nan The progressive development of microfabrics from initial deposition to slump deformation: an example from a modern sedimenary melange on the Nankai Prism By jgs.lyellcollection.org Published On :: 2020-05-04T02:10:48-07:00 The progressive development of microfabrics from initial deposition to slump deformation and then a submarine slide was investigated in an active subduction zone using cores recovered during the Integrated Ocean Drilling Program Expedition 333. A Pleistocene–Holocene sequence was recovered at Site C0018A, which was located on a slope basin on the footwall of the megasplay fault in the Nankai Trough, SW Japan. Six mass-transport deposit units intercalated with coherent intervals were recovered from the upper 190 m of the drilled succession. The initial microfabrics in the undeformed hemipelagic sediments were characterized by random and porous fabrics composed predominantly of clay aggregations and connectors. The initial fabrics were cardhouse fabrics, which consist of clay flakes with edge-to-edge (E–E) and/or edge-to-face (E–F) contacts. These initial microfabrics developed into compacted microfabrics, which are random and consolidated fabrics (bookhouse fabrics) that consist of clay flakes with E–F and/or face-to-face (F–F) contacts and develop during burial as a pure shear deformation. During slumping, these fabrics were then deformed under simple shear to become predominantly F–F contacts and form clay chains. Thus, the microfabrics in these submarine slides are a sedimentary mélange that developed locally into a preferred clay orientation with F–F contacts. Supplementary material: A schematic illustration showing sedimentation processes and fabrics is available at https://doi.org/10.6084/m9.figshare.c.4483385 Thematic collection: This article is part of the Polygenetic mélanges collection available at: https://www.lyellcollection.org/cc/polygenetic-melanges Full Article
nan Rituximab, MS, and pregnancy By nn.neurology.org Published On :: 2020-05-01T12:45:10-07:00 Objective To describe the safety and efficacy of rituximab (RTX) in MS and pregnancy, we conducted a retrospective cohort study of 74 pregnancies among 55 women treated with RTX for MS and their offspring. Methods We used prospectively collected information from the electronic health record at Kaiser Permanente Southern California between 2012 and 2019 of mother and baby to identify treatment history, pregnancy outcomes, and relapses. Results Last RTX exposure before conception occurred between 1.8 and 5.2 months in 32 (49%) of 65 pregnancies and accidentally during the first trimester in 9 (12%). Among 38 live births, adverse pregnancy outcomes were as follows: 3 preterm deliveries (including 1 set of twins), 1 neonatal death (preterm twin), and 1 perinatal stroke (full-term). No stillbirths, chorioamnionitis, or major malformations were found. Fifteen (27%) women had at least one first-trimester miscarriage, of whom 8 (53%) had a history of infertility. Cumulative dose or timing of last RTX infusion was not associated with an increased risk of miscarriage. Only 2 (5.4%) women experienced relapses, one during pregnancy and the other postpartum. Conclusion We observed no increase in adverse pregnancy outcomes compared with expected national incidence rates and remarkably little disease activity in RTX-treated women with MS, particularly when compared with periconceptional natalizumab-treated cohorts. However, larger studies are needed to fully assess the safety of RTX use before pregnancy, especially risks associated with prolonged B-cell depletion and hypogammaglobulinemia. Until these data are available, we recommend restricting RTX use before pregnancy to women who require highly effective MS treatments. Classification of evidence This study provides Class IV evidence that for pregnant women with MS, RTX controls disease activity and does not increase adverse pregnancy outcomes. Full Article
nan Monoclonal antibody treatment during pregnancy and/or lactation in women with MS or neuromyelitis optica spectrum disorder By nn.neurology.org Published On :: 2020-04-23T12:45:10-07:00 Objective To assess possible adverse effects on breastfed infants of mothers receiving monoclonal antibodies (MAbs) during pregnancy and/or lactation. Methods We identified 23 patients from the German Multiple Sclerosis and Pregnancy Registry (DMSKW) who received MAbs (17 natalizumab and 6 anti-CD20) during lactation. Thirteen were already exposed to natalizumab during the third trimester of pregnancy, and 1 received ocrelizumab during pregnancy. Data were obtained from standardized, telephone-administered questionnaires completed by the mother during pregnancy and at 1, 3, 6, and 12 months postpartum. Natalizumab concentration in mother’s milk was analyzed in 3 patients and natalizumab serum concentration in 2 of these patients and their breastfed infants. Results We did not observe a negative impact on infant health and development attributable to breast milk exposure after a median follow-up of 1 year. Infants exposed to natalizumab during the third trimester had a lower birth weight and more hospitalizations in the first year of life. The concentration of natalizumab in breast milk and serum of infants was low; B cells normal in infants breastfed under anti-CD20. Conclusion More data on the effect of Mab exposure during pregnancy are needed. Otherwise, our data suggest that treatment with natalizumab, ocrelizumab, or rituximab during lactation might be safe for breastfed infants. Full Article
