bluuebunny/crossref_metadata_2025 huggingface dataset:
Camera trapping and transect counts yield complementary insights into an endangered island endemic rail
Authors: Znidersic Elizabeth , Flores Trish , Macrae Ismail , Woinarski John C. Z. , Watson David M.
Published: February 2019

Island endemic species are disproportionately represented in the tally of global extinctions. The island endemic Cocos buff-banded rail (Hypotaenidia philippensis andrewsi) is classified under the Australian Environment Protection and Biodiversity Conservation Act 1999 (EPBC Act) as Endangered. It is restricted to the remote Cocos (Keeling) Islands in the Indian Ocean where, until 2013, only the island Pulu Keeling supported a population of this species, following earlier extirpations of the bird from islands in the southern atoll. To establish a second viable population to mitigate against potential extinction of this subspecies, 39 rails were reintroduced from Pulu Keeling to Horsburgh Island in April 2013. As a component of post-translocation monitoring, we conducted intensive camera trapping from 29 May 2015 to 30 June 2016 (397 calendar days) to investigate recruitment success, behaviour and potential threats to the population. Biannual transect sampling to monitor and investigate long-term population density was also conducted. We found Cocos buff-banded rail persisting on Horsburgh Island with an increase in the founder population to 97 rails in February 2016. Ongoing recruitment with breeding activity on Horsburgh Island and the emigration of rails to nearby (2.5km) Direction Island is indicative of short-term success. Images from the camera traps have documented behaviours that have not previously been described for the species. House mice were also identified as a potential threat to the Horsburgh Island rail population. Island rail species have suffered a high rate of extinctions, and their conservation remains a formidable challenge, given the risks of continuing introductions of invasive mammalian predator species.
SinNLRR: a robust subspace clustering method for cell type detection by non-negative and low-rank representation
Authors: Zheng Ruiqing , Li Min , Liang Zhenlan , Wu Fang-Xiang , Pan Yi , Wang Jianxin
Published: February 2019

Motivation

The development of single-cell RNA-sequencing (scRNA-seq) provides a new perspective to study biological problems at the single-cell level. One of the key issues in scRNA-seq analysis is to resolve the heterogeneity and diversity of cells, which is to cluster the cells into several groups. However, many existing clustering methods are designed to analyze bulk RNA-seq data, it is urgent to develop the new scRNA-seq clustering methods. Moreover, the high noise in scRNA-seq data also brings a lot of challenges to computational methods.

Results

In this study, we propose a novel scRNA-seq cell type detection method based on similarity learning, called SinNLRR. The method is motivated by the self-expression of the cells with the same group. Specifically, we impose the non-negative and low rank structure on the similarity matrix. We apply alternating direction method of multipliers to solve the optimization problem and propose an adaptive penalty selection method to avoid the sensitivity to the parameters. The learned similarity matrix could be incorporated with spectral clustering, t-distributed stochastic neighbor embedding for visualization and Laplace score for prioritizing gene markers. In contrast to other scRNA-seq clustering methods, our method achieves more robust and accurate results on different datasets.

Availability and implementation

Our MATLAB implementation of SinNLRR is available at, https://github.com/zrq0123/SinNLRR.

Supplementary information

Supplementary data are available at Bioinformatics online.
SW-Tandem: a highly efficient tool for large-scale peptide identification with parallel spectrum dot product on Sunway TaihuLight
Authors: Li Chuang , Li Kenli , Chen Tao , Zhu Yunping , He Qiang
Published: February 2019

Tandem mass spectrometry based database searching is a widely acknowledged and adopted method that identifies peptide sequence in shotgun proteomics. However, database searching is extremely computationally expensive, which can take days even weeks to process a large spectra dataset. To address this critical issue, this paper presents SW-Tandem, a new tool for large-scale peptide sequencing. SW-Tandem parallelizes the spectrum dot product scoring algorithm and leverages the advantages of Sunway TaihuLight, the No. 1 supercomputer in the world in 2017. Sunway TaihuLight is powered by the brand new many-core SW26010 processors and provides a peak computation performance greater than 100PFlops. To fully utilize the Sunway TaihuLights capacity, SW-Tandem employs three mechanisms to accelerate large-scale peptide identification, memory-access optimizations, double buffering and vectorization. The results of experiments conducted on multiple datasets demonstrate the performance of SW-Tandem against three state-of-the-art tools for peptide identification, including X!! Tandem, MR-Tandem and MSFragger. In addition, it shows high scalability in the experiments on extremely large datasets sized up to 12 GB.

Availability and implementation

SW-Tandem is an open source software tool implemented in C++. The source code and the parameter settings are available at https://github.com/Logic09/SW-Tandem.

