bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rac1 GTPase Promotes Interaction of Hematopoietic Stem/Progenitor Cell with Niche and Participates in Leukemia Initiation and Maintenance in Mouse
Authors: Chen Shuying , Li Huan , Li Shouyun , Yu Jing , Wang Min , Xing Haiyan , Tang Kejing , Tian Zheng , Rao Qing , Wang Jianxiang 
Published: March 2016

Abstract
Interaction between hematopoietic stem/progenitor cells (HSPCs) with their niche is critical for HSPC function. The interaction also plays an important role in the multistep process of leukemogenesis. Rac1 GTPase has been found to be highly expressed and activated in leukemia patients. Here, by forced expression of constitutively active form of Rac1 (Rac1-V12) in HSPCs, we demonstrate that active Rac1 promotes interaction of HSPC with niche. We then established an active Rac1 associated acute myeloid leukemia (AML) model by expression of Rac1-V12 cooperated with AML1-ETO9a (AE9a) in mouse HSPCs. Compared with AE9a alone, Rac1-V12 cooperated with AE9a (AER) drives an AML with a short latency, demonstrating that activation of Rac1 GTPase in mice promotes AML development. The mechanism of this AML promotion is by a better homing and lodging of leukemia cells in niche, which further enhancing their colony formation, quiescence and preventing leukemia cells from apoptosis. Further study showed that an inhibitor targeting activated Rac1 can increase the efficacy of chemotherapeutic agents to leukemia cells. This study provides evidence that activation of Rac1 promotes leukemia development through enhancing leukemia cells' homing and retention in niche, and suggests that inhibition of Rac1 GTPase could be an effective way of eliminating AML cells.
Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause
Authors: Van Oudenhove Jennifer J. , Grandy Rodrigo A. , Ghule Prachi N. , del Rio Roxana , Lian Jane B. , Stein Janet L. , Zaidi Sayyed K. , Stein Gary S. 
Published: March 2016

Abstract
Human embryonic stem cells (hESCs) have an abbreviated G1 phase of the cell cycle that allows rapid proliferation and maintenance of pluripotency. Lengthening of G1 corresponds to loss of pluripotency during differentiation. However, precise mechanisms that link alterations in the cell cycle and early differentiation remain to be defined. We investigated initial stages of mesendodermal lineage commitment in hESCs, and observed a cell cycle pause. Transcriptome profiling identified several genes with known roles in regulation of the G2/M transition that were differentially expressed early during lineage commitment. WEE1 kinase, which blocks entry into mitosis by phosphorylating CDK1 at Y15, was the most highly expressed of these genes. Inhibition of CDK1 phosphorylation by a specific inhibitor of WEE1 restored cell cycle progression by preventing the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but not ectodermal, lineages. Functionally, WEE1 inhibition during meso- and endodermal differentiation selectively decreased expression of definitive endodermal markers SOX17 and FOXA2. Our findings identify a novel G2 cell cycle pause that is required for endodermal differentiation and provide important new mechanistic insights into early events of lineage commitment.
Pubertal exposure to ethinylestradiol promotes different effects on the morphology of the prostate of the male and female gerbil during aging
Authors: Perez Ana P. S. , Biancardi Manoel F. , Caires Cássia R. S. , Falleiros Luiz R. , Góes Rejane M. , Santos Fernanda C. A. , Taboga Sebastião R. 
Published: March 2016

ABSTRACTIn rodents, the final growth and maturation of the prostate occur at puberty, a crucial period for prostate development. The present study is a serological, morphological, morphometric, and immunohistochemical analysis of the effects of exposure to ethinylestradiol (EE) (15 µg/kg/day) during puberty (EE/PUB group) on the male ventral and female prostate in senile gerbils. In the study, male and female gerbils (Meriones unguiculatus) (42 days) received by gavage 15 μg/kg/day of EE (a component of the contraceptive pill), diluted in 100 µL of Nujol® for 1 week (EE/PUB group). In the control group, males and females were not treated. Animals were killed (n = 5) after 12 months in the experimental groups. In the senile male in the EE/PUB group, we observed a reduction in testosterone levels and a decrease in the prostatic epithelial thickness, as well as in the thickness of the muscle layer. In addition, an increase in PIN multiplicity and prostatic inflammation was observed. In the senile female in the EE/PUB group, we observed increased testosterone and estradiol levels, an enhanced prostatic epithelial thickness and an increase in the thickness of the muscle layer. Immunohistochemical analysis revealed an increase in positive cells (%) for AR and PCNA in the male prostate and an increase in positive basal cells for p63 in the female prostate of the EE/PUB group. Exposure to EE during puberty resulted in an inhibitory action on the male ventral prostate and an anabolic effect on the female prostate in senile gerbils. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 477–489, 2017.
Focus on Methodology: Beyond paper and pencil: Conducting computer‐assisted data collection with adolescents in group settings
Authors: Raffaelli Marcela , Armstrong Jessica , Tran Steve P. , Griffith Aisha N. , Walker Kathrin , Gutierrez Vanessa 
Published: March 2016

