bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating AI Proficiency in Nuclear Cardiology: Large Language Models take on the Board Preparation Exam
Authors: Builoff Valerie , Shanbhag Aakash , Miller Robert JH , Dey Damini , Liang Joanna X. , Flood Kathleen , Bourque Jamieson M. , Chareonthaitawee Panithaya , Phillips Lawrence M. , Slomka Piotr J
Published: July 2024

Background

Previous studies evaluated the ability of large language models (LLMs) in medical disciplines; however, few have focused on image analysis, and none specifically on cardiovascular imaging or nuclear cardiology.

Objectives

This study assesses four LLMs - GPT-4, GPT-4 Turbo, GPT-4omni (GPT-4o) (Open AI), and Gemini (Google Inc.) - in responding to questions from the 2023 American Society of Nuclear Cardiology Board Preparation Exam, reflecting the scope of the Certification Board of Nuclear Cardiology (CBNC) examination.

Methods

We used 168 questions: 141 text-only and 27 image-based, categorized into four sections mirroring the CBNC exam. Each LLM was presented with the same standardized prompt and applied to each section 30 times to account for stochasticity. Performance over six weeks was assessed for all models except GPT-4o. McNemar’s test compared correct response proportions.

Results

GPT-4, Gemini, GPT4-Turbo, and GPT-4o correctly answered median percentiles of 56.8% (95% confidence interval 55.4% - 58.0%), 40.5% (39.9% - 42.9%), 60.7% (59.9% - 61.3%) and 63.1% (62.5 – 64.3%) of questions, respectively. GPT4o significantly outperformed other models (p=0.007 vs. GPT-4Turbo, p<0.001 vs. GPT-4 and Gemini). GPT-4o excelled on text-only questions compared to GPT-4, Gemini, and GPT-4 Turbo (p<0.001, p<0.001, and p=0.001), while Gemini performed worse on image-based questions (p<0.001 for all).

Conclusion

GPT-4o demonstrated superior performance among the four LLMs, achieving scores likely within or just outside the range required to pass a test akin to the CBNC examination. Although improvements in medical image interpretation are needed, GPT-4o shows potential to support physicians in answering text-based clinical questions.
Generalizing AI-driven Assessment of Immunohistochemistry across Immunostains and Cancer Types: A Universal Immunohistochemistry Analyzer
Authors: Brattoli Biagio , Mostafavi Mohammad , Lee Taebum , Jung Wonkyung , Ryu Jeongun , Park Seonwook , Park Jongchan , Pereira Sergio , Shin Seunghwan , Choi Sangjoon , Kim Hyojin , Yoo Donggeun , Ali Siraj M. , Paeng Kyunghyun , Ock Chan-Young , Cho Soo Ick , Kim Seokhwi
Published: July 2024

Despite advancements in methodologies, immunohistochemistry (IHC) remains the most utilized ancillary test for histopathologic and companion diagnostics in targeted therapies. However, objective IHC assessment poses challenges. Artificial intelligence (AI) has emerged as a potential solution, yet its development requires extensive training for each cancer and IHC type, limiting versatility. We developed a Universal IHC (UIHC) analyzer, an AI model for interpreting IHC images regardless of tumor or IHC types, using training datasets from various cancers stained for PD-L1 and/or HER2. This multi-cohort trained model outperforms conventional single-cohort models in interpreting unseen IHCs (Kappa score 0.578 vs. up to 0.509) and consistently shows superior performance across different positive staining cutoff values. Qualitative analysis reveals that UIHC effectively clusters patches based on expression levels. The UIHC model also quantitatively assesses c-MET expression with MET mutations, representing a significant advancement in AI application in the era of personalized medicine and accumulating novel biomarkers.
2023-24 dengue outbreak in Valle del Cauca, Colombia caused by multiple virus serotypes and lineages
Authors: Grubaugh Nathan D , Torres-Hernandez Daniela , Murillo-Ortiz Monica A. , Davalos Diana M. , Lopex Pio , Hurtado Isabel C. , Breban Mallery I. , Bourgikos Ellie , Hill Verity , Lopez-Medina Eduardo
Published: July 2024

Global dengue cases rapidly rose to record levels in 2023-24. We investigated this trend in Valle del Cauca, Colombia to determine if specific dengue virus serotypes or lineages were responsible for the large outbreak. We detected all four serotypes and multiple lineages, suggesting that other factors, such as climatic conditions, are likely responsible.
Long-read sequencing identifies copy-specific markers ofSMNgene conversion in spinal muscular atrophy
Authors: Zwartkruis M.M. , Elferink M.G. , Gommers D. , Signoria I. , Blasco-Pérez L. , Costa-Roger M. , van der Sel J. , Renkens I.J. , Green J.W. , Kortooms J.V. , Vermeulen C. , Straver R. , van Deutekom H.W.M. , Veldink J.H. , Asselman F. , Tizzano E.F. , Wadman R.I. , van der Pol W.L. , van Haaften G.W. , Groen E.J.N.
Published: July 2024

