Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced efficacy of curcumin with phosphatidylserine-decorated nanoparticles in the treatment of hepatic fibrosis

Abstract Hepatic macrophages have been considered as a therapeutic target for liver fibrosis treatment, and phosphatidylserine (PS)-containing nanoparticles are commonly used to mimic apoptotic cells that can specifically regulate macrophage functions, resulting in anti-inflammatory effects. This study was designed to test the efficacy of PS-modified nanostructured lipid carriers (mNLCs) containing curcumin (Cur) (Cur-mNLCs) in the treatment of liver fibrosis in a rat model. Carbon tetrachloride-induced liver fibrosis in rats was used as an experimental model, and the severity of the disease was examined by both biochemical and histological methods. Here, we showed that mNLCs were spherical nanoparticles with decreased negative zeta potentials due to PS decoration, and significantly increased both mean residence time and area under the curve of Cur. In the rats with liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting to the diseased liver, which was evidenced by their highest accumulation in the liver. As compared to all the controls, Cur-mNLCs were significantly more effective at reducing the liver damage and fibrosis, which were indicated by in Cur-mNLCs-treated rats the least increase in liver enzymes and pro-inflammatory cytokines in the circulation, along with the least increase in collagen fibers and alpha smooth muscle actin and the most increased hepatocyte growth factors (HGF) and matrix metalloprotease (MMP) two in the livers. In conclusion, PS-modified NLCs nanoparticles prolonged the retention time of Cur, and enhanced its bioavailability and delivery efficiency to the livers, resulting in reduced liver fibrosis and up-regulating hepatic expression of HGF and MMP-2.
Management of cancerization field with a medical device containing photolyase: a randomized, double‐blind, parallel‐group pilot study

References 1 Yasuda M, Tamura A, Shimizu A, Takahashi A, Ishikawa O. Bowen’s disease involving the urethra. J Dermatol 2005; 32: 210–213. 2 Pedrosa JA, Amstutz SP, Bihrle R, Mellon MJ. Distal urethrectomy for localized penile squamous carcinoma in situ extending into the urethra: an update series. Int Urol Nephrol 2014; 46: 1551–1555. 3 Hammer-Hansen N, Hoyer S, Jensen JB. Occult distal urethral carcinoma presenting as metastatic carcinoma in the inguinal lymph nodes. Scand J Urol 2015; 49: 79–80. 4 Hakenberg OW, Comperat EM, Minhas S, Necchi A, Protzel C, Watkin N. EAU guidelines on penile cancer: 2014 update. Eur Urol 2015; 67: 142–150. 5 Morton CA, Birnie AJ, Eedy DJ. British Association of Dermatologists’ guidelines for the management of squamous cell carcinoma in situ (Bowen’s disease) 2014. Br J Dermatol 2014; 170: 245–260. 6 Gakis G, Witjes JA, Comperat E et al. EAU guidelines on primary urethral carcinoma. Eur Urol 2013; 64: 823–830. 7 Doiron PR, Bunker CB. Expanding the benefits of HPV vaccination to boys and men. Lancet 2016; 388: 659.
Hamiltonian Mechanics2

We develop a general framework for solving the hybrid system reachability problem, and indicate how several published techniques fit into this framework. The key unresolved need of any hybrid system reachability algorithm is the computation of continuous reachable sets; consequently, we present new results on techniques for calculating numerical approximations of such sets evolving under general nonlinear dynamics with inputs. Our tool is based on a local level set procedure for boundary propagation in continuous state space, and has been implemented using numerical schemes of varying orders of accuracy. We demonstrate the numerical convergence of these schemes to the viscosity solution of the Hamilton-Jacobi equation, which was shown in earlier work to be the exact representation of the boundary of the reachable set. We then describe and solve a new benchmark example in nonlinear hybrid systems: an auto-lander for a commercial aircraft in which the switching logic and continuous control laws are designed to maximize the safe operating region across the hybrid state space.
A Structured Approach to Goal Formulation in Psychotherapy: Differences between Patients and Controls

