Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the Origin and Diversity of Macrophages to Tailor Their Targeting in Solid Cancers

Tumor-associated macrophages (TAMs) are a major component of the tumor immune microenvironment (TIME) and are associated with a poor prognostic factor in several cancers. TAMs promote tumor growth by facilitating immunosuppression, angiogenesis, and inflammation, and can promote tumor recurrence post-therapeutic intervention. Major TAM-targeted therapies include depletion, reprogramming, as well as disrupting the balance of macrophage recruitment and their effector functions. However, intervention-targeting macrophages have been challenging, since TAM populations are highly plastic and adaptation or resistance to these approaches often arise. Defining a roadmap of macrophage dynamics in the TIME related to tissue and tumor type could represent exploitable vulnerabilities related to their altered functions in cancer malignancy. Here, we review multiple macrophage-targeting strategies in brain, liver, and lung cancers, which all emerge in tissues rich in resident macrophages. We discuss the successes and failures of these therapeutic approaches as well as the potential of personalized macrophage-targeting treatments in combination therapies.
Leadership Training to Increase Need Satisfaction at Work: A Quasi-Experimental Mixed Method Study

With a growing number of studies showing the applicability of the self-determination theory for various work and organizational outcomes, the next logical step is to investigate if and how employee need satisfaction at work can be purposefully increased through an intervention. The purpose of the present study was to test whether we could train managers’ display of autonomy, competence, and relatedness support toward employees and whether this resulted in improved employee need satisfaction, well-being, and job performance. Data were obtained from 37 managers (rated by N = 538 subordinates) assigned to either an experimental or control condition at three time points: before, during, and after the training. We also used focus group interviews to evaluate the experience of the training. The quantitative analyses showed no statistically significant improvement in managers’ display of needs support or employee need satisfaction. However, the qualitative data pointed toward important factors related to the implementation of need supportive leadership training that should be considered.
Identifying Patients With Coronary Artery Disease Using Rest and Exercise Seismocardiography

Coronary artery disease (CAD) is the most common cause of death globally. Patients with suspected CAD are usually assessed by exercise electrocardiography (ECG). Subsequent tests, such as coronary angiography and coronary computed tomography angiography (CCTA) are performed to localize the stenosis and to estimate the degree of blockage. The present study describes a non-invasive methodology to identify patients with CAD based on the analysis of both rest and exercise seismocardiography (SCG). SCG is a non-invasive technology for capturing the acceleration of the chest induced by myocardial motion and vibrations. SCG signals were recorded from 185 individuals at rest and immediately after exercise. Two models were developed using the characterization of the rest and exercise SCG signals to identify individuals with CAD. The models were validated against related results from angiography. For the rest model, accuracy was 74%, and sensitivity and specificity were estimated as 75 and 72%, respectively. For the exercise model accuracy, sensitivity, and specificity were 81, 82, and 84%, respectively. The rest and exercise models presented a bootstrap-corrected area under the curve of 0.77 and 0.91, respectively. The discrimination slope was estimated 0.32 for rest model and 0.47 for the exercise model. The difference between the discrimination slopes of these two models was 0.15 (95% CI: 0.10 to 0.23, p < 0.0001). Both rest and exercise models are able to detect CAD with comparable accuracy, sensitivity, and specificity. Performance of SCG is better compared to stress-ECG and it is identical to stress-echocardiography and CCTA. SCG examination is fast, inexpensive, and may even be carried out by laypersons.
LC-MS-Based Metabolomic Approach Revealed the Significantly Different Metabolic Profiles of Five Commercial Truffle Species

Truffles are ascomycetous ectomycorrhizal fungi that have elevated status in the culinary field due to their unique aroma and taste as well as their nutritional value and potential biological activities. Tuber melanosporum, T. indicum, T. panzhihuanense, T. sinoaestivum, and T. pseudoexcavatum are five commercial truffle species mainly distributed in Europe or China. In this study, an untargeted metabolomics technology based on an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was applied to analyze the metabolic profiles and variations among these five truffle species. In our results, a total of 2376 metabolites were identified under positive ion mode, of which 1282 had significantly differential amounts and covered 110 pathways or metabolisms. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) revealed a clear separation from each of these five truffles, indicating a significantly different metabolic profile among them, with the biggest difference between T. melanosporum and the other four truffles. The differential metabolites covered various chemical categories, and a detailed analysis was performed for nine metabolic categories, including amino acids, saccharides and nucleosides, organic acids, alkaloids, flavonoids, carnitines, phenols and alcohols, esters, and sulfur compounds. For each of the nine categories, most of metabolites predominantly accumulated in T. melanosporum compared with the other four truffles. Meanwhile, there were significant differences of the average ion intensity in each category among the five truffles, e.g., higher amounts of amino acids was detected in T. panzhihuanense and T. pseudoexcavatum; T. indicum contained significantly more carnitines, while there were more alkaloids in T. melanosporum. Additionally, some metabolites with biological activities were discussed for each category, such as acetyl-L-carnitine, adenine, neobavaisoflavone, and anandamide. Generally, this study may provide the valuable information regarding the variation of the metabolic composition of these five commercial truffle species, and the biological significance of these metabolites was uncovered to explore the metabolic mechanisms of truffles, which would be helpful for further research on the compounds and potential biological functions in truffles that have not yet been investigated.
Cyclophosphamide Treatment Mimics Sub-Lethal Infections With Encephalitozoon intestinalis in Immunocompromised Individuals

Microsporidia, including Encephalitozoon intestinalis, are emerging pathogens which cause opportunistic infections in immunocompromised patients, such as those with AIDS, cancer, the elderly and people on immunosuppressive drugs. Intestinal mucosa (IM) is crucial for developing an efficient adaptive immune response against pathogenic micro-organisms, thereby preventing their colonization and subsequent infection. As immunosuppressive drugs affect the intestinal immune response is little known. In the present study, we investigated the immune response to E. intestinalis infection in the IM and gut-associated lymphoid tissue (GALT) in cyclophosphamide (Cy) immunosuppressed mice, to mimic an immunocompromised condition. Histopathology revealed lymphoplasmacytic enteritis at 7 and 14 days-post-infection (dpi) in all infected groups, however, inflammation diminished at 21 and 28 dpi. Cy treatment also led to a higher number of E. intestinalis spores and lesions, which reduced at 28 dpi. In addition, flow cytometry analysis demonstrated CD4+ and CD8+ T cells to be predominant immune cells, with up-regulation in both Th1 and Th2 cytokines at 7 and 14 dpi, as demonstrated by histopathology. In conclusion, Cy treatment reduced GALT (Peyer’s plaques and mesenteric lymph nodes) and peritoneum populations but increased the T-cell population in the intestinal mucosa and the production of pro-and anti-inflammatory cytokines, which were able to eliminate this opportunistic fungus and reduced the E. intestinalis infection.
Potential of Host Serum Protein Biomarkers in the Diagnosis of Tuberculous Meningitis in Children

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and results in high morbidity and mortality in children. Diagnostic delay contributes to the poor outcome. There is an urgent need for new tools for the rapid diagnosis of TBM, especially in children. Methods: We collected serum samples from children in whom TBM was suspected at a tertiary hospital in Cape Town, South Africa. Children were subsequently classified as having TBM or no TBM using a published uniform research case-definition. Using a multiplex cytokine array platform, we investigated the concentrations of serum biomarkers comprising biomarkers that were previously found to be of value in the diagnosis of adult pulmonary TB (CRP, SAA, CFH, IFN-γ, IP-10, Apo-AI, and transthyretin) plus other potentially useful host biomarkers as diagnostic candidates for TBM. Findings: Out of 47 children included in the study, 23 (48.9%) had a final diagnosis of TBM and six were HIV infected. A modified version of the adult 7-marker biosignature in which transthyretin was replaced by NCAM1, diagnosed TBM in children with AUC of 0.80 (95% CI, 0.67–0.92), sensitivity of 73.9% (95% CI, 51.6–89.8%) and specificity of 66.7% (95% CI, 44.7–84.4%), with the other six proteins in the signature (CRP, IFN-γ, IP-10, CFH, Apo-A1, and SAA) only achieving and AUC of 0.75 (95% CI, 0.61–0.90) when used in combination. A new childhood TBM specific 3-marker biosignature (adipsin, Aβ42, and IL-10) showed potential in the diagnosis of TBM, with AUC of 0.84 (95% CI, 0.73–0.96), sensitivity of 82.6% (95 CI, 61.2–95.0%) and specificity of 75.0% (95% CI, 53.3–90.2%) after leave-one-out cross validation. Conclusion: A previously described adult 7-marker serum protein biosignature showed potential in the diagnosis of TBM in children. However, a smaller childhood TBM-specific 3-marker signature demonstrated improved performance characteristics. Our data indicates that blood-based biomarkers may be useful in the diagnosis of childhood TBM and requires further validation in larger cohort studies.
Home Away from Home: Japanese Corporate Wives in the United States

