bluuebunny/crossref_metadata_2025 huggingface dataset:
Are trends in billing for high-intensity emergency care explained by changes in services provided in the emergency department? An observational study among US Medicare beneficiaries
Authors: Burke Laura G , Wild Robert C , Orav E John , Hsia Renee Y
Published: January 2018

Objective

There has been concern that an increase in billing for high-intensity emergency care is due to changes in coding practices facilitated by electronic health records. We sought to characterise the trends in billing for high-intensity emergency care among Medicare beneficiaries and to examine the degree to which trends in high-intensity billing are explained by changes in patient characteristics and services provided in the emergency department (ED).

Design, setting and participants

Observational study using traditional Medicare claims to identify ED visits at non-federal acute care hospitals for elderly beneficiaries in 2006, 2009 and 2012.

Outcomes measures

Billing intensity was defined by emergency physician evaluation and management (E&M) codes. We tested for overall trends in high-intensity billing (E&M codes 99285, 99291 and 99292) and in services provided over time using linear regression models, adjusting for patient characteristics. Additionally, we tested for time trends in rates of admission to the hospital and to the intensive care unit (ICU). Next, we classified outpatient visits into 39 diagnosis categories and analysed the change in proportion of high-intensity visits versus the change in number of services. Finally, we quantified the extent to which trends in high-intensity billing are explained by changes in patient demographics and services provided in the ED using multivariable modelling.

Results

High-intensity visits grew from 45.8% of 671 103 visits in 2006 to 57.8% of 629 010 visits in 2012 (2.0% absolute increase per year; 95% CI 1.97% to 2.03%) as did the mean number of services provided for admitted (1.28 to 1.41; +0.02 increase in procedures per year; 95% CI 0.018 to 0.021) and discharged ED patients (7.1 to 8.6; +0.25 increase in services per year; 95% CI 0.245 to 0.255). There was a reduction in hospital admission rate from 40.1% to 35.9% (−0.68% per year; 95% CI −0.71% to −0.65%; P<0.001), while the ICU rate of admission rose from 11.7% to 12.3% (+0.11% per year; 95% CI 0.09% to 0.12%; P<0.001). When we stratified by diagnosis category, there was a moderate correlation between change in visits billed as high intensity and the change in mean number of services provided per visit (r=0.38; 95% CI 0.07 to 0.63). Trends in patient characteristics and services provided accounted moderately for the trend in practice intensity for outpatient visits (pseudo R2of 0.47) but very little for inpatient visits (0.051) and visits overall (0.148).

Conclusions

Increases in services provided in the ED moderately account for the trends in billing for high-intensity emergency care for outpatient visits.
Health science communication strategies used by researchers with the public in the digital and social media ecosystem: a systematic scoping review protocol
Authors: Fontaine Guillaume , Lavallée Andréane , Maheu-Cadotte Marc-André , Bouix-Picasso Julien , Bourbonnais Anne
Published: January 2018

Introduction

The optimisation of health science communication (HSC) between researchers and the public is crucial. In the last decade, the rise of the digital and social media ecosystem allowed for the disintermediation of HSC. Disintermediation refers to the public’s direct access to information from researchers about health science-related topics through the digital and social media ecosystem, a process that would otherwise require a human mediator, such as a journalist. Therefore, the primary aim of this scoping review is to describe the nature and the extent of the literature regarding HSC strategies involving disintermediation used by researchers with the public in the digital and social media ecosystem. The secondary aim is to describe the HSC strategies used by researchers, and the communication channels associated with these strategies.

Methods and analysis

We will conduct a scoping review based on the Joanna Briggs Institute’s methodology and perform a systematic search of six bibliographical databases (CINAHL, EMBASE, IBSS, PubMed, Sociological Abstracts and Web of Science), four trial registries and relevant sources of grey literature. Relevant journals and reference lists of included records will be hand-searched. Data will be managed using the EndNote software and the Rayyan web application. Two review team members will perform independently the screening process as well as the full-text assessment of included records. Descriptive data will be synthesised in a tabular format. Data regarding the nature and the extent of the literature, the HSC strategies and the associated communication channels will be presented narratively.

Ethics and dissemination

This review does not require institutional review board approval as we will use only collected and published data. Results will allow the mapping of the literature about HSC between researchers and the public in the digital and social media ecosystem, and will be published in a peer-reviewed journal.
Man in his 50s with chest pain and dyspnoea
Authors: Obayashi Yuki , Izumi Chisato , Nakagawa Yoshihisa
Published: January 2018

Clinical introduction

A man in his 50s with sudden-onset chest pain and dyspnoea was transferred to the emergency room. He had a history of aortic valve replacement due to aortic regurgitation with a mechanical valve 6 years previously. Heart rate was 90 bpm, and blood pressure was too low to measure. In the emergency room, he presented with severe dyspnoea and a chest X-ray showed severe lung congestion (figure 1A). ECG showed complete left bundle branch block. His respiratory status rapidly worsened, and he went into cardiopulmonary arrest. After cardiopulmonary resuscitation, transthoracic echocardiography was performed (figure 1B, online supplementary video 1).

Supplementary file 1

Figure 1

(A) Chest X-ray. (B) Colour Doppler image from apical five-chamber view.

Question

What is the most likely cause of the patient’s cardiopulmonary arrest?

Myocardial infarction in left main trunk

Aortic dissection

Prosthetic valve thrombosis

Prosthetic valve embolisation

Pulmonary embolism
Sickness absence due to different musculoskeletal diagnoses by occupational class: a register-based study among 1.2 million Finnish employees
Authors: Pekkala Johanna , Rahkonen Ossi , Pietiläinen Olli , Lahelma Eero , Blomgren Jenni
Published: January 2018

Objectives

Those in lower occupational classes have an increased risk of sickness absence due to musculoskeletal diseases (MSDs), but studies examining the associations simultaneously across specified diagnostic groups within MSDs are lacking. We examined occupational class differences in the occurrence and length of long-term sickness absence due to different musculoskeletal diagnoses.

Methods

A 70% random sample of employed Finns aged 25–64 years old at the end of 2013 was linked to data on sickness absence of over 10 working days obtained from The Social Insurance Institution of Finland and occupational class from Statistics Finland. Sickness absences due to MSDs initiated in 2014 were followed until the end of each episode for female (n=675 636) and male (n=604 715) upper non-manuals, lower non-manuals and manual workers. Negative binomial hurdle models were used to analyse the associations.

Results

Within the studied MSDs, the most common causes of absence were back disorders, particularly back pain, and shoulder disorders. Osteoarthritis, disc disorders and rheumatoid arthritis induced the longest episodes of absence. Clear hierarchical class differences were found throughout, but the magnitude of the differences varied across the diagnostic causes. The largest class differences in the occurrence were detected in shoulder disorders and back pain. The class differences in length were greatest in rheumatoid arthritis, disc disorders and, among men, also in hip osteoarthritis.

Conclusions

Hierarchical occupational class differences were found across different MSDs, with large differences in back and shoulder disorders. Occupational class and diagnosis should be considered when attempting to reduce sickness absence due to MSDs.
Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury
Authors: Proudfoot Alastair , Bayliffe Andrew , O’Kane Cecilia M , Wright Tracey , Serone Adrian , Bareille Philippe Jean , Brown Vanessa , Hamid Umar I , Chen Younan , Wilson Robert , Cordy Joanna , Morley Peter , de Wildt Ruud , Elborn Stuart , Hind Matthew , Chilvers Edwin R , Griffiths Mark , Summers Charlotte , McAuley Daniel Francis
Published: January 2018

Background

Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects.

Methods

We investigated the in vitro effects of GSK1995057 on human pulmonary microvascular endothelial cells (HMVEC-L) and then assessed the effects of pretreatment with nebulised GSK1995057 in a non-human primate model of acute lung injury. We then tested translation to humans by investigating the effects of a single nebulised dose of GSK1995057 in healthy humans (n=37) in a randomised controlled clinical trial in which subjects were subsequently exposed to inhaled endotoxin.

Results

Selective inhibition of TNFR1 signalling potently inhibited cytokine and neutrophil adhesion molecule expression in activated HMVEC-L monolayers in vitro (P<0.01 and P<0.001, respectively), and also significantly attenuated inflammation and signs of lung injury in non-human primates (P<0.01 in all cases). In a randomised, placebo-controlled trial of nebulised GSK1995057 in 37 healthy humans challenged with a low dose of inhaled endotoxin, treatment with GSK1995057 attenuated pulmonary neutrophilia, inflammatory cytokine release (P<0.01 in all cases) and signs of endothelial injury (P<0.05) in bronchoalveolar lavage and serum samples.

Conclusion

These data support the potential for pulmonary delivery of a selective TNFR1 dAb as a novel therapeutic approach for the prevention of acute respiratory distress syndrome.

Trial registration number

ClinicalTrials.gov NCT01587807.
Acute graft-versus-host disease following lung transplantation in a patient with a novel TERT mutation
Authors: Brestoff Jonathan R , Vessoni Alexandre T , Brenner Kirsten A , Uy Geoffrey L , DiPersio John F , Blinder Morey , Witt Chad A , Byers Derek E , Hachem Ramsey R , Truclock Elbert P , Early Dayna S , Anadkat Milan J , Musiek Amy , Javidan-Nejad Cylen , Balfe Dennis M , Rosman Ilana S , Liu Chang , Zhang Lingxin , Despotis George J , Ruzinova Marianna B , Sehn Jennifer K , Amarillo Ina , Heusel Jonathan W , Swat Wojcieh , Kim Brian S , Wartman Lukas D , Yusen Roger D , Batista Luis F Z
Published: January 2018

Familial pulmonary fibrosis is associated with loss-of-function mutations in telomerase reverse transcriptase (TERT) and short telomeres. Interstitial lung diseases have become the leading indication for lung transplantation in the USA, and recent data indicate that pathogenic mutations in telomerase may cause unfavourable outcomes following lung transplantation. Although a rare occurrence, solid organ transplant recipients who develop acute graft-versus-host disease (GVHD) have very poor survival. This case report describes the detection of a novel mutation in TERT in a patient who had lung transplantation for familial pulmonary fibrosis and died from complications of acute GVHD.
Inlet and outlet boundary conditions for the discrete velocity direction model
Authors: Zhang Zhenyu , Zhao Wei , Zhao Qingjun , Lu Guojing , Xu Jianzhong
Published: January 2018