nan Nanopore Sequencing Reveals Novel Targets for Detection and Surveillance of Human and Avian Influenza A Viruses [Virology] By jcm.asm.org Published On :: 2020-04-23T08:00:29-07:00 Accurate detection of influenza A virus (IAV) is crucial for patient management, infection control, and epidemiological surveillance. The World Health Organization and the Centers for Disease Control and Prevention have recommended using the M gene as the diagnostic gene target for reverse-transcription-PCR (RT-PCR). However, M gene RT-PCR has reduced sensitivity for recent IAV due to novel gene mutations. Here, we sought to identify novel diagnostic targets for the molecular detection of IAV using long-read third-generation sequencing. Direct nanopore sequencing from 18 nasopharyngeal specimens and one saliva specimen showed that the 5' and 3' ends of the PB2 gene and the entire NS gene were highly abundant. Primers selected for PB2 and NS genes were well matched with seasonal or avian IAV gene sequences. Our novel PB2 and NS gene real-time RT-PCR assays showed limits of detection similar to or lower than that of M gene RT-PCR and achieved 100% sensitivity and specificity in the detection of A(H1N1), A(H3N2), and A(H7N9) in nasopharyngeal and saliva specimens. For 10 patients with IAV detected by M gene RT-PCR conversion in sequentially collected specimens, NS and/or PB2 gene RT-PCR was positive in 2 (20%) of the initial specimens that were missed by M gene RT-PCR. In conclusion, we have shown that PB2 or NS gene RT-PCRs are suitable alternatives to the recommended M gene RT-PCR for diagnosis of IAV. Long-read nanopore sequencing facilitates the identification of novel diagnostic targets. Full Article
nan NO-Releasing Nanoparticles Ameliorate Detrusor Overactivity in Transgenic Sickle Cell Mice via Restored NO/ROCK Signaling [Cellular and Molecular] By jpet.aspetjournals.org Published On :: 2020-04-13T13:53:50-07:00 Sickle cell disease (SCD) is associated with overactive bladder (OAB). Detrusor overactivity, a component of OAB, is present in an SCD mouse, but the molecular mechanisms for this condition are not well-defined. We hypothesize that nitric oxide (NO)/ ras homolog gene family (Rho) A/Rho-associated kinase (ROCK) dysregulation is a mechanism for detrusor overactivity and that NO-releasing nanoparticles (NO-nps), a novel NO delivery system, may serve to treat this condition. Male adult SCD transgenic, combined endothelial NO synthases (eNOSs) and neuronal NOS (nNOS) gene-deficient (dNOS–/–), and wild-type (WT) mice were used. Empty nanoparticle or NO-np was injected into the bladder, followed by cystometric studies. The expression levels of phosphorylated eNOS (Ser-1177), protein kinase B (Akt) (Ser-473), nNOS (Ser-1412), and myosin phosphatase target subunit 1 (MYPT1) (Thr-696) were assessed in the bladder. SCD and dNOS–/– mice had a greater (P < 0.05) number of voiding and nonvoiding contractions compared with WT mice, and they were normalized by NO-np treatment. eNOS (Ser-1177) and AKT (Ser-473) phosphorylation were decreased (P < 0.05) in the bladder of SCD compared with WT mice and reversed by NO-np. Phosphorylated MYPT1, a marker of the RhoA/ROCK pathway, was increased (P < 0.05) in the bladder of SCD mice compared with WT and reversed by NO-np. nNOS phosphorylation on positive (Ser-1412) regulatory site was decreased (P < 0.05) in the bladder of SCD mice compared with WT and was not affected by NO-np. NO-nps did not affect any of the measured parameters in WT mice. In conclusion, dysregulation of NO and RhoA/ROCK pathways is associated with detrusor overactivity in SCD mice; NO-np reverses these molecular derangements in the bladder and decreases detrusor overactivity. SIGNIFICANCE STATEMENT Voiding abnormalities commonly affect patients with sickle cell disease (SCD) but are problematic to treat. Clarification of the science for this condition in an animal model of SCD may lead to improved interventions for it. Our findings suggest that novel topical delivery of a vasorelaxant agent nitric oxide into the bladder of these mice corrects overactive bladder by improving deranged bladder physiology regulatory signaling. Full Article
nan Correction to "Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence" [Erratum] By jpet.aspetjournals.org Published On :: 2020-04-13T13:53:50-07:00 Full Article
nan Genetic Determinants of Pheochromocytoma and Paraganglioma Imaging Phenotypes By jnm.snmjournals.org Published On :: 2020-05-01T06:31:37-07:00 Parallel to the application of new PET radiopharmaceuticals for pheochromocytoma and paraganglioma (collectively named PPGLs) imaging, several studies have increased our understanding on their biology, genetics, metabolomics, and embryologic origin. In this review, we highlight the current relationship between genotypes and molecular imaging phenotypes. Additionally, we summarize the referral guidelines for imaging of PPGL patients with or without knowledge of their genetic background. Full Article
nan Picking nannofossils: How and why By jm.lyellcollection.org Published On :: 2017-08-10T08:29:36-07:00 Calcareous nannofossils are a group of micrometric fossils abundantly found in marine sediments. This group is mainly composed of coccoliths, platelets produced by the unicellular algae coccolithophores, and nannoliths whose biological affinity remains unknown. Calcareous nannofossils have a continuous record for the past 215 myr (Bown 1998) and can be found in almost every marine environment from coast to open oceans and from the Equator to the poles in surface waters (Winter et al. 1994). These microfossils are also made of low-Mg calcite (Siesser 1977; Stoll et al. 2001) which is resistant to dissolution and a common matrix for geochemical analyses in palaeoceanography. Hence, calcareous nannofossils could be one of the best fossils for palaeoceanographical studies for the last 215 myr. Their use in geochemistry is, however, less common than planktic foraminifera due to their small sizes, masses (10–1000 pg) and complex vital effects. Despite the fact that nannofossils are very small (2–20 µm), the development of high-resolution analytical devices opens up the opportunity to analyse single nannofossils or even parts of them. This is a growing field of nannofossil research. Full Article
