Are Preoperative Kattan and Stephenson Nomograms Predicting Biochemical Recurrence after Radical Prostatectomy Applicable in the Chinese Population?

Purpose. Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population. Patients and Methods. A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment. Results. The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71). Conclusions. The incidence of prostate cancer in Hong Kong is increasing together with the patients’ awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well

Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period

__Background:__ The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. __Methods:__ A scoping review was conducted following the methodological framework suggested by Arksey and O'Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors' affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. __Results:__ Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus' origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as

The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis

Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders

Image Texture Characterization Using the Discrete Orthonormal S-Transform

We present a new efficient approach for characterizing image texture based on a recently published discrete, orthonormal space-frequency transform known as the DOST. We develop a frequency-domain implementation of the DOST in two dimensions for the case of dyadic frequency sampling. Then, we describe a rapid and efficient approach to obtain local spatial frequency information for an image and show that this information can be used to characterize the horizontal and vertical frequency patterns in synthetic images. Finally, we demonstrate that DOST components can be combined to obtain a rotationally invariant set of texture features that can accurately classify a series of texture patterns. The DOST provides the computational efficiency and multi-scale information of wavelet transforms, while providing texture features in terms of Fourier frequencies. It outperforms leading wavelet-based texture analysis methods

PIWI Associated siRNAs and piRNAs Specifically Require the Caenorhabditis elegans HEN1 Ortholog henn-1

Small RNAs—including piRNAs, miRNAs, and endogenous siRNAs—bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1, one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA. We show that 26G siR-O7 acts in trans to initiate 22G siRNA formation from the X-cluster. The presence of several mispairs between 26G siR-O7 and the X-cluster mRNA, as well as mutagenesis of the siRNA sensor, indicates that siRNA target recognition is permissive to a degree of mispairing. From a candidate reverse genetic screen, we identified several factors required for 22G siR-1 activity, including the chromatin factors mes-4 and gfl-1, the Argonaute ergo-1, and the 3′ methyltransferase henn-1. Quantitative RT–PCR of small RNAs in a henn-1 mutant and deep sequencing of methylated small RNAs indicate that siRNAs and piRNAs that associate with PIWI clade Argonautes are methylated by HENN-1, while siRNAs and miRNAs that associate with non-PIWI clade Argonautes are not. Thus, PIWI-class Argonaute proteins are specifically adapted to associate with methylated small RNAs in C. elegans

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

Multiple Redox Modes in the Reversible Lithiation of High-Capacity, Peierls-Distorted Vanadium Sulfide.

This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/jacs.5b03395Vanadium sulfide VS4 in the patronite mineral structure is a linear chain compound comprising vanadium atoms coordinated by disulfide anions [S2](2-). (51)V NMR shows that the material, despite having V formally in the d(1) configuration, is diamagnetic, suggesting potential dimerization through metal-metal bonding associated with a Peierls distortion of the linear chains. This is supported by density functional calculations, and is also consistent with the observed alternation in V-V distances of 2.8 and 3.2 Å along the chains. Partial lithiation results in reduction of the disulfide ions to sulfide S(2-), via an internal redox process whereby an electron from V(4+) is transferred to [S2](2-) resulting in oxidation of V(4+) to V(5+) and reduction of the [S2](2-) to S(2-) to form Li3VS4 containing tetrahedral [VS4](3-) anions. On further lithiation this is followed by reduction of the V(5+) in Li3VS4 to form Li3+xVS4 (x = 0.5-1), a mixed valent V(4+)/V(5+) compound. Eventually reduction to Li2S plus elemental V occurs. Despite the complex redox processes involving both the cation and the anion occurring in this material, the system is found to be partially reversible between 0 and 3 V. The unusual redox processes in this system are elucidated using a suite of short-range characterization tools including (51)V nuclear magnetic resonance spectroscopy (NMR), S K-edge X-ray absorption near edge spectroscopy (XANES), and pair distribution function (PDF) analysis of X-ray data.SB acknowledges Schlumberger Stichting Fund and European Research Council (EU ERC) for funding. JC thanks BK21 plus project of Korea. We thank Phoebe Allan and Andrew J. Morris, University of Cambridge, for useful discussions. We also thank Trudy Bolin and Tianpin Wu of Beamline 9-BM, Argonne National Laboratory for help with XANES measurements. The DFT calculations were performed at the UCSB Center for Scientific Computing at UC Santa Barbara, supported by the California Nanosystems Institute (NSF CNS-0960316), Hewlett-Packard, and the Materials Research Laboratory (DMR-1121053). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.</p

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions