Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostate cancer: feasibility and preliminary experience of a diffusional kurtosis model for detection and assessment of aggressiveness of peripheral zone cancer.

PURPOSE To assess the feasibility of diffusional kurtosis (DK) imaging for distinguishing benign from malignant regions, as well as low- from high-grade malignant regions, within the peripheral zone (PZ) of the prostate in comparison with standard diffusion-weighted (DW) imaging. MATERIALS AND METHODS The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Forty-seven patients with prostate cancer underwent 3-T magnetic resonance imaging by using a pelvic phased-array coil and DW imaging (maximum b value, 2000 sec/mm2). Parametric maps were obtained for apparent diffusion coefficient (ADC); the metric DK (K), which represents non-Gaussian diffusion behavior; and corrected diffusion (D) that accounts for this non-Gaussianity. Two radiologists reviewed these maps and measured ADC, D, and K in sextants positive for cancer at biopsy. Data were analyzed by using mixed-model analysis of variance and receiver operating characteristic curves. RESULTS Seventy sextants exhibited a Gleason score of 6; 51 exhibited a Gleason score of 7 or 8. K was significantly greater in cancerous sextants than in benign PZ (0.96±0.24 vs 0.57±0.07, P<.001), as well as in cancerous sextants with higher rather than lower Gleason score (1.05±0.26 vs 0.89±0.20, P<.001). K showed significantly greater sensitivity for differentiating cancerous sextants from benign PZ than ADC or D (93.3% vs 78.5% and 83.5%, respectively; P<.001), with equal specificity (95.7%, P>.99). K exhibited significantly greater sensitivity for differentiating sextants with low- and high-grade cancer than ADC or D (68.6% vs 51.0% and 49.0%, respectively; P≤.004) but with decreased specificity (70.0% vs 81.4% and 82.9%, respectively; P≤.023). K had significantly greater area under the curve for differentiating sextants with low- and high-grade cancer than ADC (0.70 vs 0.62, P=.010). Relative contrast between cancerous sextants and benign PZ was significantly greater for D or K than ADC (0.25±0.14 and 0.24±0.13, respectively, vs 0.18±0.10; P<.001). CONCLUSION Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment.
Evaluation of the Hodge Test and the Imipenem-EDTA Double-Disk Synergy Test for Differentiating Metallo-β-Lactamase-Producing Isolates of Pseudomonas spp. and Acinetobacter spp

ABSTRACT Gram-negative bacilli with acquired metallo-β-lactamase (MBL) production have been increasingly reported in some countries, necessitating their detection. The aim of this study was to evaluate the performance of the Hodge test and those of the imipenem (IPM)-EDTA, ceftazidime (CAZ)-mercaptopropionic acid (MPA), and CAZ-sodium mercaptoacetic acid (SMA) double-disk synergy tests (DDSTs). The efficiencies of testing CAZ-resistant and IPM-nonsusceptible isolates were also compared. Strains used for the evaluation were known IMP-1 and VIM-2 MBL-producing isolates and consecutive and CAZ-nonsusceptible isolates of pseudomonads and acinetobacters. The performance of the Hodge test was improved by addition of zinc sulfate (140 μg/disk) to an IPM disk. In DDSTs, EDTA (ca. 1,900 μg) disks were better at detecting MBL-producing strains among pseudomonads, while MPA (3 μl) and SMA (3 mg) disks performed better for acinetobacters. EDTA (ca. 750 μg)-plus-SMA (ca. 2 mg) disks performed better than EDTA, MPA, or SMA disks with both organisms. CAZ-SMA DDSTs failed to detect 22 of 80 (28%) MBL-producing acinetobacters. In conclusion, use of an IPM disk and an EDTA (750 μg)-plus-SMA (2 mg) disk improves performance, and testing IPM-nonsusceptible isolates rather than CAZ-resistant isolates could reduce screening work. Further evaluation of the test is required for the detection of other types of MBL-producing gram-negative bacilli.
Ferric α-Hydroxyheme Bound to Heme Oxygenase Can Be Converted to Verdoheme by Dioxygen in the Absence of Added Reducing Equivalents*

