Miracle-dz/UniFAR-FTUs huggingface dataset:
X‐linked inhibitor of apoptosis inhibition sensitizes acute myeloid leukemia cell response to TRAIL and chemotherapy through potentiated induction of proapoptotic machinery

Acute myeloid leukemia (AML) is an aggressive disease with an increasing incidence and relatively low 5‐year survival rate. Unfortunately, the underlying mechanism of leukemogenesis is poorly known, and there has been little progress in the treatment for AML. Studies have shown that X‐linked inhibitor of apoptosis (XIAP), one of the inhibitors of apoptosis proteins (IAPs), is highly expressed and contributes to chemoresistance in AML. Hence, a novel drug, RO6867520 (RO‐BIR2), developed by Roche targeting the BIR2 domain in XIAP to reactivate blocked apoptosis, is a promising therapy for AML. The monotherapy of RO‐BIR2 had minimal effect on most of the AML cell lines tested except U‐937. In contrast to AML cell lines, in general, RO‐BIR2 alone has been shown to inhibit the proliferation of primary AML patient samples effectively and induced apoptosis in a dose‐dependent manner. A combination of RO‐BIR2 with TNF‐related apoptosis‐inducing ligand (TRAIL) led to highly synergistic effect on AML cell lines and AML patient samples. This combination therapy is capable of inducing apoptosis, thereby leading to an increase in specific apoptotic cell population, along with the activation of caspase 3/7. A number of apoptotic‐related proteins such as XIAP, cleavage of caspase 3, cleavage of caspase 7, and cleaved PARP were changed upon combination therapy. Combination of RO‐BIR2 with Ara‐C had similar effect as the TRAIL combination. Ara‐C combination also led to synergistic effect on AML cell lines and AML patient samples with low combination indexes (CIs). We conclude that the combination of RO‐BIR2 with either TRAIL or Ara‐C represents a potent therapeutic strategy for AML and is warranted for further clinical trials to validate the synergistic benefits in patients with AML, especially for the elderly who are abstaining from intensive chemotherapy.
Pseudotumors in association with well-functioning metal-on-metal hip prostheses: a case-control study using three-dimensional computed tomography and magnetic resonance imaging.

INTRODUCTION Many papers have been published recently on the subject of pseudotumors surrounding metal-on-metal hip resurfacing and replacement prostheses. These pseudotumors are sterile, inflammatory lesions within the periprosthetic tissues and have been variously termed masses, cysts, bursae, collections, or aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL). The prevalence of pseudotumors in patients with a well-functioning metal-on-metal hip prosthesis is not well known. The purpose of this study was to quantify the prevalence of pseudotumors adjacent to well-functioning and painful metal-on-metal hip prostheses, to characterize these lesions with use of magnetic resonance imaging, and to assess the relationship between their presence and acetabular cup position with use of three-dimensional computed tomography. METHODS We performed a case-control study to compare the magnetic resonance imaging findings of patients with a well-functioning unilateral metal-on-metal hip prosthesis and patients with a painful prosthesis (defined by either revision arthroplasty performed because of unexplained pain or an Oxford hip score of <30 of 48 possible points). Thirty patients with a painful hip prosthesis and twenty-eight controls with a well-functioning prosthesis were recruited consecutively. All patients also underwent computed tomography to assess the position of the acetabular component. RESULTS Thirty-four patients were diagnosed with a pseudotumor. However, the prevalence of pseudotumors in patients with a painful hip (seventeen of thirty, 57%) was not significantly different from the prevalence in the control group (seventeen of twenty-eight, 61%). No objective differences in pseudotumor characteristics between the groups were identified. No clear association between the presence of a pseudotumor and acetabular component position was identified. The Oxford hip score in the group with a painful hip (mean, 20.2; 95% confidence interval [CI], 12.7 to 45.8) was poorer than that in the control group (mean, 41.2; 95% CI, 18.5 to 45.8; p ≤ 0.0001). CONCLUSIONS A periprosthetic cystic pseudotumor was diagnosed commonly (in thirty-four [59%] of the entire study cohort) with use of metal artifact reduction sequence (MARS) magnetic resonance imaging in this series of patients with a metal-on-metal hip prosthesis. The prevalence of pseudotumors was similar in patients with a well-functioning hip prosthesis and patients with a painful hip. Pseudotumors were also diagnosed commonly in patients with a well-positioned acetabular component. Although magnetic resonance imaging is useful for surgical planning, the presence of a cystic pseudotumor may not necessarily indicate the need for revision arthroplasty. Further correlation of clinical and imaging data is needed to determine the natural history of pseudotumors to guide clinical practice.
Protease Cleavage Sites in HIV-1 gp120 Recognized by Antigen Processing Enzymes Are Conserved and Located at Receptor Binding Sites

ABSTRACT The identification of vaccine immunogens able to elicit broadly neutralizing antibodies (bNAbs) is a major goal in HIV vaccine research. Although it has been possible to produce recombinant envelope glycoproteins able to adsorb bNAbs from HIV-positive sera, immunization with these proteins has failed to elicit antibody responses effective against clinical isolates of HIV-1. Thus, the epitopes recognized by bNAbs are present on recombinant proteins, but they are not immunogenic. These results led us to consider the possibility that changes in the pattern of antigen processing might alter the immune response to the envelope glycoprotein to better elicit protective immunity. In these studies, we have defined protease cleavage sites on HIV gp120 recognized by three major human proteases (cathepsins L, S, and D) important for antigen processing and presentation. Remarkably, six of the eight sites identified in gp120 were highly conserved and clustered in regions of the molecule associated with receptor binding and/or the binding of neutralizing antibodies. These results suggested that HIV may have evolved to take advantage of major histocompatibility complex (MHC) class II antigen processing enzymes in order to evade or direct the antiviral immune response.
Determinants of spontaneous surface antigen loss in hepatitis B e antigen–negative patients with a low viral load

Loss of hepatitis B surface antigen (HBsAg) usually indicates the cure of hepatitis B virus (HBV) infection. In spontaneous hepatitis B e antigen (HBeAg) seroconverters, lower serum HBsAg and HBV DNA levels have been shown to be associated with HBsAg loss over time. However, little is known about their impacts on HBsAg loss in HBeAg‐negative patients with limited viral replication. A total of 688 HBeAg‐negative patients with baseline serum HBV DNA levels <2000 IU/mL were enrolled in Taiwan. The relationships of HBsAg and HBV DNA levels with subsequent HBsAg loss were investigated. In a mean follow‐up of 11.6 years, the average annual rate of HBsAg loss was 1.6%. Baseline HBsAg and HBV DNA levels were inversely associated with subsequent HBsAg loss. When compared to patients who had HBsAg levels >1000 IU/mL, the rates of HBsAg loss were significantly higher in patients with HBsAg levels of 100‐999, 10‐99, and <10 IU/mL, with hazard ratios of 2.5 (95% confidence interval [CI], 1.6‐4.0), 2.8 (95% CI, 1.6‐5.0), and 13.2 (95% CI, 8.1‐21.5), respectively. Multivariate analysis showed that HBsAg level, but not HBV DNA, remained as an independent factor. The adjusted hazard ratio of HBsAg loss was 13.2 (95% CI, 7.8‐22.1) for HBsAg level <10 versus ≥1000 IU/mL. When compared to HBV DNA level by receiver operating characteristic curve analysis, HBsAg level served as a better predictor of both 5‐year and 10‐year HBsAg loss. Conclusion: In HBeAg‐negative patients with HBV genotype B or C infection who have HBV DNA level <2000 IU/mL, HBsAg level <10 IU/mL is the strongest predictor of HBsAg loss. (HEPATOLOGY 2012;55:68–76)
Safety of Lienal Polypeptide Injection Combined with Chemotherapy in Treating Patients with Advanced Cancer.

OBJECTIVE To assess the safety of Liena polypeptide injection (produced by JILIN FSENS PHARMACEUTICAL CO.,LTD) combined with chemotherapy in treating patients with advanced cancers. METHOD A consecutive cohort of patients with advanced cancers were treated with Liena polypeptide injection combined with chemotherapy. And chemotherapy for patients with advanced cancers were adopted from regimens suggested by NCCN guideline. Liena polypeptide injection was intravenously injected at a dosage of 2 ml plus 100ml normal saline for continuous 7 days during chemotherapy as one course. After at least two courses of treatment, safety and side effects were evaluated. RESULTS There were 20 female and 14 male patients with advanced cancer recruited into this study, including 10 patients with breast, 8 patients with colorectal, 8 patients with lung, 4 patients with gastric, and 1 patient with esophageal cancer, as well as 1 patient with non-Hodgkin's lymphoma, 1 patient with low pharyngeal and 1 patient with urethral cancer. The median age of patients was 59 (40-82) years. Incidences of Grade 1 to 2 myelosuppression was observed in 5/34 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 3/34 patients. Adverse effects on the gastrointestinal tract were documented in 5/34 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. CONCLUSIONS Liena polypeptide injection combined with chemotherapy was safe in treating several sites of tumors, that mainly included lung, colorectal and breast cancer. However, further study should be conducted to clarify the effectiveness of this treatment.
Global status report on road safety

The World Health Organization has just released the Global status report on road safety —the first broad assessment that describes the road safety situation in 178 countries, using data drawn from a standardised survey. The results provide a benchmark that countries can use to assess their road safety position relative to other countries, while at the international level these findings can be considered as a “baseline”, against which regional and global level progress can be measured. The questionnaire used for this survey was developed in consultation with an expert committee of road safety researchers and practitioners. Data collection was carried out using a self-administered questionnaire, the content of which was based on the recommendations of the World report on road traffic injury prevention , developed by WHO, the World Bank and many other partners in 2004. The methodology used involved the identification of a National Data Coordinator in each country who identified up to seven other national road safety experts from multiple sectors who could complete the questionnaire. A consensus meeting was then held involving all …
Dendritic Cells Phagocytose and Are Activated byTreponema pallidum

ABSTRACT Cell-mediated immune processes play a prominent role in the clinical manifestations of syphilis, a sexually transmitted disease of humans caused by spirochetal bacterium Treponema pallidum. The immune cell type that initiates the early immune response toT. pallidum thus far has not been identified. However, dendritic cells (DCs) are the first immune-competent cells to encounter antigens within skin or mucous membranes, the principal sites of early syphilitic infection. In the present study, immature DC line XS52, derived from murine skin, was utilized to examine T. pallidum-DC interactions and subsequent DC activation (maturation). Electron microscopy revealed that T. pallidumwas engulfed by DCs via both coiling and conventional phagocytosis and was delivered to membrane-bound vacuoles. The XS52 DC line expressed surface CD14 and mRNA for Toll-like receptors 2 and 4, molecules comprising important signaling components for immune cell activation by bacterial modulins. Both T. pallidum and a synthetic lipopeptide (corresponding to the 47-kDa major membrane lipoprotein) activated the XS52 DC line, as indicated by the secretion of interleukin-12 (IL-12), IL-1β, tumor necrosis factor alpha, and IL-6 and elevated surface expression of CD54. The combined data support the contention that DCs stimulated by T. pallidum and/or its proinflammatory membrane lipoproteins are involved in driving the cellular immune processes that typify syphilis.
Low testosterone has a similar prevalence among men with sexual dysfunction due to either Peyronie's disease or erectile dysfunction and does not correlate with Peyronie's disease severity.

INTRODUCTION Low testosterone (T) has been suggested as a risk factor for Peyronie's disease (PD) that may correlate with disease severity. Low T is common in men with sexual dysfunction but its role in the pathogenesis of PD remains unclear. AIM The aim of this study was to compare the prevalence of low T (<300 ng/dL) in patients presenting with PD or erectile dysfunction (ED), as well as disease severity between men with PD and either low T or normal T (≥300 ng/dL). METHODS Retrospective review of 300 men with either PD or ED was conducted. Men were excluded for combined PD and ED, psychogenic ED, or prior T use. For men with PD, plaque size, degree of curvature, and surgical correction rate were compared. MAIN OUTCOME MEASURES The main outcome measures were (i) mean T levels in men with PD or ED and (ii) plaque size, degree of curvature, and surgical correction rates among men with PD and either low T or normal T. RESULTS Eighty-seven men with PD and 98 men with ED were identified. Men with PD had mean total T and free T of 328 ng/dL and 11.5 ng/dL, while men with ED had mean levels of 332 ng/dL and 12.1 ng/dL, respectively (P > 0.05). Of PD men, 52.9% had low T, compared with 45.9% of men with ED (P = 0.35). T levels did not correlate with plaque size or degree of curvature in the PD group (P > 0.05). CONCLUSIONS Men with sexual dysfunction characterized by either PD or ED had similarly low T levels, and low T did not correlate with PD severity or surgical correction rate. The comparable prevalence of low T in men with PD or ED suggests the high rate of low T in PD men may be related to a common process among men with abnormal erectile physiology and not specifically causative in plaque formation.
Electron-emission yield of Al, Cu, and Au for the impact of swift bare light ions.

