Miracle-dz/UniFAR-FTUs huggingface dataset:
CD155/CD226‐interaction impacts on the generation of innate CD8+ thymocytes by regulating iNKT‐cell differentiation

The cell surface receptor CD155 influences a variety of immune processes by binding to its ligands CD226, CD96, or TIGIT. Here, we report that the interaction of CD155 with CD226 in the thymus of BALB/c mice has a dual function. It directly influences the dwell time of memory‐like CD8+ T cells, while it is indirectly involved in generating these cells. It was shown earlier that a massive emergence of memory‐like CD8 T cells in thymus crucially depends on abundant IL‐4, secreted in steady state by iNKT2 (where iNKT is invariant NKT) cells, a subclass of iNKT cells. Here, we show that absence of either CD155 or CD226 in BALB/c mice causes a profound shift in the iNKT subtype composition in thymus, expanding the frequency and numbers of iNKT1 cells at the expense of iNKT2 cells, as well as iNKT17 cells. This shift results in a drop of available IL‐4 and creates a scenario similar to that observed in C57BL/6 mice, where iNKT1 cells predominate and iNKT2 cells are much less frequent when compared with BALB/c mice. Yet also in C57BL/6 mice, lack of CD155 or CD226 provokes a further decline in iNKT2 cells, suggesting that the observed effects are not restricted to a particular inbred strain.
CARDIOPROTECTIVE EFFECT OF THERAPEUTIC HYPOTHERMIA FOR POSTRESUSCITATION MYOCARDIAL DYSFUNCTION

Mild-to-moderate therapeutic hypothermia after resuscitation from cardiac arrest is neuroprotective, but its effect on postresuscitation myocardial dysfunction is not clear. We hypothesized that therapeutic hypothermia is cardioprotective in postresuscitation. Male adult Wistar rats underwent asphyxia-induced cardiac arrest and manual resuscitation with epinephrine. Therapeutic hypothermia is induced immediately after successful resuscitation and the return of spontaneous circulation (ROSC). One hour after ROSC, the rats achieved a target temperature of 30°C to 31°C, which was maintained for 1.5 h and then transitioned to the passive rewarming process in the hypothermia group. A temperature between 36.5°C and 37.5°C was maintained in the normothermia group. Echocardiography revealed that hypothermia resulted in significantly better systolic function of fractional shortening in 60 and 120 min after ROSC (both P < 0.05). The benefit of cardioprotection was also confirmed by the general linear mixed-models analysis of dP/dt, which revealed significantly better systolic function in positive dP/dtR(40) and diastolic function in maximal negative dP/dt (both P < 0.001). The 4-h and 3-day survival analyses both revealed better outcomes in the hypothermia groups in the log-rank test (P < 0.001 for the 4-h analysis, and P < 0.05 for the 3-day analysis). Serum level of heart-type, fatty acid-binding protein at 4 h after resuscitation as the myocardium damage marker was also significantly lower in the hypothermia group (52.4 ng/mL vs 186.5 ng/mL in the normothermia group; P < 0.05). Western blotting of myocardium showed that myocardial Akt and ERK1/2 were more activated in the hypothermia group 2 h after spontaneous circulation returned. In conclusion, postresuscitation mild-to-moderate therapeutic hypothermic is cardioprotective in the asphyxia-induced cardiac arrest animal model. It stabilizes hemodynamics, improves short-term survival, and decreases myocardial damage. The cardioprotective effect is associated with Akt and ERK1/2 activation in signal transduction.
Tobacco Use and its Relationship with Health Complaints Among Employees of Kermanshah Province, Iran