The discrete velocity direction model is an approximate method to the Boltzmann equation, which is an optional kinetic method to microgas flow and heat transfer. In this paper, the treatment of the inlet and outlet boundary conditions for the model is proposed. In the computation strategy, the microscopic molecular speed distribution functions at inlet and outlet are indirectly determined by the macroscopic gas pressure, mass flux and temperature, which are all measurable parameters in microgas flow and heat transfer. The discrete velocity direction model with the pressure correction boundary conditions was applied into the plane Poiseuille flow in microscales and the calculations cover all flow regimes. The numerical results agree well with the data of the NS equation near the continuum regime and the date of linearized Boltzmann equation and the DSMC method in the transition regime and free molecular flow. The Knudsen paradox and the nonlinear pressure distributions have been accurately captured by the discrete velocity direction model with the present boundary conditions.
Repeated crossing of two concentric spherical thin-shells with charge
Authors: Mazharimousavi S. Habib , Halilsoy M.
Published: January 2018

Interaction/collision of two concentric spherical thin-shells of linear fluid resulting in collapse has been considered recently. We show that addition of finely tuned electric charges on the shells apart from the cosmological constant serves to delay the collapse indefinitely, yielding an ever colliding system of two concentric fluid shells. Given the finely tuned charges, this provides an example of a perpetual two-body motion in general relativity.
Li Zhanshu: A Key Player in Xi Jinping’s Second Term
Authors: GORE Lance L P
Published: January 2018

Xi Jinping and Li Zhanshu share many similarities and formed a bond as rooky party secretaries in counties in Hebei province in the 1980s. Xi brought Li to Beijing in 2012 and Li played a key role in drumming up support for Xi to become the “core” of the Chinese Communist Party leadership. Li is expected to join the next Politburo Standing Committee and play a more prominent role in Xi’s second term.
Democracy and the War on Terror in South Korea
Authors: TELLIDIS Ioannis , BAEK Buhm-Suk
Published: January 2018

Although South Korea has had minimal exposure to terrorism, it recently adopted a controversial Anti-Terrorism Act that is characterised by arbitrary and vague definitions of ‘terrorism’ and ‘terrorism’-related crimes. The Act risks manufacturing the ‘terrorism’ phenomenon with the unnecessary curtailing of civil liberties and stifling of political dissent. This article argues that the legislation‘s objectives are more a rhetorical device to solidify power than to sustain the vibrancy of democratic politics and provide effective human security.
From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution
Authors: Dilia Giuggioli , Michele Colaci , Emanuele Cocchiara , Amelia Spinella , Federica Lumetti , Clodoveo Ferri
Published: January 2018

Background. Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud’s phenomenon or antinuclear antibodies before the SSc onset.
A Road Layout Based Broadcast Mechanism for Urban Vehicular Ad Hoc Networks
Authors: Sung Yoonyoung , Lee Meejeong
Published: January 2018

Safety services of Vehicular Ad Hoc Network (VANET) require reliable broadcasts. We propose a reliable broadcast mechanism for urban roads called VANET Broadcasting for Urban areas based on Road Layout (VBURL), which tries to minimize the dependency on information that may become inaccurate to maximize the efficiency of broadcast. Specifically, the proposed mechanism takes into account the road layout information accessible from the digital map and only the real‐time information obtained from the broadcast messages or beacons. VBURL basically makes the vehicle that is farthest from the current forwarding vehicle take the role of next forwarding vehicle and, if possible, makes an additional broadcast happen at the intersections where the effect of signal attenuation caused by the road side obstacles is low in order to have prompt and reliable dissemination of safety messages towards all roads connected to the intersections. The simulation results verified that VBURL achieves the same high performance as that of the compared legacy schemes in terms of reliability with much higher efficiency. Even though the message reception delay of VBURL is slightly longer than those of compared schemes, it is far less significant to impair the original purpose of safety message.
A Case of First Branchial Cleft Fistula Presenting with an External Opening on the Root of the Helical Crus
Authors: Cho Sung Il
Published: January 2018

Background. First branchial cleft anomalies (FBCA) are rare clinical entities of the head and neck. Typically, the tract of the FBCA begins in the external auditory canal and ends in the postauricular or submandibular region. Case Presentation. We present a case of a 23-year-old man who had a first branchial cleft fistula with atypical opening on the root of the helical crus. Complete excision of the tract, including the cuff of surrounding cartilage, was performed. Histopathology revealed a fistular tract lined with squamous epithelium. To our knowledge, this is the first case to be reported of type I FBCA with an opening on the root of the helical crus. The low incidence and varied presentation often result in misdiagnosis and inappropriate treatment. Conclusions. In the patients with FBCA, careful recognition of atypical variants is essential for complete excision.
Hepatitis B Virus Infection in Tanzania: Current Status and Challenges
Authors: Kilonzo Semvua B. , Gunda Daniel W. , Mpondo Bonaventura C. T. , Bakshi Fatma A. , Jaka Hyasinta
Published: January 2018

Hepatitis B is one of the most common infectious diseases in the world with high prevalence in most of sub-Saharan Africa countries. The complexity in its diagnosis and treatment poses a significant management challenge in the resource-limited settings including Tanzania, where most of the tests and drugs are either unavailable or unaffordable. This mini review aims at demonstrating the current status of the disease in the country and discussing the concomitant challenges in diagnosis, treatment, and prevention.
Impact of the Ceiling-Mounted Radiation Shielding Position on the Physician’s Dose from Scatter Radiation during Interventional Procedures
Authors: Sukupova Lucie , Hlavacek Ondrej , Vedlich Daniel
Published: January 2018

The effect of the ceiling-mounted radiation shielding on the amount of the scatter radiation was assessed under conditions simulating obese patients for clinically relevant exposure parameters. Measurements were performed in different projections and with different positions of the ceiling-mounted shielding: without shielding; shielding closest to the patient; and shielding closest to the physician performing the procedure. The protection provided by the shielding was assessed for cardiology when the femoral access is used and for radiology when the physician performs the procedure in the abdominal area. The results show that the use of the ceiling-mounted shielding can decrease the dose from the scatter radiation by 95% at the position of the performing physician. In cardiology, the impact is more pronounced when the left oblique projection is used. In radiology, a large decrease was observed for right oblique projections, compared to cardiology. The ceiling-mounted shielding should be placed as close to the physician as possible. The idea of creating the largest radiation shadow by placing the radiation shielding as close to the patient as possible does not provide as effective radiation protection of the operator as it might be thought.
Role of luxS in Stress Tolerance and Adhesion Ability in Lactobacillus plantarum KLDS1.0391
Authors: Jia Fang-Fang , Zheng Hui-Qi , Sun Si-Rui , Pang Xue-Hui , Liang Yu , Shang Jia-Cui , Zhu Zong-Tao , Meng Xiang-Chen
Published: January 2018

Lactobacillus plantarum, a probiotic, has a high survival rate and high colonization ability in the gastrointestinal tract. Tolerance to the gastrointestinal environment and adhesion to intestinal epithelial cells by some Lactobacillus species (excluding L. plantarum) are related to luxS/AI-2. Here, the role of luxS in tolerance to simulated digestive juice (SDJ) and adhesion to Caco-2 cells by L. plantarum KLDS1.0391 (hereafter, KLDS1.0391) was investigated. The KLDS1.0391 luxS mutant strain was constructed by homologous recombination. When luxS was deleted, acid and bile salt tolerance and survival rates in SDJ significantly decreased (p<0.05 for all). The ability of the luxS deletion strain to adhere to Caco-2 cells was markedly lower than that of the wild-type strain (p<0.05). The ability of the luxS mutant strain to adhere (competition, exclusion, and displacement) to Escherichia coli ATCC 25922 was significantly lower than that of the wild-type strain (p<0.05 for all). A significant decrease was noted only in the exclusion adhesion inhibition of the luxS mutant strain to Salmonella typhimurium ATCC 14028 (p<0.05). These results indicate that the luxS gene plays an important role in the gastrointestinal environment tolerance and adhesion ability of KLDS1.0391.
Existence Results of Initial Value Problems for Hybrid Fractional Sum-Difference Equations
Authors: Chasreechai Saowaluck , Sitthiwirattham Thanin
Published: January 2018

We consider a hybrid fractional sum-difference initial value problem and a hybrid fractional sequential sum-difference initial value problem. The existence results of these two problems are proved by using the hybrid fixed point theorem for three operators in a Banach algebra and the generalized Krasnoselskii’s fixed point theorem, respectively.
Performance of Urinary Markers for Detection of Upper Tract Urothelial Carcinoma: Is Upper Tract Urine More Accurate than Urine from the Bladder?
Authors: Bier Simone , Hennenlotter Jörg , Esser Michael , Mohrhardt Sarah , Rausch Steffen , Schwentner Christian , Maas Moritz , Deininger Susanne , Walz Simon , Bedke Jens , Stenzl Arnulf , Todenhöfer Tilman
Published: January 2018