nan Unmet Need for Family Planning and Experience of Unintended Pregnancy Among Female Sex Workers in Urban Cameroon: Results From a National Cross-Sectional Study By ghspjournal.org Published On :: 2020-03-31T15:28:55-07:00 ABSTRACTBackground:Female sex workers (FSWs) in Cameroon commonly have unmet need for contraception posing a high risk of unintended pregnancy. Unintended pregnancy leads to a range of outcomes, and due to legal restrictions, FSWs often seek unsafe abortions. Aside from the high burden of HIV, little is known about the broader sexual and reproductive health of FSWs in Cameroon.Methods:From December 2015 to October 2016, we recruited FSWs aged ≥18 years through respondent-driven sampling across 5 Cameroonian cities. Cross-sectional data were collected through a behavioral questionnaire. Modified-robust Poisson regression was used to approximate adjusted prevalence ratios (aPR) for TOP and current use of effective nonbarrier contraception.Results:Among 2,255 FSWs (median age 28 years), 57.6% reported history of unintended pregnancy and 40.0% reported prior TOP. In multivariable analysis, TOP history was associated with current nonbarrier contraceptive use (aPR=1.23, 95% confidence interval [CI]=1.07, 1.42); ever using emergency contraception (aPR=1.34, 95% CI=1.17, 1.55); >60 clients in the past month (aPR=1.29, 95% CI= 1.07, 1.54) compared to ≤30; inconsistent condom use with clients (aPR=1.17, 95% CI=1.00, 1.37); ever experiencing physical violence (aPR=1.24, 95% CI=1.09, 1.42); and older age. Most (76.5%) women used male condoms for contraception, but only 33.2% reported consistent condom use with all partners. Overall, 26.4% of women reported currently using a nonbarrier contraceptive method, and 6.2% reported using a long-acting method. Previous TOP (aPR=1.41, 95%CI=1.16, 1.72) and ever using emergency contraception (aPR=2.70, 95% CI=2.23, 3.26) were associated with higher nonbarrier contraceptive use. Recent receipt of HIV information (aPR=0.72, 95% CI=0.59, 0.89) and membership in an FSW community-based organization (aPR=0.73, 95% CI=0.57, 0.92) were associated with lower use nonbarrier contraceptive use.Conclusions:Experience of unintended pregnancies and TOP is common among FSWs in Cameroon. Given the low use of nonbarrier contraceptive methods and inconsistent condom use, FSWs are at risk of repeat unintended pregnancies. Improved integration of client-centered, voluntary family planning within community-led HIV services may better support the sexual and reproductive health and human rights of FSWs consistent with the United Nations Declaration of Human Rights. Full Article
nan Two-Way Short Message Service (SMS) Communication May Increase Pre-Exposure Prophylaxis Continuation and Adherence Among Pregnant and Postpartum Women in Kenya By ghspjournal.org Published On :: 2020-03-31T15:28:55-07:00 ABSTRACTIntroduction:We evaluated a 2-way short message service (SMS) communication platform to improve continuation of pre-exposure prophylaxis (PrEP) for HIV prevention among Kenyan women who initiated PrEP within routine maternal child health (MCH) and family planning clinics.Methods:We adapted an existing SMS platform (Mobile WACh [mWACh]) to send PrEP-tailored, theory-based SMS and allow clients to communicate with a remote nurse. Women who did not have HIV and who were initiating PrEP at 2 MCH/family planning clinics in Kisumu County, Kenya, from February to October 2018, were offered enrollment into the mWACh-PrEP program; SMS communication was free. We evaluated acceptability, satisfaction, and implementation metrics. In a pre/postevaluation, we compared PrEP continuation at 1-month postinitiation among women who initiated PrEP in the period before (n=166) versus after mWACh-PrEP implementation, adjusting for baseline differences.Results:Of the 334 women who were screened for enrollment into the mWACh-PrEP program; 193 (58%) were eligible and of those, 190 (98%) accepted enrollment. Reasons for ineligibility (n=141) included no phone access (29%) and shared SIM cards (25%). Median age was 25 years (interquartile range=22–30), and 91% were MCH clients. Compared to women who initiated PrEP in the month before mWACh-PrEP implementation, women who enrolled in mWACh-PrEP were more likely to return for their first PrEP follow-up visit (40% vs. 53%; adjusted risk ratio [aRR]=1.26; 95% confidence interval [CI]= 1.06, 1.50; P=.008) and more likely to continue PrEP (22% vs. 43%; aRR=1.75; 95% CI=1.21, 2.55; P=.003). Among those who returned, 99% reported successful receipt of SMS through the mWACh-PrEP system and 94% reported that mWACh-PrEP helped them understand PrEP better. Concerns about PrEP use, how it works, and side effects accounted for the majority (80%) of issues raised by participants using SMS.Conclusions:Two-way SMS expanded support for PrEP and opportunities for dialogue beyond the clinic and enabled women to ask and receive answers in real time regarding PrEP, which facilitated its continued use. Full Article
nan A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials By cjasn.asnjournals.org Published On :: 2020-05-07T10:00:25-07:00 Background and objectives Tolvaptan is approved to slow kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Because in vitro studies indicated that the tolvaptan oxobutyric acid metabolite inhibits organic anion–transporting polypeptide (OATP)1B1 and OATP1B3, United States prescribing information advises avoiding concurrent use with OATP1B1/1B3 substrates, including hepatic hydroxymethyl glutaryl–CoA reductase inhibitors (statins). This post hoc analysis of the pivotal phase 3 tolvaptan trials (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes [TEMPO] 3:4 trial [NCT00428948] and Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD [REPRISE] trial [NCT02160145]) examined the safety of concurrent tolvaptan/statin use. Design, setting, participants, & measurements The trials randomized a combined total of 2815 subjects with early- to late-stage ADPKD to tolvaptan (n=1644) or placebo (n=1171) for 3 years (TEMPO 3:4) and 1 year (REPRISE). Statin use was unrestricted, and 597 subjects (21.2% overall; 332 [20.2%] tolvaptan, 265 [22.6%] placebo) received statins. Statin use (duration, dose change, statin change, permanent discontinuation), incidences of statin-related adverse events, and hepatic transaminase elevations were determined for subjects who received tolvaptan+statin, placebo+statin, tolvaptan alone, and placebo alone. Results No differences in statin use parameters between tolvaptan- and placebo-treated subjects were observed. No statistically significant increases in commonly reported statin-related adverse events (e.g., musculoskeletal disorders, gastrointestinal symptoms) were seen between subjects receiving tolvaptan+statin and placebo+statin. For example, in TEMPO 3:4, frequencies were 5.4% and 7.8%, respectively, for myalgia (difference –2.4%; 95% confidence interval, –11.2% to 6.4%) and 9.3% and 7.8%, respectively, for abdominal pain (difference 1.5%; –7.9% to 10.9%). In an analysis that excluded participants concurrently using allopurinol, the frequency of alanine transaminase or aspartate transaminase >3x upper limit of normal in the pooled study populations was 3.6% for the tolvaptan+statin group and 2.3% for the placebo+statin group (difference 1.4%; –2.0% to 4.7%). Conclusions Tolvaptan has been used safely in combination with statins in clinical trials. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_06_CJN.08170719.mp3 Full Article
nan IL1{alpha} Antagonizes IL1{beta} and Promotes Adaptive Immune Rejection of Malignant Tumors By cancerimmunolres.aacrjournals.org Published On :: 2020-05-01T00:05:25-07:00 We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β–/–, IL1α–/–, and IL1R1–/– mice. Tumors grew progressively in IL1R–/– and IL1α–/– mice but were often absent in IL1β–/– mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true across multiple distinct tumor lineages. Antibodies to IL1β prevented tumor growth in wild-type (WT) mice but not in IL1R1–/– or IL1α–/– mice. Antibodies to IL1α promoted tumor growth in IL1β–/– mice and reversed the tumor-suppressive effect of anti-IL1β in WT mice. Depletion of CD8+ T cells and blockade of lymphocyte mobilization abrogated the IL1β–/– tumor suppressive effect, as did crossing IL1β–/– mice to SCID or Rag1–/– mice. Finally, blockade of IL1β synergized with blockade of PD-1 to inhibit tumor growth in WT mice. These results suggest that IL1β promotes tumor growth, whereas IL1α inhibits tumor growth by enhancing T-cell–mediated antitumor immunity. Full Article
nan Inactivation of Pseudomonas aeruginosa Biofilms by 405-Nanometer-Light-Emitting Diode Illumination [Physiology] By aem.asm.org Published On :: 2020-05-05T08:00:35-07:00 Biofilm formation by Pseudomonas aeruginosa contributes to its survival on surfaces and represents a major clinical threat because of the increased tolerance of biofilms to disinfecting agents. This study aimed to investigate the efficacy of 405-nm light-emitting diode (LED) illumination in eliminating P. aeruginosa biofilms formed on stainless steel coupons under different temperatures. Time-dependent killing assays using planktonic and biofilm cells were used to determine the antimicrobial and antibiofilm activities of LED illumination. We also evaluated the effects of LED illumination on the disinfectant susceptibility, biofilm structure, extracellular polymeric substance (EPS) structure and composition, and biofilm-related gene expression of P. aeruginosa biofilm cells. Results showed that the abundance of planktonic P. aeruginosa cells was reduced by 0.88, 0.53, and 0.85 log CFU/ml following LED treatment for 2 h compared with untreated controls at 4, 10, and 25°C, respectively. For cells in biofilms, significant reductions (1.73, 1.59, and 1.68 log CFU/cm2) were observed following LED illumination for 2 h at 4, 10, and 25°C, respectively. Moreover, illuminated P. aeruginosa biofilm cells were more sensitive to benzalkonium chloride or chlorhexidine than untreated cells. Scanning electron microscopy and confocal laser scanning microscopic observation indicated that both the biofilm structure and EPS structure were disrupted by LED illumination. Further, reverse transcription-quantitative PCR revealed that LED illumination downregulated the transcription of several genes associated with biofilm formation. These findings suggest that LED illumination has the potential to be developed as an alternative method for prevention and control of P. aeruginosa biofilm contamination. IMPORTANCE Pseudomonas aeruginosa can form biofilms on medical implants, industrial equipment, and domestic surfaces, contributing to high morbidity and mortality rates. This study examined the antibiofilm activity of 405-nm light-emitting diode (LED) illumination against mature biofilms formed on stainless steel coupons. We found that the disinfectant susceptibility, biofilm structure, and extracellular polymeric substance structure and composition were disrupted by LED illumination. We then investigated the transcription of several critical P. aeruginosa biofilm-related genes and analyzed the effect of illumination temperature on the above characteristics. Our results confirmed that LED illumination could be developed into an effective and safe method to counter P. aeruginosa biofilm contamination. Further research will be focused on the efficacy and application of LED illumination for elimination of complicated biofilms in the environment. Full Article
