bluuebunny/crossref_metadata_2025 huggingface dataset:
Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment
Authors: Naude James , Wang Meng , Leon Rebeca , Smith Eric , Ismail Zahinoor
Published: February 2024

Mild Behavioral Impairment (MBI) leverages later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Phosphorylated tau (p-tau) is a hallmark biological manifestation of Alzheimer disease (AD). We investigated associations between MBI and tau accumulation in early-stage AD cortical regions. In 442 Alzheimer’s Disease Neuroimaging Initiative participants with normal cognition or mild cognitive impairment, MBI status was determined alongside corresponding p-tau and Aβ. Two meta-regions of interest were generated to represent Braak I and III neuropathological stages. Multivariable linear regression modelled the association between MBI as independent variable and tau tracer uptake as dependent variable. Among Aβpositive individuals, MBI was associated with tau uptake in Braak I (β=0.45(0.15),p<.01) and Braak III (β=0.24(0.07),p<.01) regions. In Aβnegative individuals, MBI was not associated with tau in the Braak I region (p=.11) with a negative association in Braak III (p=.01). These findings suggest MBI may be a sequela of neurodegeneration, and can be implemented as a cost-effective framework to help improve screening efficiency for AD.
Cranial sexual dimorphism levels in modern humans: Supporting a global expansion originating in southern Africa
Authors: Cenac Zarus
Published: February 2024

Modern humans are acknowledged to have expanded across Earth from Africa. Biological measures have appeared to reflect this expansion, such as genetic diversity and cranial sexual size dimorphism. Admixture is known to be an issue for using diversity to locate where the expansion set out from in Africa; using cranial dimorphism should make admixture less of an issue. Therefore, cranial dimorphism could be of importance for clarifying the origin. This study used data sourced from the Howells dataset to infer if cranial form and shape dimorphisms indicate the expansion, and understand why cranial size dimorphism looks indicative. Form and shape dimorphisms were calculated through RMET. Size dimorphism was calculated beforehand. Cranial form and shape dimorphisms increased with distance from Africa. Form dimorphism suggested an area of origin which was predominantly in Africa and marginally in Asia. For shape dimorphism, locations spanned much farther beyond Africa. Hence, cranial form dimorphism seemed to be quite indicative of the expansion, unlike cranial shape dimorphism. Form is known to feature size and shape – cranial form dimorphism may signify the expansion mainly, or only, due to cranial size dimorphism. It seemed unsettled why cranial size and form dimorphisms seem related to the expansion because it was vague whether cranial size indicates the expansion more for males than females. Previously, a collective estimate of the origin (from biological measures including cranial size dimorphism) pointed to southern Africa; in the collective estimation process, cranial size dimorphism supported the south as would cranial form and shape dimorphisms.
Contemporary Administrative Codes For Identifying Pulmonary Vein Isolation Procedures for Atrial Fibrillation
Authors: Ferro Enrico G , Reynolds Matthew R. , Jiaman Xu , Song Yang , Cohen David J. , Wadhera Rishi K , d’Avila Andre , Zimetbaum Peter J , Yeh Robert W , Kramer Daniel B
Published: February 2024

Introduction

Use of pulmonary vein isolation (PVI) to treat atrial fibrillation continues to grow. Despite great interest in leveraging administrative data for real-world analyses, reliability of contemporary procedural codes for identifying PVI have not been carefully examined.

Methods

Inpatient PVIs were identified among US Medicare fee-for-service beneficiaries using Current Procedural Terminology (CPT) code 93656 in the Carrier Line Files. Each patient was cross-matched by procedure date with claims from Medicare Provider Analysis and Review Files (MedPAR) in order to compare CPT claims with International Classification of Diseases-10thRevision Procedure Coding System (ICD-10-PCS) claims submitted by healthcare facilities to bill for the same procedure. We performed the reverse analysis for commonly matched ICD-10-PCS codes to identify their corresponding CPT-billed procedures. Lastly, we reviewed a random selection of 100 institutional cases for additional comparison of CPT and ICD-10-PCS assignation.

Results

We identified 25,617 inpatient PVIs from 1/2017 to 12/2021, of which 18,165 (71%) were linked to MedPAR by same-day procedure date. Of these, 16,672 (92%) were coded as ICD-10 02583ZZ “Destruction of Conduction Mechanism, Percutaneous Approach”, with lower use of other codes. The reverse process yielded heterogeneous results: among 75,003 procedures billed as ICD-10 02583ZZ, only 15,691 (21%) matched with CPT 93656 (PVI), as several other procedures were interchangeably billed under this same ICD-10 code. Institutional case review confirmed the greater specificity of CPT codes for identifying PVIs.

