bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Impact of an Enhanced Recovery Program for Lower Extremity Bypass
Authors: Tariq Marvi , Novak Zdenek , Spangler Emily L. , Passman Marc A. , Patterson Mark A. , Pearce Benjamin J. , Sutzko Danielle C. , Brokus S. Danielle , Busby Courtney , Beck Adam W.
Published: January 2024

Objective:

To determine the association of Enhanced Recovery Program (ERP) implementation with length of stay (LOS) and perioperative outcomes after lower extremity bypass (LEB).

Background:

ERPs have been shown to decrease hospital LOS and improve perioperative outcomes, but their impact on patients undergoing vascular surgery remains unknown.

Methods:

Patients undergoing LEB who received or did not receive care under the ERP were included: pre-ERP (1/1/2016–05/13/2018) and ERP (05/14/2018–7/31/2022). Clinicopathologic characteristics and perioperative outcomes were analyzed.

Results:

Of 393 patients who underwent LEB (pre-ERP, n=161 (41%); ERP, n=232 (59%)), most were male (n=254, 64.6%), white (n=236, 60%), and government-insured (n=265, 67.4%). Pre-ERP patients had higher BMI (28.8±6.0 vs. 27.4±5.7, P=0.03) and rates of diabetes (52% vs. 36%, P=0.002). ERP patients had shorter total (6 (3-13) vs. 7 (5-14) days, P=0.01) and postoperative LOS (5 (3-8) vs. 6 (4-8) days, P<0.001). Stratified by indication, postoperative LOS was shorter in ERP patients with claudication (3 vs. 5 d, P=0.01), rest pain (5 vs. 6 d, P=0.02) and tissue loss (6 vs. 7 d, P=0.03). ERP patients with rest pain also had a shorter total LOS (6 vs. 7 d, P=0.04) and lower 30-day readmission rates (32% to 17%, P=0.02). After ERP implementation, the average daily oral morphine equivalents (OMEs) decreased (median (IQR) 52.5 (26.6-105.0) vs. 44.12 (22.2-74.4), P=0.019), while the rates of direct discharge to home increased (83% vs. 69%, P=0.002).

Conclusions:

This is the largest single center cohort study evaluating ERP in LEB, showing that ERP implementation is associated with shorter LOS and improved perioperative outcomes.
Rising Clindamycin Resistance in Group A Streptococcus in an Irish Healthcare Institution
Authors: Lapthorne Susan , McWade Robert , Scanlon Nuala , Ní Bhaoill Saoirse , Page Aoife , O'Donnell Clare , Dornikova Gabriela , Hannan Margaret , Lynch Breda , Lynch Maureen , Brady Deirdre
Published: January 2024

Group A streptococcus (GAS) can cause serious invasive disease in humans with a high mortality rate. An increase in GAS infections was reported in Ireland in 2022, and this increase has been sustained in 2023 and is paralleled by similar trends in Europe. Rising antimicrobial resistance is a global problem and presents significant challenges to clinicians treating GAS infection. There was a reported increase in clindamycin resistance in GAS isolates in Ireland in 2022.
We examined antimicrobial susceptibility patterns of GAS isolates in our institution in 2022. Although all GAS isolates included in our study were susceptible to penicillin, we noted a high clindamycin resistance rate of 28% in our invasive GAS isolates. We also noted high tetracycline and erythromycin resistance, 43% and 30%, respectively.
Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, which often include clindamycin as an antitoxin agent. In addition, macrolides are often the first line recommended antibiotic for patients with anaphylaxis to penicillin.
This study emphasises the importance of continuous surveillance and antimicrobial susceptibility testing of invasive and non-invasive isolates in order to monitor trends in increasing antimicrobial resistance.
LSD1 inhibition suppresses ASCL1 and de-represses YAP1 to drive potent activity against neuroendocrine prostate cancer
Authors: Mandl A , Jasmine S , Krueger TEG , Kumar R , Coleman IM , Dalrymple SL , Antony L , Rosen DM , Jing Y , Hanratty B , Patel RA , Jin-Yih L , Dias J , Celatka CA , Tapper AE , Kleppe M , Kanayama M , Speranzini V , Wang YZ , Luo J , Corey E , Sena LA , Casero RA , Lotan T , Trock BJ , Kachhap SK , Denmeade SR , Carducci MA , Mattevi A , Haffner MC , Nelson PS , Rienhoff HY , Isaacs JT , Brennen WN
Published: January 2024

