bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I manage patients with Fanconi anaemia
Authors: Dufour Carlo 
Published: May 2017

SummaryFanconi Anaemia is a rare, genetic heterogeneous multisystem disease that is the most common congenital syndrome of marrow failure. Twenty genes have been reported to cause the disease. Remarkable progress has been made over the last 20 years in the understanding of the genetic and pathophysiological mechanisms. Unfortunately, these advances have not been completely paralleled by advances in medical treatment, where the most important component remains stem cell transplantation. This therapy, although contributing to long‐term negative effects, such as increased occurrence of late malignancies, is the only current option capable of prolonging the survival of patients. In spite of relevant recent progress in matched unrelated donor transplants, the largest studies with longer follow‐up still show a superiority of matched sibling donor transplants with a success rate, in selected cohorts, of over 90%. This article reviews different aspects of the disease, including genetics, diagnosis and treatment options, with special focus on stem cell transplantation, comprehensive post‐diagnosis management, decision‐making processes and long‐term follow‐up.
What actually is Vriesea? A total evidence approach in a polyphyletic genus of Tillandsioideae (Bromeliaceae, Poales)
Authors: Gomes‐da‐Silva Janaína , Souza‐Chies Tatiana T. 
Published: May 2017

AbstractThe taxonomic delimitation of Vriesea is challenging because several diagnostic traits of the genus are shared with other genera in Tillandsioideae. The genus has no unique morphological features that distinguish it from other taxa. Earlier phylogenetic studies suggested a polyphyletic status of this genus, but taxon sampling was limited, and tests of congruence for morphological characters have not yet been performed. Here we used a total evidence approach and a more comprehensive Brazilian taxon sampling to help circumscribe Vriesea s.s. (the lineage that contains the type species). We concatenated morphological and molecular datasets for the first time to reconstruct phylogenetic hypotheses. We used 99 morphological characters and ~4 kb of plastid data (psbA‐trnH, trnK5′‐rps16, matK, trnL‐trnF) for 172 terminals, including nine genera of Tillandsioideae. We analysed datasets by parsimony analyses, with several weighting schemes considered for character‐state changes (equal weights and an implied weighting scheme that we used as a sensitivity analysis). The concatenated data resulted in a well‐resolved phylogenetic inference that provided strong evidence that the genus is not monophyletic as traditionally circumscribed. Given the congruence between morphological, molecular and geographical sources of data, we separated Vriesea into distinct lineages, and proposed a new circumscription that includes only species of Vriesea s.s. found in the Chacoan and Parana subregions.
Influence of cholangitis after preoperative endoscopic biliary drainage on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures
Authors: Kaneko Toru , Imaizumi Hiroshi , Kida Mitsuhiro , Miyata Eiji , Yamauchi Hiroshi , Okuwaki Kosuke , Iwai Tomohisa , Koizumi Wasaburo 
Published: May 2017

Background and AimPreoperative cholangitis after preoperative drainage has been reported to increase postoperative complications, particularly pancreatic fistula. We therefore examined the effects of cholangitis after preoperative endoscopic biliary drainage (EBD) on postoperative pancreatic fistula in patients with middle and lower malignant biliary strictures.MethodsThe study group comprised 102 patients who underwent EBD among patients who underwent surgery.ResultsOf the 102 patients, 33 (32%) had postoperative pancreatic fistulas, and 56 (55%) had preoperative cholangitis after preoperative drainage. Analysis of risk factors for preoperative cholangitis showed that a total bilirubin level of 2.9 mg/dL or higher (hazard ratio [HR], 2.95; 95% confidence interval [CI], 1.223–7.130; P = 0.016) and a surgical waiting time of 29 days or longer (HR, 4.23; 95% CI, 1.681–10.637; P = 0.02) were independent risk factors for cholangitis. Patients with preoperative cholangitis had a significantly higher incidence of pancreatic fistula than did patients without preoperative cholangitis (78.8 vs 21.2%; P = 0.001). Patients with biliary cancer had a significantly higher incidence of pancreatic fistula than did those with pancreatic cancer (72.7 vs 27.2%; P = 0.005). Multivariate analysis showed that preoperative cholangitis (HR, 4.8; 95% CI, 1.785–12.992; P = 0.001) and biliary cancer (HR, 3.5; 95% CI, 1.335–8.942; P = 0.006) were significant independent risk factors for postoperative pancreatic fistula.ConclusionPrevention of preoperative cholangitis, a risk factor for postoperative pancreatic fistula, is likely to decrease the incidence of postoperative pancreatic fistula.
Connexin36 localization to pinealocytes in the pineal gland of mouse and rat
Authors: Wang S. G. , Tsao D. D. , Vanderpool K. G. , Yasumura T. , Rash J. E. , Nagy J. I. 
Published: May 2017