Conclusions

The ICD-10-PCS code most commonly associated with CPT-billed PVI procedures actually refers to ablation of the atrio-ventricular junction. Yet this same ICD-10-PCS code also matches with a wide range of other procedures distinct from PVI. We conclude that ICD-10-PCS codes alone are neither sensitive nor specific for identifying PVIs in claims. CPT codes should be used for health services research on this important procedure.
From multiplicity of infection to force of infection for sparsely sampledPlasmodium falciparumpopulations at high transmission
Authors: Zhan Qi , Tiedje Kathryn , Day Karen Patricia , Pascual Mercedes
Published: February 2024

High multiplicity of infection or MOI, the number of genetically distinct parasite strains co-infecting a single human host, characterizes infectious diseases including falciparum malaria at high transmission. It accompanies high asymptomaticPlasmodium falciparumprevalence despite high exposure, creating a large transmission reservoir challenging intervention. High MOI and asymptomatic prevalence are enabled by immune evasion of the parasite achieved via vast antigenic diversity. Force of infection or FOI, the number of new infections acquired by an individual host over a given time interval, is the dynamic sister quantity of MOI, and a key epidemiological parameter for monitoring the impact of antimalarial interventions and assessing vaccine or drug efficacy in clinical trials. FOI remains difficult, expensive, and labor-intensive to accurately measure, especially in high-transmission regions, whether directly via cohort studies or indirectly via the fitting of epidemiological models to repeated cross-sectional surveys. We propose here the application of queuing theory to obtain FOI on the basis of MOI, in the form of either a two-moment approximation method or Little's law. We illustrate these methods with MOI estimates obtained under sparse sampling schemes with the recently proposed "varcoding" method, based on sequences of thevarmultigene family encoding for the major variant surface antigen of the blood stage of malaria infection. The methods are evaluated with simulation output from a stochastic agent-based model, and are applied to an interrupted time-series study from Bongo District in northern Ghana before and immediately after a three-round transient indoor residual spraying (IRS) intervention. We incorporate into the sampling of the simulation output, limitations representative of those encountered in the collection of field data, including under-sampling ofvargenes, missing data, and usage of antimalarial drug treatment. We address these limitations in MOI estimates with a Bayesian framework and an imputation bootstrap approach. We demonstrate that both proposed methods give good and consistent FOI estimates across various simulated scenarios. Their application to the field surveys shows a pronounced reduction in annual FOI during intervention, of more than 70%. The proposed approach should be applicable to the many geographical locations where cohort or cross-sectional studies with regular and frequent sampling are lacking but single-time-point surveys under sparse sampling schemes are available, and for MOI estimates obtained in different ways. They should also be relevant to other pathogens of humans, wildlife and livestock whose immune evasion strategies are based on large antigenic variation resulting in high multiplicity of infection.
Liver Intrinsic Function Evaluation (LIFE): Multi-parametric Liver Function Profiles of Patients Undergoing Hepatectomy
Authors: Simonsson Christian , Bartholomä Wolf Claus , Larsson Anna Lindhoff , Karlsson Markus , Cai Shan , Tellman Jens , Norén Bengt , Björnsson Bergthor , Cedersund Gunnar , Dahlström Nils , Sandström Per , Lundberg Peter
Published: February 2024

Background & Aims

For a range of liver malignancies, the only curative treatment option may be hepatectomy, which may have fatal complications. Therefore, an unbiased pre-operative risk assessment is vital, however, at present the assessment is typically based on global liver function only. Magnetic resonance imaging (MRI) modalities have the possibility to aid this assessment, by introducing additional characterization of liver parenchymal, such as non-invasive quantification of steatosis, fibrosis, and uptake function, both for global and regional assessment. To this cause, we here present a prospective observation study (LIFE), in which patients underwent extensive MR-examinations both before and after resective-surgery.

Approach and Results

A total of 13 patients undergoing hepatectomy underwent a pre- (n=13) and post (m=5) multimodal MRI examination (within 3-5 days of the surgery) (Fig. 1B). The multimodal MR-examination included DCE, 3D-MRE, fat fraction measurements (PDFF by MRS, 6PD). Using these measurements, we also construct individual patient profiles by including conventional functional, and volumetric measurements, into a multi-parametric space. As a proof of concept, the areas of each profile, denoted ‘multiparametric profile area’ (MPA, and aMPA) were calculated, to create a measurement comprising information from all modalities.

At a group-level, no clear pattern emerged of MPA or aMPA between groups with different extent of resection. In contrast, on a case-by-case basis, several parameters contributed to high individual MPA or aMPA-values, suggesting tissue abnormalities. With respect to regional DCE measurements,i.e., relative enhancement at 20 minutes, a clear variation between function in segments, within and between the individuals, was observed.

Conclusions

In this combined pre- and post-observational case-based study ranging from very extensive (i) liver surgery to minor (ii), or none (iii), we aimed to describe how a multi-modal MRI examination before hepatectomy could yield valuable information for the pre-operative assessment, with a particular focus on a Couinaud-segmental level. The use of a multi-modal approach allows for a broad spectral characterization of several aspects of the remnant tissue. However, the effectiveness and clinical benefit of each parameter, and how to further optimize an abbreviated clinical MR-protocol needs to be confirmed.
Deep Learning for Multi-Label Disease Classification of Retinal Images: Insights from Brazilian Data for AI Development in Lower-Middle Income Countries
Authors: Gould Dewi S.W. , Yang Jenny , Clifton David A.
Published: February 2024