ABSTRACTComputer‐assisted data collection offers advantages over traditional paper and pencil measures; however, little guidance is available regarding the logistics of conducting computer‐assisted data collection with adolescents in group settings. To address this gap, we draw on our experiences conducting a multi‐site longitudinal study of adolescent development. Structured questionnaires programmed on laptop computers using Audio Computer Assisted Self‐Interviewing (ACASI) were administered to groups of adolescents in community‐based and afterschool programs. Although implementing ACASI required additional work before entering the field, we benefited from reduced data processing time, high data quality, and high levels of youth motivation. Preliminary findings from an ethnically diverse sample of 265 youth indicate favorable perceptions of using ACASI. Using our experiences as a case study, we provide recommendations on selecting an appropriate data collection device (including hardware and software), preparing and testing the ACASI, conducting data collection in the field, and managing data.
A comparison of the usage of anal verge and dentate line in measuring distances within the rectum
Authors: Chang K.H. , Johnson J.A. , Waldron D. , Condon E.T. , El-Bassiouni M. , Coffey J.C. 
Published: March 2016

ABSTRACT

Introduction:
The anal verge is key in determining measurement-based suitability for neoadjuvant radiotherapy in rectal cancer. The dentate line is a distinct anatomic landmark and may permit more accurate measurement for rectal lesions. This study aimed to establish measurative ranges for distances of the rectal valves from the dentate line and the anal verge and to compare variability between the two.

Methods:
Patients (n = 104) undergoing colonoscopy and sigmoidoscopy were prospectively accrued. The distances of rectal valves were measured from the anal verge and the dentate line respectively by using a vector subtraction-based approach. Distances were correlated with gender, age and body mass index. Standard deviation was the measure of variability.

Results:
The gross topography of the rectum was remarkably consistent with three valves identifiable in the majority (99 of 104) of patients. The median distance between the dentate line and the anal verge was 2.0 cm. The distances of each rectal valve (proximal to distal) to the anal verge and dentate line were 11.4 ± 2.0 cm, 8.6 ± 2.0 cm, 6.0 ± 1.7 cm and 9.1 ± 1.6 cm, 6.3 ± 1.6 cm, 3.7 ± 1.5 cm, respectively. Between-group variability was minimally reduced when using the dentate line as a reference point. Obesity was associated with an increased distance of the proximal rectal valve from the anal verge and the dentate line (p = 0.004 and 0.015 respectively).

Conclusions:
Rectal valve anatomy is remarkably consistent. Both dentate line and anal verge are reliable landmarks from which distances can be measured within the rectum.

Highlights:
Overview of smartphone applications for sleep analysis
Authors: Ong Adrian A. , Gillespie M. Boyd 
Published: March 2016

AbstractObjectiveTo review and assess the current selection of sleep analysis smartphone applications (apps) available for download.MethodsThe iOS and Google Play mobile app store were searched for sleep analysis apps targeted for consumer use. Alarm clock, sleep‐aid, snoring and sleep‐talking recorder, fitness tracker apps, and apps geared towards health professionals were excluded. App information and features were obtained from in‐store descriptions, and the app developer website.ResultsA total of 51 unique sleep apps in both iOS and Google Play stores were included. The apps were rated 3.8/5 in both stores, and had an average price of $1.12 in the iOS store and $0.58 in the Google Play store. >65% of sleep apps report on sleep structure, including duration, time awake, and time in light/deep sleep, while reporting of REM was limited. The availability of extra features was variable, ranging from 4% to 73% of apps.ConclusionsThere are a variety of sleep analysis apps with a range of functionality. The apps with the most reviews from the each store are featured. Many apps provide data on sleep structure; however the algorithms are not validated by scientific literature or studies. Since patients may inquire about their sleep habits from these apps, it is necessary for physicians to be aware of the most common apps and the features offered and their limitations in order to properly counsel patients.
Search for soft X-ray flashes at the fireball phase of classical/recurrent novae using MAXI/GSC data
Authors: Morii Mikio , Yamaoka Hitoshi , Mihara Tatehiro , Matsuoka Masaru , Kawai Nobuyuki 
Published: March 2016