Background: Identifying the pattern of tobacco use and its related factors in employees is crucial. This study aimed to investigate the pattern of tobacco use and its related factors in employees of Kermanshah Province, Iran. Methods: In 2012, 7129 employees were investigated in a cross-sectional study using the census method. Data on tobacco use and on several chronic diseases obtained using a standardized questionnaire on noncommunicable diseases risk factors of the World Health Organization through face-to-face interviews. Statistical analysis was performed based on the Chi-square test and multivariate logistic regression. Results: In general, the prevalence of tobacco use, smoking cigarettes, and smoking waterpipe was 9.9%, 8.9%, and 1.2% among the employees, respectively. Tobacco use was significantly higher in the age group over 40 (14.0%), in male gender (13.3%), in married individuals (10.8%) and in those with diploma and lower degree (16.4%), (P < 0.001). At the individual level, the odds ratio of tobacco use was 1.5 (95% confidence interval [CI]: 1.2–1.8) in hypertensive, 1.8 (95% CI: 1.2–2.6) in diabetic employees and 1.7 (95% CI: 1.3–2.3) in those with heart diseases, compared to healthy individuals. After adjusting for age, gender, marital status and educational level, there was not any significant relationship between tobacco use and health complaints and only the demographic variables remained significant. Conclusions: Preventive public health policies are mandatory especially in younger ages and male employees to promote their knowledge on disadvantages of tobacco use.
Serum γ‐glutamyltransferase and development of impaired fasting glucose or type 2 diabetes in middle‐aged Japanese men

Abstract. Nakanishi N, Nishina K, Li W, Sato M, Suzuki K, Tatara K (Osaka University Graduate School of Medicine, Osaka; and Japan Labor and Welfare Association, Tokyo; Japan). Serum γ‐glutamyltransferase and development of impaired fasting glucose or type 2 diabetes in middle‐aged Japanese men. J Intern Med 2003; 254: 287–295.
Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic Acid-guided surgery.

BACKGROUND There is evidence in the literature supporting that fluorescent tissue signal in fluorescence-guided surgery extends farther than tissue highlighted in gadolinium in T1 sequence magnetic resonance imaging (MRI), which is the standard to quantify the extent of resection. OBJECTIVE To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI. METHODS A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated on with the use of fluorescence-guided surgery with 5-aminolevulinic acid. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale, O-methylguanine methyltransferase methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy. RESULTS The median overall survival was 27.0 months (confidence interval = 22.4-31.6) in patients with nonresidual fluorescence (n = 25) and 17.5 months (confidence interval = 12.5-22.5) for the group with residual fluorescence (n = 27) (P = .015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, hazard ratio = 2.5 (P = .041). The neurological complication rate was 18.5% in patients with nonresidual fluorescence and 8% for the group with residual fluorescence (P = .267). CONCLUSION GBM patients with CRET in early MRI and no fluorescent residual tissue had longer overall survival than patients with CRET and residual fluorescent tissue.
Perfectionism in anorexia nervosa: variation by clinical subtype, obsessionality, and pathological eating behavior.

OBJECTIVE The purpose of this study was to examine the role of perfectionism as a phenotypic trait in anorexia nervosa and its relevance across clinical subtypes of this illness. METHOD The Multidimensional Perfectionism Scale and the perfectionism subscale of the Eating Disorder Inventory were administered to 322 women with a history of anorexia nervosa who were participating in an international, multicenter genetic study of anorexia nervosa. All participants were additionally interviewed with the Yale-Brown Obsessive Compulsive Scale and the Yale-Brown-Cornell Eating Disorder Scale. Mean differences on dependent measures among women with anorexia nervosa and comparison subjects were examined by using generalized estimating equations. RESULTS Persons who had had anorexia nervosa had significantly higher total scores on the Multidimensional Perfectionism Scale than did the healthy comparison subjects. In addition, scores of the anorexia subjects on the Eating Disorder Inventory-2 perfectionism subscale exceeded Eating Disorder Inventory-2 normative data. For the anorexia nervosa participants, the total score on the Multidimensional Perfectionism Scale and the Eating Disorder Inventory-2 perfectionism subscale score were highly correlated. Total score on the Multidimensional Perfectionism Scale was also significantly related to the total score and the motivation-for-change subscale score of the Yale-Brown-Cornell Eating Disorder Scale. CONCLUSIONS These data show that perfectionism is a robust, discriminating characteristic of anorexia nervosa. Perfectionism is likely to be one of a cluster of phenotypic trait variables associated with a genetic diathesis for anorexia nervosa.
Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis

Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor antagonists have been reported to exert anti-inflammatory effects. Herein, we assessed the impact of platelet inhibition with the P2Y12 receptor antagonist ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Animals were treated with ticagrelor (100 mg/kg) or vehicle prior to CLP induction. Edema formation and bronchoalveolar neutrophils as well as lung damage were quantified. Flow cytometry was used to determine expression of platelet–neutrophil aggregates, neutrophil activation and CD40L expression on platelets. CLP-induced pulmonary infiltration of neutrophils at 24 hours was reduced by 50% in ticagrelor-treated animals. Moreover, ticagrelor abolished CLP-provoked lung edema and decreased lung damage score by 41%. Notably, ticagrelor completely inhibited formation of platelet–neutrophil aggregates and markedly reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a potential role for platelet antagonists, such as ticagrelor, in the management of patients with abdominal sepsis.
Anthropometric Analysis of the Face

Background:Facial anthropometric analysis is essential for planning cosmetic and reconstructive facial surgery, but has not been available in detail for modern Greeks. In this study, multiple measurements of the face were performed on young Greek males and females to provide a complete facial anthropometric profile of this population and to compare its facial morphology with that of North American Caucasians. Materials and Methods:Thirty-one direct facial anthropometric measurements were obtained from 152 Greek students. Moreover, the prevalence of the various face types was determined. The resulting data were compared with those published regarding North American Caucasians. Results:A complete set of average anthropometric data was obtained for each sex. Greek males, when compared to Greek females, were found to have statistically significantly longer foreheads as well as greater values in morphologic face height, mandible width, maxillary surface arc distance, and mandibular surface arc distance. In both sexes, the most common face types were mesoprosop, leptoprosop, and hyperleptoprosop. Greek males had significantly wider faces and mandibles than the North American Caucasian males, whereas Greek females had only significantly wider mandibles than their North American counterparts. Conclusions:Differences of statistical significance were noted in the head and face regions among sexes as well as among Greek and North American Caucasians. With the establishment of facial norms for Greek adults, this study contributes to the preoperative planning as well as postoperative evaluation of Greek patients that are, respectively, scheduled for or are to be subjected to facial reconstructive and aesthetic surgery.
Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue

Background Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven't been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans. Methods We collected benign breast tissue of 125 women who had been stratified according to age at first pregnancy and the occurrence of subsequent breast cancer, and performed immunohistochemistry for PR, Wnt4 and the Wnt-target Versican. Results The number of PR positive epithelial cells was significantly lower in the group of women with early pregnancy and no subsequent breast cancer compared to the group of nulliparous women with subsequent invasive breast cancer (p = 0.0135). In women with early pregnancy, expression of Versican and Wnt4 was significantly lower compared to nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican expression was also significant lower compared to women with late pregnancy (p < 0.0001). Discussion Our results confirm prior observations in mice and suggest a role of downregulation of epithelial Wnt signaling in the protective effect of early pregnancy in humans. This results in a decreased proliferation of stem/progenitor cells; therefore, the Wnt signaling pathway may represent a potential target for breast cancer prevention in humans.
Secondary cytoreductive surgery and peri‐operative intraperitoneal chemotherapy for peritoneal recurrence of colorectal and appendiceal peritoneal carcinomatosis following prior primary cytoreduction

Primary cytoreductive surgery (CRS) and peri‐operative intraperitoneal chemotherapy (PIC) is the only curative option for patients with colorectal cancer peritoneal carcinomatosis (PC). A significant proportion of patients develop peritoneal recurrence. Outcomes of patients undergoing secondary CRS and PIC for recurrent PC were examined.
Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)*

