bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae–Induced Rash and Mucositis Concept
Authors: Mayor‐Ibarguren Ander , Feito‐Rodriguez Marta , González‐Ramos Jéssica , del Rosal‐Rabes Teresa , González‐Sainz Francisco Javier , Sánchez‐Orta Alba , de Lucas‐Laguna Raul 
Published: June 2017

AbstractThe term Mycoplasma pneumoniae–induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens–Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.
Low Cryptococcus Antigen Titers as Determined by Lateral Flow Assay Should Be Interpreted Cautiously in Patients without Prior Diagnosis of Cryptococcal Infection
Authors: Dubbels Marie , Granger Dane , Theel Elitza S. 
Published: June 2017

ABSTRACT

Detection of
Cryptococcus
antigen (CrAg) is invaluable for establishing cryptococcal disease. Multiple different methods for CrAg detection are available, including a lateral flow assay (LFA). Despite excellent performance of the CrAg LFA, we have observed multiple cases of low-titer (≤1:5) positive CrAg LFA results in patients for whom cryptococcosis was ultimately excluded. To investigate the accuracy of low-titer positive CrAg LFA results, we performed chart reviews for all patients with positive CrAg LFA results between June 2014 and December 2016. During this period, serum and/or cerebrospinal fluid (CSF) samples from 3,969 patients were tested with the CrAg LFA, and 55 patients (1.5%) tested positive. Thirty-eight of those patients lacked a history of cryptococcal disease and were the focus of this study. Fungal culture or histopathology confirmed
Cryptococcus
infection for 20 patients (52.6%), and CrAg LFA titers in serum and CSF samples ranged from 1:5 to ≥1:2,560. For the 18 patients (47.4%) without culture or histopathological confirmation, the CrAg LFA results were considered true-positive results for 5 patients (titer range, 1:10 to ≥1:2,560), due to clinical improvement with targeted therapy and decreasing CrAg LFA titers. The remaining 13 patients had CrAg LFA titers of 1:2 (
n
= 11) or 1:5 (
n
= 2) and were ultimately diagnosed with an alternative condition (
n
= 11) or began therapy for possible cryptococcosis without improvement (
n
= 2), leading to an overall CrAg LFA false-positive rate of 34%. We recommend careful clinical correlation prior to establishing a diagnosis of cryptococcal infection for patients with first-time positive CrAg LFA titers of 1:2.
Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus
Authors: Liu Baocheng , Dong Shishang , Li Guobang , Wang Wenming , Liu Xiang , Wang Yantong , Yang Cheng , Rao Zihe , Guo Yu 
Published: June 2017

ABSTRACT

Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form a ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNPs undergo a transition from an RNA-bound form to a template-free form, to open access for the interaction between the viral polymerase and the RNA template. In filoviruses, this transition is regulated by VP35 peptide and other viral components. To further understand the dynamic process of filovirus RNP formation, we report here the structure of MARV NP
core
, both in the apo form and in the VP35 peptide-chaperoned form. These structures reveal a typical bilobed structure, with a positive-charged RNA binding groove between two lobes. In the apo form, the MARV NP exists in an interesting hexameric state formed by the hydrophobic interaction within the long helix of the NP
core
C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NP
core
remains in a monomeric state and completely loses its affinity for single-stranded RNA (ssRNA). The structural comparison reveals that the RNA binding groove undergoes a transition from closed state to open state, chaperoned by VP35 peptide, thus preventing the interaction for viral RNA. Our investigation provides considerable structural insight into the filovirus RNP working mechanism and may support the development of antiviral therapies targeting the RNP formation of filovirus.

