bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiographic tool to detect pulmonary arteriovenous malformations in single ventricle physiology
Authors: Spurgin Stephen B. , Arar Yousef M. , Zellers Thomas M. , Wang Jijia , Madsen Nicolas L. , Veeram Reddy Surendranath R. , Cleaver Ondine , Divekar Abhay A.
Published: May 2024

Objective:

Individuals with single ventricle physiology who are palliated with superior cavopulmonary anastomosis (Glenn surgery) may develop pulmonary arteriovenous malformations. The traditional tools for pulmonary arteriovenous malformation diagnosis are often of limited diagnostic utility in this patient population. We sought to measure the pulmonary capillary transit time to determine its value as a tool to identify pulmonary arteriovenous malformations in patients with single ventricle physiology.

Methods:

We defined the angiographic pulmonary capillary transit time as the number of cardiac cycles required for transit of contrast from the distal pulmonary arteries to the pulmonary veins. Patients were retrospectively recruited from a single quaternary North American paediatric centre, and angiographic and clinical data were reviewed. Pulmonary capillary transit time was calculated in 20 control patients and compared to 20 single ventricle patients at the pre-Glenn, Glenn, and Fontan surgical stages (which were compared with a linear-mixed model). Correlation (Pearson) between pulmonary capillary transit time and haemodynamic and injection parameters was assessed using angiograms from 84 Glenn patients. Five independent observers calculated pulmonary capillary transit time to measure reproducibility (intraclass correlation coefficient).

Results:

Mean pulmonary capillary transit time was 3.3 cardiac cycles in the control population, and 3.5, 2.4, and 3.5 in the pre-Glenn, Glenn, and Fontan stages, respectively. Pulmonary capillary transit time in the Glenn population did not correlate with injection conditions. Intraclass correlation coefficient was 0.87.

Conclusions:

Pulmonary angiography can be used to calculate the pulmonary capillary transit time, which is reproducible between observers. Pulmonary capillary transit time accelerates in the Glenn stage, correlating with absence of direct hepatopulmonary venous flow.
The BIALL Salary Survey 2023
Authors: Christmas Julie , Mazer Claire ,   CB Resourcing
Published: May 2024

For the vast majority of us salary is one of the key reasons we work. With bills to pay and mouths to feed we want to know we are being fairly compensated for the jobs we do. One way to check this is to use the BIALL Annual Salary Survey which considers not only salaries but also working conditions and benefits, offering a comparison to similar organisations and roles. In this article Julie Christmas, Claire Mazer and the team from CB Resourcing highlight some of the findings from the 2023 survey and consider the reasons behind these.
The Redox State of the Asthenospheric Mantle and the Onset of Melting Beneath Mid‐Ocean Ridges
Authors: Zhang Fangyi , Lai Shaocong , Stagno Vincenzo , Chen Lihui , Zhang Chao , Zhu Renzhi , Zhu Yu , Wang Xiaojun , Qin Jiangfeng , Wang Jixin
Published: May 2024

The redox state of the convective asthenospheric mantle governs the speciation of volatile elements such as carbon and, therefore, influences the depth at which (redox) melting can occur, with implications for seismic signals. Geophysical observations suggest the potential presence of carbonatite melts at a depth of 200–250 km. However, thermodynamic models indicate that the onset of (redox) melting would occur at 100–150 km for a mantle with 3%–4% of Fe3+/∑Fe. Here, we present a new oxybarometer that is based on the V/Sc exchange coefficient between olivine and the melt, which is insensitive to surficial alteration, volatile degassing, electron exchange reactions and fractional crystallization. By applying this method to primary mid‐ocean ridge basalts (MORBs) from Southwest Indian Ridge and East Pacific Rise, we demonstrate that the average oxygen fugacity (fo2) of MORBs corrected for the depth of formation is 0.78 ± 0.26 (1σ) log units above the fayalite‐magnetite‐quartz (FMQ) buffer, which is slightly more oxidized than previously estimated (near FMQ buffer). Our findings indicate that the convective asthenospheric mantle exhibits higher oxygen fugacity than the continental lithospheric mantle. Along an adiabat, carbonatitic melts can form from a CO2‐bearing source at a depth of 200–250 km, explaining the asthenospheric mantle's electrical conductivity and seismic velocity anomaly.
Elastic Stress Coupling Between Supraglacial Lakes
Authors: Stevens Laura A. , Das Sarah B. , Behn Mark D. , McGuire Jeffrey J. , Lai Ching‐Yao , Joughin Ian , Larochelle Stacy , Nettles Meredith
Published: May 2024