nan Emergency department use by pregnant women in Ontario: a retrospective population-based cohort study By www.cmajopen.ca Published On :: 2020-04-28T01:30:11-07:00 Background: Peripregnancy emergency department use may be common, but data specific to health care systems like that in Canada are lacking. As prior research was limited to livebirths, omitting pregnancies ending in miscarriage or induced abortion, the current study quantified and characterized emergency department use among women in Ontario with a recognized pregnancy. Methods: This retrospective population-based cohort study included all recognized pregnancies among Ontario residents aged 10–55 years with an estimated date of conception between Apr. 1, 2002, and Mar. 31, 2017. We defined peripregnancy emergency department use as any emergency department visit during pregnancy or within 42 days after pregnancy. We used modified Poisson regression with a robust error variance to generate relative risks (RRs) and 95% confidence intervals (CIs) for the outcome of any peripregnancy emergency department use in association with maternal age, parity, residential income quintile, location of residence, immigrant status, antenatal care provider and number of comorbidities within 120 days before the clinical start of the pregnancy (expressed as total number of Aggregated Diagnosis Groups [ADGs] obtained with the Johns Hopkins Adjusted Clinical Group System). All RRs, except for number of comorbidities, were further adjusted for number of ADGs. Results: Peripregnancy emergency department use occurred in 1 075 991 (39.4%) of 2 728 236 recognized pregnancies, including 35.8% of livebirths, 47.3% of stillbirths, 73.7% of miscarriages and 84.8% of threatened abortions. A peripregnancy emergency department visit was more likely among women who were less than 25 years of age (adjusted RR 1.16, 95% CI 1.16–1.17), were nulliparous (adjusted RR 1.13, 95% CI 1.13–1.13), resided in the lowest income quintile area (adjusted RR 1.16, 95% CI 1.15–1.16) or in a rural area (adjusted RR 1.50, 95% CI 1.50–1.51), were Canadian-born (adjusted RR 1.22, 95% CI 1.22–1.23), were not seen by an obstetrician (adjusted RR 1.66, 95% CI 1.54–1.80) or had a greater number of ADGs. Emergency department use peaked in the first trimester and in the first week postpartum. Compared to women residing in urban areas, those residing in rural areas had an odds ratio (OR) of 3.44 (95% CI 3.39–3.49) for 3 or more emergency department visits. Women with 3–4 (OR 1.99, 95% CI 1.97–2.01), 5–6 (OR 3.55, 95% CI 3.49–3.61), or 7 or more (OR 7.59, 95% CI 7.39–7.78) prepregnancy comorbidities were more likely to have 3 or more peripregnancy emergency department visits than were those with 2 or fewer comorbidities. Interpretation: Peripregnancy emergency department use occurred in nearly 40% of pregnancies, notably in the first trimester and early in the postpartum period. Efforts are needed to streamline rapid access to ambulatory obstetric care during these peak periods, when women are susceptible to miscarriage or a complication after a livebirth. Full Article
nan Pregnancy-adapted YEARS algorithm: can YEARS do more for pregnant women? By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 Venous thromboembolism (VTE), as a term that encompasses pulmonary embolism (PE) and deep vein thrombosis (DVT), is one of the leading causes of maternal morbidity and mortality [1], especially in developed countries, where PE takes second place after complications of hypertensive disorders [2]. When compared to non-pregnant women of similar age, pregnant women have an approximately four to five times higher risk of VTE [3], with an incidence of 1 in 1000 pregnancies [4]. Approximately 20–25% of VTE cases are caused by PE and 75–80% of cases are caused by DVT [5]. About 60% of DVT occurs antepartum, with the highest risk of antepartum pregnancy-associated VTE being in the third trimester.However, about 60% of PE occurs postpartum [3]. Full Article
nan Predominance of Central Memory T Cells with High T-Cell Receptor Repertoire Diversity is Associated with Response to PD-1/PD-L1 Inhibition in Merkel Cell Carcinoma By clincancerres.