Retinal fundus imaging is a powerful tool for disease screening and diagnosis in opthalmology. With the advent of machine learning and artificial intelligence, in particular modern computer vision classification algorithms, there is broad scope for technology to improve accuracy, increase accessibility and reduce cost in these processes. In this paper we present the first deep learning model trained on the first Brazilian multi-label opthalmological datatset. We train a multi-label classifier using over 16,000 clinically-labelled fundus images. Across a range of 13 retinal diseases, we obtain frequency-weighted AUC and F1 scores of0.92and0.70respectively. Our work establishes a baseline model on this new dataset and furthermore demonstrates the applicability and power of artificial intelligence approaches to retinal fundus disease diagnosis in under-represented populations.
Association of multidrug-resistant bacteria and clinical outcomes in patients with infected diabetic foot in a Peruvian Hospital: A retrospective cohort analysis
Authors: Yovera-Aldana Marlon , Sifuentes-Hermenegildo Paola , Cervera-Ocaña Martha Sofia , Mezones-Holguin Edward
Published: February 2024

Objective

To evaluate the association of multidrug-resistant bacteria (MDRB) and adverse clinical outcomes in patients with infected diabetic foot (IDF) in a Peruvian hospital.

Materials and Methods

This retrospective cohort study evaluated patients treated in the Diabetic Foot Unit of a General Hospital in Lima, Peru. MDRB was based on resistance to more than two pharmacological groups across six clinically significant genera. The primary outcome was death due to complications of the IDF and/or major amputation. Other outcomes included minor amputation, hospitalization, and a hospital stay longer than 14 days. Relative risks were estimated using Poisson regression for all outcomes.

Results

The study included 192 IDF patients with a mean age of 59.9 years; 74% were males. A total of 80.8% exhibited MDRB. The primary outcome had an incidence rate of 23.2% and 5.4% in patients with and without MDRB, respectively (p = 0.01). After adjusting for sex, age, bone involvement, severe infection, ischemia, diabetes duration, and glycosylated hemoglobin, MDRB showed no association with the primary outcome (RR 3.29; 95% CI, 0.77 - 13.9), but did with hospitalization longer than 14 days (RR 1.43; 95% CI, 1.04 - 1.98).

Conclusions

Our study found no association between MDRB and increased mortality and/or major amputation but did find a correlation with prolonged hospitalization. The high proportion of MDRB could limit the demonstration of the relationship. It is urgent to apply continuous evaluation of bacterial resistance, implement a rational plan for antibiotic use, and maintain biosafety to confront this threat.
Low-dose cryo-electron ptychography of proteins at sub-nanometer resolution
Authors: Küçükoğlu Berk , Mohammed Inayathulla , Guerrero-Ferreira Ricardo C. , Kube Massimo , Radecke Julika , Ribet Stephanie M. , Varnavides Georgios , Leidl Max Leo , Lau Kelvin , Nazarov Sergey , Myasnikov Alexander , Sachse Carsten , Müller-Caspary Knut , Ophus Colin , Stahlberg Henning
Published: February 2024

Cryo-transmission electron microscopy (cryo-EM) of frozen hydrated specimens is an efficient method for the structural analysis of purified biological molecules. However, cryo-EM and cryo-electron tomography are limited by the low signal-to-noise ratio (SNR) of recorded images, making detection of smaller particles challenging. For dose-resilient samples often studied in the physical sciences, electron ptychography – a coherent diffractive imaging technique using 4D scanning transmission electron microscopy (4D-STEM) – has recently demonstrated excellent SNR and resolution down to tens of picometers for thin specimens imaged at room temperature.

Here we applied 4D-STEM and ptychographic data analysis to frozen hydrated proteins, reaching sub-nanometer resolution 3D reconstructions. We employed low-dose cryo-EM with an aberration-corrected, convergent electron beam to collect 4D-STEM data for our reconstructions. The high frame rate of the electron detector allowed us to record large datasets of electron diffraction patterns with substantial overlaps between the interaction volumes of adjacent scan positions, from which the scattering potentials of the samples were iteratively reconstructed. The reconstructed micrographs show strong SNR enabling the reconstruction of the structure of apoferritin protein at up to 5.8 Å resolution. We also show structural analysis of the Phi92 capsid and sheath, tobacco mosaic virus, and bacteriorhodopsin at slightly lower resolutions.
Phototropin connects blue light perception to starch metabolism in green algae
Authors: Yuan Yizhong , Iannetta Anthony A , Kim Minjae , Sadecki Patric W. , Arend Marius , Tsichla Angeliki , Ruiz-Sola M. Águila , Kepesidis Georgios , Falconet Denis , Thevenon Emmanuel , Tardif Marianne , Brugière Sabine , Couté Yohann , Kleman Jean Philippe , Sizova Irina , Schilling Marion , Jouhet Juliette , Hegemann Peter , Li-Beisson Yonghua , Nikoloski Zoran , Bastien Olivier , Hicks Leslie M. , Petroutsos Dimitris
Published: February 2024

In photosynthetic organisms light acts as an environmental signal to control their development and physiology, and as energy source to drive the conversion of CO2into carbohydrates used for growth or storage. The main storage carbohydrate in green algae is starch, which accumulates during the day and is broken down at night to meet cellular energy demands. The signalling role of light quality in the regulation of starch accumulation remains unexplored. Here, we identify PHOTOTROPIN-MEDIATED SIGNALLING KINASE 1 (PMSK1) as a key regulator of starch metabolism inChlamydomonas reinhardtii. In its phosphorylated form (PMSK1-P), it activates GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAP1), promoting starch biosynthesis. We show that blue light, perceived by PHOTOTROPIN, induces PMSK1 dephosphorylation that in turn represses GAP1 mRNA levels and reduces starch accumulation. These findings reveal a novel blue light-mediated signaling pathway that advances our understanding of photoreceptor-controlled carbon metabolism in microalgae.

One-Sentence Summary

Blue light perception by PHOTOTROPIN triggers kinase-mediated signaling to inhibit starch accumulation in the green algaChlamydomonas.
Adaptation of turnip mosaic virus toArabidopsis thalianainvolves rewiring of VPg - host proteome interactions
Authors: Carrasco José L. , Ambrós Silvia , Gutiérrez Pablo A. , Elena Santiago F.
Published: February 2024

The outcome of a viral infection depends on a complex interplay between the host physiology and the virus, mediated through numerous protein-protein interactions. In a previous study we used high-throughput yeast two-hybrid (HT-Y2H) to identify proteins inArabidopsis thalianathat bind to the proteins encoded by the turnip mosaic virus (TuMV) genome. Furthermore, after experimental evolution of TuMV lineages in plants with mutations in defense-related or proviral genes, most mutations observed in the evolved viruses affected the VPg cistron. Among these mutations, D113G was a convergent mutation selected in many lineages across different plant genotypes. In contrast, mutation R118H specifically emerged in thejin1mutant with affected jasmonate signaling. Using the HT-Y2H system, we analyzed the impact of these two mutations on VPg’s interaction with plant proteins. Interestingly, both mutations severely compromised the interaction of VPg with the translation initiation factor eIF(iso)4E, a crucial interactor for potyvirus infection. Moreover, mutation D113G, but not R118H, adversely affected the interaction with RHD1, a zinc-finger homeodomain transcription factor involved in regulating DNA demethylation. Our results suggest that RHD1 enhances plant tolerance to TuMV infection.
Intermolecular Energy Migration via HomoFRET Captures the Modulation in the Material Property of Phase-Separated Biomolecular Condensates
Authors: Joshi Ashish , Walimbe Anuja , Sarkar Snehasis , Arora Lisha , Kaur Gaganpreet , Jhandai Prince , Chatterjee Dhruba , Banerjee Indranil , Mukhopadhyay Samrat
Published: February 2024

Biomolecular condensation via phase separation of proteins and nucleic acids has emerged as a crucial mechanism underlying the spatiotemporal organization of cellular components into functional membraneless organelles. However, aberrant maturation of these dynamic, liquid-like assemblies into irreversible gel-like or solid-like aggregates is associated with a wide range of fatal neurodegenerative diseases. New tools are essential to dissect the changes in the internal material properties of these biomolecular condensates that are often modulated by a wide range of factors involving the sequence composition, truncations, mutations, post-translational modifications, and the stoichiometry of nucleic acids and other biomolecules. Here, we employ homo-Förster Resonance Energy Transfer (homoFRET) as a proximity ruler to study intermolecular energy migration that illuminates the molecular packing in the nanometric length-scale within biomolecular condensates. We used the homoFRET efficiency, measured by a loss in the fluorescence anisotropy due to rapid depolarization, as a readout of the molecular packing giving rise to material properties of biomolecular condensates. Using single-droplet anisotropy imaging, we recorded spatially-resolved homoFRET efficiencies of condensates formed by fluorescent protein-tagged Fused in Sarcoma (FUS). By performing single-droplet picosecond time-resolved anisotropy measurements, we were able to discern various energy migration events within the dense network of polypeptide chains in FUS condensates. Our homoFRET studies also captured the modulation of material properties by RNA, ATP, and post-translational modification. Additionally, we utilized mammalian cell lines stably expressing FUS to study nuclear FUS and oxidative stress-induced stress granule formation in the cytoplasm. Our studies demonstrate that spatially-resolved homoFRET methodology offers a potent tool for studying intracellular phase transitions in cell physiology and disease.
GenomicSEM Modelling of Diverse Executive Function GWAS Improves Gene Discovery
Authors: Perry Lucas C ,   CHARGE Consortium, Chevalier Nicolas , Luciano Michelle
Published: February 2024

Previous research has supported the use of latent variables as the gold-standard in measuring executive function. However, for logistical reasons genome-wide association studies (GWAS) of executive function have largely eschewed latent variables in favour of singular task measures. As low correlations have traditionally been found between individual executive function (EF) tests, it is unclear whether these GWAS have truly been measuring the same construct. In this study, we addressed this question by performing a factor analysis on summary statistics from eleven GWAS of EF taken from five studies, using GenomicSEM. Models demonstrated a bifactor structure consistent with previous research, with factors capturing common EF and working memory-specific variance. Furthermore, the GWAS performed on this model identified 20 new genomic risk loci for common EF and 4 for working memory reaching genome-wide significance beyond what was found in the constituent GWAS, together resulting in 29 newly mapped EF genes. These results help to clarify the underlying genetic structure of EF and support the idea that EF GWAS are capable of measuring genetic variance related to latent EF constructs even when not using factor scores. Furthermore, they demonstrate that GenomicSEM can combine GWAS with divergent and non-ideal measures of the same phenotype to improve statistical power.
Nanoscale Structure, Interactions, and Dynamics of Centromere Nucleosomes
Authors: Filliaux Shaun , Sun Zhiqiang , Lyubchenko Yuri L.
Published: February 2024