The electron emission yield induced by mega-electron-volt H{sup +}, He{sup 2+}, Li{sup 3+}, B{sup 5+}, and C{sup 6+} impact on aluminum, copper, and gold targets was measured. We found a significant deviation of the results from a simple proportionality to the stopping power, especially for heavier ions and low projectile velocities. Using a slightly modified model by J. E. Borovsky and D. M. Suszcynsky [Phys. Rev. A {bold 43}, 1433 (1991)] our experiments could be well represented. In this model the collective electric field generated along the projectile`s path was taken into account. Consequently, the positive ion channel appears to be the dominant mechanism that leads beyond a projectile-independent yield--to--stopping power ratio.
Intermittent exotropia: continued controversies and current management

Purpose of review Continued controversy exists regarding intermittent exotropia and its management. Although it has been studied extensively, the indication for and timing of intervention and what therapy is most efficacious remains unclear. This article reviews the most recent research and the controversies surrounding the disease classification and treatment options in the management of intermittent exotropia. Recent findings Current studies are underway to uncover the natural history of the intermittent exotropia. Patching and observation are reasonable treatment options in the first 6 months of the disease presentation. As the disease progresses and nonsurgical management fails, botulinum toxin may play a role or be an alternative option in the early treatment of intermittent exotropia. Surgical treatment with orthoptic therapy may result in improved postoperative outcomes. Summary Although significant investigations have been performed on this entity, there remains poor cohesiveness between clinical trials resulting in lack of clarity regarding when and how to treat intermittent exotropia. As the natural history of the disease is elucidated and researchers standardize their assessment of the control of the strabismus and what constitutes a successful treatment outcome, better understanding may occur to develop more efficacious remedies. Despite being less known and utilized, botulinum toxin and orthoptic therapy are options for treatment for intermittent exotropia and should be considered for appropriate patient's treatment protocol.
A natural heme‐signature variant of CYP267A1 from Sorangium cellulosum So ce56 executes diverse ω‐hydroxylation

A novel naturally occurring heme‐signature variant of CYP267A1 from myxobacterium Sorangium cellulosum So ce56 and its mutant L366F, the actual mimic of the ‘conserved’ heme‐signature of cytochromes P450, were heterologously expressed in Escherichia coli in a soluble form and purified. The UV–visible characteristics of both variants were highly similar. Although leucine replaced the phenylalanine in the heme‐signature domain of CYP267A1, EPR measurements of the ligand‐free wild‐type CYP267A1 and the mutant L366F showed low‐spin rhombic species suggesting a conserved heme environment of the P450s. The need of primary redox partners for the orphan P450 was sustained by the bovine redox system and a class‐I electron transfer path was provided during fatty acid hydroxylation. CYP267A1 showed higher activity and produced more diverse ω‐hydroxylated products compared with L366F. In both enzymes the regioselectivity of the fatty acid hydroxylation shifted towards the inner carbon atoms of the fatty acid chains with increasing carbon chain lengths. Our docking results in a homology model of the protein showed that longer fatty acids need to be folded to fit into the binding pocket. In the mutant L366F, the ω‐1 and ω‐2 positions which exhibit the largest electron density of the highest occupied molecular orbital are preferred. It is speculated that the leucine heme‐signature variant of P450 might have evolved under selective evolutionary pressure, which confers an increased advantage to generate a broader spectrum of related alcohols and carboxylic acids required for the bacterial homeostasis or metabolism in a particular ecological niche.
I–Thomas Hurka

Using Bernard Suits's brilliant analysis ( contra Wittgenstein) of playing a game, this paper examines the intrinsic value of game-playing. It argues that two elements in Suits's analysis make success in games difficult, which is one ground of value, while a third involves choosing a good activity for the property that makes it good, which is a further ground. The paper concludes by arguing that game-playing is the paradigm modern (Marx, Nietzsche) as against classical (Aristotle) value: since its goal is intrinsically trivial, its value is entirely one of process rather than product, journey rather than destination.
Fine needle aspiration biopsy in the diagnosis of thyroid cancer and thyroid disease

