Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial Intelligence for Surveillance in Public Health

Summary Objectives: To introduce and summarize current research in the field of Public Health and Epidemiology Informatics. Methods: The 2018 literature concerning public health and epidemiology informatics was searched in PubMed and Web of Science, and the returned references were reviewed by the two section editors to select 15 candidate best papers. These papers were then peer-reviewed by external reviewers to give the editorial team an enlightened selection of the best papers. Results: Among the 805 references retrieved from PubMed and Web of Science, three were finally selected as best papers. All three papers are about surveillance using digital tools. One study is about the surveillance of flu, another about emerging animal infectious diseases and the last one is about foodborne illness. The sources of information are Google news, Twitter, and Yelp restaurant reviews. Machine learning approaches are most often used to detect signals. Conclusions: Surveillance is a central topic in public health informatics with the growing use of machine learning approaches in regards of the size and complexity of data. The evaluation of the approaches developed remains a serious challenge.
The plant pathogen Pectobacterium atrosepticum contains a functional formate hydrogenlyase‐2 complex

Pectobacterium atrosepticum SCRI1043 is a phytopathogenic Gram‐negative enterobacterium. Genomic analysis has identified that genes required for both respiration and fermentation are expressed under anaerobic conditions. One set of anaerobically expressed genes is predicted to encode an important but poorly understood membrane‐bound enzyme termed formate hydrogenlyase‐2 (FHL‐2), which has fascinating evolutionary links to the mitochondrial NADH dehydrogenase (Complex I). In this work, molecular genetic and biochemical approaches were taken to establish that FHL‐2 is fully functional in P. atrosepticum and is the major source of molecular hydrogen gas generated by this bacterium. The FHL‐2 complex was shown to comprise a rare example of an active [NiFe]‐hydrogenase‐4 (Hyd‐4) isoenzyme, itself linked to an unusual selenium‐free formate dehydrogenase in the final complex. In addition, further genetic dissection of the genes encoding the predicted membrane arm of FHL‐2 established surprisingly that the majority of genes encoding this domain are not required for physiological hydrogen production activity. Overall, this study presents P. atrosepticum as a new model bacterial system for understanding anaerobic formate and hydrogen metabolism in general, and FHL‐2 function and structure in particular.
Investigations into ventral prefrontal cortex using mediation models

The ventral prefrontal cortex (vPFC) is a major focus of investigation in neuroscience, particularly in the studies of emotion and emotion‐cognition integration. A crucial question concerning the regulatory function of vPFC is how it is recruited, especially how the function maps onto the structure and determines appropriate behavior. In social exclusion studies, mediation model analyses suggest that vPFC regulates distress by disrupting anterior cingulate cortex (ACC) activities, whereas I recently report (Hu, 2018; Neuropsychologia) that ventral medial prefrontal cortex appears to defend the organism from acute stress by activating ACC. In this review, I synthesize and highlight functional imaging research with mediation analysis that over the past decades has begun to offer new insights into the brain mechanisms underlying vPFC. Toward this end, the first section of the paper outlines a model of the processes and neural systems involved in the interaction of emotion and cognition. The second and third sections survey recent research on emotional regulation with negative and positive pathways, respectively, emanating from vPFC. The fourth section summarizes the current dynamic network findings. Functional mediation analysis helps to identify signals within vPFC and others that are common and/or specific to particular information processing. Finally, I provide a personal perspective of the adoption of mediation model analysis in the investigations into vPFC.
Experimental Multicenter and Multivendor Evaluation of the Performance of PET Radiomic Features Using 3-Dimensionally Printed Phantom Inserts

