bluuebunny/crossref_metadata_2025 huggingface dataset:
CytoBackBone: an algorithm for merging of phenotypic information from different cytometric profiles
Authors: Leite Pereira Adrien , Lambotte Olivier , Le Grand Roger , Cosma Antonio , Tchitchek Nicolas
Published: March 2019

Motivation

Flow and mass cytometry are experimental techniques used to measure the level of proteins expressed by cells at the single-cell resolution. Several algorithms were developed in flow cytometry to increase the number of simultaneously measurable markers. These approaches aim to combine phenotypic information of different cytometric profiles obtained from different cytometry panels.

Results

We present here a new algorithm, called CytoBackBone, which can merge phenotypic information from different cytometric profiles. This algorithm is based on nearest-neighbor imputation, but introduces the notion of acceptable and non-ambiguous nearest neighbors. We used mass cytometry data to illustrate the merging of cytometric profiles obtained by the CytoBackBone algorithm.

Availability and implementation

CytoBackBone is implemented in R and the source code is available at https://github.com/tchitchek-lab/CytoBackBone.

Supplementary information

Supplementary data are available at Bioinformatics online.
Oxytocin involves in chronic stress-evoked melanoma metastasis via β-arrestin 2-mediated ERK signaling pathway
Authors: Ji Haoyi , Liu Na , Li Jing , Chen Dawei , Luo Dan , Sun Qian , Yin Yingchun , Liu Yanli , Bu Bing , Chen Xiaoyang , Li Jingxin
Published: March 2019

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of OXTRs dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via β-arrestin 2-dependent ERK-VEGF/MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or β-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a β-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.
Dopamine Receptor Expression Among Local and Visual Cortex-Projecting Frontal Eye Field Neurons
Authors: Mueller Adrienne , Krock Rebecca M , Shepard Steven , Moore Tirin
Published: March 2019

Dopaminergic modulation of prefrontal cortex plays an important role in numerous cognitive processes, including attention. The frontal eye field (FEF) is modulated by dopamine and has an established role in visual attention, yet the underlying circuitry upon which dopamine acts is not known. We compared the expression of D1 and D2 dopamine receptors (D1Rs and D2Rs) across different classes of FEF neurons, including those projecting to dorsal or ventral extrastriate cortex. First, we found that both D1Rs and D2Rs are more prevalent on pyramidal neurons than on several classes of interneurons and are particularly prevalent on putatively long-range projecting pyramidals. Second, higher proportions of pyramidal neurons express D1Rs than D2Rs. Third, overall a higher proportion of inhibitory neurons expresses D2Rs than D1Rs. Fourth, among inhibitory interneurons, a significantly higher proportion of parvalbumin+ neurons expresses D2Rs than D1Rs, and a significantly higher proportion of calbindin+ neurons expresses D1Rs than D2Rs. Finally, compared with D2Rs, virtually all of the neurons with identified projections to both dorsal and ventral extrastriate visual cortex expressed D1Rs. Our results demonstrate that dopamine tends to act directly on the output of the FEF and that dopaminergic modulation of top-down projections to visual cortex is achieved predominately via D1Rs.
Antiviral Therapy for Hepatitis B Prevents Liver Injury in Patients With Tuberculosis and Hepatitis B Coinfection
Authors: Lui Grace C Y , Wong Ngai-Sze , Wong Rity Y K , Tse Yee-Kit , Wong Vincent W S , Leung Chi-Chiu , Chan Henry L Y , Wong Grace L H
Published: March 2019

Background

Chronic hepatitis B virus (HBV) infection increases the risk of liver injury in patients who undergo antituberculosis treatment. It is uncertain whether antiviral treatment for HBV at the time of tuberculosis diagnosis would reduce the risk of liver injury.

Methods

We performed a population-level, retrospective, cohort study that involved all patients with tuberculosis–HBV coinfection treated in public hospitals in Hong Kong over a 16-year period. Patients who received antiviral treatment at the time of tuberculosis diagnosis were considered “patients on antiviral therapy.” A multivariable Cox proportional hazards model was used to determine the adjusted hazard ratio of hospitalization due to drug-induced liver injury within 1 year in patients on antiviral therapy, adjusting for the propensity score.

Results

Of 3698 patients with tuberculosis–HBV coinfection, 488 (13.2%) were patients on antiviral therapy. Of the remaining 3210 patients, 446 (13.9%) started antiviral therapy within 1 year of tuberculosis diagnosis. Adjusting for the propensity score, patients on antiviral therapy had a lower risk of hospitalization due to drug-induced liver injury compared with those not on treatment (adjusted hazard ratio, 0.44; 95% confidence interval .26–.72). Compared with patients who started antiviral therapy within 1 year of tuberculosis diagnosis, patients on antiviral therapy also had a lower risk of hospitalization due to drug-induced liver injury and a lower risk of liver-related mortality.