Objectives. To assess the performance of urine markers determined in urine samples from the bladder compared to samples collected from the upper urinary tract (UUT) for diagnosis of UUT urothelial carcinoma (UC). Patients and Methods. The study comprised 758 urine samples either collected from the bladder (n=373) or UUT (n=385). All patients underwent urethrocystoscopy and UUT imaging or ureterorenoscopy. Cytology, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and nuclear matrix protein 22 (NMP22) were performed. Results. UUT UC was diagnosed in 59 patients (19.1%) (UUT urine) and 27 patients (7.2%) (bladder-derived urine). For UUT-derived samples, sensitivities for cytology, FISH, NMP22, and uCyt+ were 74.6, 79.0, 100.0, and 100.0, while specificities were 66.6, 50.7, 5.9, and 66.7%, respectively. In bladder-derived samples, sensitivities were 59.3, 52.9, 62.5, and 50.0% whereas specificities were 82.9, 85.0, 31.3, and 69.8%. In UUT-derived samples, concomitant bladder cancer led to increased false-positive rates of cytology and FISH. Conclusions. Urine markers determined in urine collected from the UUT exhibit better sensitivity but lower specificity compared to markers determined in bladder-derived urine. Concomitant or recent diagnosis of UC of the bladder can further influence markers determined in UUT urine.
Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody–Drug Conjugates
Authors: Zhao Hui , Atkinson John , Gulesserian Sara , Zeng Zhilan , Nater Jenny , Ou Jimmy , Yang Peng , Morrison Karen , Coleman Jeffrey , Malik Faisal , Challita-Eid Pia , Karki Sher , Aviña Hector , Hubert René , Capo Linnette , Snyder Josh , Moon Sung-Ju , Luethy Roland , Mendelsohn Brian A. , Stover David R. , Doñate Fernando
Published: January 2018

AGS-16C3F is an antibody–drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. AGS-16C3F and other ADCs have been reported to cause ocular toxicity in patients by unknown mechanisms. To investigate this toxicity, we developed an in vitro assay using human corneal epithelial cells (HCEC) and show that HCECs internalized AGS-16C3F and other ADCs by macropinocytosis, causing inhibition of cell proliferation. We observed the same mechanism for target-independent internalization of AGS-16C3F in fibroblasts and human umbilical vein endothelial cells (HUVEC). Macropinocytosis-mediated intake of macromolecules is facilitated by the presence of positive charges or hydrophobic residues on the surface of the macromolecule. Modification of AGS-16C3F, either by attachment of poly-glutamate peptides, mutation of residue K16 to D on AGS-16C3F [AGS-16C3F(K16D)], or decreasing the overall hydrophobicity via attachment of polyethylene glycol moieties, significantly reduced cytotoxicity against HCECs and other primary cells. Rabbits treated with AGS-16C3F showed significant ocular toxicity, whereas those treated with AGS-16C3F(K16D) presented with less severe and delayed toxicities. Both molecules displayed similar antitumor activity in a mouse xenograft model. These findings establish a mechanism of action for target-independent toxicities of AGS-16C3F and ADCs in general, and provide methods to ameliorate these toxicities.

Significance:These findings reveal a mechanism for nonreceptor-mediated toxicities of antibody drug conjugates and potential solutions to alleviate these toxicities. Cancer Res; 78(8); 2115–26. ©2018 AACR.
Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division in Aggressive Breast Cancer
Authors: Tracy Kirsten M. , Tye Coralee E. , Ghule Prachi N. , Malaby Heidi L.H. , Stumpff Jason , Stein Janet L. , Stein Gary S. , Lian Jane B.
Published: January 2018

Aggressive breast cancer is difficult to treat as it is unresponsive to many hormone-based therapies; therefore, it is imperative to identify novel, targetable regulators of progression. Long non-coding RNAs (lncRNA) are important regulators in breast cancer and have great potential as therapeutic targets; however, little is known about how the majority of lncRNAs function within breast cancer. This study characterizes a novel lncRNA, MANCR (mitotically-associated long noncoding RNA; LINC00704), which is upregulated in breast cancer patient specimens and cells. Depletion of MANCR in triple-negative breast cancer cells significantly decreases cell proliferation and viability, with concomitant increases in DNA damage. Transcriptome analysis, based on RNA sequencing, following MANCR knockdown reveals significant differences in the expression of >2,000 transcripts, and gene set enrichment analysis identifies changes in multiple categories related to cell-cycle regulation. Furthermore, MANCR expression is highest in mitotic cells by both RT-qPCR and RNA in situ hybridization. Consistent with a role in cell-cycle regulation, MANCR-depleted cells have a lower mitotic index and higher incidences of defective cytokinesis and cell death. Taken together, these data reveal a role for the novel lncRNA, MANCR, in genomic stability of aggressive breast cancer, and identify it as a potential therapeutic target.

Implications: The novel lncRNA, MANCR (LINC00704), is upregulated in breast cancer and is functionally linked with cell proliferation, viability, and genomic stability. Mol Cancer Res; 16(4); 587–98. ©2018 AACR.
Toxicities Associated with Docetaxel-Based Regimens in the Adjuvant Treatment of Early-Stage Breast Cancer: A Multicenter Prospective Real-Life Experience
Authors: El Rassy Elie , Ghosn Marwan , Farhat Fadi , Bakouny Ziad , Assi Tarek , Chahine Georges , Nasr Fadi , Haddad Fady Ghassan , El Karak Fadi , Kattan Joseph
Published: January 2018

Background: The present study reports on the efficacy and safety of adjuvant docetaxel in real-life patients with early-stage breast cancer. Methods: This is a prospective, multicenter, post-marketing study that evaluates the efficacy and safety of docetaxel-based regimens in patients with early breast cancer treated between 2007 and 2012. Results: A total of 698 female breast cancer patients receiving adjuvant docetaxel-based regimens were included in this study. Docetaxel monotherapy was administered in 4.2%, whilst most patients received polychemotherapy. Non-hematological adverse events included skin reactions in 32.7% of the subjects. Multiple adverse events were reported and most commonly included asthenia (66.5%), alopecia (43.4%), and diarrhea (24.2%). It is noteworthy that no fatal toxicities occurred. Several hematological adverse events were reported during treatment, with anemia being the most common. Conclusion: The results of this real-life experience, characterized by a relatively large sample size and long follow-up, confirm that docetaxel is effective and well tolerated in early-stage breast cancer patients.
Inguinal Lymph Node Metastasis of a Primary Serous Papillary Carcinoma of the Peritoneum One Year after CRS and HIPEC
Authors: Katou Shadi , Feist Mathilde , Raue Wieland , Pratschke Johann , Rau Beate , Brandl Andreas
Published: January 2018

Background: Primary peritoneal serous papillary carcinoma is a rare malignant epithelial tumor which was first described in 1959. Peritoneal serous papillary carcinoma arises from the peritoneal epithelium and originates from a single or multicentric focus of the peritoneum involving the peritoneum of the abdomen and pelvis. The involvement of retroperitoneal lymph nodes occurs in 64% of the patients diagnosed with this malignancy. So far, there is no report about inguinal lymph node metastasis in this disease. Case Report: We present a rare case of a 63-year-old female patient who developed singular inguinal lymph node metastasis 1 year after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy due to peritoneal serous papillary carcinoma. The lymph node metastasis was found by computed tomography (CT) scan and was resected and histologically confirmed. The postoperative course was uneventful, and the patient was discharged on postoperative day 1. The last CT scan 24 months after initial cytoreduction and 12 months after lymph node resection showed no further tumor recurrence. Conclusion: This case report should raise the awareness of potentially unexpected presentation of extraperitoneal metastasis and highlights the importance of patient follow-up including clinical examination and CT scans of thorax/abdomen/pelvis following a systematic schedule.
Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional Analyses
Authors: Kuźmiuk-Glembin Izabella , Adrych Dorota , Tylicki Leszek , Heleniak Zbigniew , Garnier Hanna , Wiśniewski Jakub , Rutkowski Przemysław , Rutkowski Bolesław , Dębska-Ślizień Alicja
Published: January 2018

Background/Aims: This retrospective study analysed hypertension management and adherence to blood pressure (BP) targets among renal transplant recipients (RTRs) under specialized care in the Outpatient Transplantation Unit in the Department of Nephrology, Transplantology and Internal Medicine at Gdansk University Hospital. Methods: Medical records of 101, 316, 639 and 818 RTRs diagnosed with hypertension, who received outpatient care in 2001, 2006, 2011 and 2014, respectively were analysed in four independent cross-sectional surveys. All RTRs received antihypertensive regimens. Results: The overall most commonly used antihypertensive agents were beta-blockers (BB) (range 66.3-82.5%) followed by calcium channel blockers (CCB) (range 52.8-64.2%). Whilst a significant, upward tendency of BB usage (p<0.01) was observed, CCB usage (p<0.001) displayed a downward tendency as a first line therapy in the subsequent years. The average number of antihypertensive agents used per patient increased significantly from 2.24±1.03 in 2001 to 2.55±1.25 in 2014 (p<0.05). The most frequently used combination of hypotensive therapy consisted of two or three antihypertensive drugs depending on the survey. The most common two drug combination consisted of BB and CCB followed by BB accompanied by angiotensin converting enzyme inhibitors. A significant, upward tendency in the use of four (p<0.001) and five (p<0.05) antihypertensive drugs simultaneously, was observed in subsequent years. The target values of BP i.e. <140/90 mmHg were accomplished in 47, 58, 60 and 46% of RTRs in subsequent years. In a secondary - stratified analysis of data from 2014, younger patients (p<0.05), patients with better graft function (p<0.001), patients treated with a higher number of antihypertensive agents (p<0.001) and those not treated with BB (p<0.01) were shown to reach the BP target of below 140/90 mmHg more often. Conclusion: The study showed intensification of hypertension treatment in RTRs in subsequent years with BB assuming a dominant role.
Voltage-Gated Na+ Channels are Modulated by Glucose and Involved in Regulating Cellular Insulin Content of INS-1 Cells
Authors: Chen Chong , Wang Songhua , Hu Qingjuan , Zeng Lvming , Peng Hailong , Liu Chao , Huang Li-Ping , Song Hao , Li Yuping , Yao Li-Hua , Meng Wei
Published: January 2018

