bluuebunny/crossref_metadata_2025_split huggingface dataset:
PI3K/AKT/mTOR Pathway Alterations Promote Malignant Progression and Xenograft Formation in Oligodendroglial Tumors
Authors: Tateishi Kensuke , Nakamura Taishi , Juratli Tareq A. , Williams Erik A. , Matsushita Yuko , Miyake Shigeta , Nishi Mayuko , Miller Julie J. , Tummala Shilpa S. , Fink Alexandria L. , Lelic Nina , Koerner Mara V.A. , Miyake Yohei , Sasame Jo , Fujimoto Kenji , Tanaka Takahiro , Minamimoto Ryogo , Matsunaga Shigeo , Mukaihara Shigeo , Shuto Takashi , Taguchi Hiroki , Udaka Naoko , Murata Hidetoshi , Ryo Akihide , Yamanaka Shoji , Curry William T. , Dias-Santagata Dora , Yamamoto Tetsuya , Ichimura Koichi , Batchelor Tracy T. , Chi Andrew S. , Iafrate A. John , Wakimoto Hiroaki , Cahill Daniel P. 
Published: April 2019

Abstract

Purpose:
Oligodendroglioma has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of oligodendroglioma could facilitate identification of therapeutic targets in progressive oligodendroglioma. We established multiple oligodendroglioma xenografts to determine if the PI3K/AKT/mTOR signaling pathway drives tumor progression.

Experimental Design:
Two anatomically distinct tumor samples from a patient who developed progressive anaplastic oligodendroglioma (AOD) were collected for orthotopic transplantation in mice. We additionally implanted 13 tumors to investigate the relationship between PI3K/AKT/mTOR pathway alterations and oligodendroglioma xenograft formation. Pharmacologic vulnerabilities were tested in newly developed AOD models in vitro and in vivo.

Results:
A specimen from the tumor site that subsequently manifested rapid clinical progression contained a PIK3CA mutation E542K, and yielded propagating xenografts that retained the OD/AOD-defining genomic alterations (IDH1R132H and 1p/19q codeletion) and PIK3CAE542K, and displayed characteristic sensitivity to alkylating chemotherapeutic agents. In contrast, a xenograft did not engraft from the region that was clinically stable and had wild-type PIK3CA. In our panel of OD/AOD xenografts, the presence of activating mutations in the PI3K/AKT/mTOR pathway was consistently associated with xenograft establishment (6/6, 100%). OD/AOD that failed to generate xenografts did not have activating PI3K/AKT/mTOR alterations (0/9, P &lt; 0.0001). Importantly, mutant PIK3CA oligodendroglioma xenografts were vulnerable to PI3K/AKT/mTOR pathway inhibitors in vitro and in vivo—evidence that mutant PIK3CA is a tumorigenic driver in oligodendroglioma.

Conclusions:
Activation of the PI3K/AKT/mTOR pathway is an oncogenic driver and is associated with xenograft formation in oligodendrogliomas. These findings have implications for therapeutic targeting of PI3K/AKT/mTOR pathway activation in progressive oligodendrogliomas.
HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism
Authors: Chiu Amy P. , Tschida Barbara R. , Sham Tung-Ting , Lo Lilian H. , Moriarity Branden S. , Li Xiao-Xiao , Lo Regina C. , Hinton David E. , Rowlands Dewi K. , Chan Chi-On , Mok Daniel K.W. , Largaespada David A. , Warner Nadia , Keng Vincent W. 
Published: April 2019

Abstract

Chronic hepatitis B viral (HBV) infection remains a high underlying cause for hepatocellular carcinoma (HCC) worldwide, while the genetic mechanisms behind this remain unclear. This study elucidated the mechanisms contributing to tumor development induced by the HBV X (HBx) gene of predominantly Asian genotype B HBV and its common HBx variants. To compare the potential tumorigenic effects of K130M/V131I (Mut) and wild-type (WT) HBx on HCC, the Sleeping Beauty (SB) transposon system was used to deliver HBx Mut and WT into the livers of fumarylacetoacetate hydrolase (Fah)-deficient mice and in the context of transformation related protein 53 (Trp53) deficiency. From our results, HBx Mut had a stronger tumorigenic effect than its WT variant. Also, inflammation, necrosis, and fibrosis were evident in HBx experimental animals. Reduction of forkhead box O1 (FOXO1) with increased phosphorylation of upstream serine/threonine kinase (AKT) was detected under HBx Mut overexpression. Thus, it is proposed that HBx Mut enhances disease progression by reducing FOXO1 via phosphorylation of AKT. At the metabolomic level, HBx altered the expression of genes that participated in arachidonic acid (AA) metabolism, as a result of inflammation via accumulation of proinflammatory factors such as prostaglandins and leukotriene in liver. Taken together, the increased rate of HCC observed in chronic hepatitis B patients with K130M/V131I-mutated X protein, may be due to changes in AA metabolism and AKT/FOXO1 signaling.

Implications:
Our findings suggested that HBx-K130M/V131I–mutant variant promoted HCC progression by activating AKT/FOXO1 pathway and inducing stronger inflammation in liver via AA metabolism.
Benign Intracerebral Hemorrhage: A Population at Low Risk for Hematoma Growth and Poor Outcome
Authors: Li Qi , Yang Wen‐Song , Shen Yi‐Qing , Xie Xiong‐Fei , Li Rui , Deng Lan , Yang Ting‐Ting , Lv Fa‐Jin , Lv Fu‐Rong , Wu Guo‐Feng , Tang Zhou‐Ping , Goldstein Joshua N. , Xie Peng 
Published: April 2019

Background

To define benign intracerebral hemorrhage (
ICH
) and to investigate the association between benign
ICH
, hematoma expansion, and functional outcome.

Methods and Results

We analyzed a prospectively collected cohort of patients with ICH, who presented within 6 hours of symptom onset between July 2011 and February 2017 to a tertiary teaching hospital. Follow‐up computed tomographic scanning was performed within 36 hours after initial computed tomographic scanning. Benign
ICH
was operationally defined as homogeneous and regularly shaped small
ICH
. The presence of benign
ICH
was judged by 2 independent reviewers (Q.L., W.Y.) on the basis of the admission computed tomographic scan. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between benign
ICH
, hematoma expansion, and functional outcome were assessed by using multivariable logistic regression analyses. A total of 288 patients with
ICH
were included. Benign
ICH
was found in 48 patients (16.7%). None of the patients with benign
ICH
had early hematoma expansion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of benign
ICH
for predicting functional independence at 3 months were 30.7%, 96.6%, 90.0%, 60.0%, and 0.637, respectively.

Conclusions

Patients with benign
ICH
are at low risk of hematoma expansion and poor outcome. These patients may be safe for less intensive monitoring and are unlikely to benefit from therapies aimed at preventing
ICH
expansion.
Cost savings following faecal microbiota transplantation for recurrent Clostridium difficile infection
Authors: Dehlholm-Lambertsen Emilie , Hall Bianca K. , Jørgensen Simon M. D. , Jørgensen Christine W. , Jensen Mia E. , Larsen Sara , Jensen Josephine S. , Ehlers Lars , Dahlerup Jens F. , Hvas Christian L. 
Published: April 2019

Background: Recurrent Clostridium difficile infection (rCDI) is becoming increasingly common. Faecal microbiota transplantation (FMT) is effective for rCDI, but the costs of an FMT and hospital cost savings related to FMT are unknown. The aim of this study was to calculate the cost of an FMT and the total hospital costs before and after FMT. Methods: This was an observational single-centre study, carried out in a public teaching hospital. We included all patients referred for rCDI from January 2014 through December 2015 and documented costs related to donor screening, laboratory processing, and clinical FMT application. We calculated patient-related hospital costs 1 year before FMT (pre-FMT) and 1 year after FMT (post-FMT). Sensitivity analyses were applied to assess the robustness of the results. Results: We included 50 consecutive adult patients who had a verified diagnosis of rCDI and were referred for FMT. The average cost of an outpatient FMT procedure if donor faeces were applied by colonoscopy was €3,326 per patient and €2,864 if donor faeces were applied using a nasojejunal tube. The total annual pre-FMT hospital costs per patient were €56,415 (95% confidence interval (CI) 41,133–71,697), and these costs dropped by 42% to €32,816 (22,618–42,014) post-FMT ( p = 0.004). The main cost driver was hospital admissions. Sensitivity analyses demonstrated cost reductions in all scenarios. Conclusions: In a public hospital with an implemented FMT service, the average cost of FMT applied by either colonoscopy or nasojejunal tube was €3,095. Total hospital costs dropped by 42% the first year after FMT. The reduction was mainly caused by reductions in the number of hospital admissions and in length of stay.
Tranexamic acid use is associated with lower transfusion rates in shoulder arthroplasty patients with preoperative anaemia
Authors: Clay T Bradly , Lawal A Sayo , Wright Thomas W , Patrick Matthew , Struk Aimee M , Farmer Kevin W , King Joseph J 
Published: April 2019

Background We evaluate tranexamic acid use in high-risk shoulder arthroplasty patients, hypothesizing that tranexamic acid will decrease transfusion rates in patients with low preoperative haematocrit. Methods A retrospective review of shoulder arthroplasty patients with preoperative anaemia compared those treated with and without perioperative tranexamic acid. Inclusion criterion was any shoulder arthroplasty with a preoperative haematocrit (Hct) <38%. Tranexamic acid was given generally as 1 g intravenously before incision and 1 g during wound closure; topical tranexamic acid was used in cases of contraindication to IV tranexamic acid. Preoperative Hct, postoperative Hct, estimated blood loss, preoperative anticoagulation use, American Society of Anesthesiologist score, transfusion rate and demographic data were compared between groups with and without tranexamic acid. Results Of the 435 arthroplasties performed, 109 patients had preoperative Hct < 38% (haemoglobin of 12.7 g/dL); 69 had tranexamic acid perioperatively and 40 did not. Demographics, anticoagulation use, diagnosis, arthroplasty types, estimated blood loss and preoperative Hct were similar between groups. The tranexamic acid group had a higher postoperative Hct, significantly lower transfusion rate and significantly smaller drop in Hct. Hct levels, Hct change and transfusion rate for topical versus intravenous tranexamic acid were not significantly different. Discussion Perioperative tranexamic acid in high-risk shoulder arthroplasty patients with preoperative Hct <38% is associated with higher postoperative Hct and lower transfusion rates.
Effects of patient suicide on psychiatrists: survey of experiences and support required
Authors: Gibbons Rachel , Brand Fiona , Carbonnier Anne , Croft Alison , Lascelles Karen , Wolfart Gislene , Hawton Keith 
Published: April 2019

Aims and methodDeath of patients by suicide can have powerful effects on psychiatrists. We report the findings of a survey completed by 174 psychiatrists on the effects of patient suicide on their emotional well-being and clinical practice, and the support and resources they felt would be helpful.Results and clinical implicationsThe death of a patient by suicide usually had a major effect on respondents. Clinical practice was often negatively affected, and over a quarter of respondents considered a change of career path as a result. There were some gender differences in responses, with women reporting more sense of responsibility for the deaths and a greater effect on their clinical confidence. Desired support included a senior suicide lead clinician, support during formal post-suicide processes, opportunity for reflection on practice, information about resources to support families and help communicating with families and friends of the deceased.
Effect of Right-Lateral Versus Left-Lateral Tilt Position on Compression of the Inferior Vena Cava in Pregnant Women Determined by Magnetic Resonance Imaging
Authors: Fujita Nobuko , Higuchi Hideyuki , Sakuma Shiori , Takagi Shunichi , Latif Mahbub A. H. M. , Ozaki Makoto 
Published: April 2019

BACKGROUND:
Despite the existing dogma that women undergoing cesarean delivery under spinal anesthesia should be positioned with a 15° left-lateral tilt, the patients were actually positioned in a right-lateral tilt position in several of the original studies. The superiority of right versus left positioning for optimal inferior vena cava volume is unknown. We used magnetic resonance imaging to compare the effects of right-lateral and left-lateral tilt positions on abdominal aortic and inferior vena cava volumes in pregnant women.

METHODS:
Thirteen women with singleton pregnancies and gestational age 31–39 weeks underwent magnetic resonance imaging while in the supine position, and in the left-lateral (15° and 30°) and right-lateral tilt (15° and 30°) positions, which were maintained by placing a 1.5-m–long piece of polyethylene foam under either side of the body. Abdominal aorta and inferior vena cava volume were measured between the L1–L2 disk and L3–L4 disk levels using magnetic resonance images.

RESULTS:
Aortic volume did not differ significantly among any of the positions examined. Mean inferior vena cava volume was significantly greater in the 30° left-lateral tilt position than in the 15° right-lateral tilt (10.7 ± 7.5 vs 5.9 ± 5.1 mL; mean difference, 4.8; 95% CI, 1.2–8.5; P = .002) and 30° right-lateral tilt (10.7 ± 7.5 vs 5.9 ± 2.5 mL; mean difference, 4.8; 95% CI, 1.2–8.4; P = .002) positions. Mean inferior vena cava volume in the 15° left-lateral tilt position did not differ significantly from that in the 15° right-lateral tilt (mean difference, 0.4; 95% CI, −3.2 to 4.0; P = 1.000) or 30° right-lateral tilt (mean difference, 0.4; 95% CI, −3.3 to 4.0; P = 1.000) positions. Mean inferior vena cava volume in the supine position only differed significantly from that in the 30° left-lateral tilt position (5.2 ± 3.8 vs 10.7 ± 7.5 mL; mean difference, 5.5; 95% CI, 1.8–9.1; P < .001). The greatest inferior vena cava volume was observed in the 30° left-lateral tilt position in 9 of 13 subjects (70%), and in the 30° right-lateral tilt in 3 subjects (23%).