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Purpose: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, which can be effectively controlled by immunotherapy with PD-1/PD-L1 checkpoint inhibitors. However, a significant proportion of patients are characterized by primary therapy resistance. Predictive biomarkers for response to immunotherapy are lacking. Experimental Design: We applied Bayesian inference analyses on 41 patients with MCC testing various clinical and biomolecular characteristics to predict treatment response. Further, we performed a comprehensive analysis of tumor tissue–based immunologic parameters including multiplexed immunofluorescence for T-cell activation and differentiation markers, expression of immune-related genes and T-cell receptor (TCR) repertoire analyses in 18 patients, seven objective responders, and 11 nonresponders. Results: Bayesian inference analyses demonstrated that among currently discussed biomarkers only unimpaired overall performance status and absence of immunosuppression were associated with response to therapy. However, in responders, a predominance of central memory T cells and expression of genes associated with lymphocyte attraction and activation was evident. In addition, TCR repertoire usage of tumor-infiltrating lymphocytes (TILs) demonstrated low T-cell clonality, but high TCR diversity in responding patients. In nonresponders, terminally differentiated effector T cells with a constrained TCR repertoire prevailed. Sequential analyses of tumor tissue obtained during immunotherapy revealed a more pronounced and diverse clonal expansion of TILs in responders indicating an impaired proliferative capacity among TILs of nonresponders upon checkpoint blockade. Conclusions: Our explorative study identified new tumor tissue–based molecular characteristics associated with response to anti–PD-1/PD-L1 therapy in MCC. These observations warrant further investigations in larger patient cohorts to confirm their potential value as predictive markers. Full Article
nan Predominant Distribution of OXA-48-Like Carbapenemase in Fecal Colonization [Letters] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Full Article
nan Noncoding Variants Connect Enhancer Dysregulation with Nuclear Receptor Signaling in Hematopoietic Malignancies [Research Articles] By cancerdiscovery.aacrjournals.org Published On :: 2020-05-01T00:05:26-07:00 Mutations in protein-coding genes are well established as the basis for human cancer, yet how alterations within noncoding genome, a substantial fraction of which contain cis-regulatory elements (CRE), contribute to cancer pathophysiology remains elusive. Here, we developed an integrative approach to systematically identify and characterize noncoding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage–associated CREs and mutation discovery, we uncovered 1,836 recurrently mutated CREs containing leukemia-associated noncoding variants. By enhanced CRISPR/dCas9–based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor-suppressive CREs in human leukemia. Noncoding variants at KRAS and PER2 enhancers reside in proximity to nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently colocalize with noncoding variants across cancer types. Hence, recurrent noncoding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies. Significance: We describe an integrative approach to identify noncoding variants in human leukemia, and reveal cohorts of variant-associated oncogenic and tumor-suppressive cis-regulatory elements including KRAS and PER2 enhancers. Our findings support a model in which noncoding regulatory variants connect enhancer dysregulation with nuclear receptor signaling to modulate gene programs in hematopoietic malignancies. See related commentary by van Galen, p. 646. This article is highlighted in the In This Issue feature, p. 627 Full Article
nan Plasma DNA End-Motif Profiling as a Fragmentomic Marker in Cancer, Pregnancy, and Transplantation [Research Briefs] By cancerdiscovery.aacrjournals.org Published On :: 2020-05-01T00:05:26-07:00 Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy in oncology, noninvasive prenatal testing, and transplantation monitoring. Significance: Plasma DNA molecules originating from the liver, HCC and other cancers, placenta, and hematopoietic cells each harbor a set of characteristic plasma DNA end motifs. Such markers carry tissue-of-origin information and represent a new class of biomarkers in the nascent field of fragmentomics. This article is highlighted in the In This Issue feature, p. 627 Full Article
nan Method Enables Nanoscale Mapping of Protein Interactions on Live Cells [Techniques] By cancerdiscovery.aacrjournals.org Published On :: 2020-05-01T00:05:26-07:00 A new method called MicroMapping can identify nanoscale protein–protein interactions on live cells. Full Article
nan Sensitive Determination of Infectious Titer of Recombinant Adeno-Associated Viruses (rAAVs) Using TCID50 End-Point Dilution and Quantitative Polymerase Chain Reaction (qPCR) By cshprotocols.cshlp.org Published On :: 2020-05-01T06:29:31-07:00 Adeno-associated virus (AAV) recombinants are currently the vector of choice for many gene therapy applications. As experimental therapies progress to clinical trials, the need to characterize recombinant adeno-associated viruses (rAAVs) accurately and reproducibly increases. Accurate determination of rAAV infectious titer is important for determining the activity of each vector lot and for ensuring lot-to-lot consistency. The following protocol developed in our laboratory uses a 96-well TCID50 format and quantitative polymerase chain reaction (qPCR) detection for the determination of rAAV infectious titer. Full Article