The complex 2 Mbsurvival motor neuron (SMN)locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing geneSMN1and modifierSMN2, remains incompletely resolved due to numerous segmental duplications. Variation inSMN2copy number, presumably influenced bySMN1toSMN2gene conversion, affects disease severity, thoughSMN2copy number alone has insufficient prognostic value due to limited genotype-phenotype correlations. With advancements in newborn screening andSMN-targeted therapies, identifying genetic markers to predict disease progression and treatment response is crucial. Progress has thus far been limited by methodological constraints. To address this, we used targeted nanopore long-read sequencing to analyze copy-specific variation inSMNand neighboring genes. In 25 healthy controls, we identified single nucleotide variants (SNVs) specific toSMN1andSMN2haplotypes that could serve as gene conversion markers. In 31 SMA patients, 45% of haplotypes showed varyingSMN1toSMN2gene conversion breakpoints, serving as direct evidence of gene conversion as a common genetic characteristic in SMA and prompting further investigation into gene conversion markers as disease modifiers. Our findings illustrate that both methodological advances and the analysis of patient samples are required to advance our understanding of complex genetic loci and address critical clinical challenges.
Deep learning based treatment remission prediction to transcranial direct current stimulation in bipolar depression using EEG power spectral density
Authors: Chettuthara Moncy Jijomon , Fan Yong , Woodham Rachel D. , Ghazi-Noori Ali-Reza , Rezaei Hakimeh , Xiao Wenyi , Bramon Elvira , Ritter Philipp , Bauer Michael , Young Allan H. , Fu Cynthia H.Y.
Published: July 2024

Bipolar Depression (BD) characterised by changes in mood and activity levels is a leading cause of disability worldwide. Current treatments show limited efficacy. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that is a potential treatment for bipolar depression. We sought to investigate the application of deep learning methods to electroencephalogram (EEG) signals to predict clinical remission. Resting-state EEG data were acquired in 21 BD participants (mean age 51.38 + 10.59 years) at baseline, using a portable 4 electrode EEG device (AF7, AF8, TP9, TP10). Treatment was 6 weeks of home-based tDCS sessions, consisting of 5 sessions per week for 3 weeks and 3 sessions per week for 3 weeks. tDCS was provided in bifrontal montage, anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC, 2 mA, 30 minutes per session. Remission was defined as Montgomery-Åsberg Depression Rating Scale score of less than 8. Power spectral density was derived from EEG signals. Deep learning methods: 1D convolutional neural networks (1DCNNs), long short-term memory (LSTM), gated recurrent units (GRU) and their hybrid models, were investigated for prediction of remission and non-remission status following treatment. Hybrid 1DCNN and GRU model using a combination of delta, theta, and gamma band PSD from AF7 and TP10 electrodes achieved a treatment remission prediction accuracy of 79.55% (sensitivity 76.95%, specificity 83.02%). Compelling prediction accuracy for prediction of treatment remission to a course of tDCS in bipolar depression is achieved from deep learning analysis of resting-state EEG at baseline.
Impact of Midwifery-led units in Spain: lessons from the first 5 years
Authors: Palau-Costafreda Roser , Orus-Covisa Lluna , Vicente-Castellví Edgar , Espada-Trespalacios Xavier , Medina Català Albert , Alcover Carlota , Obregón Gutiérrez Noemí , Escuriet Ramon
Published: July 2024

Introduction

The global rise in medical interventions during childbirth, such as caesarean sections, has raised concerns regarding their necessity and impact on maternal and neonatal outcomes. Midwifery-led units (MLUs) have demonstrated lower intervention rates and higher maternal satisfaction.This study evaluates the implementation and effects of the first MLU in the Spanish National Health System.

Methods

A retrospective cross-sectional trend study and a cohort study were conducted to compare childbirth interventions and outcomes at XX with other hospitals of varying complexities.

Results

The introduction of the MLU at XX resulted in a significant reduction in caesarean sections, decreasing from 23.5% to 13.5%, and an increase in spontaneous vaginal births, rising from 64.2% to 78.7%. These trends reversed following the MLU’s closure in 2022, with caesarean sections increasing to 22.9% and spontaneous births dropping to 69.0%. The MLU served 1286 women, with the majority classified as low-risk pregnancies. Obstetric emergencies in the MLU were low and comparable to those in countries with established MLUs.

Discussion

This study highlights the potential benefits of integrating MLUs into traditionally medicalized healthcare systems to promote physiological childbirth and reduce unnecessary interventions. The positive outcomes achieved at HM are comparable to those in countries with more established MLU practices, reflecting the unit’s commitment to evidence-based care. The increasing interest among women in midwifery-led care indicates a broader demand for supportive, less medicalized childbirth environments.

Conclusions

MLU can lead to lower caesarean section rates and higher spontaneous vaginal birth rates, contributing to more positive maternal and neonatal outcomes. However, sustained support and investment in these units are crucial to maintain these benefits. Policymakers and healthcare providers should consider expanding the integration of MLUs within the Spanish National Health System to enhance maternal care quality and align with best practices.
The impact of genome-wide histocompatibility on liver transplantation outcomes
Authors: Semenova M , Liukkonen V , Markkinen S , Färkkilä M , Nordin A , Partanen J , Åberg F , Hyvärinen K
Published: July 2024

Liver transplantation (LT) is the standard treatment for end-stage liver diseases. However, the role of human leukocyte antigen (HLA)-matching in LT remains unclear. Immunological allograft injury and rejection are ongoing concerns, particularly when efforts are made to minimize immunosuppression. Although HLA matching currently has no established role in LT, interest in non-HLA compatibility in the field of transplantation is growing.