Background: Tissue factor pathway inhibitor (TFPI) inhibits coagulation factors Xa and VIIa. Results: A de novo synthesized 20-mer peptide that binds to TFPI was structurally and functionally characterized. Conclusion: The peptide binds to the Kunitz domain 1 of TFPI and blocks inhibition of factor Xa and factor VIIa by TFPI. Significance: The peptide can potentially prevent bleeding in hemophilia patients. Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex. Inhibition of TFPI enhances coagulation in hemophilia models. Using a library approach, we selected and subsequently optimized peptides that bind TFPI and block its anticoagulant activity. One peptide (termed compound 3), bound with high affinity to the Kunitz-1 (K1) domain of TFPI (Kd ∼1 nm). We solved the crystal structure of this peptide in complex with the K1 of TFPI at 2.55-Å resolution. The structure of compound 3 can be segmented into a N-terminal anchor; an Ω-shaped loop; an intermediate segment; a tight glycine-loop; and a C-terminal α-helix that is anchored to K1 at its reactive center loop and two-stranded β-sheet. The contact surface has an overall hydrophobic character with some charged hot spots. In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nm) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI (EC50 = 2 nm). The peptide prevented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the loose FXa-TFPI complex. The K1 domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa. Because compound 3 binds to K1, our data show that K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to the tight FXa-TFPI complex. This mode of action translates into normalization of coagulation of hemophilia plasmas. Compound 3 thus bears potential to prevent bleeding in hemophilia patients.
Familial Multiple Sclerosis and Other Inherited Disorders of the White Matter

Background:An objective demonstration of lesions disseminated in time and space remains the core of the last revision of diagnostic criteria for multiple sclerosis (MS), but this update is now empowered by a weighted use of magnetic resonance imaging (MRI), which results in an earlier and more unambiguous diagnosis (“MS,” “not MS,” or “possible MS”). Nevertheless, the exclusion of other entities still remains an integral element of the diagnostic process. Review Summary:Exclusion of genetic disorders can be challenging in some cases with familial recurrence of MS, particularly when the transmission is mimicking a mendelian or a maternal pattern of inheritance. Vice versa, many forms of mendelian leukodystrophies and leukoencephalopathies present with juvenile or adult onset, progressive or relapsing-remitting courses, intrafamilial phenotypic heterogeneity and MRI signs of multifocal white matter (WM) pathology, features potentially leading to a temporary confusion with MS. With the recent availability of disease modifying medications in MS, the development of specific molecular therapies in inherited WM disorders, and the general recognition of the effectiveness of early treatments, the accuracy of initial diagnostic assessment has become critical. Conclusion:Considering the importance of disease specific treatments, here we review the major characteristics of familial MS and some of the inheritable diseases of the WM. Although no direct genetic link between MS and these WM abnormalities is known, molecular data from the field of rare genetic disorders may also provide some experimental paradigms to a further exploration of MS.
Increased serum levels of β2m‐free HLA class I heavy chain in multiple myeloma

Serum levels of β2‐microglobulin (β2m)‐free HLA class I heavy chain (FHC) in 94 patients with multiple myeloma (MM) were higher than in 29 patients with monoclonal gammopathy of undetermined significance (MGUS) (P = 0.023) and in 97 sex‐ and age‐matched healthy controls (P < 0.0001). Spearman correlation analysis indicated that in MM, FHC correlated with β2m (r = 0.31, P = 0.003) and the percentage of bone marrow plasma cells (BMPC%) (r = 0.36, P = 0.002), whereas β2m, in addition to BMPC% (r = 0.43, P = 0.0003), also correlated with creatinine levels (r = 0.63, P < 0.0001), haemoglobin levels (r = −0.35, P = 0.0007) and patient age (r = 0.34, P < 0.0011). Furthermore, MM patients with poor prognosis (β2m 6 mg/l) displayed higher FHC levels than those with a better prognosis (β2m < 6mg/l) (P < 0.021). At variance from β2m, these levels were not influenced by renal failure, as indicated by the lack of Spearman correlation of FHC with creatinine concentration and of statistical significance between the median FHC concentration of MM patients with creatinine < 176.6 μmol/l and those with creatinine 176.6 μmol/l (P = 0.3). Stratification of patients according to disease activity and stage showed that FHC levels were only statistically different (P = 0.04) for disease activity, whereas β2m and C‐reactive protein were not. Taken together, our data indicate that serum FHC may be a useful disease marker in MM.
A Randomized Controlled Trial of an Educational Intervention to Prevent the Chronic Pain of Whiplash Associated Disorders Following Rear-End Motor Vehicle Collisions