nan Titration of Recombinant Adeno-Associated Virus (rAAV) Genome Copy Number Using Real-Time Quantitative Polymerase Chain Reaction (qPCR) By cshprotocols.cshlp.org Published On :: 2020-05-01T06:29:31-07:00 This protocol is used to determine the concentration of DNase-resistant vector genomes (i.e., packaged in the capsid) in purified recombinant adeno-associated virus (rAAV) preparations. The protocol begins with treatment of the vector stock with DNase I to eliminate unencapsidated AAV DNA or contaminating plasmid DNA. This is followed by a heat treatment to heat-inactivate DNase I, to disrupt the viral capsid, and to release the packaged vector genomes for quantification by real-time polymerase chain reaction (PCR) using a set of standards (linearized plasmid used for vector production) containing known copy numbers. To accomplish high-throughput titration, the primer and probe sets used in real-time PCR are usually designed to target common elements present in most rAAV genomes, such as promoters and poly(A) signals. This strategy significantly reduces the number of PCRs, controls, and turnaround time. Several important controls should be included in the assay as follows: The first two controls should have a known copy number of the rAAV genome plasmid treated or not treated with DNase I. This control tests the effectiveness of DNase treatment. To control for potential cross-contamination between samples during the preparation process, a blank control containing nuclease-free water only should be processed and tested in parallel. A validation vector sample with a known titer should be included in every assay to monitor interassay variability. Finally, for the PCR run, a no-template control (NTC) is included to indicate cross-contamination during PCR setup. Full Article
nan Purification of Recombinant Adeno-Associated Virus 2 (rAAV2) by Heparin Column Affinity Chromatography By cshprotocols.cshlp.org Published On :: 2020-05-01T06:29:31-07:00 This protocol describes a simple single-step column purification (SSCP) of rAAV2 by gravity flow based on its affinity to heparin, without ultracentrifugation. Full Article
nan Vinhomes Ba Son Q1, CH đa năng giá phải chăng, 1PN 16tr, 2PN 20tr, 3PN 28tr, 4PN 60tr. 0903049288 By batdongsan.com.vn Published On :: Thu, 30 Apr 2020 21:57:34 GMT Vinhomes Golden River.- 1PN 50m2 có bồn tắm nằm giá 16tr - 17tr/th bao phí. - 2PN 70 - 87m2 có bồn nằm giá 20tr - 25tr/th bao phí. - 3PN 100 - 121 m2 có bồn nằm giá 29tr - 42tr/th bao phí. - 4PN 154m2 - 159m2 giá 70 - 80tr/th không bao phí.Lưu Ý: Giá trên là giá thực tế, thương l... Full Article
nan Công ty CP Chứng Khoán Đà Nẵng By batdongsan.com.vn Published On :: Wed, 19 Feb 2014 15:44:00 GMT Full Article
nan [Infographic] Cẩm nang dành cho người mua chung cư lần đầu By batdongsan.com.vn Published On :: 14:44 06/01/2020 Căn hộ chung cư là loại hình nhà ở nằm trong một dự án gồm nhiều căn hộ, quá trình mua bán, chất lượng bàn giao và việc hoàn thiện đều được thực hiện theo hợp đồng ký với chủ đầu tư. Để giúp người mua chung cư lần đầu không bỡ ngỡ, Batdongsan.com.vn tổng hợp những thông tin chính mà người mua cần tìm hiểu trước khi thực hiện giao dịch như sau: Full Article
nan Mê đắm những mẫu phòng tắm lộ thiên xua tan nắng hè By batdongsan.com.vn Published On :: 08:52 08/07/2019 Bạn đã từng ao ước được đắm chìm trong không gian phòng tắm hoang dã, mộc mạc và gần gũi với thiên nhiên? Những mẫu phòng tắm lộ thiên dưới đây sẽ cho bạn thấy rằng mùa hè là khoảng thời gian lý tưởng nhất để đưa hơi thở thiên nhiên vào trong nhà. Full Article
nan Wyndham Soleil - One-bedroom condo for sale in Danang By batdongsan.com.vn Published On :: Wed, 23 Oct 2019 08:43:11 GMT Wyndham Soleil Danang is a four-tower complex consisting of one hotel and three condotel buildings meeting five-star standards in the 50-57 storeys range. When completed, Wyndham Soleil Danang will be an iconic Landmark in Danang City. Soliel invites investors to experience luxur... Full Article
nan One-bedroom condotel for sale in Wyndham Soleil Project - Danang City - Call 0935 38 48 27 By batdongsan.com.vn Published On :: Wed, 23 Oct 2019 08:43:16 GMT One-bedroom condotel for sale in Danang City Location: diamond location - four facades - in front of the beach: - North: in Morrison Street - West: in Ho Nghinh Street - South: in Pham Van Dong Street - East: in Vo Nguyen Giap StreetHotline: 0935 38 48 27Wyndham Soleil Danang is ... Full Article
nan Hot! Wyndham Soleil Danang apartment for sale, frontage on Pham Van Dong street By batdongsan.com.vn Published On :: Thu, 14 Nov 2019 14:59:54 GMT Da Nang Soleil Project Project 1- Located on YELLOW land of Danang city2- Convergence of delicate and modern essence of the world.The project of Condotel Anh Duong Soleil Da Nang was determined to become a new symbol of Danang city by the investor, An Thinh, along with the famous... Full Article
nan Wyndham Soleil Danang - one-bedroom condo for sale at only 989k USD By batdongsan.com.vn Published On :: Tue, 10 Dec 2019 14:35:46 GMT WYNDHAM SOLEIL DA NANGStudio APARTMENT Construction area: 30.72m2 - 41.78m2 Clearance area: 26.87m2 - 37.14m2 1 Bedroom Apartment Construction area: 60.64m2 - 86.31m2 Carpet area: 54.98m2 - 79.17m2 2 Bedrooms Apartment Construction area: 111.4m2 - 125.7m2 Carpet area: 102.46m2 - ... Full Article
nan Officially open for sale - Soleil Anh Duong Danang - Hotline: 0935 38 48 27 By batdongsan.com.vn Published On :: Tue, 10 Dec 2019 15:07:53 GMT One-Bedroom Condotel for sale in Danang Location: diamond location - four facades - in front of the beach: - North: in Morrison Street - West: in Ho Nghinh Street - South: in Pham Van Dong Street - East: in Vo Nguyen Giap StreetHotline: (+84) O935 38 48 27Wyndham Soleil Danang i... Full Article
nan Looking for an apartment in Da Nang, 1 billion VND budget By batdongsan.com.vn Published On :: Wed, 18 Mar 2020 17:40:00 GMT Looking for an apartment in Da Nang - Area: 50m2 and so on - High floor - Maybe new building - Budget: 1 billion VND... Full Article
nan Cầu thang gỗ đa năng trong nhà phố nhỏ ở Nhật By batdongsan.com.vn Published On :: 10:20 03/04/2020 Diện tích nhà nhỏ nhưng vẫn cần có không gian để trưng bày tranh, ảnh và đồ trang trí. Bằng cách thiết kế cầu thang gỗ đa năng, vừa giữ vai trò giao thông, vừa để lưu trữ và trưng bày, kiến trúc sư đã khiến gia chủ hài lòng 100%. Full Article