IMPORTANCE
Marburg virus is one of the most dangerous viruses, with high morbidity and mortality. A recent outbreak in Angola in 2005 caused the deaths of 272 persons. NP is one of the most essential proteins, as it encapsidates and protects the whole virus genome simultaneously with self-assembly oligomerization. Here we report the structures of MARV NP
core
in two different forms. In the MARV NP apo form, we identify an interesting hexamer formed by hydrophobic interaction within a long helix, which is highly conserved and flexible among filoviruses and may indicate its critical function during the virus RNP formation. Moreover, the structural comparison with the NP-VP35 peptide complex reveals a structural transition chaperoned by VP35, in which the RNA binding groove undergoes a transition from closed state to open state. Finally, we discussed the high conservation and critical role of the VP35 binding pocket and its potential use for therapeutic development.
The effect of substrate bias on the characteristics of CrN coatings deposited by DC-superimposed HiPIMS system
Authors: Zuo X. , Xia F. , Zhang D. , Ke P. L. , Wang Q. M. , Wang A. Y. 
Published: June 2017

Chromium nitride coatings were prepared by reactive DC-superimposed high-power-impulse magnetron sputtering (HiPIMS) system. The influence of substrate bias on the microstructure and mechanical properties of CrN coatings was investigated. XRD and cross-sectional SEM were utilized to characterize the film structures. Mechanical properties were characterized by nanoindentation and Vickers indentation test. The results revealed that the microstructure and mechanical properties of CrN coatings were affected by bias voltage. The CrN coatings exhibited dense and fine columnar grain structure with the hardness of about 18.7 GPa. The fracture toughness of CrN coatings was around 3.16 MPa ⋅ m[Formula: see text]. However, further increase of the bias voltage from −250 V to −300 V led to the degradation of coating properties.
The importance of illitic minerals in shale instability and in unconventional hydrocarbon reservoirs
Authors: Wilson M. J. , Wilson L. , Shaldybin M. V. 
Published: June 2017

Abstract
It is generally accepted that the clay mineralogy of the shale formation is a primary causative factor of shale instability. This review considers a scenario of shale instability relating to illitic minerals. From the literature the thickness of the double electric layer (DEL) of the aqueous solutions associated with the charged external surfaces of clay minerals is of the same order or even thicker than the sizes of a significant proportion of the pores found in shales. In these circumstances, overlap of the DELs associated with the exposed outer surfaces of clay minerals on opposing sides of slit-like micropores (<2 nm in diameter) and mesopores (2–50 nm in diameter) in a lithostatically compressed shale would bring about electrostatic repulsion and lead to increased pore/hydration pressure in illitic shales. In shales and sandstones, illitic material is usually described in terms of two different phases, namely illite per se and mixed-layer illite–smectite (I/S). Evidence is presented to show that it is often the case that only one illite phase exists and that in reality the mixed-layer I/S is simply very thin illite (<5 nm in thickness) in the early stages of its growth. Such material is of common occurrence in the unconventional hydrocarbon reservoirs of the USA.
Microstructural controls on the pressure-dependent permeability of Whitby mudstone
Authors: McKernan Rosanne , Mecklenburgh Julian , Rutter Ernie , Taylor Kevin 
Published: June 2017

Abstract

A combination of permeability and ultrasonic velocity measurements allied with image analysis is used to distinguish the primary microstructural controls on effective-pressure-dependent permeability. Permeabilities of cylindrical samples of Whitby mudstone were measured using the oscillating pore-pressure method at confining pressures ranging between 30 and 95 MPa, and at pore pressures ranging between 1 and 80 MPa. The permeability–effective pressure relationship is empirically described using a modified effective pressure law in terms of confining pressure, pore pressure and a Klinkenberg effect. Measured permeability ranges between 3×10
−21
and 2×10
−19
m
2
(3 and 200 nd), and decreases by approximately one order of magnitude across the applied effective pressure range. Permeability is shown to be less sensitive to changes in pore pressure than changes in confining pressure, yielding permeability effective pressure coefficients (χ) between 0.42 and 0.97. Based on a pore-conductivity model, which considers the measured changes in acoustic wave velocity and pore volume with pressure, the observed loss of permeability with increasing effective pressure is attributed dominantly to the progressive closure of bedding-parallel, crack-like pores associated with grain boundaries. Despite only constituting a fraction of the total porosity, these pores form an interconnected network that significantly enhances permeability at low effective pressures.

Supplementary material:
A CSV file containing all experimental conditions and a tabulation of results is available at
https://doi.org/10.6084/m9.figshare.c.3785741
Reflex cardiorespiratory events from esophageal origin are heightened by preterm birth
Authors: Nault Stéphanie , Samson Nathalie , Nadeau Charlène , Djeddi Djamal , Praud Jean-Paul 
Published: June 2017

The involvement of gastroesophageal refluxes in cardiorespiratory events of preterm infants remains controversial. While a few studies in full-term newborn animals have shown that stimulation of esophageal receptors leads to cardiorespiratory reflexes, the latter remain largely unknown, especially after premature birth. The present study aimed to 1) characterize the cardiorespiratory reflexes originating from esophageal receptors in newborn lambs and 2) test the hypotheses that preterm birth enhances reflex cardiorespiratory inhibition and that C-fibers are involved in these reflexes. Eight full-term lambs and 10 lambs born 14 days prematurely were studied. Following surgical instrumentation, a 6-h polysomnography was performed without sedation to record electrocardiogram, respiratory movements, arterial pressure, laryngeal constrictor muscle activity, state of alertness, and hemoglobin oxygen saturation. Five esophageal stimulations of the upper and/or lower esophagus, including rapid balloon inflation and/or HCl injection, were performed in random order. A second recording was performed in full-term lambs 24 h later, after C-fiber blockade by capsaicin. Results confirmed that esophageal stimulations induced inhibitory cardiorespiratory reflexes combined with protective mechanisms, including laryngeal closure, swallowing, coughing, increased arterial pressure, and arousal. Preterm birth heightened cardiorespiratory inhibition. The strongest cardiorespiratory inhibition was observed following simultaneous stimulation of the lower and upper esophagus. Finally, cardiorespiratory inhibition was decreased after C-fiber blockade. In conclusion, esophageal stimulation induces inhibitory cardiorespiratory reflexes, which are partly mediated by C-fibers and more pronounced in preterm lambs. Clinical relevance of these findings requires further studies, especially in conditions associated with increased cardiorespiratory events, e.g., neonatal infection. NEW & NOTEWORTHY Preterm birth heightens the cardiorespiratory events triggered by esophageal stimulation. The most extensive cardiorespiratory events are induced by simultaneous stimulation of the proximal and distal esophagus.
Pediatric Cancer Predisposition and Surveillance: An Overview, and a Tribute to Alfred G. Knudson Jr
Authors: Brodeur Garrett M. , Nichols Kim E. , Plon Sharon E. , Schiffman Joshua D. , Malkin David 
Published: June 2017

Abstract
The prevalence of childhood cancer attributable to genetic predisposition was generally considered very low. However, recent reports suggest that at least 10% of pediatric cancer patients harbor a germline mutation in a cancer predisposition gene. Although some of these children will have a family history suggestive of a cancer predisposition syndrome, many others will not. Evidence from recent pediatric studies suggests that surveillance and early detection of cancer in individuals carrying a germline cancer predisposing mutation may result in improved outcomes. However, there is a lack of consistency in the design of cancer surveillance regimens across centers both nationally and internationally. To standardize approaches, the Pediatric Cancer Working Group of the American Association for Cancer Research (AACR) convened a workshop, during which consensus screening recommendations for children with the most common cancer predisposition syndromes were developed. In general, we considered a 5% or greater chance of developing a childhood cancer to be a reasonable threshold to recommend screening. Conditions for which the cancer risk was between 1% to 5% were addressed individually. In a series of manuscripts accompanying this article, we provide recommendations for surveillance, focusing on when to initiate and/or discontinue specific screening measures, which modalities to use, and the frequency of screening. Points of controversy are also reviewed. We present the outcome of our deliberations on consensus screening recommendations for specific disorders in 18 position articles as Open Access publications, which are freely available on an AACR-managed website. Clin Cancer Res; 23(11); e1–e5. ©2017 AACR.
See all articles in the online-only CCR Pediatric Oncology Series.
Efficacy of AKT Inhibitor ARQ 092 Compared with Sorafenib in a Cirrhotic Rat Model with Hepatocellular Carcinoma
Authors: Roth Gaël S. , Macek Jilkova Zuzana , Zeybek Kuyucu Ayca , Kurma Keerthi , Ahmad Pour Séyédéh Tayébéh , Abbadessa Giovanni , Yu Yi , Busser Benoit , Marche Patrice N. , Leroy Vincent , Decaens Thomas 
Published: June 2017

Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide. The AKT pathway has been found activated in 50% of HCC cases, making it a promising target. Therefore, we assess efficacy of the allosteric AKT inhibitor ARQ 092 compared with untreated control and standard treatment, sorafenib, in vitro and in vivo. ARQ 092 blocked phosphorylation of AKT in vitro and strongly inhibited cell growth with significantly higher potency than sorafenib. Similarly, apoptosis and cell migration were strongly reduced by ARQ 092 in vitro. To mimic human advanced HCC, we used a diethylnitrosamine-induced cirrhotic rat model with fully developed HCC. MRI analyses showed that ARQ 092 significantly reduced overall tumor size. Furthermore, number of tumors was decreased by ARQ 092, which was associated with increased apoptosis and decreased proliferation. Tumor contrast enhancement was significantly decreased in the ARQ 092 group. Moreover, on tumor tissue sections, we observed a vascular normalization and a significant decrease in fibrosis in the surrounding liver of animals treated with ARQ 092. Finally, pAKT/AKT levels in ARQ 092–treated tumors were reduced, followed by downregulation of actors of AKT downstream signaling pathway: pmTOR, pPRAS40, pPLCγ1, and pS6K1. In conclusion, we demonstrated that ARQ 092 blocks AKT phosphorylation in vitro and in vivo. In the HCC-rat model, ARQ 092 was well tolerated, showed antifibrotic effect, and had stronger antitumor effect than sorafenib. Our results confirm the importance of targeting AKT in HCC. Mol Cancer Ther; 16(10); 2157–65. ©2017 AACR.
mTORC1 Inhibition Induces Resistance to Methotrexate and 6-Mercaptopurine in Ph+ and Ph-like B-ALL
Authors: Vo Thanh-Trang T. , Lee J. Scott , Nguyen Duc , Lui Brandon , Pandori William , Khaw Andrew , Mallya Sharmila , Lu Mengrou , Müschen Markus , Konopleva Marina , Fruman David A. 
Published: June 2017

Abstract
Elevated activity of mTOR is associated with poor prognosis and higher incidence of relapse in B-cell acute lymphoblastic leukemia (B-ALL). Thus, ongoing clinical trials are testing mTOR inhibitors in combination with chemotherapy in B-ALL. However, the combination of mTOR inhibitors with standard of care chemotherapy drugs has not been studied extensively in high-risk B-ALL subtypes. Therefore, we tested whether mTOR inhibition can augment the efficacy of current chemotherapy agents in Ph+ and Ph-like B-ALL models. Surprisingly, inhibiting mTOR complex 1 (mTORC1) protected B-ALL cells from killing by methotrexate and 6-mercaptopurine, two antimetabolite drugs used in maintenance chemotherapy. The cytoprotective effects correlated with decreased cell-cycle progression and were recapitulated using cell-cycle inhibitors, palbociclib or aphidicolin. Dasatinib, a tyrosine kinase inhibitor currently used in Ph+ patients, inhibits ABL kinase upstream of mTOR. Dasatinib resistance is mainly caused by ABL kinase mutations, but is also observed in a subset of ABL unmutated cases. We identified dasatinib-resistant Ph+ cell lines and patient samples in which dasatinib can effectively reduce ABL kinase activity and mTORC1 signaling without causing cell death. In these cases, dasatinib protected leukemia cells from killing by 6-mercaptopurine. Using xenograft models, we observed that mTOR inhibition or dasatinib increased the numbers of leukemia cells that emerge after cessation of chemotherapy treatment. These results demonstrate that inhibitors targeting mTOR or upstream signaling nodes should be used with caution when combined with chemotherapeutic agents that rely on cell-cycle progression to kill B-ALL cells. Mol Cancer Ther; 16(9); 1942–53. ©2017 AACR.
Elevated plasma TFPI activity causes attenuated TF-dependent thrombin generation in early onset preeclampsia
Authors: Egan Karl , O’Connor Hugh , Kevane Barry , Malone Fergal , Lennon Aine , Zadjali Amani , Cooley Sharon , Monteith Cathy , Maguire Patricia , Szklanna Paulina , Allen Seamus , McCallion Naomi , Áinle Fionnuala 
Published: June 2017