Lysine-specific demethylase 1 (LSD1 orKDM1A) has emerged as a critical mediator of tumor progression in metastatic castration-resistant prostate cancer (mCRPC). Among mCRPC subtypes, neuroendocrine prostate cancer (NEPC) is an exceptionally aggressive variant driven by lineage plasticity, an adaptive resistance mechanism to androgen receptor axis-targeted therapies. Our study shows that LSD1 expression is elevated in NEPC and associated with unfavorable clinical outcomes. Using genetic approaches, we validated the on-target effects of LSD1 inhibition across various models. We investigated the therapeutic potential of bomedemstat, an orally bioavailable, irreversible LSD1 inhibitor with low nanomolar potency. Our findings demonstrate potent antitumor activity against CRPC models, including tumor regressions in NEPC patient-derived xenografts. Mechanistically, our study uncovers that LSD1 inhibition suppresses the neuronal transcriptional program by downregulating ASCL1 through disrupting LSD1:INSM1 interactions and de-repressing YAP1 silencing. Our data support the clinical development of LSD1 inhibitors for treating CRPC – especially the aggressive NE phenotype.

Statement of Significance

Neuroendocrine prostate cancer presents a clinical challenge due to the lack of effective treatments. Our research demonstrates that bomedemstat, a potent and selective LSD1 inhibitor, effectively combats neuroendocrine prostate cancer by downregulating the ASCL1- dependent NE transcriptional program and re-expressing YAP1.
Evaluation of genetic associations with clinical phenotypes of kidney stone disease
Authors: Hsi Ryan S , Zhang Siwei , Triozzi Jefferson L , Hung Adriana M , Xu Yaomin , Bejan Cosmin A
Published: January 2024

Introduction and Objective

We sought to replicate and discover genetic associations of kidney stone disease within a large-scale electronic health record (EHR) system.

Methods

We performed genome-wide association studies (GWASs) for nephrolithiasis from genotyped samples of 5,571 cases and 83,692 controls. Among the significant risk variants, we performed association analyses of stone composition and first-time 24-hour urine parameters. To assess disease severity, we investigated the associations of risk variants with age at first stone diagnosis, age at first procedure, and time from first to second procedure.

Results

The main GWAS analysis identified 10 significant loci, each located on chromosome 16 within coding regions of theUMODgene, which codes for uromodulin, a urine protein with inhibitory activity for calcium crystallization. The strongest signal was from SNP 16:20359633-C-T (odds ratio [OR] 1.17, 95% CI 1.11-1.23), with the remaining significant SNPs having similar effect sizes. In subgroup GWASs by stone composition, 19 significant loci were identified, of which two loci were located in coding regions (brushite;NXPH1, rs79970906 and rs4725104). TheUMODSNP 16:20359633-C-T was associated with differences in 24-hour excretion of urinary calcium, uric acid, phosphorus, sulfate; and the minor allele was positively associated with calcium oxalate dihydrate stone composition (p<0.05). No associations were found betweenUMODvariants and disease severity.

Conclusions

We replicated germline variants associated with kidney stone disease risk atUMODand reported novel variants associated with stone composition. Genetic variants ofUMODare associated with differences in 24-hour urine parameters and stone composition, but not disease severity.
Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal
Authors: Wang Xiaoning , Zhao Jinxiang , Xu Jiehuan , Li Bowen , Liu Xia , Xie Gangcai , Duan Xuchu , Liu Dong
Published: January 2024

Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. We have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the endothelial cells in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that reducedfoxo1amediated the excessive angiogenesis induced by monosaccharides via up-regulating the expression ofmarcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.
Exploring athlete pain assessment experiences and priorities; A two-part qualitative series of athlete and physiotherapist interactions. Part Two. “Forging Our Future” - Athlete and physiotherapists’ priorities for pain assessment and beyond
Authors: Purcell Ciarán , Walsh Caoimhe Barry , Van Oirschot Garett , Fullen Brona M , Ward Tomás , Caulfield Brian M
Published: January 2024

Objectives

To explore the priorities and directions of athlete upper and lower limb pain assessment by facilitating shared understandings of athletes and sports physiotherapists.

Design

Qualitative Research using a hermeneutic phenomenological approach.

Methods

We carried out focus groups using a deliberate criterion sample and a constructivist perspective. At the end of each focus group, we used the nominal group technique method to generate a list of consensus-based priorities for future pain assessment. Our paper follows the consolidated criteria for reporting qualitative research (COREQ) guidelines.

Results

We completed five focus groups, comprising twelve athletes (female, n=5, male n=7) and four sports physiotherapists (male, n=4) Two final themes (and six subthemes) were developed; (i) Enhanced Communication and Pain Descriptions (describing and representing pain, better communication, the role of technology, providing direction and setting the pace), (ii) Integrating Sport Specific and Multidimensional Assessments (broadening the pain assessment toolkit, the role of technology). We developed a set of thirteen practical priorities for pain assessment that span the subjective, objective, and general aspects of the athlete pain assessment.