The sensitivity of radiomic features to several confounding factors, such as reconstruction settings, makes clinical use challenging. To investigate the impact of harmonized image reconstructions on feature consistency, a multicenter phantom study was performed using 3-dimensionally printed phantom inserts reflecting realistic tumor shapes and heterogeneity uptakes. Methods: Tumors extracted from real PET/CT scans of patients with non–small cell lung cancer served as model for three 3-dimensionally printed inserts. Different heterogeneity pattern were realized by printing separate compartments that could be filled with different activity solutions. The inserts were placed in the National Electrical Manufacturers Association image-quality phantom and scanned various times. First, a list-mode scan was acquired and 5 statistically equal replicates were reconstructed. Second, the phantom was scanned 4 times on the same scanner. Third, the phantom was scanned on 6 PET/CT systems. All images were reconstructed using EANM Research Ltd. (EARL)–compliant and locally clinically preferred reconstructions. EARL-compliant reconstructions were performed without (EARL1) or with (EARL2) point-spread function. Images were analyzed with and without resampling to 2-mm cubic voxels. Images were discretized with a fixed bin width (FBW) of 0.25 and a fixed bin number (FBN) of 64. The intraclass correlation coefficient (ICC) of each scan setup was calculated and compared across reconstruction settings. An ICC above 0.75 was regarded as high. Results: The percentage of features yielding a high ICC was largest for the statistically equal replicates (70%–91% for FBN; 90%–96% for FBW discretization). For scans acquired on the same system, the percentage decreased, but most features still resulted in a high ICC (FBN, 52%–63%; FBW, 75%–85%). The percentage of features yielding a high ICC decreased more in the multicenter setting. In this case, the percentage of features yielding a high ICC was larger for images reconstructed with EARL-compliant reconstructions: for example, 40% for EARL1 and 60% for EARL2 versus 21% for the clinically preferred setting for FBW discretization. When discretized with FBW and resampled to isotropic voxels, this benefit was more pronounced. Conclusion: EARL-compliant reconstructions harmonize a wide range of radiomic features. FBW discretization and a sampling to isotropic voxels enhances the benefits of EARL-compliant reconstructions.
Effects of acute prolonged sitting on cerebral perfusion and executive function in young adults: A randomized cross-over trial.

Exposure to acute prolonged sitting reportedly leads to decreased cerebral blood flow. However, it is unclear whether this exposure translates to decreased cerebral perfusion and executive function or whether simple strategies to break up sitting can maintain cerebral perfusion and executive function. This study sought to answer two questions: in young, healthy adults, (a) does prolonged (3 hr) sitting lead to decreased cerebral perfusion and executive function? and (b) does breaking up prolonged sitting, using intermittent calf raise exercises, prevent changes in cerebral perfusion and executive function? Twenty young, healthy participants (21.7 [2.5] years, 70% female, 25.5 [6.1] kg/m2 ) were randomized to 3 hr sitting with 10 calf raises every 10 min (CALF) and 3 hr sitting without intermittent calf raises (CON). Prefrontal cortex perfusion was assessed using near-infrared spectroscopy to monitor total hemoglobin (tHB) concentration and tissue saturation index (TSI, oxygenated hemoglobin). Executive function was assessed using the Stroop word and color tasks. Following 3 hr sitting, tHb was significantly lower in CALF versus CON (-2.1 μM, 95% CI [-3.1, -1.1]). TSI was not significantly different between conditions (p = .667). Word (1.6 ms, 95% CI [0.7, 2.5]) and color (1.3 ms, 95% CI [-0.2, 2.8]) completion times were longer (worse) for CALF compared to CON. In conclusion, calf raises decreased both cerebral perfusion and executive function. Simple strategies, such as fidgeting or calf raises, which have been reported to preserve vascular function in the legs, appear not to be sufficient to benefit cerebral perfusion or executive function.
Impact of nanosystems in Staphylococcus aureus biofilms treatment

ABSTRACT Staphylococcus aureus (S. aureus) is considered by the World Health Organization as a high priority pathogen for which new therapies are needed. This is particularly important for biofilm implant-associated infections once the only available treatment option implies a surgical procedure combined with antibiotic therapy. Consequently, these infections represent an economic burden for Healthcare Systems. A new strategy has emerged to tackle this problem: for small bugs, small particles. Here, we describe how nanotechnology-based systems have been studied to treat S. aureus biofilms. Their features, drawbacks and potentialities to impact the treatment of these infections are highlighted. Furthermore, we also outline biofilm models and assays required for preclinical validation of those nanosystems to smooth the process of clinical translation.
The mode of action of Fruitless: Is it an easy matter to switch the sex?