CONCLUSIONS:
The 30° left-lateral tilt position most consistently reduced inferior vena cava compression by the gravid uterus compared with the supine position. Mean inferior vena cava volume in pregnant women was not increased at either angle of the right-lateral tilt position compared with the 30° left-lateral tilt position. However, in a subset of patients, the 30° right-lateral tilt position achieved the optimal inferior vena cava volume. Further investigation to understand this variability is warranted.
Kinetics of Left Ventricular Mechanics during Transition from Rest to Exercise
Authors: IZEM OMAR , MAUFRAIS CLAIRE , OBERT PHILIPPE , RUPP THOMAS , SCHUSTER IRIS , NOTTIN STÉPHANE 
Published: April 2019

ABSTRACT

Purpose
At the onset of physical exercise, oxygen (O2) transport adapts to meet the working muscle O2 demands. Cardiac output abruptly increases through the concomitant changes of HR and stroke volume (SV), which is conditioned by the left ventricular (LV) function. The purpose of this study was to investigate the contribution of many LV diastolic and systolic function parameters, including twist–untwist mechanics, to SV adaptation during the first minutes after exercise onset.

Methods
Diastolic and systolic myocardial strains and twist were monitored by two-dimensional speckle-tracking echocardiography with high temporal resolution in 28 young men (mean age, 23 ± 4 yr) who performed five similar constant work-load exercises on a cycloergometer (target HR: 125 bpm). Two-dimensional cine-loops were recorded every 15 s during the first minute of exercise, and then every 30 s for the next 3 min.

Results
During the first 60 s of exercise, SV (from 104 ± 15 mL to 126 ± 21 mL, P < 0.001) increased concomitantly with LV strain and strain rates. Early filling was the main SV determinant during this phase, probably linked to the increase of venous return (at the very beginning of exercise), LV relaxation (from 1.5 ± 0.3 s to 2.5 ± 0.4 s, P < 0.001) and untwisting (from −78 ± 34°·s−1 to −165 ± 61°·s−1, P < 0.001). After the first minute, SV remained constant, whereas LV untwisting continued to increase (from −165 ± 61°·s−1 to −187 ± 60°·s−1, P < 0.001) and the other systolic and diastolic parameters reached a plateau.

Conclusions
This study gives new mechanical insights into LV kinetics to address the challenge of SV response at the onset of exercise.
Ácido tânico como agente biomodificador de dentina
Authors: Mendes Talita Arrais Daniel , Pascoal Samuel Chillavert Dias , Lemos Marcelo Victor Sidou , Santiago Sérgio Lima , Mendonça Juliano Sartori 
Published: April 2019

Introdução: a utilização de diferentes polifenóis no aumento das propriedades mecânicas do colágeno dentinário tem sido bastante empregada, sendo o ácido tânico um polifenol com propriedade biológica bastante pronunciada. Objetivo: o objetivo deste estudo é avaliar o potencial biomodificador do ácido tânico (AT) em diferentes concentrações em colágeno dentinário. Métodos: os fatores sob investigação foram módulo de elasticidade, mensurado por meio de um ensaio de flexão de três pontos (n=10) e variação de massa (n=10), aferidos com uma balança de precisão, sendo, para tanto, avaliados os seguintes elementos: ácido tânico (0,1; 1 e 10%), proantocianidina (6,5%) e água destilada (controle). Resultados: quanto ao módulo de elasticidade, os grupos tratados com ácido tânico apresentaram valores, estatisticamente, superiores (p<0,05) aos demais grupos, não sendo observadas diferenças entre suas diferentes concentrações. Para os valores de variação de massa, os grupos que foram imersos em agentes biomodificadores apresentaram valores estatisticamente (p<0,05) superiores ao grupo controle. Conclusão: o ácido tânico se apresenta como um potencial agente biomodificador do colágeno dentinário, independente da concentração utilizada, aumentando o seu módulo de elasticidade e gerando um ganho de massa após uma hora de imersão.
Developing acceptable contraceptive methods: Mixed-method findings on preferred method characteristics from Burkina Faso and Uganda
Authors: Brunie Aurélie , Callahan Rebecca L. , Mackenzie Amelia , Kibira Simon P.S. , Wayack-Pambè Madeleine 
Published: April 2019

Background: Unmet need remains high in developing regions. New contraceptive technologies may improve uptake and use. This study examines desirable product characteristics. Methods: We added a module to the female questionnaire of the PMA2020 surveys in Burkina Faso and Uganda and conducted 50 focus group discussions (FGDs) with women, 10 FGDs with men, and 37 in-depth interviews (IDIs) with providers across the two countries. FGDs with women and IDIs with providers included a semi-structured ranking exercise on pre-selected product characteristics. Results: Effectiveness, duration, few side effects, cost, and access were the characteristics most commonly reported as important in choosing a method by survey respondents across both countries. Half or more of women surveyed in each country would like a method that lasts at least one year, while 65% in Burkina Faso and 40% in Uganda said they would use a method causing amenorrhea. Qualitative findings show that women want methods with minimal and predictable side effects. Reactions to increased bleeding were negative, especially in Burkina Faso, but perspectives on reduced bleeding were more mixed. Women and providers preferred methods that are discreet and not user-dependent, and associate duration with convenience of use. Some women in Uganda expressed concerns about the invasive nature of long-acting methods, and cost was an important consideration in both countries. In the ranking exercise, discreet use and few side effects often ranked high, while causing amenorrhea and not requiring a pelvic exam often ranked low. Conclusion: Product development should consider user preferences for success in these settings.
Pengaruh Pajanan Gas Hidrogen Sulfida (H2S) terhadap Keluhan Saluran Pernafasan pada Pemulung di Tempat Pembuangan Akhir (TPA) Ganet Kota Tanjungpinang Tahun 2018
Authors: Simbolon Veronika Amelia , Nurmaini Nurmaini , Hasan Wirsal 
Published: April 2019

Latar belakang : Hidrogen Sulfida (H2S) merupakan gas yang tidak mudah terbakar, tidak berwarna dan berbau seperti telur busuk dan masuk ke tubuh manusia terutama melalui udara yang dihirup. Paparan konsentrasi rendah Hidrogen Sulfida (H2S) dapat menyebabkan iritasi pada mata, hidung, atau tenggorokan. Penelitian ini bertujuan untuk mengetahui pengaruh pajanan gas Hidrogen Sulfida (H2S) terhadap keluhan saluran pernafasan pada pemulung, di TPA Ganet Kota Tanjungpinang.Metode : Jenis penelitian ini adalah survei bersifat analitik deskriptif dengan desain cross sectional. Sampel dalam penelitian ini yaitu pemulung yang pekerjaannya hanya sebagai pemulung dengan lama bekerja ≥ 3 tahun dan durasi terpapar ≥ 40 jam/minggu dengan jumlah sampel memenuhi syarat 27 pemulung.Hasil : Berdasarkan uji statistik dengan Fisher,s Exact Test diketahui ada pengaruh jenis kelamin (p = 0,019 PR = 1,9) dan intake (p = 0,039 PR = 2,1) terhadap keluhan saluran pernafasan. Variabel yang paling berpengaruh dominan pada uji regresi logistik antara jenis kelamin, konsentrasi H2S dan intake terhadap keluhan saluran pernafasan pada pemulung di TPA Ganet Tahun 2018 yaitu jenis kelamin dan intake dengan probabilitas 97,9 %.Simpulan : Ada pengaruh yang signifikan antara jenis kelamin dan intake dengan keluhan saluran pernafasan pada pemulung di TPA Ganet Kota Tanjungpinang. ABSTRACTTitle: The Effect of Exposure Hydrogen Sulfide Gas (H2S) on the Complaints of Respiratory Track in Scavengers at the Ganet’s Final Waste Disposal of Tanjungpinang 2018Background : Hydrogen Sulfide (H2S) is a gas that is not flammable, colorless and smells like rotten eggs and enters the human body primarily through inhaled air. Exposure on low concentrations of Hydrogen Sulfide (H2S) can cause irritation to the eyes, nose or throat. This study aims to determine the effect of exposure to Hydrogen Sulfide (H2S) gas the respiratory tract complaints in scavengers at the Ganet’s final waste disposal of Tanjungpinang.Methods : This type of research is a descriptive analytic survey with a cross sectional design. The samples in this study were scavengers whose works were only as scavengers with length of work ≥ 3 years and duration of exposure ≥ 40 hours / week with the number of samples fulfilling the requirements of 27 scavengers.Results : Based on the statistical test with Fisher,s Exact Test it is found that there was influence of sex (p = 0.019 PR = 1.9) and intake (p = 0.039 PR = 2.1) on respiratory complaints. The most dominant variable influenced the logistic regression test between gender, H2S concentration and intake of respiratory tract complaints on scavengers in 2018 TPA Ganet, were gender and intakes with a probability of 97.9%.Conclusion : There is a significant influence between gender and intake with complaints of respiratory tract on scavengers in TPA Ganet, Tanjungpinang City.