Centromeres are specific segments of chromosomes responsible for the accurate chromosome segregation process. Centromeres are comprised of two types of nucleosomes: canonical nucleosomes containing an octamer of H2A, H2B, H3, and H4 histones, and CENP-A nucleosomes in which H3 is replaced with its analog CENP-A histone. This modification leads to the difference in the nuclear of DNA turns around the histone core, wrapping efficiency. This value is 121 bp of DNA, considerably less than 147 bp found in canonical nucleosomes. We used Atomic Force Microscopy (AFM) to characterize nanoscale features for both types of nucleosomes assembled on the same template, enabling us to evaluate the effect of internucleosomal interaction. We found that CENP-A mononucleosomes have a lower internucleosomal affinity than canonical H3 nucleosomes. We applied time-lapse, high-speed AFM (HS-AFM) to characterize the dynamics of nucleosomes. For both nucleosomes, spontaneous unwrapping of DNA was observed, and this process occurs via a transient state with ∼100 bp DNA wrapped around the core, followed by a rapid dissociation of DNA. The unwrapping process is asymmetric, so when the dissociation starts on one arm, it enlarges the size of the dissociated arm. Additionally, HS-AFM revealed higher stability of CENP-nucleosomes compared with H3 ones, in which dissociation of the histone core occurs prior to the nucleosome dissociation. The histone core of CENP-A nucleosomes remains intact even after the dissociation of DNA.
A nociceptive amygdala-striatal pathway for chronic pain aversion
Authors: Wojick Jessica A. , Paranjapye Alekh , Chiu Juliann K. , Mahmood Malaika , Oswell Corinna , Kimmey Blake A. , Wooldridge Lisa M. , McCall Nora M. , Han Alan , Ejoh Lindsay L. , Chehimi Samar Nasser , Crist Richard C. , Reiner Benjamin C. , Korb Erica , Corder Gregory
Published: February 2024

The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble ofnociceptive BLA projection neurons (BLAnociensemble). However, the role of the BLAnociensemble in mediating behavior changes and the molecular signatures and downstream targets distinguishing this ensemble remain poorly understood. Here, we show that the same BLAnociensemble neurons are required for both acute and chronic neuropathic pain behavior. Using single nucleus RNA-sequencing, we characterized the effect of acute and chronic pain on the BLA and identified enrichment for genes with known functions in axonal and synaptic organization and pain perception. We thus examined the brain-wide targets of the BLAnociensemble and uncovered a previously undescribednociceptive hotspot of the nucleus accumbens shell (NAcSh) that mirrors the stability and specificity of the BLAnociensemble and is recruited in chronic pain. Notably, BLAnociensemble axons transmit acute and neuropathicnociceptive information to the NAcSh, highlighting thisnociceptive amygdala-striatal circuit as a unique pathway for affective-motivational responses across pain states.
Short-term memory capacity predicts willingness to expend cognitive effort for reward
Authors: Forys Brandon J. , Winstanley Catharine A. , Kingstone Alan , Todd Rebecca M.
Published: February 2024

We must often decide whether the effort required for a task is worth the reward. Past rodent work suggests that willingness to deploy cognitive effort can be driven by individual differences in perceived reward value, depression, or chronic stress. However, many factors driving cognitive effort deployment - such as short-term memory ability - cannot easily be captured in rodents. Furthermore, we do not fully understand how individual differences in short-term memory ability, depression, chronic stress, and reward anticipation impact cognitive effort deployment for reward. Here, we examined whether these factors predict cognitive effort deployment for higher reward in an online visual short-term memory task. Undergraduate participants were grouped into high and low effort groups (nHighEffort= 348,nLowEffort= 81;nFemale= 332,nMale= 92,MAge= 20.37,RangeAge= 16-42) based on decisions in this task. After completing a monetary incentive task to measure reward anticipation, participants completed short-term memory task trials where they could choose to encode either fewer (low effort/reward) or more (high effort/reward) squares before reporting whether or not the colour of a target square matched the square previously in that location. We found that only greater short-term memory ability predicted whether participants chose a much higher proportion of high vs. low effort trials. Drift diffusion modeling showed that high effort group participants were more biased than low effort group participants towards selecting high effort trials. Our findings highlight the role of individual differences in cognitive effort ability in explaining cognitive effort deployment choices.