Whether or not reducing equivalents are indispensable for the conversion of ferric α-hydroxyheme bound to heme oxygenase-1 to verdoheme remains controversial (Matera, K. M., Takahashi, S., Fujii, H., Zhou, H., Ishikawa, K., Yoshimura, T., Rousseau, D. L., Yoshida, T., and Ikeda-Saito, M. (1996)J. Biol. Chem. 271, 6618–6624; Liu, Y. , Moënne-Loccoz, P., Loehr, T. M. , and Ortiz de Montellano, P. R. (1997) J. Biol. Chem. 272, 6906–6917). To resolve this controversy, we have prepared a ferric α-hydroxyheme-heme oxygenase-1 complex and titrated the complex with O2 under strictly anaerobic conditions. The formation of verdoheme was monitored by optical and electron spin resonance spectroscopies. Electron spin resonance spectra of the complex showed that α-hydroxyheme exists as a mixture of resonance structures composed of the iron(III) porphyrin and the iron(II) porphyrin π neutral radical. Upon addition of CO the latter species becomes dominant. The results obtained from these titration experiments indicate that α-hydroxyheme can be converted to verdoheme by an approximately equimolar amount of O2 without any requirement for exogenous electrons. The verdoheme formed from α-hydroxyheme was shown to be in the ferrous oxidation state by the addition of CO or potassium ferricyanide to the resultant verdoheme-heme oxygenase-1 complex.
Full-length transcriptome sequences and splice variants obtained by a combination of sequencing platforms applied to different root tissues of Salvia miltiorrhiza and tanshinone biosynthesis.

Danshen, Salvia miltiorrhiza Bunge, is one of the most widely used herbs in traditional Chinese medicine, wherein its rhizome/roots are particularly valued. The corresponding bioactive components include the tanshinone diterpenoids, the biosynthesis of which is a subject of considerable interest. Previous investigations of the S. miltiorrhiza transcriptome have relied on short-read next-generation sequencing (NGS) technology, and the vast majority of the resulting isotigs do not represent full-length cDNA sequences. Moreover, these efforts have been targeted at either whole plants or hairy root cultures. Here, we demonstrate that the tanshinone pigments are produced and accumulate in the root periderm, and apply a combination of NGS and single-molecule real-time (SMRT) sequencing to various root tissues, particularly including the periderm, to provide a more complete view of the S. miltiorrhiza transcriptome, with further insight into tanshinone biosynthesis as well. In addition, the use of SMRT long-read sequencing offered the ability to examine alternative splicing, which was found to occur in approximately 40% of the detected gene loci, including several involved in isoprenoid/terpenoid metabolism.
Differences in the Extent of Primary Ischemic Damage between Middle Cerebral Artery Coagulation and Intraluminal Occlusion Models

The authors studied the differences between heat-shock/stress protein 70 (hsp70) gene expression and protein synthesis in the unilateral middle cerebral artery (MCA) microsurgical direct occlusion (Tamura's) model and the unilateral intraluminal occlusion model. In Tamura's model, expression of hsp70 mRNA and HSP70 protein and decreased protein synthesis were detected in the ischemic areas, including the ipsilateral cortex and caudate. These phenomena, however, were not observed in the areas outside the MCA territory, including the ipsilateral thalamus, hippocampus, and substantia nigra. These results were consistent among the experimental rats. In the intraluminal occlusion model, however, induction of both hsp70 mRNA and HSP70 protein and impairment of protein synthesis were noted in the areas outside the MCA territory, including the ipsilateral thalamus, hypothalamus, hippocampus, and substantia nigra, as well as in the MCA territory, including the ipsilateral cortex and caudate. These results were not consistent among the experimental rats. These different results might be due to widespread damage resulting from internal carotid artery (ICA) occlusion in the intraluminal occlusion model. Accordingly, the authors suggest that this model be called an ICA occlusion model, rather than a pure MCA occlusion model.
Gray matter involvement in patients with multiple sclerosis as shown by magnetic resonance imaging.