We compared 666 LT recipient-donor pairs and identified amino acid-changing genetic mismatches outside the HLA gene segment in different protein groups, and mismatches in 40 common gene deletions.

We evaluated the association between mismatches and LT outcomes by using adjusted Cox models for missense variant mismatches and deletion analyses. The primary endpoints were acute rejection, late rejection, graft loss, and overall survival. Statistical significance was set at a false discovery rate (FDR) <0.05.

Mismatches in missense variants coding for all proteins were associated with late rejection, with an adjusted hazard ratio (aHR) of 0.998 (95% confidence interval [CI]: 0.996–0.999;P= 0.011, FDR <0.05). Deletion mismatches tagged with rs11985201, rs2342606, rs2174926, and rs1944862 were identified as risk factors for LT outcomes. The sum of mismatches in deletion variants rs11985201, rs2342606, and rs1944862 was associated with time to acute rejection, with an aHR of 1.377 (95% CI: 1.139– 1.664,P= 0.001, FDR <0.05).

Genome-wide mismatches outside of the HLA region contribute to the risk of LT complications. Robust, large-scale studies are required to validate these results.
The Healthy Life in an Urban Setting (HELIUS) study in Amsterdam, The Netherlands: cohort update 2024 and key findings
Authors: Galenkamp Henrike , Koopman Anitra D.M. , Esi van der Zwan J. , van den Born Bert-Jan H. , Lok Anja , Moll van Charante Eric P. , Prins Maria , Verhoeff Arnoud P. , Zwinderman Aeilko H. , Stronks Karien
Published: July 2024

The Healthy Life in an Urban Setting (HELIUS) study is an ongoing prospective multi-ethnic cohort study, in Amsterdam, The Netherlands that started in 2011. The principle aim of the HELIUS study is to investigate the causes of (the unequal burden of) diseases across ethnic groups, with emphasis on mental disorders, cardiovascular disease and infectious disease, and their interrelationships. Stratified sampling by ethnic group was used to allow for an equal representation of the largest ethnic groups resulting in similar-sized samples of individuals of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan origin. A total of 24,780 individuals participated in the baseline examination that consisted of a questionnaire, physical examination and collection of biological material. Follow-up data have been collected through linkage with health care registries and a first follow-up data collection that took part between 2019 and 2022 and included 11,035 participants with an average follow-up time of 6.4 years. The data collection included information on demographics, medical history (including medication use and mental health status), anthropometrics, and fasting blood, urine and stool samples. Here we give an update on the HELIUS study and its methods regarding the first follow-up data collection, data linkage, and additional analyses using stored biomaterials. In addition, we provide a summary of key findings.
Growing up in poverty, growing old with multimorbidity in America, Britain, China, Europe and Indonesia: a retrospective and prospective study in 31 countries
Authors: Tampubolon Gindo
Published: July 2024

The childhood poor in rich countries have reported worse cognitive, muscle and mental functions in old age. But it is uncertain whether the childhood poor around the world are at higher risks of multimorbidity because childhood recollections are often erroneous.

METHODS

Some 81,804 older adults over 50 years in 31 countries recalled their childhood conditions at ten to fourteen and prospectively reported their chronic conditions. Childhood conditions in Britain and Europe include numbers of books, rooms and people, presence of running hot water and central heating. Across in America, these are mostly replaced with financial hardship or family indebtedness, in China starvation to death due to government edict while in Indonesia presence of running cold water. Per prior practice childhood poverty is a latent construct of these error-laced recollections while multimorbidity is defined as at least two from a set of chronic conditions. Associations with multimorbidity are obtained with fixed effects probit model, controlling for age, education, wealth, marital status and youth illness. Extensive sensitivity analyses assessed robustness.

RESULTS

Childhood poverty associates with higher probabilities of multimorbidity (0.088, [95% confidence interval 0.057 – 0.118]) in 31 rich and developing countries. And women reported lower probabilities of multimorbidity (−0.071, [-0.096 – -0.047]). Frequencies of multimorbidity vary across countries, and likewise age profiles of multimorbidity in later life.