Supraglacial lakes have been observed to drain within hours of each other, leading to the hypothesis that stress transmission following one drainage may be sufficient to induce hydro‐fracture‐driven drainages of other nearby lakes. However, available observations characterizing drainage‐induced stress perturbations have been insufficient to evaluate this hypothesis. Here, we use ice‐sheet surface‐displacement observations from a dense global positioning system array deployed in the Greenland Ice Sheet ablation zone to investigate elastic stress transmission between three neighboring supraglacial lake basins. We find that drainage of a central lake can place neighboring basins in either tensional or compressional stress relative to their hydro‐fracture scarp orientations, either promoting or inhibiting hydro‐fracture initiation beneath those lakes. For two lakes located within our array that drain close in time, we identify tensional surface stresses caused by ice‐sheet uplift due to basal‐cavity opening as the physical explanation for these lakes' temporally clustered hydro‐fracture‐driven drainages and frequent triggering behavior. However, lake‐drainage‐induced stresses in the up‐flowline direction remain low beyond the margins of the drained lakes. This short stress‐coupling length scale is consistent with idealized lake‐drainage scenarios for a range of lake volumes and ice‐sheet thicknesses. Thus, on elastic timescales, our observations and idealized‐model results support a stress‐transmission hypothesis for inducing hydro‐fracture‐driven drainage of lakes located within the region of basal cavity opening produced by the initial drainage, but refute this hypothesis for distal lakes.
Holocene Variability of the Atlantic Multidecadal Oscillation and the Pacific Decadal Oscillation Inferred From Chinese Speleothem δ18O Records
Authors: Fan Haowen , Hu Zunyu , Liu Yuhui , Wang Mengyu , Hu Chaoyong
Published: May 2024

The current reconstructions of the Atlantic Multidecadal Oscillation (AMO) and Pacific Decadal Oscillation (PDO) primarily rely on marine sediment proxies. However, the limited resolution of these records makes it difficult to precisely understand the short‐term dynamics of the PDO and AMO, and consequently, their influence on global climate. This study unveils two new Holocene reconstructions of AMO and PDO derived from a large‐scale compilation of speleothem isotope records (δ18Os) from Chinese monsoon region, in which spatial patterns of summer rainfall are generally accepted as good indicators of internal variability. Principal component analysis applied to Chinese δ18Os records identifies the first principal component as representative of Holocene Asian monsoon (AM) variation. This data‐driven approach reveals a significant shift in hydroclimatic conditions after 8.2 ka, potentially providing valuable insights into the underlying forcing mechanisms driving these changes. The remanent components, which show spatial rainfall patterns, are effectively validated through independent records of AMO and PDO derived from the previous paleo‐proxy based reconstructions and model simulations. The present reconstructions suggest a significantly enhanced stability of the AMO and PDO in the middle Holocene, which may explain the concurrent more stable and optimum climate observed in the AM region. These findings also imply that the Holocene AM intensity recorded in Chinese cave records is largely controlled by external forcing, whereas the regionally heterogenous rainfall is regulated by internal variability. The successful attempt on the Holocene AMO and PDO reconstructions indicates an effective isolation between different modes of climate variability from paleoclimate records.
Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment
Authors: Oquendo Maria A. , Galfalvy Hanga C. , Choo Tse-Hwei , Herzog Sarah , Burke Ainsley K. , Sublette M. Elizabeth , Mann J. John , Stanley Barbara H.
Published: May 2024

Decedents with no known mental disorder comprise 5–40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs’ and patients’ SI score change from the previous epoch’s SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs’ SI was less pronounced than MDD patients’, but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, “decreased wish to live”). However, passive SI (viz, “desire for death”), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.
The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review
Authors: Vakilpour Azin , Amini-Salehi Ehsan , Soltani Moghadam Arman , Keivanlou Mohammad-Hossein , Letafatkar Negin , Habibi Arman , Hashemi Mohammad , Eslami Negar , Zare Reza , Norouzi Naeim , Delam Hamed , Joukar Farahnaz , Mansour-Ghanaei Fariborz , Hassanipour Soheil , Samethadka Nayak Sandeep
Published: May 2024

Background

Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action.

Methods

A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed.

Results

Gut microbial therapy significantly decreased HOMA-IR (ES: −0.41; 95%CI: −0.52, −0.31; P < 0.001) and FI (ES: −0.59; 95%CI: −0.77, −0.41; P < 0.001). However, no significant effect was observed on FBS (ES: −0.17; 95%CI: −0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics.

Conclusion

Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.
Epithelial−mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer
Authors: Jeong Hyein , Koh Jaemoon , Kim Sehui , Song Seung Geun , Lee Soo Hyun , Jeon Youngjoo , Lee Chul-Hwan , Keam Bhumsuk , Lee Se-Hoon , Chung Doo Hyun , Jeon Yoon Kyung
Published: May 2024

Background

We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial−mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy.

Methods

PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed.

Results

RNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-β (TGFβ). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFβ production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration.

Conclusions

Tumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC.
Comprehensive genomic and transcriptomic characterization of high-grade gastro-entero-pancreatic neoplasms
Authors: Angerilli Valentina , Sabella Giovanna , Simbolo Michele , Lagano Vincenzo , Centonze Giovanni , Gentili Marco , Mangogna Alessandro , Coppa Jorgelina , Munari Giada , Businello Gianluca , Borga Chiara , Schiavi Francesca , Pusceddu Sara , Leporati Rita , Oldani Simone , Fassan Matteo , Milione Massimo
Published: May 2024

Background

High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55).

Methods

We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1.

Results

Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 (p = 0.02) mutations, while both NECs groups were enriched in TP53 (p = 0.001), APC (p = 0.002) and KRAS (p = 0.02) mutations and tumors with TMB ≥ 10 muts/Mb (p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs ≥55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4+ and CD8+ T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival.

Conclusions

This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs ≥55%, and provided molecular findings with prognostic and potentially predictive value.
Consensus-building conversation leads to neural alignment
Authors: Sievers Beau , Welker Christopher , Hasson Uri , Kleinbaum Adam M. , Wheatley Thalia
Published: May 2024

Conversation is a primary means of social influence, but its effects on brain activity remain unknown. Previous work on conversation and social influence has emphasized public compliance, largely setting private beliefs aside. Here, we show that consensus-building conversation aligns future brain activity within groups, with alignment persisting through novel experiences participants did not discuss. Participants watched ambiguous movie clips during fMRI scanning, then conversed in groups with the goal of coming to a consensus about each clip’s narrative. After conversation, participants’ brains were scanned while viewing the clips again, along with novel clips from the same movies. Groups that reached consensus showed greater similarity of brain activity after conversation. Participants perceived as having high social status spoke more and signaled disbelief in others, and their groups had unequal turn-taking and lower neural alignment. By contrast, participants with central positions in their real-world social networks encouraged others to speak, facilitating greater group neural alignment. Socially central participants were also more likely to become neurally aligned to others in their groups.
Spin-orbit-splitting-driven nonlinear Hall effect in NbIrTe4
Authors: Lee Ji-Eun , Wang Aifeng , Chen Shuzhang , Kwon Minseong , Hwang Jinwoong , Cho Minhyun , Son Ki-Hoon , Han Dong-Soo , Choi Jun Woo , Kim Young Duck , Mo Sung-Kwan , Petrovic Cedomir , Hwang Choongyu , Park Se Young , Jang Chaun , Ryu Hyejin
Published: May 2024

The Berry curvature dipole (BCD) serves as a one of the fundamental contributors to emergence of the nonlinear Hall effect (NLHE). Despite intense interest due to its potential for new technologies reaching beyond the quantum efficiency limit, the interplay between BCD and NLHE has been barely understood yet in the absence of a systematic study on the electronic band structure. Here, we report NLHE realized in NbIrTe4 that persists above room temperature coupled with a sign change in the Hall conductivity at 150 K. First-principles calculations combined with angle-resolved photoemission spectroscopy (ARPES) measurements show that BCD tuned by the partial occupancy of spin-orbit split bands via temperature is responsible for the temperature-dependent NLHE. Our findings highlight the correlation between BCD and the electronic band structure, providing a viable route to create and engineer the non-trivial Hall effect by tuning the geometric properties of quasiparticles in transition-metal chalcogen compounds.
Nested non-covalent interactions expand the functions of supramolecular polymer networks
Authors: Lundberg David J. , Brown Christopher M. , Bobylev Eduard O. , Oldenhuis Nathan J. , Alfaraj Yasmeen S. , Zhao Julia , Kevlishvili Ilia , Kulik Heather J. , Johnson Jeremiah A.
Published: May 2024