OBJECTIVE To summarize the main findings seen on conventional and advanced magnetic resonance imaging (MRI) used to assess gray matter (GM) involvement in patients with multiple sclerosis (MS). DATA SOURCES The data used in this review were obtained mainly from studies reported in the PubMed database using the terms of multiple sclerosis, gray matter, magnetic resonance imaging. STUDY SELECTION Relevant literatures on studies of GM involvement in MS patients were identified, retrieved and reviewed. RESULTS MS is the most common chronic, disabling central nervous system disease in young adults. Although traditional thinking has considered MS to be a chronic inflammatory demyelinating condition affecting solely the white matter (WM) of the central nervous system, over the last few years it has been shown that GM pathology is also common and extensive. GM demyelinating lesions can not only be found in the cerebral cortex but also in the deep gray nuclei. Apart from focal demyelinated lesions, diffuse neuronal loss and atrophy is also present in the GM of MS patients. CONCLUSIONS The widespread use of conventional and quantitative MRI based techniques in MS has led to an improved understanding of the mechanisms underlying the inflammatory and neurodegenerative processes of the disease. However, more researches are needed to unravel GM pathology in MS patients, which at present remains enigmatic.
Donation intentions for cancer genetics research among African Americans.

AIMS Scientific agencies rely on individuals to donate their DNA to support research on chronic conditions that disproportionately affect African Americans; however, donation is variable in this population. The purpose of this study was to identify sociodemographic characteristics, health care variables, and cultural values having significant independent associations with intentions to donate blood or saliva samples for cancer genetics research among African American adults. METHOD Cross-sectional survey of donation intentions. RESULTS The majority of respondents (73%) were willing to donate a biological sample for cancer genetics research. The results of the multivariate regression model found that respondents who received care at a facility other than a doctor's office (e.g., community center) were about five times more likely to be willing to donate a sample for cancer genetics research (odds ratio [OR]=5.28, 95% confidence interval [CI]=1.16-24.12, p=0.03); whereas, greater levels of religiosity (OR=0.09, 95% CI=0.01-0.75, p=0.02) and present temporal orientation (OR=0.23, 95% CI=0.06-0.79, p=0.02) were associated with a lower likelihood of donating a sample. CONCLUSION Efforts to enhance donation of biological samples for cancer genetics research may need to target diverse clinical sites for recruitment. Additionally, recruitment materials may need to address cultural values related to religiosity and present temporal orientation.
Quantitative Mapping of Reversible Mitochondrial Complex I Cysteine Oxidation in a Parkinson Disease Mouse Model*

Differential cysteine oxidation within mitochondrial Complex I has been quantified in an in vivo oxidative stress model of Parkinson disease. We developed a strategy that incorporates rapid and efficient immunoaffinity purification of Complex I followed by differential alkylation and quantitative detection using sensitive mass spectrometry techniques. This method allowed us to quantify the reversible cysteine oxidation status of 34 distinct cysteine residues out of a total 130 present in murine Complex I. Six Complex I cysteine residues were found to display an increase in oxidation relative to controls in brains from mice undergoing in vivo glutathione depletion. Three of these residues were found to reside within iron-sulfur clusters of Complex I, suggesting that their redox state may affect electron transport function.
Pharmacokinetics and first-pass elimination of metoprolol in rats: contribution of intestinal first-pass extraction to low bioavailability of metoprolol

