Miracle-dz/UniFAR-FTUs huggingface dataset:
Applications and Outcomes of Extracorporeal Life Support Use in Adult Liver Transplantation: A Case Series and Review of Literature

The use of extracorporeal life support (ECLS) is increasingly reported in adult liver transplantation (LT). However, neither the role of ECLS in the perioperative setting for LT nor its outcomes has been well defined. We performed a retrospective chart review of all adult LT patients at our institution who received ECLS from 2004 to 2021. We also conducted a comprehensive literature search for adult LT cases that involved perioperative ECLS for respiratory or cardiac failure. Over the study period, 11 LT patients required ECLS at our institution, two for respiratory and nine for cardiac failure. Both patients with respiratory failure received ECLS as a bridge to LT and survived to discharge. Nine patients required ECLS for acute cardiac failure either intraoperatively or postoperatively, and two survived to discharge. In the literature, we identified 35 cases of respiratory failure in LT patients requiring perioperative ECLS. Applications included preoperative bridge to LT (n = 6) and postoperative rescue (n = 29), for which overall survival was 44%. We identified 31 cases of cardiac failure in LT patients requiring either ECLS or cardiopulmonary bypass for cardiac support or rescue for intraoperative or postoperative cardiac failure (n = 30). There is evidence for consideration of ECLS as a bridge to LT in patients with potentially reversible respiratory failure or as rescue therapy for respiratory failure in posttransplant patients. ECLS has a prohibitively high risk of futility in pretransplant patients with cardiac failure but may have a role in LT patients with a functioning graft and potentially reversible cardiac failure.
A Combination Strategy of Solubility Enhancers for Effective Production of Soluble and Bioactive Human Enterokinase

Enterokinase is one of the hydrolases that catalyze hydrolysis to regulate biological processes in intestinal visceral mucosa. Enterokinase plays an essential role in accelerating the process of protein digestion as it converts trypsinogen into active trypsin by accurately recognizing and cleaving a specific peptide sequence, (Asp)4-Lys. Due to its exceptional substrate specificity, enterokinase is widely used as a versatile molecular tool in various bioprocessing, especially in removing fusion tags from recombinant proteins. Despite its biotechnological importance, mass production of soluble enterokinase in bacteria still remains an unsolved challenge. Here, we present an effective production strategy of human enterokinase using tandemly linked solubility enhancers consisting of thioredoxin, phosphoglycerate kinase or maltose-binding protein. The resulting enterokinases exhibited significantly enhanced solubility and bacterial expression level while retaining enzymatic activity, which demonstrates that combinatorial design of fusion proteins has the potential to provide an efficient way to produce recombinant proteins in bacteria.
Cardiovascular risk associated with allopurinol vs. benzbromarone in patients with gout

Abstract Aims With the high prevalence of gout and associated cardiovascular (CV) diseases, information on the comparative CV safety of individual urate-lowering drugs becomes increasingly important. However, few studies examined the CV risk of uricosuric agents. We compared CV risk among patients with gout who initiated allopurinol vs. benzbromarone. Methods and results Using the Korean National Health Insurance claims data (2002–17), we conducted a cohort study of 124 434 gout patients who initiated either allopurinol (n = 103 695) or benzbromarone (n = 20 739), matched on propensity score at a 5:1 ratio. The primary outcome was a composite CV endpoint of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. To account for competing risk of death, we used cause-specific hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes comparing allopurinol initiators with benzbromarone. Over a mean follow-up of 1.16 years, 2258 patients developed a composite CV event. The incidence rate of the composite CV event was higher in allopurinol initiators (1.81 per 100 person-years) than benzbromarone (1.61 per 100 person-years) with a HR of 1.22 (95% CI 1.05–1.41). The HR for all-cause mortality was 1.66 (95% CI 1.43–1.93) among allopurinol initiators compared with benzbromarone. Conclusion In this large population-based cohort of gout patients, allopurinol was associated with an increased risk of composite CV events and all-cause mortality compared to benzbromarone. Benzbromarone may reduce CV risk and mortality in patients with gout, although more studies are necessary to confirm our findings and to advance our understanding of the underlying mechanisms.
20-Year Follow-up Study of Celiac Patients Identified in a Mass School Screening: Compliance to Gluten-Free Diet and Autoimmunity

