Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative dynamic near-infrared fluorescence imaging using indocyanine green for analysis of bowel perfusion after mesenteric resection

Abstract. Significance: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has proven to be a feasible application for real-time intraoperative assessment of tissue perfusion, although quantification of NIR fluorescence signals is pivotal for standardized assessment of tissue perfusion. Aim: Four patients are described with possible compromised bowel perfusion after mesenteric resection. Based on these patients we want to emphasize the difficulties in the quantification of NIR fluorescence imaging for perfusion analysis. Approach: During image-guided fluorescence assessment, 5 mg of ICG (2.5 mg/ml) was intravenously administered by the anesthesiologist. NIR fluorescence imaging was done with the open camera system of Quest Medical Imaging. Fluorescence data taken from the regions of interest (bowel at risk, transition zone of bowel at risk and adjacent normally perfused bowel, and normally perfused reference bowel) were quantitatively analyzed after surgery for fluorescence intensity-and perfusion time-related parameters. Results: Bowel perfusion, as assessed clinically by independent surgeons based on NIR fluorescence imaging, resulted in different treatment strategies, three with excellent clinical outcome, but one with a perfusion related complication. Post-surgery quantitative analysis of fluorescence dynamics showed different patterns in the affected bowel segment compared to the unaffected reference segments for the four patients. Conclusions: Similar intraoperative fluorescence results could lead to different surgical treatment strategies, which demonstrated the difficulties in interpretation of uncorrected fluorescence signals. Real-time quantification and standardization of NIR fluorescence perfusion imaging could probably aid surgeons in the nearby future.
Characterizing public perceptions of social and cultural impacts in policy decisions

Significance Large infrastructure projects such as highways, pipelines, and ports undergo formal impact evaluations to assess the likely impacts to social and cultural priorities, the economy, public health, and the environment. Several scientific and citizen groups have expressed concern that social and cultural impacts are not given sufficient consideration as compared to more tangible impacts such as economic concerns. In two large surveys, we find that the public does differentiate impacts, using qualities such as tangibility and scope, and we provide evidence supporting the widespread public perception that many policy decisions fail to reflect concerns about a range of social and cultural impacts. Knowing more about public perceptions of impacts could help aid the development of more equitable impact assessment procedures. Social scientists and community advocates have expressed concerns that many social and cultural impacts important to citizens are given insufficient weight by decision makers in public policy decision-making. In two large cross-sectional surveys, we examined public perceptions of a range of social, cultural, health, economic, and environmental impacts. Findings suggest that valued impacts are perceived through an initial lens that highlights both tangibility (how difficult it is to understand, observe, and make changes to an impact) and scope (how broadly an impact applies). Valued impacts thought to be less tangible and narrower in scope were perceived to have less support by both decision makers and the public. Nearly every valued impact was perceived to have more support from the public than from decision makers, with the exception of three economic considerations (revenues, profits, and costs). The results also demonstrate that many valued impacts do not fit neatly into the single-category distinctions typically used as part of impact assessments and cost–benefit analyses. We provide recommendations for practitioners and suggest ways that these results can foster improvements to the quality and defensibility of risk and impact assessments.
The impact of organizational culture on professional fulfillment and burnout in an academic department of medicine

Physician wellness is vital to career satisfaction, provision of high quality patient care, and the successful education of the next generation of physicians. Despite this, the number of physicians experience symptoms of burnout is rising. To assess the impact of organizational culture on physicians’ professional fulfillment and burnout, we surveyed full-time Department of Medicine members at the University of Toronto. A cross-sectional survey assessed: physician factors (age, gender, minority status, disability, desire to reduce clinical workload); workplace culture (efforts to create a collegial environment, respectful/civil interactions, confidence to address unprofessionalism without reprisal, witnessed and/or personally experienced unprofessionalism); professional fulfillment and burnout using the Stanford Professional Fulfillment Index. We used multivariable linear regression to examine the relationship of measures of workplace culture on professional fulfillment and burnout (scores 0–10), controlling for physician factors. Of 419 respondents (52.0% response rate), we included 400 with complete professional fulfillment and burnout data in analyses (60% ≤ age 50, 45% female). Mean scores for professional fulfillment and burnout were 6.7±1.9 and 2.8±1.9, respectively. Controlling for physician factors, professional fulfillment was associated with satisfaction with efforts to create a collegial environment (adjusted beta 0.45, 95% CI 0.21 to 0.70) and agreement that colleagues were respectful/civil (adjusted beta 0.85, 95% CI 0.53 to 1.17). Lower professional fulfillment was associated with higher burnout scores. Controlling for professional fulfillment and physician factors, lower confidence in taking action to address unprofessionalism (adjusted beta -0.22, 95% CI -0.40 to -0.03) was associated with burnout. Organizational culture and physician factors had an impact on professional fulfillment and burnout. Professional fulfillment partially mediated the relationship between organizational culture and burnout. Strategies that promote inclusion, respect and civility, and safe ways to report workplace unprofessionalism are needed in academic medicine.
CMAP Scan Examination of the First Dorsal Interosseous Muscle After Spinal Cord Injury

