bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis
Authors: Guo Jinbang , Hardie William D. , Cleveland Zackary I. , Davidson Cynthia , Xu Xuefeng , Madala Satish K. , Woods Jason C. 
Published: February 2019

To longitudinally monitor progressive fibrosis in the transforming growth factor-α (TGF-α) transgenic mouse model of lung fibrosis, we used retrospective self-gating ultrashort echo time (UTE) magnetic resonance imaging (MRI) to image mouse lung at baseline and after 4 and 8 wk of fibrosis initiation via doxycycline administration. Only bitransgenic mice were used in this study and divided into two cohorts: six mice were fed doxycycline food to induce lung fibrosis (referred to as Dox cohort), and five other mice were fed normal food (referred to as control cohort). Lung mechanics, histology, and hydroxyproline were assessed after the final MRI. A linear mixed-effects model was used to analyze MRI-derived longitudinal lung-function parameters. Tidal volume decreased at a rate of −0.016 ± 0.002 ml/week [χ2(1) = 16.48, P < 0.001] for Dox cohort and increased at a rate of 0.010 ± 0.003 ml/week [χ2(1) = 6.37, P = 0.01] for control cohort. Minute ventilation decreased at a rate of −1.71 ± 0.26 ml·min-1·wk-1 [χ2(1) = 14.04, P < 0.001] for Dox cohort but did not change significantly over time for control cohort. High-density lung volume percentage increased at a rate of 3.9 ± 0.7%/wk for Dox cohort [χ2(1) = 11.47, P < 0.001] but did not change significantly over time for control cohort. MRI-derived lung structure and function parameters were strongly correlated with pleural thickness, hydroxyproline content, lung compliance, airway resistance, and airway elastance. We conclude that self-gating UTE MRI could be used to longitudinally monitor lung fibrosis in the TGF-α transgenic mouse model. NEW & NOTEWORTHY Self-gating UTE MRI was used to monitor morphology and physiology in lung fibrosis in a transforming growth factor-α transgenic mouse model. Tidal volume was shown for the first time to correlate strongly with conventional metrics of fibrosis such as hydroxyproline and pleural thickness.
Regional distribution of chest wall displacements in infants during high-frequency ventilation
Authors: Zannin Emanuela , Ventura Maria Luisa , Dognini Giulia , Veneroni Chiara , Pillow Jane J. , Tagliabue Paolo E. , Dellacà Raffaele L. 
Published: February 2019

The distribution of ventilation during high-frequency ventilation (HFV) is asynchronous, nonhomogeneous, and frequency dependent. We hypothesized that differences in the regional distribution of ventilation at different oscillatory frequencies may affect gas exchange efficiency. We studied 15 newborn infants with a median gestational age of 28.9 (26.4–30.3) wk and body weight of 1.0 (0.8–1.4) kg. Five ventilation frequencies (5, 8, 10, 12, and 15 Hz) were tested, keeping carbon dioxide diffusion coefficient constant. The displacements of 24 passive markers placed on the infant’s chest wall were measured by optoelectronic plethysmography. We evaluated the amplitude and phase shift of displacements of single markers placed along the midline and the regional displacements of the chest wall surface. Blood gases were unaffected by frequency. Chest wall volume changes decreased from 1.6 (0.4) ml/kg at 5 Hz to 0.7 ml/kg at 15 Hz. At all frequencies, the abdomen (AB) oscillated more markedly than the ribcage (RC). The mean (SD) AB/RC ratio was 1. 95 (0.7) at 5 Hz, increased to 2.1 (1.3) at 10 Hz, and then decreased to 1.1 (0.5) at 15 Hz ( P < 0.05 vs. 10 Hz). Volume changes in the AB lagged the RC and this phase shift increased with frequency. The AB oscillated more than the RC at all frequencies. Regional oscillations were highly inhomogeneous up to 10 Hz, and they became progressively more asynchronous with increasing frequency. When the carbon dioxide diffusion coefficient is held constant, such differences in regional chest wall expansion do not affect gas exchange. NEW & NOTEWORTHY We characterized the regional distribution of chest wall displacements in infants receiving high-frequency oscillatory ventilation at different frequencies. When carbon dioxide diffusion coefficient is held constant, there is no combination of frequency and tidal volume that optimizes gas exchange. The relative displacement between different chest wall compartments is not affected by frequency. However, at high frequencies, chest wall displacements are lower, with the potential to reduce total and regional overdistension without affecting gas exchange.
Phosphatase 1 Nuclear Targeting Subunit Mediates Recruitment and Function of Poly (ADP-Ribose) Polymerase 1 in DNA Repair
Authors: Wang Feifei , Zhu Songli , Fisher Laura A. , Wang Ling , Eurek Nicholas J. , Wahl James K. , Lan Li , Peng Aimin 
Published: February 2019

