bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo
Authors: Allweiss Lena , Giersch Katja , Pirosu Andrea , Volz Tassilo , Muench Robert C , Beran Rudolf K , Urban Stephan , Javanbakht Hassan , Fletcher Simon P , Lütgehetmann Marc , Dandri Maura 
Published: January 2021

ObjectiveTherapeutic strategies silencing and reducing the hepatitis B virus (HBV) reservoir, the covalently closed circular DNA (cccDNA), have the potential to cure chronic HBV infection. We aimed to investigate the impact of small interferring RNA (siRNA) targeting all HBV transcripts or pegylated interferon-α (peg-IFNα) on the viral regulatory HBx protein and the structural maintenance of chromosome 5/6 complex (SMC5/6), a host factor suppressing cccDNA transcription. In particular, we assessed whether interventions lowering HBV transcripts can achieve and maintain silencing of cccDNA transcription in vivo.DesignHBV-infected human liver chimeric mice were treated with siRNA or peg-IFNα. Virological and host changes were analysed at the end of treatment and during the rebound phase by qualitative PCR, ELISA, immunoblotting and chromatin immunoprecipitation. RNA in situ hybridisation was combined with immunofluorescence to detect SMC6 and HBV RNAs at single cell level. The entry inhibitor myrcludex-B was used during the rebound phase to avoid new infection events.ResultsBoth siRNA and peg-IFNα strongly reduced all HBV markers, including HBx levels, thus enabling the reappearance of SMC5/6 in hepatocytes that achieved HBV-RNA negativisation and SMC5/6 association with the cccDNA. Only IFN reduced cccDNA loads and enhanced IFN-stimulated genes. However, the antiviral effects did not persist off treatment and SMC5/6 was again degraded. Remarkably, the blockade of viral entry that started at the end of treatment hindered renewed degradation of SMC5/6.ConclusionThese results reveal that therapeutics abrogating all HBV transcripts including HBx promote epigenetic suppression of the HBV minichromosome, whereas strategies protecting the human hepatocytes from reinfection are needed to maintain cccDNA silencing.
Ambient air pollution exposure and chronic bronchitis in the Lifelines cohort
Authors: Doiron Dany , Bourbeau Jean , de Hoogh Kees , Hansell Anna L 
Published: January 2021

BackgroundFew large studies have assessed the relationship of long-term ambient air pollution exposure with the prevalence and incidence of symptoms of chronic bronchitis and cough.MethodsWe leveraged Lifelines cohort data on 132 595 (baseline) and 65 009 (second assessment) participants linked to ambient air pollution estimates. Logistic regression models adjusted for sex, age, educational attainment, body mass index, smoking status, pack-years smoking and environmental tobacco smoke at home were used to assess associations of air pollution with prevalence and incidence of chronic bronchitis (winter cough and sputum almost daily for ≥3 months/year), chronic cough (winter cough almost daily for ≥3 months/year) and prevalence of cough and sputum symptoms, irrespective of duration.ResultsAssociations were seen for all pollutants for prevalent cough or sputum symptoms. However, for prevalent and incident chronic bronchitis, statistically significant associations were seen for nitrogen dioxide (NO2) and black carbon (BC) but not for fine particulate matter (PM2.5). For prevalent chronic bronchitis, associations with NO2showed OR: 1.05 (95% CI: 1.02 to 1.08) and with BC OR: 1.06 (95% CI: 1.03 to 1.09) expressed per IQR; corresponding results for incident chronic bronchitis were NO2OR: 1.07 (95% CI: 1.02 to 1.13) and BC OR: 1.07 (95% CI: 1.02 to 1.13). In subgroup analyses, slightly stronger associations were observed among women, never smokers and younger individuals.ConclusionThis is the largest analysis to date to examine cross-sectional and longitudinal associations between ambient air pollution and chronic bronchitis. NO2and BC air pollution was associated with increased odds of prevalent and incident chronic bronchitis.
Measurement of the helicity asymmetry E for the reaction $$ \gamma p\rightarrow \pi ^0 p$$
Authors: Gottschall M. , Afzal F. , Anisovich A. V. , Bayadilov D. , Beck R. , Bichow M. , Brinkmann K. Th. , Crede V. , Dieterle M. , Dietz F. , Dutz H. , Eberhardt H. , Elsner D. , Ewald R. , Fornet-Ponse K. , Friedrich St. , Frommberger F. , Gridnev A. , Grüner M. , Gutz E. , Hammann Ch. , Hannappel J. , Hartmann J. , Hillert W. , Hoffmeister Ph. , Honisch Ch. , Jude T. , Kammer S. , Kalinowsky H. , Keshelashvili I. , Klassen P. , Klein F. , Klempt E. , Koop K. , Krusche B. , Kube M. , Lang M. , Lopatin I. , Mahlberg P. , Makonyi K. , Metag V. , Meyer W. , Müller J. , Müllers J. , Nanova M. , Nikonov V. , Novotny R. , Piontek D. , Reicherz G. , Rostomyan T. , Sarantsev A. , Schmidt Ch. , Schmieden H. , Seifen T. , Sokhoyan V. , Spieker K. , Thiel A. , Thoma U. , Urban M. , Pee H. van , Walther D. , Wendel Ch. , Werthmüller D. , Wiedner U. , Wilson A. , Winnebeck A. , Witthauer L. , Wunderlich Y. 
Published: January 2021

AbstractA measurement of the double-polarization observable E for the reaction $$\gamma p\rightarrow \pi ^0 p$$

γ
p
→

π
0

p

is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C$$_4$$

4

H$$_9$$

9

OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from $$E_\gamma =600$$

E
γ

=
600

to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.
Factors Associated with Mortality in Severe Acute Cholangitis in a Moroccan Intensive Care Unit: A Retrospective Analysis of 140 Cases
Authors: Touzani Soumaya , El Bouazzaoui Abderrahim , Bouyarmane Fatima , Faraj Kaoutar , Houari Nawfal , Boukatta Brahim , Kanjaa Nabil 
Published: January 2021

Background. Severe acute cholangitis is a life-threatening biliary infection, leading to organ dysfunction, septic shock, and naturally death. Mortality has dropped significantly in the past years through improving resuscitation and biliary drainage techniques. The aim of our study is to analyze our daily practice and the factors associated with mortality. Methods. A retrospective study including severe acute cholangitis patients admitted to our unit from January 2009 to December 2018. Variables analyzed (univariate then multivariate analysis) were age, sex, history, origin, evolution time, bilirubin, etiology, organ dysfunction, qSOFA, SOFA, TOKYO, biliary drainage timing and technique, shock, antibiotherapy, and resuscitation. Results. 140 patients were included in this study. Average age was 61. Sex ratio M/F was 0.59. Lithiasis etiology was dominant (69%). SOFA average score upon admission was 8. Ceftriaxone + metronidazole was the empirical antibiotic used in 87%. Average time to biliary drainage was

1.58
±
0.89

days

. Endoscopic unblocking was the technique used in 76%. Mean duration of ICU stay was 6 days. Mortality rate was 28%. Statistically significant factors for mortality (

p
<
0.05

) were history of taking anticoagulant treatment, use of catecholamines and mechanical ventilation during ICU stay, and delay in consultation and administration of antibiotic therapy. Conclusions. Early recognition, antibiotics, resuscitation, and minimally invasive biliary drainage have improved patient outcomes although there is still progress to be made. Moreover, as multiple organ failure is often associated with mortality in severe acute cholangitis, predictive risk factors of organ failure should be more investigated.
Eternal Domination of Generalized Petersen Graph
Authors: Shaheen Ramy , Kassem Ali 
Published: January 2021

An eternal dominating set of a graph

G

is a set of guards distributed on the vertices of a dominating set so that each vertex can be occupied by one guard only. These guards can defend any infinite series of attacks; an attack is defended by moving one guard along an edge from its position to the attacked vertex. We consider the “all guards move” of the eternal dominating set problem, in which one guard has to move to the attacked vertex and all the remaining guards are allowed to move to an adjacent vertex or stay in their current positions after each attack in order to form a dominating set on the graph and at each step can be moved after each attack. The “all guards move model” is called the

m

-eternal domination model. The size of the smallest

m

-eternal dominating set is called the

m

-eternal domination number and is denoted by

γ

m

∞

G

. In this paper, we find

γ

m

∞

P

n
,
1

and

γ

m

∞

P

n
,
3

for

n
≡
0

mod

4

. We also find upper bounds for

γ

m

∞

P

n
,
2

and

γ

m

∞

P

n
,
3

when

n

is arbitrary.
Antibacterial Filtration Using Polyethylene Terephthalate Filters Coated with Copper Nanoparticles
Authors: Nguyen Vinh Tien , Vu Quang Hoang Anh , Pham Thi Ngoc Nhi , Trinh Khanh Son 
Published: January 2021

The purpose of this study is to produce antibacterial filters based on a commercial polyethylene terephthalate (PET) filter with pores larger than bacterial cells. The antibacterial agent was copper nanoparticles (CuNP) which were synthesized and deposited on the PET filter by reducing copper(II) ions using sodium hypophosphite (NaH2PO2) as the reducing agent and polyvinylpyrrolidone (PVP) as the capping agent. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed the presence of 150–300 nm CuNP on the surface of PET filters. We evaluated the amounts of deposited CuNP using a colorimetric method and the antibacterial-filtration capacity of CuNP/PET filters against Escherichia coli using the colony counting method. The reaction conditions were optimized successively using the one-factor-at-a-time approach for the concentration of copper precursor, the concentration of PVP, and the reaction time. The results showed that an initial 1 M CuSO4, 0.8%

w
/
v

PVP, and 10-20 min of reaction resulted in a CuNP/PET filter with the highest antibacterial activity: 5.2 log cfu/mL reduction for Escherichia coli and 5.6 log cfu/mL reduction or Staphylococcus aureus. SEM images demonstrated the damages of the bacterial cells after passing through the CuNP/PET filter. ICP-MS analysis of the first liter of filtrate showed that the copper concentration of released copper was

0.6
±
0.1

ppm, which is below the WHO standard for drinking water. Therefore, these CuNP/PET filters are promising for point-of-use disinfection of water, where clean potable water is not sufficient.
Retinal Thickness Asymmetry in Highly Myopic Eyes with Early Stage of Normal-Tension Glaucoma
Authors: Lin Pei-Wen , Chang Hsueh-Wen , Poon Yi-Chieh 
Published: January 2021

Purpose. To investigate the retinal thickness asymmetry parameters of circumpapillary retinal nerve fiber layer (cpRNFL) and macular layers measured by spectral-domain optical coherence tomography in highly myopic (HM) patients with an early stage of normal-tension glaucoma (NTG). Methods. This cross-sectional study included 55 eyes of HM patients with early NTG and 37 eyes of HM normal participants. High myopia was defined as spherical equivalence more myopic than −6 diopters. Thickness differences and asymmetry indices (AIs) of cpRNFL between superior and inferior corresponding parts and thickness differences and AIs of the total macular layer (TML) and inner macular layers between superior and inferior hemispheres were calculated. The areas under the receiver operating characteristic curves (AROCs) were analyzed and compared. Results. In the cpRNFL asymmetry analysis, the thickness differences and AIs of cpRNFL between temporal-superior and temporal-inferior sectors (

P

< 0.0001 and

P

< 0.0001, respectively) and between superior and inferior quadrants (

P

= 0.002 and

P

< 0.0001, respectively) were significantly different between HM control subjects and HM NTG patients. In the macular asymmetry analysis, the thickness difference and AI of TML were significantly different between superior and inferior hemispheres (

P

< 0.0001 and

P

< 0.0001, respectively). The thickness difference and AI of the macular ganglion cell layer (mGCL) were significantly different between superior and inferior hemispheres (

P

< 0.0001 and

P

< 0.0001, respectively). The AROCs for thickness difference of TML (0.845) and thickness difference of mGCL (0.773) were comparable to AROCs for average cpRNFL thickness (0.842), macular retinal nerve fiber layer thickness (mRNFL) thickness (0.871), and mGCL thickness (0.822). Conclusion. In our study, HM NTG patients had retinal thickness asymmetry in cpRNFL, TML, and mGCL. The diagnostic capabilities for thickness asymmetry of TML and mGCL were comparable to the diagnostic capabilities for cpRNFL thickness, mRNFL thickness, and mGCL thickness. Asymmetry analysis of retinal thickness can be an adjunctive tool for the early detection of HM NTG.
Zinner Syndrome with Ectopic Ureter Emptying into Seminal Vesicle
Authors: Hevia Palacios M. , Álvarez-Maestro M. , Gómez Rivas J. , Aguilera Bazan A. , Martínez-Piñeiro L. 
Published: January 2021