Conclusions

We show that antiviral treatment for HBV given at the time of tuberculosis diagnosis reduced the risk of liver injury in tuberculosis–HBV coinfected patients.
Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome–like Clinical Presentation in Human Immunodeficiency Virus–infected Children in Malawi
Authors: El-Mallawany Nader Kim , Kamiyango William , Villiera Jimmy , Peckham-Gregory Erin C , Scheurer Michael E , McAtee Casey L , Allen Carl E , Kovarik Carrie L , Frank Dale , Eason Anthony B , Caro-Vegas Carolina , Chiao Elizabeth Y , Schutze Gordon E , Ozuah Nmazuo W , Mehta Parth S , Kazembe Peter N , Dittmer Dirk P
Published: March 2019

We describe 7 human immunodeficiency virus–infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6.
Blood Transcriptomic Stratification of Short-term Risk in Contacts of Tuberculosis
Authors: Roe Jennifer , Venturini Cristina , Gupta Rishi K , Gurry Celine , Chain Benjamin M , Sun Yuxin , Southern Jo , Jackson Charlotte , Lipman Marc C , Miller Robert F , Martineau Adrian R , Abubakar Ibrahim , Noursadeghi Mahdad
Published: March 2019

Background

The highest risk of tuberculosis arises in the first few months after exposure. We reasoned that this risk reflects incipient disease among tuberculosis contacts. Blood transcriptional biomarkers of tuberculosis may predate clinical diagnosis, suggesting they offer improved sensitivity to detect subclinical incipient disease. Therefore, we sought to test the hypothesis that refined blood transcriptional biomarkers of active tuberculosis will improve stratification of short-term disease risk in tuberculosis contacts.

Methods

We combined analysis of previously published blood transcriptomic data with new data from a prospective human immunodeficiency virus (HIV)–negative UK cohort of 333 tuberculosis contacts. We used stability selection as an alternative computational approach to identify an optimal signature for short-term risk of active tuberculosis and evaluated its predictive value in independent cohorts.

Results

In a previously published HIV-negative South African case-control study of patients with asymptomatic Mycobacterium tuberculosis infection, a novel 3-gene transcriptional signature comprising BATF2, GBP5, and SCARF1 achieved a positive predictive value (PPV) of 23% for progression to active tuberculosis within 90 days. In a new UK cohort of 333 HIV-negative tuberculosis contacts with a median follow-up of 346 days, this signature achieved a PPV of 50% (95% confidence interval [CI], 15.7–84.3) and negative predictive value of 99.3% (95% CI, 97.5–99.9). By comparison, peripheral blood interferon gamma release assays in the same cohort achieved a PPV of 5.6% (95% CI, 2.1–11.8).

Conclusions

This blood transcriptional signature provides unprecedented opportunities to target therapy among tuberculosis contacts with greatest risk of incident disease.
Tbx1 regulates extracellular matrix-cell interactions in the second heart field
Authors: Alfano Daniela , Altomonte Alessandra , Cortes Claudio , Bilio Marchesa , Kelly Robert G , Baldini Antonio
Published: March 2019

Tbx1, the major candidate gene for DiGeorge or 22q11.2 deletion syndrome, is required for efficient incorporation of cardiac progenitors of the second heart field (SHF) into the heart. However, the mechanisms by which TBX1 regulates this process are still unclear. Here, we have used two independent models, mouse embryos and cultured cells, to define the role of TBX1 in establishing morphological and dynamic characteristics of SHF in the mouse. We found that loss of TBX1 impairs extracellular matrix (ECM)-integrin-focal adhesion (FA) signaling in both models. Mosaic analysis in embryos suggested that this function is non-cell autonomous, and, in cultured cells, loss of TBX1 impairs cell migration and FAs. Additionally, we found that ECM-mediated integrin signaling is disrupted upon loss of TBX1. Finally, we show that interfering with the ECM-integrin-FA axis between E8.5 and E9.5 in mouse embryos, corresponding to the time window within which TBX1 is required in the SHF, causes outflow tract dysmorphogenesis. Our results demonstrate that TBX1 is required to maintain the integrity of ECM-cell interactions in the SHF and that this interaction is critical for cardiac outflow tract development. More broadly, our data identifies a novel TBX1 downstream pathway as an important player in SHF tissue architecture and cardiac morphogenesis.
A truly non-occlusive stent-graft moulding balloon for thoracic endovascular aortic repair
Authors: Gottardi Roman , Mudge Teddy , Czerny Martin , Seitelberger Rainald , Williams David F , Scherman Jacques , Bezuidenhout Deon , Zilla Peter
Published: March 2019

Endovascular treatment of thoracic aortic pathologies has recently progressed towards more proximal pathologies, including those of the aortic arch and ascending aorta where there is a higher risk for stent-graft migration during the deployment or the moulding procedure due to the beating and ejecting heart. Typical measures to prevent dislodgement of the balloon or the stent-graft during the procedure are rapid pacing or pharmacologically induced hypotension. We present a circular and fully non-occlusive stent-graft moulding balloon that does not require any reduction of cardiac output or hypotension during inflation, moulding and deflation of the balloon.
Hyperimmune Bovine Colostral Anti-CS17 Antibodies Protect Against Enterotoxigenic Escherichia coli Diarrhea in a Randomized, Doubled-Blind, Placebo-Controlled Human Infection Model
Authors: Savarino Stephen J , McKenzie Robin , Tribble David R , Porter Chad K , O’Dowd Aisling , Sincock Stephanie A , Poole Steven T , DeNearing Barbara , Woods Colleen M , Kim Hye , Grahek Shannon L , Brinkley Carl , Crabb Joseph H , Bourgeois A Louis
Published: March 2019

Background

Enterotoxigenic Escherichia coli (ETEC) commonly cause diarrhea in children living in developing countries and in travelers to those regions. ETEC are characterized by colonization factors (CFs) that mediate intestinal adherence. We assessed if bovine colostral IgG (bIgG) antibodies against a CF, CS17, or antibodies against CsbD, the minor tip subunit of CS17, would protect subjects against diarrhea following challenge with a CS17-expressing ETEC strain.