DISCUSSION

Evidence is accumulating that childhood lasts a life time in rich and developing nations. The various childhood recollections indicating poverty show that the childhood poor grow old with more chronic conditions. Because population ageing is posing a momentous challenge across the world, more research is needed on the life course shaping of healthy ageing. But this strong evidence calls for urgent actions to eliminate child poverty on account of its lifelong rewards. [287 + 4233 words]
Proteomic analysis identifies dysregulated proteins in albuminuria: a South African pilot study
Authors: Khoza Siyabonga , George Jaya A. , Naicker Previn , Stoychev Stoyan H. , Fabian June , Govender Ireshyn S.
Published: July 2024

Albuminuria may precede decreases in glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. A case-controlled study that compared urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) <3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of Black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC coupled to a Sciex 5600 Triple-TOF in data-independent acquisition mode. Data were searched on SpectronautTM15. Differentially abundant proteins (DAPs) were filtered ≥ 2.25-fold change and false discovery rate ≤ 1%. Receiver operating characteristic curves were used to assess the discriminating ability of proteins of interest. Pathway analysis was performed using Enrichr software. The albuminuric group had a higher uACR (7.9 vs 0.55 mg/mmol,p<0.001). The median eGFR (mL/min/1.73m2) showed no difference between the groups (111 vs 114,p=0.707). We identified 80 DAPs in the albuminuria group compared to normoalbuminuria, of which 59 proteins increased while 21 proteins decreased in abundance. We found 12 urinary proteins with AUC > 0.8, andp-value <0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC >0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis associated with DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease.
Functional genomics of chitin degradation byVibrio parahaemolyticusreveals finely integrated metabolic contributions to support environmental fitness
Authors: Getz Landon P. , Robinson Oriana , Thomas Nikhil A.
Published: July 2024

Vibriospecies are marine prokaryotes that inhabit diverse ecological niches, colonizing abiotic and biotic surfaces. These bacteria are vital players in the global carbon cycle, assimilating billions of tonnes of chitin for carbon (and nitrogen) metabolites. Many bacterial proteins involved in the process-including chitinases, sugar transporters, and modifying enzymes-have been well studied. However, the genetic functional interplay and key drivers ofVibriocompetitive survival in the presence of chitin as the dominant carbon source is not understood. To address this question, we carried out transposon sequencing (Tn-seq) to determine the genetic fitness ofVibrio parahaemolyticusmutants grown on chitin as a sole carbon source. Along with validating knownVibriogenes associated with chitin metabolism, our data newly identified vital roles for an unclassified OprD-like import porin and a HexR family transcriptional regulator. Furthermore, we functionally implicated HexR in regulating multiple physiological processes involved inV. parahaemolyticusenvironmental survival including carbon assimilation and cell growth, biofilm formation, and cell motility. Notably, our data revealed a strict requirement for HexR in filamentous cell morphology, a critical trait forV. parahaemolyticusenvironmental fitness. Therefore, a vital import porin and genomic regulation mediated by HexR supports multiple physiological processes forVibriochitinolytic growth and environmental fitness.
The SARS-CoV-2 nucleocapsid protein inhibits the cellular Nonsense-Mediated mRNA Decay (NMD) pathway preventing the full enzymatic activation of UPF1
Authors: Nuccetelli Veronica , Mghezzi-Habellah Makram , Deymier Séverine , Roisin Armelle , Gerard-Baraggia Francine , Rocchi Cecilia , Coureux Pierre-Damien , Gouet Patrice , Cimarelli Andrea , Mocquet Vincent , Fiorini Francesca
Published: July 2024

The Nonsense-mediated mRNA decay (NMD) pathway triggers the degradation of defective mRNAs and governs the expression of mRNAs with specific characteristics. Current understanding indicates that NMD is often significantly suppressed during viral infections to protect the viral genome. In numerous viruses, this inhibition is achieved through direct or indirect interference with the RNA helicase UPF1, thereby promoting viral replication and enhancing pathogenesis.

In this study, we employed biochemical, biophysical assays, and cellular investigations to explore the interplay between UPF1 and the Nucleocapsid (Np) protein of SARS-CoV-2. We evaluated their direct interaction and its impact on inhibiting cellular NMD. Furthermore, we characterized how this interaction affects UPF1’s enzymatic function. Our findings demonstrate that Np inhibits the unwinding activity of UPF1 by physically obstructing its access to structured nucleic acid substrates. Additionally, we showed that Np binds directly to UPF2, disrupting the formation of the UPF1/UPF2 complex essential for NMD progression. Intriguingly, our research also uncovered a surprising pro-viral role of UPF1 and an antiviral function of UPF2.

These results unveil a novel, multi-faceted mechanism by which SARS-CoV-2 evades the host’s defenses and manipulates cellular components. This underscores the potential therapeutic strategy of targeting Np-UPF1/UPF2 interactions to treat COVID-19.
Cryo-EM Structures ofSaccharolobus solfataricusInitiation Complexes with Leaderless mRNAs Highlight Archaeal Features and Eukaryotic Proximity
Authors: Bourgeois Gabrielle , Coureux Pierre-Damien , Lazennec-Schurdevin Christine , Madru Clément , Gaillard Thomas , Duchateau Magalie , Chamot-Rooke Julia , Bourcier Sophie , Mechulam Yves , Schmitt Emmanuelle
Published: July 2024

The archaeal ribosome is of the eukaryotic type. Genomic and phylogenetic studies have indicated that TACK and Asgard, the closest relatives of eukaryotes, have ribosomes containing eukaryotic ribosomal proteins not found in other archaeal branches, eS25, eS26 and eS30. In our study, we investigated the case ofSaccharolobus solfataricus, a crenarchaeon belonging to the TACK branch, which mainly uses leaderless mRNAs. We characterized the small ribosomal subunit ofS. solfataricusbound to SD-leadered or leaderless mRNAs (lmRNAs). Cryo-EM structures show for the first time archaeal versions of eS25, eS26 and eS30 proteins bound to the small subunit. In addition, we identify two novel ribosomal proteins named aS33 and aS34 as well as a domain of eS6, that highlight the diversity of archaeal ribosomes. Leaderless mRNAs are bound to the small ribosomal subunit, and the 5’-triphosphate group contributes to their binding. Archaeal eS26 is in the mRNA exit channel wrapped around the 3’ end of ribosomal RNA, as it is in eukaryotes. Its position is not compatible with an SD:antiSD duplex in the mRNA exit channel. Overall, our results suggest a role of eS26 in translation regulation and possible evolutionary routes from archaeal to eukaryotic translation.
MELATONIN INDUCES CHANGES ON THE CIRCADIAN RHYTHMS OF REPRODUCTIVE HORMONES DURING SPERMATOGENESIS IN PUBERTAL MALE SEA BASS,Dicentrarchus labrax
Authors: Alvarado M.Victoria , Espigares Felipe , Carrillo Manuel , Felip Alicia
Published: July 2024

Reproduction is a highly demanding biological process that occurs at the optimal time of the year and day to ensure the success of spawn and offspring. Melatonin is a hormone that, secreted mainly by the pineal gland, plays a critical role in the integration of the photoneuroendocrine information from environment (annual and daily variations) to modulate reproductive activity and gonadal development in fish. In this study we assessed the effect of exogenous melatonin on the circadian levels of sex steroids and gonadotropins in pubertal 2 yr-old male sea bass during their reproductive cycle including, pre-spermatogenesis (Pspg), spermiation (Spm) and post-spermiation (PSpm) stages. Our results demonstrated that all reproductive hormones displayed circadian variations along the entire reproductive cycle in pubertal fish. Circulating levels of the luteinizing hormone (Lh) were affected by both melatonin injection and the daily timing of administration during the Spm and PSpm stages, thus evoking variations of Lh levels at night. Melatonin also significantly affected circadian rhythms of Fsh during the Spm stage. Overall, both 11-Kt and T plasma levels displayed circadian variations during the reproductive cycle in the sea bass which were not prevented by melatonin. However, melatonin showed a significant decrease of plasma levels of 11-Kt 1h after dusk during the Pspg stage, while it increased those levels of T 5 h after dusk during the PSpm stage. These findings provide new insights into the role of melatonin in fish reproduction as a key factor in regulation of daily variation of key hormones involved in gonadal development. This circumstance may have implications in the control of gametogenesis and management of fish in aquaculture.

Highlights

Plasma levels of Fsh, Lh, T and 11-Kt show daily rhythms in pubertal male sea bass.

Melatonin evokes changes in daily rhythms of Lh during the reproductive cycle.

Melatonin yields Fsh plasma level differences during spermiation stage.

Melatonin elicits T and 11-Kt plasma level differences depending on reproductive stage and time.
In vitroevolution of ciprofloxacin resistance inNeisseriacommensals and derived mutation population dynamics in naturalNeisseriapopulations
Authors: Robinson Leah R. , McDevitt Caroline J. , Regan Molly R. , Quail Sophie L. , Wadsworth Crista B.
Published: July 2024

CommensalNeisseriaare members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we usein vitroselection to assess the mutations that emerge in response to ciprofloxacin selection in commensalNeisseriaby passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing. 10/16 selected cells lines across the 4 species evolved ciprofloxacin resistance (≥ 1 ug/ml); with resistance-contributing mutations primarily emerging inDNA gyrase subunit AandB(gyrAandgyrB),topoisomerase IV subunits CandE(parCandparE), and themultiple transferable efflux pump repressor(mtrR). Of note, these derived mutations appeared in the same loci responsible for ciprofloxacin reduced susceptibility in the pathogenicNeisseria, suggesting conserved mechanisms of resistance across the genus. Additionally, we tested for zoliflodacin cross-resistance in evolved strain lines and found 6 lineages with elevated zoliflodacin minimum inhibitory concentrations. Finally, to interrogate the likelihood of experimentally derived mutations emerging and contributing to resistance in naturalNeisseria, we used a population-based approach and identified GyrA 91I as a substitution circulating within commensalNeisseriapopulations and ParC 85C in a single gonococcal isolate. Small clusters of gonococcal isolates had commensal-like alleles atparCandparE, indicating recent cross-species recombination events.
Diffusing protein binders to intrinsically disordered proteins
Authors: Liu Caixuan , Wu Kejia , Choi Hojun , Han Hannah , Zhang Xulie , Watson Joseph L. , Shijo Sara , Bera Asim K. , Kang Alex , Brackenbrough Evans , Coventry Brian , Hick Derrick R. , Hoofnagle Andrew N. , Zhu Ping , Li Xingting , Decarreau Justin , Gerben Stacey R. , Yang Wei , Wang Xinru , Lamp Mila , Murray Analisa , Bauer Magnus , Baker David
Published: July 2024

Proteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general methodology for targeting IDPs/IDRs has yet to be developed. Here, we show that starting only from the target sequence of the input, and freely sampling both target and binding protein conformation, RFdiffusion can generate binders to IDPs and IDRs in a wide range of conformations. We use this approach to generate binders to the IDPs Amylin, C-peptide and VP48 in a range of conformations with Kds in the 3 -100nM range. The Amylin binder inhibits amyloid fibril formation and dissociates existing fibers, and enables enrichment of amylin for mass spectrometry-based detection. For the IDRs G3bp1, common gamma chain (IL2RG) and prion, we diffused binders to beta strand conformations of the targets, obtaining 10 to 100 nM affinity. The IL2RG binder colocalizes with the receptor in cells, enabling new approaches to modulating IL2 signaling. Our approach should be widely useful for creating binders to flexible IDPs/IDRs spanning a wide range of intrinsic conformational preferences.
Axion magnetic resonance: A novel enhancement in axion-photon conversion
Authors: Seong Hyeonseok , Sun Chen , Yun Seokhoon
Published: July 2024

We identify a new resonance, axion magnetic resonance, that can greatly enhance the conversion rate between axions and photons. A series of axion search experiments rely on converting them into photons inside a constant magnetic field background. A common bottleneck of such experiments is the conversion amplitude being suppressed by the axion mass when ma≳10−4  eV. We point out that a spatial or temporal variation in the magnetic field can cancel the difference between the photon dispersion relation and that of the axion, hence greatly enhancing the conversion probability. We demonstrate that the enhancement can be achieved by both a helical magnetic field profile and a harmonic oscillation of the magnitude. Our approach can extend the projected ALPS II reach in the axion-photon coupling (gaγ) by two orders of magnitude at ma=10−3  eV with moderate assumptions (see .)

Published by the American Physical Society
2024
Cosmologically consistent analysis of gravitational waves from hidden sectors
Authors: Feng Wan-Zhe , Li Jinzheng , Nath Pran
Published: July 2024

Production of gravitational waves in the early Universe is discussed in a cosmologically consistent analysis within a first-order phase transition involving a hidden sector feebly coupled with the visible sector. Each sector resides in its own heat bath leading to a potential dependent on two temperatures and on two fields: one a standard model Higgs field and the other a scalar arising from a hidden sector U(1) gauge theory. A synchronous evolution of the hidden and visible sector temperatures is carried out from the reheat temperature down to the electroweak scale. The hydrodynamics of two-field phase transitions, one for the visible and the other for the hidden is discussed, which leads to separate tunneling temperatures and different sound speeds for the two sectors. Gravitational waves emerging from the two sectors are computed and their imprint on the measured gravitational wave power spectrum vs frequency is analyzed in terms of bubble nucleation signature, i.e., detonation, deflagration, and hybrid. It is shown that the two-field model predicts gravitational waves accessible at several proposed gravitational wave detectors: LISA, DECIGO, BBO, and Taiji, and their discovery would probe specific regions of the hidden sector parameter space and may also shed light on the nature of bubble nucleation in the early Universe. The analysis presented here indicates that the cosmologically preferred models are those where the tunneling in the visible sector precedes the tunneling in the hidden sector and the sound speed cs lies below its maximum, i.e., cs2<13. It is of interest to investigate if these features are universal and applicable to a wider class of cosmologically consistent models.

Published by the American Physical Society
2024
Detecting ultralight dark matter gravitationally with laser interferometers in space
Authors: Yu Jiang-Chuan , Cao Yan , Tang Yong , Wu Yue-Liang
Published: July 2024

Ultralight dark matter (ULDM) is one of the leading well-motivated dark matter candidates, predicted in many theories beyond the standard model of particle physics and cosmology. There has been increasing interest in searching for ULDM in physical and astronomical experiments, mostly assuming there are additional interactions other than gravity between ULDM and normal matter. Here we demonstrate that even if ULDM has only gravitational interaction, it shall induce gravitational perturbations in solar system that may be large enough to cause detectable signals in future gravitational-wave (GW) laser interferometers in space. We investigate the sensitivities of Michelson time-delay interferometer to ULDM of various spins, and show vector ULDM with mass m≲10−18  eV can be probed by space-based GW detectors aiming at μHz frequencies. Our findings exhibit that GW detectors may directly probe ULDM in some mass ranges that otherwise are challenging to examine.

Published by the American Physical Society
2024
Mass and isospin breaking effects in the Skyrme model and in holographic QCD
Authors: Bartolini Lorenzo , Bolognesi Stefano , Gudnason Sven Bjarke , Rainaldi Tommaso
Published: July 2024

We discuss how the quark masses and their mass splitting affect the baryons in the Skyrme model as well as the Witten-Sakai-Sugimoto (WSS) model. In both cases, baryons are described by solitonic objects, i.e., Skyrmions and instantons, respectively. After the quantization of their zero modes, the nucleons become quantum states of a rotor. We show how the quark mass affects the moment of inertia and we provide a semianalytic approach valid in the small-mass limit. Additionally, we show how the two lightest quarks’ mass splitting affects the moments of inertia of the Skyrmion and induces an isospin breaking effect. This effect turns out not to be enough to split the degeneracy in the neutron-proton multiplet, but it splits some of the states in the Δ multiplet. Unlike the basic Skyrme model, the WSS model already includes vector mesons and another mechanism to transfer isospin breaking from quark masses to the solitons is known. We compute the splitting of the moment of inertia in the small-mass limit in the WSS model and combine the two effects on the spectrum of baryons, in particular the Δ’s.

Published by the American Physical Society
2024
Zemach and Friar radii of the proton and neutron from lattice QCD
Authors: Djukanovic Dalibor , von Hippel Georg , Meyer Harvey B. , Ottnad Konstantin , Salg Miguel , Wittig Hartmut
Published: July 2024

We present the first lattice-QCD result for the Zemach and Friar radii of the proton and neutron. Our calculation includes both quark-connected and -disconnected diagrams and assesses all sources of systematic uncertainties arising from excited-state contributions, finite-volume effects, and the continuum extrapolation. At the physical point, we obtain for the proton rZp=(1.013±0.010(stat)±0.012(syst))  fm and rFp=(1.301±0.012(stat)±0.014(syst))  fm. These numbers suggest small values of the Zemach and Friar radii of the proton but are compatible with most of the experimental studies.

Published by the American Physical Society
2024
Robust Effective Ground State in a Nonintegrable Floquet Quantum Circuit
Authors: Ikeda Tatsuhiko N. , Sugiura Sho , Polkovnikov Anatoli
Published: July 2024

An external periodic (Floquet) drive is believed to bring any initial state to the featureless infinite temperature state in generic nonintegrable isolated quantum many-body systems in the thermodynamic limit, irrespective of the driving frequency Ω. However, numerical or analytical evidence either proving or disproving this hypothesis is very limited and the issue has remained unsettled. Here, we study the initial state dependence of Floquet heating in a nonintegrable kicked Ising chain of length up to L=30 with an efficient quantum circuit simulator, showing a possible counterexample: the ground state of the effective Floquet Hamiltonian is exceptionally robust against heating, and could stay at finite energy density even after infinitely many Floquet cycles, if the driving period is shorter than a threshold value. This sharp energy localization transition or crossover does not happen for generic excited states. The exceptional robustness of the ground state is interpreted by (i) its isolation in the energy spectrum and (ii) the fact that those states with L-independent ℏΩ energy above the ground state energy of any generic local Hamiltonian, like the approximate Floquet Hamiltonian, are atypical and viewed as a collection of noninteracting quasiparticles. Our finding paves the way for engineering Floquet protocols with finite driving periods realizing long-lived, or possibly even perpetual, Floquet phases by initial state design.

Published by the American Physical Society
2024
Supersymmetric States in Anti–de Sitter
D=3
Supergravity with Chiral Torsion
Authors: Andrianopoli Laura , Noris Ruggero , Trigiante Mario , Zanelli Jorge
Published: July 2024

In this Letter, we construct a supersymmetric model, obtained by deforming N=2 anti–de Sitter D=3 supergravity through a chiral vector component of the torsion. Moreover, we study the existence of supersymmetric states of such theory by inspecting the presence of Killing spinors on a specific bosonic solution.

Published by the American Physical Society
2024
Symmetry-Enforced Many-Body Separability Transitions
Authors: Chen Yu-Hsueh , Grover Tarun
Published: July 2024

We study quantum many-body mixed states with a symmetry from the perspective of , i.e., whether a mixed state can be expressed as an ensemble of short-range-entangled symmetric pure states. We provide evidence for “symmetry-enforced separability transitions” in a variety of states, where in one regime the mixed state is expressible as a convex sum of symmetric short-range-entangled pure states, while in the other regime, such a representation is not feasible. We first discuss the Gibbs state of Hamiltonians that exhibit spontaneous breaking of a discrete symmetry, and argue that the associated thermal phase transition can be thought of as a symmetry-enforced separability transition. Next we study cluster states in various dimensions subjected to local decoherence, and identify several distinct mixed-state phases and associated separability phase transitions, which also provides an alternative perspective on recently discussed “average symmetry-protected topological order.” We also study decohered p+ip superconductors, and find that if the decoherence breaks the fermion parity explicitly, then the resulting mixed state can be expressed as a convex sum of nonchiral states, while a fermion parity–preserving decoherence results in a phase transition at a nonzero threshold that corresponds to spontaneous breaking of fermion parity. Finally, we briefly discuss systems that satisfy the no low-energy trivial state property, such as the recently discovered good low-density parity-check codes, and argue that the Gibbs state of such systems exhibits a temperature-tuned separability transition.

Published by the American Physical Society
2024
Resonant neutron scattering lengths
Authors: Von Dreele Robert B.
Published: July 2024

Unlike most of the periodic table, many rare-earth elements display considerable resonant scattering for thermal neutrons. Although this property is accompanied by strong neutron absorption, modern high-intensity neutron sources make diffraction experiments possible with these elements. Computation of scattering intensities is accomplished by fitting the variation in resonant scattering lengths (b
0, b′ and b′′) to a semi-empirical Breit–Wigner formalism, which can be evaluated over the range of neutron energies useful for diffraction, typically E = 10–600 meV; λ = 0.4–2.8 Å (with good extrapolation to longer wavelengths).
DFT2FEFFIT: a density-functional-theory-based structural toolkit to analyze EXAFS spectra
Authors: Manceau Alain , Brossier Romain , Mathon Olivier , Lomachenko Kirill A. , Retegan Marius , Glatzel Pieter , Steinmann Stephan N.
Published: July 2024

This article presents a Python-based program, DFT2FEFFIT, to regress theoretical extended X-ray absorption fine structure (EXAFS) spectra calculated from density functional theory structure models against experimental EXAFS spectra. To showcase its application, Ce-doped fluorapatite [Ca10(PO4)6F2] is revisited as a representative of a material difficult to analyze by conventional multi-shell least-squares fitting of EXAFS spectra. The software is open source and publicly available.
Crystal structure of bis[(η5-tert-butylcyclopentadienyl)tricarbonylmolybdenum(I)](Mo—Mo)
Authors: Ibrahimova Nigar Z. , Tagiyev Dilgam B. , Lyatifov Iltifat U. , Akkurt Mehmet , Hasanov Khudayar I. , Bhattarai Ajaya
Published: July 2024

The dinuclear molecule of the title compound, [Mo2(C9H13)2(CO)6] or [Mo(
t
BuCp)(CO)3]2 where
t
Bu and Cp are tert-butyl and cyclopentadienyl, is centrosymmetric and is characterized by an Mo—Mo bond length of 3.2323 (3) Å. Imposed by inversion symmetry, the
t
BuCp and the carbonyl ligands are in a transoid arrangement to each other. In the crystal, intermolecular C—H...O contacts lead to the formation of layers parallel to the bc plane.
Inclusive value chain analysis of alligator meat in the Lago do Cuniã extractive reserve in Brazilian Amazon
Authors: Guimaraes Marcelo Macedo , Bernardes-de-Souza Dércio , da Costa Maria Clarice Alves , Paes Diego Cristóvão Alves de Souza , de Souza Mariluce Paes , Riva Fabiana Rodrigues
Published: July 2024

Purpose

The aim of this paper was to analyze the role of the Cooperative of Farmers and Fishermen of the Lago do Cuniã Extractive Reserve (COOPCUNIÃ) in the inclusion of residents in the caiman meat value chain in Porto Velho, Brazil.

Design/methodology/approach

A total of six interviews were conducted with key actors to investigate the research problem in the Lago do Cuniã EXRES, namely the president and project advisor of the cooperative, two extractivist members of the cooperative and two non-member residents. The key actors were selected based on the following criteria: being over 18 years old, residing within the reserve and having participated in some stage of the caiman meat value chain.

Findings

The results demonstrate that the cooperative contributes to the inclusion of extractivist residents in the value chain, income generation and poverty reduction, enabling the production and marketing of caiman meat. Additionally, it overcomes challenges and improves the quality of life of the local population.

Practical implications

This study emphasizes the social and economic benefits for isolated regions with low productive development. For public policymakers, the results demonstrate that inclusion has enabled access to technology and markets. For the cooperative, it showcases actions oriented towards development, social inclusion and quality of life.

Originality/value

The originality of the article lies in the analysis of the role of a value chain within an environmental protection area in the Amazon, balancing economic, social and environmental factors.
Corporate digital transformation and rank and file employee satisfaction
Authors: Zhang Bo , Wang Shengjun , Zhou Ruixue
Published: July 2024

Purpose

This paper examines the impact of corporate digital transformation on employee satisfaction. Therefore, this study extends our understanding of the economic consequences of corporate digital transformation from employees’ perspectives.

Design/methodology/approach

The data used to construct our main proxy of employee satisfaction are collected from Kanzhun.com, which provides reviews by rank-and-file employees on their employers. This study uses a large sample of Chinese firms and adopts various empirical methods to examine the impact of digital transformation on employee satisfaction.

Findings

We find a significant positive relationship between corporate digital transformation and employee satisfaction. Moreover, we document that the relationship between corporate digital transformation and employee satisfaction is more pronounced in firms with higher labor intensity and in state-owned enterprises (SOE).

Research limitations/implications

One significant limitation is that corporate digital transformation is constructed based on word frequency analysis. This approach may be influenced by variations in corporate disclosure practices and might not accurately capture the true extent of corporate digital transformation. This limitation is not only present in our research but is also pervasive in many other studies that utilize similar methodologies. Therefore, our results should be interpreted with this caveat in mind.

Practical implications

Our study suggests that corporate digital transformation enhances employee satisfaction, providing direct evidence for managers and regulators to promote corporate digital transformation. Through digital transformation, companies can not only improve operational efficiency but also foster employee satisfaction. This dual benefit underscores the importance of investing in corporate digital transformation for long-term success.

Social implications

Our study suggests that corporate digital transformation enhances employee satisfaction, providing direct evidence for managers and regulators to promote corporate digital transformation. Through digital transformation, companies can not only improve operational efficiency but also foster employee satisfaction. This dual benefit underscores the importance of investing in corporate digital transformation for long-term success.

Originality/value

Our study contributes to the literature on the economic consequences of corporate digital transformation and extends existing research on the determinants of employee satisfaction. Additionally, it provides a novel measurement of employee satisfaction for a large sample of Chinese firms.