The fruitless (fru) locus was originally defined by a male sterile mutation that promotes male‐to‐male courtship while suppressing male‐to‐female courtship in Drosophila melanogaster. The fru promoter‐1 pre‐RNA generates a set of BTB‐zinc finger family FruM proteins expressed exclusively in the male neurons, leading to the formation of sexual dimorphisms in neurons via male‐specific neuroblast proliferation, male‐specific neural survival, male‐specific neuritegenesis or male‐specific arbor patterning. Such a wide spectrum of phenotypic effects seems to result from chromatin modifications, in which FruBM recruits Bonus, Histone deacetylase 1 (HDAC1) and/or Heterochromatin protein 1a (HP1a) to ~130 target sites. One established FruBM transcriptional target is the axon guidance protein gene robo1. Multiple transcriptional regulator‐binding sites are nested around the FruBM‐binding site, and mediate sophisticated modulation of the repressor activity of FruBM. FruBM also binds to the Lola‐Q transcriptional repressor to protect it from proteasome‐dependent degradation in male but not female neurons as FruBM exists only in male neurons, leading to the formation of sexually dimorphic neural structures. These findings shed light on the multilayered network of transcription regulation orchestrated by the master regulator FruBM.
Glucolipotoxicity Alters Insulin Secretion via Epigenetic Changes in Human Islets

Type 2 diabetes (T2D) is characterized by insufficient insulin secretion and elevated glucose levels, often in combination with high levels of circulating fatty acids. Long-term exposure to high levels of glucose or fatty acids impair insulin secretion in pancreatic islets, which could partly be due to epigenetic alterations. We studied the effects of high concentrations of glucose and palmitate combined for 48 h (glucolipotoxicity) on the transcriptome, the epigenome, and cell function in human islets. Glucolipotoxicity impaired insulin secretion, increased apoptosis, and significantly (false discovery rate <5%) altered the expression of 1,855 genes, including 35 genes previously implicated in T2D by genome-wide association studies (e.g., TCF7L2 and CDKN2B). Additionally, metabolic pathways were enriched for downregulated genes. Of the differentially expressed genes, 1,469 also exhibited altered DNA methylation (e.g., CDK1, FICD, TPX2, and TYMS). A luciferase assay showed that increased methylation of CDK1 directly reduces its transcription in pancreatic β-cells, supporting the idea that DNA methylation underlies altered expression after glucolipotoxicity. Follow-up experiments in clonal β-cells showed that knockdown of FICD and TPX2 alters insulin secretion. Together, our novel data demonstrate that glucolipotoxicity changes the epigenome in human islets, thereby altering gene expression and possibly exacerbating the secretory defect in T2D.
Force depression following a stretch‐shortening cycle depends on the amount of residual force enhancement established in the initial stretch phase