AbstractPARP, particularly PARP1, plays an essential role in the detection and repair of DNA single-strand breaks and double-strand breaks. PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein poly ADP-ribosylation (PARylation). However, the molecular mechanisms underlying the recruitment and activation of PARP1 in DNA repair are not fully understood. Here we show that phosphatase 1 nuclear targeting subunit 1 (PNUTS) is a robust binding partner of PARP1. Inhibition of PNUTS led to strong accumulation of endogenous DNA damage and sensitized the cellular response to a wide range of DNA-damaging agents, implicating PNUTS as an essential and multifaceted regulator of DNA repair. Recruitment of PNUTS to laser-induced DNA damage was similar to that of PARP1, and depletion or inhibition of PARP1 abrogated recruitment of PNUTS to sites of DNA damage. Conversely, PNUTS was required for efficient induction of substrate PARylation after DNA damage. PNUTS bound the BRCA1 C-terminal (BRCT) domain of PARP1 and was required for the recruitment of PARP1 to sites of DNA damage. Finally, depletion of PNUTS rendered cancer cells hypersensitive to PARP inhibition. Taken together, our study characterizes PNUTS as an essential partner of PARP1 in DNA repair and a potential drug target in cancer therapy.Significance:These findings reveal PNUTS as an essential functional partner of PARP1 in DNA repair and suggest its inhibition as a potential therapeutic strategy in conjunction with DNA-damaging agents or PARP inhibitors.See related commentary by Murai and Pommier, p. 2460
A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer
Authors: Lévesque Eric , Caron Patrick , Lacombe Louis , Turcotte Véronique , Simonyan David , Fradet Yves , Aprikian Armen , Saad Fred , Carmel Michel , Chevalier Simone , Guillemette Chantal 
Published: February 2019

Abstract

Background:
In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression.

Methods:
The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.

Results:
The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054).

Conclusions:
In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.

Impact:
The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.
Diabetes Mellitus and Age are Risk Factors of Interval Colon Cancer: A Case-Control Study
Authors: Laish Ido , Mizrahi Joseph , Naftali Timna , Konikoff Fred M. 
Published: February 2019

<b><i>Background and Aims:</i></b> Interval colorectal cancer (CRC) is largely related to a poor endoscopic performance or different biology in the development of the polyp. However, patient-related factors were less investigated for their association with interval cancer. We thus evaluated tumor and patient characteristics as predictors of interval cancer in a population from Israel. <b><i>Methods:</i></b> In this retrospective study, patients that were diagnosed with colon cancer in our institution and had 2 colonoscopies were included. Demographic parameters and tumor characteristics were compared between 84 cases with interval cancer, occurring 1–10 years after a negative colonoscopy, and 983 patients with primary CRC. In addition, patient-related features, including diabetes and diverticulosis, were compared between 51 patients with interval cancer after negative colonoscopy and 255 controls with no cancer and a previous negative colonoscopy. <b><i>Results:</i></b> Compared to “positive” controls with primary cancer, patients with interval cancer were older (age 71.3 vs. 67.6, <i>p</i> = 0.003), had proximal tumor location (57 vs. 34%, <i>p</i> &#x3c; 0.001) and non-advanced (0–2) tumor staging (78.5 vs. 64.8%, <i>p</i> = 0.014). Compared with ­“negative” healthy controls, cases with interval cancer had only higher prevalence of diabetes (31 vs. 15%, <i>p</i> = 0.002). No significant differences were seen between patients with interval cancer occurring &#x3c; 3 years and after 3–10 years. <b><i>Conclusions:</i></b> Patients with Interval cancer tend to be older and have diabetes. These patient groups should be more carefully or more frequently screened for pre-malignant lesions.
Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3
Authors: Rao Vaishnavi , Christensen Søren , Yennu Amarnath , Mlynash Michael , Zaharchuk Greg , Heit Jeremy , Marks Michael P. , Lansberg Maarten G. , Albers Gregory W. 
Published: February 2019

Background and Purpose—
Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume.

Methods—
Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses.

Results—

Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization (
r
=0.83;
P
<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization (
r
=0.77;
P
<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125;
r
=0.83;
P
<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes.

Conclusions—
The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02586415.
DEFUSE 3 Non-DAWN Patients
Authors: Leslie-Mazwi Thabele M. , Hamilton Scott , Mlynash Michael , Patel Aman B. , Schwamm Lee H. , Lansberg Maarten G. , Marks Michael , Hirsch Joshua A. , Albers Gregory W. 
Published: February 2019

Background and Purpose—
DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established thrombectomy for patients with emergent large vessel occlusions presenting 6 to 24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3, we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN.

Methods—
Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts.