Supplementary information

Supplementary data are available at Bioinformatics online.
SOX8 acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer
Authors: Tang Hailin , Chen Bo , Liu Peng , Xie Xinhua , He Rongfang , Zhang Lijuan , Huang Xiaojia , Xiao Xiangsheng , Xie Xiaoming
Published: February 2019

The molecular mechanisms underlying triple-negative breast cancer (TNBC) pathology are not fully understood. Here, we reviewed the SOX8 transcript level in 24 types of cancer and normal tissues and the SOX8 expression pattern in breast cancer from the TCGA and METABRIC data sets and found that SOX8 was highly expressed in TNBC. We investigated the effect of SOX8 on tumorigenicity, migration and apoptosis in TNBC cell lines and xenografts models. We identified SOX8 as a functional oncogene that involved in the maintenance of stem-like capacities in TNBC cells. Through a promoter truncation experiment and ChIP experiment, we verified zinc finger E-box binding homeobox 1 (ZEB1) as a transcriptional activator of SOX8 that enhanced SOX8 expression by binding to its promoter. We evaluated the ZEB1 and the SOX8 levels in 240 TNBC patients and high expression of ZEB1 and SOX8 were significantly associated with poor prognosis. We demonstrated the significance of the ZEB1–SOX8 axis in regulating TNBC cancer stem-like cells (CSCs) and its connection with poor prognosis. Due to its vital role in TNBC CSCs, the ZEB1–SOX8 regulatory axis could be a promising therapeutic target for TNBC.
RAB14 activates MAPK signaling to promote bladder tumorigenesis
Authors: Chao Haichao , Deng Leihong , Xu Fanghua , Fu Bin , Zhu Zunwei , Dong Zhifeng , Liu Yen-Nien , Zeng Tao
Published: February 2019

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential and its abundance was significantly associated with lymph node metastasis (P = 0.001), a high-grade tumor stage (P = 0.009), poor differentiation (P < 0.001) and unfavorable prognoses of BC patients (P = 0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein and inhibited cell migration and invasion (P < 0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling through upregulation of MAPK1/MAPK8 and downregulation of dual-specificity protein phosphatase 6/Src homology 2 domain containing transforming protein/Fos proto-oncogene, AP-1 transcription factor subunit (FOS). We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.
Corticostriatal Circuits Encode the Subjective Value of Perceived Control
Authors: Wang Kainan S , Delgado Mauricio R
Published: February 2019

The ability to perceive and exercise control over an outcome is both desirable and beneficial to our well-being. It has been shown that animals and humans alike exhibit behavioral bias towards seeking control and that such bias recruits the ventromedial prefrontal cortex (vmPFC) and striatum. Yet, this bias remains to be quantitatively captured and studied neurally. Here, we employed a behavioral task to measure the preference for control and characterize its neural underpinnings. Participants made a series of binary choices between having control and no-control over a game for monetary reward. The mere presence of the control option evoked activity in the ventral striatum. Importantly, we manipulated the expected value (EV) of each choice pair to extract the pairing where participants were equally likely to choose either option. The difference in EV between the options at this point of equivalence was inferred as the subjective value of control. Strikingly, perceiving control inflated the reward value of the associated option by 30% and this value inflation was tracked by the vmPFC. Altogether, these results capture the subjective value of perceived control inherent in decision making and highlight the role of corticostriatal circuitry in the perception of control.
Immune cells as targets for cardioprotection: new players and novel therapeutic opportunities
Authors: Andreadou Ioanna , Cabrera-Fuentes Hector A , Devaux Yvan , Frangogiannis Nikolaos G , Frantz Stefan , Guzik Tomasz , Liehn Elisa A , Gomes Clarissa P C , Schulz Rainer , Hausenloy Derek J
Published: February 2019

New therapies are required to reduce myocardial infarct (MI) size and prevent the onset of heart failure in patients presenting with acute myocardial infarction (AMI), one of the leading causes of death and disability globally. In this regard, the immune cell response to AMI, which comprises an initial pro-inflammatory reaction followed by an anti-inflammatory phase, contributes to final MI size and post-AMI remodelling [changes in left ventricular (LV) size and function]. The transition between these two phases is critical in this regard, with a persistent and severe pro-inflammatory reaction leading to adverse LV remodelling and increased propensity for developing heart failure. In this review article, we provide an overview of the immune cells involved in orchestrating the complex and dynamic inflammatory response to AMI—these include neutrophils, monocytes/macrophages, and emerging players such as dendritic cells, lymphocytes, pericardial lymphoid cells, endothelial cells, and cardiac fibroblasts. We discuss potential reasons for past failures of anti-inflammatory cardioprotective therapies, and highlight new treatment targets for modulating the immune cell response to AMI, as a potential therapeutic strategy to improve clinical outcomes in AMI patients. This article is part of a Cardiovascular Research Spotlight Issue entitled ‘Cardioprotection Beyond the Cardiomyocyte’, and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
Unifocalization cannot rely exclusively on native pulmonary arteries: the importance of recruitment of major aortopulmonary collaterals in 249 cases†
Authors: Barron David J , Kutty Ramesh S , Stickley John , Stümper Oliver , Botha Phil , Khan Natasha E , Jones Timothy J , Drury Nigel E , Brawn William J
Published: February 2019

OBJECTIVES:

We sought to define the early and late outcomes of unifocalization based on a classification of the native pulmonary artery (nPA) system and major aortopulmonary collateral arteries (MAPCAs) with a policy of combined recruitment and rehabilitation and to analyse the role of unifocalization by leaving the ventricular septal defect (VSD) open with a limiting right ventricle-pulmonary artery (RV-PA) conduit in borderline cases.

METHODS:

An analysis of 271 consecutive patients assessed for unifocalization at a single institution between 1988 and 2016 was performed. Patients were classified according to the pulmonary blood supply: group A, unifocalization based on nPA only; group B, based on nPA and MAPCAs; group C, MAPCAs only (absent nPAs).

RESULTS:

Unifocalization was achieved in 249 (91.9%) cases with an early mortality of 2.8%. Group A included 72 (28.9%) patients, group B 119 (47.8%) patients and group C 58 (23.3%) patients with no difference in early survival between groups. Survival at 5, 10 and 15 years was 90.0% (85.9–94.3), 87.2% (83.5–91.2) and 82.3% (75.2–89.9), respectively. Late survival in groups A and B was similar but 10- and 15-year survival in group C decreased to 79.2% (68.2–92.1) and 74.3% (61.1–90.4) (P = 0.02), respectively. A mean of 1.9 (±0.6) MAPCAs were recruited per patient (range 0–6). The VSD was left open with a limiting RV-PA conduit in 97 (39.0%) cases, but subsequently closed in 48 patients, giving a total of 200 (80.3%) patients achieving VSD closure (full repair). Delaying VSD closure was not associated with increased risk for early or late survival. A central shunt to rehabilitate the nPAs was used in 56 (22.5%) cases. This was associated with a reduction in the number of MAPCAs recruited, but still required a mean of 1.8 (±0.5) MAPCAs recruited per patient to achieve unifocalization. In multivariate risk analysis, those suitable for single-stage full repair had the best long-term outcomes. Group C anatomy was associated with poor late survival compared to groups A and B (hazard ratio 2.7).

CONCLUSIONS:

Survival is maximized by a combined approach of rehabilitation and recruitment. MAPCAs should always be recruited if they supply areas with absent nPA supply. A strategy of leaving the VSD open with a limiting RV-PA conduit is a safe and effective way of managing borderline cases.
Management of asymptomatic arrhythmias: a European Heart Rhythm Association (EHRA) consensus document, endorsed by the Heart Failure Association (HFA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Cardiac Arrhythmia Society of Southern Africa (CASSA), and Latin America Heart Rhythm Society (LAHRS)
Authors: Arnar David O , Mairesse Georges H , Boriani Giuseppe , Calkins Hugh , Chin Ashley , Coats Andrew , Deharo Jean-Claude , Svendsen Jesper Hastrup , Heidbüchel Hein , Isa Rodrigo , Kalman Jonathan M , Lane Deirdre A , Louw Ruan , Lip Gregory Y H , Maury Philippe , Potpara Tatjana , Sacher Frederic , Sanders Prashanthan , Varma Niraj , Fauchier Laurent ,   ESC Scientific Document Group, Haugaa Kristina , Schwartz Peter , Sarkozy Andrea , Sharma Sanjay , Kongsgård Erik , Svensson Anneli , Lenarczyk Radoslaw , Volterrani Maurizio , Turakhia Mintu , Obel Isreal W P , Abello Mauricio , Swampillai Janice , Kalarus Zbigniew , Kudaiberdieva Gulmira , Traykov Vassil B ,   EHRA Scientific Documents Committee, Dagres Nikolaos , Boveda Serge , Vernooy Kevin , Kalarus Zbigniew , Kudaiberdieva Gulmira , Mairesse Georges H , Kutyifa Valentina , Deneke Thomas , Hastrup Svendsen Jesper , Traykov Vassil B , Wilde Arthur , Heinzel Frank R
Published: February 2019

Asymptomatic arrhythmias are frequently encountered in clinical practice. Although studies specifically dedicated to these asymptomatic arrhythmias are lacking, many arrhythmias still require proper diagnostic and prognostic evaluation and treatment to avoid severe consequences, such as stroke or systemic emboli, heart failure, or sudden cardiac death. The present document reviews the evidence, where available, and attempts to reach a consensus, where evidence is insufficient or conflicting.
The Calabi Flow with Rough Initial Data
Authors: He Weiyong , Zeng Yu
Published: February 2019

In this paper, we prove that there exists a dimensional constant $\delta> 0$ such that given any background Kähler metric $\omega $, the Calabi flow with initial data $u_0$ satisfying $$\begin{equation*} \partial \bar \partial u_0 \in L^\infty (M)\ \textrm{and}\ (1- \delta )\omega < \omega_{u_0} < (1+\delta )\omega, \end{equation*}$$admits a unique short-time solution, and it becomes smooth immediately, where $\omega _{u_0}: = \omega +\sqrt{-1}\partial \bar \partial u_0$. The existence time depends on initial data $u_0$ and the metric $\omega $. As a corollary, we get that the Calabi flow has short-time existence for any initial data satisfying $$\begin{equation*} \partial \bar \partial u_0 \in C^0(M)\ \textrm{and}\ \omega_{u_0}> 0, \end{equation*}$$which should be interpreted as a “continuous Kähler metric”. A main technical ingredient is a new Schauder-type estimates for biharmonic heat equation on Riemannian manifolds with time-weighted Hölder norms.
The effect of medication cost transparency alerts on prescriber behavior
Authors: Monsen Craig B , Liao Joshua M , Gaster Barak , Flynn Kevin J , Payne Thomas H
Published: February 2019

Objective

The purpose of this study was to determine if medication cost transparency alerts provided at time of prescribing led ambulatory prescribers to reduce their use of low-value medications.

Materials and Methods

Provider-level alerts were deployed to ambulatory practices of a single health system from February 2018 through April 2018. Practice sites included 58 primary care and 152 specialty care clinics totaling 1896 attending physicians, residents, and advanced practice nurses throughout western Washington. Prescribers in the randomly assigned intervention arm received a computerized alert whenever they ordered a medication among 4 high-cost medication classes. For each class, a lower cost, equally effective, and safe alternative was available. The primary outcome was the change in prescribing volume for each of the 4 selected medication classes during the 12-week intervention period relative to a prior 24-week baseline.

Results

A total of 15 456 prescriptions for high-cost medications were written during the baseline period including 7223 in the intervention arm and 8233 in the control arm. During the intervention period, a decrease in daily prescribing volume was noted for all high-cost medications including 33% for clobetasol propionate (p < .0001), 59% for doxycycline hyclate (p < .0001), 43% for fluoxetine tablets (p < .0001), and a non-significant 3% decrease for high-cost triptans (p = .65). Prescribing volume for the high-cost medications overall decreased by 32% (p < .0001).

Conclusion

Medication cost transparency alerts in an ambulatory setting lead to more cost-conscious prescribing. Future work is needed to predict which alerts will be most effective.
Absence of Day 3 Steroid Response Predicts Colitis-Related Complications and Colectomy in Hospitalized Ulcerative Colitis Patients
Authors: Leung Kristel , Rhee Glara , Parlow Simon , Bollu Apoorva , Sabri Elham , McCurdy Jeffrey D , Murthy Sanjay K
Published: February 2019

Background and Aims

Rates and predictors of complications among hospitalized ulcerative colitis (UC) patients requiring high-dose corticosteroids have not been well-characterized, especially in the era of biologics.

Methods

We retrospectively studied consecutive UC admitted for a colitis flare requiring high-dose corticosteroids between April 2006 and December 2016. We evaluated rates and determinants of serious in-hospital complications (colitis-related complications, systemic complications, peri-operative complications and death) and colectomy. We performed multivariable logistic regression analysis to assess the independent association between day 3 steroid response and the risk of incurring in-hospital complications and colectomy.

Results

Of 427 consecutive admissions, serious in-hospital complications occurred in 87 cases (20%), while colitis-related complications occurred in 47 cases (11%). There were significantly fewer colitis-related complications during the 2012 to 2016 period as compared to the 2006 to 2011 period (7% versus 16%, P < 0.01), but significantly more systemic complications (16% versus 5%, P = 0.001). In-hospital colectomy occurred in 50 hospitalizations (12%). Day 3 steroid response was achieved in 167 hospitalizations (39%). Day 3 steroid nonresponse was significantly associated with colitis-related complications among males (adjusted odds ratio [aOR] 8.22, 95% confidence interval [CI] 1.77 to 38.17), but not among females (aOR 1.39, 95% CI 0.54 to 3.60). Older age, C. difficile infection and admission to a non-gastroenterology service were also associated with a higher risk of in-hospital complications. Day 3 steroid nonresponse was significantly associated with in-hospital colectomy (aOR 10.10, 95% CI 3.56 to 28.57).

Conclusion

In our series of UC hospitalizations for a colitis flare, absence of day 3 steroid response was associated with an increased risk of colitis-related complications among males and of in-hospital colectomy. Clinicians should recognize the importance of early steroid response as a marker to guide the need for treatment optimization.
Cumulative Toxicity in Targeted Therapies: What to Expect at the Recommended Phase II Dose
Authors: Altzerinakou Maria-Athina , Collette Laurence , Paoletti Xavier
Published: February 2019

Background

In the era of molecularly targeted agents (MTAs), it is recommended to account for toxicity over several cycles to identify the recommended phase II dose (RP2D). We investigated the relationship between the risk of toxicity at cycle 1 and the cumulative incidence of toxicity over subsequent cycles in trials of single MTAs.

Methods

On individual patient data from 26 phase I clinical trials of single MTAs provided by the National Cancer Institute, we estimated the probability of first-severe toxicity per treatment cycle as well as the cumulative incidence at, below, and above the maximum tolerated dose (MTD). Toxicity was further subclassified into nonhematologic and hematologic. A prediction table was developed to estimate the cumulative incidence up to six cycles based on the toxicity rate observed in the first cycle.

Results

Overall, 942 patients were included. For patients treated at the MTD, the probability of first-severe toxicity decreased from 24.8% (95% prediction interval [PI] = 20.3% to 32.9%) to 2.2% (95% PI = 0.1% to 7.7%) from cycle 1 to 6, whereas the cumulative incidence of toxicity reached 51.7% (95% PI = 40.5% to 66.3%) after six cycles. Toxicity rates ranging from 20.0% to 30.0% in the first cycle were associated with 46.8% (95% PI = 39.5% to 54.2%) and 65.8% (95% PI = 57.7% to 73.1%) cumulative incidence after six cycles.

Conclusion

This study examined the risk of severe toxicity over time of single MTAs. The cumulative incidence of toxicity at the MTD was higher than the usually accepted toxicity targets, challenging the definition of the RP2D of MTAs. The prediction table may help calibrate the target rate at the RP2D.
Intravenous Tissue Plasminogen Activator for Large Vessel Ischemic Stroke – Is There Still a Role?
Authors: Sawyer Robert N
Published: February 2019

While the efficacy of Intravenous tissue plasminogen activator (tPA) is well established, its impact on large vessel occlusion (LVO) is controversial. Whether IV tPA should be bypassed in favor of endovascular thrombectomy (MT) will be addressed. Compelling evidence exists to suggest tPA administration might be bypassed in tPA eligible patients in favor of MT for LVO. A trial of MT with patients randomized for IV tPA within the 4.5-h time window should conducted at comprehensive stroke centers demonstrating equipoise between time to tPA or MT with time to treatment from ED arrival of 45 min. We may do well to consider the systems pathway taken by interventional cardiologists 15 years ago.
A New Piece of the Puzzle to Understand Cervical Sagittal Alignment: Utilizing a Novel Angle δ to Describe the Relationship among T1 Vertebral Body Slope, Cervical Lordosis, and Cervical Sagittal Alignment
Authors: Goldschmidt Ezequiel , Angriman Federico , Agarwal Nitin , Trevisan Marcos , Zhou James , Chen Katherine , Gerszten Peter C , Kanter Adam S , Okonkwo David O , Passias Peter , Scheer Justin , Protopsaltis Themistocles , Lafage Virginie , Lafage Renaud , Schwab Frank , Bess Shay , Ames Christopher , Smith Justin S , Shaffrey Christopher I , Miller Emily , Jain Amit , Neuman Brian , Sciubba Daniel M , Burton Douglas , Hamilton D Kojo ,   International Spine Study Group (ISSG)
Published: February 2019

Cervical alignment has become increasingly important in the planning of spine surgery. A relationship between the slope of T1 (T1S), the cervical lordosis (CL), and the overall cervical sagittal vertical axis (cSVA) has previously been demonstrated, but the exact nature of this relationship is poorly understood. In this study, we derive theoretical and empirical equations to better understand how T1S and CL affect cSVA. The first equation was developed on a theoretical basis using inherent trigonometric relationships of the cervical spine. By treating the cervical spine as the arc of a circumference, and by taking into account the cervical height (CH), the geometric relationship between theT1S, CL, and cSVA was described via a trigonometric identity utilizing a novel angle δ subtended by the CH and cSVA (δ = T1S-CL/2). The second equation was developed on an empiric basis by performing a multiple linear regression on data obtained from a retrospective review of a large multicenter deformity database. The theoretical equation determined that the value of cSVA could be expressed as:

. The empirical equation determined that value of cSVA could be expressed as:

. In both, the sagittal alignment of the head over the shoulders is directly proportional to the T1S and inversely proportional to CL/2. These 2 equations may allow surgeons to better understand how the CL compensates for the T1S, to accurately predict the postoperative cSVA, and to customize cervical interbody grafts by taking into consideration each individual patient's specific cervical spine parameters.
Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model
Authors: Gerhardson Tyler , Sukovich Jonathan R , Chaudhary Neeraj , Chenevert Thomas L , Ives Kim , Hall Timothy L , Camelo-Piragua Sandra , Xu Zhen , Pandey Aditya S
Published: February 2019

BACKGROUND

Intracerebral hemorrhage (ICH) is characterized by a 30-d mortality rate of 40% and significant disability for those who survive.

OBJECTIVE

To investigate the initial safety concerns of histotripsy mediated clot liquefaction and aspiration in a porcine ICH model. Histotripsy is a noninvasive, focused ultrasound technique that generates cavitation to mechanically fractionate tissue. Histotripsy has the potential to liquefy clot in the brain and facilitate minimally invasive aspiration.

METHODS

About 1.75-mL clots were formed in the frontal lobe of the brain (n = 18; n = 6/group). The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Pigs underwent magnetic resonance imaging (MRI) 7 to 8 d after clot formation and were subsequently euthanized. Neurological behavior was assessed throughout. Histological analysis was performed on harvested brains. A subset of pigs underwent acute analysis (≤6 h).

RESULTS

Histotripsy was able to liquefy the center of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups.

CONCLUSION

This study presents the first analysis of histotripsy-based liquefaction of ICH in vivo. Histotripsy safely liquefies clots without significant additional damage to the perihematomal region. The liquefied content of the clot can be easily evacuated, and the undrained clot has no effect on pig survival or neurological behavior.
X-ray spectra of Sagittarius A East and diffuse X-ray background near the Galactic center
Authors: Ono Akiko , Uchiyama Hideki , Yamauchi Shigeo , Nobukawa Masayoshi , Nobukawa Kumiko K , Koyama Katsuji
Published: February 2019

This paper reports the analysis procedure and results of simultaneous spectral fits of the Suzaku archive data for Sagittarius (Sgr) A East and the nearby Galactic center X-ray emission (GCXE). The results are that the mixed-morphology supernova remnant Sgr A East has a recombining plasma (RP) with Cr and Mn Heα lines, and a power-law component (PL) with an Fe i Kα line. The nearby GCXE has a ∼1.5-times larger surface brightness than the mean GCXE far from Sgr A East, although the spectral shape is almost identical. Based on these results, we interpret that the origins of the RP and the PL with the Fe i Kα line are past big flares of Sgr A⋆.
Where is the Hoechst Insulin?: The Role of Diabetics and Their Doctors as Consumers During the German Democratic Republic’s Autarkic Policy of ‘Making Free From Disturbance’, 1961–1966
Authors: Hiepko Kathrin A
Published: February 2019

This article examines the treatment of the chronic disease, diabetes mellitus, during and immediately after the German Democratic Republic (GDR)’s autarkic policy of Störfreimachung, literally translated as ‘making free from disturbance’. I look specifically at an insulin favoured by East German diabetes specialists and their patients delivered from the West German pharmaceutical company, Hoechst AG, and the consequences of preventing this insulin from being imported. By using insulin as a case study, a medication necessary for the survival of insulin-dependent diabetics, the article offers a close analysis of the complex relationship between ordinary citizens, medical professionals and the ruling Socialist Unity Party (SED) following the building of the Berlin Wall. I argue that the intense focus on the issue of consumption in the competition between the GDR and West Germany shaped both the attitude of the SED and those responding to the policy of Störfreimachung. The SED regime and leading health officials espoused a highly ‘productionist’ medical ethos that was somewhat at odds with their growing desire to meet increasing consumer demands. This collision opened up ideological contradictions, which provided an opportunity for those on the receiving end of the policy to discredit it, and, by extension, justify the continued use of their preferred choice of insulin from Hoechst. I draw, in particular, on patient Eingaben (petitions) and reports by district diabetologists in order to uncover this trend.
Abu Dhabi Foundations Regime: strategic location in the Middle East for legacy planning towards emerging high growth markets
Authors: Mrazek Yann
Published: February 2019

Most Middle East entrepreneurial families are familiar with foreign offshore trusts and foundations, and have been using these tools to ensure wealth preservation and inter-generational continuity for several generations. In that context, the new foundation regime was introduced in 2017 in the Abu Dhabi Global Market, a Middle East common law familiar jurisdiction, meeting all the requirements for a simple-to-understand, cost-effective, and sustainable vehicle dedicated to wealth management and preservation, family succession planning, tax planning, asset protection, corporate structuring, and for public interest foundations (excluding charities). The purpose of this article is to present to the reader the context, mechanisms, and interests to use Abu Dhabi Global Market private foundations.
Nonpharmacologic options for treating irritable bowel syndrome
Authors: Kay Emelia , Hawramee Sham , Pollani Stephen , Mandel Ellen D.
Published: February 2019

Irritable bowel syndrome (IBS) is a chronic functional disorder with no organic cause. Risk factors are multifactorial and treatment typically consists of antimotility or stimulant laxatives and antidepressants. This article reviews several newer areas of interest: probiotics, fecal microbiota transplant, a low FODMAP diet, and cognitive behavioral therapy.
Asthma 101
Authors: Chike-Harris Katherine E. , Kinyon-Munch Kathryn
Published: February 2019

Providers across the spectrum of healthcare must be aware of their patients' inhaler use. This article addresses common errors and the proper use of pressurized metered-dose inhalers in pediatric patients.
Challenges Associated With Moving the United States Medical Licensing Examination (USMLE) Step 1 to After the Core Clerkships and How to Approach Them
Authors: Pock Arnyce , Daniel Michelle , Santen Sally A. , Swan-Sein Aubrie , Fleming Amy , Harnik Vicky
Published: February 2019

An increasing number of medical schools have moved away from traditional 2 + 2 curricular structures toward curricula that intentionally integrate basic, clinical, and health systems science, with the goal of graduating physicians who consistently apply their foundational knowledge to clinical practice to improve the care of patients and populations. These curricular reforms often include a shortened preclerkship phase with earlier introduction of learners into clinical environments. This has led schools to reconsider the optimal timing of United States Medical Licensing Examination Step 1. A number of schools have shifted the exam to the period immediately after core clerkships. Although this shift can provide pedagogical advantages, there are potential challenges that must be anticipated and proactively addressed. As more institutions consider making this change, key educational leaders from five schools that repositioned the Step 1 exam after core clerkships share strategies for mitigating some of the potential challenges associated with this approach. The authors describe six possible challenges: lack of readiness without consolidation of basic science knowledge prior to clerkships; risk that weaker students will not be identified and provided academic support early; clerkship or clinical shelf exam performance weaknesses; extension of Step 1 study time; an increase in student anxiety about residency specialty choices; and/or a reduced time frame to take and pass board exams. These potential challenges may be addressed using three main strategies: effective communication with all stakeholders; curricular design and assessments that facilitate integration of basic and clinical sciences; and proactive student coaching and advising.
How Patients’ Stories Shape Their Votes: The Role of Health Care in the 2018 U.S. Midterm Elections
Authors: Gordon Paul , Shapiro Eve
Published: February 2019

Reflecting on the 2018 U.S. midterm elections, it is clear that health care coverage once again played an important role. This prompted the authors to look back on their 2016 bike listening tour across the country when they asked people about their views on the Affordable Care Act. Through those conversations, the authors observed that a common thread was the rampant misunderstanding of health insurance coverage and the central role that politicians had in the creation of policy. In this Invited Commentary, the authors explore the results of the 2018 election, particularly in the rural northern areas where they toured in 2016, and the contradictions between what people say they want, what the candidates say they support, and what the facts actually show. They offer suggestions for the role physicians might play with patients in correcting misunderstandings about the health care system and the policies that shape it. Patients do not always make decisions as physicians do. As opposed to evidence and data, they might rely on personal experiences and stories. The authors suggest that physicians might be able to help patients use these stories to inform their decisions, and to help them understand the connection between their personal health care experiences and the votes they cast in elections.
ICU Survivors Have a Substantial Higher Risk of Developing New Chronic Conditions Compared to a Population-Based Control Group
Authors: van Beusekom Ilse , Bakhshi-Raiez Ferishta , van der Schaaf Marike , Busschers Wim B. , de Keizer Nicolette F. , Dongelmans Dave A.
Published: February 2019

Objectives:

To describe the types and prevalence of chronic conditions in an ICU population and a population-based control group during the year before ICU admission and to quantify the risk of developing new chronic conditions in ICU patients compared with the control group.

Design:

We conducted a retrospective cohort study, combining a national health insurance claims database and a national quality registry for ICUs. Claims data in the timeframe 2012–2014 were combined with clinical data of patients who had been admitted to an ICU during 2013. To assess the differences in risk of developing new chronic conditions, ICU patients were compared with a population-based control group using logistic regression modeling.

Setting:

Eighty-one Dutch ICUs.

Patients:

All patients admitted to an ICU during 2013. A population-based control group was created, and weighted on the age, gender, and socio-economic status of the ICU population.

Interventions:

None.

Measurements and Main Results:

ICU patients (n = 56,760) have more chronic conditions compared with the control group (n = 75,232) during the year before ICU admission (p < 0.0001). After case-mix adjustment ICU patients had a higher risk of developing chronic conditions, with odds ratios ranging from 1.67 (CI, 1.29–2.17) for asthma to 24.35 (CI, 14.00–42.34) for epilepsy, compared with the control group.

Conclusions:

Due to the high prevalence of chronic conditions and the increased risk of developing new chronic conditions, ICU follow-up care is advised and may focus on the identification and treatment of the new developed chronic conditions.
Pregnancy outcomes of elective induction in low-risk term pregnancies
Authors: Na Eun Duc , Chang Sung Woon , Ahn Eun Hee , Jung Sang Hee , Kim Young Ran , Jung Inkyung , Cho Hee Young
Published: February 2019

We investigated the mode of delivery and perinatal outcomes in low-risk pregnant women whose labor was electively induced or expectantly managed at term.

Healthy women with viable, vertex singleton pregnancies at 37+0 to 40+6 weeks of gestation were included. Women electively induced (n = 416) in each week (37+0–37+6, 38+0–38+6, 39+0–39+6, 40+0–40+6 weeks) were compared with pregnant women with spontaneous labor (n = 487). The primary outcome was mode of delivery. A propensity score (PS) was derived using logistic regression to model the probability of elective induction group as a function of potential confounders. Altogether, 284 women with elective induction were matched with 284 women who underwent expectant management to create a PS-matched population. All analysis was performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC). All P values reported of the significance level was set at <.05.

There are no significant differences of delivery mode, neonatal intensive care unit (NICU) admission, and neonatal complication between PS-matched groups. Incidence of antepartum complications showed higher in the elective induction group compared to the spontaneous labor group (P = .04). When comparing each gestational week, incidence of NICU admission at 38 weeks in the elective induction group [10/74 (13.5%)] was significantly higher than in and the spontaneous labor group [2/74 (2.7%)] (P = .04).