Studies on residual force enhancement (rFE) and residual force depression (rFD) of the muscle‐tendon unit (MTU) have typically been conducted independent of each other, with little information available on how stretch‐induced rFE affects the shortening phase and the steady‐state MTU isometric force at the end of stretch‐shortening cycles (SSCs). We showed previously that when rFE is kept constant, but the force at the end of the stretch is varied by changing the stretch speed, the steady‐state forces at the end of SSCs were the same. These results led to the hypothesis that the amount of rFE of the MTU established in the initial stretch phase of SSCs determines the steady‐state force following the shortening phase of SSCs. This study was aimed at testing this hypothesis. Steady‐state MTU isometric thumb adduction forces were measured for pure isometric contractions, following pure shortening contractions, following pure stretch contractions, and following SSCs with constant shortening speed and magnitude. However, two stretch magnitudes (30° and 10° thumb abduction) and stretch speeds (15°/sec and ~ 60°/sec, respectively) were chosen such that forces at the end of the stretch phase of the SSCs were the same, while rFE differed substantially. As hypothesized, the steady‐state isometric MTU forces following SSCs were positively related to the stretch‐magnitude dependent amount of rFE established in the stretch phase and were independent of the force reached at the end of the stretch phase in SSCs. Among many competing theories, these results can potentially be explained with the idea that there is a length‐specific engagement of a passive structural element at the initial length of muscle activation.
Solutions to the technical challenges embedded in the current methods for intraoperative peripheral nerve action potential recordings.

OBJECTIVE Intraoperative nerve action potential (NAP) recording is a useful tool for surgeons to guide decisions on surgical approaches during nerve repair surgeries. However, current methods remain technically challenging. In particular, stimulus artifacts that contaminate or mask the NAP and therefore impair the interpretation of the recording are a common problem. The authors' goal was to improve intraoperative NAP recording techniques by revisiting the methods in an experimental setting. METHODS First, NAPs were recorded from surgically exposed peripheral nerves in monkeys. For the authors to test their assumptions about observed artifacts, they then employed a simple model system. Finally, they applied their insights to clinical cases in the operating room. RESULTS In monkey peripheral nerve recordings, large stimulus artifacts obscured NAPs every time the nerve segment (length 3-5 cm) was lifted up from the surrounding tissue, and NAPs could not be recorded. Artifacts were suppressed, and NAPs emerged when "bridge grounding" was applied, and this allowed the NAPs to be recorded easily and reliably. Tests in a model system suggested that exaggerated stimulus artifacts and unmasking of NAPs by bridge grounding are related to a loop effect that is created by lifting the nerve. Consequently, clean NAPs were acquired in "nonlifting" recordings from monkey peripheral nerves. In clinical cases, bridge grounding efficiently unmasked intraoperative NAP recordings, validating the authors' principal concept in the clinical setting and allowing effective neurophysiological testing in the operating room. CONCLUSIONS Technical challenges of intraoperative NAP recording are embedded in the current methods that recommend lifting the nerve from the tissue bed, thereby exaggerating stimulus artifacts by a loop effect. Better results can be achieved by performing nonlifting nerve recording or by applying bridge grounding. The authors not only tested their findings in an animal model but also applied them successfully in clinical practice.
The cAMP–Adenosine Feedback Loop Maintains the Suppressive Function of Regulatory T Cells

Key Points Intracellular cAMP regulates CD39-dependent adenosine production in Tregs. Extracellular cAMP directly participates in Treg-derived adenosine production. Increasing the intracellular cAMP level improves the therapeutic efficacy of iTregs. Visual Abstract Therapeutic manipulation of regulatory T cells (Tregs) has been regarded as a promising approach for the treatment of immune disorders. However, a better understanding of the immunomodulatory mechanisms of Tregs and new safe and effective methods to improve the therapeutic effects of Tregs are highly desired. In this study, we have identified the key roles of a cAMP–adenosine positive feedback loop in the immunomodulatory function of Tregs. Adult male C57BL/6J mice were used for an experimental autoimmune uveitis (EAU) model, Tregs, and uveitogenic T cells (UTs). In established EAU, induced Tregs (iTregs) administration alleviated the inflammatory response. In vitro, iTregs inhibited UTs proliferation and inflammatory cytokine production. Mechanistically, cAMP is partially responsible for iTreg-mediated inhibition on UTs. Importantly, intracellular cAMP regulates CD39 expression and CD39-dependent adenosine production in iTregs, and cAMP directly participates in iTreg-derived adenosine production by a CD39 signaling–independent extracellular cAMP–adenosine pathway. Moreover, extracellular adenosine increases the intracellular cAMP level in Tregs. More importantly, increasing the cAMP level in iTregs before transfer improves their therapeutic efficacy in established EAU. Notably, the cAMP–adenosine loop exists in both iTregs and naturally occurring Tregs. These findings provide new insights into the immunosuppressive mechanisms of Tregs and suggest a new strategy for improving the therapeutic efficacy of Tregs in established autoimmune disease.
CD8αα homodimers function as a coreceptor for KIR3DL1

