bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis
Authors: Siemieniuk Reed A , Foroutan Farid , Mirza Reza , Mah Ming Jinell , Alexander Paul E , Agarwal Arnav , Lesi Olufunmilayo , Merglen Arnaud , Chang Yaping , Zhang Yuan , Mir Hassan , Hepworth Elliot , Lee Yung , Zeraatkar Dena , Guyatt Gordon H
Published: December 2018

Objective

To assess the impact of various antiretroviral/antiviral regimens in pregnant women living with HIV or hepatitis B virus (HBV).

Design

We performed random effects meta-analysis for HIV-related outcomes and network meta-analysis for HBV outcomes, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess quality separately for each outcome.

Data sources

Embase and Medline to February 2017.

Eligibility criteria

For maternal outcomes, we considered randomised controlled trials (RCTs) comparing tenofovir-based regimens with those with alternative nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). For child outcomes, we included RCTs and comparative observational studies of tenofovir-based regimens versus alternative NRTIs regimens or, for HBV, placebo.

Results

Ten studies (seven RCTs) met the inclusion criteria for maternal and child outcomes, and an additional 33 studies (12 RCTs) met the inclusion criteria for HBV-specific outcomes. The most common comparison was tenofovir and emtricitabine versus zidovudine and lamivudine. There was no apparent difference between tenofovir-based regimens and alternatives in maternal outcomes, including serious laboratory adverse events (low certainty) and serious clinical adverse events (moderate certainty). There was no difference between NRTIs in vertical transmission of HIV: 1 more per 1000, 8 fewer to 10 more, low certainty; or vertical transmission of HBV: 7 fewer per 1000, 10 fewer to 38 more, moderate certainty. We found moderate certainty evidence that tenofovir/emtricitabine increases the risk of stillbirths and early neonatal mortality (51 more per 1000, 11 more to 150 more) and the risk of early premature delivery at <34 weeks (42 more per 1000, 2 more to 127 more).

Conclusions

Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine, but certainty is low when they are not coprescribed with lopinavir/ritonavir. Other outcomes are likely similar between antiretrovirals.

PROSPERO registration number

CRD42017054392.
Illness as a phenomenon of being-in-the-world with others: Plato’sCharmides, Kleinman and Merleau-Ponty
Authors: Bredlau Susan
Published: December 2018

Plato’sCharmides, I argue, is a remarkably productive text for confronting and questioning some common presuppositions about the body and illness, particularly when we take seriously Socrates’ claim that healing Charmides’ headaches requires first examining—and perhaps healing—his soul. I begin by turning to the work of the psychiatrist and medical anthropologist Arthur Kleinman to argue that even if the pain Charmides experiences is more ‘physical’than ‘mental’, a physical exam and physical intervention alone will not necessarily be effective in treating his headaches. Next, I turn to the work of the phenomenologist Maurice Merleau-Ponty and his discussion of the phenomenon of the ‘phantom limb’ to argue that the body, rather than simply being a physical object is, instead, primarily an experiencing subject; the body is fundamentally our way of having a world. Furthermore, illness, rather than being conceived of as either a physical or mental disorder, should instead be understood in terms of a person’s being-in-the-world with others. Finally, I return to Plato’sCharmidesand argue that, just as the phantom limb reflects the destruction of a specific way of being-in-the-world with others, Charmides’ headaches reflect the construction of a specific way of being-in-the-world with others.
Contractility surrogates derived from three-dimensional lead motion analysis and prediction of acute haemodynamic response to CRT
Authors: Ross Stian , Odland Hans Henrik , Fischer Trent , Edvardsen Thor , Gammelsrud Lars Ove , Haland Trine Fink , Cornelussen Richard , Hopp Einar , Kongsgaard Erik
Published: December 2018

Background

Patient-specific left ventricular (LV) lead optimisation strategies with immediate feedback on cardiac resynchronisation therapy (CRT) effectiveness are needed. The purpose of this study was to compare contractility surrogates derived from biventricular lead motion analysis to the peak positive time derivative of LV pressure (dP/dtmax)in patients undergoing CRT implantation.

Methods

Twenty-seven patients underwent CRT implantation with continuous haemodynamic monitoring. The right ventricular (RV) lead was placed in apex and a quadripolar LV lead was placed laterally. Biplane fluoroscopy cine films facilitated construction of three-dimensional RV–LV interlead distance waveforms at baseline and under biventricular pacing (BIVP) from which the following contractility surrogates were derived; fractional shortening (FS), time to peak systolic contraction and peak shortening of the interlead distance (negative slope). Acute haemodynamic CRT response was defined as LV ∆dP/dtmax≥ 10 %.