Supramolecular polymer networks contain non-covalent cross-links that enable access to broadly tunable mechanical properties and stimuli-responsive behaviors; the incorporation of multiple unique non-covalent cross-links within such materials further expands their mechanical responses and functionality. To date, however, the design of such materials has been accomplished through discrete combinations of distinct interaction types in series, limiting materials design logic. Here we introduce the concept of leveraging “nested” supramolecular crosslinks, wherein two distinct types of non-covalent interactions exist in parallel, to control bulk material functions. To demonstrate this concept, we use polymer-linked Pd2L4 metal–organic cage (polyMOC) gels that form hollow metal–organic cage junctions through metal–ligand coordination and can exhibit well-defined host-guest binding within their cavity. In these “nested” supramolecular network junctions, the thermodynamics of host-guest interactions within the junctions affect the metal–ligand interactions that form those junctions, ultimately translating to substantial guest-dependent changes in bulk material properties that could not be achieved in traditional supramolecular networks with multiple interactions in series.
Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Authors: Lauer Simon M. , Reepmeyer Maren , Berendes Ole , Klepacki Dorota , Gasse Jakob , Gabrielli Sara , Grubmüller Helmut , Bock Lars V. , Krizsan Andor , Nikolay Rainer , Spahn Christian M. T. , Hoffmann Ralf
Published: May 2024

Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis by binding to the polypeptide exit tunnel (PET) near the peptidyl transferase center. Api137, an optimized derivative of honeybee PrAMP apidaecin, inhibits protein expression by trapping release factors (RFs), which interact with stop codons on ribosomes to terminate translation. This study uses cryo-EM, functional assays and molecular dynamic (MD) simulations to show that Api137 additionally occupies a second binding site near the exit of the PET and can repress translation independently of RF-trapping. Api88, a C-terminally amidated (-CONH2) analog of Api137 (-COOH), binds to the same sites, occupies a third binding pocket and interferes with the translation process presumably without RF-trapping. In conclusion, apidaecin-derived PrAMPs inhibit bacterial ribosomes by multimodal mechanisms caused by minor structural changes and thus represent a promising pool for drug development efforts.
An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries
Authors: Petersen Brian M. , Kirby Monica B. , Chrispens Karson M. , Irvin Olivia M. , Strawn Isabell K. , Haas Cyrus M. , Walker Alexis M. , Baumer Zachary T. , Ulmer Sophia A. , Ayala Edgardo , Rhodes Emily R. , Guthmiller Jenna J. , Steiner Paul J. , Whitehead Timothy A.
Published: May 2024

Antibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition. In part, this is because limited experimental platforms exist for assessing quantitative and simultaneous sequence-function relationships for multiple antibodies. Here we present MAGMA-seq, an integrated technology that combines multiple antigens and multiple antibodies and determines quantitative biophysical parameters using deep sequencing. We demonstrate MAGMA-seq on two pooled libraries comprising mutants of nine different human antibodies spanning light chain gene usage, CDR H3 length, and antigenic targets. We demonstrate the comprehensive mapping of potential antibody development pathways, sequence-binding relationships for multiple antibodies simultaneously, and identification of paratope sequence determinants for binding recognition for broadly neutralizing antibodies (bnAbs). MAGMA-seq enables rapid and scalable antibody engineering of multiple lead candidates because it can measure binding for mutants of many given parental antibodies in a single experiment.
Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data
Authors: Su Yaqi , Yu Zhejian , Jin Siqian , Ai Zhipeng , Yuan Ruihong , Chen Xinyi , Xue Ziwei , Guo Yixin , Chen Di , Liang Hongqing , Liu Zuozhu , Liu Wanlu
Published: May 2024

The advancement of Long-Read Sequencing (LRS) techniques has significantly increased the length of sequencing to several kilobases, thereby facilitating the identification of alternative splicing events and isoform expressions. Recently, numerous computational tools for isoform detection using long-read sequencing data have been developed. Nevertheless, there remains a deficiency in comparative studies that systemically evaluate the performance of these tools, which are implemented with different algorithms, under various simulations that encompass potential influencing factors. In this study, we conducted a benchmark analysis of thirteen methods implemented in nine tools capable of identifying isoform structures from long-read RNA-seq data. We evaluated their performances using simulated data, which represented diverse sequencing platforms generated by an in-house simulator, RNA sequins (sequencing spike-ins) data, as well as experimental data. Our findings demonstrate IsoQuant as a highly effective tool for isoform detection with LRS, with Bambu and StringTie2 also exhibiting strong performance. These results offer valuable guidance for future research on alternative splicing analysis and the ongoing improvement of tools for isoform detection using LRS data.
Efficient characterizations of multiphoton states with an ultra-thin optical device
Authors: An Kui , Liu Zilei , Zhang Ting , Li Siqi , Zhou You , Yuan Xiao , Wang Leiran , Zhang Wenfu , Wang Guoxi , Lu He
Published: May 2024