nan Nhà phố 3 tầng chữ L - bố trí mặt bằng công năng và nội thất sao cho tiện nghi? By batdongsan.com.vn Published On :: 19:22 03/04/2020 Nhà phố 3 tầng chữ L sở hữu hình dạng đặc biệt với lợi thế hai mặt thoáng. Chiến lược thiết kế của kiến trúc sư là tận dụng tối đa các mặt thoáng để trổ cửa sổ và ban công nhằm đưa ánh sáng tự nhiên, gió trời vào sâu bên trong mọi ngóc ngách trong nhà, tạo nên không gian sống thoáng đãng, hài hòa và tiết kiệm năng lượng sử dụng. Full Article
nan Hô biến căn hộ nhỏ thành phòng tập khiêu vũ trong tích tắc với nội thất đa năng By batdongsan.com.vn Published On :: 18:42 06/04/2020 Chủ nhân căn hộ nhỏ vốn là vũ công ballet chuyên nghiệp. Đặc thù công việc buộc anh thường xuyên phải luyện tập tại nhà trong một không gian trống tương đối rộng. Điều này đã truyền cảm hứng cho đội ngũ thiết kế nảy ra nhiều giải pháp độc đáo và vô cùng thú vị. Full Article
nan Cẩm nang làm việc với kiến trúc sư (phần 1) By batdongsan.com.vn Published On :: 15:24 29/04/2020 Chi phí để thiết kế, xây dựng lên ngôi nhà mơ ước không hề nhỏ. Ngoài việc lựa chọn kiến trúc sư phù hợp và nhà thầu có năng lực thì việc giao tiếp với kiến trúc sư rất quan trọng, quyết định sự thành bại của dự án. Sự giao tiếp trôi chảy, thấu hiểu sẽ giúp hiện thực hóa những ước muốn, nhu cầu của gia chủ. Full Article
nan Cho thuê phòng 70m2 có bể bơi tại naman retreatment 5 sao tại đà nẵng từ ngày 1/6-7/6/2020 By batdongsan.com.vn Published On :: Tue, 05 May 2020 17:21:00 GMT Cho thuê phòng 70m2 có bể bơi tại resort 5 sao Naman Retreat từ ngày 1/6 - 7/6/2020 giá 1,5 triệu/ngày. Điện thoại liên hệ 0949183160.... Full Article
nan Quy hoạch Đà Nẵng trở thành “Thành phố ngàn hồ” By batdongsan.com.vn Published On :: 12:04 20/03/2020 Trong đồ án điều chỉnh Quy hoạch chung TP. Đà Nẵng đến năm 2030, tầm nhìn đến năm 2045, một trong những ý tưởng về chiến lược phát triển hạ tầng là quy hoạch Đà Nẵng thành thành phố ngàn hồ. Full Article
nan Điều chỉnh vị trí, chức năng hàng loạt lô đất tại khu đô thị Ecopark By batdongsan.com.vn Published On :: 14:02 23/03/2020 UBND tỉnh Hưng Yên vừa điều chỉnh vị trí, chức năng của hàng loạt lô đất thuộc khu đô thị Ecopark, huyện Văn Giang. Các lô đất xây nhà cao tầng sẽ trở thành khu shophouse, công trình công cộng. Full Article
nan Bình Định điều chỉnh chức năng khu đất “vàng” tại TP. Quy Nhơn By batdongsan.com.vn Published On :: 14:31 24/03/2020 Khu đất "vàng" K200, nằm trên đường An Dương Vương, phường Nguyễn Văn Cừ, TP. Quy Nhơn, tỉnh Bình Định được điều chỉnh chức năng sử dụng đất. Full Article
nan Quy hoạch khu trung tâm Đà Nẵng rộng 1.866ha By batdongsan.com.vn Published On :: 10:50 03/04/2020 Tổng diện tích nghiên cứu thiết kế đô thị trung tâm TP. Đà Nẵng gồm toàn bộ quận Hải Châu và một phần các quận Cẩm Lệ, Thanh Khê. Full Article
nan 5 cách kích hoạt năng lượng tốt cho phòng làm việc đầu năm mới By batdongsan.com.vn Published On :: 16:44 31/01/2019 Đầu năm là khoảng thời gian thích hợp nhất cho việc sắp xếp, bố trí lại văn phòng làm việc để mong muốn một năm phát triển sự nghiệp, đạt nhiều thành tựu. Sau đây là 5 cách kích hoạt năng lượng cho phòng làm việc mà các chuyên gia phong thủy hiện đại đúc kết từ quá trình tư vấn phong thủy cho khách hàng. Full Article
nan Làm sao để phát huy tối đa năng suất làm việc tại nhà? By batdongsan.com.vn Published On :: 08:15 03/06/2019 Với sự phát triển mạnh mẽ của công nghệ, ngày càng có nhiều người lựa chọn phương án làm việc tại gia. Vậy làm sao để phát huy được tối đa năng suất làm việc khi ở nhà? Dưới đây là 7 lời khuyên hữu ích được chuyên gia phong thủy đưa ra, giúp giải đáp tốt câu hỏi này. Full Article
nan Kích hoạt năng lượng tốt cho khoang làm việc để sự nghiệp thăng tiến By batdongsan.com.vn Published On :: 15:20 24/10/2019 Hiện nay đa số các văn phòng đều sử dụng khoang làm việc cho từng nhân viên để đảm bảo riêng tư và tiết kiệm diện tích. Các khoang thường được bố trí liền nhau, có thể thành một dãy dài để chia sẻ không gian. Các khoang làm việc được ngăn cách với nhau bằng vách kính, gỗ… Full Article
nan Che chắn nhà mùa nắng: Cách dùng lam tránh nóng và cân bằng âm dương By batdongsan.com.vn Published On :: 17:40 06/05/2020 Với đặc trưng khí hậu nhiệt đới của Việt Nam, việc chọn giải pháp chống nóng luôn là mối bận tâm của các chủ nhà. Trong đó, dùng lam che chắn là giải pháp hữu hiệu, nếu khéo còn giúp cân bằng âm dương, tăng lợi thế phong thủy cho ngôi nhà. Full Article
nan Lãi suất thả nổi sẽ là gánh nặng với người mua NOXH By batdongsan.com.vn Published On :: 15:25 13/09/2016 Dự án nhà ở xã hội (NOXH) Topaz Home có giá thấp nhất 13,8 triệu đồng/m2, rẻ hơn căn hộ thương mại cùng dự án hơn 2 triệu đồng/m2, tuy nhiên không được hưởng gói ưu đãi lãi suất. Full Article
nan Căn hộ bị tường kính rọi nắng gay gắt vào nhà phải làm gì? By batdongsan.com.vn Published On :: 16:31 13/03/2020 Hỏi: Căn hộ chung cư tôi ở đối diện một tòa nhà của ngân hàng. Mặt ngoài tòa nhà này ốp toàn bộ kính, ánh nắng hắt ngược vào trong căn hộ rất khó chịu. Full Article
nan By 2025, Hanoi, Da Nang and HCMC will become smart cities? By batdongsan.com.vn Published On :: 17:07 03/10/2019 According to Deputy Minister of Construction Nguyen Viet Sinh, Vietnam will have at least 3 smart cities in 3 key economic regions: North, Central and South. Thus, by the next 6 years, Hanoi, Da Nang and Ho Chi Minh City will become smart cities. Full Article
nan Đà Nẵng: Từ ngày 5/5, giá đất cao nhất là 98,8 triệu đồng/m2 By batdongsan.com.vn Published On :: 14:07 21/04/2020 Từ ngày 5/5, giá đất thương mại dịch vụ tại đô thị Đà Nẵng cao nhất là 79 triệu đồng/m2. Giá đất ở đô thị cao nhất là 98,8 triệu đồng/m2. Full Article