Methods

Adult subjects were randomized (1:1:1) to receive oral bIgG against CS17, CsbD, or placebo. Two days prior to challenge, subjects began dosing 3 times daily with the bIgG products (or placebo). On day 3, subjects ingested 5 × 109 cfu ETEC strain LSN03-016011/A in buffer. Subjects were assessed for diarrhea for 120 hours postchallenge.

Results

A total of 36 subjects began oral prophylaxis and 35 were challenged with ETEC. While 50.0% of the placebo recipients had watery diarrhea, none of the subjects receiving anti-CS17 had diarrhea (P = .01). In contrast, diarrhea rates between placebo and anti-CsbD recipients (41.7%) were comparable (P = 1.0).

Conclusions

This is the first study to demonstrate anti-CS17 antibodies provide significant protection against ETEC expressing CS17. More research is needed to better understand why anti-CsbD was not comparably efficacious.

Clinical Trials Registration. NCT00524004
Effectiveness of birthing kits for clean childbirth: a systematic review
Authors: Lassi Zohra S , Fisher Zeshi , Andraweera Prabha , Cummins Alexandra , Roberts Claire T
Published: March 2019

Poor infection control practices during childbirth are recognised as a critical factor leading to life-threatening maternal and newborn sepsis. Therefore, this paper assesses the effectiveness of clean birth kits (CBKs) to ensure a safe birthing environment. We searched PubMed, Cochrane Library and CINAHL, as well as Google Scholar, to identify both qualitative and quantitative studies on CBKs published in English up to November 2018. Studies were included if the pregnant women or women giving birth intended to use or used a CBK. The methodological quality of included papers was assessed. A total of 37 studies, 26 quantitative and 11 qualitative studies, were included. Quantitative studies showed a positive impact of CBKs on reducing the incidence of puerperal sepsis and neonatal tetanus. The review also identified CBK use to be associated with a reduction in perinatal, neonatal and young infant mortality. Qualitative studies suggested that a lack of awareness of the importance of CBKs and clean delivery practices, unavailability of CBKs and financial constraints to purchase CBKs were the potential barriers. CBKs appear to be a promising strategy to reduce maternal and neonatal morbidity and mortality. However, the current evidence is limited and further large-scale trials are required.
Characterization of linezolid-resistance-associated mutations in Mycobacterium tuberculosis through WGS
Authors: Pi Rui , Liu Qingyun , Jiang Qi , Gao Qian
Published: March 2019

Objectives

Linezolid is becoming an important antibiotic for treating MDR/XDR TB, but the mutations conferring resistance to linezolid remain inadequately characterized. Herein, we investigated the linezolid-resistance-associated mutations on a whole-genome scale through parallel selections of resistant isolates in vitro.

Methods

Ten parallel Mycobacterium tuberculosis H37Rv cultures were subjected to spontaneous mutant selection on 7H11 agar plates containing 2.5 mg/L linezolid. The linezolid resistance of resulting colonies was confirmed by growth on a second linezolid plate. WGS was then performed to identify mutations associated with linezolid resistance.

Results

Of 181 colonies appearing on the initial linezolid plates, 154 were confirmed to be linezolid resistant. WGS showed that 88.3% (136/154) of these isolates had a T460C mutation in rplC, resulting in a C154R substitution. The other 18 isolates harboured a single mutation in the rrl gene, with G2814T and G2270T mutations accounting for 7.8% (12/154) and 3.9% (6/154), respectively.

Conclusions

No mutations in novel genes were associated with linezolid resistance in a whole-genome investigation of 154 linezolid-resistant isolates selected in vitro. These results emphasize that rrl and rplC genes should be the major targets for molecular detection of linezolid resistance.
Discordance Between Serology and Histology for Celiac Disease in a Cohort with Coexisting Liver Disorders
Authors: Cvetkovic Lena , Bernard Gabriel , Galette Nathanaelle , Hétu Pierre-Olivier , Vincent Catherine , Bouin Mickael , Therrien Amelie
Published: March 2019

Background

The liver and celiac disease (CeD) share a complex relationship. While in some patients, isolated hypertransaminasemia is the only manifestation of CeD, liver diseases (LD) may also be associated with the presence of isolated tissue transglutaminase antibodies IgA (tTG IgA) without histologic evidence of CeD.

Aims

To examine the yield of tTG IgA testing (a) in the workup for chronic liver disease (CLD) or cytolysis and (b) to identify biopsy-confirmed CeD (BxCeD) among patients with concomitant LD.