Metasurface enables the generation and manipulation of multiphoton entanglement with flat optics, providing a more efficient platform for large-scale photonic quantum information processing. Here, we show that a single metasurface optical device would allow more efficient characterizations of multiphoton entangled states, such as shadow tomography, which generally requires fast and complicated control of optical setups to perform information-complete measurements, a demanding task using conventional optics. The compact and stable device here allows implementations of general positive operator valued measures with a reduced sample complexity and significantly alleviates the experimental complexity to implement shadow tomography. Integrating self-learning and calibration algorithms, we observe notable advantages in the reconstruction of multiphoton entanglement, including using fewer measurements, having higher accuracy, and being robust against experimental imperfections. Our work unveils the feasibility of metasurface as a favorable integrated optical device for efficient characterization of multiphoton entanglement, and sheds light on scalable photonic quantum technologies with ultra-thin optical devices.
Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Authors: Nicoloff Hervé , Hjort Karin , Andersson Dan I. , Wang Helen
Published: May 2024

Heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Heteroresistance reduces treatment efficacy across diverse bacterial species and antibiotic classes, yet its genetic and physiological mechanisms remain poorly understood. Here, we investigated a multi-resistant Klebsiella pneumoniae isolate and identified three primary drivers of gene dosage-dependent heteroresistance for several antibiotic classes: tandem amplification, increased plasmid copy number, and transposition of resistance genes onto cryptic plasmids. All three mechanisms imposed fitness costs and were genetically unstable, leading to fast reversion to susceptibility in the absence of antibiotics. We used a mouse gut colonization model to show that heteroresistance due to elevated resistance-gene dosage can result in antibiotic treatment failures. Importantly, we observed that the three mechanisms are prevalent among Escherichia coli bloodstream isolates. Our findings underscore the necessity for treatment strategies that address the complex interplay between plasmids, resistance cassettes, and transposons in bacterial populations.
Mutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO)
Authors: Ayuso-Fernández Iván , Emrich-Mills Tom Z. , Haak Julia , Golten Ole , Hall Kelsi R. , Schwaiger Lorenz , Moe Trond S. , Stepnov Anton A. , Ludwig Roland , Cutsail III George E. , Sørlie Morten , Kjendseth Røhr Åsmund , Eijsink Vincent G. H.
Published: May 2024

Oxidoreductases have evolved tyrosine/tryptophan pathways that channel highly oxidizing holes away from the active site to avoid damage. Here we dissect such a pathway in a bacterial LPMO, member of a widespread family of C-H bond activating enzymes with outstanding industrial potential. We show that a strictly conserved tryptophan is critical for radical formation and hole transference and that holes traverse the protein to reach a tyrosine-histidine pair in the protein’s surface. Real-time monitoring of radical formation reveals a clear correlation between the efficiency of hole transference and enzyme performance under oxidative stress. Residues involved in this pathway vary considerably between natural LPMOs, which could reflect adaptation to different ecological niches. Importantly, we show that enzyme activity is increased in a variant with slower radical transference, providing experimental evidence for a previously postulated trade-off between activity and redox robustness.
Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression
Authors: Li-Bao Lin , Díaz-Díaz Covadonga , Raiola Morena , Sierra Rocío , Temiño Susana , Moya Francisco J. , Rodriguez-Perales Sandra , Santos Elisa , Giovinazzo Giovanna , Bleckwehl Tore , Rada-Iglesias Álvaro , Spitz Francois , Torres Miguel
Published: May 2024

MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.
Distributed representations of prediction error signals across the cortical hierarchy are synergistic
Authors: Gelens Frank , Äijälä Juho , Roberts Louis , Komatsu Misako , Uran Cem , Jensen Michael A. , Miller Kai J. , Ince Robin A. A. , Garagnani Max , Vinck Martin , Canales-Johnson Andres
Published: May 2024

