Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression

Background and Aims: The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis). Approach and Results: Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1+CD16lowCD163low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1+ hepatic macrophages originated from bone marrow–derived monocytes. Using an unbiased, machine learning–based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining–predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis. Conclusions: Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1+CD163low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies. Multiplex immunostaining applied to large scan of human samples showed dramatic and quantifiable changes in liver histology. Chronic liver diseases across varying conditions are characterized by extensive loss of parenchymal areas, and the expansion of perilobular septa populated with heterogeneous fibrogenic and immune cell populations. This study notably identified the accumulation of IBA1+ CD16lo CD163lo macrophages as a key marker of advanced liver disease. Created with BioRender.com.
Role of short-dwell daily ethanol-lock therapy in the management of hemodialysis tunneled cuffed catheter-related bloodstream infection.

BACKGROUND Catheter-Related Blood Stream Infection (CRBSI) is the major limitation of using Tunneled cuffed catheter (TCC) for long-term Hemodialysis. The standard therapy of CRBSI involves systemic antibiotics with catheter replacement/removal. As antibiotic alone is rarely effective therapy for CRBSI, biofilm eradication using antimicrobial locking solutions is a promising modality for CRBSI treatment, hence catheter salvage. The present study evaluated the efficacy and safety of Ethanol-lock therapy (ELT) in combination with systemic antibiotics for the management of CRBSI associated with hemodialysis TCC. METHOD 56 patients with CRBSI were treated with 70% ELT (1 h daily for 5 days) along with systemic antibiotics. Seventeen patients with CRBSI who didn't consent to ELT were treated with antibiotics alone. The effect of ELT was evaluated as clinical cure (fever resolution and negative surveillance cultures), infection-free TCC survival duration and adverse events of ELT among patients with CRBSI. The parameters were compared with 17 patients treated with antibiotics alone. RESULTS ELT was successful in 50 out of 56 patients (89.28%); compared to 41.17% (seven out of 17) with antibiotics alone (p < 0.001). Mean TCC survival was also significantly higher with ELT combined with systemic antibiotics (126.23 ± 18.67 days) compared to antibiotics alone (38.76 ± 9.91) (p = 0.006). No systemic adverse effects were noted with ELT; two patients receiving ELT had catheter breakage during the study period. CONCLUSION We conclude that short-dwell daily ELT with systemic antibiotics is an effective therapy for CRBSI in hemodialysis patients with TCC.
Relationship between gut microbiota and vascular calcification in hemodialysis patients

Abstract Introduction Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC is complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences in gut microbiota between the different VC groups and the main bacteria associated with VC in hemodialysis (HD) patients in an attempt to open up new preventive and therapeutic approaches and define the probable mechanism for VC in HD patients in the future. Methods A total of 73 maintenance HD patients were enrolled in this cross-sectional study. According to the abdominal aortic calcification (AAC) scores, the participants were divided into the high AAC score group and the low AAC score group. High-throughput sequencing of the gut microbiota was performed and the results were evaluated by alpha diversity, beta diversity, species correlation, and model predictive analyses. Results The prevalence of VC was 54.79% (40/73) in the study. The majority of phyla in the two groups were the same, including Firmicutes, Actinobacteriota, Proteobacteria, and Bacteroidota. The microbial diversity in the high AAC score group had a decreasing trend (p = 0.050), and the species abundance was significantly lower (p = 0.044) than that in the low AAC score group. The HD patients with high AAC scores showed an increased abundance of Proteobacteria and decreased abundances of Bacteroidota and Synergistota at the phylum level; increased abundances of Escherichia-Shigella, Ruminococcus_gnavus_group, and Lactobacillus; and decreased abundances of Ruminococcus and Lachnospiraceae_NK4A136_group at the genus level (p<0.05). Escherichia-Shigella and Ruminococcus_gnavus_group were positively correlated with VC, and Ruminococcus, Adlercreutzia, Alistipes, and norank_f__Ruminococcaceae were negatively correlated with VC. Escherichia-Shigella had the greatest influence on VC in HD patients, followed by Ruminococcus and Butyricimonas. Conclusions Our results provide clinical evidence that there was a difference in gut microbiota between the different VC groups in HD patients. Escherichia–Shigella, a lipopolysaccharide (LPS)-producing bacterium, was positively correlated with VC and had the greatest influence on VC. Ruminococcus, a short-chain fatty acid (SCFA)-producing bacterium, was negatively correlated with VC and had the second strongest influence on VC in HD patients. The underlying mechanism is worth studying. These findings hint at a new therapeutic target.
Geotail energetic particles and ion composition instrument