A 66-year-old male patient in follow-up in the urology department for a non-muscle-invasive bladder cancer was detected by ultrasound to have absence of the left kidney and a cystic, multilobed image at the location of the seminal vesicle. Magnetic resonance imaging reveals left renal agenesis and the existence of multiple cysts in the ipsilateral seminal vesicle that reaches a size of

6.9
×
3.7

cm

, as well as a ureteral remnant that opens into the seminal vesicle. The patient does not present urinary symptoms, neither pain with ejaculation nor hematuria. A triad of seminal vesicle cyst, ipsilateral renal agenesis, and ipsilateral ejaculatory duct obstruction is known as Zinner syndrome. Congenital anomalies of the seminal vesicles are rare; some of them are associated with malformations of the upper urinary system. Seminal vesicle cysts are associated with ipsilateral renal agenesis and ectopic or dysplastic ureter. Patients may remain asymptomatic and be diagnosed incidentally or may present with symptoms such as increased urinary frequency, dysuria, recurrent infections, pain with ejaculation, and perineal discomfort.
Relationship between Poorly Controlled Asthma and Sleep-Related Breathing Disorders in Children with Asthma: A Two-Center Study
Authors: Guo Yun , Zhang Xiuqing , Liu Feng , Li Ling , Zhao Deyu , Qian Jun 
Published: January 2021

Objective. Asthma and sleep-related breathing disorders (SRBD) are common chronic respiratory diseases in children. The relationship between asthma and SRDB is bidirectional. However, only a few studies have analyzed the relationship between asthma control status and risk of SRBD. The aim of this study was to evaluate the relationship between asthma control and SRBD and further assess the relationship between therapy/atopy/lung function of children with asthma and SRBD. Methods. A total of 209 children aged 3–16 years were enrolled in this study. Pediatric sleep questionnaire (PSQ) scores were used to identify children at high risk of developing SRBD. Data on asthma control status, therapy, allergy, lung function, and exhaled nitric oxide were collected. Results. A significantly higher risk of SRBD was found among children with poorly controlled asthma (34.25% vs. 13.97%,

P

< 0.01) and allergic rhinitis (AR) (34.29% vs. 13.92%,

P

< 0.01) than among children with well-controlled asthma and AR. The prevalence of SRBD was also significantly higher in asthmatic children with obesity than that with just obesity (42.11% vs. 20.00%,

P

< 0.05). Multiple logistic regression analysis showed that poorly controlled asthma (OR, 2.746 (95% CI, 1.215–6.209);

P

< 0.05) and poorly controlled AR (OR, 3.284 (95% CI, 1.430–7.544);

P

< 0.01) increased the odds of having SRBD. Conclusion. Poorly controlled asthma and AR increase the risk of SRBD. A routine check of the level of asthma control and appropriate use of medication for AR are important because of their influence on SRBD.
3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer
Authors: Peck Barrie , Bland Philip , Mavrommati Ioanna , Muirhead Gareth , Cottom Hannah , Wai Patty T. , Maguire Sarah L. , Barker Holly E. , Morrison Eamonn , Kriplani Divya , Yu Lu , Gibson Amy , Falgari Giulia , Brennan Keith , Farnie Gillian , Buus Richard , Marlow Rebecca , Novo Daniela , Knight Eleanor , Guppy Naomi , Kolarevic Daniela , Susnjar Snezana , Milijic Natasa Medic , Naidoo Kalnisha , Gazinska Patrycja , Roxanis Ioannis , Pancholi Sunil , Martin Lesley-Ann , Holgersen Erle M. , Cheang Maggie C.U. , Noor Farzana , Postel-Vinay Sophie , Quinn Gerard , McDade Simon , Krasny Lukas , Huang Paul , Daley Frances , Wallberg Fredrik , Choudhary Jyoti S. , Haider Syed , Tutt Andrew N. , Natrajan Rachael 
Published: January 2021

Abstract

Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies for this hard-to-treat patient population, yet studies using high-throughput and accurate models to define the functions of driver genes in TNBC to date have been limited. Here, we employed unbiased functional genomics screening of the 200 most frequently mutated genes in breast cancer, using spheroid cultures to model in vivo–like conditions, and identified the histone acetyltransferase CREBBP as a novel tumor suppressor in TNBC. CREBBP protein expression in patient tumor samples was absent in 8% of TNBCs and at a high frequency in other tumors, including squamous lung cancer, where CREBBP-inactivating mutations are common. In TNBC, CREBBP alterations were associated with higher genomic heterogeneity and poorer patient survival and resulted in upregulation and dependency on a FOXM1 proliferative program. Targeting FOXM1-driven proliferation indirectly with clinical CDK4/6 inhibitors (CDK4/6i) selectively impaired growth in spheroids, cell line xenografts, and patient-derived models from multiple tumor types with CREBBP mutations or loss of protein expression. In conclusion, we have identified CREBBP as a novel driver in aggressive TNBC and identified an associated genetic vulnerability in tumor cells with alterations in CREBBP and provide a preclinical rationale for assessing CREBBP alterations as a biomarker of CDK4/6i response in a new patient population.

Significance:
This study demonstrates that CREBBP genomic alterations drive aggressive TNBC, lung cancer, and lymphomas and may be selectively treated with clinical CDK4/6 inhibitors.
The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention
Authors: Khan Tashbib , Kryza Thomas , Lyons Nicholas J. , He Yaowu , Hooper John D. 
Published: January 2021

Abstract
CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for oncogenic signaling and its key roles in malignant transformation and summarize approaches focused on exploiting it for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with progressive disease and markedly poorer survival. Predominantly located on the cell surface, CDCP1 lies at the nexus of key tumorigenic and metastatic signaling cascades, including the SRC/PKCδ, PI3K/AKT, WNT, and RAS/ERK axes, the oxidative pentose phosphate pathway, and fatty acid oxidation, making important functional contributions to cancer cell survival and growth, metastasis, and treatment resistance. These findings have stimulated the development of agents that target CDCP1 for detection and treatment of a range of cancers, and results from preclinical models suggest that these approaches could be efficacious and have manageable toxicity profiles.
Drugging the “Undruggable” MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers
Authors: Wolpaw Adam J. , Bayliss Richard , Büchel Gabriele , Dang Chi V. , Eilers Martin , Gustafson W. Clay , Hansen Gwenn H. , Jura Natalia , Knapp Stefan , Lemmon Mark A. , Levens David , Maris John M. , Marmorstein Ronen , Metallo Steven J. , Park Julie R. , Penn Linda Z. , Rape Michael , Roussel Martine F. , Shokat Kevan M. , Tansey William P. , Verba Kliment A. , Vos Seychelle M. , Weiss William A. , Wolf Elmar , Mossé Yaël P. 
Published: January 2021

AbstractEffective treatment of pediatric solid tumors has been hampered by the predominance of currently “undruggable” driver transcription factors. Improving outcomes while decreasing the toxicity of treatment necessitates the development of novel agents that can directly inhibit or degrade these elusive targets. MYCN in pediatric neural-derived tumors, including neuroblastoma and medulloblastoma, is a paradigmatic example of this problem. Attempts to directly and specifically target MYCN have failed due to its similarity to MYC, the unstructured nature of MYC family proteins in their monomeric form, the lack of an understanding of MYCN-interacting proteins and ability to test their relevance in vivo, the inability to obtain structural information on MYCN protein complexes, and the challenges of using traditional small molecules to inhibit protein–protein or protein–DNA interactions. However, there is now promise for directly targeting MYCN based on scientific and technological advances on all of these fronts. Here, we discuss prior challenges and the reasons for renewed optimism in directly targeting this “undruggable” transcription factor, which we hope will lead to improved outcomes for patients with pediatric cancer and create a framework for targeting driver oncoproteins regulating gene transcription.