Results—

There were 71 DEFUSE 3 non-DAWN patients; 31 patients with NIHSS 6 to 9, 33 with core too large, and 13 with premorbid modified Rankin Scale score of 2 (some patients met multiple criteria). For core-too-large patients, median 24-hour infarct volume was 119 mL (interquartile range, 74.6–180) versus 31.5 mL (interquartile range, 17.6–64.3) for core-not-too-large patients (
P
<0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in core-too-large patients compared with the remaining DEFUSE 3 non-DAWN patients conveyed benefit for functional outcome (odds ratio, 20.9; CI, 1.3–337.8). Comparing the NIHSS 6 to 9 group with the NIHSS ≥10 patients, modified Rankin Scale score 0 to 2 outcomes were achieved in 74% versus 22% (
P
<0.001), with mortality in 6% versus 23% (
P
=0.024), respectively. For patients with NIHSS 6 to 9 compared with the remaining DEFUSE 3 non-DAWN patients, thrombectomy trended toward a better chance of functional outcome (odds ratio, 1.86; CI, 0.36–9.529).

Conclusions—
Patients with pretreatment core infarct volumes <70 mL but too large for inclusion by DAWN criteria demonstrate benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. In contrast to data supporting a beneficial treatment effect across the full range of NIHSS scores in the entire DEFUSE 3 population, only a trend toward benefit of thrombectomy in patients with NIHSS 6 to 9 was found in this small subgroup.
The Ethiopian Second Republic and the Fragile “Social Contract”
Authors: Abbink Jon 
Published: February 2019

Eighteen years after the change of power and the ushering in of the second Ethiopian republic in 1991, the political process in Ethiopia has, according to most observers, rigidified and largely closed the space for representative democracy. This paper will look at the main organizing political ideas or ideology of the current Ethiopian republic and to the nature of its governance techniques in the face of domestic and international challenges with reference to the debate on “failing” or “fragile” states. The new “social contract” defined after 1991 and codified in the 1994 Constitution is precarious. Dissent and ethno-regional resistance to federal policies are dealt with mainly by coercion and discursive isolation. Oppositional forces voice the need for a rethinking of the organizing ideas and institutions of the second republic in order to enhance political consensus and a shared political arena, but get little response. The paper will sketch an interpretation of governance in Ethiopia, focusing on the dilemma of reconciling local and modernist political practices, and will discuss the status of “republican” ideas, in name important in Ethiopia but mostly absent in practice. Explicit debate of these ideas is usually sidelined – also in academic commentaries – in favour of a focus on the ethno-federal ideology of the Ethiopian state.
Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder
Authors: Reddy YC Janardhan , Jhanwar Venugopal , Nagpal Rajesh , Reddy MS , Shah Nilesh , Ghorpade Sanman , Kulkarni Sujay 
Published: February 2019

Objective: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. Method: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. Results: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. Limitations: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. Conclusion: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists’ practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.
Effect of N-methyl-D-aspartate-receptor-enhancing agents on cognition in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials
Authors: Chang Chun-Hung , Lane Hsien-Yuan , Tseng Ping-Tao , Chen Shaw-Ji , Liu Chieh-Yu , Lin Chieh-Hsin 
Published: February 2019

Background: Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia. However, the results of studies have been conflicting. This updated meta-analysis explored the effect of NMDA-receptor-enhancing agents on cognitive function. Methods: We searched PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials and Cochrane Systematic Reviews for studies on the effect of NMDA-receptor-enhancing agents on cognitive function in patients with schizophrenia up to September 2018. Double-blind randomised placebo trials with cognition rating scales were included. We pooled studies by using a random-effect model for comparisons with add-on NMDA-receptor-enhancing agents. Cognitive function scores were compared between baseline and subsequent levels, and NMDA-receptor-positive modulators were assessed using the standardised mean difference (SMD) with 95% confidence intervals (CIs). We evaluated statistical heterogeneity through visual inspection of funnel plots and by using the I2 statistic. Results: We identified 25 trials with 1951 participants meeting the inclusion criteria. NMDA-receptor-enhancing agents had a small but nonsignificant effect compared with the placebo on overall cognitive function (SMD = 0.068, CI = −0.056 to 0.193, P = 0.283). We identified trials enrolling patients aged between 30 and 39 years old, which reported significant positive effects (SMD: 0.163, 95% CI: 0.016–0.310, P = 0.030). Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function. Moreover, subgroup meta-analysis of cognitive domains revealed that N-acetyl cysteine (NAC) had a significant effect on working memory ( P-value for interaction = 0.038; SMD = 0.679, CI = 0.397–0.961, P < 0.001). Conclusions: Our meta-analysis revealed no significant effect of NMDA-enhancing agents on overall cognition. However, subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia, and NAC may have an effect on working memory. Additional trials with larger samples are suggested to evaluate these cognitive domains and ascertain the possible mechanisms.
Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells
Authors: Qiang Zhanrong , Meng Lingyu , Yi Caixia , Yu Lianying , Chen Wenxia , Sha Weihong 
Published: February 2019

Objective PD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric cancer effects. Methods The cell counting kit-8 assay was used to detect cell proliferation of the human gastric cancer MGC-803 cell line. Flow cytometry was performed to detect apoptosis. Western blotting was used to detect phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21). Results A dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced. Conclusion PD98059 combined with curcumin may be a potential strategy for managing gastric cancer.