bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing and type of adverse life events: Impact on substance use among high-risk adolescents
Authors: Zarchev Milan , Kamperman Astrid M. , El Marroun Hanan , Bloemendaal Anthony , Mulder Cornelis L. , Hoogendijk Witte J.G. , Grootendorst-van Mil Nina H.
Published: July 2023

A robust association has been reported between childhood adverse life events (ALEs) and risky substance use in adolescence. It remains unclear, however, what the impact of type and timing of these ALEs is. We investigated the association between ALEs and substance use in adolescents. ALEs were operationalized as broad (e.g., moving, parental divorce, family sickness) or physically threatening (physical and/or sexual abuse). First, we examined lifetime ALEs, followed by an investigation into their timing. The sample consisted of 909 adolescents (aged 12–18 years) from a cohort oversampled on high levels of emotional and behavioral problems. The primary caregiver indicated which ALEs each adolescent experienced across their lifetime. Adolescents self-reported on number and frequency of substances used. Poisson and ordinal regression models were used to model the associations. The associations between lifetime ALEs and a substance used were observed only for physical ALEs (incidence rate ratio 1.18 [1.03, 1.35], p = 0.02). When investigating timing, physical ALEs after the age of 12 predicted number of substances used (IRR 1.36 [1.13, 1.63], p < .001). Recent ALEs (occurring after age 12) seem to have considerable impact on substance use. Alcohol and drugs as a coping mechanism were considered a plausible explanation for the results.
‘They’re all individuals, none of them are on the same boat’: barriers to weight management in general practice from the rural nurse perspective
Authors: Norman Kimberley , Burrows Lisette , Chepulis Lynne , Mullins Hilde , Lawrenson Ross
Published: July 2023

Aim:

To explore nurses’ experiences with, and barriers to, obesity healthcare in rural general practice.

Background:

Obesity is a significant health risk worldwide, which can lead to many other physical and psychosocial health issues that contribute to a poor quality of life. Primary care is considered the most suitable context to deliver obesity management healthcare across the world, including New Zealand, which reportedly has 34% of all adults (and 51% Indigenous Māori) classed as obese. Nurses in primary care have a significant role in the multidisciplinary team and deliver obesity healthcare in general practice contexts. Yet, there is little focus on the nurse perspective of weight management, specifically in rural areas where medical staff and resources are limited, and obesity rates are high.

Methods:

This was a qualitative research design. Semi-structured interviews with 10 rural nurses from indigenous and non-indigenous health providers were analyzed guided by Braun and Clarke (2006) approach to thematic analysis.

Findings:

Three themes were identified: limitations of a nurse role; patient-level barriers; and cultural barriers. Nurses reported experiencing significant barriers to delivering effective weight management in their practice due to factors outside the scope of their practice such as patient-level factors, social determinants of health, rural locality restrictions, and limitations to their role. While this study highlights that practice nurses are versatile with an invaluable skill repertoire, it also demonstrates the near impossibility for rural nurses to meet their rural patient’s complex weight management needs, as there are many social determinants of health, sociocultural, and rural locality factors acting as barriers to effective weight management. Nurses experienced a lack of systemic support in the form of time, resources, funding, and effective weight management referral options. Future investigation should look to address the unique rural weight management healthcare needs that experience many barriers.
Learnability with PAC Semantics for Multi-agent Beliefs
Authors: MOCANU IONELA G. , BELLE VAISHAK , JUBA BRENDAN
Published: July 2023

The tension between deduction and induction is perhaps the most fundamental issue in areas such as philosophy, cognition, and artificial intelligence. In an influential paper,Valiantrecognized that the challenge of learning should be integrated with deduction. In particular, he proposed a semantics to capture the quality possessed by the output ofprobably approximately correct(PAC) learning algorithms when formulated in a logic. Although weaker than classical entailment, it allows for a powerful model-theoretic framework for answering queries. In this paper, we provide a new technical foundation to demonstrate PAC learning with multi-agent epistemic logics. To circumvent the negative results in the literature on the difficulty of robust learning with the PAC semantics, we consider so-called implicit learning where we are able to incorporate observations to the background theory in service of deciding the entailment of an epistemic query. We prove correctness of the learning procedure and discuss results on the sample complexity, that is how many observations we will need to provably assert that the query is entailed given a user-specified error bound. Finally, we investigate under what circumstances this algorithm can be made efficient. On the last point, given that reasoning in epistemic logics especially in multi-agent epistemic logics is PSPACE-complete, it might seem like there is no hope for this problem. We leverage some recent results on the so-calledRepresentation Theoremexplored for single-agent and multi-agent epistemic logics with theonly knowingoperator to reduce modal reasoning to propositional reasoning.
Herbicide resistance in Bromus spp.: a global review
Authors: Ribeiro Victor H. V. , Barroso Judit , Brunharo Caio A. C. G. , Mallory-Smith Carol
Published: July 2023