Elective induction of labor at term is not associated with increased risk of cesarean delivery. However, overall incidence of NICU admission at 38 gestational weeks seems to be increased in elective induction.
High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China
Authors: Shen Fang-Fang , Pan Ying , Li Jing-Zhong , Zhao Fang , Yang Hai-Jun , Li Jun-Kuo , Gao Zhao-Wei , Su Jing-Fen , Duan Li-Juan , Lun Shu-Min , Zhang Peng , Tian Lin-Qiang , Sun Gang , Huang Da , Cao Yan-Tian , Zhou Fu-You
Published: February 2019

Background:

Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC.

Methods:

We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed.

Result:

Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues (P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC.

Conclusions:

Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.
Association between CXCL9/10 polymorphisms and acute rejection of liver allograft
Authors: Ostojic Ana , Markotic Antonio , Kelava Tomislav , Mrzljak Anna
Published: February 2019

While increased serum concentrations of CXCL9/10 are associated with acute cellular rejection (ACR) occurrence, the association between CXCL9/10 single nucleotide polymorphisms (SNPs) and ACR after liver transplantation (LT) remains unknown.

In the present case-control study, polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) were determined by polymerase chain reaction in 215 liver transplant recipients. ACR was defined as biopsy proven within 6 months after LT. As selected SNPs were in 3’-UTR region, their possible association with protein synthesis was assessed by measuring the plasma concentration of CXCL9/10 in a cohort of 40 new transplant patients using ELISA.

There was no association between CXCL9/10 genotypes and overall incidence of ACR. However, patients with CXCL9 genotype AA developed ACR earlier than patients with GG genotype (P = .003), with similar results for CXCL10 gene (CC vs GG; P = .005). There was no statistically significant difference in plasma concentrations of CXCL9/10 between the rejectors and the non-rejectors. Of note, patients with AA CXCL9 genotype had significantly higher CXCL9 plasma concentrations than patients with AG (P = .01) or GG genotype (P = .045).

In conclusion, the SNPs of CXCL9 (rs10336) and CXCL10 (rs3921) are not associated with the incidence of ACR. However, patients with CXCL9 genotype AA developed ACR earlier and the same genotype was associated with greater plasma concentrations suggesting the involvement of CXCL9 mediated processes in ACR development.
Auriculotherapy for sleep quality in people with primary insomnia
Authors: Ren Runyuan , Zhang Jiayuan , Zhang Tingting , Peng Yangzhi , Tang Chenjian , Zhang Qi
Published: February 2019

Background:

Primary insomnia is one of the common sleep disorders. Auriculotherapy originated from traditional Chinese medicine, has been thought as a promising treatment for primary insomnia. We aim to evaluate the efficacy and safety of auriculotherapy for patients with primary insomnia through this systematic review.

Methods:

Five English databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, and CINAHL), 4 Chinese databases (CBM, CNKI, CQVIP, and Wanfang), and 5 clinical trial registration databases (ClinicalTrials.gov, ANZCTR, EU-CTR, ChiCTR, and ICTRP) will be searched from establishment of the database until November 2018. Articles written in English or Chinese languages will be included. The randomized controlled trials of auriculotherapy (auricular acupuncture and auricular acupressure) for patients with primary insomnia will be included. The primary outcome will be assessed according to the Pittsburgh sleep quality index. Meta-analysis will be conducted with the use of RevMan 5.3. The specific process will refer to the Cochrane Handbook 5.1 for Systematic Review.

Results:

High-quality synthesis of current evidence on the efficacy and safety of auriculotherapy for primary insomnia will be provided in this study.

Conclusion:

This systematic review aims to present evidence for whether auriculotherapy is an effective intervention which can improve sleep quality in patients suffering primary insomnia.

PROSPERO registration number:

CRD42019106422.
Unrecognized esophageal fish bone impaction with delayed presentation of acute spastic central chest pain
Authors: Liu Ching-Han , Huang Shih-Chung , Lin Wei-Shiang , Lin Chin-Sheng
Published: February 2019

Rationale:

Esophageal chest pain is difficult to be identified, and the diagnosis requires a high index of clinical suspicion. Upon presentation, they are difficult to be differentiated from acute coronary syndrome (ACS) by symptomatology alone.

Patient concerns:

We report a 71-year-old woman with multiple risk factors for coronary heart disease who presented with acute central spastic chest pain and was diagnosed as ACS in emergency department.

Diagnoses:

Chest computed tomography revealed 1 radiopaque lesion over the upper-third of the esophagus. One fishbone with 3-pointed heads stuck in the esophagus was noted under esophagogastroscopic examination.

Interventions:

The fishbone was extracted successfully via endoscopy under general anesthesia.

Outcomes:

The woman was discharged uneventfully after 3 days’ hospitalization.

Lessons:

This case illustrates that, even in emergency, clinicians should always keep in mind the possibility of esophageal foreign body impaction when confronted with frank central chest pain without associated gastrointestinal symptoms. This holds true even in the scenario of multiple cardiovascular risk factors and absence of ingestion history.