Significance statement

We must often make decisions about when cognitive effort is worth the potential reward. Reward value, depression, and chronic stress in rodents can impact cognitive effort deployment decisions for reward, but factors like short-term memory ability can only be easily characterized in humans. We examined whether short-term memory ability, depression, chronic stress, and reward anticipation predict cognitive effort decisions for reward. In a short-term visual memory task with a choice of easier or harder trials for low vs. high reward, we found that only short-term memory ability predicted more choices of high vs. low effort trials. This research suggests that cognitive effort decisions could be driven by cognitive effort ability more than motivational factors like depression or chronic stress.
Mitochondrial bioenergetics stimulates autophagy for pathological tau clearance in tauopathy neurons
Authors: Jia Nuo , Ganesan Dhasarathan , Guan Hongyuan , Jeong Yu Young , Han Sinsuk , Nissenbaum Marialaina , Kusnecov Alexander W. , Cai Qian
Published: February 2024

Hyperphosphorylation and aggregation of microtubule-associated tau is a pathogenic hallmark of tauopathies and a defining feature of Alzheimer’s disease (AD). Pathological tau is targeted by autophagy for clearance, but autophagy dysfunction is indicated in tauopathy. While mitochondrial bioenergetic failure has been shown to precede the development of tau pathology, it is unclear whether energy metabolism deficiency is involved in tauopathy-related autophagy defects. Here, we reveal that stimulation of anaplerotic metabolism restores defective oxidative phosphorylation (OXPHOS) in tauopathy which, strikingly, leads to enhanced autophagy and pronounced tau clearance. OXPHOS-induced autophagy is attributed to increased ATP-dependent phosphatidylethanolamine biosynthesis in mitochondria. Excitingly, early bioenergetic stimulation boosts autophagy activity and reduces tau pathology, thereby counteracting memory impairment in tauopathy mice. Taken together, our study sheds light on a pivotal role of bioenergetic dysfunction in tauopathy-linked autophagy defects and suggests a new therapeutic strategy to prevent toxic tau buildup in AD and other tauopathies.
Metabolites that feed upper glycolytic branches support glucose independent human cytomegalovirus replication
Authors: Mokry Rebekah L. , Purdy John G.
Published: February 2024

The broad tissue distribution and cell tropism of human cytomegalovirus indicates that the virus successfully replicates in tissues with various nutrient environments. HCMV requires and reprograms central carbon metabolism for viral replication. However, many studies focus on reprogramming of metabolism in high nutrient conditions that do not recapitulate physiological nutrient environments in the body. In this study, we investigate how HCMV successfully replicates when nutrients are suboptimal. We limited glucose following HCMV infection to determine how glucose supports virus replication and how nutrients potentially present in the physiological environment contribute to successful glucose independent HCMV replication. Glucose is required for HCMV viral genome synthesis, viral protein production and glycosylation, and virus production. However, supplement of glucose-free cultures with uridine, ribose, or UDP-GlcNAc—metabolites that support upper glycolytic branches—resulted in partially restored viral genome synthesis and subsequent partial restoration of viral protein levels. Low levels of virus production were also restored. Supplementing lower glycolysis in glucose-free cultures using pyruvate had no effect on virus replication. These results indicate nutrients that support upper glycolytic branches like the pentose phosphate pathway and hexosamine pathway can compensate for glucose during HCMV replication to support low levels of virus production. More broadly, our findings suggest that HCMV could successfully replicate in diverse metabolic niches, including those in the body with low levels of glucose, through alternative nutrient usage.

IMPORTANCE

The metabolic environment is a determinant in the ability of a virus to successfully replicate. HCMV has broad cell tropism and replicates in various tissues that have diverse and/or limiting metabolic environments. We know that HCMV reprograms host central carbon metabolism to support viral replication, but we have little understanding of HCMV replication in diverse metabolic niches as most studies use high nutrient culture media. Here, we show that glucose limitation suppresses virus production through loss of viral genome synthesis and viral protein glycosylation. However, nutrient compensation by uridine, ribose, and UDP-GlcNAc, metabolites that fuel upper glycolytic branches such as the non-oxidative pentose phosphate pathway support low levels of glucose-independent virus production. Our work indicates that metabolite compensation may facilitate HCMV replication in nutrient limited niches in the body.
Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis
Authors: Boles Jake Sondag , Holt Jenny , Cole Cassandra L. , Neighbarger Noelle K. , Urs Nikhil M. , Huarte Oihane Uriarte , Tansey Malú Gámez
Published: February 2024