AbstractSeveral cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein andmRNAhas been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36‐containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat. Immunofluorescence labelling of Cx36 was visualized exclusively as puncta or short immunopositive strands that were distributed throughout the pineal, and which were absent in pineal sections from Cx36 null mice. By double immunofluorescence labelling, Cx36 was localized to tryptophan hydroxylase‐positive and 5‐hydroxytryptamine‐positive pinealocyte cell bodies and their large initial processes, including at intersections of those processes and at sites displaying a confluence of processes. Labelling for the cell junction marker zonula occludens‐1 (ZO‐1) either overlapped or was closely associated with labelling for Cx36. Pinealocytes thus form Cx36‐containing gap junctions that also incorporate the scaffolding protein ZO‐1. FRIL revealed labelling of Cx36 at ultrastructurally defined gap junctions between pinealocytes, most of which was at gap junctions having reticular, ribbon or string configurations. The results suggest that the endocrine functions of pinealocytes and their secretion of melatonin is supported by their intercellular communication via Cx36‐containing gap junctions, which may now be tested by the use of Cx36 null mice.
Clinical efficacy of subgingivally‐delivered 0.75% boric acid gel as an adjunct to mechanotherapy in chronic periodontitis: A randomized, controlled clinical trial
Authors: Kanoriya Dharmendra , Singhal Sandeep , Garg Vibhuti , Pradeep Avani R. , Garg Shruti , Kumar Amit 
Published: May 2017

AbstractAimBorinic acid quinoline esters are a recently‐identified class of new antibacterial and anti‐inflammatory compounds known to inhibit osteoclastic bone resorption. They have proposed to have osteostimulative properties by causing osteoblast differentiation in vivo and in vitro. The purpose of this double‐masked, randomized, controlled clinical trial was to evaluate the effects of the subgingival delivery of boric acid gel as an adjunct to scaling and root planing (SRP) on clinical and radiographic parameters, and compare this method with SRP plus placebo gel alone in chronic periodontitis (CP) patients.MethodsThirty‐nine systemically‐healthy patients with CP were included in the present study. They were divided into two groups: (a) SRP + 0.75% boric acid gel (BA group); and (b) SRP + placebo gel (placebo group). At baseline, 3 and 6 months after treatment, clinical measurements, including plaque index, modified sulcus bleeding index, probing depth (PD), clinical attachment level (CAL), intrabony defect depth, and percentage change in radiographic defect depth reduction (DDR%) as radiographic parameters were assessed.ResultsThe mean PD reduction and mean CAL gain were greater in the BA group than the placebo group at 3 and 6 months. A significantly greater mean percentage of radiographic DDR% was found in the BA group (36.97±3.47%) compared to the placebo group (2.88±0.89%) after 6 months.ConclusionBA as an adjunct to SRP can provide a new insight into therapeutic strategies for the management of CP, but further clinical evaluations are needed.
Oral versus intravenous hypertonic saline for exercise‐associated hyponatraemia
Authors: Berger Israel 
Published: May 2017

AbstractExercise‐associated hyponatraemia is a potentially serious acute condition that may present early as asymptomatic or mildly symptomatic. Standard treatment is intravenous hypertonic saline, which can be challenging and carries some risk. An alternative may be oral therapy. We undertook a review of existing literature to assess whether paediatric populations should receive oral or intravenous hypertonic saline solutions. One study addressed our question but was aimed at a presumably adult population of runners. That study found that intravenous and oral solutions provide similar effects on biochemistry, but intravenous hypertonic saline provides superior effects on subjective relief and plasma volume.
Patient‐reported outcomes in patients co‐infected with hepatitis C virus and human immunodeficiency virus treated with sofosbuvir and velpatasvir: The ASTRAL‐5 study
Authors: Younossi Zobair M. , Stepanova Maria , Sulkowski Mark , Wyles David , Kottilil Shyam , Hunt Sharon 
Published: May 2017