The study assessed motor unit loss in muscles paralyzed by spinal cord injury (SCI) using a novel compound muscle action potential (CMAP) scan examination. The CMAP scan of the first dorsal interosseous (FDI) muscle was applied in tetraplegia (n = 13) and neurologically intact (n = 13) subjects. MScanFit was used for estimating motor unit numbers in each subject. The D50 value of the CMAP scan was also calculated. We observed a significant decrease in both CMAP amplitude and motor unit number estimation (MUNE) in paralyzed FDI muscles, as compared with neurologically intact muscles. Across all subjects, the CMAP (negative peak) amplitude was 8.01 ± 3.97 mV for the paralyzed muscles and 16.75 ± 3.55 mV for the neurologically intact muscles (p < 0.001). The CMAP scan resulted in a MUNE of 59 ± 37 for the paralyzed muscles, much lower than 108 ± 21 for the neurologically intact muscles (p < 0.001). No significant difference in D50 was observed between the two groups (p = 0.2). For the SCI subjects, there was no significant correlation between MUNE and CMAP amplitude, or any of the clinical assessments including pinch force, grip force, the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) score, and SCI duration (p > 0.05). The findings provide an evidence of motor unit loss in the FDI muscles of individuals with tetraplegia, which may contribute to weakness and other hand function deterioration. The CMAP scan offers several practical benefits compared with the traditional MUNE techniques because it is noninvasive, automated and can be performed within several minutes.
The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes

Significance The intra-S phase checkpoint is essential to stabilize stalling/stalled replication forks. However, the mechanism underlying checkpoint regulation is poorly understood; two key questions remain to be answered: 1) why are stalling forks unstable when checkpoint is deficient, and 2) which protein(s) is the critical target of checkpoint regulation? Here, we demonstrate that CMG replicative helicase becomes uncoupled from stalled/blocked DNA polymerases in checkpoint-deficient cds1Chk2△ cells, likely reflecting physical separation of the helicase and polymerases. This uncoupling is prevented by the Cds1Chk2-mediated phosphorylation of Cdc45. We propose that replication elongation is directly regulated in response to replication fork stalling via phosphorylation of Cdc45, which significantly reduces CMG helicase processivity, in order to prevent helicase–polymerase uncoupling and promote replication fork stability. DNA replication is dramatically slowed down under replication stress. The regulation of replication speed is a conserved response in eukaryotes and, in fission yeast, requires the checkpoint kinases Rad3ATR and Cds1Chk2. However, the underlying mechanism of this checkpoint regulation remains unresolved. Here, we report that the Rad3ATR-Cds1Chk2 checkpoint directly targets the Cdc45-MCM-GINS (CMG) replicative helicase under replication stress. When replication forks stall, the Cds1Chk2 kinase directly phosphorylates Cdc45 on the S275, S322, and S397 residues, which significantly reduces CMG helicase activity. Furthermore, in cds1Chk2-mutated cells, the CMG helicase and DNA polymerases are physically separated, potentially disrupting replisomes and collapsing replication forks. This study demonstrates that the intra-S phase checkpoint directly regulates replication elongation, reduces CMG helicase processivity, prevents CMG helicase delinking from DNA polymerases, and therefore helps preserve the integrity of stalled replisomes and replication forks.
Acceptability of the Medication Event Reminder Monitor for Promoting Adherence to Multidrug-Resistant Tuberculosis Therapy in Two Indian Cities: Qualitative Study of Patients and Health Care Providers

Background Patients with multidrug-resistant tuberculosis (MDR-TB) face challenges adhering to medications, given that treatment is prolonged and has a high rate of adverse effects. The Medication Event Reminder Monitor (MERM) is a digital pillbox that provides pill-taking reminders and facilitates the remote monitoring of medication adherence. Objective This study aims to assess the MERM’s acceptability to patients and health care providers (HCPs) during pilot implementation in India’s public sector MDR-TB program. Methods From October 2017 to September 2018, we conducted qualitative interviews with patients who were undergoing MDR-TB therapy and were being monitored with the MERM and HCPs in the government program in Chennai and Mumbai. Interview transcripts were independently coded by 2 researchers and analyzed to identify the emergent themes. We organized findings by using the Unified Theory of Acceptance and Use of Technology (UTAUT), which outlines 4 constructs that predict technology acceptance—performance expectancy, effort expectancy, social influence, and facilitating conditions. Results We interviewed 65 patients with MDR-TB and 10 HCPs. In patient interviews, greater acceptance of the MERM was related to perceptions that the audible and visual reminders improved medication adherence and that remote monitoring reduced the frequency of clinic visits (performance expectancy), that the device’s organization and labeling of medications made it easier to take them correctly (effort expectancy), that the device facilitated positive family involvement in the patient’s care (social influences), and that remote monitoring made patients feel more cared for by the health system (facilitating conditions). Lower patient acceptance was related to problems with the durability of the MERM’s cardboard construction and difficulties with portability and storage because of its large size (effort expectancy), concerns regarding stigma and the disclosure of patients’ MDR-TB diagnoses (social influences), and the incorrect understanding of the MERM because of suboptimal counseling (facilitating conditions). In their interviews, HCPs reported that MERM implementation resulted in fewer in-person interactions with patients and thus allowed HCPs to dedicate more time to other tasks, which improved job satisfaction. Conclusions Several features of the MERM support its acceptability among patients with MDR-TB and HCPs, and some barriers to patient use could be addressed by improving the design of the device. However, some barriers, such as disease-related stigma, are more difficult to modify and may limit use of the MERM among some patients with MDR-TB. Further research is needed to assess the accuracy of MERM for measuring adherence, its effectiveness for improving treatment outcomes, and patients’ sustained use of the device in larger scale implementation.
Astrocyte‐selective STAT3 knockdown rescues methamphetamine withdrawal‐disrupted spatial memory in mice via restoring the astrocytic capacity of glutamate clearance in dCA1

Methamphetamine (METH) is a common abused drug. METH‐triggered glutamate (Glu) levels in dorsal CA1 (dCA1) could partially explain the etiology of METH‐caused abnormal memory, but the synaptic mechanism remains unclear. Here, we found that METH withdrawal disrupted spatial memory in mice, accompanied by the increases in Glu levels and postsynaptic neuronal activities at dCA1 synapses. METH withdrawal weakened the capacity of Glu clearance in astrocytes, as indicated by increasing the A1‐like astrocytes and phosphorylated signal transducer and activator of transcription 3 (p‐STAT3), decreasing the Glu transporter 1(GLT‐1, also known as EAAT2 or SLC1A2), Glu‐aspartate‐transporter (GLAST also known as EAAT1 or SLC1A3) and astrocytic glutamine synthase (GS), but failed to affect the presynaptic Glu release from dCA3 within dCA1. Moreover, we identified that in vitro A1‐like astrocytes exhibited an increased STAT3 activation and the impaired capacity of Glu clearance. Most importantly, selective knockdown of astrocytic STAT3 in vivo in dCA1 restored the astrocytic capacity of Glu clearance, normalized Glu levels at dCA1 synapses, and finally rescued METH withdrawal‐disrupted spatial memory in mice. Thus, astrocytic Glu clearance system, especially STAT3, serves as a novel target for future therapies against METH neurotoxicity.
Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type specific vulnerability, their progression and histopathological classification remain controversial. Here using single-cell electrophysiology in vivo and immediate early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rats and mice in vivo. Bulk tissue and single-nucleus expression profiling disclosed sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage-channels, synaptic signalling and cell adhesion molecules were deregulated by epilepsy differently across sublayers, while neurodegenerative signatures primarily involved superficial cells. Pseudotime analysis of gene expression in single-nuclei and in situ validation revealed separated trajectories from health to epilepsy across cell types, and identified a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate sublayer- and cell type-specific changes associated with selective CA1 neuronal damage contributing to progression of hippocampal sclerosis.
A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease

Alexander disease (AxD) is a cerebral white matter disease affecting a wide range of ages, from infants to adults. In the present study, two cases of bulbospinal form AxD were reported, and a preliminary exploration of AxD was conducted thorough clinical, functional magnetic resonance imaging (fMRI) and functional analyses. In total, two de novo mutations in the glial fibrillary acidic protein (GFAP) gene (c.214G>A and c.1235C>T) were identified in unrelated patients (one in each patient). Both patients showed increased regional neural activity and functional connectivity in the cerebellum and posterior parietal cortex according to fMRI analysis. Notably, grey matter atrophy was discovered in the patient with c.214G>A variant. Functional experiments revealed aberrant accumulation of mutant GFAP and decreased solubility of c.1235C>T variant. Under pathological conditions, autophagic flux was activated for GFAP aggregate degradation. Moreover, transcriptional data of AxD and healthy human brain samples were obtained from the Gene Expression Omnibus database. Gene set enrichment analysis revealed an upregulation of immune-related responses and downregulation of ion transport, synaptic transmission and neurotransmitter homeostasis. Enrichment analysis of cell-specific differentially expressed genes also indicated a marked inflammatory environment in AxD. Overall, the clinical features of the two patients with bulbospinal form AxD were thoroughly described. To the best of our knowledge, the brain atrophy pattern and spontaneous brain functional network activity of patients with AxD were explored for the first time. Cytological experiments provided evidence of the pathogenicity of the identified variants. Furthermore, bioinformatics analysis found that inflammatory immune-related reactions may play a critical role in AxD, which may be conducive to the understanding of this disease.
CsrA regulation via binding to the base‐pairing small RNA Spot 42

The carbon storage regulator system and base‐pairing small RNAs (sRNAs) represent two predominant modes of bacterial post‐transcriptional regulation, which globally influence gene expression. Binding of CsrA protein to the 5′ UTR or initial mRNA coding sequences can affect translation, RNA stability, and/or transcript elongation. Base‐pairing sRNAs also regulate these processes, often requiring assistance from the RNA chaperone Hfq. Transcriptomics studies in Escherichia coli have identified many new CsrA targets, including Spot 42 and other base‐pairing sRNAs. Spot 42 synthesis is repressed by cAMP‐CRP, induced by the presence of glucose, and Spot 42 post‐transcriptionally represses operons that facilitate metabolism of nonpreferred carbon sources. CsrA activity is also increased by glucose via effects on CsrA sRNA antagonists, CsrB/C. Here, we elucidate a mechanism wherein CsrA binds to and protects Spot 42 sRNA from RNase E‐mediated cleavage. This protection leads to enhanced repression of srlA by Spot 42, a gene required for sorbitol uptake. A second, independent mechanism by which CsrA represses srlA is by binding to and inhibiting translation of srlM mRNA, encoding a transcriptional activator of srlA. Our findings demonstrate a novel means of regulation, by CsrA binding to a sRNA, and indicate that such interactions can help to shape complex bacterial regulatory circuitry.
Effect of portable non-invasive ventilation on thoracoabdominal volumes in recovery from intermittent exercise in patients with COPD.

BACKGROUND We previously showed that use of portable non-invasive ventilation (pNIV) during recovery periods within intermittent exercise improved breathlessness and exercise tolerance in COPD patients compared to pursed-lip breathing (PLB). However, in a minority of patients recovery from dynamic hyperinflation (DH) was better with PLB, based on inspiratory capacity. We further explored this using Optoelectronic Plethysmography to assess total and compartmental thoracoabdominal volumes. METHODS Fourteen COPD patients (mean±SD) (FEV1: 55±22% predicted) underwent, in a balanced order sequence, two intermittent exercise protocols on the cycle ergometer consisting of five repeated 2-min exercise bouts at 80% peak capacity, separated by 2-min recovery periods, with application of pNIV or PLB in the first minute of recovery. RESULTS Our findings identified 7 patients showing clinically meaningful recovery in DH with pNIV (DH responders) while 7 showed similar or better recovery in DH with PLB. When pNIV was applied, DH responders compared to DH non-responders exhibited greater tidal volume (by 0.8±0.3 L, p=0.015), inspiratory flow rate (by 0.6±0.5 L/sec, p=0.049), prolonged expiratory time (by 0.6±0.5 sec, p=0.006) and duty cycle (by 0.7±0.6 sec, p=0.007). DH responders showed a clinically meaningful reduction in end-expiratory thoracoabdominal DH (by 265±633 ml) predominantly driven by reduction in the abdominal compartment (by 210±494 ml); this effectively offset end-inspiratory rib-cage DH. Compared to DH non-responders, DH responders had significantly greater BMI by 8.4±3.2, p=0.022 and tended towards less severe resting hyperinflation by 0.3±0.3 L. CONCLUSION COPD patients who mitigate end-expiratory rib-cage DH by expiratory abdominal muscle recruitment benefit from pNIV application.
Temporal Network Embedding for Link Prediction via VAE Joint Attention Mechanism

Network representation learning or embedding aims to project the network into a low-dimensional space that can be devoted to different network tasks. Temporal networks are an important type of network whose topological structure changes over time. Compared with methods on static networks, temporal network embedding (TNE) methods are facing three challenges: 1) it cannot describe the temporal dependence across network snapshots; 2) the node embedding in the latent space fails to indicate changes in the network topology; and 3) it cannot avoid a lot of redundant computation via parameter inheritance on a series of snapshots. To overcome these problems, we propose a novel TNE method named temporal network embedding method based on the VAE framework (TVAE), which is based on a variational autoencoder (VAE) to capture the evolution of temporal networks for link prediction. It not only generates low-dimensional embedding vectors for nodes but also preserves the dynamic nonlinear features of temporal networks. Through the combination of a self-attention mechanism and recurrent neural networks, TVAE can update node representations and keep the temporal dependence of vectors over time. We utilize parameter inheritance to keep the new embedding close to the previous one, rather than explicitly using regularization, and thus, it is effective for large-scale networks. We evaluate our model and several baselines on synthetic data sets and real-world networks. The experimental results demonstrate that TVAE has superior performance and lower time cost compared with the baselines.