bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of fMRI presurgical mapping techniques with intraoperative brain mapping-based validation
Authors: Radwan Ahmed M. , Emsell Louise , Vansteelandt Kristof , Cleeren Evy , Peeters Ronald , De Vleeschouwer Steven , Theys Tom , Dupont Patrick , Sunaert Stefan
Published: October 2023

Introduction

Resting-state functional MRI (rs-fMRI) could enable preoperative risk assessment and intraoperative guidance for patients who cannot undergo task-based fMRI (tbfMRI). We investigated differences in accuracy between tbfMRI and rsfMRI acquired with single (sTE) at voxel size of 2mm and 3mm, and multi-echo (mTE) scans using intraoperative mapping with direct electrical stimulations (DES) as the ground truth.

Material and methods

Functional sensory-motor mapping results of hands and feet were spatially compared relative to positive (pDES, functional effect) and negative (nDES, no functional effect) coordinates in 16 preoperative patients. General linear model analysis was used for tbfMRI, and seed-based analysis (SBA) for rsfMRI. Minimum Euclidean distances between fMRI and DES were calculated and compared between fMRI methods. Receiver-operating characteristic (ROC) curves were used to compare accuracy and determine distance cutoffs for fMRI agreement with DES, and binary agreement rates were compared at different cutoffs. Two-part mixed-effects linear models were used to compare fMRI methods while accounting for unequal inter-subject DES repetition.

Results

Only minor differences were found between fMRI methods in unthresholded distances (mean differences ∼ 2 mm). ROCs and binary agreement measures showed comparable accuracy for tbfMRI and sTE-rsfMRI 2mm, but mildly worse for sTE-rsfMRI 3mm and mTE-rsfMRI. However, differences in relative accuracy between sTE- and mTE-rsfMRI were minor when the same distance cutoff was applied to all methods. This was also reflected on comparing rates of binary agreement and confirmed by the two-part linear models, which showed no significant differences between fMRI methods and a significant effect of DES response.

Conclusion

The similar accuracy for SBA rsfMRI functional sensory-motor mapping compared to tbfMRI for the hands and feet, indicate that rsfMRI may be suitable for presurgical mapping. The differences in relative accuracy between sTE- and mTE rsfMRI warrant further investigation in a larger sample.
Separating representational and noise components of speech prosody perception after stroke
Authors: Zarrabi Aynaz Adl , Jeulin Mélissa , Bardet Pauline , Commère Pauline , Naccache Lionel , Aucouturier JJ , Ponsot Emmanuel , Villain Marie
Published: October 2023

After a right hemisphere stroke, more than half of the patients are impaired in their capacity to produce or comprehend speech prosody. Yet, and despite its social-cognitive consequences for patients, aprosodia following stroke has received scant attention. In this report, we introduce a novel, simple psychophysical procedure which, by combining systematic digital manipulations of speech stimuli and reverse-correlation analysis, allows estimating the internal sensory representations that subtend how individual patients perceive speech prosody, and the level of internal noise that govern behavioral variability in how patients apply these representations. Tested on a sample of N=22 right-hemisphere stroke survivors and N=12 healthy controls, the representation+noise model provides a promising alternative to the clinical gold standard for evaluating aprosodia (MEC): both parameters strongly associate with receptive, and not expressive, aprosodia measured by MEC within the patient group; they have better sensitivity than MEC for separating high-functioning patients from controls; and have good specificity with respect to non-prosody-related impairments of auditory attention and processing. Taken together, individual differences in either internal representation, internal noise, or both, paint a potent portrait of the variety of sensory/cognitive mechanisms that can explain impairments of prosody processing after stroke.
Mechanism and cellular function of direct membrane binding by the ESCRT and ERES-associated Ca2+-sensor ALG-2
Authors: Shukla Sankalp , Chen Wei , Rao Shanlin , Yang Serim , Ou Chenxi , Larsen Kevin P. , Hummer Gerhard , Hanson Phyllis I. , Hurley James H.
Published: October 2023