Abstract
We searched for precursive soft X-ray flashes (SXFs) associated with optically discovered classical or recurrent novae in the data of five years’ all-sky observations with the Gas Slit Camera (GSC) of the Monitor of All-sky X-ray Image (MAXI). We first developed a tool to measure the fluxes of point sources by fitting the event distribution with a model that incorporates the point-spread function (PSF-fit) to minimize the potential contamination from nearby sources. Then we applied the PSF-fit tool to 40 classical/recurrent novae that were discovered in optical observations from 2009 August to 2014 August. We found no precursive SXFs with significance above the 3 σ level in the energy range of 2–4 keV between td − 10 d and td, where td is the date when each nova was discovered. We obtained the upper limits for the bolometric luminosity of SXFs, and compared them with the theoretical prediction and that observed for MAXI J0158−744. This result could constrain the population of massive white dwarfs with a mass of roughly 1.40 solar mass, or larger, in binary systems.
Molecular Mechanisms Linking Autonomic Dysfunction and Impaired Cardiac Contractility in Critical Illness*
Authors: Ackland Gareth L. , Whittle John , Toner Andrew , Machhada Asif , Del Arroyo Ana Gutierrez , Sciuso Alberto , Jenkins Nicholas , Dyson Alex , Struthers Richard , Sneyd J. Robert , Minto Gary , Singer Mervyn , Shah Ajay M. , Gourine Alexander V. 
Published: March 2016

Objectives:
Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein–coupled receptor kinase 2, a key negative regulator of cardiac function.

Design:
Laboratory/clinical investigations.

Setting:
University laboratory/medical centers.

Subjects:
Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2–deficient mice; elective surgical patients.

Interventions:
Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein–coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of <6 ms mm Hg–1). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed.

Measurements and Main Results:
Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein–coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein–coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein–coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with baroreflex dysfunction (relative risk, 1.66 [95% CI, 1.16–2.39]; p = 0.006).

Conclusions:
Reduced baroreflex sensitivity is associated with nicotinamide adenine dinucleotide phosphate oxidase subunit-2–mediated upregulation of G-protein–coupled receptor kinase 2 expression in cardiomyocytes and impaired cardiac contractility. Autonomic dysfunction predisposes patients to the development of critical illness and increases mortality.
Assessment of Depression, Anxiety, and Quality of Life in Singaporean Patients With Glaucoma
Authors: Lim Nigel C.S. , Fan Chara H.J. , Yong Michael K.H. , Wong Elizabeth P.Y. , Yip Leonard W. Y. 
Published: March 2016

Purpose:
To determine the prevalence and risk factors for anxiety disorder and depression among glaucoma patients in Singapore, and to assess the relationship between quality of life (QOL) and depression/anxiety.

Methods:
In this cross-sectional study, glaucoma patients aged 21 and above with a known diagnosis of primary open-angle glaucoma or primary angle-closure glaucoma were recruited from a tertiary care hospital. Patients with other types of glaucoma, and coexisting ocular or psychiatric disorders were excluded.
Ophthalmic examination was carried out on all participants, which included best-corrected visual acuity (BCVA), intraocular pressure (IOP), gonioscopy, standard automated perimetry, and optic disc evaluation. Sociodemographic information and treatment histories were also collected.
The Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Visual Function Questionnaire (VFQ25) were administered to evaluate for depression, anxiety, and impact on QOL, respectively.

Results:
A total of 100 patients were included in this study. The mean age was 67.1±12.0 years (range, 24 to 90 y). The frequency of depression and anxiety among our patients was 30% and 64%, respectively. The mean HAM-D score was 4.37±4.17 (range, 0 to 17), whereas the mean HAM-A score was 2.38±2.80 (range, 0 to 13). The mean VFQ25 score was 78.8±16.0 (range, 42.4 to 97.0). The poorest subscale on the VFQ25 was driving, with a mean score of 42.4±42.6 (range, 0.0 to 100.0).
We did not find any significant difference between the presence of depression/anxiety between patients with primary open-angle glaucoma (P=0.263) and primary angle-closure glaucoma (P=0.830). Risk factors for depression included: female sex (P=0.020), higher logMAR BCVA in the worse eye (P=0.004), higher cup-disc ratio (P=0.016), lower MD in the better and worse eye (P=0.022 and 0.001, respectively), and lower mean VFQ25 score (P<0.001). Risk factors for anxiety included: lower MD in the worse eye (P=0.004) and lower mean VFQ25 score (P=0.004). There was also no significant association between the use of topical β-blockers/carbonic anhydrase inhibitors with depression (P=0.793) or anxiety (P=0.282).