A relevant question concerning inter-areal communication in the cortex is whether these interactions are synergistic. Synergy refers to the complementary effect of multiple brain signals conveying more information than the sum of each isolated signal. Redundancy, on the other hand, refers to the common information shared between brain signals. Here, we dissociated cortical interactions encoding complementary information (synergy) from those sharing common information (redundancy) during prediction error (PE) processing. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded synergistic and redundant information about PE processing. The information conveyed by ERPs and BB signals was synergistic even at lower stages of the hierarchy in the auditory cortex and between auditory and frontal regions. Using a brain-constrained neural network, we simulated the synergy and redundancy observed in the experimental results and demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback, and feedforward connections. These results indicate that distributed representations of PE signals across the cortical hierarchy can be highly synergistic.
Human-induced intensified seasonal cycle of sea surface temperature
Authors: Liu Fukai , Song Fengfei , Luo Yiyong
Published: May 2024

Changes in the seasonal cycle of sea surface temperature (SST) have far-reaching ecological and societal implications. Previous studies have found an intensified SST seasonal cycle under global warming, but whether such changes have emerged in historical records remains largely unknown. Here, we reveal that the SST seasonal cycle globally has intensified by 3.9 ± 1.6% in recent four decades (1983–2022), with hotspot regions such as the northern subpolar gyres experiencing an intensification of up to 10%. Increased greenhouse gases are the primary driver of this intensification, and decreased anthropogenic aerosols also contribute. These changes in anthropogenic emissions lead to shallower mixed layer depths, reducing the thermal inertia of upper ocean and enhancing the seasonality of SST. In addition, the direct impacts of increased ocean heat uptake and suppressed seasonal amplitude of surface heat flux also contribute in the North Pacific and North Atlantic. The temperature seasonal cycle is intensified not only at the ocean surface, but throughout the mixed layer. The ramifications of this intensified SST seasonal cycle extend to the seasonal variation in upper-ocean oxygenation, a critical factor for most ocean ecosystems.
A nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Authors: Chauvier Adrien , Dandpat Shiba S. , Romero Rosa , Walter Nils G.
Published: May 2024

Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches – like most structured RNAs – are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single-molecule and bulk approaches, we discover how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the representative Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.
Implementing no-signaling correlations as a service
Authors: Koniorczyk Mátyás , Naszvadi Péter , Bodor András , Hanyecz Ottó , Adam Peter , Pintér Miklós
Published: May 2024

We deal with no-signaling correlations that include Bell-type quantum nonlocality. We consider a logical implementation using a trusted central server with encrypted connections to clients. We show that in this way it is possible to implement two-party no-signaling correlations in an asynchronous manner. While from the point of view of physics our approach can be considered as the computer emulation of the results of measurements on entangled particles, from the software engineering point of view it introduces a primitive in communication protocols that can be capable of coordinating agents without revealing the details of their actions. We present an actual implementation in the form of a Web-based application programming interface (RESTful Web API). We demonstrate the use of the API via the simple implementation of the Clauser–Horne–Shimony–Holt game.
Spatial–temporal transmission dynamics of HIV-1 CRF01_AE in Indonesia
Authors: Khairunisa Siti Qamariyah , Indriati Dwi Wahyu , Megasari Ni Luh Ayu , Ueda Shuhei , Kotaki Tomohiro , Fahmi Muhamad , Ito Masahiro , Rachman Brian Eka , Hidayati Afif Nurul , Nasronudin  , Kameoka Masanori
Published: May 2024

Human immunodeficiency virus type 1 (HIV-1) remains a serious health threat in Indonesia. In particular, the CRF01_AE viruses were the predominant HIV-1 strains in various cities in Indonesia. However, information on the dynamic transmission characteristics and spatial–temporal transmission of HIV-1 CRF01_AE in Indonesia is limited. Therefore, the present study examined the spatial–temporal transmission networks and evolutionary characteristics of HIV-1 CRF01_AE in Indonesia. To clarify the epidemiological connection between CRF01_AE outbreaks in Indonesia and the rest of the world, we performed phylogenetic studies on nearly full genomes of CRF01_AE viruses isolated in Indonesia. Our results showed that five epidemic clades, namely, IDN clades 1–5, of CRF01_AE were found in Indonesia. To determine the potential source and mode of transmission of CRF01_AE, we performed Bayesian analysis and built maximum clade credibility trees for each clade. Our study revealed that CRF01_AE viruses were commonly introduced into Indonesia from Southeast Asia, particularly Thailand. The CRF01_AE viruses might have spread through major pandemics in Asian countries, such as China, Vietnam, and Laos, rather than being introduced directly from Africa in the early 1980s. This study has major implications for public health practice and policy development in Indonesia. The contributions of this study include understanding the dynamics of HIV-1 transmission that is important for the implementation of HIV disease control and prevention strategies in Indonesia.
Development of a dual point humidity sensor using POF based on twisted fiber structure
Authors: Hussian Sadam , Mehdi Mujahid , Ghaffar Abdul , Lan Kun , Hu Yanjun , Lin Huan , Qaisrani Mumtaz A. , Ali Sikandar , Lin Jie , Mehdi Rehan , Ma Rui
Published: May 2024