Conclusion

We have presented stakeholder-generated perspectives, directions, and priorities for athlete pain assessment. Athletes and Physiotherapists must continue to work together to achieve a comprehensive sport-specific multidimensional pain assessment experience alongside their wider support networks to ensure optimal representation and communication. We have highlighted some available pain assessment tools and strategies and outlined how novel tools may address certain gaps in the assessment process. Researchers, clinicians, and athletes can consider the practical guidance we have provided to address these priorities.
IMPDH2 filaments protect from neurodegeneration in AMPD2 deficiency
Authors: Flores-Mendez Marco , Ohl Laura , Roule Thomas , Zhou Yijing , Tintos-Hernández Jesus A , Walsh Kelsey , Ortiz-González Xilma R , Akizu Naiara
Published: January 2024

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that AMPD deficiency in mice primarily leads to hippocampal dentate gyrus degeneration despite causing a generalized reduction of brain GTP levels. Remarkably, we found that neurodegeneration resistant regions accumulate micron sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis. In contrast, IMPDH2 filaments are barely detectable in the hippocampal dentate gyrus, which shows a progressive neuroinflammation and neurodegeneration. Furthermore, using a human AMPD2 deficient neural cell culture model, we show that blocking IMPDH2 polymerization with a dominant negativeIMPDH2variant, impairs AMPD2 deficient neural progenitor growth. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation in neurons with available GTP precursor molecules, providing resistance to neurodegeneration. Our findings open the possibility of exploring the involvement of IMPDH2 assembly as a therapeutic intervention for neurodegeneration.
Individual variability in neural representations of mind-wandering
Authors: Kucyi Aaron , Anderson Nathan , Bounyarith Tiara , Braun David , Shareef-Trudeau Lotus , Treves Isaac , Braga Rodrigo M. , Hsieh Po-Jang , Hung Shao-Min
Published: January 2024

Mind-wandering is a frequent, daily mental activity, experienced in unique ways in each person. Yet neuroimaging evidence relating mind-wandering to brain activity, for example in the default mode network (DMN), has relied on population-rather than individual-based inferences due to limited within-individual sampling. Here, three densely-sampled individuals each reported hundreds of mind-wandering episodes while undergoing multi-session functional magnetic resonance imaging. We found reliable associations between mind-wandering and DMN activation when estimating brain networks within individuals using precision functional mapping. However, the timing of spontaneous DMN activity relative to subjective reports, and the networks beyond DMN that were activated and deactivated during mind-wandering, were distinct across individuals. Connectome-based predictive modeling further revealed idiosyncratic, whole-brain functional connectivity patterns that consistently predicted mind-wandering within individuals but did not fully generalize across individuals. Predictive models of mind-wandering and attention that were derived from larger-scale neuroimaging datasets largely failed when applied to densely-sampled individuals, further highlighting the need for personalized models. Our work offers novel evidence for both conserved and variable neural representations of self-reported mind-wandering in different individuals. The previously-unrecognized inter-individual variations reported here underscore the broader scientific value and potential clinical utility of idiographic approaches to brain-experience associations.
A complexPlasmodium falciparumcryptotype circulating at low frequency across the African continent
Authors: Miotto Olivo , Amambua-Ngwa Alfred , Amenga-Etego Lucas , Abdel Hamid Muzamil M , Adam Ishag , Aninagyei Enoch , Apinjoh Tobias , Awandare Gordon A , Bejon Philip , Bertin Gwladys I , Bouyou-Akotet Marielle , Claessens Antoine , Conway David J , D’Alessandro Umberto , Diakite Mahamadou , Djimdé Abdoulaye , Dondorp Arjen M , Duffy Patrick , Fairhurst Rick M , Fanello Caterina I , Ghansah Anita , Ishengoma Deus , Lawniczak Mara , Maïga-Ascofaré Oumou , Auburn Sarah , Rosanas-Urgell Anna , Wasakul Varanya , White Nina FD , Almagro-Garcia Jacob , Pearson Richard D , Goncalves Sonia , Ariani Cristina , Bozdech Zbynek , Hamilton William , Simpson Victoria , Kwiatkowski Dominic P
Published: January 2024

The population structure of the malaria parasitePlasmodium falciparumcan reveal underlying demographic and adaptive evolutionary processes. Here, we analyse population structure in 4,376P. falciparumgenomes from 21 countries across Africa. We identified a strongly differentiated cluster of parasites, comprising ∼1.2% of samples analysed, geographically distributed over 13 countries across the continent. Members of this cluster, named AF1, carry a genetic background consisting of a large number of highly differentiated variants, rarely observed outside this cluster, at a multitude of genomic loci distributed across most chromosomes. At these loci, the AF1 haplotypes appear to have common ancestry, irrespective of the sampling location; outside the shared loci, however, AF1 members are genetically similar to their sympatric parasites. AF1 parasites sharing up to 23 genomic co-inherited regions were found in all major regions of Africa, at locations over 7,000 km apart. We coined the termcryptotypeto describe a complex common background which is geographically widespread, but concealed by genomic regions of local origin. Most AF1 differentiated variants are functionally related, comprising structural variations and single nucleotide polymorphisms in components of the MSP1 complex and several other genes involved in interactions with red blood cells, including invasion and erythrocyte antigen export. We propose that AF1 parasites have adapted to some as yet unidentified evolutionary niche, by acquiring a complex compendium of interacting variants that rarely circulate separately in Africa. As the cryptotype spread across the continent, it appears to have been maintained mostly intact in spite of recombination events, suggesting a selective advantage. It is possible that other cryptotypes circulate in Africa, and new analysis methods may be needed to identify them.
Don’t put words in my mouth: Speech perception can generate False Positive activation of a speech BCI
Authors: Schippers A. , Vansteensel M.J. , Freudenburg Z.V. , Ramsey N.F.
Published: January 2024