Results

We observed a mean increase in dP/dtmaxunder BIVP (899±205 mm Hg/s vs 777±180 mm Hg/s, p<0.001). Based on ΔdP/dtmax, 18 patients were classified as acute CRT responders and nine as non-responders (23.3%±10.6% vs 1.9±5.3%, p<0.001). The baseline RV–LV interlead distance was associated with echocardiographic LV dimensions (end diastole: R=0.61, p=0.001 and end systole: R=0.54, p=0.004). However, none of the contractility surrogates could discriminate between the acute CRT responders and non-responders (ΔFS: −2.5±2.6% vs − 2.0±3.1%, p=0.50; Δtime to peak systolic contraction: −9.7±18.1% vs −10.8±15.1%, p=0.43 and Δpeak negative slope: −8.7±45.9% vs 12.5±54.8 %, p=0.09).

Conclusion

The baseline RV–LV interlead distance was associated with echocardiographic LV dimensions. In CRT recipients, contractility surrogates derived from the RV–LV interlead distance waveform could not discriminate between acute haemodynamic responders and non-responders.
Yang–Mills theory in the SO(2,3)⋆ model of noncommutative gravity
Authors: Dimitrijević-Ćirić Marija , Gočanin Dragoljub , Konjik Nikola , Radovanović Voja
Published: December 2018

According to the standard cosmological model, thermodynamic conditions of the early Universe were such that nuclear matter existed in the state of quark–gluon plasma, rather than hadrons. On the other hand, it is generally believed that quantum gravity effects become ever more stronger as we approach the Big Bang, in particular, we expect that the phenomenon of space–time noncommutativity will be significant. Thus we are led to consider the properties of quarks and gluons in noncommutative space–time. For this, we employ the [Formula: see text] model of noncommutative gravity. As a first step towards the full theoretical treatment of the effects of noncommutativity on quark–gluon plasma, our main goal in this paper is to consistently incorporate Yang–Mills gauge fields in the [Formula: see text] framework and investigate their coupling to gravity that arises due to space–time noncommutativity. We construct an action that is invariant under deformed [Formula: see text] gauge transformations and expand it perturbatively in orders of the canonical deformation parameter [Formula: see text] via Seiberg–Witten map. In particular, we analyze the flat-space–time limit and demonstrate that residual noncommutativity induces various new couplings of quarks and gluons.
Exploring Dynamics and Structure of Biomolecules, Cryoprotectants, and Water Using Molecular Dynamics Simulations: Implications for Biostabilization and Biopreservation
Authors: Weng Lindong , Stott Shannon L. , Toner Mehmet
Published: December 2018

Successful stabilization and preservation of biological materials often utilize low temperatures and dehydration to arrest molecular motion. Cryoprotectants are routinely employed to help the biological entities survive the physicochemical and mechanical stresses induced by cold or dryness. Molecular interactions between biomolecules, cryoprotectants, and water fundamentally determine the outcomes of preservation. The optimization of assays using the empirical approach is often limited in structural and temporal resolution, whereas classical molecular dynamics simulations can provide a cost-effective glimpse into the atomic-level structure and interaction of individual molecules that dictate macroscopic behavior. Computational research on biomolecules, cryoprotectants, and water has provided invaluable insights into the development of new cryoprotectants and the optimization of preservation methods. We describe the rapidly evolving state of the art of molecular simulations of these complex systems, summarize the molecular-scale protective and stabilizing mechanisms, and discuss the challenges that motivate continued innovation in this field.
Academic Discovery of Anticancer Drugs: Historic and Future Perspectives
Authors: Carugo Alessandro , Draetta Giulio F.
Published: December 2018

The identification and prosecution of meritorious anticancer drug targets and the discovery of clinical candidates represent an extraordinarily time- and resource-intensive process, and the current failure rate of late-stage drugs is a critical issue that must be addressed. Relationships between academia and industry in drug discovery and development have continued to change over time as a result of technical and financial challenges and, most importantly, to the objective of translating impactful scientific discoveries into clinical opportunities. This Golden Age of anticancer drug discovery features an increased appreciation for the high-risk, high-innovation research conducted in the nonprofit sector, with the goals of infusing commercial drug development with intellectual capital and curating portfolios that are financially tenable and clinically meaningful. In this review, we discuss the history of academic-industry interactions in the context of antidrug discovery and offer a view of where these interactions are likely headed as we continue to reach new horizons in our understanding of the immense complexities of cancer biology.
Superfluid3He in Aerogel
Authors: Halperin W.P.
Published: December 2018

Superfluid3He is an unconventional neutral superfluid in a p-wave state with three different superfluid phases, each identified by a unique set of characteristic broken symmetries and nontrivial topology. Despite natural immunity of3He from defects and impurity of any kind, it has been found that they can be artificially introduced with high-porosity silica aerogel. Furthermore, it has been shown that this modified quantum liquid becomes a superfluid with remarkably sharp thermodynamic transitions from the normal state and between its various phases. These phases include new superfluid phases that are stabilized by anisotropy from uniform strain imposed on the silica aerogel framework, and they include new phenomena in a new class of anisotropic aerogels consisting of nematically ordered alumina strands. The study of superfluid3He in the presence of correlated, quenched disorder from aerogel serves as a model for understanding the effect of impurities on the symmetry and topology of unconventional superconductors.
Emerging Cellular Therapies for Cancer
Authors: Guedan Sonia , Ruella Marco , June Carl H.
Published: December 2018

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that engineered immune cells can serve as a powerful new class of cancer therapeutics. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Advances in T cell engineering, genetic editing, the selection of optimal lymphocytes, and cell manufacturing have the potential to broaden T cell–based therapies and foster new applications beyond oncology, in infectious diseases, organ transplantation, and autoimmunity.
Determination of Moisture Sorption Isotherm of Crosslinked Millet Flour and Oxirane Using GAB and BET
Authors: Alamri M. S. , Mohamed A. A. , Hussain S. , Ibraheem M. A. , Abdo Qasem Akram A.
Published: December 2018

Epoxy resin was prepared by crosslinking epoxidized oil and millet flour. The reaction was carried out at three different temperatures (25, 40, and 55°C) and zinc chloride levels (1, 2, and 3%). Moisture sorption isotherms were determined at 0.1 to 0.9 water activity (aw) using a gravimetric sorption analyzer (Q 2000). The sigmoidal shape (type II) of the resin isotherms exhibited lower equilibrium moisture content (EMC) at higher temperature. The experimental data were modeled using GAB (Guggenheim–Anderson–de Boer) and BET (Brunauer–Emmett–Teller). The EMC of the resin was significantly lower than that of the flour, which could be attributed to the decrease in the number of water-binding sites due to the creation of dense areas during crosslinking. The low root-mean-square error (RMSE) indicates that GAB and BET were suitable for predicting the water sorption isotherm for millet flour resin. The heat of sorption of the resin was large at low moisture content and increased at higher relative humidity. It is recommended that millet flour resin be used at relative humidity below 60%.
Effects of Renal Denervation via Renal Artery Adventitial Cryoablation on Atrial Fibrillation and Cardiac Neural Remodeling
Authors: Wang Wei , Jiang Zhaolei , Lu Rongxin , Liu Hao , Ma Nan , Cai Jie , Tang Min , Mei Ju
Published: December 2018

Introduction. Catheter-based renal denervation (RDN) could reduce cardiac sympathetic nerve activity (SNA) and inhibit atrial fibrillation (AF). However, the reliability is uncertain, because the renal sympathetic nerves are mainly distributed in the adventitial surface of the renal artery. Objective. The aims of this study were to test the hypothesis that renal artery adventitial ablation (RAAA) definitely had the effects of RDN and to study the effects of RDN via renal artery adventitial cryoablation (RAAC) on AF and cardiac neural remodeling. Methods. Twenty beagle canines were randomly assigned to two groups: the left RDN group (LRDN, n=10), which underwent left RDN via RAAC; the Sham group (n=10). After 2 months of postoperative recovery, AF vulnerability, AF duration, and histological examination were performed in both groups. Results. Compared with the Sham group, left stellate ganglion (LSG) tissue fibrosis was increased in the LRDN group. LRDN significantly increased the percentage of TH-negative ganglionic cells and decreased the density of TH-positive nerves in the LSG (P<0.001). Also, the densities of TH-positive nerves and GAP43 immunoreactivity within the left atrium (LA) were significantly decreased in the LRDN group (P<0.05). After LA burst pacing, all 10 canines (100%) could be induced AF in the Sham group, but only 4 of 10 canines (40%) could be induced AF in the LRDN group (P=0.011). The percentage of LA burst stimulation with induced AF was 26.7% (8/30) in the LRDN group, which was significantly decreased compared with that of the Sham group (53.3%, 16/30) (P=0.035). In addition, AF duration was also significantly decreased in the LRDN group (13.3 ± 5.1 s) compared with that of the Sham group (20.3 ± 7.3 s, P=0.024). Conclusions. RDN via RAAC could cause cardiac neural remodeling and effectively inhibit AF inducibility and shorten AF duration. It may be useful in selecting therapeutic approaches for AF patients.
HPGraph: High-Performance Graph Analytics with Productivity on the GPU
Authors: Yang Haoduo , Su Huayou , Lan Qiang , Wen Mei , Zhang Chunyuan
Published: December 2018

The growing use of graph in many fields has sparked a broad interest in developing high-level graph analytics programs. Existing GPU implementations have limited performance with compromising on productivity. HPGraph, our high-performance bulk-synchronous graph analytics framework based on the GPU, provides an abstraction focused on mapping vertex programs to generalized sparse matrix operations on GPU as the backend. HPGraph strikes a balance between performance and productivity by coupling high-performance GPU computing primitives and optimization strategies with a high-level programming model for users to implement various graph algorithms with relatively little effort. We evaluate the performance of HPGraph for four graph primitives (BFS, SSSP, PageRank, and TC). Our experiments show that HPGraph matches or even exceeds the performance of high-performance GPU graph libraries such as MapGraph, nvGraph, and Gunrock. HPGraph also runs significantly faster than advanced CPU graph libraries.
Autocrine TGFβ Is a Survival Factor for Monocytes and Drives Immunosuppressive Lineage Commitment
Authors: Gonzalez-Junca Alba , Driscoll Kyla E. , Pellicciotta Ilenia , Du Shisuo , Lo Chen Hao , Roy Ritu , Parry Renate , Tenvooren Iliana , Marquez Diana M. , Spitzer Matthew H. , Barcellos-Hoff Mary Helen
Published: December 2018