Parkinson’s disease (PD) is characterized by a decades-long prodrome, consisting of a collection of non-motor symptoms that emerges prior to the motor manifestation of the disease. Of these non-motor symptoms, gastrointestinal dysfunction and deficits attributed to central norepinephrine (NE) loss, including mood changes and sleep disturbances, are frequent in the PD population and emerge early in the disease. Evidence is mounting that injury and inflammation in the gut and locus coeruleus (LC), respectively, underlie these symptoms, and the injury of these systems is central to the progression of PD. In this study, we generate a novel two-hit mouse model that captures both features, using dextran sulfate sodium (DSS) to induce gut inflammation and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to lesion the LC. We first confirmed the specificity of DSP-4 for central NE using neurochemical methods and fluorescence light-sheet microscopy of cleared tissue, and established that DSS-induced outcomes in the periphery, including weight loss, gross indices of gut injury and systemic inflammation, the loss of tight junction proteins in the colonic epithelium, and markers of colonic inflammation, were unaffected with DSP-4 pre-administration. We then measured alterations in neuroimmune gene expression in the ventral midbrain in response to DSS treatment alone as well as the extent to which prior LC injury modified this response. In this two-hit model we observed that DSS-induced colitis activates the expression of key cytokines and chemokines in the ventral midbrain only in the presence of LC injury and the typical DSS-associated neuroimmune is blunted by pre-LC lesioning with DSP-4. In all, this study supports the growing appreciation for the LC as neuroprotective against inflammation-induced brain injury and draws attention to the potential for NEergic interventions to exert disease-modifying effects under conditions where peripheral inflammation may compromise ventral midbrain dopaminergic neurons and increase the risk for development of PD.
Frequency and spectrum of mutations in human sperm measured using duplex sequencing correlate with trio-basedde novomutation analyses
Authors: Axelsson Jonatan , LeBlanc Danielle , Shojaeisaadi Habiballah , Meier Matthew J , Fitzgerald Devon M. , Nachmanson Daniela , Carlson Jedidiah , Golubeva Alexandra , Higgins Jake , Smith Thomas , Lo Fang Yin , Pilsner Richard , Williams Andrew , Salk Jesse , Marchetti Francesco , Yauk Carole
Published: February 2024

De novomutations (DNMs) are drivers of genetic disorders. However, the study of DNMs is hampered by technological limitations preventing accurate quantification of ultra-rare mutations. Duplex Sequencing (DS) theoretically has < 1 error/billion base-pairs (bp). To determine the utility of DS to quantify and characterize DNMs, we analyzed DNA from blood and spermatozoa from six healthy, 18-year-old Swedish men using the TwinStrand DS mutagenesis panel (48 kb spanning 20 genic and intergenic loci). The mean single nucleotide variant mutation frequency (MF) was 1.2 x 10-7per bp in blood and 2.5 x 10-8per bp in sperm, with the most common base substitution being C>T. Blood MF and substitution spectrum were similar to those reported in blood cells with an orthogonal method. The sperm MF was in the same order of magnitude and had a strikingly similar spectrum to DNMs from publicly available whole genome sequencing data from human pedigrees (1.2 x 10-8per bp). DS revealed much larger numbers of insertions and deletions in sperm over blood, driven by an abundance of putative extra-chromosomal circular DNAs. The study indicates the strong potential of DS to characterize human DNMs to inform factors that contribute to disease susceptibility and heritable genetic risks.
Real-time adaptive estimation of decoherence timescales for a single qubit
Authors: Arshad Muhammad Junaid , Bekker Christiaan , Haylock Ben , Skrzypczak Krzysztof , White Daniel , Griffiths Benjamin , Gore Joe , Morley Gavin W. , Salter Patrick , Smith Jason , Zohar Inbar , Finkler Amit , Altmann Yoann , Gauger Erik M. , Bonato Cristian
Published: February 2024

Characterizing the time over which quantum coherence survives is critical for any implementation of quantum bits, memories, and sensors. The usual method for determining a quantum system’s decoherence rate involves a suite of experiments probing the entire expected range of this parameter, and extracting the resulting estimation in postprocessing. Here we present an adaptive multiparameter Bayesian approach, based on a simple analytical update rule, to estimate the key decoherence timescales (T1, T2∗, and T2) and the corresponding decay exponent of a quantum system in real time, using information gained in preceding experiments. This approach reduces the time required to reach a given uncertainty by a factor up to an order of magnitude, depending on the specific experiment, compared to the standard protocol of curve fitting. A further speedup of a factor approximately 2 can be realized by performing our optimization with respect to sensitivity as opposed to variance.

Published by the American Physical Society
2024
1-Ethyl-3,3-dimethylspiro[indoline-2,8′-phenaleno[1,9-fg]chromene]
Authors: Zhu. Xiaoming , Jiang Zhen , Liu Zhiqiang
Published: February 2024

The title pyrene-fused spiropyran derivative, C30H25NO, crystallizes with two molecules in the asymmetric unit with dihedral angles between their fused-ring sub units of 76.20 (8) and 89.38 (9)°. In the crystal, weak C—H...π interactions link the molecules into a three-dimensional network.
Design and analysis of electric spring based on battery-less current-source inverter
Authors: He Yumin , Gu Tingyun , Li Bowen , Wang Yu , Qiu Dongyuan , Zhang Yang , Qiu Peicheng
Published: February 2024

Purpose

Electric spring (ES) is a demand response method that can stabilize the voltage of critical loads and improve power quality, especially in a weak power grid with a high proportion of renewable energy sources. Most of existing ESs are implemented by voltage-source inverter (VSI), which has some shortcomings. For example, the DC-link capacitor limits the service life of ES, and the battery is costly and hard to recycle. Besides, conventional VSI cannot boost the voltage, which limits the application of ES in high-voltage occasions. This study aims to propose a novel scheme of ES to solve the above problems.

Design/methodology/approach

In this work, an ES topology based on current-source inverter (CSI) without a battery is presented, and a direct current control strategy is proposed. The operating principles, voltage regulation range and parameter design of the proposed ES are discussed in detail.