Recent studies have demonstrated that speech can be decoded from brain activity and used for brain-computer interface (BCI)-based communication. It is however also known that the area often used as a signal source for speech decoding BCIs, the sensorimotor cortex (SMC), is also engaged when people perceive speech, thus making speech perception a potential source of false positive activation of the BCI. The current study investigated if and how speech perception may interfere with reliable speech BCI control. We recorded high-density electrocorticography (HD-ECoG) data from five subjects while they performed a speech perception and speech production task and trained a support-vector machine (SVM) on the produced speech data. Our results show that decoders that are highly reliable at detecting self-produced speech from brain signals also generate false positives during the perception of speech. We conclude that speech perception interferes with reliable BCI control, and that efforts to limit the occurrence of false positives during daily-life BCI use should be implemented in BCI design to increase the likelihood of successful adaptation by end users.
DODGE: Automated point source bacterial outbreak detection using cumulative long term genomic surveillance
Authors: Payne Michael , Hu Dalong , Wang Qinning , Sullivan Geraldine , Graham Rikki M , Rathnayake Irani U , Jennison Amy V , Sintchenko Vitali , Lan Ruiting
Published: January 2024

The reliable and timely recognition of outbreaks is a key component of public health surveillance for foodborne diseases. Whole genome sequencing (WGS) offers high resolution typing of foodborne bacterial pathogens and facilitates the accurate detection of outbreaks. This detection relies on grouping WGS data into clusters at an appropriate genetic threshold, however, methods and tools for selecting and adjusting such thresholds according to the required resolution of surveillance and epidemiological context are lacking. Here we present DODGE (Dynamic Outbreak Detection for Genomic Epidemiology), an algorithm to dynamically select and compare these genetic thresholds. DODGE can analyse expanding datasets over time and clusters that are predicted to correspond to outbreaks (or ‘investigation clusters’) can be named with the established genomic nomenclature systems to facilitate integrated analysis across jurisdictions. DODGE was tested in two real-world genomic surveillance datasets of different duration, two months from Australia and nine years from the UK. In both cases only a minority of isolates were identified as investigation clusters. Two known outbreaks in the UK dataset were detected by DODGE and were recognised at an earlier timepoint than the outbreaks were reported. These findings demonstrated the potential of the DODGE approach to improve the effectiveness and timeliness of genomic surveillance for foodborne diseases and the effectiveness of the algorithm developed.

Availability and implementation

DODGE is freely available athttps://github.com/LanLab/dodgeand can easily be installed using Conda.

Supplementary information

Supplementary Tables, Results, Figure 1 and Figure 2
Lysosomal degradation of PD-L1 is associated with immune-related adverse events during anti-PD-L1 immunotherapy in NSCLC patients
Authors: Kashiwada Takeru , Takano Ryotaro , Ando Fumihiko , Kuroda Shoko , Miyabe Yoshishige , Asatsuma-Okumura Tomoko , Hashiguchi Masaaki , Kanazawa Yoshikazu , Yoshida Hiroshi , Seike Masahiro , Gemma Akihiko , Iwai Yoshiko
Published: January 2024

BACKGROUND

Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). However, the biological mechanisms underlying irAEs are not well understood. We previously developed an ELISA system to specifically detect soluble PD-L1 (sPD-L1) with PD-1-binding capacity (bsPD-L1). Here, we investigated the relationship between sPD-L1 and bsPD-L1 in gastric cancer (GC) and non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 blockade and their association with irAEs.

METHODS

We examined sPD-L1, bsPD-L1, matrix metalloproteinases (MMPs), and proinflammatory cytokine levels by ELISA in plasma samples from 117 GC patients prior to surgery and 72 NSCLC patients prior to and at 2 months after ICI treatment (anti-PD-1, n = 48; anti-PD-L1, n = 24). In mice treated with anti-PD-1/PD-L1 antibodies (Abs), sPD-L1 levels and localization of Abs were examined by ELISA and immunohistochemistry, respectively.

