, respectively. Regardless of the atomic-scale irregularity in defect distribution at the doping ratio, the activation energy is largely suppressed to 0.43 eV, compared with ~0.9 eV measured in otherwise rigid phases. From first-principles calculations, we propose that the effective short-range attraction between two positively charged oxygen vacancies sharing lattice deformation not only forms the defect orders but also suppresses the activation energy through concerted hopping.
Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy
Authors: Sun Rong , Liu Mingzhu , Lu Jianping , Chu Binbin , Yang Yunmin , Song Bin , Wang Houyu , He Yao
Published: September 2022

Bacteria can bypass the blood-brain barrier (BBB), suggesting the possibility of employment of bacteria for combating central nervous system diseases. Herein, we develop a bacteria-based drug delivery system for glioblastoma (GBM) photothermal immunotherapy. The system, which we name as ‘Trojan bacteria’, consists of bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles. In an orthotopic GBM mouse model, we demonstrate that the intravenously injected bacteria bypass the BBB, targeting and penetrating GBM tissues. Upon 808 nm-laser irradiation, the photothermal effects produced by ICG allow the destruction of bacterial cells and the adjacent tumour cells. Furthermore, the bacterial debris as well as the tumour-associated antigens promote antitumor immune responses that prolong the survival of GBM-bearing mice. Moreover, we demonstrate the residual bacteria are effectively eliminated from the body, supporting the potential therapeutic use of this system.
Percolation transition prescribes protein size-specific barrier to passive transport through the nuclear pore complex
Authors: Winogradoff David , Chou Han-Yi , Maffeo Christopher , Aksimentiev Aleksei
Published: September 2022

Nuclear pore complexes (NPCs) control biomolecular transport in and out of the nucleus. Disordered nucleoporins in the complex’s pore form a permeation barrier, preventing unassisted transport of large biomolecules. Here, we combine coarse-grained simulations of experimentally derived NPC structures with a theoretical model to determine the microscopic mechanism of passive transport. Brute-force simulations of protein transport reveal telegraph-like behavior, where prolonged diffusion on one side of the NPC is interrupted by rapid crossings to the other. We rationalize this behavior using a theoretical model that reproduces the energetics and kinetics of permeation solely from statistics of transient voids within the disordered mesh. As the protein size increases, the mesh transforms from a soft to a hard barrier, enabling orders-of-magnitude reduction in permeation rate for proteins beyond the percolation size threshold. Our model enables exploration of alternative NPC architectures and sets the stage for uncovering molecular mechanisms of facilitated nuclear transport.
Determining the credibility of commitments in international climate policy
Authors: Victor David G. , Lumkowsky Marcel , Dannenberg Astrid
Published: September 2022

The Paris Agreement on climate change aims to improve cooperation by allowing governments to set their own commitments. Its success hinges on whether governments and investors believe those national commitments. To assess credibility, we interrogate a large novel sample of climate policy elites with decades of experience and well-placed to evaluate whether nations’ policy pledges are aligned with what they are politically and administratively able to implement. This expert assessment reveals that countries making the boldest pledges are also making the most credible pledges, contrasting theoretical warnings of a trade-off between ambition and credibility. We find that the quality of national political institutions is the largest explanator of the variation in credibility, and Europe’s credibility is exceptionally high. We also find that economic factors, such as the costs and benefits of controlling emissions, are statistically unimportant in explaining the credibility of national pledges to cooperate.
A multidevice and multimodal dataset for human energy expenditure estimation using wearable devices
Authors: Gashi Shkurta , Min Chulhong , Montanari Alessandro , Santini Silvia , Kawsar Fahim
Published: September 2022

We present a multi-device and multi-modal dataset, called WEEE, collected from 17 participants while they were performing different physical activities. WEEE contains: (1) sensor data collected using seven wearable devices placed on four body locations (head, ear, chest, and wrist); (2) respiratory data collected with an indirect calorimeter serving as ground-truth information; (3) demographics and body composition data (e.g., fat percentage); (4) intensity level and type of physical activities, along with their corresponding metabolic equivalent of task (MET) values; and (5) answers to questionnaires about participants’ physical activity level, diet, stress and sleep. Thanks to the diversity of sensors and body locations, we believe that the dataset will enable the development of novel human energy expenditure (EE) estimation techniques for a diverse set of application scenarios. EE refers to the amount of energy an individual uses to maintain body functions and as a result of physical activity. A reliable estimate of people’s EE thus enables computing systems to make inferences about users’ physical activity and help them promoting a healthier lifestyle.
Carbon Monitor Cities near-real-time daily estimates of CO2 emissions from 1500 cities worldwide
Authors: Huo Da , Huang Xiaoting , Dou Xinyu , Ciais Philippe , Li Yun , Deng Zhu , Wang Yilong , Cui Duo , Benkhelifa Fouzi , Sun Taochun , Zhu Biqing , Roest Geoffrey , Gurney Kevin R. , Ke Piyu , Guo Rui , Lu Chenxi , Lin Xiaojuan , Lovell Arminel , Appleby Kyra , DeCola Philip L. , Davis Steven J. , Liu Zhu
Published: September 2022