Therapeutic goals are considered a vital component in psychological treatments, but to date relatively little attention has been paid to the assessment and evaluation of these goals. In order to validate of a self-rating version of the Bern Inventory of Therapeutic goals checklist (BIT-C), the present study investigated if goals, measured this way, can differentiate between patients (n= 147) and healthy controls (n= 106). Results suggested that BIT-C was successful in discriminating between client and non-clients. Most importantly, clients had a higher tendency to endorse goal categories related to depressive symptoms, substance abuse, coping with somatic problems and current relationships, but a lower tendency to endorse goal categories relating to eating behaviors compared to non-patients. Further, patients perceived attainment of prioritized goals as more distant than non-patients did. The results were discussed in terms of BIT-C being a measure that can be readily applied to identify key targets in psychological treatments.
Elderly cases of Churg–Strauss syndrome: Case report and review of Japanese cases

Churg–Strauss syndrome (CSS) is a vasculitis usually thought to affect comparatively young individuals, however, elderly cases of CSS are being reported increasingly. We report two elderly cases of CSS and review 123 cases of CSS reported in Japan between 2003 and 2010. The two patients showed typical features of CSS such as asthma, chronic sinusitis, purpura and mononeuritis multiplex. The biopsy specimens demonstrated leukocytoclastic vasculitis with infiltration of eosinophils. Both patients responded well to oral prednisolone. The age of the CSS cases we reviewed ranged from the teens to the 80s, with 47.2% of the patients aged 60 years or older. These patients tended more frequently to have complications such as gastrointestinal involvement, and a higher mortality rate. Elderly cases of CSS are not rare. Correct diagnosis at an earlier stage and careful, long‐term follow up are of particular importance in preventing a fatal outcome.
Enzyme-histochemical changes in arteries of genetically hypertensive rats (SHR, SP-SHR).

To determine the effect of the duration and severity of hypertension on arterial wall metabolism 28 enzyme activities and several macromolecular complexes were histochemically studied in normotensive (WK), moderately (SHR) and strongly hypertensive (SP-SHR) rats at various ages. The results indicate that the abnormalities of 5' nucleotidase, acid esterase, cholinesterase and Alk.P. appeared in prehypertensive 4 w.old SHR. The posthypertensive changes, fluctuating in relation to the duration of hypertension, concerned: the pentose pathway, Krebs cycle and glycolosis -linked dehydrogenases; lysosomal enzymes; glycogen-phosphorylase and MAO; glycosaminoglycan and glycoprotein content. The structural and metabolic response presented several local and regional differences. The metabolic changes were greater in the aorta than in the caudal and femoral arteries. The comparison between SHR and SP-SHR indicates that the blood pressure (BP) at 170 mm Hg seems well tolerated during a long period of time. Severe lesions such as degeneration and failure of lipolytic activity in aortic smooth muscle cells (SMC), notable and early (8 mo.) in SP-SHR with 240 mm Hg were less intense and appeared later (13 mo.) in SHR with 190 mm Hg. The level of hypertension, rather than its duration, appears as a determining factor of posthypertensive vascular damage.
AC_ICAP: A Flexible High Speed ICAP Controller

The Internal Configuration Access Port (ICAP) is the core component of any dynamic partial reconfigurable system implemented in Xilinx SRAM-based Field Programmable Gate Arrays (FPGAs). We developed a new high speed ICAP controller, named AC_ICAP, completely implemented in hardware. In addition to similar solutions to accelerate the management of partial bitstreams and frames, AC_ICAP also supports run-time reconfiguration of LUTs without requiring precomputed partial bitstreams. This last characteristic was possible by performing reverse engineering on the bitstream. Besides, we adapted this hardware-based solution to provide IP cores accessible from the MicroBlaze processor. To this end, the controller was extended and three versions were implemented to evaluate its performance when connected to Peripheral Local Bus (PLB), Fast Simplex Link (FSL), and AXI interfaces of the processor. In consequence, the controller can exploit the flexibility that the processor offers but taking advantage of the hardware speed-up. It was implemented in both Virtex-5 and Kintex7 FPGAs. Results of reconfiguration time showed that run-time reconfiguration of single LUTs in Virtex-5 devices was performed in less than 5 µs which implies a speed-up ofmore than 380x compared to the Xilinx XPS_HWICAP controller.
Measuring adult literacy in health care: performance of the newest vital sign.

OBJECTIVE To compare performance of the newest vital sign (NVS) with existing literacy measures. METHODS We administered the NVS and REALM to 129 patients, and NVS and S-TOFHLA to 119 patients all in public clinics. RESULTS The NVS demonstrated high sensitivity for detecting limited literacy and moderate specificity (area under the receiver operating characteristic [AUROC] curve 0.71-0.73). The NVS was less effective than the S-TOFHLA for predicting health outcomes. CONCLUSION The NVS is able to identify patients with limited literacy skills, but may misclassify those with adequate literacy according to the REALM and S-TOFHLA. NVS scores were not associated with health outcomes.
Reflection-Type Bi-Phase Amplitude Modulator with Improved Performance Using Feedback

The analogue reflection-type attenuator using FETs as variable resistance reflection terminations is widely used as a bi-phase amplitude modulator for digital communication. However, FET parasitics cause considerable performance degradation in terms of amplitude and phase error in the signal constellation. In this paper, it is shown for the first time that simple resistive feedback can be applied to the standard modulator to improve performance dramatically. The analysis of the technique is presented, along with practical results for a 900 MHz demonstration circuit.
Structural and functional smooth muscle injury after surgical preparation of reversed and non‐reversed (in situ) saphenous vein bypass grafts

Intimal hyperplasia and isolated stenoses are major factors in determining the long‐term patency of reversed and in situ vein grafts. Surgical handling causes functional endothelial damage in reversed vein grafts but the effects of valvulotome use are unknown. Saphenous vein samples were taken after minimal dissection (control), distension with saline, or after the passage of a valvulotome. Rectangular strips of vein were mounted in an organ bath and cumulative noradrenaline (10−8‐10−5M) dose contraction curves were performed. Compared with controls there was a significant reduction in the contractile response of both the distended and valvulotome‐prepared veins (P < 0.05). Histological studies revealed partial endothelial cell loss in the distended group and total endothelial cell loss with patchy necrosis of the smooth muscle in the valvulotome group. These results suggest that the current use of a valvulotome not only renders the valves incompetent but also seriously damages the function of the smooth muscle layer.
Induced Volatiles in Elicitor-treated and Rice Blast Fungus-inoculated Rice Leaves

The volatiles released from elicitor (copper chloride, jasmonic acid, UV, L-methionine and chitosan oligomer)-treated and rice blast fungus-inoculated rice leaves were collected by the solid-phase microextraction technique and analyzed by GC-MS. (Z)-3-Hexen-1-ol, monoterpenes, methyl salicylate, and sesquiterpenes were identified as elicitor-induced volatiles by a comparison of their GC retention times and mass spectra with those of authentic compounds. The different elicitors resulted in some qualitative and quantitative differences in the production of volatiles. Monoterpenes and sesquiterpenes were identified as the rice blast fungus-induced volatiles.
Racial and economic disparities in transplant outcomes: The not‐so‐hidden morbidities

The Institute of Medicine (IOM) notes that equity is fundamental to the quality of health care (1). In this issue Thamanna and colleagues (2) present us with an important and challenging paper. They undertake careful analyses to document racial/ethnic inequities in liver transplant outcomes. As with any empirical analysis, the optimal conclusion relates both to the methods and to the underlying conceptual frame. This paper reports differences in outcomes and shows that several variables may attenuate the magnitude of such differences. How best should we understand this important contribution?
[Curative effect evaluation and complication analysis of Bryan artificial cervical disc replacement].