RESULTS

sPD-L1 was detected with higher frequency in GC patients (76.9%) than in NSCLC patients (8.3%), whereas bsPD-L1 was detected with similar frequencies in GC and NSCLC patients (14.5% and 22.2%, respectively). sPD-L1 levels were correlated with IL-1α, IL-1β, TNF-α, and IL-6 levels, while bsPD-L1 levels were correlated with MMP13, MMP3, and IFN-γ levels. In NSCLC patients, anti-PD-L1, but not anti-PD-1, treatment increased sPD-L1, which was associated with irAE development, but not with clinical outcomes. In mice, trafficking of anti-PD-L1 Abs to lysosomes in F4/80+macrophages resulted in sPD-L1 production, which was suppressed by treatment with lysosomal degradation inhibitor chloroquine and macrophage depletion.

CONCLUSIONS

Anti-PD-L1-mediated lysosomal degradation induces sPD-L1 production, which can serve as an indicator to predict irAE development during anti-PD-L1 treatment.
Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions
Authors: Guinee Emily P. , Raza Haniya , Ballard Elizabeth D. , Shaw Jacob S. , Liang C. Jason , Sneller Michael C. , Chung Joyce Y.
Published: January 2024

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17p:0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60;p:0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.
Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing
Authors: Reichmann Jakob , Sarrazin Clement , Schmale Sebastian , Blaurock Claudia , Balkema-Buschmann Anne , Schmitzer Bernhard , Salditt Tim
Published: January 2024

X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratoryμCT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
Dynamic Modulation of Representational Trajectories Through Selective Attention
Authors: Zhou Yu , Zhang Liang , Axmacher Nikolai , Pacheco Estefan Daniel , Wang DaHui , Dai Yujian , Peng Xiaojing , Xue Gui
Published: January 2024

Mounting evidence indicates that information processing in the visual hierarchy follows a sequential progression from low-level perceptual to high-level conceptual features during visual perception, with the reverse order during memory retrieval. However, the nature of this hierarchical processing and its modulation by selective attention remains unclear. By integrating a deep neural network with the drift-diffusion model on reaction time data, we identified parallel processing of perceptual and conceptual features during perception, rather than sequential processing. The slower reaction times observed in conceptual tasks compared to perceptual tasks were primarily driven by the larger decision boundary and longer non-decision time associated with conceptual features, which could not be compensated by their faster evidence accumulation rates. Using single-trial multivariate decoding of MEG (magnetoencephalography) data to examine the timing of neural representations of different features, we found that selective attention reversed the onset times of perceptual and conceptual features in the occipital and parietal lobes during perception. This led to earlier detection of conceptual features compared to perceptual features in the animacy and size tasks. During retrieval, the colour task exhibited earlier peak times for perceptual features compared to conceptual features in the frontal lobe, indicating that perceptual features were reconstructed with the highest fidelity before conceptual features. These findings provide novel insights into the hierarchical nature of information processing during perception and retrieval, emphasizing the crucial role of selective attention in modulating the speed of feature information accumulation.
Discovery of the 1-naphthylamine biodegradation pathway reveals an enzyme that catalyzes 1-naphthylamine glutamylation
Authors: Zhang Shu-Ting , Deng Shi-Kai , Li Tao , Maloney Megan E. , Li De-Feng , Spain Jim C. , Zhou Ning-Yi
Published: January 2024

1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in isolatePseudomonassp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a cluster of 5 genes encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. Enzymatic analysis showed that NpaA1 catalyzed conversion of various anilines and naphthylamine derivatives. Structural and biochemical studies of NpaA1 revealed that the broad substrate specificity of NpaA1 is due to a large hydrophobic pocket, which is different from type I glutamine synthetase (GSI). The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.
Obesity differentially effects the somatosensory cortex and striatum of TgF344-AD rats
Authors: Ahmed Minhal , Lai Aaron Y. , Hill Mary E. , Ribeiro Jessica A. , Amiraslani Ashley , McLaurin JoAnne
Published: January 2024

1

Lifestyle choices leading to obesity, hypertension and diabetes in mid-life contribute directly to the risk of late-life Alzheimer’s disease (AD). However, in late-life or in late-stage AD conditions, obesity reduces the risk of AD and disease progression. To examine the mechanisms underlying this paradox, TgF344-AD rats were fed a varied high-carbohydrate, high-fat (HCHF) diet to induce obesity from nine months of age representing early stages of AD to twelve months of age in which rats exhibit the full spectrum of AD symptomology. We hypothesized regions primarily composed of gray matter, such as the somatosensory cortex (SSC), would be differentially affected compared to regions primarily composed of white matter, such as the striatum. We found increased myelin and oligodendrocytes in the somatosensory cortex of rats fed the HCHF diet with an absence of neuronal loss. We observed decreased inflammation in the somatosensory cortex despite increased AD pathology. Compared to the somatosensory cortex, the striatum had fewer changes. Overall, our results suggest that the interaction between diet and AD progression affects myelination in a brain region specific manner such that regions with a lower density of white matter are preferentially effected. Our results offer a possible mechanistic explanation for the obesity paradox.
Structure of hepatitis B/D antiviral drug Bulevirtide bound to its receptor protein NTCP
Authors: Liu Hongtao , Zakrzewicz Dariusz , Nosol Kamil , Irobalieva Rossitza N. , Mukherjee Somnath , Bang-Sørensen Rose , Goldmann Nora , Kunz Sebastian , Rossi Lorenzo , Kossiakoff Anthony A. , Urban Stephan , Glebe Dieter , Geyer Joachim , Locher Kaspar P.
Published: January 2024

Cellular entry of the hepatitis B and D viruses (HBV/HDV) require binding of the viral surface polypeptide preS1 to the hepatobiliary transporter NTCP. This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. To elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor’s extracellular surface. The N-terminally attached myristoyl group of BLV interacts with the lipid-exposed surface of NTCP. Our structure reveals how BLV inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infection, and provides a basis for understanding the host specificity of HBV/HDV. Our results provide opportunities for structure-guided development of inhibitors that target HBV/HDV docking to NTCP.
Mechanism of chaperone coordination during cotranslational protein folding in bacteria
Authors: Roeselová Alžběta , Maslen Sarah L. , Shivakumaraswamy Santosh , Pellowe Grant A. , Howell Steven , Joshi Dhira , Redmond Joanna , Kjaer Svend , Skehel J. Mark , Balchin David
Published: January 2024

Protein folding is assisted by molecular chaperones that bind nascent polypeptides during mRNA translation. Several structurally-distinct classes of chaperone promotede novofolding, suggesting that their activities are coordinated at the ribosome. We used biochemical reconstitution and structural proteomics to explore the molecular basis for cotranslational chaperone action in bacteria. We found that chaperone binding is disfavoured close to the ribosome, allowing folding to precede chaperone recruitment. Trigger factor subsequently recognises compact folding intermediates exposing extensive non-native surface and dictates DnaJ access to nascent chains. DnaJ uses a large surface to bind structurally diverse intermediates, and recruits DnaK to sequence-diverse solvent-accessible sites. Neither Trigger factor, DnaJ nor DnaK destabilize cotranslational folding intermediates. Instead, the chaperones collaborate to create a protected space for protein maturation that extends well beyond the ribosome exit tunnel. Our findings show how the chaperone network selects and modulates cotranslational folding intermediates.
Culture-free whole genome sequencing ofMycobacterium tuberculosisusing ligand-mediated bead enrichment method
Authors: Vasanthaiah Shruthi , Verma Renu , Kumar Ajay , Bandari Aravind , George John , Rastogi Mona , Manjunath Gowrang Kasaba , Sharma Jyoti , Kumar Abhishek , Subramani Janavi , Chawla Kiran , Pandey Akhilesh
Published: January 2024

Background

Direct whole genome sequencing (WGS) ofMycobacterium tuberculosis(Mtb) can be used as a tool to study drug resistance, mixed infections, and within host diversity. However, WGS is challenging from clinical samples due to low number of bacilli against a high background.

Methods

We prospectively collected 34 samples (sputum, n=17; bronchoalveolar lavage, BAL, n=13 and pus, n=4) from patients with active tuberculosis (TB). Prior to DNA extraction, we used a ligand-mediated magnetic bead method to enrichMtbfrom clinical samples and performed WGS on Illumina platform.

Results

Mtbwas definitively identified based on WGS from 88.2% (30/34) of the samples of which 35.3% (12/34) were smear negative. The overall median genome coverage was 15.2% (IQR = 7.9-39.3). There was a positive correlation between load of bacilli on smears and genome coverage (p-value < 0.001). We detected 58 genes listed in the WHO mutation catalogue in each positive sample (median coverage = 85%, IQR = 61%-94%), enabling the identification of mutations missed by routine diagnostics. Mutations causing resistance to rifampicin, isoniazid, streptomycin, and ethambutol were detected in 5/34 (14.7%) samples, including therpoBS441A mutation that confers resistance to rifampicin which is not covered by Xpert MTB/RIF. This approach also allowed us to identify mixed infections in eight samples (BAL=4/8, pus=2/3 and sputum= 2/10) including samples that were infected with three or more different strains ofMtb.