Methods

Retrospective study including two cohorts. Cohort 1 represented 444 consecutive individuals without known CeD for which liver specialists requested tTG IgA. Incidence of positive tTG and BxCeD was evaluated. Cohort 2 included 212 consecutive individuals with positive tTG IgA and subsequent duodenal biopsies. The frequency and clinical characteristics of individuals without BxCeD were examined, with and without concurrent LD.

Results

The rate of first time positive tTG IgA among the tests requested by a liver specialist (cohort 1) was 2.0% (n = 9). However, 33.0% (n = 3) of these patients did not have BxCeD. Cohort 2 included 33 individuals with coexisting LD, of which 42.4% did not have BxCeD, compared with 16.2% of the patients without LD (P < 0.001). The majority of the patients without BxCeD (65.1%) showed an increase < 3 times upper limit of normal of tTG IgA.

Conclusions

Although there is clinical value in testing for CeD in the context of LD, there could be a high rate of positive CeD serology unaccompanied by histologic signs in patients with coexisting LD.
The Harmonic-Bass Divorce in Rock
Authors: De Clercq Trevor
Published: March 2019

Prior authors have identified cases of independence between melody and harmony in rock, dubbed the “melodic-harmonic divorce” (e.g., Temperley 2007). This article shows that a similar type of independence often exists between harmony and bass, which I refer to as the “harmonic-bass divorce.” I categorize instances of harmonic-bass divorce using the three types of melodic-harmonic divorce introduced by Nobile (2015): hierarchy, syntax, and loop divorce. Although the concept of harmonic-bass divorce intersects with extant theoretical constructs, I argue that viewing the bass and harmony as separate layers helps explain the organization of what might otherwise appear to be arbitrary chord extensions.
Beliefs and Self-reported Practices of Health Care Professionals Regarding Electronic Nicotine Delivery Systems: A Mixed-Methods Systematic Review and Synthesis
Authors: Erku Daniel A , Gartner Coral E , Morphett Kylie , Steadman Kathryn J
Published: March 2019

Aims

This review explores the (1) beliefs and attitudes of health care professionals (HCPs) toward electronic nicotine delivery systems (ENDS) including use as a smoking cessation aid and/or harm reduction, safety and regulation, and (2) the extent and content of patient–HCP communication about ENDS.

Methods

PubMed, Embase, CINAHL, and PsycINFO were searched to identify articles published since 2003. The Mixed Methods Appraisal Tool and Strengthening the Reporting of Observational Studies in Epidemiology checklists were used to assess the quality of studies. Thematic synthesis was used to analyze qualitative data.

Results

A total of 45 articles (32 quantitative, 12 qualitative, and 1 mixed) were included. There was wide variation regarding beliefs about the efficacy of ENDS as a cessation aid. Although the majority of HCPs believes that ENDS are safer than combustible cigarettes, they also have concern about the short and long-term safety of ENDS, uptake by adolescents, and the potential for ENDS to act as a “gateway” to smoking cigarettes. Beliefs about ENDS are influenced by media stories and experiences provided by patients. Although most HCPs do not proactively recommend ENDS, they are more likely to support ENDS use among patients with smoking related comorbidities, heavy smokers with previous unsuccessful quit attempts, or patients who express interest in trying them.

Conclusions

Overall, HCPs hold diverse views about the efficacy of ENDS and expressed wariness over their potential health effects. HCP endorsement of ENDS use seems to depend largely on patient health status, the presence of other competing risk factors and patient preferences.

Implication

Although evidence on safety and efficacy of ENDS is emerging, HCPs should be honest with their clients, stating that the long-term safety is not yet established but what is known is that they appear to be a lower risk alternative to cigarettes. Our review highlights a need for further training and support for HCPs regarding ENDS use, which would enable them to guide their clients in making evidence-based decisions.
Multifactor Assessment of Non-Antimicrobial Soap Performance
Authors: Bingham James , Cartner Todd J , Mays Suko Patricia A , Leslie Rachel A
Published: March 2019

A non-antimicrobial soap was benchmarked against 2 reference soaps for microbial removal and skin compatibility, key factors in soap effectiveness and usage. The non-antimicrobial test soap removed more Staphylococcus aureus (P = .024) when applied to nonwetted hands and showed no difference in skin barrier function compared with the reference soaps (P = .736).
Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of a Ventricular Shunt: Technical Report
Authors: Yang Andrew I , Chaibainou Hanane , Wang Sumei , Hitti Frederick L , McShane Brendan J , Tilden David , Korn Matthew , Blanke Aaron , Dayan Mor , Wolf Ronald L , Baltuch Gordon H
Published: March 2019

BACKGROUND

A recent randomized controlled trial of magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) for essential tremor (ET) demonstrated safety and efficacy. Patients with ventricular shunts may be good candidates for FUS to minimize hardware-associated infections.

OBJECTIVE

To demonstrate feasibility of FUS in this subset of patients.

METHODS

A 74-yr-old male with medically refractory ET, and a right-sided ventricular shunt for normal pressure hydrocephalus, underwent FUS to the right ventro-intermedius (VIM) nucleus. The VIM nucleus was directly targeted using deterministic tractography. Clinical outcomes were measured using the Clinical Rating Scale for Tremor.