This review summarizes what is currently known about herbicide resistance in Bromus spp. worldwide. Additional information on the biology and genetics of Bromus spp. is provided to further the understanding of resistance evolution and dispersal of the different species. Cases of herbicide resistance have been confirmed in Bromus catharticus Vahl., Bromus commutatus Schrad. (syn.: Bromus racemosus L.), Bromus diandrus Roth, Bromus japonicus Thunb. (syn.: Bromus arvensis L.), Bromus madritensis L., Bromus rigidus Roth (syn.: Bromus diandrus Roth ssp. diandrus), Bromus rubens L., Bromus secalinus L., Bromus sterilis L., and Bromus tectorum L. in 11 countries. Bromus spp. populations have evolved cross- and multiple resistance to six herbicide sites of action: acetyl-coenzyme A carboxylase, acetolactate synthase, photosystem II, very-long-chain fatty-acid, 5-enolpyruvylshikimate-3-phosphate synthase, and 4-hydroxyphenylpyruvate dioxygenase inhibitors. Resistance mechanisms varied from target-site to non–target site or a combination of both. Bromus spp. are generally highly self-pollinated, but outcrossing can occur at low levels in some species. Bromus spp. have different ploidy levels, ranging from diploid (2n = 2x = 14) to duodecaploid (2n = 12x = 84). Herbicide resistance in Bromus spp. is a global issue, and the spread of herbicide-resistance alleles primarily occurs via seed-mediated gene flow. However, the transfer of herbicide-resistance alleles via pollen-mediated gene flow is possible.
Limb and cardiovascular event risk in type 1 and 2 diabetic patients with peripheral artery disease
Authors: Sykora Daniel , Firth Christine , Girardo Marlene , Tseng Andrew , Wennberg Paul , Liedl David , Shamoun Fadi
Published: July 2023

Summary: Background: Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that coexists with type 1 (T1) and 2 (T2) diabetes mellitus (DM). Little is known about comparative risk of LE and CVE in T1/T2 DM patients with PAD. Patients and methods: We queried our database of 40,144 patients ≥18 years old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated T1/T2 DM patients with PAD diagnosed by ankle brachial index (ABI; low [<1.0] or elevated [>1.4]) and retrieved demographics including glycated hemoglobin (HbA1c). Primary outcomes were LE (critical limb ischemia/vascular amputation) and CVE (myocardial infarction/ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for pertinent risk factors including age, hypertension, hyperlipidemia, smoking, and HbA1c. Results: Our study found 10,156 patients with PAD and DM (34% T1DM, 66% T2DM) with median follow-up time 34 mo (IQR 85 mo). T1DM patients were younger than T2DM (mean age 67 vs. 70 years), with higher median HbA1c (7.7 [IQR 1.9] vs. 6.7% [IQR 1.6]), and more prevalent hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use was equivocal. Elevated ABI was more common in T1DM (47 vs. 28%). LE occurred in 23% and CVE in 12% patients. LE risk was higher in T1 than T2 DM patients (HR 1.58 [95% CI 1.44, 1.73], p<0.0001), but CVE and all-cause mortality were equivocal. These observations were preserved across ABI and HbA1c subgroup analyses. Conclusions: PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for glycemic control and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed.
Prognostic impact of secondary versus de novo ontogeny in acute myeloid leukemia is accounted for by the European LeukemiaNet 2022 risk classification
Authors: Hochman Michael J. , Othus Megan , Hasserjian Robert P. , Ambinder Alex , Brunner Andrew , Percival Mary-Elizabeth M. , Hourigan Christopher S. , Swords Ronan , DeZern Amy E. , Estey Elihu H. , Karp Judith E.
Published: July 2023

Secondary AML (sAML), defined by either history of antecedent hematologic disease (AHD) or prior genotoxic therapy (tAML), is classically regarded as having worse prognosis than de novo disease (dnAML). Clinicians may infer a new AML diagnosis is secondary based on a history of antecedent blood count (ABC) abnormalities in the absence of known prior AHD, but whether abnormal ABCs are associated with worse outcomes is unclear. Secondary-type mutations have recently been incorporated into the European LeukemiaNet (ELN) 2022 guidelines as adverse-risk features, raising the question of whether clinical descriptors of ontogeny (i.e., de novo or secondary) are prognostically significant when accounting for genetic risk by ELN 2022. In a large multicenter cohort of patients (n = 734), we found that abnormal ABCs are not independently prognostic after adjusting for genetic characteristics in dnAML patients. Furthermore, history of AHD and tAML do not confer increased risk of death compared to dnAML on multivariate analysis, suggesting the prognostic impact of ontogeny is accounted for by disease genetics as stratified by ELN 2022 risk and TP53 mutation status. These findings emphasize the importance that disease genetics should play in risk stratification and clinical trial eligibility in AML.
Diversification during cross-kingdom microbial experimental evolution
Authors: Kovács Ákos T
Published: July 2023