Conclusions

We demonstrate the feasibility of magnetic bead-based enrichment for culture-free WGS ofMtbfrom clinical specimens, including smear-negative samples. This approach can also be integrated with low-cost sequencing workflows such as targeted sequencing for rapid detection ofMtband drug resistance.
Hidden charmonium decays of spin-2 partner of
X(3872)
Authors: Zheng Yuanxin , Cai Zuxin , Li Gang , Liu Shidong , Wu Jiajun , Wu Qi
Published: January 2024

The Belle Collaboration recently reported a promising candidate for the spin-2 D*D¯* partner of the X(3872), called the X2 for short, having a mass of (4014.3±4.0±1.5)  MeV and a width of (4±11±6)  MeV. Assuming the X2 as a pure molecule of the D*D¯*, we calculated in detail the hidden charmonium decays of the X2→J/ψV and X2→ηcP via the intermediate meson loops, where V=ρ0,ω and P=π0,η,η′. The results indicate that the decay widths are strongly dependent on the X2 mass. At present center value of the mass 4014.3 MeV, the width for the X2→J/ψρ0 is predicted to be a few tens of keV, while it is on the order of 102−3  keV for the X2→J/ψω; the predicted width for the X2→ηcπ0 is about a few keV, while the widths for X2→ηcη and ηcη′ are around a few tens and tenths of keV, respectively. We also investigated the dependence of the ratios between these widths on the X2 mass and on the η−η′ mixing angle, which may be good quantities for experiments. We hope that the present calculations will be checked experimentally in the future.

Published by the American Physical Society
2024
Generation of isolated attosecond electron sheet via relativistic spatiotemporal optical manipulation
Authors: Sun Fengyu , Wang Wenpeng , Dong Hao , He Jianzhi , Shi Zhiyong , Lv Zhengxing , Zhan Qiwen , Leng Yuxin , Zhuang Songlin , Li Ruxin
Published: January 2024

Novel phase-locked acceleration of a relativistic isolated attosecond electron sheet was realized using a relativistic reflected spatiotemporal optical vortex (STOV) pulse in three-dimensional particle-in-cell simulations. Electrons can be trapped in a spatiotemporal phase singularity within the STOV pulse center, modulated into an approximately 600-attosecond duration sheet. Furthermore, electrons can be phase-locked accelerated to the order of GeV in the longitudinal direction. Such an isolated attosecond electron sheet driven by the intense STOV pulse can be used in isolated attosecond pulse generation, ultrashort x/-ray radiation, and attosecond electron diffraction.

Published by the American Physical Society
2024
Crystal structure of the RNA-recognition motif of Drosophila melanogaster tRNA (uracil-5-)-methyltransferase homolog A
Authors: Witzenberger Monika , Janowski Robert , Niessing Dierk
Published: January 2024

Human tRNA (uracil-5-)-methyltransferase 2 homolog A (TRMT2A) is the dedicated enzyme for the methylation of uridine 54 in transfer RNA (tRNA). Human TRMT2A has also been described as a modifier of polyglutamine (polyQ)-derived neuronal toxicity. The corresponding human polyQ pathologies include Huntington's disease and constitute a family of devastating neurodegenerative diseases. A polyQ tract in the corresponding disease-linked protein causes neuronal death and symptoms such as impaired motor function, as well as cognitive impairment. In polyQ disease models, silencing of TRMT2A reduced polyQ-associated cell death and polyQ protein aggregation, suggesting this protein as a valid drug target against this class of disorders. In this paper, the 1.6 Å resolution crystal structure of the RNA-recognition motif (RRM) from Drosophila melanogaster, which is a homolog of human TRMT2A, is described and analysed.
Numerical calculation of shock wave overpressure produced by multiple cloud detonation
Authors: Fu Zeye , Zou Jiahao , Han Luxin , Zhang Qi
Published: January 2024

Purpose

A model for calculating the global overpressure time history of a single cloud detonation from overpressure time history of discrete positions in the range of single cloud detonation is to be proposed and verified. The overpressure distribution produced by multiple cloud detonation and the influence of cloud spacing and fuel mass of every cloud on the overpressure distribution are to be studied.

Design/methodology/approach

A calculation method is used to obtain the global overpressure field distribution after single cloud detonation from the overpressure time history of discrete distance to detonation center after single cloud detonation. On this basis, the overpressure distribution produced by multi-cloud under different cloud spacing and different fuel mass conditions is obtained.

Findings

The results show that for 150 kg fuel, when the spacing of three clouds is 40 m, 50 m, respectively, the overpressure range of larger than 0.1 MPa is 5496.48 mˆ2 and 6235.2 mˆ2, which is 2.89 times and 3.28 times of that of single cloud detonation. The superposition effect can be ignored when the spacing between the three clouds is greater than 60 m. In the case of fixed cloud spacing, once the overpressure forms continuous effective superposition, the marginal utility of fuel decreases.