The humidity has often been measured through a single point sensor. Where, the humidity could be varied at different locations as well as depending on environmental conditions. The present paper developed the dual point humidity measuring sensor by using a polymer optical fiber (POF) based on a single illuminating fiber. The sensor’s basic structure is to twist two fibers and bend them at a certain radius. However, the dual point sensor is developed through the cascading of twisted micro bend (TMB-1 and TMB-2). The twisting of fibers couples the light from one fiber to another fiber through the side coupling method. An increase in the humidity level leads to a change in the reflective index, which helps to get variation in coupled light intensity. To measure the humidity, the dual point sensors are placed into the control humidity chamber at two random positions. The power reading variation is significantly linear when the humidity level increases from 30 to 80%. The sensor has a fast response of about 1 s and a recovery time of about 4 s. Furthermore, the chemical coating is applied to improve the sensor’s sensitivity. Between 30 and 80% range of humidity, the both sensors of dual point TMB-1 and TMB-2 have appropriate sensitivity and detection limits, which is about 680.8 nW/% and 763.9 nW/% and 1.37% and 1.98%, respectively. To measure the humidity at variable positions, the present dual points humidity sensor is well-stable, easy, and straightforward, which uses a less expensive method.
Enhanced adsorption and removal of Cd(II) from aqueous solution by amino-functionalized ZIF-8
Authors: Khosravi Amir , Habibpour Razieh , Ranjbar Maryam
Published: May 2024

Zeolite imidazolate framework-8 (ZIF-8), which is a special subgroup of metal–organic frameworks (MOFs), was synthesized and modified by ethylenediamine (ZIF-8-EDA) to prepare an efficient adsorbent for the high sorption of Cd2+ions from solution. The synthesized and modified ZIF-8 (ZIF-8-EDA) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, Brunauer–Emmett–Teller (BET), field emission scanning electron microscopy (FE-SEM) with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) analysis. The optimum conditions for dosage of adsorbent, initial ion concentration, pH, and contact time were 0.05 g/l, 50 mg/l, 6, and 60 min, respectively, for cadmium ion sorption from aqueous solutions with a removal efficiency of 89.7% for ZIF-8 and 93.5% for ZIF-8-EDA. Adsorption kinetics and equilibrium data were analyzed using the Langmuir and Freundlich equations. The Langmuir model fitted the equilibrium data better than the Freundlich model. According to the Langmuir equation, the maximum uptake for the cadmium ions was 294.11(mg/g). The calculated thermodynamic parameters (ΔG°, ΔH°, and ΔS°) indicated that the adsorption process was feasible, spontaneous, and endothermic at 20–50 °C. Based on the results, the amino functionalized ZIF-8 had improved adsorption performance due to the replacing of the starting linker with organic ligands that had effective functional groups, leading to chemical coordination due to the interaction of metal ions with the non-bonding pair of electrons on the N atoms of the amino functional group. The selectivity toward metal ion adsorption by ZIF-8-EDA was Cd2+ > Pb2+ > Ni2+‏.
Unsupervised multimodal modeling of cognitive and brain health trajectories for early dementia prediction
Authors: Burkhart Michael C. , Lee Liz Y. , Vaghari Delshad , Toh An Qi , Chong Eddie , Chen Christopher , Tiňo Peter , Kourtzi Zoe
Published: May 2024