Transforming growth factor β (TGFβ) is an effector of immune suppression and contributes to a permissive tumor microenvironment that compromises effective immunotherapy. We identified a correlation between TGFB1 and genes expressed by myeloid cells, but not granulocytes, in The Cancer Genome Atlas lung adenocarcinoma data, in which high TGFB1 expression was associated with poor survival. To determine whether TGFβ affected cell fate decisions and lineage commitment, we studied primary cultures of CD14+ monocytes isolated from peripheral blood of healthy donors. We discovered that TGFβ was a survival factor for CD14+ monocytes, which rapidly executed an apoptotic program in its absence. Continued exposure to TGFβ in combination with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL6) amplified HLA-DRlowCD14+CD11b+CD33+ myeloid-derived suppressor cells (MDSCs) at the expense of macrophage and dendritic cell (DC) differentiation. MDSCs generated in the presence of TGFβ were more effective in suppressing T-cell proliferation and promoted the T regulatory cell phenotype. In contrast, inhibition of TGFβ signaling using a small-molecule inhibitor of receptor kinase activity in CD14+ monocytes treated with GM-CSF and IL6 decreased MDSC differentiation and increased differentiation to proinflammatory macrophages and antigen-presenting DCs. The effect of autocrine and paracrine TGFβ on myeloid cell survival and lineage commitment suggests that pharmacologic inhibition of TGFβ-dependent signaling in cancer would favor antitumor immunity.
Patient Perspective in Obesity Surgery: Goals for Weight Loss and Improvement of Body Shape in a Prospective Cohort Study
Authors: Nickel Felix , Schmidt Lukas , Sander Johannes , Tapking Christian , Bruckner Thomas , Müller-Stich Beat-Peter , Fischer Lars
Published: December 2018

Objective: Obesity surgery provides sustainable weight loss, improvement of comorbidities, and improved quality of life (QOL). There is few evidence on the patient perspective and goals. This study compared expected and achieved weight loss, body shape, and QOL. Methods: Patients completed the Moorehead-Ardelt QOL questionnaire (MAQOL) and questionnaires on actual and expected weight loss and body shape, comorbidities, and goals of obesity surgery preoperatively and within 24 months postoperatively. Results: 44 patients completed questionnaires pre- and postoperatively. BMI, MAQOL and comorbidities significantly improved postoperatively. Patients’ expected weight loss goal corresponded to a postoperative BMI of 32.6 ± 5.6 kg/m2 and was not different from their achieved BMI within 24 months after surgery (33.9 ± 6.3 kg/m2, p = 0.276). Self-reported body shape improved but did not reach preoperatively expected goals. During the weight loss period, patients adapted their weight loss and body shape goals to higher levels. Patients attributed a higher part of their success in weight loss to surgery postoperatively (79.5 ± 22.0 vs. 89.1 ± 18.4%, p = 0.028). Conclusion: Patients lost as much weight as they had expected and later modified the goals to even greater weight loss. Body shape improved but did not reach expected levels. QOL improved independently from weight loss and body shape. Patients attributed successful weight loss predominantly to surgery.
Cortisol Stress Reactivity to the Trier Social Stress Test in Obese Adults
Authors: Herhaus Benedict , Petrowski Katja
Published: December 2018

Objective: Approximately 600 million adults worldwide suffer from obesity. In addition to individual’s eating behavior and lack of physical activity in the development of obesity and overweight, psychosocial stress as well as hormonal stress reactivity must also be considered as important contributing factors. In the current study we compared the cortisol stress response pathway in a psychosocial stress induction (Trier Social Stress Test; TSST) with obese individuals and normal-weight controls. Method: 32 obese individuals (17 females; mean age = 33.94 years, SD = 11.31 years) and 32 normal-weight controls (17 females; mean age = 29.09 years, SD = 10.46 years) underwent the TSST. The salivary cortisol responses and three appraisal questionnaires (Primary Appraisal Secondary Appraisal, Visual Analogue Scale, Trier Inventory for Chronic Stress) were measured. Results: After stress induction, there was a significant main group difference between the obese individuals and the normal-weight controls for cortisol, with lower baseline and post-stress cortisol levels in the obese individuals. Nevertheless, the obese individuals as well as the normal-weight controls showed no significant difference in the self-reported assessment of the stress condition but some significant differences in the cognitive appraisal of the TSST. Conclusion: In conclusion, the induction of psychosocial stress showed differences in the cortisol patterns between the obese individuals and the normal-weight controls. Furthermore, the present data suggest that obesity leads to lower cortisol activity, which may indicate alterations in the Hypothalamic-pituitary-adrencortical (HPA) axis.
Buccal Fat Pad: Report of 24 Cases and Literature Review of 1,635 Cases of Oral Defect Reconstruction
Authors: Mannelli Giuditta , Arcuri Francesco , Comini Lara Valentina , Valente Domenico , Spinelli Giuseppe
Published: December 2018

Objective: The buccal fat pad (BFP) has been progressively introduced into clinical practice for oral defect reconstruction. This study describes our experience with this technique and compares indications in the literature and outcomes. Methods: We prospectively enrolled 24 patients presenting oral surgical defects and treated between January 2012 and January 2015 at our institution. They all were eligible for BFP defect reconstruction. A comprehensive literature review was performed from 1977 onwards and surgical indications and results were compared. Results: All 24 BFP procedures showed excellent recovery and uneventful follow-up. Literature review confirmed a global success rate of 96.2% for a reported number of 1,635 patients with multiple surgical indications. BFP showed very low morbidity and failure rates in accordance with the outcomes reported in the literature, and the high patient compliance together with the easy harvesting of this surgical technique make it a good reconstructive option in cases of small-to-medium size oral defects in patients with a high rate of comorbidities or as salvage/second option. Conclusion: The BFP is worthy of consideration for the reconstruction of selected mouth defects, due to its easy mobilization, excellent blood supply, and minimal donor-site morbidity, where shape and size represent its main limitations, and a defect’s location influences its pliability.
Electrochemotherapy in the Treatment of Breast Cancer Metastasis to the Skin and Subcutaneous Tissue - Multicenter Experience
Authors: Wichtowski Mateusz , Murawa Dawid , Czarnecki Roman , Piechocki Jacek , Nowecki Zbigniew , Witkiewicz Wojciech
Published: December 2018

Introduction: Breast cancer is responsible for more than 50% of cutaneous metastases. One of the treatment options is electrochemotherapy (ECT). It is an effective method of local tumor ablation through the application of electroporation. The primary objective of the study was to demonstrate a response to the treatment in our group of patients. Methods: Between February 2015 and October 2016, in 3 centers in Poland, 47 ECT procedures were performed in 38 patients with metastasis of breast cancer to the skin. Results: At 12 weeks after the procedures, 71% of patients showed a positive response to the treatment (42% with complete response, and 29% with partial response). Multivariate analysis demonstrated that only the estrogen receptor status and the size of the metastatic lesion were predictive of overall response (p = 0.0243 and p = 0.03716, respectively). Conclusion: The results of our study demonstrate a high effectiveness of ECT in the treatment of cutaneous metastasis from breast cancer. This method, although used for palliative treatment, brings a significant improvement in the quality of life of patients.
Silurana Chromosomal Evolution: A New Piece to the Puzzle
Authors: Knytl Martin , Tlapakova Tereza , Vankova Tereza , Krylov Vladimir
Published: December 2018

The African clawed frogs of the subgenus Silurana comprise both diploid and tetraploid species. The root of the polyploidization event leading to the extant Xenopus calcaratus, X. mellotropicalis, and X. epitropicalis is not fully understood so far. In X. mellotropicalis, we previously proposed 2 evolutionary scenarios encompassing complete (scenario A) or incomplete (scenario B) translocation of a heterochromatic block from chromosome 9 to 2 in a diploid ancestor. To resolve this puzzle, we performed FISH coupled with tyramide signal amplification (FISH-TSA) using 5 X. tropicalis and X. mellotropicalis single copy gene probes (gyg2, cept1, fn1, ndufs1, and sf3b1) reflecting borders of the heterochromatic blocks in X. tropicalis chromosome 9 (XTR 9) and X. mellotropicalis chromosome 9b (XME 9b) and XME 2a. cDNA sequencing recognized both homoeologous genes in X. mellotropicalis. Comparison of gene physical mapping between X. tropicalis and X. mellotropicalis clearly confirmed complete rather than incomplete translocation t(9;2) of the heterochromatic block in the diploid predecessor and thus favored scenario A regarding the formation of an ancestral allotetraploid karyotype.
Effects of Light Treatment on Sleep, Cognition, Mood, and Behavior in Alzheimer’s Disease: A Systematic Review
Authors: Mitolo Micaela , Tonon Caterina , La Morgia Chiara , Testa Claudia , Carelli Valerio , Lodi Raffaele
Published: December 2018