Experimental evolution in a laboratory helps researchers to understand the genetic and phenotypic background of adaptation under a particular condition. Simultaneously, the simplified environment that represents certain aspects of a complex natural niche permits the dissection of relevant parameters behind the selection, including temperature, oxygen availability, nutrients, and biotic factors. The presence of other microorganisms or a host has a major influence on microbial evolution that often differs from the adaptation paths observed in response to abiotic conditions. In the current issue of the ISME Journal, Cosetta and colleagues reveal how cross-kingdom interaction representing the cheese microbiome succession promotes distinct evolution of the food- and animal-associated bacterium, Staphylococcus xylosus. The authors also identified a global regulator-dependent adaption that leads to evolved derivatives exhibiting reduced pigment production and colony morphologies in addition to altered differentiation phenotypes that potentially contribute to increased fitness.
CellDeathPred: a deep learning framework for ferroptosis and apoptosis prediction based on cell painting
Authors: Schorpp Kenji , Bessadok Alaa , Biibosunov Aidin , Rothenaigner Ina , Strasser Stefanie , Peng Tingying , Hadian Kamyar
Published: July 2023

Cell death, such as apoptosis and ferroptosis, play essential roles in the process of development, homeostasis, and pathogenesis of acute and chronic diseases. The increasing number of studies investigating cell death types in various diseases, particularly cancer and degenerative diseases, has raised hopes for their modulation in disease therapies. However, identifying the presence of a particular cell death type is not an obvious task, as it requires computationally intensive work and costly experimental assays. To address this challenge, we present CellDeathPred, a novel deep-learning framework that uses high-content imaging based on cell painting to distinguish cells undergoing ferroptosis or apoptosis from healthy cells. In particular, we incorporate a deep neural network that effectively embeds microscopic images into a representative and discriminative latent space, classifies the learned embedding into cell death modalities, and optimizes the whole learning using the supervised contrastive loss function. We assessed the efficacy of the proposed framework using cell painting microscopy data sets from human HT-1080 cells, where multiple inducers of ferroptosis and apoptosis were used to trigger cell death. Our model confidently separates ferroptotic and apoptotic cells from healthy controls, with an average accuracy of 95% on non-confocal data sets, supporting the capacity of the CellDeathPred framework for cell death discovery.
Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis
Authors: Lee Haena , Seo Pooreum , Teklay Salina , Yuguchi Emily , Benetta Elena Dalla , Werren John H. , Ferree Patrick M.
Published: July 2023

B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR’s own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp’s genome also seem to evade chromatin disruption by PSR, suggesting that PSR’s genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.
Fluorocarbonylation via palladium/phosphine synergistic catalysis
Authors: Zhao Mingxin , Chen Miao , Wang Tian , Yang Shuhan , Peng Qian , Tang Pingping
Published: July 2023

Despite the growing importance of fluorinated organic compounds in pharmaceuticals, agrochemicals, and materials science, the introduction of fluorine into organic molecules is still a challenge, and no catalytic fluorocarbonylation of aryl/alkyl boron compounds has been reported to date. Herein, we present the development of palladium and phosphine synergistic redox catalysis of fluorocarbonylation of potassium aryl/alkyl trifluoroborate. Trifluoromethyl arylsulfonate (TFMS), which was used as a trifluoromethoxylation reagent, an easily handled and bench-scale reagent, has been employed as an efficient source of COF2. The reaction operates under mild conditions with good to excellent yields and tolerates diverse complex scaffolds, which allows efficient late-stage fluorocarbonylation of marked small-molecule drugs. Mechanistically, the key intermediates of labile Brettphos-Pd(II)-OCF3 complex and difluoro-Brettphos were synthesized and spectroscopically characterized, including X-ray crystallography. A detailed reaction mechanism involving the synergistic redox catalytic cycles Pd(II)/(0) and P(III)/(V) was proposed, and multifunction of phosphine ligand was identified based on 19F NMR, isotope tracing, synthetic, and computational studies.
The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes
Authors: Djakovic Lara , Hennig Thomas , Reinisch Katharina , Milić Andrea , Whisnant Adam W. , Wolf Katharina , Weiß Elena , Haas Tobias , Grothey Arnhild , Jürges Christopher S. , Kluge Michael , Wolf Elmar , Erhard Florian , Friedel Caroline C. , Dölken Lars
Published: July 2023

Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.
Wireless electromagnetic neural stimulation patch with anisotropic guidance
Authors: Jensen Bjarke Nørrehvedde , Wang Yuting , Le Friec Alice , Nabavi Sadegh , Dong Mingdong , Seliktar Dror , Chen Menglin
Published: July 2023

The human body is limited in healing neurological damage caused by diseases or traumatic injuries. Bioelectricity is a quintessential characteristic of neural tissue and has a crucial role in physiological and neurological therapeutics development. Here, a wireless electromagnetic neural stimulation patch was created, combining stimulation through electromagnetic induction with physical guidance cues through structural anisotropy. The melt electrowritten biocompatible, bioresorbable polycaprolactone anisotropic structure with glancing angle deposition of 80 nm gold directly endowed incorporation of a wireless energy harvesting component in the patch, as an electromagnetic stimulation delivery system directly interfacing with neural cells. The biocompatibility and the capacity of the patch to deliver electromagnetic stimulation and promote neurite outgrowth was confirmed in vitro. Electromagnetically (60 mV, 40 kHz, 2 h/day, 5 days) stimulated PC12 cells showed 73.2% increased neurite outgrowth compared to PC12 cells grown without electromagnetic stimulation. The neural stimulation patch shows great potential for wireless electromagnetic stimulation for non-invasive neurological therapeutics advancement.
A data-driven Boolean model explains memory subsets and evolution in CD8+ T cell exhaustion
Authors: Ildefonso Geena V. , Finley Stacey D.
Published: July 2023

T cells play a key role in a variety of immune responses, including infection and cancer. Upon stimulation, naïve CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types; however, failure to clear antigens causes prolonged stimulation of CD8+ T cells, ultimately leading to T cell exhaustion (TCE). The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the underlying gene expression state changes are not completely understood. Here, we utilize a previously published data-driven Boolean model of gene regulatory interactions shown to mediate TCE. Our network analysis and modeling reveal the final gene expression states that correspond to TCE, along with the sequence of gene expression patterns that give rise to those final states. With a model that predicts the changes in gene expression that lead to TCE, we could evaluate strategies to inhibit the exhausted state. Overall, we demonstrate that a common pathway model of CD8+ T cell gene regulatory interactions can provide insights into the transcriptional changes underlying the evolution of cell states in TCE.
Experimentally determined traits shape bacterial community composition one and five years following wildfire
Authors: Johnson Dana B. , Woolet Jamie , Yedinak Kara M. , Whitman Thea
Published: July 2023

Wildfires represent major ecological disturbances, burning 2–3% of Earth’s terrestrial area each year with sometimes drastic effects above- and belowground. Soil bacteria offer an ideal, yet understudied system within which to explore fundamental principles of fire ecology. To understand how wildfires restructure soil bacterial communities and alter their functioning, we sought to translate aboveground fire ecology to belowground systems by determining which microbial traits are important post-fire and whether changes in bacterial communities affect carbon cycling. We employed an uncommon approach to assigning bacterial traits, by first running three laboratory experiments to directly determine which microbes survive fires, grow quickly post-fire and/or thrive in the post-fire environment, while tracking CO2 emissions. We then quantified the abundance of taxa assigned to each trait in a large field dataset of soils one and five years after wildfires in the boreal forest of northern Canada. We found that fast-growing bacteria rapidly dominate post-fire soils but return to pre-burn relative abundances by five years post-fire. Although both fire survival and affinity for the post-fire environment were statistically significant predictors of post-fire community composition, neither are particularly influential. Our results from the incubation trials indicate that soil carbon fluxes post-wildfire are not likely limited by microbial communities, suggesting strong functional resilience. From these findings, we offer a traits-based framework of bacterial responses to wildfire.
Drought re-routes soil microbial carbon metabolism towards emission of volatile metabolites in an artificial tropical rainforest
Authors: Honeker Linnea K. , Pugliese Giovanni , Ingrisch Johannes , Fudyma Jane , Gil-Loaiza Juliana , Carpenter Elizabeth , Singer Esther , Hildebrand Gina , Shi Lingling , Hoyt David W. , Chu Rosalie K. , Toyoda Jason , Krechmer Jordan E. , Claflin Megan S. , Ayala-Ortiz Christian , Freire-Zapata Viviana , Pfannerstill Eva Y. , Daber L. Erik , Meeran Kathiravan , Dippold Michaela A. , Kreuzwieser Jürgen , Williams Jonathan , Ladd S. Nemiah , Werner Christiane , Tfaily Malak M. , Meredith Laura K.
Published: July 2023