The Energetic Particles and Ion Composition (EPIC) instrument, flown onboard the GEOTAIL satellite, is designed to measure the characteristics of particle populations important to understanding the make-up and dynamics of the earth's geomagnetic tail. To do this, EPIC, a joint endeavor between the Technical University of Braunschweig (TUB), the University of Maryland (UM), and The Johns Hopkins University Applied Physics Laboratory (JHU/APL), is made up of five subassemblies: the Supra-Thermal Ion Composition Spectrometer (STICS) sensor, the STICS analog electronics, the Ion Composition System (ICS) sensor, the ICS analog electronics, and the Data Processing Unit (DPU). The STICS sensor provides ∼4π angular coverage, composition and spectral observations, with charge state determination for all ions from 30 keV to 230 keV/e, and mass per charge measurements ≥7.5 keV/e. The ICS sensor provides flux, composition, spectra, and angular distributions over two polar angles of the elemental species protons through iron from ≥50 keV to 3 MeV along with angular distributions in one plane of electron fluxes >32 keV and >110 keV. The DPU provides the capability of numerous operating modes from which a small number will be selected to optimize data collection throughout the many phases of the GEOTAIL mission. To date the EPIC instrument performance has been very successful. In this paper we describe the instrument, its operation, and show some of our early results.
The Association Between Frailty and a Nurse-Identified Need for Comprehensive Geriatric Assessment Referral from the Emergency Department

Background Emergency nurses commonly conduct geriatric assessments in the emergency department (ED). However, little is known about what geriatric syndromes or clinical presentations prompt a nurse to document an identified need for comprehensive geriatric assessment (CGA). Objectives To examine the association between geriatric syndromes, like frailty, and a nurse-identified need for a CGA following emergency care. Methods We conducted a secondary analysis of a multi-province Canadian cohort from the InterRAI Multinational Cohort Study. We collected data at ED registration from patients 75 years of age and older (n = 2,274) from eight ED sites across Canada between November 2009 and April 2012. Geriatric syndromes were assessed by trained emergency nurses using the interRAI ED Contact Assessment; and we retrospectively calculated the ED frailty index. We employed binary logistic regression to determine the adjusted associations between geriatric syndromes and a nurse-identified need for a CGA. Results Approximately one-quarter (28%) of older adults were identified to need a CGA following emergency care. A 0.1 unit increase in the ED frailty index increased the likelihood of a nurse identify a need for CGA (RD: 6.6; 95% CI = 5.5–7.9). Most geriatric syndromes increased the probability of a nurse documenting the need for a CGA. Conclusion When assessed by emergency nurses, the identified need for CGA is strongly linked to the presence of geriatric syndromes, including frailty. We provide face validity for the continued use of emergency nurses for screening and assessing older ED patients.
Social Mediators of the Association Between Depression and Falls Among Older Adults

Objectives To investigate the role of social factors in the association between depression and falls among older adults. Methods The sample included data from 3443 older adults from three waves of the Health and Retirement Study (2010–2014). A Lifestyle Questionnaire was used to measure social engagement, social network contact, and neighborhood social context. Mediating effects of social factors were estimated through causal mediation analysis. Results: Poorer social engagement and network contact were associated with greater likelihood of falls, while poorer neighborhood context was associated with greater likelihood of fall injuries. Social engagement mediated a significant portion of the effect of depression on falls (OR: 1.03, 95% CI: 1.00, 1.06), and neighborhood context mediated a portion of the effect of depression on fall injuries (OR: 1.03, 95% CI: 1.00, 1.07). Discussion: The direct and indirect impacts of social factors suggest that considering them may help improve existing fall prevention approaches.
Lactate as a myokine and exerkine: drivers and signals of physiology and metabolism