Apoptosis Linked Gene-2 (ALG-2) is a multifunctional intracellular Ca2+sensor and the archetypal member of the penta-EF hand protein family. ALG-2 functions in the repair of damage to both the plasma and lysosome membranes and in COPII-dependent budding atendoplasmicreticulumexitsites (ERES). In the presence of Ca2+, ALG-2 binds to ESCRT-I and ALIX in membrane repair and to SEC31A at ERES. ALG-2 also binds directly to acidic membranes in the presence of Ca2+by a combination of electrostatic and hydrophobic interactions. By combining GUV-based experiments and molecular dynamics simulations, we show that charge-reversed mutants of ALG-2 at these locations disrupt membrane recruitment. ALG-2 membrane binding mutants have reduced or abrogated ERES localization in response to Thapsigargin-induced Ca2+release but still localize to lysosomes following lysosomal Ca2+release.In vitroreconstitution shows that the ALG-2 membrane-binding defect can be rescued by binding to ESCRT-I. These data thus reveal the nature of direct Ca2+-dependent membrane binding and its interplay with Ca2+-dependent protein binding in the cellular functions of ALG-2.
Dicer deficiency in microglia leads to accelerated demyelination and failed remyelination
Authors: Tripathi Ajai , Rai Nagendra , Perles Aaron , Jones Claire , Dutta Ranjan
Published: October 2023

Microglia are the resident immune cells of the central nervous system (CNS) and are important regulators of normal brain functions. In CNS demyelinating diseases like multiple sclerosis (MS), the functions of these cells are of particular interest. Here we probed the impact of microRNA (miRNA)-mediated post-transcriptional gene regulation using a mouse model lacking microglia/macrophage-specificDicerexpression during demyelination and remyelination. ConditionalDicerablation and loss of miRNAs in adult microglia led to extensive demyelination and impaired myelin processing. Interestingly, demyelination was accompanied by increased apoptosis of mature oligodendrocytes (OLs) and arresting OL progenitor cells (OPCs) in the precursor stage. At the transcriptional level,Dicer-deficient microglia led to downregulation of microglial homeostatic genes, increased cell proliferation, and a shift towards a disease-associated phenotype. Loss of remyelination efficiency in these mice was accompanied by stalling of OPCs in the precursor stage. Collectively, these results highlight a new role of microglial miRNAs in promoting a pro-regenerative phenotype in addition to promoting OPC maturation and differentiation during demyelination and remyelination.

Graphical Abstract
Guanine quadruplexes mediate mitochondrial RNA polymerase pausing
Authors: Snyder Ryan , Delker Don , Burdick Joshua T , Cheung Vivian G. , Watts Jason A.
Published: October 2023

The information content within nucleic acids extends beyond the primary sequence to include secondary structures with functional roles in cells. Guanine-rich sequences form structures called guanine quadruplexes (G4) that result from non-canonical base pairing between guanine residues. These stable structures are enriched in gene promoters and have been correlated with the locations of RNA polymerase II pausing (Pol II). While promoter-proximal RNA polymerase pausing regulates gene expression, the effects of guanine quadruplexes on gene transcription have been less clear. We determined the pattern of mitochondrial RNA polymerase (mtRNAP) pausing in human fibroblasts and found that it pauses over 400 times on the mitochondrial genome. We identified quadruplexes as a mediator of mtRNAP pausing and show that stabilization of quadruplexes impeded transcription by mtRNAP. Gene products encoded by the mitochondrial genome are required for oxidative phosphorylation and the decreased transcription by mtRNAP resulted in lower expression of mitochondrial genes and significantly reduced ATP generation. Energy from mitochondria is essential for transport function in renal epithelia, and impeded mitochondrial transcription inhibits transport function in renal proximal tubule cells. These results link formation of guanine quadruplex structures to regulation of mtRNAP elongation and mitochondrial function.
De novogeneration of antibody CDRH3 with a pre-trained generative large language model
Authors: He Haohuai , He Bing , Guan Lei , Zhao Yu , Chen Guanxing , Zhu Qingge , Chen Calvin Yu-Chian , Li Ting , Yao Jianhua
Published: October 2023

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed throughin-silicoanalysis andin-vitroassays. Thein-vitroassays validated that PALM-generated antibodies achieve high binding affinity and potent neutralization capability against both wild-type and XBB spike proteins of SARS-CoV-2. Meanwhile, A2binder demonstrated exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism into the PALM model, we have improved its interpretability, providing crucial insights into the fundamental principles of antibody design.
N-acetyl Cysteine attenuates intrinsic functional connectivity, but not neural alcohol cue reactivity, in treatment-seeking individuals with alcohol use disorder
Authors: Logge Warren B , Haber Paul S , Hurzeler Tristan P , Towers Ellen E , Morley Kirsten C
Published: October 2023