Background/Aims: Islet beta cells (β-cells) are unique cells that play a critical role in glucose homeostasis by secreting insulin in response to increased glucose levels. Voltage-gated ion channels in β-cells, such as K+ and Ca2+ channels, contribute to insulin secretion. The response of voltage-gated Na+ channels (VGSCs) in β-cells to the changes in glucose levels remains unknown. This work aims to determine the role of extracellular glucose on the regulation of VGSC. Methods: The effect of glucose on VGSC currents (INa) was investigated in insulin-secreting β-cell line (INS-1) cells of rats using whole-cell patch clamp techniques, and the effects of glucose on insulin content and cell viability were determined using Enzyme-Linked Immunosorbent Assay (ELISA) and Methylthiazolyldiphenyl-tetrazolium Bromide (MTT) assay methods respectively. Results: Our results show that extracellular glucose application can inhibit the peak of INa in a concentration-dependent manner. Glucose concentration of 18 mM reduced the amplitude of INa, suppressed the INa of steady-state activation, shifted the steady-state inactivation curves of INa to negative potentials, and prolonged the time course of INa recovery from inactivation. Glucose also enhanced the activity-dependent attenuation of INa and reduced the fraction of activated channels. Furthermore, 18 mM glucose or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited the activity of VGSC and also improved insulin synthesis. Conclusion: These results revealed that extracellular glucose application enhances the insulin synthesis in INS-1 cells and the mechanism through the partial inhibition on INa channel is involved. Our results innovatively suggest that VGSC plays a vital role in modulating glucose homeostasis.
Os inventários de dementes: Os processos de curadoria e a relação da justiça régia com a loucura nas Minas Gerais do século XVIII
Authors: Souza Maria Eliza de Campos
Published: January 2018

Pretende-se analisar a atuação da Justiça régia em relação a um grupo de súditos que nas Minas viveram a experiência do enlouquecimento e foram declarados incapazes perante a lei. A investigação sobre a atuação dos juízes de órfãos responsáveis pelos autos sumários de demência, pela feitura e condução dos processos de inventários dos dementes e pelo acompanhamento das curadorias permitirá compreender melhor o papel e o alcance dessa Justiça, exercida em nome do rei, no que diz respeito à regulação e ao ordenamento da vida social local. Trata-se de um estudo dos processos de inventários dos indivíduos declarados dementes na Comarca do Rio das Velhas ao longo do século XVIII. São dezesseis processos encontrados para a vila de Sabará e seu termo que permitem compreender uma faceta muito peculiar da atuação dos juízes de órfãos e também a própria história social da loucura nas áreas periféricas do Império português.
Páginas da escravidão: raça e gênero nas representações de cativos brasileiros na imprensa e na literatura Oitocentista.
Authors: Maia Ludmila de Souza
Published: January 2018

Com a proibição do comércio atlântico de escravos em 1850 para o Brasil, as elites proprietárias tiveram que se adaptar a essa nova realidade, e tanto literatura como imprensa discutiram a questão escrava e seu futuro. Nesse contexto, é perceptível a emergência de uma nova sensibilidade em relação à escravidão, em que se observa a centralidade da mulher escravizada na década de 1850. Eu argumento que tais discussões apresentam um sentido duplo, pois tanto se relacionam com os debates antiescravistas que ocorriam em outras partes do Atlântico, como também com a questão brasileira que se via diante da necessidade de reproduzir a escravidão internamente. Essa análise se baseia nos textos de duas escritoras, a francesa Adèle Toussaint e a brasileira Nísia Floresta, e os discuto em diálogo com outras obras literárias e artigos da imprensa da década de 1850. Este artigo pretende-se, ainda, uma contribuição aos estudos sobre ideias antiescravistas para períodos anteriores à década de 1860 e, principalmente, considera a participação de mulheres nesses debates.
Corromper repúblicas, espoliar conquistas
Authors: Silveira Marco Antonio
Published: January 2018

Resenha crítica: ROMEIRO, Adriana. Corrupção e poder. Uma história, séculos XVI a XVIII. Belo Horizonte: Autêntica Editora, 2017, 397 p.
A Abolição revisitada: entre continuidades e rupturas
Authors: Salles Ricardo
Published: January 2018

A resenha analisa criticamente e termos comparativos as obras Flores, votos e balas, de Angela Alonso, e Tornando-se livre, organizada por Maria Helena P. T. Machado e Celso Castilho.
Outcome After Reperfusion Therapies in Patients With Large Baseline Diffusion-Weighted Imaging Stroke Lesions
Authors: Gautheron Vincent , Xie Yu , Tisserand Marie , Raoult Hélène , Soize Sébastien , Naggara Olivier , Bourcier Romain , Richard Sébastien , Guillemin Francis , Bracard Serge , Oppenheim Catherine
Published: January 2018

Background and Purpose—

Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWI
volume
>70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome.

Methods—

We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically.

Results—

Among 53 patients with DWI
volume
>70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38;
P
=0.046) and less history of smoking (1/10 versus 12/31;
P
=0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L–occluded patients (
P
=0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40;
P
=0.050).