Study Design. Concealed allocation, multicenter, single-blind, randomized controlled clinical trial. Objective. To assess the efficacy of an educational video in the tertiary prevention of persistent WAD symptoms following rear-end motor vehicle collisions (MVCs). Summary of Background Data. Whiplash-associated disorders (WAD) are an important and costly health problem. There is a lack of high quality evidence surrounding efficacy of treatments for WAD. Existing research supports active interventions and early return to regular activities. Methods. Consecutive patients presenting to four tertiary care emergency departments following rear-end MVCs were eligible. Following informed consent, patients were allocated, using central randomization, to receive an educational video plus usual care or usual care alone. The video provided reassurance, and advice about posture, return to regular activities, exercises, and pain-relief methods. Data were collected by telephone using standardized questionnaires. The primary outcome was presence of Persistent WAD Symptoms at 24 weeks postinjury, based on the frequency and severity of neck, shoulder, or upper back pain. The absolute difference in proportion of patients with persistent WAD symptoms and rate ratios were calculated. Changes in pain scores were compared using the Mann-Whitney U test. Results. The intervention (n = 206) and control (n = 199) groups were similar at baseline (mean age 38.4 years; 64% female). Overall, the proportion of subjects with Persistent WAD Symptoms decreased from 89.1% at baseline to 33.6% at 24 weeks after injury. At 24 weeks, the proportion of subjects with persistent WAD symptoms in the intervention group was 7.9% (95% CI, −2.0, 17.8) lower than the control group. The median improvement in pain score at 24 weeks was 3 for the intervention group and 2 for the control group (P = 0.016). Conclusion. The presence of persistent WAD symptoms following simple rear-end MVCs was high in this sample. The video group demonstrated a trend toward less severe WAD symptoms. We recommend evaluating other educational interventions that could reduce WAD symptoms.
Macrophage polarization to a unique phenotype driven by B cells

Regulation of adaptive immunity by innate immune cells is widely accepted. Conversely, adaptive immune cells can also regulate cells of the innate immune system. Here, we report for the first time the essential role of B cells in regulating macrophage (Mϕ) phenotype. In vitro B cell/Mϕ co‐culture experiments together with experiments in transgenic mice models for B‐cell deficiency or overexpression showed B1 cells to polarize Mϕ to a distinct phenotype. This was characterized by downregulated TNF‐α, IL‐1β and CCL3, but upregulated IL‐10 upon LPS stimulation; constitutive expression of M2 Mϕ markers (e.g. Ym1, Fizz1) and overexpression of TRIF‐dependent cytokines (IFN‐β, CCL5). Mechanistically, this phenotype was linked to a defective NF‐κB activation, but a functional TRIF/STAT1 pathway. B1‐cell‐derived IL‐10 was found to be instrumental in the polarization of these Mϕ. Finally, in vivo relevance of B1‐cell‐induced Mϕ polarization was confirmed using the B16 melanoma tumor model where adoptive transfer of B1 cells induced an M2 polarization of tumor‐associated Mϕ. Collectively, our results define a new mechanism of Mϕ polarization wherein B1 cells play a key role in driving Mϕ to a unique, but M2‐biased phenotype. Future studies along these lines may lead to targeting of B1 cells to regulate Mϕ response in inflammation and cancer.