Abstract

N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates i) alcohol cue-elicited activation, and ii) intrinsic functional connectivity compared to placebo in patients with AUD. Twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day,n= 9), or a placebo (n= 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising a resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 376 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by- time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC- treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. The reduced intrinsic functional connectivity pattern seen may signify reduced external processing of environmental alcohol cues, though no reduced visual cue reactivity associations were evidenced.
Deciphering the Effect of High-Density Lipoprotein Cholesterol on Renal Function: a Mendelian Randomization Study
Authors: Le Nhu Ngoc , Tran Tran Quoc Bao , Gill Dipender , Padmanabhan Sandosh
Published: October 2023

Background

The causal relationship between high-density lipoprotein cholesterol (HDL) and cardiovascular protection remains unresolved. Mounting evidence now points towards a link between lipid levels, including HDL, and renal function. However, previous epidemiological and animal studies provide a mixed picture. This study investigates the causal interplay between HDL and renal function by leveraging the specific and substantial increase in HDL achieved with cholesteryl ester transfer protein (CETP) inhibition.

Method and Results

Two-sample and multivariable Mendelian randomization (MR) methods were used to explore the causal impact of HDL through genetically-proxied CETP inhibition on serum cystatin C-estimated glomerular filtration rate (eGFRcys). Secondary analyses delved into other renal markers and systolic blood pressure (SBP). Summary-based Mendelian Randomization (SMR) and genetic colocalisation analyses were used to evaluate the probability of shared causal variants within a 100Kb window of the gene.

Genetically-proxied CETP inhibition, using HDL level as a biomarker, was linked to lower eGFRcys (effect size per 1 SD increase in HDL, −0.008, 95% CI −0.011 to - 0.005; p = 1.38 × 10−06) and reduced chronic kidney disease (CKD) risk (OR 0.895 [0.838, 0.956]; p = 0.001). The HDL-eGFRcys relationship persisted after adjusting for low-density lipoprotein cholesterol (LDL) and SBP in multivariable MR, but the association with CKD risk attenuated. Decreased CETP expression in blood was associated with lower eGFRcys (effect size per 1-SD, −0.008 [−0.016, −0.001]; pSMR= 0.029), a reduced CKD risk (OR, 0.85 [0.74, 0.98]; pSMR= 0.03), and lower SBP (−0.71 [−1.177, −0.244]; pSMR= 0.003). Colocalisation results indicated low posterior probabilities for both shared and distinct causal variants between CETP gene expression and eGFRcys.

Conclusion

MR analyses support a causal inverse relationship between HDL and eGFRcys that is independent of SBP. The results warrant further studies to validate the nuanced roles of HDL and LDL on renal function.
DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain
Authors: Gadd Danni A. , Smith Hannah M. , Mullin Donncha , Chybowska Ola , Hillary Robert F. , Kimenai Dorien M , Bernabeu Elena , Cheng Yipeng , Fawns-Ritchie Chloe , Campbell Archie , Page Danielle , Taylor Adele , Corley Janie , Valdés-Hernández Maria Del C. , Maniega Susana Muñoz , Bastin Mark E. , Wardlaw Joanna M. , Walker Rosie M. , Evans Kathryn L. , McIntosh Andrew M. , Hayward Caroline , Russ Tom , Harris Sarah E. , Welsh Paul , Sattar Naveed , Cox Simon R. , McCartney Daniel L. , Marioni Riccardo E.
Published: October 2023

Background

Plasma growth differentiation factor 15 (GDF15) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

Results

In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR< 0.05). Bayesian Epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP that were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (Hazard Ratios (HR) range 1.36 – 1.41, PFDR<0.03). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population.