Findings

The proposed ES is applicable to various voltage levels, and the harmonics are effectively suppressed, which have been validated via the experimental results in both ideal and distorted grid conditions.

Originality/value

An ES topology based on battery-less CSI is proposed for the first time, which reduces the cost and prolongs the service time of ES. A novel control strategy is proposed to realize the functions of voltage regulation and harmonic suppression.
Contextual factors and virtual professional learning communities in Maldivian schools
Authors: Rasheed Aminath Adhala , Albattat Ahmad , Azam S. M. Ferdous
Published: February 2024

Purpose

Virtual professional learning communities provide digital platforms for teachers across the globe to join learning networks and engage in continuous and unrestricted learning. This study aimed to explore the impact of contextual factors on establishing virtual professional learning communities in Maldivian schools.

Design/methodology/approach

This quantitative study used a sample of 420 Maldivian in-service teachers chosen using two-stage cluster sampling and a stratified random sampling method.

Findings

The findings revealed that all three contextual factors – micro-, meso- and macro-contextual – positively and significantly influenced the virtual professional learning communities.

Practical implications

These findings recommend an integrated framework with micro-, meso- and macro-contextual factors as valuable instruments for educational leaders striving to establish virtual Professional Learning Communities (PLCs).

Originality/value

This study is among the first to examine the association of contextual factors of schools with the establishment of virtual PLCs in a country such as the Maldives, with geographically dispersed islands and limited resources.
Perceived interactivity in real estate APP increases consumers' psychological well-being: a moderated mediation model
Authors: Yang Maosheng , Feng Lei , Zhou Honghong , Chen Shih-Chih , Lim Ming K. , Tseng Ming-Lang
Published: February 2024

Purpose

This study aims to empirically analyse the influence mechanism of perceived interactivity in real estate APP which affects consumers' psychological well-being. With the growing application of human–machine interaction in real estate APP, it is crucial to utilize human–machine interaction to stimulate perceived interactivity between humans and machines to positively impact consumers' psychological well-being and sustainable development of real estate APP. However, it is unclear whether perceived interactivity improves consumers' psychological well-being.

Design/methodology/approach

This study proposes and examines a theoretical model grounded in the perceived interactivity theory, considers the relationship between perceived interactivity and consumers' psychological well-being and explores the mediating effect of perceived value and the moderating role of privacy concerns. It takes real estate APP as the research object, analyses the data of 568 consumer samples collected through questionnaires and then employs structural equation modelling to explore and examine the proposed theoretical model of this study.

Findings

The findings are that perceived interactivity (i.e. human–human interaction and human–information interaction) positively influences perceived value, which in turn affects psychological well-being, and that perceived value partially mediates the effect of perceived interaction on psychological well-being. More important findings are that privacy concerns not only negatively moderate human–information interaction on perceived value, but also negatively moderate the indirect effects of human–information interaction on users' psychological well-being through perceived value.

Originality/value

This study expands the context on perceived interaction and psychological well-being in the field of real estate APP, validating the mediating role and boundary conditions of perceived interactivity created by human–machine interaction on consumers' psychological well-being, and suggesting positive implications for practitioners exploring human–machine interaction technologies to improve the perceived interaction between humans and machines and thus enhance consumer psychological well-being and span sustainable development of real estate APP.
Climate change management in manufacturing industry: a greenhouse gas inventorisation and mitigation approach
Authors: Dwarakanath M. , Gedam Vidyadhar , Krishna Kadirvelu , M.S. Narassima , Prabhu P. , Nandi Varman
Published: February 2024

Purpose

Industries worldwide have been striving to serve the increasing demand of consumers alongside providing importance to environmental issues. Yet, there are concern-raising changes on the planet, such as greenhouse gas (GHG) emissions resulting in a temperature rise. India remains a vital party of the United Nations Convention on Climate Change. Henceforth, the paper aims to study the increased emissions of GHG in Puducherry, an Indian Union Territory that faces tremendous pressure owing to its denser population.

Design/methodology/approach

The research is designed as a case study conducted in a tyre manufacturing unit in Puducherry. The industrial sector was chosen, as it is the largest contributor (78%) of the total GHG emissions. Case studies were chosen to analyse the GHG emissions and the effects of implementing the policies and imposing interventions over time. The identified areas of improvement, proposed changes and the implemented ones with the results over a three-year period have been discussed.

Findings

The present study’s GHG inventorisation for Puducherry paved the way for preparing mitigation and adaptation plans. A total of 21 and 48 changes were incorporated to conserve fuel and power, respectively. A significant 11% reduction in power consumption and 1,113,008/litres of furnace oil was achieved. This translates to 5,115 tCO2 and 3,306 tCO2, respectively.

Practical implications

This research will help to improve the importance of climate change management in the manufacturing sector, and it will pave the way for achieving effective sustainable practices.

Originality/value

Such case studies could cumulatively impact the policy directives/ interventions on GHG emissions. Though this seems a small leap, putting them into practice at firm levels would contribute significantly towards achieving Sustainable Development Goals.