Background: Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer’s disease (AD) patients. Recently, a handful of studies also focused on the effect on cognition and behavior. Conflicting findings are reported in the literature, and no definite conclusions have been drawn about its specific therapeutic effect. Summary: The aim of this review is to provide a critical evaluation of available evidence in this field, highlighting the specific characteristics of effective bright light treatment. Eligible studies were required to assess at least one of the following outcome measures: sleep, cognition, mood, and/or behavior (e.g., depression, agitation). A total of 32 articles were included in this systematic review and identified as research intervention studies about light treatment in AD. The quality of the papers was evaluated based on the US Preventive Service Task Force guidelines. Key Messages: Overall, the current literature suggests that the effects of light treatment in AD patients are mixed and may be influenced by several factors, but with a general trend toward a positive effect. Bright light seems to be a promising intervention treatment without significant adverse effects; therefore, further well-designed randomized controlled trials are needed taking into account the highlighted recommendations.
The Efficacy of Concurrent or Sequential Intravenous and Intratympanic Steroid for Idiopathic Sudden Sensorineural Hearing Loss
Authors: Chu Chia-Huei , Chiou Shiau-Ru , Wang Mao-Che , Shiao An-Suey , Tu Tzong-Yang , Lin Liang-Yu , Huang Chii-Yuan , Liao Wen-Huei
Published: December 2018

Objective: The purpose of this retrospective study was to investigate the difference in treatment outcomes for patients with idiopathic sudden sensorineural hearing loss (SSNHL) undergoing concurrent or sequential intravenous (IV) and intratympanic (IT) steroid therapies. Methods: Patients with idiopathic SSNHL admitted to Taipei Veterans Hospital from August 2011 to August 2012 were enrolled. Patients were treated with both IV dexamethasone 5 mg b.i.d. for 5 days, then tapered over 6 days, and IT injections of dexamethasone 5 mg daily. The administration of IV and IT steroids was given either concurrently or sequentially (IV steroid was administered from days 1–5 followed by IT steroid treatment starting on day 4 or day 5). The hearing outcomes of the concurrent and sequential groups were analyzed. Results: Overall, after ≥2 months following treatment, across frequencies ranging from 250 to 8,000 Hz and pure-tone average (PTA) assessments, hearing improvements were similar between treatment groups, except at the frequencies of 4,000 and 8,000 Hz where the concurrent treatment group had greater hearing gain than the sequential group (4,000 Hz: 30.68 ± 28.96 vs. 14.52 ± 24.06 dB, respectively, p = 0.042; 8,000 Hz: 22.62 ± 23.59 vs. 7.67 ± 21 dB, p = 0.030). Across frequencies and PTA assessments, a similar percentage of patients had ≥20-dB gains in hearing compared with patients treated sequentially, except at 8,000 Hz where a greater percentage of patients in the concurrent group (57.1%) than the sequential group (23.3%) (p = 0.014) had ≥20-dB hearing gains. Conclusion: The findings suggest that both concurrent and sequential treatment improve hearing in patients with idiopathic SSNHL, and that concurrent treatment may show greater benefit than sequential therapy, particularly at high frequencies.
Ocular Complications from Retained Intraocular Ointment Discovered 33 Months after Cataract Surgery
Authors: Sanders Riley N. , Warner David B. , Adams Lindsey R. , Sallam Ahmed A. , Uwaydat Sami H.
Published: December 2018

Topical antibiotic and steroid ointments are sometimes used topically at the conclusion of intraocular surgery, and inadvertent entry into the eye has been reported. Dispersed ointment droplets or consolidated globules in the anterior chamber (AC) can sometimes be visualized on exam. Occasionally, intraocular ointment is found incidentally without apparent toxic effect, but retained ointment usually presents with early or delayed intraocular inflammation, pressure rise, macular edema, or corneal edema. The usual treatment for toxicity from retained ointment is removal of the ointment. While the complication of ointment-induced cystoid macular edema has been reported, there is paucity of literature on the anatomical response and eventual visual outcome of patients who have been treated for long-standing edema from retained ointment. We present a case of a patient who presented with history of poor vision since the time of cataract surgery 33 months prior, who had cystoid macular edema, reduced endothelial cell count, and apparent Maxitrol ointment (neomycin, polymyxin B sulfate, and dexamethasone in paraffin vehicle; Novartis Pharmaceuticals UK) floating in the AC. The patient was treated with AC washout and sub-Tenon injection of triamcinolone. His vision, retinal architecture by optical coherence tomography, endothelial cell count, and pachymetry has been followed for 9 months following this treatment.
Palliative Care in Patients with Hematological Malignancies
Authors: Oechsle Karin
Published: December 2018