AbstractBackground & AimThe fixed‐dose combination of sofosbuvir and velpatasvir (SOF/VEL) is a ribavirin‐free pan‐genotypic regimen with high efficacy. We assessed the impact of SOF/VEL on patient‐reported outcomes (PRO) of HIV‐HCV co‐infected patients.MethodsHIV‐HCV co‐infected patients were treated with 12 weeks of SOF/VEL (400 mg/100 mg daily). All subjects completed four PRO questionnaires [CLDQ‐HCV, SF‐36, FACIT‐F and WPAI:SHP] before, during and post‐treatment.ResultsASTRAL‐5 enrolled 106 HIV‐HCV co‐infected patients on stable antiretroviral therapy (age: 54.2±0.9 years, cirrhosis: 17.9%, HCV genotype 1: 73.6%). SVR‐12 was achieved by 95.3% of subjects. By week 4 of treatment, PRO scores improved from the baselines levels in 12 out of 26 calculated PRO domains (on average, +1.9 to +7.4 points on a universal 0‐100 PRO scale, all P<.05). By the end of treatment, improvements were seen in 20/26 PRO domains (+2.5% to +11.9%, P<.03). There were no significant decrements in any PRO domains during treatment. By follow‐up week 12, patients who achieved SVR‐12 experienced significant improvement in 19/26 of their PRO domains (+3.2% to +13.3%, P<.05). After controlling for baseline psychiatric co‐morbidities, improvements in PRO scores during treatment with SOF/VEL were similar to those seen in matched HCV‐mono‐infected patients treated with the same regimen (ASTRAL‐1 study). In multivariate analysis, pre‐treatment anxiety and concomitant use of opioids were the most consistent significant (P<.05) predictors of PRO impairment in HIV‐HCV patients.ConclusionsPatients with HIV‐HCV treated with SOF/VEL experience very high efficacy accompanied by early and sustained improvement of patient‐reported outcomes covering all aspects of patients’ experience.
Genome Sequence of Foot-and-Mouth Disease Virus Serotype O Lineage Ind-2001d Collected in Vietnam in 2015
Authors: Arzt Jonathan , Brito Barbara , Pauszek Steven J. , Hartwig Ethan J. , Smoliga George R. , Vu Le T. , Vu Pham P. , Stenfeldt Carolina , Rodriguez Luis L. , Long Ngo T. , Dung Do H. 
Published: May 2017

ABSTRACT
In 2015, foot-and-mouth disease (FMD) virus lineage Ind-2001 was detected for the first time in Southeast Asia. This report contains the first near-complete genome sequence of a viral isolate from this lineage collected from an outbreak in Vietnam. This novel incursion has substantial implications for regional FMD control measures.
Complete Coding Genome Sequence for Mogiana Tick Virus, a Jingmenvirus Isolated from Ticks in Brazil
Authors: Villa Erika C. , Maruyama Sandra R. , de Miranda-Santos Isabel K. F. , Palacios Gustavo , Ladner Jason T. 
Published: May 2017

ABSTRACT
Mogiana tick virus (MGTV) is a segmented jingmenvirus isolated in 2011 from cattle ticks in Brazil. Here, we present a complete coding genome sequence for MGTV isolate MGTV/V4/11, including all four segments. MGTV is evolutionarily related to the Jingmen tick virus isolates SY84 and RC27.
Complete Genome Sequence of Dolosigranulum pigrum from a Patient with Interstitial Lung Disease Using Single-Molecule Real-Time Sequencing Technology
Authors: Mukhopadhyay Rituparna , Joaquin Joselita , Hogue Robin , Fitzgerald Susan , Jospin Guillaume , Mars Kristin , Eisen Jonathan A. , Chaturvedi Vishnu 
Published: May 2017

ABSTRACT

The whole genome sequence of
Dolosigranulum pigrum
isolated from the blood of a patient with interstitial lung disease was sequenced with the Pacific Biosciences RS II platform. The genome size is 2.1 Mb with 2,127 annotated coding sequences; it contained two clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) systems.
Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration
Authors: Gilbert-Girard Shella , Gravel Annie , Artusi Sara , Richter Sara N. , Wallaschek Nina , Kaufer Benedikt B. , Flamand Louis 
Published: May 2017

ABSTRACTHuman herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency (P< 0.002); in contrast, BRACO-19 had no effect on HHV-6 integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A.IMPORTANCEHHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3′ extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the current study, we have examined the effects of a G-quadruplex binding and stabilizing agent, BRACO-19, on HHV-6A chromosomal integration. By stabilizing G-quadruplex structures, BRACO-19 affects the ability of the telomerase complex to elongate telomeres. Our results indicate that BRACO-19 reduces the number of clones harboring integrated HHV-6A. This study is the first of its kind and suggests that telomerase activity is essential to restore a functional telomere of adequate length following HHV-6A integration.
Why are there discrepancies between depressed patients’ Global Rating of Change and scores on the Patient Health Questionnaire depression module? A qualitative study of primary care in England
Authors: Robinson Jude , Khan Naila , Fusco Louise , Malpass Alice , Lewis Glyn , Dowrick Christopher 
Published: May 2017