Drought impacts on microbial activity can alter soil carbon fate and lead to the loss of stored carbon to the atmosphere as CO2 and volatile organic compounds (VOCs). Here we examined drought impacts on carbon allocation by soil microbes in the Biosphere 2 artificial tropical rainforest by tracking 13C from position-specific 13C-pyruvate into CO2 and VOCs in parallel with multi-omics. During drought, efflux of 13C-enriched acetate, acetone and C4H6O2 (diacetyl) increased. These changes represent increased production and buildup of intermediate metabolites driven by decreased carbon cycling efficiency. Simultaneously,13C-CO2 efflux decreased, driven by a decrease in microbial activity. However, the microbial carbon allocation to energy gain relative to biosynthesis was unchanged, signifying maintained energy demand for biosynthesis of VOCs and other drought-stress-induced pathways. Overall, while carbon loss to the atmosphere via CO2 decreased during drought, carbon loss via efflux of VOCs increased, indicating microbially induced shifts in soil carbon fate.
Isothermal self-assembly of multicomponent and evolutive DNA nanostructures
Authors: Rossi-Gendron Caroline , El Fakih Farah , Bourdon Laura , Nakazawa Koyomi , Finkel Julie , Triomphe Nicolas , Chocron Léa , Endo Masayuki , Sugiyama Hiroshi , Bellot Gaëtan , Morel Mathieu , Rudiuk Sergii , Baigl Damien
Published: July 2023

Thermal annealing is usually needed to direct the assembly of multiple complementary DNA strands into desired entities. We show that, with a magnesium-free buffer containing NaCl, complex cocktails of DNA strands and proteins can self-assemble isothermally, at room or physiological temperature, into user-defined nanostructures, such as DNA origamis, single-stranded tile assemblies and nanogrids. In situ, time-resolved observation reveals that this self-assembly is thermodynamically controlled, proceeds through multiple folding pathways and leads to highly reconfigurable nanostructures. It allows a given system to self-select its most stable shape in a large pool of competitive DNA strands. Strikingly, upon the appearance of a new energy minimum, DNA origamis isothermally shift from one initially stable shape to a radically different one, by massive exchange of their constitutive staple strands. This method expands the repertoire of shapes and functions attainable by isothermal self-assembly and creates a basis for adaptive nanomachines and nanostructure discovery by evolution.
Critical slowing down near a magnetic quantum phase transition with fermionic breakdown
Authors: Yang Chia-Jung , Kliemt Kristin , Krellner Cornelius , Kroha Johann , Fiebig Manfred , Pal Shovon
Published: July 2023

When a system close to a continuous phase transition is subjected to perturbations, it takes an exceptionally long time to return to equilibrium. This critical slowing down is observed universally in the dynamics of bosonic excitations, such as order-parameter collective modes, but it is not generally expected to occur for fermionic excitations. Here using terahertz time-domain spectroscopy, we find evidence for fermionic critical slowing down in YbRh2Si2 close to a quantum phase transition between an antiferromagnetic phase and a heavy Fermi liquid. In the latter phase, the relevant quasiparticles are a quantum superposition of itinerant and localized electronic states with a strongly enhanced effective mass. As the temperature is lowered on the heavy-Fermi-liquid side of the transition, the heavy-fermion spectral weight builds up until the Kondo temperature TK ≈ 25 K, then decays towards the quantum phase transition and is, thereafter, followed by a logarithmic rise of the quasiparticle excitation rate below 10 K. A two-band heavy-Fermi-liquid theory shows that this is indicative of the fermionic critical slowing down associated with heavy-fermion breakdown near the quantum phase transition. The critical exponent of this breakdown could be used to classify this system among a wider family of fermionic quantum phase transitions that is yet to be fully explored.
Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial
Authors: Shah Manish A. , Shitara Kohei , Ajani Jaffer A. , Bang Yung-Jue , Enzinger Peter , Ilson David , Lordick Florian , Van Cutsem Eric , Gallego Plazas Javier , Huang Jing , Shen Lin , Oh Sang Cheul , Sunpaweravong Patrapim , Soo Hoo Hwoei Fen , Turk Haci Mehmet , Oh Mok , Park Jung Wook , Moran Diarmuid , Bhattacharya Pranob , Arozullah Ahsan , Xu Rui-Hua
Published: July 2023

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544–0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615–0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507.
A type-augmented knowledge graph embedding framework for knowledge graph completion
Authors: He Peng , Zhou Gang , Yao Yao , Wang Zhe , Yang Hao
Published: July 2023