ABSTRACT Objectives: To investigate the compliance to the gluten-free diet in a cohort of adult celiac patients 20 years after the diagnosis, received in childhood through a mass screening. Methods: This is an observational historic cohort follow-up study. It was carried out at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Two matched cohorts of adult celiac patients, diagnosed in childhood through a mass screening or for symptoms were enrolled. Adherence to the gluten free-diet and development of autoimmune diseases were investigated through a questionnaire administrated in the course of a phone interview. The primary study outcome was the adherence to the gluten-free diet, measured through the Biagi questionnaire, in the two cohorts of celiac patients. Results: We contacted 25 patients (mean age 28 years, 19 females) diagnosed with screening and 34 patients (mean age 25 years, 26 females) diagnosed in the same period for symptoms. After 20 years, in the cohort diagnosed with screening and in the cohort diagnosed for symptoms the adherence to the gluten-free diet was optimal in 14 (56%) and 26 (81%), improvable in 5 (20%) and 3 (9%), inadequate in 6 (24%) and 3 (9%), respectively. In the two cohorts, four patients (16%) and six patients (18%) developed other autoimmune diseases. Conclusions: Twenty years after the diagnosis, near half of the patients diagnosed in a mass screening, does not have an optimal adherence to the gluten-free diet and a remarkable proportion of them have developed another autoimmune disease.
Evaluation and Revision of the Kiersma-Chen Empathy Scale

Objective. This study aimed to provide further validity evidence for the Kiersma-Chen Empathy Scale (KCES) by analyzing data collected from multiple administrations of the scale and conducting cognitive interviews of students in pharmacy and nursing programs to identify needed revisions. Methods. De-identified data from previous administrations of the KCES were used to evaluate the scale. Evidence of response process was enhanced through cognitive interviews with 20 pre-pharmacy and pharmacy students at Cedarville University. After survey revisions, the cognitive interview process was repeated with 10 University of Wyoming nursing students. Results. Based on psychometric data and cognitive interviews, the KCES was revised as follows: key components of cognitive and affective empathy were retained, scaling was changed to reflect necessity and empathy ability, negatively worded items were removed, and the single scale was converted into two parallel subscales. Conclusion. This study used data from thousands of geographically and professionally diverse samples. Based on potential problems identified in quantitative analyses, cognitive interviews with nursing and pharmacy students were conducted, and modifications to the KCES were made. Further psychometric validation is needed regarding the KCES-R.
Glucoside xylosyltransferase 2 as a diagnostic and prognostic marker in gastric cancer via comprehensive analysis

ABSTRACT To investigate the potential role of GXYLT2 (glucoside xylosyltransferase 2) in gastric cancer (GC), the TCGA (The Cancer Genome Atlas) database and Gene Expression Omnibus (GEO) dataset were used to evaluate GXYLT2 mRNA expression, and the standardized mean difference and diagnostic value were comprehensively assessed. Survival analysis and univariate/multivariate cox regression analysis were performed to evaluate the prognostic value of GXYLT2 in GC patients. The correlation between GXYLT2 and tumor immune cells was identified by using the CIBERSORT algorithm. The results showed that GXYLT2 expression level was significantly increased in GC tissues. GXYLT2 expression was significantly correlated with the grade, stage, and invasion depth of gastric cancer. Overall survival was reduced in the high GXYLT2 expression group. Univariate and multivariate Cox regression analyses showed that GXYLT2 was a reliable prognostic factor. GSEA showed that GXYLT2 might participate in the development of GC through tumor-related pathways. The expression of GXYLT2 was positively correlated with 5 tumor-infiltrating immune cells (resting dendritic cells, m2 macrophages, monocytes, active NK cells and resting mast cells), and was negatively correlated with 6 tumor-infiltrating immune cells (plasma cells, activated memory CD4 T cells, resting NK cells, activated dendritic cells, and activated neutrophils and mast cells). Through cell experiment verification, GXYLT2 expression level in gastric cancer cells was found to be high, which verified the results from the bioinformatics analysis. Furthermore, immunohistochemical staining results also showed that GC tissues had positive GXYLT2 expression. In summary, GXYLT2 might be a potential diagnostic and prognostic biomarker for gastric cancer.
Metabolic Control of Sensory Neuron Survival by the p75 Neurotrophin Receptor in Schwann Cells