Conclusions—

Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory.
A Kernel Embedding–Based Approach for Nonstationary Causal Model Inference
Authors: Hu Shoubo , Chen Zhitang , Chan Laiwan
Published: January 2018

Although nonstationary data are more common in the real world, most existing causal discovery methods do not take nonstationarity into consideration. In this letter, we propose a kernel embedding–based approach, ENCI, for nonstationary causal model inference where data are collected from multiple domains with varying distributions. In ENCI, we transform the complicated relation of a cause-effect pair into a linear model of variables of which observations correspond to the kernel embeddings of the cause-and-effect distributions in different domains. In this way, we are able to estimate the causal direction by exploiting the causal asymmetry of the transformed linear model. Furthermore, we extend ENCI to causal graph discovery for multiple variables by transforming the relations among them into a linear nongaussian acyclic model. We show that by exploiting the nonstationarity of distributions, both cause-effect pairs and two kinds of causal graphs are identifiable under mild conditions. Experiments on synthetic and real-world data are conducted to justify the efficacy of ENCI over major existing methods.
Robust Modulation of Integrate-and-Fire Models
Authors: Van Pottelbergh Tomas , Drion Guillaume , Sepulchre Rodolphe
Published: January 2018

By controlling the state of neuronal populations, neuromodulators ultimately affect behavior. A key neuromodulation mechanism is the alteration of neuronal excitability via the modulation of ion channel expression. This type of neuromodulation is normally studied with conductance-based models, but those models are computationally challenging for large-scale network simulations needed in population studies. This article studies the modulation properties of the multiquadratic integrate-and-fire model, a generalization of the classical quadratic integrate-and-fire model. The model is shown to combine the computational economy of integrate-and-fire modeling and the physiological interpretability of conductance-based modeling. It is therefore a good candidate for affordable computational studies of neuromodulation in large networks.
Mating system, male territoriality and agility as predictors of the evolution of sexual size dimorphism in hummingbirds (Aves: Trochilidae)
Authors: Nuñez-Rosas L. , Arizmendi M.C. , Cueva del Castillo R. , Serrano-Meneses M.A.
Published: January 2018

Male and female animals often exhibit differences in body size; this difference is known as sexual size dimorphism (SSD). Hummingbirds are an excellent model system to test functional hypotheses of SSD because they exhibit a wide range of body sizes and reproductive behaviour between the sexes. Here, using phylogenetic comparative methods, we tested whether mating system, male territoriality and agility predicted the evolution of SSD in this avian family. Our results first suggest that evolutionary increases in male-biased SSD are related to increases in lekking behaviour. Second, we found that male agility is positively related to increases in male biased-SSD albeit this is only likely to occur in males of territorial species. Finally, we found an allometric pattern for SSD consistent with Rensch’s rule that was not explained by our estimates of male competition and agility.
The effect of storage time and temperature on the population dynamics and vitality of Meloidogyne chitwoodi in potato tubers
Authors: Teklu Misghina G. , Schomaker Corrie H. , Been Thomas H.
Published: January 2018

The population densities of Meloidogyne chitwoodi in potato tubers stored at 4, 8 and 12°C after 0, 60, 120, 180 and 240 days of storage were assessed. Compared to day 0, storage temperatures of 4 and 8°C reduced population densities to 9 and 35%, respectively, after 240 days of storage, while nematode numbers in tubers stored at 12°C increased 2.5 times. The maximum hatching rate of nematodes from tubers stored at 8 and 12°C increased linearly with storage time. At 4°C it remained constant. The time required for the hatching process to reach the maximum number of second-stage juveniles (J2) decreased with increasing storage temperature. Recovered juveniles of M. chitwoodi from tubers after 180 and 240 days of storage at all three temperatures were still infective and able to multiply on ‘Desiree’ with estimates of the maximum multiplication rate (a) and the maximum population density (M) of 63.6 and 70.8 J2 (g dry soil)−1, respectively.
Two new species of Ozothamnus (Asteraceae: Gnaphalieae) from Australia
Authors: SCHMIDT-LEBUHN ALEXANDER N. , PUTTOCK CHRISTOPHER F. , DAVIS ROBERT W. , WEGE JULIET
Published: January 2018

Two new species of shrubs endemic to western and central Australia, respectively, are described as Ozothamnus vespertinus R.W.Davis, Wege & Schmidt-Leb. and O. filifolius Puttock. A dichotomous key to the species of Ozothamnus and Cassinia known from Western Australia and the Northern Territory is provided.
Influence of Midlatitude Surface Thermal Anomalies on the Polar Midtroposphere in an Idealized Moist Model
Authors: Fajber Robert , Kushner Paul J. , Laliberté Frédéric
Published: January 2018

Evidence from models and observations suggests that the vertical distribution of entropy in the extratropical troposphere reflects the horizontal distribution of entropy at the surface. This isentropic linkage, which is accomplished through moist isentropic mass transport driven by extratropical waves, becomes more apparent when the effect of latent heat release by condensing moist parcels is accounted for. This study focuses on the stratification of the Arctic troposphere, which is connected by moist isentropes to the midlatitude surface. A relatively simple moist general circulation model without radiative feedbacks involving water vapor or clouds is used to study the linkage between the midlatitude surface and the Arctic midtroposphere. Zonally symmetric midlatitude thermal perturbations switched on at the surface drive a moist potential temperature response in the Arctic midtroposphere with a lag of about 2 weeks. This response increases the gross moist vertical stability in the Arctic while generally decreasing it, or increasing it only weakly, in the midlatitudes. The moist isentropic streamfunction is shifted poleward owing to the poleward entropy flux response and is shifted upward (i.e., to higher entropy) owing to the zonal-mean entropy response. The results suggest a potential novel mechanism by which the midlatitudes might influence polar lapse rates and their associated radiative feedbacks.