SummaryEarly onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin. Twenty-six cases of EOP were recruited over a 21-month period, out of 15,299 deliveries at the Rotunda. Blood samples were collected into sodium citrate plus corn trypsin inhibitor anticoagulated vacutainers, platelet-poor plasma was prepared, and calibrated automated thrombography was used to assess thrombin generation. Results were compared to age and sex-matched non-pregnant controls (n=13) and age-and gestation-matched pregnant controls (n=20). The rate and extent of thrombin generation triggered by low-dose tissue factor (TF) was significantly reduced in patients with EOP compared to pregnant controls, most significantly in cases of severe EOP. EOP patients displayed a trend towards an increased response to endogenous activated protein C and thrombomodulin relative to pregnant controls. Plasma tissue factor pathway inhibitor (TFPI) activity was increased in EOP patients. Inhibition of TFPI abolished the attenuation of thrombin generation stimulated by low-dose TF. In conclusion, patients with EOP are characterised by an attenuated coagulation response characterised by reduced thrombin generation stimulated by low-dose TF and elevated plasma TFPI activity. These changes in coagulation may modulate thrombotic risk and bleeding risk in patients with EOP.
Age-Related Autonomous Aldosteronism
Authors: Nanba Kazutaka , Vaidya Anand , Williams Gordon H. , Zheng Isabel , Else Tobias , Rainey William E. 
Published: June 2017

Background:
Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood.

Methods:
The relationship between age and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 127 normal adrenal glands from deceased kidney donors (age, 9 months to 68 years). Following immunohistochemistry, CYP11B2-expressing area and areas of abnormal foci of CYP11B2-expressing cells, called aldosterone-producing cell clusters, were analyzed. In a separate ancillary clinical study of 677 participants without primary aldosteronism, who were studied on both high and restricted sodium diets (age, 18–71 years), we used multivariable linear regression to assess the independent associations between age and renin-angiotensin-aldosterone system physiology.

Results:

In adrenal tissue, the total CYP11B2-expressing area was negatively correlated with age (
r
=−0.431,
P
<0.0001), whereas the total aldosterone-producing cell cluster area was positively correlated with age (
r
=0.390,
P
<0.0001). The integrated ratio of aldosterone-producing cell cluster to CYP11B2-expressing area was most strongly and positively correlated with age (
r
=0.587,
P
<0.0001). When participants in the clinical study were maintained on a high sodium balance, renin activity progressively declined with older age, whereas serum and urinary aldosterone did not significantly decline. Correspondingly, the aldosterone-to-renin ratio was positively and independently associated with older age (adjusted β=+5.54 ng/dL per ng/mL per hour per 10 years,
P
<0.001). In contrast, when participants were assessed under sodium-restricted conditions, physiological stimulation of aldosterone was blunted with older age (β=−4.6 ng/dL per 10 years,
P
<0.0001).

Conclusions:
Aging is associated with a pattern of decreased normal zona glomerulosa CYP11B2 expression and increased aldosterone-producing cell cluster expression. This histopathologic finding parallels an age-related autonomous aldosteronism and abnormal aldosterone physiology that provides 1 potential explanation for age-related cardiovascular risk.