RESULTS

Shunt components required 6% of the total ultrasound transducer elements to be shut off. Eight therapeutic sonications were delivered (maximum temperature, 64°), leading to a 90% improvement in hand tremor and a 100% improvement in functional disability at the 3-mo follow-up. No complications were noted.

CONCLUSION

This is the first case of FUS thalamotomy in a patient with a shunt. Direct VIM targeting and achievement of therapeutic temperatures with acoustic energy is feasible in this subset of patients.
Go for the Gold: A “Plane” and Simple Technique for Resecting Benign Peripheral Nerve Sheath Tumors
Authors: Stone Jonathan J , Spinner Robert J
Published: March 2019

BACKGROUND

Intraneural dissection is a useful technique for achieving gross total resection and preserving functional fascicles for peripheral nerve tumors. Finding the correct tissue plane is the critical step for safe successful enucleation. The authors hypothesized that the yellow color of benign nerve tumors can be used to identify surgical planes.

OBJECTIVE

To describe a technique to find the correct intraneural dissection plane based on a quantified yellow appearance during resection of benign peripheral nerve sheath tumors.

METHODS

Intraoperative photographs were reviewed to determine the percentage of yellow that tumors appeared at different phases of surgery. A technique was developed to quantitatively measure the amount of yellow using Photoshop. Previously published journal articles containing color images of peripheral nerve tumor resections were also analyzed for yellow tumor color.

RESULTS

There were 24 patients with suitable images to permit measurement of color for 3 steps of the procedure. The average percentages of yellow for tumor exposure, tumor resection, and removed specimen were 36.5%, 59.1%, and 80.4%, respectively (P < .001). Three publications were found that contained high-quality images of at least 2 phases of the surgery with average yellow content of 47.4% and 84% (P < .01).

CONCLUSION

The simple observation that a benign nerve sheath tumor is yellow in color can be used to guide surgical resection and achieve excellent outcomes. Intraneural dissection through the pseudocapsule should be pursued layer by layer until a yellow true capsule is found. By sparing functional nervous tissue within the pseudocapsule, this technique may lead to improved neurological outcomes.
The Activity of Commercial Lobbies in the Israeli Knesset During 2015–2018: Undermining or Realising the Democratic Foundations?
Authors: Cohen Erez
Published: March 2019

The growth of political lobbyism in democratic countries in recent years is characteristic of Israel as well. This activity makes it possible for private and business entities to influence decision-making processes and the shaping of public policy in these countries. Side by side with its contribution to important democratic principles such as representing interests and political participation, it is also strongly criticised and said to be a real danger to democracy; due to this hazard, many countries, including Israel normally regulate this activity by means of the law. In contrast, some argue that this activity reflects one of the basic tenets of democracy, which includes freedom of occupation and equal opportunities. This study examines measures of commercial lobbying in Israel during the 20th Knesset’s term, presenting the number of lobbies, number of clients and degree of centralisation in this commercial industry and weighing the research data against democratic principles in general and Israel’s values. The research findings show an increase in Israel’s lobbyist activity during the 20th Knesset’s term (2015–2018), both with regard to the number of lobbyists and with regard to the number of clients represented by them.
Multi-stage Reactive Formation of Troctolites in Slow-spreading Oceanic Lithosphere (Erro–Tobbio, Italy): a Combined Field and Petrochemical Study
Authors: Basch Valentin , Rampone Elisabetta , Crispini Laura , Ferrando Carlotta , Ildefonse Benoit , Godard Marguerite
Published: March 2019

Many recent studies have investigated the replacive formation of troctolites from mantle protoliths and the compositional evolution of the percolating melt during melt–rock interaction processes. However, strong structural and geochemical constraints for a replacive origin have not yet been established. The Erro–Tobbio impregnated mantle peridotites are primarily associated with a hectometre-size troctolitic body and crosscutting gabbroic dykes, providing a good field control on melt–rock interaction processes and subsequent magmatic intrusions. The troctolitic body exhibits high inner complexity, with a host troctolite (Troctolite A) crosscut by a second generation of troctolitic metre-size pseudo-tabular bodies (Troctolite B). The host Troctolite A is characterized by two different textural types of olivine, corroded deformed millimetre- to centimetre-size olivine and fine-grained rounded undeformed olivine, both embedded in interstitial to poikilitic plagioclase and clinopyroxene. Troctolite A shows melt–rock reaction microstructures indicative of replacive formation after percolation and impregnation of mantle dunites by a reactive melt. The evolution of the texture and crystallographic preferred orientation (CPO) of olivine are correlated and depend on the melt/rock ratio involved in the impregnation process. A low melt/rock ratio allows the preservation of the protolith structure, whereas a high melt/rock ratio leads to the disaggregation of the pre-existing matrix. The mineral compositions in Troctolite A define reactive trends, indicative of the buffering of the melt composition by assimilation of olivine during impregnation. The magmatic Troctolite B bodies are intruded within the pre-existing Troctolite A and are characterized by extreme textural variations of olivine, from decimetre-size dendritic to fine-grained euhedral crystals embedded in poikilitic plagioclase. This textural variability is the result of olivine assimilation during melt–rock reaction and the correlated increase in the degree of undercooling of the percolating melt. In the late gabbroic intrusions, mineral compositions are consistent with the fractional crystallization of melts modified after the reactive crystallization of Troctolites A and B. The Erro–Tobbio troctolitic body has a multi-stage origin, marked by the transition from reactive to fractional crystallization and diffuse to focused melt percolation and intrusion, related to progressive exhumation. During the formation of the troctolitic body, the melt composition was modified and controlled by assimilation and concomitant crystallization reactions occurring at low melt supply. Similar processes have been described in ultraslow-spreading oceanic settings characterized by scarce magmatic activity.
The Posterior Lumbar Epidural Space: Three-Dimensional Reconstruction of High-Resolution MRI: Real and Potential Epidural Spaces and Their Content In Vivo
Authors: Boezaart André P , Prats-Galino Alberto , Nin Olga C , Carrera Anna , Barberán José , Escobar José M , Reina Miguel A
Published: March 2019