No longer viewed as a metabolic waste product and cause of muscle fatigue, a contemporary view incorporates the roles of lactate in metabolism, sensing and signaling in normal as well as pathophysiological conditions. Lactate exists in millimolar concentrations in muscle, blood and other tissues and can rise more than an order of magnitude as the result of increased production and clearance limitations. Lactate exerts its powerful driver-like influence by mass action, redox change, allosteric binding, and other mechanisms described in this article. Depending on the condition, such as during rest and exercise, following injury, or pathology, lactate can serve as a myokine or exerkine with autocrine-, paracrine-, and endocrine-like functions that have important basic and translational implications. For instance, lactate signaling is: involved in reproductive biology, fueling the heart, muscle and brain, controlling cardiac output and breathing, growth and development, and a treatment for inflammatory conditions. Ironically, lactate can be disruptive of normal processes such as insulin secretion when insertion of lactate transporters into pancreatic Beta-cell membranes is not suppressed and in carcinogenesis. Lactate signaling is important in areas of intermediary metabolism, redox biology, mitochondrial biogenesis, cardiovascular and pulmonary regulation, genomics, neurobiology, gut physiology, appetite regulation, nutrition and overall health and vigor. The various roles of lactate as a myokine and exerkine are reviewed.
A hybrid MM‐PO method combining UV technique for scattering from two‐dimensional target above a rough surface

In this article, an efficient hybrid MM‐PO method combining UV technique is applied to calculate the EM scattering from a 2D PEC target above a PEC rough surface. Considering the target as the MM region and the rough surface as the PO region, the current on the rough surface is obtained through the PO approximation, leaving only unknowns on the target region. Furthermore, a UV technique is used to accelerate the coupling interaction between the target and the rough surface. With this hybrid method, large scale target/rough surface scattering problems can be solved more effectively. Using the Monte‐Carlo method to generate the rough surface, the bistatic difference field radar cross‐section of the target above a Pierson‐Morkowitz rough surface is numerically simulated. The results show good agreement when compared with the other methods. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 2957–2960, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22922
Environmental eustress promotes liver regeneration through the sympathetic regulation of type 1 innate lymphoid cells to increase IL-22 in mice

Background and Aims: The liver has the unique ability of regeneration, which is extremely important for restoring homeostasis after liver injury. Although clinical observations have revealed an association between psychological stress and the liver, whether stress has a causal influence on the liver regeneration remains markedly less defined. Approach and Results: Rearing rodents in an enriched environment (EE) can induce eustress or positive psychological stress. Herein, EE-induced eustress was found to significantly enhance the ability of liver regeneration after partial hepatectomy or carbon tetrachloride-induced liver injury based on the more rapid restoration of liver/body weight ratio and the significantly increased number of proliferating hepatocytes in EE mice. Mechanistically, the cytokine array revealed that IL-22 was markedly increased in the regenerating liver in response to EE. Blockade of IL-22 signaling abrogated the enhanced liver regeneration induced by EE. Group 1 innate lymphoid cells (ILCs), including type 1 ILCs (ILC1s), have been identified as the major sources of IL-22 in the regenerating liver. EE housing led to a rapid accumulation of hepatic ILC1s after partial hepatectomy and the EE-induced enhancement of liver regeneration and elevation of IL-22 was nearly eliminated in ILC1-deficient Tbx21 -/- mice. Chemical sympathectomy or blockade of β-adrenergic signaling also abolished the effect of EE on ILC1s and attenuated the enhanced liver regeneration of EE-housed mice. Conclusion: The study findings support the brain-liver axis and suggest that environment-induced eustress promotes liver regeneration through the sympathetic nerve/ILC1/IL-22 axis.
Video-Conference-Based Graphomotor Examination for Children: A Validation Study

Background: Telehealth can assist with providing accessible pediatric occupational therapy services. Objectives: This study aimed to investigate the acceptability, inter-rater reliability, and concurrent validity of the Gilboa Functional Test (GIFT) as a video-conference-based graphomotor examination for children (GIFT-Online). Methodology: A community-based sample of 157 children aged 3 to 7 years was screened using the GIFT-Online. Findings: Inter-rater reliability was excellent (r = 0.97; p < .001; n = 40). In addition, significant correlations were found between the total GIFT-Online scores and the Developmental Coordination Disorder Questionnaire 2007 (DCDQ’07), the Little DCDQ (LDCDQ) (r = 0.29, p < .001; n = 157), and the Drawing Proficiency Screening Questionnaire (DPSQ) (r = −0.35, p < .001; n = 157); demonstrating construct and concurrent validity. The online assessment was well received by parents and children. Conclusions: The GIFT-Online was found to be an acceptable method of assessing graphomotor performance. Our results support the validity and reliability of the GIFT-Online as a screening tool administered remotely, thereby overcoming physical distancing and travel restrictions.
Ocular myasthenia gravis-like symptoms associated with erenumab: Case report.