Patients with hematologic malignancies (HM) nowadays rarely receive palliative or hospice care, and studies on potential effects of integrated palliative care are rare. This narrative review provides a comprehensive overview on their current end-of-life care, first data on integrated specialist palliative care (SPC) and potential barriers. Symptom burden and distress in patients with HM seem to be comparable to other cancer patients, but their performance status and specific symptoms are even worse. Prolongation of life usually remains the main focus until the last days or weeks of life. Their chance to die in hospital is twice as high, but their chance to receive specialist palliative or hospice care is only half of that of other cancer patients. Prospective studies indicate a high acceptability and positive effects of integrated SPC, e.g. clarification of treatment goals, stabilization of quality of life, decreased depression, anxiety, symptom burden, and post-traumatic stress disorders. Interdisciplinary cooperation, timely discussions about SPC referral, and indicators to ‘flag' patients in need for SPC are important, but they are largely missing. In conclusion, further studies have to evaluate factors identifying patients with HM in need for SPC. Further models of early integrated palliative care should be evaluated in prospective studies and established in daily clinical practice.
Invasive Pulmonary Adenocarcinoma with Lepidic Growth Pattern in a Pregnant Patient
Authors: Jiménez-Zarazúa Omar , Vélez-Ramírez Lourdes N. , Padilla–López José C. , García-Ramírez Juana R. , González–Carillo Pedro L. , Mondragón Jaime D.
Published: December 2018

Among the differential diagnoses that should be considered in acute respiratory failure (ARF) are infectious processes, autoimmune diseases, interstitial pulmonary fibrosis, and pulmonary neoplasia. Timely diagnosis of lung neoplasia is complicated in the early stages. An opportune diagnosis, as well as the specific treatment, decrease mortality. ARF occurs 1 in 500 pregnancies and is most common during the postpartum period. Among the specific etiologies that cause ARF during pregnancy that must be considered are: (1) preeclampsia; (2) embolism of amniotic fluid; (3) peripartum cardiomyopathy; and (4) trophoblastic embolism. The case of a 36-year-old patient with a 33-week pregnancy and ARF is presented. The patient presented dyspnea while exerting moderate effort that progressed to orthopnea and type 1 respiratory insufficiency. Imaging studies showed bilateral alveolar infiltrates and predominantly right areas of consolidation. Blood cultures, a galactomannan assay and IgG antibodies against mycoplasma pneumoniae, were reported as negative. Autoimmune etiology was ruled out through an immunoassay. A percutaneous pulmonary biopsy was performed and an invasive pulmonary adenocarcinoma with lepidic growth pattern (i.e. lepidic pulmonary adenocarcinoma, LPA) result was reported. This etiology is rare and very difficult to recognize in acute respiratory failure cases. After infectious, autoimmune and interstitial lung fibrosis have been excluded the clinician must suspect of lung cancer in a patient with acute respiratory failure and chest imaging compatible with the presence of ground-glass nodular opacities, a solitary nodule or mass with bronchogram, and lung consolidation. In the presence of acute respiratory failure, the suspicion of pulmonary neoplasia in an adult of reproductive age must be timely. Failure to recognize this etiology can lead to fatal results.
Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice
Authors: Luo Qin , Guo Hongrui , Kuang Ping , Cui Hengmin , Deng Huidan , Liu Huan , Lu Yujiao , Wei Qin , Chen Linlin , Fang Jing , Zuo Zhicai , Deng Junliang , Li Yinglun , Wang Xun , Zhao Ling
Published: December 2018

Background/Aims: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. Methods: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. Results: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. Conclusion: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.
PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer
Authors: Fu Deyuan , He Chunlan , Wei Jinli , Zhang Zhengquan , Luo Yulin , Tan Haosheng , Ren Chuanli
Published: December 2018

Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.
Protective Mechanism of Adipose-Derived Stem Cells in Remodelling of the Skin Stem Cell Niche During Photoaging
Authors: Gong Meihua , Zhang Pan , Li Chunyang , Ma Xu , Yang Daping
Published: December 2018

Background/Aims: Skin photoaging is primarily caused by the functional attrition of skin stem cells. The skin stem cell niche plays an important role in maintaining stem cell survival and behaviour. In our study, we hypothesized that UVB irradiation induces skin photoaging by changing skin stem cell niches and that transferred adipose-derived stem cells (ADSCs) can remodel the niches by affecting the BMP signalling pathway and transdifferentiating into skin stem cells. Methods: Sixty-four C57BL/6J mice were divided into the following groups: a control group, the UVB group and the UVB+ADSCs group. Western blot assays, immunofluorescence analysis and real-time PCR were used to measure differences in the expression of niche components among the three groups. Furthermore, we tested whether transplanted ADSCs express skin stem cell markers, such as p63, α6-integrin and CD34. Results: The expression levels of Bmp4, its downstream factors Smad1 and MAPK1 and a regulatory factor of the niche, i.e., NFATc1, were lower in the UVB group than were those in the control group (P< 0.05) but higher in the UVB+ADSCs group than were those in the UVB group (P< 0.05). Compared with Bmp4, Nanog (a downstream factor of Bmp4), and MMP13 (a regulatory factor of the niche), ICAM-1 (a proinflammatory gene), p63 (a basal transcription factor), β1-integrin, Mtnr1a and Tyr (melanogenesis-related factors) showed the opposite expression trends (P< 0.05). Bmp2 and Collagen IV levels did not significantly change among the three groups (P> 0.05). Skin stem cell markers, such as p63, α6-integrin and CD34, were coexpressed in the ADSCs, which suggested the ADSCs may transdifferentiate into skin stem cells. Conclusion: We found that UVB irradiation results in typical photoaging signs by altering skin stem cell niches and that Bmp4 was a key factor in BMP signalling in hair follicles. ADSCs reversed these typical photoaging signs by remodelling skin stem cell niches through BMP4 pathway modulation and transdifferentiation into skin stem cells.
Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone
Authors: Zhao Chenglong , Wang Dongsheng , Tang Liang , Zhang Zhichao , Li Song , Qian Ming , Wu Zhipeng , Zhou Wang , Liu Mingyao , Luo Jian , Liu Tielong , Li Zhenxi , Xiao Jianru
Published: December 2018