Objective

Our aim was to study the posterior lumbar epidural space with 3D reconstructions of magnetic resonance images (MRIs) and to compare and validate the findings with targeted anatomic microdissections.

Design

We performed 3D reconstructions of high-resolution MRIs from seven patients and normal-resolution MRIs commonly used in clinical practice from 196 other random patients. We then dissected and photographed the lumbar spine areas of four fresh cadavers.

Results

From the 3D reconstructions of the MRIs, we verified that the distribution of the posterior fat pad had an irregular shape that resembled a truncated pyramid. It spanned between the superior margin of the lamina of the caudad vertebra and beyond the inferior margin to almost halfway underneath the cephalad lamina of the cranial vertebra, and it was not longitudinally or circumferentially continuous. The 3D reconstructions of the high-definition MRI also consistently revealed a prelaminar fibrous body that was not seen in most of the usually used low-definition MRI reconstructions. Targeted microdissections confirmed the 3D reconstruction findings and also showed the prelaminar tissue body to be fibrous, crossing from side to side anterior to the cephalad half of each lamina, and spanning from the dural sac to the laminae.

Conclusions

Three-dimensional reconstructions and targeted microdissection revealed the unique appearance of posterior fat pads and a prelaminar fibrous body. The exact consistency, presence, prevalence with age, presence in other regions, and function of this body are unknown and require further research.
Inhibition of in-stent restenosis after graphene oxide double-layer drug coating with good biocompatibility
Authors: Ge Shuang , Xi Yadong , Du Ruolin , Ren Yuzhen , Xu Zichen , Tan Youhua , Wang Yazhou , Yin Tieying , Wang Guixue
Published: March 2019

In this study, we designed a double layer-coated vascular stent of 316L stainless steel using an ultrasonic spray system to achieve both antiproliferation and antithrombosis. The coating included an inner layer of graphene oxide (GO) loaded with docetaxel (DTX) and an outer layer of carboxymethyl chitosan (CMC) loaded with heparin (Hep). The coated surface was uniform without aggregation and shedding phenomena before and after stent expanded. The coating treatment was able to inhibit the adhesion and activation of platelets and the proliferation and migration of smooth muscle cells, indicating the excellent biocompatibility and antiproliferation ability. The toxicity tests showed that the GO/DTX and CMC/Hep coating did not cause deformity and organ abnormalities in zebrafish under stereomicroscope. The stents with GO double-layer coating were safe and could effectively prevent thrombosis and in-stent restenosis after the implantation into rabbit carotid arteries for 4–12 weeks.
Functional and structural magnetic resonance imaging correlates of fatigue in patients with rheumatoid arthritis
Authors: Basu Neil , Kaplan Chelsea M , Ichesco Eric , Larkin Tony , Schrepf Andrew , Murray Alison D , Clauw Daniel J , Waiter Gordon D , Harris Richard E
Published: March 2019

Objectives

Fatigue is a major burden among patients with RA, yet is poorly understood. We sought to conduct the first imaging study to investigate the neurobiological correlates of fatigue in RA and to improve upon the methodological limitations of previous neuroimaging studies that have investigated this symptom in other populations.

Methods

Chronically fatigued RA patients were clinically characterized before undertaking a combined functional and structural mode MRI brain scan. The functional sequences were acquired during a fatigue-evoking task, then network-to-whole-brain analyses were undertaken. The structural analyses employed voxel-based morphometry in order to quantify regional grey matter volume. The scan was repeated 6 months later to test reproducibility.

Results

Fifty-four participants attended both scans [n = 41 female; baseline mean (s.d.) age 54.94 (11.41) years]. A number of significant functional and structural neural imaging correlates of fatigue were identified. Notably, patients who reported higher levels of fatigue demonstrated higher levels of functional connectivity between the Dorsal Attention Network and medial prefrontal gyri, a finding that was reproduced in the repeat scans. Structurally, greater putamen grey matter volumes significantly correlated with greater levels of fatigue.