Originality/value

A model for calculating the global overpressure time history of a single cloud detonation from overpressure time history of discrete positions in the range of single cloud detonation is proposed and verified. Based on this method, the global overpressure field of single cloud detonation is reconstructed, and the superimposed overpressure distribution characteristics of three cloud detonation are calculated and analyzed.
Abusive supervisor triggers counterproductive work behaviors in nursing staff: role of psychological contract breach and Islamic work ethics
Authors: Maqbool Mehak , Lyu Bei , Ullah Sami , Khan Muhammad Tasnim , Abeden Ali Zain ul , Kukreti Mohit
Published: January 2024

Purpose

Abusive supervision (AS) provides insights into the darker aspects of leadership behavior and its effects on employees. Understanding and addressing AS can contribute to creating healthier work environments and promoting employee well-being. The effect of abusive leadership (AS) on counterproductive work behaviors (CWB) in nursing staff is examined through the theoretical lens of the social exchange theory.

Design/methodology/approach

Data were collected from 302 nursing staff working at public and private hospitals through a self-administered questionnaire. Measurement scales were adapted from the literature and the data were tested for validity and reliability before performing hypotheses testing through structural equation modeling in SmartPLS 4.0.

Findings

AS positively affects CWB, and psychological contract breach mediates this relationship. However, employees with high Islamic work ethics (IWE) are less concerned with supervisors' dysfunctional behaviors and pay less attention to them; thus, IWE buffers the effect of AS on CWBs.

Originality/value

A positive and supportive organizational climate is crucial for attracting and retaining skilled healthcare professionals. When healthcare professionals are subjected to abusive behaviors, their ability to share knowledge, adopt safety protocols and provide the best patient care may be hampered. Therefore, addressing AS in hospitals is vital to promoting a positive work environment, enhancing employee well-being and improving patient care.
Impact of individual-focused transformational leadership on individual work performance: mediating role of work engagement and moderating role of regulatory focus
Authors: Fernando Panawannage Bhagya Dewmini , Jayawardana Ananda K.L.
Published: January 2024

Purpose

This study aims to investigate how the individual-focused transformational leadership effect of transformational leadership impacts the team member’s individual work performance through the intermediary mechanisms of work engagement and regulatory focus.

Design/methodology/approach

A moderated mediation model was analyzed through PLS-SEM by using a sample of 462 team members across diverse work teams in Sri Lankan organizations.

Findings

Results revealed that individual-focused transformational leadership positively impacts the team member’s individual work performance through the mediation of the team member’s work engagement. The direct relationship between individual-focused transformational leadership and the team member’s work engagement was found to be positively moderated by the team member’s promotion regulatory focus.

Practical implications

This paper demonstrates implications for team designing and leadership development and highlights the importance of team leaders utilizing individual-focused transformational leadership to gain improved work performance from each team member.

Originality/value

This study provides empirical evidence for the mediating role of work engagement and the moderating role of promotion regulatory focus in deriving the team member’s work performance, which contributes to constructing a more refined profile of individual-focused transformational leadership.
Functional traits and size interact to influence growth and carbon sequestration among trees in urban greenspaces
Authors: Simovic Milos , Mueller Kevin E. , McMahon Sean M. , Medeiros Juliana S.
Published: January 2024

There is persistent uncertainty about how integrated plant functions, like growth, are mechanistically constrained and practically predicted by functional traits. For trees, these knowledge gaps persist for two reasons: First, studies of ‘natural’ forests are observational, with highly variable and confounding resource limitation and competition; second, most studies investigate only a few popular traits and ignore context‐dependencies in trait effects on growth (e.g. trait–environment or trait–ontogeny interactions).

We assessed 17 traits as predictors of radial growth and aboveground carbon sequestration for 182 trees, including individuals of 42 species common to temperate cities. By focusing exclusively on planted trees growing in isolation, our unique study is a pseudo‐experiment that spans a large range of taxonomic and trait variability, and minimizes confounding effects of environmental heterogeneity (e.g. shifts in light availability with tree size). Focal traits included not only commonly measured traits related to leaf economics and plant size, but also wood traits and whole‐plant phenology.

Models with indices of tree ontogeny (size) and traits explained 80% and 72% of variability in relative growth and carbon sequestration, respectively, and traits accounted for ~20% of the variation. Traits related to said tree functions included leaf dry matter content (LDMC), leaf N content, mature height, wood anatomy and phenology. LDMC was positively correlated with wood growth and C sequestration across all size classes, while the positive effects of leaf N, mature height and wood density were only apparent for smaller trees. Ring‐porous species had higher rates of growth and C sequestration than diffuse‐porous species.

Consistent with recent theory, growth rates of isolated, urban trees vary as function of simple and interactive effects of traits and size. Our findings are useful for optimizing reforestation efforts in temperate cities, where planners and land managers can select species for rapid growth and C sequestration using freely available data for the ‘effect’ traits we identified, including wood anatomy and density, leaf N, and LDMC. Lastly, the trait–growth relationships we describe here may reflect those of ‘naturally’ isolated trees growing in savannas and/or woodlands and provide an insightful frame of reference for trees in closed‐canopy forests.

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