The pharmacokinetics of metoprolol after intravenous (IV) (0.5, 1, and 2 mg/kg) and oral (1, 2, and 5 mg/kg) administration, and the intestinal and hepatic first-pass extraction of metoprolol after IV, intraportal, and intraduodenal (1 and 2 mg/kg) administration were comprehensively assessed in rats. Metoprolol exhibited dose-independent pharmacokinetics after IV administration, and dose-dependent pharmacokinetics after oral administration probably due to the saturable first-pass extraction of metoprolol. At doses where metoprolol exhibited dose-independent pharmacokinetics (1 and 2 mg/kg), complete absorption (>99.2%) and low F (<0.245) after oral administration were observed. The intestinal and hepatic first-pass extraction ratio (EG and EH, respectively) of metoprolol were approximately 0.45 and 0.60, respectively (equivalent to approximately 45% and 30% of orally administered dose, respectively), suggesting considerable contribution of intestinal first-pass extraction to the low F of metoprolol in rats. The EG in rats was predicted from in vitro clearance and/or permeability data utilizing the QGut model and well-stirred model (0.347 and 0.626, respectively). The predicted EG values were in good agreement with the observed in vivo EG (0.492–0.443), suggesting the utility of the prediction of in vivo intestinal first-pass extraction from the in vitro clearance using intestinal microsomes.
Facile Preparation of Doxorubicin‐Loaded Upconversion@Polydopamine Nanoplatforms for Simultaneous In Vivo Multimodality Imaging and Chemophotothermal Synergistic Therapy

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T 1‐weighted magnetic resonance imaging (MRI), X‐ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA5‐PEG‐DOX). For generating the UCNP@PDA5‐PEG‐DOX, a near‐infrared light (NIR)‐absorbing polydopamine (PDA) shell is directly coated on oleic‐acid‐capped β‐NaGdF4:Yb3+,Er3+@β‐NaGdF4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core–shell‐structured nanosphere via water‐in‐oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA5‐PEG‐DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse‐bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA5‐PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR‐absorbing polymers, important for developing multi‐mode nanoprobes for biomedical applications.
Evidence based public health policy and practice-Putting public health evidence into practice: Increasing the prevalence of working smoke alarms in disadvantaged inner city housing

Study objectives: The UK government recommends that local authorities install battery operated smoke alarms to prevent fire related injury. However, a randomised controlled trial of smoke alarm installation in local authority housing found a low level of working alarms at follow up. Qualitative work, which accompanied the trial explored barriers and levers to the use of this public health intervention. Design: Semi-structured group and individual interviews were conducted with a sample of the adult participants in a randomised controlled trial of free smoke alarm installation. Group interviews and ’’draw and write’’ exercises were conducted with children at a local primary school. Participants: A sample of trial participants and primary school children in the trial neighbourhood. Setting: An inner city housing estate in central London. Main results: The main barrier to smoke alarm use was the distress caused by false alarms. Although trial participants considered themselves to be at high risk for fires and would recommend smoke alarms to others, respondents’ reports on the distress caused by false alarms suggest that people balance immediate and longer term risks to their health and wellbeing when they disable alarms. Conclusions: This study identified some of the reasons for the low level of functioning smoke alarms, and problems experienced with alarms. The results have implications for the implementation of this public health intervention. The effectiveness of smoke alarm installation could be improved if alarm manufacturers and those responsible for implementation programmes considered ways of tackling the issues raised in this study.
Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction

Background Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium.
Factors Which Affect Mortality and Admission to Intensive Care in Penetrating Thorax and Abdominal Injuries

The purpose of this study is to examine the relationship between mortality and stay times in intensive care and hematocrit value as of the time of application with trauma scores and hemodynamic measurements in patients with thorax and abdominal injuries due to stab wounds in the intensive care unit. Sosyodemographic data, vital signs, blood parameters, characteristics of injuries recorded and GCS, RTS, PATI, ISS, shock index were calculated for each patient from hospital records. 661 patients included to the study. 342 patients (51.7%) were identified with only thoracic, 224 (33.9%) with only abdominal and 95 (14.4%) with both thoracic and abdominal injuries. 14 (2.1%) of the patients who applied to the emergency service were mortal, 255 (38.6%) were admitted in intensive care for observation. In the multiariate regression analyses made to determine if age, operation, shock index, systolic blood pressure, pulse, respiratory rate, first hematocrit, GCS, ISS, RTS, PATI and blood transfusion were independent indicators for mortality and admission in intensive care, none of these parameters were identified as an independent variable for mortality. In conclusion shock index, pulse, systolic blood pressure, ISS and first hematocrit values demonstrated differences in both mortal patients and patients admitted in intensive care, no independent variable was identified for mortality.
Editing tools for 3D medical imaging

A set of tools called MPR Edit (multiplanar reconstruction editor) is presented. Designed like a paint and drawing program for 3-D data sets, MPR Edit allows the interactive creation of shapes that define volumes of interest in images of medical data. The implementation of MPR Edit is described, and examples of its use are given. Clinical applications are discussed. <<ETX>>
Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers. Results from the Copenhagen High-Risk Study.