Building on near-real-time and spatially explicit estimates of daily carbon dioxide (CO2) emissions, here we present and analyze a new city-level dataset of fossil fuel and cement emissions, Carbon Monitor Cities, which provides daily estimates of emissions from January 2019 through December 2021 for 1500 cities in 46 countries, and disaggregates five sectors: power generation, residential (buildings), industry, ground transportation, and aviation. The goal of this dataset is to improve the timeliness and temporal resolution of city-level emission inventories and includes estimates for both functional urban areas and city administrative areas that are consistent with global and regional totals. Comparisons with other datasets (i.e. CEADs, MEIC, Vulcan, and CDP-ICLEI Track) were performed, and we estimate the overall annual uncertainty range to be ±21.7%. Carbon Monitor Cities is a near-real-time, city-level emission dataset that includes cities around the world, including the first estimates for many cities in low-income countries.
Identifying Datasets for Cross-Study Analysis in dbGaP using PhenX
Authors: Pan Huaqin , Bakalov Vesselina , Cox Lisa , Engle Michelle L. , Erickson Stephen W. , Feolo Michael , Guo Yuelong , Huggins Wayne , Hwang Stephen , Kimura Masato , Krzyzanowski Michelle , Levy Josh , Phillips Michael , Qin Ying , Williams David , Ramos Erin M. , Hamilton Carol M.
Published: September 2022

Identifying relevant studies and harmonizing datasets are major hurdles for data reuse. Common Data Elements (CDEs) can help identify comparable study datasets and reduce the burden of retrospective data harmonization, but they have not been required, historically. The collaborative team at PhenX and dbGaP developed an approach to use PhenX variables as a set of CDEs to link phenotypic data and identify comparable studies in dbGaP. Variables were identified as either comparable or related, based on the data collection mode used to harmonize data across mapped datasets. We further added a CDE data field in the dbGaP data submission packet to indicate use of PhenX and annotate linkages in the future. Some 13,653 dbGaP variables from 521 studies were linked through PhenX variable mapping. These variable linkages have been made accessible for browsing and searching in the repository through dbGaP CDE-faceted search filter and the PhenX variable search tool. New features in dbGaP and PhenX enable investigators to identify variable linkages among dbGaP studies and reveal opportunities for cross-study analysis.
Modulatory effect of Gracilaria gracilis on European seabass gut microbiota community and its functionality
Authors: Gonçalves Ana Teresa , Simões Marco , Costa Cátia , Passos Ricardo , Baptista Teresa
Published: September 2022

Seaweeds are an important source of nutrients and bioactive compounds and have a high potential as health boosters in aquaculture. This study evaluated the effect of dietary inclusion of Gracilaria gracilis biomass or its extract on the European seabass (Dicentrarchus labrax) gut microbial community. Juvenile fish were fed a commercial-like diet with 2.5% or 5% seaweed biomass or 0.35% seaweed extract for 47 days. The gut microbiome was assessed by 16S rRNA amplicon sequencing, and its diversity was not altered by the seaweed supplementation. However, a reduction in Proteobacteria abundance was observed. Random forest analysis highlighted the genera Photobacterium, Staphylococcus, Acinetobacter, Micrococcus and Sphingomonas, and their abundances were reduced when fish were fed diets with algae. SparCC correlation network analysis suggested several mutualistic and other antagonistic relationships that could be related to the predicted altered functions. These pathways were mainly related to the metabolism and biosynthesis of protective compounds such as ectoine and were upregulated in fish fed diets supplemented with algae. This study shows the beneficial potential of Gracilaria as a functional ingredient through the modulation of the complex microbial network towards fish health improvement.
Variations of follicular fluid extracellular vesicles miRNAs content in relation to development stage and season in buffalo
Authors: Capra Emanuele , Kosior Michal Andrzej , Cocchia Natascia , Lazzari Barbara , Del Prete Chiara , Longobardi Valentina , Pizzi Flavia , Stella Alessandra , Frigerio Roberto , Cretich Marina , Consiglio Anna Lange , Gasparrini Bianca
Published: September 2022

In buffalo (Bubalus bubalis) reproductive seasonality, causing cycles of milk production, is one of the major factors affecting farming profitability. Follicular fluid (FF) contains extracellular vesicles (EVs) playing an important role in modulating oocyte developmental competence and carrying microRNAs (miRNAs) essential for in vitro fertilization outcomes. The aim of this work was to characterize the FF-EVs-miRNA cargo of antral (An) and preovulatory (pO) follicles collected in the breeding (BS) and non-breeding (NBS) seasons, to unravel the molecular causes of the reduced oocyte competence recorded in buffalo during the NBS. In total, 1335 miRNAs (538 known Bos taurus miRNAs, 324 homologous to known miRNAs from other species and 473 new candidate miRNAs) were found. We identified 413 differentially expressed miRNAs (DE-miRNAs) (FDR < 0.05) between An and pO groups. A subset of the most significant DE-miRNAs between An and pO groups targets genes which function is related to the lipid and steroid metabolism, response to glucocorticoid and oestradiol stimulus. Comparison between BS and NBS showed 14 and 12 DE-miRNAs in An-FF-EVs and pO-FF-EVs, which regulate IL6 release and cellular adhesion, respectively. In conclusion, these results demonstrated that the miRNA cargo of buffalo FF-EVs varies in relation to both follicular development and season.
Detecting early safety signals of infliximab using machine learning algorithms in the Korea adverse event reporting system
Authors: Lee Jeong-Eun , Kim Ju Hwan , Bae Ji-Hwan , Song Inmyung , Shin Ju-Young
Published: September 2022

There has been a growing attention on using machine learning (ML) in pharmacovigilance. This study aimed to investigate the utility of supervised ML algorithms on timely detection of safety signals in the Korea Adverse Event Reporting System (KAERS), using infliximab as a case drug, between 2009 and 2018. Input data set for ML training was constructed based on the drug label information and spontaneous reports in the KAERS. Gold standard dataset containing known AEs was randomly divided into the training and test sets. Two supervised ML algorithms (gradient boosting machine [GBM], random forest [RF]) were fitted with hyperparameters tuned on the training set by using a fivefold validation. Then, we stratified the KAERS data by calendar year to create 10 cumulative yearly datasets, in which ML algorithms were applied to detect five pre-specified AEs of infliximab identified during post-marketing surveillance. Four AEs were detected by both GBM and RF in the first year they appeared in the KAERS and earlier than they were updated in the drug label of infliximab. We further applied our models to data retrieved from the US Food and Drug Administration Adverse Event Reporting System repository and found that they outperformed existing disproportionality methods. Both GBM and RF demonstrated reliable performance in detecting early safety signals and showed promise for applying such approaches to pharmacovigilance.
In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face
Authors: Pena Ana-Maria , Baldeweck Thérèse , Decencière Etienne , Koudoro Serge , Victorin Steeve , Raynaud Edouard , Ngo Blandine , Bastien Philippe , Brizion Sébastien , Tancrède-Bohin Emmanuelle
Published: September 2022

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals’ intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas—ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal–epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.
Prediction of maternal complications and neonatal outcome in dichorionic diamniotic twins with fetal weight discordancy measured by ultrasonography
Authors: Kim Hyun Mi , Cha Hyun-Hwa , Seong Won Joon , Lee Hye Jin , Kim Mi Ju
Published: September 2022

This study aimed to determine the relationship between estimated fetal weight discordance by ultrasonography and maternal and neonatal outcomes in dichorionic diamniotic twin pregnancies. We conducted a retrospective review of the medical records of 106 twin pregnancies delivered at a single tertiary center between January 2011 and February 2020. At 20–24 and 28–32 weeks of gestation, participants were divided into two groups: discordant twins with an estimated fetal weight difference of more than 20% and concordant twins with a weight difference of less than 20%. Maternal complications and neonatal outcomes were compared between the two groups. Although the incidences of preeclampsia and placenta previa were significantly higher in discordant twins measured between 20 and 24 weeks, no statistical significance was found in neonatal outcomes. Delivery times were earlier, and neonatal weights were lower in discordant twins measured between 28 and 32 weeks. Neonatal outcomes such as ventilator use and neurodevelopment were also significantly different. Discordance in estimated fetal weight measured using ultrasonography between 20 and 24 weeks can be a risk factor for maternal preeclampsia and placenta previa, whereas discordance at 28–32 weeks may predict poor neonatal outcomes.
The synthesis of novel thioderivative chalcones and their influence on NF-κB, STAT3 and NRF2 signaling pathways in colorectal cancer cells
Authors: Papierska Katarzyna , Krajka-Kuźniak Violetta , Kleszcz Robert , Stefański Tomasz , Kurczab Rafał , Kubicki Maciej
Published: September 2022

This study aimed to synthesize new thioderivative chalcones and analyze their impact on the NF-κB, STAT3, EGFR and Nrf2 signaling pathways in colorectal cancer cells. Among the studied compounds, derivatives 4 and 5 decreased the activation of NF-κB and the expression of the target gene COX-2. In the case of STAT3, we observed the inhibition of activation of this signaling pathway after influencing derivative 4. Increased activation of the Nrf2 signaling pathway was demonstrated for derivatives 5 and 7 in DLD-1 and HCT116 cells. The results of this study indicated that new chalcone derivatives, especially compounds 4, 5, and—to some degree—7, possess potential applications in the prevention of colorectal cancer.