Background/Aims: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. Methods: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. Results: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. Conclusion: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.
Predictive Value of Age-Bilirubin-International Normalized Ratio-Creatinine Score in Short-Term Survival of Acute-on-Chronic Hepatitis B Liver Failure
Authors: Chen Liang , Zheng Jun , Cai Jianye , Jie Yusheng , Zhang Yingcai , Li Hui , Lu Tongyu , He Liying , Xiao Cuicui , Zeng Kaining , Fu Hongyuan , Li Haibo , Ouyang Bin , Chen Guihua , Yao Jia , Gong Jiao , Yang Yang
Published: December 2018

Background/Aims: The age-bilirubin-international normalized ratio-creatinine (ABIC) score, which is a predictive model commonly used for alcoholic hepatitis, has not yet been studied in acute-on-chronic hepatitis B liver failure (HBV-ACLF). We aimed to investigate the predictive value of the ABIC score in patients with HBV-ACLF. Methods: This retrospective study involved 398 patients diagnosed with HBV-ACLF, who were divided into a training cohort of 305 patients and a validation cohort of 93 patients. Univariate and multivariate Cox regression models were used to determine risk factors for mortality. Area under the receiver operating characteristic curve (AUC) was calculated to estimate and compare the predictive values of different prognostic scores. Results: The ABIC score was significantly higher in the death group of the training cohort than in its survival group. Independent risk factors for mortality identified by multivariate Cox analysis included blood urea nitrogen, ABIC score, and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score. For predicting 1- and 3-month mortality, AUC was higher for the ABIC score than for the Model for End-stage Liver Diseases (MELD) score (0.732 vs. 0.653, P < 0.05, 0.695 vs. 0.619, P < 0.05, respectively), CLIF-C OF score (0.693, P=0.353, 0.656, P=0.341, respectively), and Child-Pugh score (0.675, P=0.189, 0.656, P=0.300, Respectively). Patients with ABIC score > 9.44 had reduced 1- and 3-month survival rates. Conclusion: ABIC score is superior to MELD score in predicting short-term survival in HBV-ACLF patients. ABIC score > 9.44 predicts high short-term mortality risk in HBV-ACLF patients.
Blue Rubber Bleb Nevus Syndrome: A Possible Cause for Growth Retardation and Pubertal Delay
Authors: Pan Yi , Zhang Lu , Duan Minghui , Yang Hong , Zhao Duoduo , Li Weifeng
Published: December 2018

Objective: The aim of this paper was to describe a rare case of blue rubber bleb nevus (BRBNS) with growth retardation and pubertal delay. Clinical Presentation and Intervention: A 16-year-old boy with severe iron deficiency anemia was diagnosed with BRBNS, showing growth retardation and pubertal delay simultaneously. The patient was treated conservatively with intravenous iron therapy, and his puberty advanced gradually. Conclusion: Given that growth retardation and pubertal delay are rare in BRBNS patients, this case reminds us to include BRBNS in the differential diagnosis of growth retardation.
Trajetória de Leo Sammer em 2666, de Roberto Bolaño
Authors: Brito Jr Antonio Barros de
Published: December 2018

Em seu romance 2666, Roberto Bolaño apresenta-nos a personagem de Leo Sammer, funcionário nazista encarregado do transporte de trabalhadores e mantimentos para o Reich. Um dia, Sammer recebe por engano quinhentos judeus oriundos da Grécia e destinados aos campos de extermínio. Sem poder devolver os judeus para seu lugar de origem, Sammer recebe a ordem de exterminá-los. A partir deste fato, desdobra-se toda uma dimensão ética da personagem, que será o tema deste artigo. Primeiramente, Sammer é comparado à figura histórica de Adolf Eichmann, um proeminente nazista, a fim de avaliar a sua responsabilidade e sua culpa no contexto do regime totalitário. Depois, a orientação ética de Sammer é analisada com base nas ideias de Ricoeur, Badiou e Lévinas, considerando questões como o Mesmo, o Outro, a autonomia do sujeito diante do Mal. Por fim, o artigo conclui que o discurso ambivalente da defesa de Sammer na verdade é a mera repetição do padrão totalitário do qual ele insistentemente tenta se descolar.