OBJECTIVE We present a case of a patient who developed myasthenia gravis (MG)-like symptoms during erenumab treatment. CASE REPORT The patient had a years-long history of chronic migraine with visual and sensory aura. Two months after the beginning of erenumab therapy, she reported intermittent bilateral weakness of the eyelids, with ptosis. The eyelid ptosis was severe enough to block the patient's vision. The symptoms would usually last between 5 and 10 minutes and resolve completely spontaneously, but they repeated on a daily basis. Antibodies against acetylcholine receptors and muscle-specific kinase were all negative, and other work-up excluded the usual etiology of ptosis. Since the cause of symptoms was not detected, we suspected they were induced by erenumab. The treatment was discontinued, and after 7 weeks from the last dose of erenumab, ocular symptoms resolved completely. In the presented case, other possible causes of MG-like symptoms were excluded by diagnostic tests and clinical course of the disease. The temporal relationship between the administration of erenumab and occurrence of ptosis, with regression of the symptoms after the drug discontinuation supports the hypothesis of causal relationship with erenumab. According to the Naranjo's Adverse Drug Reaction Probability Scale, erenumab-related MG-like symptoms were rated 'probable'. Reviewing the literature, we identified no similar case reports. CONCLUSION Drug-induced MG-like symptoms might be life threatening. Therefore, clinicians should be aware of these adverse reactions during the use of erenumab.
Wouldn't It Be Nice …? The Automatic Unbiasedness of OLS (and GLS)

In a recent issue of this journal, Larocca (2005) makes two notable claims about the best linear unbiasedness of ordinary least squares (OLS) estimation of the linear regression model. The first, drawn from McElroy (1967), is that OLS remains best linear unbiased in the face of a particular kind of autocorrelation (constant for all pairs of observations). The second, much larger and more heterodox, is that the disturbance need not be assumed uncorrelated with the regressors for OLS to be best linear unbiased. The assumption is unnecessary, Larocca says, because “orthogonality [of disturbance and regressors] is a property of all OLS estimates” (p. 192). Of course OLS's being best linear unbiased still requires that the disturbance be homoskedastic and (McElroy's loophole aside) nonautocorrelated, but Larocca also adds that the same automatic orthogonality obtains for generalized least squares (GLS), which is also therefore best linear unbiased, when the disturbance is heteroskedastic or autocorrelated.
Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Background The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.
The Effect of Photobiomodulation Therapy on Inflammation Following Dental Prophylaxis

To evaluate the effectiveness of photobiomodulation therapy (PBMT) in reducing gingivitis following professional dental prophylaxis in dogs in a prospective, randomly controlled, double-blind study. The study included 47 dogs (male n = 23, female n = 24), with a mean age of 6.5 ± 2.6 years and a bodyweight of 28.9 ± 5.3 kg. Breeds included: Belgian Malinois Shepherd Dogs (n = 23), German Shepherd Dogs (n = 14), Labrador Retriever (n = 4), and Dutch Shepherd Dogs (n = 3). The left side of the mouth was treated by performing dental prophylaxis (control group). The right side received dental prophylaxis and a single session of PBMT using a Class IV therapeutic laser (treatment group). Each side was graded individually for periodontal disease (PD), gingivitis, and calculus. Follow-up observations were conducted on days 1, 3, 8, and 15 post-treatment. Results were compared using a Mann-Whitney Test. Multiple regression was run to predict PD, gingivitis, and calculus scores using age, sex, and breed. A p < . 05 was considered significant. The PBMT group (PG) showed significantly lower gingivitis scores from day 1 to 15 post-treatment. PD had an increasing prevalence with age. Age and breed contributed to the prediction of PD, gingivitis, and calculus grading. This study showed that PBMT significantly reduced the grade of gingivitis following dental prophylaxis, and may be a useful adjuvant procedure following dental prophylaxis.