OBJECTIVE To observe the curative effects and complications of Bryan cervical disc replacement for cervical disc herniation. METHODS From Jannary 2005 to December 2008,39 patients with cervical disc herniation were treated with Bryan cervical disc replacement. There were 20 males and 19 females,with an average age of 47 years old (ranged, 35 to 59). Spinal compression symptom (20 cases) and nerve root symptom (19 cases) were main clinical symptoms. Single level disc was replaced in 35 cases and two-level replaced in 4 cases. Offset and activity of prosthesis,cervical physiological curvature, heterotopic ossification, prosthetic fusion were observed by dynamic X-ray. According to Odom's standard and JOA score,nerve function were evaluated; and depending on NDI standard,clinical symptom and daily function status were recorded. RESULTS All the patients were followed up from 16 to 36 months with an average of 24 months. Nerve function obviously improved and radiating pain of upper limb completely relieved. No patient with prosthetic anterior-posterior offset more than 2 mm was found. Prosthetic flexion and extention angle was (8.5+-1.8)degrees,left and right flexion range respectively were (3.5+/-1.2)degrees and (3.3+/-1.5)degrees. Cervical physiological curvature improved obviously or recovered normally. Three cases occurred in heterotopic ossification and 2 cases occurred in prosthetic fusion. According to Odom's standard,25 cases got an excellent results,9 good, 5 fair, the rate of excellent and good was 87.2%. JOA score increased from preoperative (8.26+/-1.32) to (15.71+/-1.89) at final follow-up and NDI decreased from preoperative (43.7+/-3.8) to (20.1+/-2.9) at final follow-up. CONCLUSION Treatment of cervical disc herniation with Bryan cervical disc replacement can get the good curative effects,which can obtain good nerve functional recovery,cervical stability and activity. Nevertheless,the operation has typical complication such as heterotopic ossification and prosthetic fusion. Thus,it is important in chosing indication and operative procedure.
The Use of Cold Therapy After Anterior Cruciate Ligament Reconstruction

We performed a randomized, prospective study to as sess the effectiveness of postoperative cold therapy in patients who had anterior cruciate ligament reconstruc tions. Drain output, length of hospital stay, range of motion, and use of pain medication were all assessed. Patients were randomized into one of four groups after surgery. Group 1 patients had a cooling pad applied to the knee postoperatively and set at a temperature of 40° to 50°F, Group 2 had the cooling pad set at 70° to 80°F, Group 3 received ice packs, and Group 4 re ceived no cold therapy of any kind. The skin tempera tures in Groups 1 and 3 were significantly lower than the skin temperatures in Groups 2 and 4 (P < 0.001). The length of hospital stay, range of motion at dis charge, use of oral and intramuscular pain medicine, and drain output were not significantly different be tween groups. No complications related to the type of cold therapy were seen in any group. Thus, both ice packs and cooling pads significantly decreased knee temperature, but we found no objective benefits in the early postoperative course due to this decrease in temperature.
A cyclophilin‐like peptidyl‐prolyl cis/trans isomerase from Legionella pneumophila – characterization, molecular cloning and overexpression

Legionella pneumophila is the causative agent of a severe form of pneumonia in humans (Legionnaires’disease). A major virulence factor, the Mip protein (FK506‐binding protein, FKBP25mem), belongs to the enzyme family of peptidyl‐prolyl cis/trans isomerases (PPIases). Here we show that L. pneumophila Philadelphia I possesses an additional cytoplasmic PPiase at a level of enzyme activity comparable to that of FKBP25mem. The N‐terminal amino acid sequence of the purified protein was obtained by Edman degradation and showed that the protein is a member of the cyclophilin family of PPIases. The Icy gene (Legionella cycophn) was cloned and sequenced. It encodes a putative 164‐amino‐acid protein with a molecular mass of 17 968 Da called L. pneumophila cyclophilin 18 (L. p. Cyp18). Amino acid sequence comparison displays considerable similarity to the cytoplasmic and the periplasmic cyclophilins of Escherichia coll with 60.5% and 51.5% identity, respectively. The substrate specificity and inhibition by cyclosporin A revealed a pattern that is typically found for other bacterial cyclophilins. An L. pneumophila Cyp18 derivative with a 19‐amino‐acid polypeptide extension including a 6‐histi‐dine tag and an enterokinase cleavage site exhibits
Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment.