Drawing attention to domestic space as the critical juncture between the global and the local, Home Away from Home is an innovative ethnography of the daily lives of middle-class Japanese housewives who accompany their husbands on temporary corporate job assignments in the United States. These women are charged with the task of creating and maintaining restful Japanese homes in a foreign environment so that their husbands are able to remain productive, loyal workers for Japanese multinationals and their children are properly socialized and educated as Japanese citizens abroad. Arguing that the homemaking components of transnational communities have not received adequate attention, Sawa Kurotani demonstrates how gender dynamics and the politics of the domestic sphere are integral to understanding national identity and transnational mobility. Kurotani interviewed and spent time with more than 120 women in three U.S. locations with sizable expatriate Japanese communities: Centerville, a pseudonymous Midwestern town; the New York metropolitan area; and North Carolina’s Research Triangle area. She highlights the contradictory situations faced by the transient wives. Their husbands’ assignments in the United States typically last from three to five years, and they frequently emphasize the temporariness of their situation, referring to it as a “long vacation. ” Yet they are responsible for creating comfortable homes for their families, which necessitates producing a familiar and permanent environment. Kurotani looks at the dynamic friendships that develop among the wives and describes their feelings about returning to Japan. She conveys how their sense of themselves as Japanese women, of home, and of their relationships with family members are altered by their personal experiences of transnational homemaking.
A population-level evaluation of barriers and facilitators to referral in Cytoreduction/Hyperthermic Intraperitoneal Chemotherapy using knowledge translation methodology.

Introduction: Referral for CS/HIPEC is variable, and barriers encountered by referring physicians are unknown. Identification of such barriers is useful for the creation of tailored knowledge translation (KT) strategies. Methods: Interviews of 20 medical oncologists and surgeons in the New York (NY) area were completed to identify barrier topics, using the Pathman framework of uptake of innovations (awareness, agreement, adoption, adherence) at the various levels of the individual, practice group, and organization. Barriers were used to structure a survey for evaluation of prevalence at the population level of medical oncologists and surgeons in NY State. Results: Barrier topics of awareness included training at a CS/HIPEC center, and availability of multidisciplinary cancer conferences. Agreement barriers centered mainly on quality of published literature, and the paradigm shift of carcinomatosis as a systemic to locoregional disease process. Adoption barriers included knowledge of outcomes of a CS/HIPEC surgeon, and concerns with morbidity/mortality rates. Adherence barriers included the lack of reflection of CS/HIPEC in current CPGs, financial/resource and logistic concerns of referrals, and lack of quality measures for the procedure. For the survey, 119 responded (12% response rate), including 42 medical oncologist and 77 surgeons. The majority were aware of CS/HIPEC (n=113, 95%). Medical oncologists were less likely than surgeons to agree with CS/HIPEC related to published evidence (76% vs 92 %, p = 0.02). Surgeons were more likely to be aware of where to refer patients for the procedure, and were less likely to have concerns regarding morbidity/mortality, compared with medical oncologists (p = 0.05, p = 0.04). Representation of CS/HIPEC in CPGs and quality measures/outcomes data was felt to result in adherence to a regular referral practice. Discussion: This prospective study of stakeholders for CS/HIPEC is the first to evaluate and characterize barriers to referral for this complex and controversial surgical innovation, with prevalence at the population level.
The role of urea in neuronal degeneration and sensitization: An in vitro model of uremic neuropathy

