Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinoid X receptor suppresses a metastasis-promoting transcriptional program in myeloid cells via a ligand-insensitive mechanism

Significance Metastasis formation from malignant tumors is the leading cause of cancer-related deaths. There is an increasing body of evidence indicating that immune cells in distant organs actively contribute to this process by establishing a tissue environment that is hospitable for cancer cells. In this study, we show that deletion of retinoid X receptor (RXR), a cellular sensor of vitamin A metabolites, specifically in the myeloid lineage of the immune system, leads to an enhanced metastasis rate. We also demonstrate that RXR inhibits the expression of a number of genes that encode proteins involved in the promotion of metastasis formation. Surprisingly, our results suggest that this activity of RXR is independent of the presence of its activators. Retinoid X receptor (RXR) regulates several key functions in myeloid cells, including inflammatory responses, phagocytosis, chemokine secretion, and proangiogenic activity. Its importance, however, in tumor-associated myeloid cells is unknown. In this study, we demonstrate that deletion of RXR in myeloid cells enhances lung metastasis formation while not affecting primary tumor growth. We show that RXR deficiency leads to transcriptomic changes in the lung myeloid compartment characterized by increased expression of prometastatic genes, including important determinants of premetastatic niche formation. Accordingly, RXR-deficient myeloid cells are more efficient in promoting cancer cell migration and invasion. Our results suggest that the repressive activity of RXR on prometastatic genes is mediated primarily through direct DNA binding of the receptor along with nuclear receptor corepressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) corepressors and is largely unresponsive to ligand activation. In addition, we found that expression and transcriptional activity of RXRα is down-modulated in peripheral blood mononuclear cells of patients with lung cancer, particularly in advanced and metastatic disease. Overall, our results identify RXR as a regulator in the myeloid cell-assisted metastatic process and establish lipid-sensing nuclear receptors in the microenvironmental regulation of tumor progression.
Demographics, treatment, and early outcomes in penetrating vascular combat trauma.

OBJECTIVES To describe arterial and venous injuries and their management and short-term outcomes in a wartime hospital. DESIGN Retrospective review of patients with vascular injuries. Mechanism, location, method of repair, and outcomes were analyzed with descriptive and inferential statistics. SETTING The 31st Combat Support Hospital, Operation Iraqi Freedom. PATIENTS A total of 153 patients with 218 vascular injuries from January 1, 2004, to December 30, 2004. MAIN OUTCOME MEASURES Limb salvage and mortality rates. RESULTS The overall limb salvage rate was 80%, while all-cause mortality was 6%. Most vascular injuries were sustained by blast and fragmentation mechanisms. Not surprisingly, most vascular injuries were in lower extremity vessels (57% arterial, 50% venous), with a high predominance of superficial femoral vessel injuries. Vascular injuries to the upper extremities were associated with a higher limb salvage rate (95%) than injuries to the lower extremities (71%). Variable follow-up data for 63 (41%) patients revealed that 32 underwent further procedures outside the combat theater, 12 of which were delayed amputations. Of all arterial injuries, 36% were primarily repaired, 34% were repaired with a vein interposition graft, 29% were ligated, and 2% were repaired with a prosthetic graft. A majority of venous injuries (56%) were ligated. CONCLUSIONS There is an acceptable early patency and limb salvage rate in combat vascular repairs. A majority of penetrating vascular injuries occur in the lower extremities. Overall, penetrating vascular trauma is often a survivable injury.
Phytochemical Screening and Antibacterial Activity of Lawsonia inermis Leaf Extract

The present study is the continuation of a program aimed at investigation of antimicrobial and photochemical properties of Lawsonia inermis leaf extract to justify the traditional claim endowed upon this herbal drug as a rasayana in Ayurveda. The antimicrobial activity was evaluated according to the disk diffusion method by using Gram positive; B. subtilius, S. aureus and S. epidermidis and Gram negative; E. coli, S. flexneri, P. aeruginosa bacteria. This study show that methanolic leaves extracts of Lawsonia inermis Linn inhibit the growth of micro organisms dose dependently. Phytochemical screening of the extracts showed the presence of glycosides, phytosterol, steroids, saponins, tannins and flavonoids. The presence of flavonoids and glycosides as major constituents of the plant leaves that are commonly known to posses antimicrobial activity. These results confirm the antibacterial activity of Lawsonia inermis leaves and support the traditional use of the plant in therapy of bacterial infection.
Gender schema and prostate cancer: Veterans' cultural model of masculinity

Coming to terms with disease, chronic illness, and aging may be challenging for men who adhere to an inflexible gender schema. In this study of elder U.S. veterans' ideas about masculinity, we find that prostate cancer patients reaffirm a strongly moral normalizing discourse about "being a man" yet tend to separate roles and values from male physical and sexual attributes. Using systematic data collection methods taken from cognitive anthropology, we map veterans' schema of masculinity and examine the relative importance that cancer patients and non-patients give to gender attributes. The results demonstrate the complementarity between cognitive and narrative approaches in medical anthropology. This research also suggests the hypotheses that (1) coming to terms with iatrogenesis may involve a subtle reformulation of masculinity and that (2) men with a fixed view of masculinity may have worse health outcomes than do those who accept the changes accompanying their treatment for prostate cancer.
Biochemical and biophysical characterisation of haloalkane dehalogenases DmrA and DmrB in Mycobacterium strain JS60 and their role in growth on haloalkanes

Haloalkane dehalogenases (HLDs) catalyse the hydrolysis of haloalkanes to alcohols, offering a biological solution for toxic haloalkane industrial wastes. Hundreds of putative HLD genes have been identified in bacterial genomes, but relatively few enzymes have been characterised. We identified two novel HLDs in the genome of Mycobacterium rhodesiae strain JS60, an isolate from an organochlorine‐contaminated site: DmrA and DmrB. Both recombinant enzymes were active against C2–C6 haloalkanes, with a preference for brominated linear substrates. However, DmrA had higher activity against a wider range of substrates. The kinetic parameters of DmrA with 4‐bromobutyronitrile as a substrate were Km = 1.9 ± 0.2 mM, kcat = 3.1 ± 0.2 s−1. DmrB showed the highest activity against 1‐bromohexane. DmrA is monomeric, whereas DmrB is tetrameric. We determined the crystal structure of selenomethionyl DmrA to 1.7 Å resolution. A spacious active site and alternate conformations of a methionine side‐chain in the slot access tunnel may contribute to the broad substrate activity of DmrA. We show that M. rhodesiae JS60 can utilise 1‐iodopropane, 1‐iodobutane and 1‐bromobutane as sole carbon and energy sources. This ability appears to be conferred predominantly through DmrA, which shows significantly higher levels of upregulation in response to haloalkanes than DmrB.
Running a record label when records don't sell anymore: empirical evidence from Poland

Abstract From an economic point of view, the business of record labels until recently boiled down to managing a portfolio of artists, with successful stars bringing the label enough money to recoup investments in market flops. The decline in record sales has called this model into question and forced labels to look for new sources of revenue. Employing qualitative data gathered in Poland, this paper demonstrates how labels react to adverse market conditions and what determines these reactions. The paper shows that these reactions include the monetisation of the relationship that a label has with artists through signing 360° deals, the commercial exploitation of artists’ brand names, and concentration on niche markets, either foreign or format-based (e.g. the market for vinyl). The paper concludes that record labels, regardless of which approach they choose to deal with the adverse market conditions, still think in terms of managing a portfolio of artists. What is more, there is no universal strategy which can be applied by every label to deal with declining record sales.
A Promoter Polymorphism of the Alpha 8 Integrin Gene and the Progression of Autosomal-Dominant Polycystic Kidney Disease

Background/Aims: Dysregulation of integrins is a feature of tissue remodeling in autosomal-dominant polycystic kidney disease (ADPKD). The alpha 8 beta 1 integrin (α8β1) affects kidney development and the susceptibility to renal injury in mice. We investigated whether the –414 T/C polymorphism in the promoter region of the alpha 8 integrin chain gene (ITGA8) is associated with the progression of renal disease in ADPKD. Methods: Genotyping for the –414 T/C polymorphism was performed by allelic separation using RT-PCR in 294 patients with ADPKD. Alpha 8 integrin expression was detected by RT-PCR and immunohistochemistry. Results: 41% of the study population reached end stage renal disease at a mean age of 51 ± 12 years. The frequency of the –414 C allele was 0.194 in ADPKD. C allele carriers (CC and TC genotypes) were compared with patients homozygous for the T allele (TT genotype). Kaplan-Meier analysis revealed that end-stage renal failure occurred at a significantly younger age in TT homozygotes (median age, 47 years; 95% CI, 46–49 years) than in C allele carriers (median age, 51 years; 95% CI, 49–53 years; p = 0.046 by the log-rank test). When parameters of ADPKD patients were compared between genotype by analysis of variance, only age at onset of end-stage renal failure was significantly different (p = 0.026) whereas age at onset of hypertension, body surface area, 24-hour systolic and diastolic blood pressure did not differ. In kidneys of ADPKD, expression of alpha 8 integrin is increased and found de novo in cystic epithelia. Conclusion: A polymorphism of the ITGA8 promoter modifies the progression of renal failure in ADPKD.
Lumbar myelography enhanced with ion free contrast medium – pro and against. Presentation a new technique improving quality of the image in the area of lateral recesus of vertebral canal

Address for correspondence: Dimitar Stefanov Cholakov, MD Department of Neurosurgery University of Medicine – Plovdiv 66 “Peshtersko shose” blv. 4000 Plovdiv Bulgaria +359887869273 e-mail: dimcholakov@hotmail.bg
Statistics of buoy-observed waves during typhoons at Taiwanese Waters from 1997 to 2008

Twelve data buoys are being operated at Taiwanese Waters in East Asia Pacific Ocean. Typhoon-induced sea-states are the main targets of measurements. In this study, ocean waves generated by typhoons from 1997 to 2008 are analyzed. Preliminary results show that the trends of increasing scale of maximum wave heights and the duration of severe sea-states during typhoons are found. In addition, extreme large wave was also recorded. All the identities show the changing of wave climate. This may bring large impacts for the coast as well as for ocean, is an un-pretermitted issue.
Proteomic characteristics of human sperm cryopreservation

Human sperm cryopreservation in assisted reproductive technology is the only proven method that enables infertile men to father their own children. However, freezing and thawing reduces spermatozoon motility, viability, and fertilizing ability. An association between dysfunctional spermatozoa due to cryoinjury and protein changes has not been established. We investigated through proteomic analysis the differential protein characteristics between freeze‐thawed and fresh sperm samples obtained from nine normozoospermic donors. Twenty‐seven proteins differed in abundance between the two groups, and results were verified for four proteins via Western blot and immunofluorescent staining. These proteins are putatively involved in sperm motility, viability, acrosomal integrity, ATP and isocitrate content, mitochondrial membrane potential, capacitation, acrosome reaction, and intracellular calcium concentration. These marked differences suggest that dysfunctional spermatozoon after cryopreservation may be due to protein degradation and protein phosphorylation.
Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: Results from PHOENIX 2

Abstract Objective: To assess the effect of ustekinumab on productivity and work limitations among 1230 psoriasis patients treated with ustekinumab 45 mg or 90 mg or placebo during the Phase III PHOENIX 2 trial. Methods: The self-administered Work Limitations Questionnaire (WLQ) was used to determine the on-the-job limitations at baseline and weeks 12 and 24. Productivity was assessed using a Visual Analog Scale (VAS), and the number of work days missed due to psoriasis was recorded. Results: At baseline, work limitations and productivity were similar across treatment groups. At week 12, improvement in productivity VAS scores was significantly (p < 0.001) higher in the 45 mg (72.6%) and 90 mg (71.4%) ustekinumab groups versus placebo (no change), and the proportion of patients who missed work days was significantly lower (2.0% for each ustekinumab group vs 8.3% for placebo; p < 0.001). Mean improvements from baseline to week 12 were greater with ustekinumab than with placebo for WLQ domains, including time management (6.6/9.1 vs –0.7), mental-interpersonal (7.8/7.5 vs –1.1), and output demands (6.8/7.0 vs –1.1) (p < 0.001 for ustekinumab 45 mg/90 mg vs placebo). Improvements were maintained through week 24. Conclusions: Ustekinumab 45 mg or 90 mg significantly increased productivity, reduced work days missed, and improved work limitations compared with placebo in patients with moderate-to-severe psoriasis.
Falls in a Community of Older Adults

This study described the incidences of falls and injuries related to those falls in a community of older adults. It used a convenience sample of 220 older adults in a continuing care retirement community. Over a 2-year period, all residents who had a witnessed or reported fall were evaluated by a nurse or nurse practitioner and completed a Falls Data form. There were 154 falls, most of which occurred between noon and midnight, within the residents’ apartments, when walking (63%) or transferring (19%). Only 16 (10%) of the falls resulted in a fracture. The number of falls was the only variable associated with having an injurious fall. Individuals who had atrial fibrillation or neurological problems, were not married, and did not adhere to a regular exercise program were more likely to have multiple falls. The findings were used by the nurse practitioner to educate residents about falls in their community and to develop interventions to decrease the risk and incidences of falls.
Electroconvulsive therapy in older adults.

W. Bogan Brooks, MD CAse Your patient is a 78 year old widowed woman with a history of hypertension, hyperlipidemia, osteoporosis, and major depressive disorder. She was doing well on verapamil, hydrochlorothiazide, aspirin, atorvastatin, calcium with vitamin D, nortriptyline, and trazodone until the death of her brother. During a family squabble over the allocation of the brother’s assets, your patient develops chest pain, diaphoresis, and left arm heaviness & numbness. She is admitted to a hospital where workup including cardiac isoenzymes and dobutamine stress test is negative. She is discharged with a diagnosis of Atypical Chest Pain and referred for psychotherapy. Over the next few months, your patient develops poor sleep and low appetite. She can’t concentrate to pay her bills, and stops going to the senior center for aerobics classes. She believes she is dying, fears being alone, and starts relentlessly telephoning you, her therapist and her son. You switch her from nortriptyline to mirtazepine, but she only gets worse. When you see the patient with her son in your office, she is contemplating suicide. Her son asks, “Isn’t there anything you can do to help my mother? ” Since your patient has failed trials of medication & psychotherapy and is suicidal, you refer her to a geriatric psychiatry inpatient unit for electroconvulsive therapy.
Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease

Abstract. Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (≤ 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium‐derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue‐type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post‐load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post‐load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL‐1) levels were above normal. At follow‐up, vWF levels had decreased to 170% (P= 0.01) and TM levels had decreased to 49 ng mL‐1 (P= 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
Risk factors of stillbirths in Victoria (Australia): A case–control study