PURPOSE To evaluate the capacity of enriched CD34-positive (CD34+) progenitor cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients following administration of a high-dose alkylating agent chemotherapy regimen. PATIENTS AND METHODS Forty-four breast cancer patients received high-dose chemotherapy followed by autologous bone marrow support (ABMS) with CD34+ hematopoietic progenitor cells in five sequentially treated cohorts. Following infusion of CD34+ marrow, cohort no. 1 received no growth factor, cohort no. 2 received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received the CD34+ fractions of both marrow and peripheral-blood progenitor cells (PBPCs) plus G-CSF. Cohort no. 5 received only the CD34+ PBPCs plus G-CSF. Immunohistochemical staining for breast cancer was performed on all hematopoietic cell products before and after the positive selection procedure, to assess quantitatively the level of tumor-cell contamination. RESULTS Cohorts no. 1, 2, 3, 4, and 5 achieved a granulocyte count > or = 500 x 10(9)/L in a median of 23, 10, 16, 11, and 11 days, with a platelet count greater than 20,000 x 10(9)/L documented in a median of 22, 23, 32, 12, and 10 days, respectively. The time to granulocyte reconstitution was significantly shorter for patients who received CD34+ PBPCs alone (cohort no. 5), or in combination with CD34+ marrow (cohort no. 4), when compared with those who received only the CD34+ marrow fraction (P < .01). From 1 to greater than 4 logs of breast cancer cell depletion were documented after CD34-selection, for patients in whom tumor was initially detected. CONCLUSION CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.
Heterotrimeric G proteins as emerging targets for network based therapy in cancer: End of a long futile campaign striking heads of a Hydra

Most common diseases, e.g., cancer are driven by not one, but multiple cell surface receptors that trigger and sustain a pathologic signaling network. The largest fraction of therapeutic agents that target individual receptors/pathways eventually fail due to the emergence of compensatory mechanisms that reestablish the pathologic network. Recently, a rapidly emerging paradigm has revealed GIV/Girdin as a central platform for receptor cross-talk which integrates signals downstream of a myriad of cell surface receptors, and modulates several key pathways within downstream signaling network, all via non-canonical activation of trimeric G proteins. Unlike canonical signal transduction via G proteins, which is spatially and temporally restricted, the temporal and spatial features of non-canonical activation of G protein via GIV is unusually unrestricted. Consequently, the GIV●G protein interface serves as a central hub allowing for control over several pathways within the pathologic signaling network, all at once. The relevance of this new paradigm in cancer and other disease states and the pros and cons of targeting the GIV●G protein interface are discussed.
Tamoxifen-SSRIs interaction: clinical manifestations of inhibition and lack of inhibition of CYP2D6.

TO ThE EDiTOR: t amoxifen is an estrogen receptor modulator that is used for the treatment of hormone receptor positive breast cancer. As a prodrug, treatment efficacy may be mediated by 2 active metabolites: 4-hydroxytamoxifen (4-OH-TAM) and 4-hydroxy-Ndesmethyltamoxifen (endoxifen). These metabolites have at least 100-fold higher potency than the parent drug, and in vitro studies have demonstrated that cytochrome P450 2D6 (CYP2D6) is responsible for tamoxifen metabolism. There are reports that patients who are CYP2D6 poor metabolizers have a higher risk of relapse and lower incidence of hot flashes with tamoxifen treatment. This is in part because of lower levels of endoxifen. Depressive symptoms are a frequent complication of breast cancer and many patients are treated with selective serotonin reuptake inhibitors (SSRIs). Moreover, SSRIs also are used to treat hot flashes, a common side effect of tamoxifen. The SSRIs paroxetine and fluoxetine are considered strong CYP2D6 inhibitors. The inhibition of CYP2D6 may decrease tamoxifen metabolites and may adversely affect the efficacy of breast cancer treatment. CLiniCaL Vignette