OBJECTIVES To perform a long-term prospective follow-up of children at high risk for schizophrenia to identify risk factors for the development of this disorder. DESIGN Prospective follow-up population study of children of schizophrenic mothers and their matched controls from age 15 years to age 42 years, with multiple diagnostic assessments performed by senior clinicians using structured interviews blindly with respect to the group membership of the subject. PARTICIPANTS Two hundred seven offspring of schizophrenic mothers and 104 control children without schizophrenic parents matched to the index group on age, sex, paternal socioeconomic status, urban/rural residence, and the amount of time spent during childhood in institutional rearing. MAIN OUTCOME MEASURE The prevalence of the DSM-III-R disorders during the subjects lifetime. RESULTS A significant aggregation of schizophrenia (16.2%) and other nonaffective, nonorganic psychosis (4.6%), and Cluster A personality disorders (21.3%) occurred among the offspring of schizophrenic mothers compared with the controls (1.9%, 0.9%, and 5%, respectively). No evidence of increased aggregation of (psychotic and nonpsychotic) affective disorders was noted among the offspring of schizophrenics. CONCLUSION These results coincide with the results of other family studies in demonstrating a significant and specific familial aggregation of schizophrenia and nonpsychotic schizophrenia spectrum disorders among the biological relatives of schizophrenics.
Mitogenomics phylogenetic relationships of the current sloth’s genera and species (Bradypodidae and Megalonychidae)

Abstract We sequenced the complete mitogenome of 39 sloths (19 Bradypus variegatus, 4 B. tridactylus, 1 B. pygmaeus, 1 B. torquatus, 4 Choloepus didactylus, and 10 C. hoffmanni). A Bayesian tree (BI) indicated a temporal split between Bradypus and Choloepus around 31 million years ago (MYA, Oligocene) and the other major splits within each genera during the Miocene and Pliocene. A haplotype network (MJN) estimated a lower temporal split between the sloth genera (around 23.5 MYA). Both methods detected the ancestor of B. torquatus as the first to diverge within Bradypus (21 for BI and 19 MJN), followed by that of the ancestor of B. tridactylus. The split of B. pygmaeus from the common ancestor with B. variegatus was around 12 MYA (BI) or 4.3 MYA (MJN). The splits among the previous populations of B. variegatus began around 8 MYA (BI) or 3.6 MYA (MJN). The trans-Andean population was the first to diverge from the remaining cis-Andean populations of B. variegatus. The genetic differentiation of the trans-Andean B. variegatus population relative to the cis-Andean B. variegatus is similar to that found for different species of sloths. The mitogenomic analysis resolved the differentiation of C. hoffmanni from the C. didactylus individuals of the Guiana Shield. However, one C. didactylus from the Colombian Amazon specimen was inside the C. hoffmanni clade. This could be the first example of possible natural hybridization in the Amazon of both Choloepus taxa or the existence of un-differentiable phenotypes of these two species in some Amazonian areas.
Purification and quantification of lactoferrin in equine seminal plasma.

Lactoferrin with a molecular mass of 80 kDa was purified from equine seminal plasma by heparin-Agarose affinity chromatography and Sephacryl S-200 gel filtration. Purified lactoferrin was found to be highly homogeneous on the bases of its migration as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and of the monospecificity of rabbit antibodies to the purified protein in immunoblotting of seminal plasma proteins. A sandwich enzyme-linked immunosorbent assay was developed for quantifying lactoferrin in equine seminal plasma. Seminal plasma lactoferrin concentrations in 23 normal stallions ranged from 42 to 453 microg/ml, with a mean value of 157 +/- 118 microg/ml (S.D.).