Fine needle aspiration biopsy (FNAB) performed for diffuse and nodular goiter in the past 5 years, was evaluated in 1399 cases. Surgery was performed on the basis of FNAB cytologic diagnosis that was positive or suggestive of malignancy and/or a suggestive clinical history. Surgery also was performed in cases of cold nodules with negative FNAB results that did not respond to 6 months of suppressive thyroxine therapy. A correlation of cytologic findings with histologic findings was possible in 415 patients who underwent surgery: the evaluation of FNAB results yielded better results when suspicious cytologic findings were considered to be positive (2.4% false‐negative, 86.3% sensitivity) rather than negative (6.5% and 65.7%, respectively). FNAB has become a useful procedure in the study and diagnosis of thyroid diseases. It is a simple, rapid diagnostic procedure that may be used to expedite the management ofmalignant lesions. Cancer 59:1206‐1209, 1987.
Catamenial pneumothorax caused by diaphragmatic stromal endometriosis

A case of catamenial pneumothorax caused by stromal endometriosis of the diaphragm is described. A 40‐year‐old woman suffered two episodes of right‐sided pneumothorax which occurred after onset of menstruation. Thoracoscopy revealed brownish spots in the right diaphragm and partial excision of the diaphragm was performed. Histological examination showed that the lesion was characterized by sheets of cells resembling endometrial stromal cells, small thin‐walled blood vessels and extrava‐sated erythrocytes in varying proportions. Some clusters of these cells were transmural. No endometrial‐type glands were found. Immunohistochemically, the nuclei of the endometrial stromal cells were strongly positive for both estrogen and progesterone receptors. Therapy with a gonadotropin‐releasing hormone analogue was started and the patient has since been asymptomatic for 6 months. Pathologists should not overlook diaphragmatic stromal endometriosis as a possible cause of pneumothorax.
Differential Power Analysis Countermeasure for Improved DES with Dynamic Key Management

Leakage of information in the form of side channel, from cryptographic hardware has opened up new ideas for intruders to break their security. This leakage is present in all type of hardware whether cards, FPGAs or ASICs smart. One of the most popular and effective information leakage is power. Differential Power Attacks (DPA) due to their effectiveness has become a great threat in the field of cryptography. In this paper, a countermeasure based on random power masking to avoid DPA is proposed for FPGA based hardware implementation of a dynamic key management for Improved Data Encryption Standard (IDES). Dynamic key management include three different key reconfiguration systems which can independently be used to generate sub-keys. Hardware implementation include, a 16 staged fully pipelined IDES with conventional Data Encryption Standard (DES) based, Linear Feedback Shift Register (LFSR) based, and Chaos Logistic Register (CLR) based key scheduling system. IDES having a 96 bit architecture which is more complex making it more immune to cryptographic analysis can give more throughput in as compared to simple DES. Three different key scheduling systems having 128 bit architecture includes more security in comparison to the 64 bit key systems. Implementation results of Virtex 7 series FPGA are operation frequency of 570 MHz and a throughput of 54.72 Gb/s.
Effect of light irradiation on dynamics of vitamin A compounds in rotifers and Artemia

The dynamics of vitamin A (VA) compounds in live food during enrichment were examined under different light conditions. Rotifers Brachionus plicatilis and Artemia nauplii (Artemia) were enriched with or without 10 mg VA palmitate (VAp) in 1 L of culture medium for 24 h under either bright (2000 lx), or dark (<1 lx) conditions. VAp, retinol (ROH), retinal (RAL) and retinoic acid (RA) contents were analyzed at 0 h (before enrichment) and at 3, 6, 12, 18 and 24 h after the onset of enrichment. Retinoid content in rotifers enriched in darkness was always higher than that enriched under light. VAp content showed two peaks at 3 and 18 h in rotifers enriched in darkness, but it showed one peak at 3 h in rotifers enriched under light. ROH and RA contents increased over the 24-h period in rotifers enriched in darkness, whereas they decreased 12 h onward in rotifers enriched under light. In Artemia, VAp and ROH contents were always higher than when enriched under the bright condition, but their dynamics showed a similar pattern in Artemia enriched under dark and bright conditions.