ObjectivesOur aims were to investigate discrepancies between depressed patients’ GlobalRating of Change (GRC) and scores on the Patient Health Questionnaire depression module (PHQ-9). Our objectives were to ascertain patients’ views on the source and meaning of mismatches and assess their clinical significance.DesignQualitative study nested within a cohort, in a programme investigating the indications for prescribing antidepressants that will lead to a clinical benefit.SettingPrimary care practices in north-west England.ParticipantsWe invited 32 adults with a recent diagnosis of depression and evidence of mismatch between GRC and PHQ-9 Scores to participate. Of these, 29 completed our interviews; most were women, identified as white British, had high school education or higher, were employed or retired and had been depressed for a long time.Main measuresWe conducted semistructured interviews with a topic guide, focusing on experiences of depression; treatment experiences and expectations; effectiveness of the questionnaires; reasons for the mismatch; and social factors. Interviews were transcribed and subjected to interpretative phenomenological analysis.ResultsWe identified four themes as explanations for mismatch between GRC and PHQ-9: perceptions that GRC provided a more accurate assessment of current mental state than PHQ-9; impact of recent negative or positive life events on either measure; personal understanding of depression as normally fluctuating, and tendency to underscore on PHQ-9 as a means of self-motivation; and lack of recall.ConclusionsThe combined used of the PHQ-9 and a more open question better captures the patient’s unique experiences of mental health. This approach ascertains the relevance of symptoms to the individual’s experience and influences treatment decisions.Study registrationThis study was an element of NIHR Programme Grant RP-PG 0610 10048.
Deformational history and thermochronology of Wrangel Island, East Siberian Shelf and coastal Chukotka, Arctic Russia
Authors: Miller Elizabeth L. , Akinin V. V. , Dumitru T. A. , Gottlieb E. S. , Grove M. , Meisling K. , Seward G. 
Published: May 2017

Abstract

In Arctic Russia, south of Wrangel Island, Jura–Cretaceous fold belt structures are cut by
c.
108–100 Ma plutonic rocks and a
c.
103 Ma migmatitic complex (U–Pb, zircon) that cooled by
c.
96 Ma (
40
Ar/
39
Ar biotite); the structures are unconformably overlain by
c.
88 Ma and younger (U–Pb, zircon) volcanic rocks. Wrangel Island, with a similar stratigraphy and added exposure of Neoproterozoic basement rocks, was thought to represent the westwards continuation of the Jura–Cretaceous Brookian thrust belt of Alaska. A penetrative, high-strain, S-dipping foliation formed during north–south stretching in Triassic and older rocks, with stretched pebble aspect ratios of
c.
2:1:0.5 to 10:1:0.1. Deformation was at greenschist facies (chlorite+white mica; biotite at depth; temperature
c.
300–450°C). Microstructures suggest deformation mostly by pure shear and north–south stretching; the quartz textures and lattice preferred orientations suggest temperatures of
c.
300–450°C.
40
Ar/
39
Ar K-feldspar spectra (
n
=1) and muscovite (
n
=3) (total gas ages
c.
611–514 Ma) in Neoproterozoic basement rocks are consistent with a short thermal pulse during deformation at 105–100 Ma. Apatite fission track ages (
n
=7) indicate cooling to near-surface conditions at
c.
95 Ma. The shared thermal histories of Wrangel Island and Chukotka suggest that Wrangel deformation is related to post-shortening, north–south extension, not to fold–thrust belt deformation. Seismic data (line AR-5) indicate a sharp Moho and strong sub-horizontal reflectivity in the lower and middle crust beneath the region. Wrangel Island probably represents a crustal-scale extensional boudin between the North Chukchi and Longa basins.
Novel Androgen Receptor Coregulator GRHL2 Exerts Both Oncogenic and Antimetastatic Functions in Prostate Cancer
Authors: Paltoglou Steve , Das Rajdeep , Townley Scott L. , Hickey Theresa E. , Tarulli Gerard A. , Coutinho Isabel , Fernandes Rayzel , Hanson Adrienne R. , Denis Iza , Carroll Jason S. , Dehm Scott M. , Raj Ganesh V. , Plymate Stephen R. , Tilley Wayne D. , Selth Luke A. 
Published: May 2017

Abstract
Alteration to the expression and activity of androgen receptor (AR) coregulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR coregulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and colocated with AR at specific sites on chromatin to regulate genes relevant to disease progression. GRHL2 is itself an AR-regulated gene, creating a positive feedback loop between the two factors. The link between GRHL2 and AR also applied to constitutively active truncated AR variants (ARV), as GRHL2 interacted with and regulated ARVs and vice versa. These oncogenic functions of GRHL2 were counterbalanced by its ability to suppress epithelial–mesenchymal transition and cell invasion. Mechanistic evidence suggested that AR assisted GRHL2 in maintaining the epithelial phenotype. In summary, this study has identified a new AR coregulator with a multifaceted role in prostate cancer, functioning as an enhancer of the oncogenic AR signaling pathway but also as a suppressor of metastasis-related phenotypes. Cancer Res; 77(13); 3417–30. ©2017 AACR.