Stillbirth is one of the most adverse pregnancy outcomes. The rate of stillbirth in high income countries has remained stagnant in recent decades. This study aimed to determine the incidence and risk factors of stillbirths specific to hospital-based deliveries in a secondary level hospital in Melbourne, Australia, over a 5-year period. We conducted a case–control study from January 2007 to December 2011. Univariate and multivariate analyses were conducted in STATA 12.1. The 5-year cumulative incidence of still-birth was 5.3 per 1000 total births (95% CI 4.3, 6.5). Univariate analysis revealed that higher body-mass index, smoking during pregnancy, haemoglobin level (≥14.5 g/dl), previous stillbirth, primiparity, marital status, previous caesarean section and reduced foetal movement in the 2 weeks prior to delivery were associated with increased risk of stillbirth. However, after adjustment for confounders in a multiple-regression model, only previous caesarean section (p = 0.006), unmarried (p = 0.004), high haemoglobin level (p = 0.007) and reduced foetal movement in the 2 weeks prior to delivery (p < 0.001) remained significantly associated with increased risk of stillbirth. The characteristics of our study population was similar to the population of state-wide survey in 2009, however, the incidence in our study was slightly lower. We concluded that previous caesarean section, pregnancy while being unmarried, higher haemoglobin level and reduced foetal movement in the 2 weeks before delivery were significant predictors of stillbirth. The identified risk factors were similar to other studies and the obstetric practice at the hospital or the demographics of the study population did not add to additional risk.
Consumer Attitudes toward Genetically Modified Food in Norway

There is a lack of public acceptance of genetically modified (GM) food products in Europe. Using a dichotomous choice contingent valuation methodology, we find that willingness to accept (WTA) for GM food in Norway is positively affected (i.e. a greater discount is required) by higher levels of self-reported risk perceptions toward GM-food and preferences for domestically produced food. The estimation results show that self-reported knowledge about biotechnology increases WTA while higher levels of formal education decrease the WTA for GM-foods. Also, respondents who have a high level of concern about food safety have a higher WTA for GM food. Further, we estimate mean willingness to accept for GM food products. Our results indicate that our sample on average wants a 47.7% discount on GM bread compared to conventional bread. For GM-salmon a 56.0% discount compared to non-GM salmon is necessary.
Ultrafast Studies of Photochromic Spiropyrans in Solution

The photochromic reaction dynamics of the spiropyran molecule 1',3',3'-trimethyl-6-hydroxyspiro(2H- 1 -benzo- pyran-2,2'-indoline) (HBPS) in solution have been studied with picosecond and femtosecond transient electronic absorption spectroscopy. Following excitation near 300 nm, the C-0 bond of the molecule breaks in less than 100 fs to form a metastable species. A small fraction of this metastable species re-forms the broken C-0 bond on the time scale of 200 fs. The major fraction of the metastable photoproduct vibrationally relaxes in a few picoseconds, and then undergoes isomerization to form a merocyanine product with a decay time constant of about 100 ps, depending on solvent viscosity. This isomerization decay is faster at shorter probe wavelengths and slower at longer wavelengths, indicating that this isomerization gives rise to a red-shifted absorption spectrum. The final merocyanine isomers are stable on the nanosecond time scale. All the results indicate that the initial steps of the photochromic reaction process of HBPS are extremely fast. One of the most important classes of photochromic materials is spiropyran compounds. These compounds have been studied extensively,legO with the nitro derivatives of spirobenzopyran receiving the most attenti~n. '~-~~ Several models have been proposed to explain the properties and photochromic reaction mechanisms of these molecules based on both frequency domain7-'* and time domainIe2* spectroscopic studies. Time-resolved ex- periments have been carried out using techniques such as laser flash photoly~isl~-~~ and time-resolved resonance Raman scat- tering.24. 2s These studies found that the reaction dynamics for spiropyrans with a nitro group are significantly different from those for spiropyrans without a nitro group. A triplet state was found to play an important role in the photochemical reaction process of spiropyrans containing a nitro group, as indicated by the sen- sitivity of the dynamics to the presence of O2.IFz2 For molecules containing no nitro group, the photoreaction was dominated by singlet states. These studies have improved the understanding of the reaction mechanisms of photochromic spiropyrans. Previous studies have also found that the photochromic reaction of spiropyran molecules features the dissociation of a C-O bond, producing a distribution of isomer^. '^-^^ However, the rate and mechanism of the initial reaction steps for these molecules are