We report that the neurotrophin receptor p75 contributes to sensory neuron survival through the regulation of cholesterol metabolism in Schwann cells. Selective deletion of p75 in mouse Schwann cells of either sex resulted in a 30% loss of dorsal root ganglia (DRG) neurons and diminished thermal sensitivity. P75 regulates Schwann cell cholesterol biosynthesis in response to BDNF, forming a co-receptor complex with ErbB2 and activating ErbB2-mediated stimulation of sterol regulatory element binding protein 2 (SREBP2), a master regulator of cholesterol synthesis. Schwann cells lacking p75 exhibited decreased activation of SREBP2 and a reduction in 7-dehydrocholesterol (7-DHC) reductase (DHCR7) expression, resulting in accumulation of the neurotoxic intermediate, 7-dehyrocholesterol in the sciatic nerve. Restoration of DHCR7 in p75 null Schwann cells in mice significantly attenuated DRG neuron loss. Together, these results reveal a mechanism by which the disruption of lipid metabolism in glial cells negatively influences sensory neuron survival, which has implications for a wide range of peripheral neuropathies. SIGNIFICANCE STATEMENT Although expressed in Schwann cells, the role of p75 in myelination has remained unresolved in part because of its dual expression in sensory neurons that Schwann cells myelinate. When p75 was deleted selectively among Schwann cells, myelination was minimally affected, while sensory neuron survival was reduced by 30%. The phenotype is mainly due to dysregulation of cholesterol biosynthesis in p75-deficient Schwann cells, leading to an accumulation of neurotoxic cholesterol precursor, 7-dehydrocholesterol (7-DHC). Mechanism-wise, we discovered that in response to BDNF, p75 recruits and activates ErbB2 independently of ErbB3, thereby stimulating the master regulator, sterol regulatory element binding protein 2 (SREBP2). These results together highlight a novel role of p75 in Schwann cells in regulating DRG neuron survival by orchestrating proper cholesterol metabolism.
Sex workers’ self-reported physical and mental health in Greece. A repeated cross-sectional study in 2009, 2013 and 2019

Abstract In Greece, given the precarious nature of the sex work industry, sex workers health and wellbeing is of concern. However, relevant research remains limited. This study examined whether sex workers’ self-reported physical and mental health deteriorated across time points during the economic recession in Athens, Greece. The study focused on 13 areas where off-street and street-based sex work occurred. Cross-sectional data was collected from the same areas in 2009 (i.e. before the economic recession began) and in 2013 and 2019 (i.e. at time points during the recession). Self-reported physical and mental health decreased in 2013 and in 2019 compared to 2009. A positive association was found between the country’s gross domestic product and sex workers’ self-reported physical and mental health. The opposite was found for annual aggregate unemployment. The determinants of better self-reported physical and mental health were sex workers’ economic condition, Greek nationality, off-street sex work, and registered sex work status. The opposite was found for more years’ involvement in sex work and drug consumption. Findings indicate the need for more inclusive health strategies, especially during periods of economic downturn when sex workers’ physical/mental health is likely to decline. This is the first study to investigate the association between economic recession and sex workers' self-reported physical and mental health.
Association of MAFLD With Diabetes, Chronic Kidney Disease, and Cardiovascular Disease: A 4.6-Year Cohort Study in China

Abstract Context In 2020, the terminology of metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Objectives This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases. Methods A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models. Results The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes. Conclusion The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non–fatty liver.
Genetic modeling of GNAO1 disorder delineates mechanisms of Gαo dysfunction

Abstract GNAO1 encephalopathy is a neurodevelopmental disorder with a spectrum of symptoms that include dystonic movements, seizures and developmental delay. While numerous GNAO1 mutations are associated with this disorder, the functional consequences of pathological variants are not completely understood. Here, we deployed the invertebrate C. elegans as a whole-animal behavioral model to study the functional effects of GNAO1 disorder-associated mutations. We tested several pathological GNAO1 mutations for effects on locomotor behaviors using a combination of CRISPR/Cas9 gene editing and transgenic overexpression in vivo. We report that all three mutations tested (G42R, G203R and R209C) result in strong loss of function defects when evaluated as homozygous CRISPR alleles. In addition, mutations produced dominant negative effects assessed using both heterozygous CRISPR alleles and transgenic overexpression. Experiments in mice confirmed dominant negative effects of GNAO1 G42R, which impaired numerous motor behaviors. Thus, GNAO1 pathological mutations result in conserved functional outcomes across animal models. Our study further establishes the molecular genetic basis of GNAO1 encephalopathy, and develops a CRISPR-based pipeline for functionally evaluating mutations associated with neurodevelopmental disorders.
Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis

Key Points CXCL2 on macrophage EVs recruited neutrophils. CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway. Targeting EVs CXCL2 is a viable strategy for sepsis treatment. Visual Abstract Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.
Data-driven group comparisons of eye fixations to dynamic stimuli

Recent advances in software and hardware have allowed eye tracking to move away from static images to more ecologically relevant video streams. The analysis of eye tracking data for such dynamic stimuli, however, is not without challenges. The frame-by-frame coding of regions of interest (ROIs) is labour-intensive and computer vision techniques to automatically code such ROIs are not yet mainstream, restricting the use of such stimuli. Combined with the more general problem of defining relevant ROIs for video frames, methods are needed that facilitate data analysis. Here, we present a first evaluation of an easy-to-implement data-driven method with the potential to address these issues. To test the new method, we examined the differences in eye movements of self-reported politically left- or right-wing leaning participants to video clips of left- and right-wing politicians. The results show that our method can accurately predict group membership on the basis of eye movement patterns, isolate video clips that best distinguish people on the political left–right spectrum, and reveal the section of each video clip with the largest group differences. Our methodology thereby aids the understanding of group differences in gaze behaviour, and the identification of critical stimuli for follow-up studies or for use in saccade diagnosis.
Surgical Treatment for Avulsion Fractures of the Anterolateral Ligament Associated with Periarticular Fractures of the Knee

Abstract The existence and anatomy of the anterolateral ligament (ALL) of the knee are a somewhat controversial topic in orthopaedic surgery. The fixation of the avulsion fracture of the ALL (Segond fracture), associated with periarticular knee fractures, is rarely given much consideration while the major fracture fragments are reconstructed. This study aims to confirm the existence of ALL and evaluate the clinical outcomes of surgical management for avulsion fractures, involving its insertion, when associated with periarticular knee fractures. Twenty-three patients (16 males and 7 females) with avulsion fractures of the ALL associated with periarticular knee fractures were fixed with a spider plate, cannulated screw, or suture anchor. Eight patients were diagnosed with distal femoral fracture, 10 with tibial plateau fracture, and 5 with tibial eminence avulsion fracture. All patients underwent X-rays at follow-up. Clinical and functional outcomes were assessed with the pivot-shift test, objective and subjective International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale. The ALL was found and identified as a distinct ligamentous structure in all patients. Prior to Segond repair, patients had significantly more instability, as determined by pivot-shift test, than seen postoperatively (p < 0.0001). At final follow-up, the mean subjective IKDC score was 83.2 ± 10.3. Fourteen patients were graded A, 6 were graded B, and 3 was graded C on the IKDC objective score. The mean Lysholm score was 85.4 ± 12.2. The mean Tegner score was 7.5 ± 1.2. This study confirmed that the ALL is a distinct structure in the anterolateral portion of the knee. The fixation of the avulsion fracture of the ALL associated with periarticular knee fractures can be an effective procedure without specific complications. Long-term and comparative follow-up studies are necessary to confirm the effects.
Increasing and decreasing interregional brain coupling increases and decreases oscillatory activity in the human brain

Significance Oscillatory activity is prominent in the brain, and one hypothesis is that it is, in part, due to the nature of coupling or interaction patterns between brain areas. We tested this hypothesis by manipulating the strength of coupling between two brain regions (ventral premotor cortex, PMv, and motor cortex, M1) in two directions (increase or decrease) while carefully controlling for the impact each manipulation had on activity in each area. We looked at the PMv–M1 connection because it is the major cortical route by which prefrontal cortex might influence, inhibit, and curtail action-related activity in M1. Manipulating PMv–M1 coupling in accordance with Hebbian-like spike-timing–dependent plasticity resulted in changes in beta and theta frequencies linked to action control. The origins of oscillatory activity in the brain are currently debated, but common to many hypotheses is the notion that they reflect interactions between brain areas. Here, we examine this possibility by manipulating the strength of coupling between two human brain regions, ventral premotor cortex (PMv) and primary motor cortex (M1), and examine the impact on oscillatory activity in the motor system measurable in the electroencephalogram. We either increased or decreased the strength of coupling while holding the impact on each component area in the pathway constant. This was achieved by stimulating PMv and M1 with paired pulses of transcranial magnetic stimulation using two different patterns, only one of which increases the influence exerted by PMv over M1. While the stimulation protocols differed in their temporal patterning, they were comprised of identical numbers of pulses to M1 and PMv. We measured the impact on activity in alpha, beta, and theta bands during a motor task in which participants either made a preprepared action (Go) or withheld it (No-Go). Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv–M1 pathway, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. Little change was observed in the alpha rhythm. By contrast, diminishing the influence of PMv over M1 decreased oscillatory beta and theta rhythms in Go and No-Go trials, respectively. This suggests that corticocortical communication frequencies in the PMv–M1 pathway can be manipulated following Hebbian spike-timing–dependent plasticity.