Knowledge graphs (KGs) are of great importance to many artificial intelligence applications, but they usually suffer from the incomplete problem. Knowledge graph embedding (KGE), which aims to represent entities and relations in low-dimensional continuous vector spaces, has been proved to be a promising approach for KG completion. Traditional KGE methods only concentrate on structured triples, while paying less attention to the type information of entities. In fact, incorporating entity types into embedding learning could further improve the performance of KG completion. To this end, we propose a universal Type-augmented Knowledge graph Embedding framework (TaKE) which could utilize type features to enhance any traditional KGE models. TaKE automatically captures type features under no explicit type information supervision. And by learning different type representations of each entity, TaKE could distinguish the diversity of types specific to distinct relations. We also design a new type-constrained negative sampling strategy to construct more effective negative samples for the training process. Extensive experiments on four datasets from three real-world KGs (Freebase, WordNet and YAGO) demonstrate the merits of our proposed framework. In particular, combining TaKE with the recent tensor factorization KGE model SimplE can achieve state-of-the-art performance on the KG completion task.
Droplet duos on water display pairing, autonomous motion, and periodic eruption
Authors: Sumino Yutaka , Yamashita Ryo , Miyaji Kazuki , Ishikawa Hiroaki , Otani Maho , Yamamoto Daigo , Okita Erika , Okamoto Yasunao , Krafft Marie Pierre , Yoshikawa Kenichi , Shioi Akihisa
Published: July 2023

Under non-equilibrium conditions, liquid droplets dynamically couple with their milieu through the continuous flux of matter and energy, forming active systems capable of self-organizing functions reminiscent of those of living organisms. Among the various dynamic behaviors demonstrated by cells, the pairing of heterogeneous cell units is necessary to enable collective activity and cell fusion (to reprogram somatic cells). Furthermore, the cyclic occurrence of eruptive events such as necroptosis or explosive cell lysis is necessary to maintain cell functions. However, unlike the self-propulsion behavior of cells, cyclic cellular behavior involving pairing and eruption has not been successfully modeled using artificial systems. Here, we show that a simple droplet system based on quasi-immiscible hydrophobic oils (perfluorodecalin and decane) deposited on water, mimics such complex cellular dynamics. Perfluorodecalin and decane droplet duos form autonomously moving Janus or coaxial structures, depending on their volumes. Notably, the system with a coaxial structure demonstrates cyclic behavior, alternating between autonomous motion and eruption. Despite their complexity, the dynamic behaviors of the system are consistently explained in terms of the spreading properties of perfluorodecalin/decane duplex interfacial films.
Novel treatment of chalazion using light-guided-tip intense pulsed light
Authors: Zhu Yirui , Zhao Hanhe , Huang Xiaodan , Lin Lin , Huo Yanan , Qin Zhenwei , Lu Jiale , Jin Xiuming
Published: July 2023

We assessed the effectiveness of light-guided-tip intense pulsed light (IPL) with meibomian gland expression (MGX) in chalazion treatment. Ninety-five eyes with chalazion received a light-guided-tip IPL-MGX treatment (IPL-MGX group), and another 95 eyes with chalazion received incision with curettage treatment (Control group). Prior to IPL or incision, as well as 1 month after the final treatment, data were gathered pertaining to the lesion location and size, hyperemia, lesions regression or recurrence, and a comprehensive ophthalmic examination. The total size of the chalazia in the IPL-MGX group was significantly reduced after the final treatment, with an average resolution rate of 70.5%, which is comparable to excision surgery. A significant decrease in chalazion recurrence rate was apparent after treatment in the IPL-MGX group compared with control. Moreover, the IPL-MGX demonstrated significant advancements throughout noninvasive tear film breakup time (NIBUT) as well as meibum grade in comparison to baseline and those in the the Control group. The use of IPL-MGX was found to be an efficient therapy for reducing the size and recurring frequency of chalazia, as well as for improving the meibomian gland function. It may be considered as a first-line treatment for cases of primary or recurrent chalazia with inflammation.
Investigating structural and functional aspects of the brain’s criticality in stroke
Authors: Janarek Jakub , Drogosz Zbigniew , Grela Jacek , Ochab Jeremi K. , Oświęcimka Paweł
Published: July 2023

This paper addresses the question of the brain’s critical dynamics after an injury such as a stroke. It is hypothesized that the healthy brain operates near a phase transition (critical point), which provides optimal conditions for information transmission and responses to inputs. If structural damage could cause the critical point to disappear and thus make self-organized criticality unachievable, it would offer the theoretical explanation for the post-stroke impairment of brain function. In our contribution, however, we demonstrate using network models of the brain, that the dynamics remain critical even after a stroke. In cases where the average size of the second-largest cluster of active nodes, which is one of the commonly used indicators of criticality, shows an anomalous behavior, it results from the loss of integrity of the network, quantifiable within graph theory, and not from genuine non-critical dynamics. We propose a new simple model of an artificial stroke that explains this anomaly. The proposed interpretation of the results is confirmed by an analysis of real connectomes acquired from post-stroke patients and a control group. The results presented refer to neurobiological data; however, the conclusions reached apply to a broad class of complex systems that admit a critical state.
Terahertz sensing of reduced graphene oxide nanosheets using sub-wavelength dipole cavities
Authors: Sajeev Vaishnavi , Rane Shreeya , Ghosh Debal , Acharyya Nityananda , Roy Choudhury Palash , Mukherjee Arnab , Roy Chowdhury Dibakar
Published: July 2023