Conclusions

EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.
Approach in Inputs & Outputs Selection of Data Envelopment Analysis (DEA) Efficiency Measurement in Hospital: A Systematic Review
Authors: Zubir M Zulfakhar , Noor A Azimatun , Rizal AM Mohd , Harith A Aziz , Abas M Ihsannuddin , Zakaria Zuriyati , A.Bakar Anwar Fazal
Published: October 2023

Data Envelopment Analysis (DEA) has been employed as a performance evaluation tool in the evaluation of efficiency and productivity in numerous fields. This includes hospitals in particular as well as the broad healthcare industry. This review examines 89 papers that discuss the use of DEA in hospitals, paying particular attention to approaches for choosing inputs and outputs as well as the most recent developments in DEA studies. English articles with empirical data from year 2014-2022 (Web of Science, Scopus, PubMed, ScienceDirect, Springer Link, and Google Scholar) were extracted based on PRISMA methodology. DEA Model parameters were specified based on previous studies and approaches were identified narratively. The approaches can be grouped into four: (1) Literature review, (2) Data availability, (3) Systematic method and (4) Expert judgement. The approaches were applied as one strategy either by itself or in combination with others. This review’s emphasis on approaches used in hospital may constrain its conclusions. There might be another strategy or method used to select the input and output for a DEA study in a different area or strategies based on different viewpoints. The trend for DEA application were quite similar to previous studies. There is no evidence that one model fits all DEA model parameters better than another. Based on the reviewed literature, we offer some recommendations and methodological principles for DEA studies.
Artificial Intelligence in Cardiac Surgery: A Systematic Review
Authors: Sulague Ralf Martz , Beloy Francis Joshua , Medina Jillian Reeze , Mortalla Edward Daniel , Cartojano Thea Danielle , Macapagal Sharina , Kpodonu Jacques
Published: October 2023

BACKGROUND

Artificial intelligence has emerged as a tool to potentially increase efficiency and efficacy of cardiovascular care and improve clinical outcomes. This study aims to provide an overview of applications of artificial intelligence in cardiac surgery.

METHODS

A systematic literature search on artificial intelligence applications in cardiac surgery from inception to February 2024 was conducted. Articles were then filtered based on the inclusion and exclusion criteria and risk of bias was assessed. Key findings were then summarized

RESULTS

A total of 81 studies were found that reported on artificial intelligence applications in cardiac surgery. There is a rapid rise in studies since 2020. The most popular machine learning technique was Random Forest (n=48), followed by Support Vector Machine (n=33), Logistic Regression (n=32), and Extreme Gradient Boosting (n=31). Most of the studies were on adult patients, conducted in China, and involved procedures such as valvular surgery (24.7%), heart transplant (9.4%), coronary revascularization (11.8%), congenital heart disease surgery (3.5%), and aortic dissection repair (2.4%). Regarding evaluation outcomes, 35 studies examined the performance, 26 studies examined clinician outcomes, and 20 studies examined patient outcomes.

CONCLUSION

Artificial intelligence was mainly used to predict complications following cardiac surgeries and improve clinicians’ decision-making by providing better preoperative risk assessment, stratification, and prognostication. While the application of artificial intelligence in cardiac surgery has greatly progressed in the last decade, further studies need to be done to verify accuracy and ensure safety before use in clinical practice.
A Tumour-Specific Molecular Network Promotes Tumour Growth inDrosophilaby Enforcing a JNK-YKI Feedforward Loop
Authors: Waghmare Indrayani , Gangwani Karishma , Rai Arushi , Singh Amit , Kango-Singh Madhuri
Published: October 2023

Cancer cells expand rapidly in response to altered intercellular and signalling interactions to achieve hallmarks of cancer. Impaired cell polarity combined with activated oncogenes is known to promote several hallmarks of cancer e.g., activating invasion by increased activity of Jun N-terminal kinase (JNK), and sustained proliferative signalling by increased activity of Hippo effector Yorkie (Yki). Thus, JNK, Yki, and their downstream transcription factors have emerged as synergistic drivers of tumour growth through pro-tumour signalling and intercellular interactions like cell-competition. However, little is known about the signals that converge onto JNK and Yki in tumour cells that enable the tumour cells to achieve hallmarks of cancer. Here, using mosaic models of cooperative oncogenesis (RasV12, scrib-) inDrosophila, we show thatRasV12, scrib-tumour cells grow by activation of a previously unidentified network comprising Wingless (Wg), Dronc, JNK and Yki. We show thatRasV12, scrib-cells show increased Wg, Dronc, JNK, and Yki signalling, and all of these signals are required for the growth ofRasV12, scrib-tumours. We report that Wg and Dronc converge onto a JNK-Yki self-reinforcing positive feedback signal-amplification loop that promotes tumour growth. We found that Wg-Dronc-Yki-JNK molecular network is specifically activated in polarity-impaired tumour cells and not in normal cells where apical basal polarity is intact. Our findings suggest that identification of molecular networks may provide significant insights about the key biologically meaningful changes in signalling pathways, and paradoxical signals that promote Tumourigenesis.
Modeling the consequences of age-linked rDNA hypermethylation with dCas9-directed DNA methylation in human cells
Authors: Blokhina Yana , Buchwalter Abigail
Published: October 2023