Significance Inhibitory receptors specific for major histocompatibility class I (MHC-I) molecules regulate NK cell responses. Here, we describe that cluster of differentiation 8αα (CD8αα) works as a coreceptor to enhance interaction between MHC-I and one of these receptors, KIR3DL1. We further demonstrate that inhibition of NK cell activation by MHC-I and KIR3DL1 interaction is fine-tuned by CD8αα. By testing cytokine secretion ability, we found CD8αα+ NK cells are generally better educated, and thus more responsive to abnormal cells. All these results suggest that CD8αα is an important regulator of NK cell activation. Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, αα homodimer or αβ heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8αβ is a coreceptor for the T cell receptor (TCR) and binds to the same cognate pMHC-I as the TCR, thus enabling or augmenting T cell responses. The function of CD8αα homodimers is largely unknown. While CD8αβ heterodimer is expressed exclusively on CD8+ T cells, the CD8αα homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8αα homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8αα enhances binding of pMHC-I to KIR3DL1, increases KIR3DL1 clustering at the immunological synapse, and augments KIR3DL1-mediated inhibition of NK cell activation. Additionally, interactions between pMHC-I and CD8αα homodimers regulate KIR3DL1+ NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.
Southampton Arm Fracture Frailty and Sarcopenia Study (SAFFSS): a study protocol for the feasibility of assessing frailty and sarcopenia among older patients with an upper limb fracture

Introduction Falls are a major health problem for older people; 35% of people aged 65+ years fall every year, leading to fractures in 10%–15%. Upper limb fractures are often the first sign of osteoporosis and routine screening for osteoporosis is recommended by the National Institute for Health and Care Excellence to prevent subsequent hip fractures. However, both frailty and sarcopenia (muscle weakness) are associated with increased risk of falling and fracture but are not routinely identified in this group. The aim of this study is to evaluate the feasibility of assessing and managing frailty and sarcopenia among people aged 65+ years with an upper limb fracture. Methods and analysis This study will be conducted in three fracture clinics in one acute trust in England. 100 people aged 65+ years with an upper arm fracture will be recruited and assessed using six validated frailty measures and two sarcopenia tools. The prevalence of the two conditions and the best tools to use will be determined. Those with either condition will be referred to geriatric clinical teams for comprehensive geriatric assessment (CGA). We will document the proportion who are referred for CGA and those who receive CGA. Other outcome measures including falls, fractures and healthcare resource use over 6 months will be collected. In-depth interviews with a purposive sample of patients who undergo the frailty and sarcopenia assessments and healthcare professionals in fracture clinics and geriatric services will be carried out to their acceptability of assessing frailty and sarcopenia in a busy environment. Ethics and dissemination The study was given the relevant ethical approvals from NHS Research Ethics Committee (REC No: 18/NE/0377), the University Hospital Southampton NHS Foundation Trust, and the University of Southampton, Faculty of Medicine Ethics Committee and Research Governance Office. Findings will be published in scientific journals and presented to local, national and international conferences. Trial registration number ISRCTN13848445
Efficacy of THN102 (a combination of modafinil and flecainide) on vigilance and cognition during 40‐hour total sleep deprivation in healthy subjects: Glial connexins as a therapeutic target

THN102 is a novel combination of modafinil and low‐dose flecainide, targeting glial connexin activity to modulate modafinil effects. We investigated THN102 efficacy compared to modafinil and to placebo on vigilance and cognitive function during 40‐hour total sleep deprivation (TSD).