Because of extraordinary optoelectronic properties, two-dimensional (2D) materials are the subject of intense study in recent times. Hence, we investigate sub-wavelength dipole cavities (hole array) as a sensing platform for the detection of 2D reduced graphene oxide (r-GO) using terahertz time-domain spectroscopy (THz-TDS). The r-GO is obtained by reducing graphene oxide (GO) via Hummer's method. Its structural characteristics are verified using X-ray diffraction (XRD) and Raman spectroscopy. We also assessed the morphology and chemistry of r-GO nanosheets by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDAX), and Fourier Transformed Infrared (FTIR) spectroscopy. Further, we studied the surface plasmon resonance (SPR) characteristics of r-GO nanosheets hybridized dipole cavities using THz-TDS by varying the r-GO thickness on top of the dipole cavities, since these cavities are well known for sustaining strong SPRs. Based on these, we experimentally obtained a sensitivity of 12 GHz/µm for the porous r-GO film. Thus, a modification in SPR characteristics can be employed towards the identification and quantification of r-GO by suitably embedding it on an array of dipole cavities. Moreover, we have adopted a generic approach that can be expanded to sense other 2D materials like Boron Nitride (BN), phosphorene, MoS2, etc., leading to the development of novel THz nanophotonic sensing devices.
Attenuated but immunostimulatory Mycobacterium tuberculosis variant bovis strain Ravenel shows variation in T cell epitopes
Authors: Brenner Evan P. , Sreevatsan Srinand
Published: July 2023

Tuberculosis, caused by Mycobacterium tuberculosis complex (MTBC) organisms, affects a range of humans and animals globally. Mycobacterial pathogenesis involves manipulation of the host immune system, partially through antigen presentation. Epitope sequences across the MTBC are evolutionarily hyperconserved, suggesting their recognition is advantageous for the bacterium. Mycobacterium tuberculosis var. bovis (MBO) strain Ravenel is an isolate known to provoke a robust immune response in cattle, but typically fails to produce lesions and persist. Unlike attenuated MBO BCG strains that lack the critical RD1 genomic region, Ravenel is classic-type MBO structurally, suggesting genetic variation is responsible for defective pathogenesis. This work explores variation in epitope sequences in MBO Ravenel by whole genome sequencing, and contrasts such variation against a fully virulent clinical isolate, MBO strain 10-7428. Validated MTBC epitopes (n = 4818) from the Immune Epitope Database were compared to their sequences in MBO Ravenel and MBO 10-7428. Ravenel yielded 3 modified T cell epitopes, in genes rpfB, argC, and rpoA. These modifications were predicted to have little effect on protein stability. In contrast, T cells epitopes in 10-7428 were all WT. Considering T cell epitope hyperconservation across MTBC variants, these altered MBO Ravenel epitopes support their potential contribution to overall strain attenuation. The affected genes may provide clues on basic pathogenesis, and if so, be feasible targets for reverse vaccinology.
Optimized conditions for gene transduction into primary immune cells using viral vectors
Authors: Kim Yeongrin , Lee Da Yeon , Choi Ji U , Park Jin Song , Lee So Myoung , Kang Chung Hyo , Park Chi Hoon
Published: July 2023

Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising modality for anti-cancer treatment. Its efficacy is quite remarkable in hematological tumors. Owing to their excellent clinical results, gene- modified cell therapies, including T cells, natural killer (NK) cells, and macrophages, are being actively studied in both academia and industry. However, the protocol to make CAR immune cells is too complicated, so it is still unclear how to efficiently produce the potent CAR immune cells. To manufacture effective CAR immune cells, we need to be aware of not only how to obtain highly infective viral particles, but also how to transduce CAR genes into immune cells. In this paper, we provide detailed information on spinoculation, which is one of the best known protocols to transduce genes into immune cells, in a methodological view. Our data indicate that gene transduction is significantly dependent on speed and duration of centrifugation, concentration and number of viral particles, the concentration of polybrene, and number of infected immune cells. In addition, we investigated on the optimal polyethylene glycol (PEG) solution to concentrate the viral supernatant and the optimized DNA ratios transfected into 293T cells to produce high titer of viral particles. This study provides useful information for practical production of the gene-modified immune cells using viral vectors.
Reduced Southern Ocean warming enhances global skill and signal-to-noise in an eddy-resolving decadal prediction system
Authors: Yeager Stephen G. , Chang Ping , Danabasoglu Gokhan , Rosenbloom Nan , Zhang Qiuying , Castruccio Fred S. , Gopal Abishek , Cameron Rencurrel M. , Simpson Isla R.
Published: July 2023

The impact of increased model horizontal resolution on climate prediction performance is examined by comparing results from low-resolution (LR) and high-resolution (HR) decadal prediction simulations conducted with the Community Earth System Model (CESM). There is general improvement in global skill and signal-to-noise characteristics, with particularly noteworthy improvements in the eastern tropical Pacific, when resolution is increased from order 1° in all components to order 0.1°/0.25° in the ocean/atmosphere. A key advance in the ocean eddy-resolving HR system is the reduction of unrealistic warming in the Southern Ocean (SO) which we hypothesize has global ramifications through its impacts on tropical Pacific multidecadal variability. The results suggest that accurate representation of SO processes is critical for improving decadal climate predictions globally and for addressing longstanding issues with coupled climate model simulations of recent Earth system change.
A gender specific risk assessment of coronary heart disease based on physical examination data
Authors: Yang Hui , Luo Ya-Mei , Ma Cai-Yi , Zhang Tian-Yu , Zhou Tao , Ren Xiao-Lei , He Xiao-Lin , Deng Ke-Jun , Yan Dan , Tang Hua , Lin Hao
Published: July 2023

Large-scale screening for the risk of coronary heart disease (CHD) is crucial for its prevention and management. Physical examination data has the advantages of wide coverage, large capacity, and easy collection. Therefore, here we report a gender-specific cascading system for risk assessment of CHD based on physical examination data. The dataset consists of 39,538 CHD patients and 640,465 healthy individuals from the Luzhou Health Commission in Sichuan, China. Fifty physical examination characteristics were considered, and after feature screening, ten risk factors were identified. To facilitate large-scale CHD risk screening, a CHD risk model was developed using a fully connected network (FCN). For males, the model achieves AUCs of 0.8671 and 0.8659, respectively on the independent test set and the external validation set. For females, the AUCs of the model are 0.8991 and 0.9006, respectively on the independent test set and the external validation set. Furthermore, to enhance the convenience and flexibility of the model in clinical and real-life scenarios, we established a CHD risk scorecard base on logistic regression (LR). The results show that, for both males and females, the AUCs of the scorecard on the independent test set and the external verification set are only slightly lower (<0.05) than those of the corresponding prediction model, indicating that the scorecard construction does not result in a significant loss of information. To promote CHD personal lifestyle management, an online CHD risk assessment system has been established, which can be freely accessed at http://lin-group.cn/server/CHD/index.html.
Quantifying timber illegality risk in the Brazilian forest frontier
Authors: Franca Caroline S. S. , Persson U. Martin , Carvalho Tomás , Lentini Marco
Published: July 2023

Illegal logging remains widespread across the tropics, leading to extensive forest degradation and trade in illegal timber products. By adapting environmentally extended input–output modelling to timber originating from Brazilian native forests, we demonstrate how distinct illegality risks can be mapped and quantified at species-level across the supply chain. We focus on high-value ipê hardwood from the Amazon state of Pará, a leading producer of timber and contested forest frontier. Data on logging permits and state- and national-level Document of Forest Origin licences are used to estimate illegality risks due to missing or invalid logging permits, overstated ipê yields or discrepancies resulting from missing inflows of legal timber. We find that less than a quarter of all ipê entering supply chains between 2009 and 2019 is risk-free and highlight diversified strategies for the laundering of illegal timber across geographies. While legality does not ensure sustainability, this information can be leveraged to this end by supporting improved implementation and enforcement of forest regulations.
Algorithmic fairness and bias mitigation for clinical machine learning with deep reinforcement learning
Authors: Yang Jenny , Soltan Andrew A. S. , Eyre David W. , Clifton David A.
Published: July 2023

As models based on machine learning continue to be developed for healthcare applications, greater effort is needed to ensure that these technologies do not reflect or exacerbate any unwanted or discriminatory biases that may be present in the data. Here we introduce a reinforcement learning framework capable of mitigating biases that may have been acquired during data collection. In particular, we evaluated our model for the task of rapidly predicting COVID-19 for patients presenting to hospital emergency departments and aimed to mitigate any site (hospital)-specific and ethnicity-based biases present in the data. Using a specialized reward function and training procedure, we show that our method achieves clinically effective screening performances, while significantly improving outcome fairness compared with current benchmarks and state-of-the-art machine learning methods. We performed external validation across three independent hospitals, and additionally tested our method on a patient intensive care unit discharge status task, demonstrating model generalizability.