Ribosomal DNA (rDNA) genes encode the structural RNAs of the ribosome and are present in hundreds of copies in mammalian genomes. Age-linked DNA hypermethylation throughout the rDNA constitutes a robust “methylation clock” that accurately reports age, yet the consequences of hypermethylation on rDNA function are unknown. We confirmed that pervasive hypermethylation of rDNA occurs during mammalian aging and senescence while rDNA copy number remains stable. We found that DNA methylation is exclusively found on the promoters and gene bodies of inactive rDNA. To model the effects of age-linked methylation on rDNA function, we directedde novoDNA methylation to the rDNA promoter or gene body with a nuclease-dead Cas9 (dCas9) – DNA methyltransferase fusion enzyme in human cells. Hypermethylation at each target site had no detectable effect on rRNA transcription, nucleolar morphology, or cellular growth rate. Instead, human UBF and Pol I remain bound to rDNA promoters in the presence of increased DNA methylation. These data suggest that promoter methylation is not sufficient to impair transcription of the human rDNA and imply that the human rDNA transcription machinery may be resilient to age-linked rDNA hypermethylation.
Early-life gut microbiota assembly patterns are conserved between laboratory and wild mice
Authors: Hanski Eveliina , Raulo Aura , Knowles Sarah C L
Published: October 2023

Assembly of the mammalian gut microbiota during early life is known to shape key aspects of organismal development, including immunity, metabolism and behaviour. While house mice (Mus musculus) are the major laboratory model organism for gut microbiota research, their artificial lab-based lifestyle could fundamentally alter ecological processes of microbiota assembly and dynamics, in ways that affect their usefulness as a model system. To examine this, here we directly compared patterns of gut microbiota assembly in house mice from the lab and from the wild, making use of a tractable, individually-marked wild population where we could examine patterns of gut microbiota assembly during early life. Despite lab and wild mice harbouring taxonomically distinct communities, we identify striking similarities in multiple patterns of their gut microbiota assembly. Specifically, age-related changes in both alpha and beta diversity, as well as the abundance of predominant phyla and aerotolerance of the microbiota followed parallel trajectories in both settings. These results suggest some degree of intrinsic programme in gut microbiota assembly that transcends variation in taxonomic profiles, and the genetic and environmental background of the host. They further support the notion that despite their artificial environment, lab mice can provide meaningful insights into natural microbiota ecological dynamics in early life and their interplay with host development.
Dogs’ sensory-motor tuning shapes dog-human vocal interactions
Authors: Déaux E. C. , Piette T. , Gaunet F. , Legou T. , Arnal L. , Giraud A-L.
Published: October 2023

Within species, vocal and auditory systems co-evolve to converge on a critical temporal acoustic structure that can be best produced and perceived. While dogs cannot produce articulated sounds, they respond to speech, raising the question as to whether this heterospecific receptive ability is shaped by exposure to speech or bounded by their own sensorimotor capacity. Acoustic analyses of vocalisations show that dogs’ main production rhythm is slower than the dominant (syllabic) speech rate, and that human dog-directed speech falls halfway in between. Comparative exploration of neural (electroencephalography) and behavioural responses to speech reveals that comprehension in dogs relies on a slower speech rhythm tracking (delta) than humans’ (theta), even though dogs are equally sensitive to human speech content and prosody. Thus, the dog audio-motor tuning differs from humans’, who vocally adjust their speech rate to this shared temporal channel.
Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice
Authors: Quiñones-Labernik Pravda , Blocklinger Kelsey L , Bruce Matthew R , Ferri Sarah L
Published: October 2023