Conclusion

Fatigue in RA is associated with functional and structural MRI changes in the brain. The newly identified and reproduced neural imaging correlates provide a basis for future targeting and stratification of this key patient priority.
ASSESSMENT ON THE INTERCHANGEABILITY OF PERSONAL EFFECTIVE DOSE ALGORITHMS IN FLUOROSCOPY-GUIDED INTERVENTIONS USING BLAND-ALTMAN ANALYSIS
Authors: Bohari Asmah , Hashim Suhairul , Ghoshal Sib Krishna , Mohd Mustafa Siti Norsyafiqah
Published: March 2019

Long exposure to radiation from fluoroscopy-guided interventions (FGIs) can be detrimental to both patients and radiologists. The effective doses received by the interventional radiology staff after performing 230 FGIs in a year were assessed by using double dosimetry and five various algorithms. The Shapiro–Wilk test revealed normally-distributed data (p < 0.01), while the significant correlation coefficients between the effective doses ranged between 0.88 and 1.00. As for the Bland–Altman analysis, both Niklason and Boetticher algorithms strongly supported the absence of statistical significance between the estimated effective doses. This portrays that the occupational doses received by the interventional radiology staff during FGIs fall within the acceptable limit regardless of the varied algorithms applied. In short, the Niklason and Boetticher algorithms appeared to be the more interchangeable ones for effective evaluation of doses. This is in view of their strong mutual correlations and excellent agreement.
Sources and Resources Affidavits in Proceedings in Lunacy, 1719–1733: The Court of Chancery and the Fate of Lunatics in the Long Eighteenth Century
Authors: Paley Ruth
Published: March 2019

This article provides a preliminary examination of ways in which the records of the court of chancery can be used to explore the experiences of those deemed to be lunatics during the long eighteenth century. The complexity of the records and variable quality of cataloguing means that these records are difficult to access and use and that the information they contain may be contested. The affidavits in lunacy held in C 217/55 are nevertheless a source of unrivalled richness for the study of mental illness as experienced, perceived and treated in the early eighteenth century. Similarly valuable documents may survive elsewhere in the records of the court of chancery, but until detailed archival work can be carried out, they will probably remain invisible and inaccessible to researchers.
Strengthening Public Health Leadership in Africa: An Innovative Fellowship Program
Authors: Kimball Ann Marie , Harper David , Creamer Kellie , Adeyemi Ade , Yates Robert , Lillywhite Louis , Told Michaela , Heymann David L.
Published: March 2019

Problem

The Ebola virus disease crisis in West Africa revealed critical weaknesses in health policy and systems in the region, including the poor development and retention of policy leaders able to set sound policy to improve health. Innovative models for enhancing the capabilities of emerging leaders while retaining their talent in their countries are vital.

Approach

Chatham House (London, United Kingdom) established the West African Global Health Leaders Fellowship to help develop the next generation of West African public health leaders. The innovative program took a unique approach: Six weeks of intensive practical leadership and policy training in London and Geneva bookended a 10-month policy project conceived and carried out by each fellow in their home country. The program emphasized practice, site visits and observation of U.K. public health organizations, identifying resources, and networking. Strong mentorship throughout the fieldwork was a central focus. Work on the pilot phase began in June 2016; the fellows completed their program in September 2017.

Outcomes

The pilot phase of the fellowship was successful, demonstrating that this “sandwich” model for fellowships—whereby participants receive focused leadership training at the start and end of the program, minimally disrupting their lives in-country—offers exciting possibilities for enhancing leadership skills while retaining talent within Africa.

Next Steps

On the basis of this successful pilot, a second cohort of eight fellows began the program in October 2018. The expanded African Public Health Leaders Fellowship has become a central activity of Chatham House’s Centre on Global Health Security.
Do You See What I See? Reflections on the Relationship Between Transparency and Trust
Authors: O’Brien Bridget C.
Published: March 2019

The prospect of a more transparent society sounds promising. Advocates of transparency envision a future in which public trust in institutions and peoples’ trust in one another run high because all information worth viewing is readily available and open to scrutiny. As health professionals, administrators, and educators work to enact this vision, careful consideration must be given to complex processes through which transparency occurs. Using examples from the 2019 Academic Medicine Trainee-Authored Letters to the Editor, this Invited Commentary describes two ways of framing transparency. The first, and most common, characterizes transparency as the transmission of information and focuses primarily on the accuracy, objectivity, and comprehensiveness of this information. The second identifies transparency as a social process comprising communicative acts that involve three components: the content, the viewer, and the medium. By calling attention to the relationships, interactions, and materials involved when information is shared, the latter, more social perspective illuminates potential gaps in the current framing of transparency as an ideal and a valued source of knowledge and feedback for health professionals. Calling attention to the complexities of informational transparency, particularly as part of health professions education, may be an important step in efforts to fulfill the goals that likely lie at the heart of transparency efforts—namely, the desire to develop and nurture healthy relationships grounded in honesty and trust.
Contemporary treatments in prostate cancer focal therapy
Authors: Ahdoot Michael , Lebastchi Amir H. , Turkbey Baris , Wood Bradford , Pinto Peter A.
Published: March 2019

Purpose of review

Radical treatments for prostate cancer are associated with significant morbidity, including incontinence and erectile dysfunction. Advances in the field of prostate MRI and desire to reduce treatment morbidities have led to a rapid growth in focal treatments for prostate cancer. Here, we review novel focal prostate cancer treatments and their associated recent clinical data, with a particular focus on data reported within the last 24 months.

Recent findings

High-intensity focal ultrasound, focal laser ablation, irreversible electroporation, focal cryotherapy, and photodynamic therapy have been used as treatment modalities for localized prostate cancer treatment. Despite the great variety of treatment techniques, each of these modalities is characterized by a significant rate of prostate cancer persistence within treatment zones (6–50%) and the presence of residual cancer within the prostate on rebiopsy (24–49%). These treatments, however, are associated with very low rates of high-grade complications, rare incontinence, and only mild or transient reductions in erectile function. The most common adverse events are urinary tract infections, hematuria, and urinary retention.

Prostate cancer focal therapy is an attractive option for well-selected patients because of its low complication profile; however, long-term oncologic outcome is still lacking and early recurrence rates are high, limiting the ability of most urologic associations from endorsing its routine use.
Topical application of a dual PI3K/mTOR inhibitor prevents anal carcinogenesis in a human papillomavirus mouse model of anal cancer
Authors: Rademacher Brooks L. , Matkowskyj Kristina A. , LaCount Emily D. , Carchman Evie H.
Published: March 2019

Human papillomavirus (HPV) infection is the major risk factor for anal dysplasia that may progress to squamous cell carcinoma of the anus. We have previously shown that systemic administration of a PI3K/mTOR inhibitor (BEZ235), an autophagic inducer, results in decreased squamous cell carcinoma of the anus in our HPV mouse model. In this study, we investigate the effect of the local, topical application of a BEZ235 on tumor-free survival, histopathology, PI3K/mTOR, and autophagy. The rationale for investigating a topical formulation is the localized nature of anal dysplasia/cancer and the goal for creating a clinically translatable formulation to decrease anal carcinogenesis. In this study, HPV transgenic mice were given no treatment, topical BEZ235, topical 7,12 dimethylbenz[a]anthracene (DMBA) (carcinogen), or both topical DMBA + BEZ235. Mice were assessed for tumor development and treatment-related toxicities. Tissue was evaluated for histology, PI3K/mTOR inhibition (pS6 and pAkt), and autophagy (LC3β and p62). DMBA-alone mice had an average of 16.9 weeks tumor-free survival, whereas mice receiving both DMBA+topical BEZ235 had 19.3 weeks (P < 0.000001). Histopathology revealed a significant decrease in dysplasia/carcinoma with the addition of topical BEZ235 to DMBA (P < 0.000001). Comparing DMBA versus DMBA + BEZ235, topical BEZ235 resulted in a significant decrease in both pS6 and pAkt (P < 0.001). Compared with no-treatment mice, both BEZ235-treated and DMBA + BEZ235-treated mice had significantly higher LC3β expression, signifying autophagic induction (P < 0.01), whereas DMBA-treated, BEZ235-treated, and DMBA+BEZ235-treated mice had a significantly lower p62 expression, signifying active autophagy (P < 0.0005). In conclusion, consistent with systemic delivery, topical application of BEZ235 shows decreased anal carcinogenesis through the activation of autophagy.
Long noncoding RNA ZFAS1 promotes tumorigenesis through regulation of miR-150-5p/RAB9A in melanoma
Authors: Liang Lili , Zhang Zhixin , Qin Xiaowei , Gao Ying , Zhao Peng , Liu Jing , Zeng Weihui
Published: March 2019

Melanoma is the deadliest form of skin cancer and one of the most aggressive cancers. ZFAS1 is a newly identified lncRNA, playing an oncogenic role in several types of cancer. The present study aimed to investigate the function and mechanism of ZFAS1-induced regulation of melanoma. ZFAS1 expression was increased in melanoma tissues and cells compared with normal controls. ZFAS1 expression in metastatic tissues was higher than that in nonmetastatic subjects. Higher expression of ZFAS1 predicted lower survival rates. Knockdown of ZFAS1 decreased proliferation, increased apoptosis, decreased migration and invasion, and reduced epithelial–mesenchymal transition potential in melanoma cells. Moreover, ZFAS1 knockdown inhibited tumor growth in nude mice. There was a direct binding between ZFAS1 and miR-150-5p. ZFAS1 negatively regulated miR-150-5p expression and upregulation of miR-150-5p was involved in ZFAS1 knockdown-induced effect on proliferation, apoptosis, migration, and invasion. Using bioinformatics, we predicted the binding between RAB9A and miR-150-5p, and the direct interaction between RAB9A and miR-150-5p was confirmed by luciferase reporter and RNA immunoprecipitation assays. We also showed that RAB9A expression was regulated negatively by miR-150-5p, but was regulated positively by ZFAS1. Downregulation of RAB9A significantly inhibited the increase in proliferation, decrease in apoptosis, and increase in migration and invasion induced by miR-150-5p inhibitors. Moreover, RAB9A knockdown decreased proliferation, increased apoptosis, and decreased migration and invasion in melanoma cells. In summary, we confirmed the tumor-promoting role of ZFAS1 in melanoma and provide evidence for the role and mechanism of the ZFAS1/miR-150-5p/RAB9A axis. These findings may lead to novel therapeutic strategies for melanoma.