Predicting the course of neurodegenerative disorders early has potential to greatly improve clinical management and patient outcomes. A key challenge for early prediction in real-world clinical settings is the lack of labeled data (i.e., clinical diagnosis). In contrast to supervised classification approaches that require labeled data, we propose an unsupervised multimodal trajectory modeling (MTM) approach based on a mixture of state space models that captures changes in longitudinal data (i.e., trajectories) and stratifies individuals without using clinical diagnosis for model training. MTM learns the relationship between states comprising expensive, invasive biomarkers (β-amyloid, grey matter density) and readily obtainable cognitive observations. MTM training on trajectories stratifies individuals into clinically meaningful clusters more reliably than MTM training on baseline data alone and is robust to missing data (i.e., cognitive data alone or single assessments). Extracting an individualized cognitive health index (i.e., MTM-derived cluster membership index) allows us to predict progression to AD more precisely than standard clinical assessments (i.e., cognitive tests or MRI scans alone). Importantly, MTM generalizes successfully from research cohort to real-world clinical data from memory clinic patients with missing data, enhancing the clinical utility of our approach. Thus, our multimodal trajectory modeling approach provides a cost-effective and non-invasive tool for early dementia prediction without labeled data (i.e., clinical diagnosis) with strong potential for translation to clinical practice.
Effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum and ileum in broiler chickens
Authors: Campos Philip M. , Miska Katarzyna B. , Jenkins Mark C. , Yan Xianghe , Proszkowiec-Weglarz Monika
Published: May 2024

Coccidiosis, an intestinal disease caused by Eimeria parasites, is responsible for major losses in the poultry industry by impacting chicken health. The gut microbiota is associated with health factors, such as nutrient exchange and immune system modulation, requiring understanding on the effects of Eimeria infection on the gut microbiota. This study aimed to determine the effects of Eimeria acervulina infection on the luminal and mucosal microbiota of the cecum (CeL and CeM) and ileum (IlL and IlM) at multiple time points (days 3, 5, 7, 10, and 14) post-infection. E. acervulina infection decreased evenness in CeL microbiota at day 10, increased richness in CeM microbiota at day 3 before decreasing richness at day 14, and decreased richness in IlL microbiota from day 3 to 10. CeL, CeM, and IlL microbiota differed between infected and control birds based on beta diversity at varying time points. Infection reduced relative abundance of bacterial taxa and some predicted metabolic pathways known for short-chain fatty acid production in CeL, CeM, and IlL microbiota, but further understanding of metabolic function is required. Despite E. acervulina primarily targeting the duodenum, our findings demonstrate the infection can impact bacterial diversity and abundance in the cecal and ileal microbiota.
Maximally informative feature selection using Information Imbalance: Application to COVID-19 severity prediction
Authors: Wild Romina , Sozio Emanuela , Margiotta Riccardo G. , Dellai Fabiana , Acquasanta Angela , Del Ben Fabio , Tascini Carlo , Curcio Francesco , Laio Alessandro
Published: May 2024

Clinical databases typically include, for each patient, many heterogeneous features, for example blood exams, the clinical history before the onset of the disease, the evolution of the symptoms, the results of imaging exams, and many others. We here propose to exploit a recently developed statistical approach, the Information Imbalance, to compare different subsets of patient features and automatically select the set of features that is maximally informative for a given clinical purpose, especially in minority classes. We adapt the Information Imbalance approach to work in a clinical framework, where patient features are often categorical and are generally available only for a fraction of the patients. We apply this algorithm to a data set of $$\sim$$
∼
1300 patients treated for COVID-19 in Udine hospital before October 2021. Using this approach, we find combinations of features which, if used in combination, are maximally informative of the clinical fate and of the severity of the disease. The optimal number of features, which is determined automatically, turns out to be between 10 and 15. These features can be measured at admission. The approach can be used also if the features are available only for a fraction of the patients, does not require imputation and, importantly, is able to automatically select features with small inter-feature correlation. Clinical insights deriving from this study are also discussed.
Magnetic iron oxide nanoparticle enhanced microwave pretreatment for anaerobic digestion of meat industry sludge
Authors: Jákói Zoltán Péter , Hodúr Cecilia , Beszédes Sándor
Published: May 2024

Our study investigates the effects of iron oxide (Fe3O4) nanoparticles combined microwave pretreatment on the anaerobic digestibility and soluble chemical oxygen demand (SCOD) of meat industry sludge. One of our main objectives was to see whether the different microwave-based pretreatment procedures can enhance biogas production by improving the biological availability of organic compounds. Results demonstrated that combining microwave irradiation with magnetic iron oxide nanoparticles considerably increased SCOD (enhancement ratio was above 1.5), the rate of specific biogas production, and the total cumulative specific biogas volume (more than a threefold increment), while having no negative effect on the biomethane content. Furthermore, the assessment of the sludge samples’ dielectric properties (dielectric constant and loss factor measured at the frequency of 500 MHz) showed a strong correlation with SCOD changes (r = 0.9942, R2 = 0.99), offering a novel method to evaluate pretreatment efficiency.