Neurodevelopmental disorders disproportionately affect males compared to females. The biological mechanisms of this male susceptibility or female protection have not been identified. There is evidence that fetal/neonatal gonadal hormones, which play a pivotal role in many aspects of development, may contribute. Here, we investigate the effects of excess testosterone during a critical period of sex-specific brain organization on social approach and fear learning behaviors in C57BL/6J wild-type mice. Male, but not female, mice treated with testosterone on the day of birth (PN0) exhibited decreased social approach as juveniles and decreased contextual fear memory as adults, compared to vehicle-treated controls. These deficits were not driven by anxiety-like behavior or changes in locomotion or body weight. Mice treated with the same dose of testosterone on postnatal day 18 (PN18), which is outside of the critical period of brain masculinization, did not demonstrate impairments compared to the vehicle group. These findings indicate that excess testosterone during a critical period of early development, but not shortly after, induces long-term deficits relevant to the male sex bias in neurodevelopmental disorders.

Significance statement

Excess testosterone during a critical period of sex-specific brain organization, results in male-specific social and cognitive deficits in mice while testosterone treatment outside of this developmental window did not alter behavior. This time-sensitive, brief hormonal dysregulation induces long-term changes, and may be involved in the male sex bias in neurodevelopmental disorders.
Spike-phase coupling of subthalamic neurons to posterior opercular cortex predicts speech sound accuracy
Authors: Vissani Matteo , Bush Alan , Lipski Witold J. , Bullock Latané , Fischer Petra , Neudorfer Clemens , Holt Lori L. , Fiez Julie A. , Turner Robert S. , Richardson R. Mark
Published: October 2023

Speech provides a rich context for understanding how cortical interactions with the basal ganglia contribute to unique human behaviors, but opportunities for direct intracranial recordings across cortical-basal ganglia networks are rare. We recorded electrocorticographic signals in the cortex synchronously with single units in the basal ganglia during awake neurosurgeries where subjects spoke syllable repetitions. We discovered that individual STN neurons have transient (200ms) spike-phase coupling (SPC) events with multiple cortical regions. The spike timing of STN neurons was coordinated with the phase of theta-alpha oscillations in the posterior supramarginal and superior temporal gyrus during speech planning and production. Speech sound errors occurred when this STN-cortical interaction was delayed. Our results suggest that the STN supports mechanisms of speech planning and auditory-sensorimotor integration during speech production that are required to achieve high fidelity of the phonological and articulatory representation of the target phoneme. These findings establish a framework for understanding cortical-basal ganglia interaction in other human behaviors, and additionally indicate that firing-rate based models are insufficient for explaining basal ganglia circuit behavior.
The effect of UVA light/8-methoxypsoralen exposure used in Extracorporeal Photopheresis treatment on platelets and extracellular vesicles
Authors: Macleod Hayley , Weiss Luisa , Kelliher Sarah , Kevane Barry , Ní Áinle Fionnuala , Maguire Patricia B.
Published: October 2023

Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to UVA/8-methoxypsoralen is currently unknown.

Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalenin vitroand platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatmentin vitrodid not induce platelet aggregation or alter significantly levels of the platelet activation markers soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECPin vitrodoes not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistentin vivo.
Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation
Authors: van Vugt Marion , Finan Chris , Chopade Sandesh , Providencia Rui , Bezzina Connie R. , Asselbergs Folkert W. , van Setten Jessica , Schmidt A. Floriaan
Published: October 2023

Background

Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.

Methods

Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1,567 plasma proteins and performedcisMR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.

Results

We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p=0.029) and DCM for acylcarnitines (p=0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF, and RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.

Conclusion

This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.
COVID-19 cases associated with testing policies in 34 highly democratic countries, 2020-2022
Authors: Robertson Leon S.
Published: October 2023

COVID-19 testing policies varied in time from testing only the symptomatic, testing the symptomatic and persons at higher risk of severe disease, on-demand testing for people who wanted one, and two periods of government-imposed mass testing in Slovakia. Using Poisson regression, this study examines the associations of COVID-19 cases during the times that the noted policies were in effect in 34 countries rated highest on democracy scores. Statistically corrected for other risk factors, increases in negative tests were associated with subsequent surges in cases when on-demand testing was promoted, particularly when coupled with poor contact tracing. Mass testing in Slovakia was associated with reduced spread of the virus for short periods but was deemed unsustainable. The data support the hypothesis that on-demand testing resulted in the unanticipated consequence of increased travel and increased exposure of travelers to the virus.
Application of an Opioid Use Disorder Cascade of Care in a Large Public Health System
Authors: Carter Emily , Schatz Daniel , Isaacs Noah , Garcia Juan , Henry Brandy , Krawczyk Noa , Williams Arthur Robin
Published: October 2023

Background

Over the past decade, hospitals and health systems have increasingly adopted interventions to address the needs of patients with substance use disorders. The Opioid Use Disorder (OUD) Cascade of Care provides a framework for organizing and tracking patient health milestones over time, and can assist health systems in identifying areas of intervention to prevent overdose and maximize the impact of evidence-based services for patients with OUD. However, detailed protocols are needed to guide health systems in how to operationalize the OUD Cascade and track outcomes using their systems’ electronic medical records (EMR).

Objective

In this paper, we describe the process of operationalizing and implementing the OUD Cascade in one large, urban, public hospital system.

Methods

Through this case example, we describe the technical processes around data mining, as well as the decision-making processes, challenges encountered, and lessons learned from compiling patient data and defining stages and outcome measures for the OUD Cascade of Care. The current established framework and process will set the stage for subsequent research studies that quantify and evaluate patient progression through each stage of OUD treatment across the health system and identify target areas for quality improvement initiatives to better engage patients in care and improve health outcomes.

Results

The current paper can therefore serve as a primer for other health systems seeking to implement a data-informed approach to guide more efficient care and improved substance use-related outcomes.

Conclusion

An OUD Cascade of Care must be tailored to local systems based on inherent data limitations and services design.
Temporal changes of compassion in accounting and business students in an English course: a longitudinal study in higher education
Authors: Arianpoor Arash , Yazdanmehr Elham , Elahi Shirvan Majid
Published: October 2023

Purpose

To measure the dynamic features of compassion as an emotional and behavioral construct, the present research used a univariate latent growth modeling (LGM) approach within the structural equation modeling (SEM) framework. The aim was to trace the dynamic development of compassion longitudinally in accounting and business students during a three-credit English course at university.

Design/methodology/approach

The suggested method ensures the measurement invariance over time, deals with the first order latent variable, traces its growth and takes into account the measurement errors. This longitudinal analytical method was used to explore the initial state and the growth of compassion in four points of time during a language course. The data were collected from 60 adult accounting and business students in four time phases using Sprecher and Fehr's Compassionate Love Scale and were analyzed in Mplus 8.4 with univariate LGM.

Findings

The model fit was accepted and the invariance of the latent factor was confirmed over time. The negative covariance between intercept and slope (second-order latent variables) suggested that lower initial scores in L2 learners' compassion show a faster increase in compassion over time as the mean of slope is larger than that of the intercept. L2 learners who started off at a higher level of compassion showed a slower change in compassion over time. This can be at least partly explained by the teacher's motivating role or learners' compassion but needs to be further explored in complementary qualitative phases for deeper insights.

Originality/value

In the present research, awareness was raised of the developmental nature of compassion as an emotional and behavioral construct essential to the accounting and business profession. The great strength of this research lies in the dynamic approach to the compassion construct and the LGM used to capture the temporal growth of compassion and how it evolved through the L2 course.
Patterns for modeling process variability in a healthcare context
Authors: Kirchner Kathrin , Laue Ralf , Edwards Kasper , Lantow Birger
Published: October 2023

Purpose

Medical diagnosis and treatment processes exhibit a high degree of variability, as during the process execution, healthcare professionals can decide on additional steps, change the execution order or skip a task. Process models can help to document and to discuss such processes. However, depicting variability in graphical process models using standardized languages, such as Business Process Model and Notation (BPMN), can lead to large and complicated diagrams that medical staff who do not have formal training in modeling languages have difficulty understanding. This study proposes a pattern-based process visualization that medical doctors can understand without extensive training. The process descriptions using this pattern-based visualization can later be transformed into formal business process models in languages such as BPMN.

Design/methodology/approach

The authors derived patterns for expressing variability in healthcare processes from the literature and medical guidelines. Then, the authors evaluated and revised these patterns based on interviews with physicians in a Danish hospital.

Findings

A set of business process variability patterns was proposed to express situations with variability in hospital treatment and diagnosis processes. The interviewed medical doctors could translate the patterns into their daily work practice, and the patterns were used to model a hospital process.

Practical implications

When communicating with medical personnel, the patterns can be used as building blocks for documenting and discussing variable processes.

Originality/value

The patterns can reduce complexity in process visualization. This study provides the first validation of these patterns in a hospital.
Unveiling Dubai’s knowledge economy: a journey toward enhancing knowledge exchange and human capital
Authors: Al Ali Mohamed Ibrahim , Khassawneh Osama , Haak-Saheem Washika , Zeng Jing , Darwish Tamer K.
Published: October 2023

Purpose

The purpose of this study is to investigate the factors that influence the development of human capital by examining the interplay between different organizational mechanisms, including leadership, organizational culture and human resources management (HRM) practices. This study aims to enhance our understanding of how knowledge exchange influences human capital, with a specific focus on the unique context of Dubai, an area and context that have been underexplored in this research domain.

Design/methodology/approach

This study used a survey-based approach, involving 611 participants working across different sectors based in Dubai. This study used partial least squares structural equation modeling as the statistical analysis method.

Findings

The results of the study indicate that leadership behaviors have a predictive influence on organizational culture. In turn, organizational culture significantly affects knowledge exchange. Additionally, the study reveals that commitment-based HRM practices play a significant moderating role in the relationship between organizational culture and knowledge exchange.

Originality/value

This study contributes to the existing literature by providing valuable insights into the interplay between leadership, organizational culture and commitment-based HRM practices. By exploring these factors and their influence on knowledge exchange and human capital, the study enhances both the theoretical understanding and practical application in this field.
Individual stories of agency: an exploratory study into the pandemic impact on students' employability skills
Authors: Nguyen Huong Lan
Published: October 2023

Purpose

This paper aims to investigate the impact of the COVID-19 pandemic on university students' employability skills and give insights into preparation for future crises that may happen.

Design/methodology/approach

Employing an interpretative phenomenological approach with the frame of social cognitive theory, the current study examined the changes in environmental, behavioral and personal elements of human functioning for employability skills being affected by the conditions during the pandemic.

Findings

Findings based on ten in-depth semi-structured interviews with students at universities in Vietnam highlighted that the global pandemic performed as both challenge and an opportunity for employability skills development, yet the extent to which the students can benefit from the new studying conditions attributed to each individual's initiatives in taking advantages of resources and acting against difficulties.

Originality/value

Whether the pandemic became a hindrance or a motivation for students' employability skills to develop and whether students effectively utilized an agency to overcome challenges and improved their skills after the pandemic have not yet been investigated. This study added to the body of literature regarding self-regulated learners by demonstrating agency in the learning process as well as how to manage careers and improve employability skills by making use of resources in disconnected settings.
Principal time use and student academic achievement in Singapore
Authors: Huang Tiedan , Benoliel Pascale
Published: October 2023

Purpose

This study aims to test the mediated effect of school climate in the relationship of principal time use (PTU) to student academic achievement using data from Singapore's 2011 Trends in International Mathematics and Science Study (TIMSS).

Design/methodology/approach

Capitalizing on the large-scale data, the study examined how Singapore principals distributed their time across 13 leadership activities and tested using structural equation modeling (SEM) how Singapore principals' time use was related to student achievement through molding intermediate school conditions, such as school climate.

Findings

The authors' findings suggest that Singaporean principals, when allocating time, generally emphasized (1) monitoring students' learning progress, (2) promoting school vision, (3) developing curricular goals and (4) monitoring teachers in areas related to curricular goals. Furthermore, after classifying the 13 principal activities into three broad domains, the authors find that Singaporean principals prioritize the domain of vision and goals over the other two domains – facilitating teaching and learning through a safe, positive school environment and problem-solving with teachers, as well as self and organizational improvement. Finally, the authors' SEM manifested a partial mediated model, suggesting principals' strategic time use could serve as a malleable factor in yielding optimal student outcomes through developing a positive school climate.

Originality/value

This study at present is one of the early attempts linking PTU, intermediate school conditions (e.g. school climate) and student outcomes using a mediated design and corresponding statistical modeling.