Background Uremic neuropathy commonly affects patients with chronic kidney disease, with painful sensations in the feet, followed by numbness and weakness in the legs and hands. The symptoms usually resolve following kidney transplantation, but the mechanisms of uremic neuropathy and associated pain symptoms remain unknown. As blood urea levels are elevated in patients with chronic kidney disease, we examined the morphological and functional effects of clinically observed levels of urea on sensory neurons. Methods Rat dorsal root ganglion neurons were treated with 10 or 50 mmol/L urea for 48 h, fixed and immunostained for PGP9.5 and βIII tubulin immunofluorescence. Neurons were also immunostained for TRPV1, TRPM8 and Gap43 expression, and the capsaicin sensitivity of urea- or vehicle-treated neurons was determined. Results Urea-treated neurons had degenerating neurites with diminished PGP9.5 immunofluorescence, and swollen, retracted growth cones. βIII tubulin appeared clumped after urea treatment. After 48 hours urea treatment, neurite lengths were significantly reduced to 60 ± 2.6% (10 mmol/L, **P < 0.01), and to 56.2 ± 3.3% (50 mmol/L, **P < 0.01), compared with control neurons. Fewer neurons survived urea treatment, with 70.08 ± 13.3% remaining after 10 mmol/L (*P < 0.05) and 61.49 ± 7.4% after 50 mmol/L urea treatment (**P < 0.01), compared with controls. The proportion of neurons expressing TRPV1 was reduced after urea treatment, but not TRPM8 expressing neurons. In functional studies, treatment with urea resulted in dose-dependent neuronal sensitization. Capsaicin responses were significantly increased to 115.29 ± 3.4% (10 mmol/L, **P < 0.01) and 125.3 ± 4.2% (50 mmol/L, **P < 0.01), compared with controls. Sensitization due to urea was eliminated in the presence of the TRPV1 inhibitor SB705498, the mitogen-activated protein kinase kinase inhibitor PD98059, the PI3 kinase inhibitor LY294002 and the TRPM8 inhibitor N-(3-Aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)benzamide (AMTB hydrochloride). Conclusion Neurite degeneration and sensitization are consistent with uremic neuropathy and provide a disease-relevant model to test new treatments.
The Effect of 12 Weeks of β-Hydroxy-β-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study

Sarcopenia is a frequent complication in liver transplant (LT) recipients. β-hydroxy-β-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.
Food-Specific IgE and IgG Antibodies in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Case–Control Study

EPOS 2012 states that investigation is needed to study a possible role for food allergy in the initiation and perpetuation of chronic rhinosinusitis with nasal polyps (CRSwNP). Our main goal was to compare serum levels of food-specific immunoglobulin G (IgG) and IgE antibodies in patients with CRSwNP and controls. A prospective case–control study with 33 patients with CRSwNP and 31 controls without CRS was carried out. Clinical data were gathered through a systematic interview and blood sample was collected. Enzyme-linked immunosorbent assay tests using OmegaDiagnostics kit with 40 food allergens for detection of specific IgG antibodies were performed and food-specific IgE antibodies were determined by immunoassay using ImmunoCAP. Immunoglobulin classes and IgG subclasses levels were also evaluated. Statistical analysis was performed using SPSS v.23. The overall sum of food IgG antibodies was significantly lower in CRSwNP compared to control group, and this difference was also observed for different specific IgG antibodies (corn, soya, grain legumes, pear and apple, berries, citric fruit). In controls, a positive correlation between IgG1 and the sum of food IgG antibodies was seen, but in CRSwNP group a negative correlation was found. In addition, a significant higher level of IgG1 and lower IgG2 and IgG3 was found among patients with CRSwNP. Levels of serum-specific IgE antibodies against multiallergen food mix (fx5) and against shrimp, strawberry, orange, rye, or egg yolk, as well as the sum of food IgE antibodies, did not differ significantly between the groups. These findings suggest that food allergy does not have an important role in CRSwNP etiopathogenesis, whether it is IgG or IgE mediated. Moreover, the observed suppression of specific IgG antibodies against food allergens, its negative correlation with IgG1 and the IgG1 switching in CRSwNP, can be related to deviated IgG responses against other targets (eg, airborne particles) and warrants future investigation.
The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice

Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment.