Miracle-dz/UniFAR-FTUs huggingface dataset:
4-(4-Bromophenyl)-7,7-dimethyl-2-methylamino-3-nitro-7,8-dihydro-4H-chromen-5(6H)-one including an unknown solvate

In the title compound, C18H19BrN2O4, the chromene unit is not quite planar (r.m.s. deviation = 0.199 Å), with the methyl C atoms lying 0.027 (4) and 1.929 (4) Å from the mean plane of the chromene unit. The six-membered carbocyclic ring of the chromene moiety adopts an envelope conformation, with the dimethyl-substituted C atom as the flap. The methylamine and nitro groups are slightly twisted from the chromene moiety, with C—N—C—O and O—N—C—C torsion angles of 2.7 (4) and −0.4 (4)°, respectively. The dihedral angle between the mean plane of the chromene unit and the benzene ring is 85.61 (13)°. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif, which stabilizes the molecular conformation. In the crystal, molecules are linked via N—H⋯O hydrogen bonds, forming hexagonal rings lying parallel to the ab plane. A region of disordered electron density, most probably disordered ethanol solvent molecules, occupying voids of ca 432 Å3 for an electron count of 158, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148–155]. Their formula mass and unit-cell characteristics were not taken into account during refinement.
Serological & virological investigation of an outbreak of dengue fever in Gwalior, India.

BACKGROUND & OBJECTIVES An outbreak of febrile illness occurred between September to November 2001 in Gwalior, Madhya Pradesh affecting individuals mostly in the age group < 30 yr. A total of 312 febrile indoor patients suspected to have dengue infection were investigated. METHODS The investigation included examination of blood samples from patients for dengue specific IgM and IgG antibodies, isolation of virus in suckling mouse pups and in C(6/36) cell line followed by confirmation and typing through reverse transcriptase-PCR and nested PCR. RESULTS The serological analysis of the 312 samples indicated 65 per cent positivity of which 21 per cent are of recent infection as indicated by the presence of IgM antibody and 78 per cent are found to be secondary in nature by showing the presence of IgG and/or IgM antibodies. The RT-PCR analysis of patients' sera employing dengue virus group specific conserved amplimer confirmed the etiological agent as dengue complex by showing the characteristic 511 bp amplicons. None of the antibody positive samples were found to be positive by RT-PCR. A total of 13 (6%) samples positive by RT-PCR, were processed for virus isolation in mouse pups and in C(6/36) cells. Of these 9 samples (80%) were confirmed positive for virus isolation as identified by RT-PCR. INTERPRETATION & CONCLUSION The typing of isolates by nested PCR employing serotype specific amplimer revealed 119 bp amplicon characteristic of dengue virus type-2 and thus confirming the outbreak attributed to dengue virus type-2.
Multicenter Evaluation of a Semiautomated, Standardized Assay for Detection of Hepatitis B Virus DNA in Blood Donations

ABSTRACT We evaluated the COBAS Ampliscreen hepatitis B virus (HBV) test using standards, seroconversion panels, consecutive donations, and samples from patients with abnormal alanine aminotransferase and chronic hepatitis C. Specificity was 100% and sensitivity was 20 IU/ml. In seroconversion panels, HBV DNA was detected up to 4 to 18 days before HBsAg, suggesting that this assay is useful in shortening the infectious window phase.
Numerical simulation of heavy rainfall in August 2014 over Japan under Pseudo Global Warming Conditions

Climate change as a consequence of global warming may enhance severe precipitation events. This study investigated the impact of global warming on summertime heavy rainfall using the Weather Research and Forecasting model with the pseudo global warming (PGW) method. WRF simulations were conducted for August 2014 over a domain covering Japan, in which two big typhoons attacked Japan and rain fronts frequently passed over, in a baseline and two PGW (RCP4.5 and RCP8.5) conditions. The analysis showed that the future climate led to a larger amount of precipitation than the past climate during the study period in Japan. The mean increase rate of upward moisture supply from the surface of the entire modelling domain was 2.8% K−1 in RCP4.5 condition and 3.3% K−1 RCP8.5 condition. The mean increase rate of 2-m specific humidity was 6.7% K−1 in both RCP4.5 and RCP8.5 conditions, which is comparable to the Clausius-Clapeyron relationship. Therefore, the water supply from the lateral boundaries contributed to the increase in humidity largely and precipitation subsequently. The increases in precipitation related to typhoons were larger than rain fronts, in particular, the changes were remarkable over the paths of typhoons. These results show global warming will significantly increase the summertime heavy precipitation over Japan in the future.
Advances on molecular studies of the interaction soybean - Asian rust

Effective management practices are essential for controlling rust outbreaks. The main control method used is the application of fungicides, which increases substantially the cost of production and is harmful to the environment. Prevention is still the best way to avoid more significant losses in soybean yields. Alternatives, such as planting resistant varieties to the fungus, are also important. The use of resistant or tolerant varieties is the most promising method for controlling Asian soybean rust. Recently, five dominant genes resistant to soybean rust were described: Rpp1, Rpp2, Rpp3, Rpp4 and Rpp5. However, little is known about the molecular interaction among soybean plant and soybean rust and on the molecular pathway triggered by pathogen recognition. Understanding the molecular mechanisms involved in defense responses is of primary importance for planning strategies to control stress and, consequently, to increase plant adaptation to limiting conditions.
The nature of Hβ+[O III] and [O II] emitters to z ∼ 5 with HiZELS: stellar mass functions and the evolution of EWs

We investigate the properties of ∼7000 narrow-band selected galaxies with strong Hβ+[O III] and [O II] nebular emission lines from the High-z Emission-Line Survey between z ∼ 0.8 and 5.0. Our sample covers a wide range in stellar mass (M_(stellar) ∼ 10^(7.5–12.0) M_⊙), rest-frame equivalent widths (EW_(rest) ∼10–10^5 A), and line luminosities (L_(line) ∼ 10^(40.5–43.2) erg s^(−1)). We measure the Hβ+[O III]-selected stellar mass functions out to z ∼ 3.5 and find that both M_⋆ and ϕ_⋆ increases with cosmic time. The [O II]-selected stellar mass functions show a constant M_⋆ ≈ 10^(11.6) M_⊙ and a strong, increasing evolution with cosmic time in ϕ_⋆ in line with Hα studies. We also investigate the evolution of the EW_(rest) as a function of redshift with a fixed mass range (10^(9.5–10.0) M_⊙) and find an increasing trend best represented by (1 + z)^(3.81 ± 0.14) and (1 + z)^(2.72 ± 0.19) up to z ∼ 2 and ∼3 for Hβ+[O III] and [O II] emitters, respectively. This is the first time that the EW_(rest) evolution has been directly measured for Hβ+[O III] and [O II] emitters up to these redshifts. There is evidence for a slower evolution for z > 2 in the Hβ+[O III] EW_(rest) and a decreasing trend for z > 3 in the [O II] EW_(rest) evolution, which would imply low [O II] EW at the highest redshifts and higher [O III]/[O II] line ratios. This suggests that the ionization parameter at higher redshift may be significantly higher than the local Universe. Our results set the stage for future near-IR space-based spectroscopic surveys to test our extrapolated predictions and also produce z > 5 measurements to constrain the high-z end of the EW_(rest) and [O III]/[O II] evolution.
Noradrenaline enhances angiotensin II responses via p38 MAPK activation after hypoxia/re‐oxygenation in renal interlobar arteries

Hypoxia and sympathetic activation are main factors in the pathogenesis of acute kidney injury (AKI). We tested the hypothesis that noradrenaline (NE) in combination with hypoxia aggravates the vasoreactivity of renal arteries after hypoxia/re‐oxygenation (H/R). We tested the role of adrenergic receptors and p38 MAPK using an in vitro H/R protocol.
Apolipoprotein E (ApoE), a Bmp‐2 (bone morphogenetic protein) upregulated gene in mesenchymal progenitors (C3H10T1/2), is highly expressed in murine embryonic development

Apolipoprotein E (ApoE) was identified as upregulated by Bmp‐2 (bone morphogenetic protein‐2) in the murine mesenchymal progenitor cell line C3H10T1/2 by a subtractive cloning strategy. Expression of recombinant Bmps in mesenchymal C3H10T1/2 progenitors results in the differentiation into the osteogenic, the chondrogenic, and the adipogenic lineage. In addition, ApoE is also expressed in primary osteoblasts isolated from murine calvariae late in the in vitro osteoblast developmental sequence. To infer possible roles of ApoE in organogenesis and tissue differentiation, ApoE expression during mouse embryonic development was analyzed in murine midgestation and late embryonic development by in situ hybridization. ApoE is highly expressed at many sites of organ development (liver, brain, heart, eye, lung), probably in a subset of neural crest cells and ectodermal derivatives suggestive for important functions of ApoE during embryonic differentiation and organ development.
Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.
American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: Executive Summary of recommendations

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients

BACKGROUND: Although the pathogenic mechanisms of selective loss of motor neurons in amyotrophic lateral sclerosis (ALS) are unknown, there is increasing evidence for the hypothesis of an oxidative stress-related mitochondrial involvement as key determinant of motor neuron degeneration OBJECTIVE: The aim of our study has been to assess blood levels of peroxidation markers and to relate them to in-vivo oxidative metabolism in exercising muscle in patients affected by ALS. METHOD: For this purpose 10 patients (seven men and three women, mean age 58.5 - 8.2 SD), performed an incremental bicycling test for the assessment of lipoperoxides and lactate during exercise. RESULTS: At rest, the ALS patients had higher than normal levels of both lactate (2.82 - 0.76 mmol/L; normal range: 0.67-2.47 mmol/L) and lipoperoxides (361.7 - 40.2 AU; normal range: 250-320 AU), the latter corresponding to a level of moderate oxidative stress. A further increment during exercise was observed both at lactate threshold and maximal power output levels. Values of blood lipoperoxides were significantly higher ( P < 0.05) than those in control patients affected by chronic motor denervating processes of different origins and related ( P < 0.01) to lactate production on exercising. CONCLUSIONS: These findings indicate the occurrence of an abnormally increased size of blood free radical pool in resting conditions and during exercise in ALS patients. The relationship between the levels of reactive oxygen species and lactate production is indicative of a tight link between mitochondrial function and oxidative stress in ALS.
The Crucifaction Operation for Male Incontinence

Two other centres where perineal surgery is practised extensively have been developing yet another approach to this problem. Puigvert in Barcelona and Kauffman in Los Angeles have developed almost identical operations and both have recently introduced modifications, based on anatomical reasoning, that are also almost identical. Kauffman demonstrated the crucifaction operation at St Peter's Hospital in 1968, and Puigvert deEcribed his operation in 1970.
The Change in Cervical Length Over Time as a Predictor of Preterm Delivery in Asymptomatic Women With Twin Pregnancies Who Have a Normal Mid-Trimester Cervical Length

Aim: To determine whether or not the change in cervical length (CL) over time is valuable in predicting spontaneous preterm delivery (SPTD) in asymptomatic twin pregnancies with a normal mid-trimester CL (>25 mm). Methods: This was a prospective study including 190 consecutive asymptomatic twin gestations with a CL > 25 mm at 20–24 weeks. The women underwent an initial CL measurement at the time of routine ultrasound examination between 20 and 24 weeks’ gestation, followed 4–5 weeks later by a repeat CL measurement. The primary outcome measure was SPTD at <32 completed weeks’ gestation. Multicollinearity was a concern in the multivariable model since change in CL and follow-up CL were highly correlated. Results: The rate of SPTD at <32 weeks was 4.2%. Multiple logistic regression analyses demonstrated that the change in CL and the follow-up CL were significantly associated with SPTD before 32 weeks after adjusting for baseline covariate such as in vitro fertilization. The best cut-off values for the prediction of SPTD at <32 weeks’ gestation were 13% for the change in CL with a sensitivity of 87.5% and a specificity of 63.2%. There was no significant difference in the area under the receiver operating characteristic curves between the change in CL and the follow-up CL. Conclusions: A greater change in CL is a good predictor of SPTD in asymptomatic twin pregnancies with a normal mid-trimester CL. However, the change in CL cannot provide data beyond the follow-up CL. In the setting of a normal mid-trimester CL, a follow-up CL measurement should be considered in asymptomatic twin pregnancies.
Mutation of amino acids within the gibbon ape leukemia virus (GALV) receptor differentially affects feline leukemia virus subgroup B, simian sarcoma-associated virus, and GALV infections

The three type C retroviruses, gibbon ape leukemia virus (GALV), simian sarcoma-associated virus (SSAV), and feline leukemia virus subgroup B (FeLV-B), infect human cells by interacting with the same cell surface receptor, GLVR1. Using LacZ retroviral pseudotypes and murine cells transfected with mutant GLVR1 expression vectors, we show that the same 9-amino-acid region of human GLVR1 is critical for infection by the three viruses. Rat cells were not susceptible to infection by LacZ (FeLV-B) pseudotypes because of a block at the receptor level. We found multiple amino acid differences from human GLVR1 in the 9-amino-acid critical region of rat GLVR1. Expression of a human-rat chimeric GLVR1 in murine cells demonstrated that rat GLVR1 could function as a receptor for GALV and SSAV but not for FeLV-B. Substitution of human GLVR1 amino acids in the critical region of rat GLVR1 identified three amino acids as responsible for resistance to FeLV-B infection; two of these affect SSAV infection, but none affects GALV infection.
Attributing Responsibility: Hospitals Account for 20% of Variance in Acute Myocardial Infarction Patient Mortality

Abstract:Applying a log-logistic accelerated failure time mixed effects model to a sample of 95,504 in-hospital patients with acute myocardial infarction (AMI) between 2005 and 2010 in the United States, we measured the relative contribution of hospitals (vs. patients) in explaining in-hospital AMI mortality. Before adjusting for age, race, income, 29 comorbidities of AMI patients, and primary payer, hospital characteristics explained 19.93% of the variance in AMI in-hospital mortality. After controlling for these, variance explained declined by 5.65%, to 14.28%. These findings have implications for policymakers in assessing hospitals' “responsibility” for AMI patient mortality, for hospitals in allocating resources toward improving AMI patient care, and for medical intermediaries in making liability judgments and payment allocations to hospitals.
Effect of formulation factors on in vitro transcorneal permeation of voriconazole from aqueous drops

The purpose of this research was to evaluate the effect the formulation factors on in vitro permeation of voriconazole through freshly isolated goat and sheep corneas. An increase in the pH of the drops from 4.0 to 8.0 resulted in significant (P < 0.05) increase drug permeation. Raising concentration of the drops from 0.05% to 0.2% (w/v) significantly, (P < 0.05) increased drug permeation, but decreased the percent permeation. Corneal transport of voriconazole is both pH and concentration dependent. Eye drops containing disodium edetate (ethylenediaminetetraacetic acid) alone or combination with benzalkonium chloride showed significantly (P < 0.05) higher permeation as compared with control formulation. Addition of beta-cyclodextrin to the formulation enhanced corneal permeation of voriconazole. Compared with control formulation, voriconazole 0.2% (w/v) drop containing viscosity modifier produced significant (P < 0.05) decrease in permeation. Most of the formulations showed higher zone of inhibition against Candida albicans.
CLINICAL ASPECTS AND MANAGEMENT OF MYOTONIC DYSTROPHIES

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert’s disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment.
Signal Transduction Identi fi cation of mTORC 2 as a Necessary Component of HRG / ErbB 2-Dependent Cellular Transformation

Overexpression of the receptor tyrosine kinase HER2/ErbB2 (ERBB2) has been linked to a poor prognosis for patients with breast cancer; thus, its activity is a central target for cancer therapy. Likewise, overexpression of heregulin (HRG/NRG1), a growth factor responsible for ErbB2 activation, has also been shown to be a driver of breast cancer progression. Although ErbB2 inhibitors offer a major advancement in the treatment of ErbB2dependent breast cancers, patients are highly susceptible to developing clinical resistance to these drugs. Therefore, a detailed understanding of themolecular mechanism that underlies HRG/ErbB2-induced tumorigenesis is essential for the development of effective therapeutic strategies for this subset of patients with breast cancer. Here, it was demonstrated thatHRGpromoted anchorage-independent breast cancer cell growthmore potently than EGF, and that the HRG-dependent activation of phosphoinositide 3-kinase and mTORC1 are necessary events for cell transformation. Functional evaluation of two distinct mTOR (MTOR) inhibitors, rapamycin and INK-128, on HRG-dependent signaling activities, uncovered a necessary role formTORC2 in the regulation of the AKT/TSC2/ mTORC1 axis by affecting the phosphorylation of AKT at the PDK1(PDPK1)-dependent site (T308) as well as at themTORC2-dependent site (S473). The elimination of Rictor (RICTOR), a critical component of mTORC2, is detrimental to both the activation of mTORC1 and HRG-mediated cellular transformation. Similar results were obtained in multiple breast cancer model systems, highlighting an important role for mTORC2 in HRG/ErbB2dependent breast cancer. Implications:These findings suggest the potential benefits of targeting mTORC2 inHRG/ErbB2-induced breast cancer. Mol Cancer Res; 12(6); 940–52. 2014 AACR.