Conclusions:
There is a relatively high prevalence of depression (30%) and anxiety disorders (64%) among glaucoma patients in Singapore. Female glaucoma patients are more likely to suffer from depression. Other risk factors for depression include higher cup-disc ratio, higher logMAR BCVA, lower MD, and a lower mean VFQ25 score. Risk factors for anxiety disorder include lower MD and lower mean VFQ25 score. Ophthalmologists could consider use of the VFQ25 as an assessment for impairments in QOL in a glaucoma patient. If a glaucoma patient is at high risk of depression or anxiety disorder, a multidisciplinary management approach involving ophthalmology and psychiatry may be required.
Comparison of the Deep Optic Nerve Structures in Superior Segmental Optic Nerve Hypoplasia and Primary Open-Angle Glaucoma
Authors: Lee Eun Ji , Lee Kyoung Min , Lee Seung Hyen , Kim Tae-Woo 
Published: March 2016

Purpose:
The purpose of this study was to characterize the microstructure of the deep optic nerve tissues in eyes with superior segmental optic nerve hypoplasia (SSOH) in comparison with that in primary open-angle glaucoma (POAG).

Methods:
Thirty-five eyes with SSOH, 37 eyes with POAG, and 54 healthy control eyes underwent enhanced depth imaging (EDI) volume scanning of the optic nerve using spectral-domain optical coherence tomography (SD-OCT). POAG patients were matched with SSOH patients in terms of the thickness of the neuroretinal rim and the retinal nerve fiber layer in the superior sector. The lamina cribrosa thickness (LCT) was determined in 3 equidistant planes, and anterior lamina cribrosa surface depth (LCD) was determined in 5 equidistant planes. The measurements were compared between groups, and the areas under the receiver operating characteristic curves (AUC) were obtained for each parameter.

Results:
Eyes with SSOH had larger LCT and smaller LCD than POAG eyes at all locations (all P<0.001). The largest LCT was observed at the superior midperiphery in the SSOH group, but at central locations in both the POAG and control groups. The best parameters for discriminating the SSOH from glaucoma and healthy eyes were the superior midperipheral LCT (AUC=0.973) and inferior and inferior midperipheral LCD (AUCs=0.906), respectively.

Conclusions:
The LCT and LCD exhibited characteristic features in eyes with SSOH that were distinctive from those of POAG and healthy eyes. Investigation of the deep optic nerve structure using EDI SD-OCT may be beneficial for differentiating between SSOH and glaucoma, which may help to avoid both overtreatment and undertreatment.
A New Expander for Schlemm Canal Surgery in Primary Open-angle Glaucoma—Interim Clinical Results
Authors: Grieshaber Matthias C. , Grieshaber Hans R. , Stegmann Robert 
Published: March 2016

Purpose:
To evaluate a new canal expander in circumferential viscocanalostomy (canaloplasty) for whites with primary open-angle glaucoma (POAG).

Design:
Prospective, single-center, noncomparative study.

Participants:
Twenty-two eyes of 22 consecutive patients with medically uncontrolled POAG underwent primary viscocanalostomy and implantation of the Stegmann Canal Expander into Schlemm canal with a follow-up time of at least 1 year.

Materials and Methods:
Schlemm canal was unroofed ab externo, and dilated with viscoelastic material and microcatheter. The Stegmann Canal Expander is a flexible, fenestrated hollow implant of 9 mm in length. One expander was implanted into either side of the surgically created of ostium to keep the Schlemm canal permanently open. The superficial scleral flap was closed watertight. Laser goniopuncture of the trabeculo-Descemet membrane window was performed if postoperative intraocular pressure (IOP) exceeded 16 mm Hg.

Main Outcome Measures:
Complete successes were defined as a confirmed IOP≤21, ≤18, and ≤16 mm Hg without medications, respectively, combined with a 30% IOP reduction. Number of antiglaucomatous medications, best-corrected visual acuity, and intraoperative and postoperative complications were recorded.

Results:
The mean IOP dropped from 27.1±5.3 mm Hg preoperatively to 13.6±1.6 mm Hg at 6 months, 13.0±1.5 mm Hg at 9 months, and 13.1±2.2 mm Hg at 12 months (P<0.001). The complete success rates for an IOP≤21, ≤18, and ≤16 mm Hg combined with a 30% IOP reduction were 91% [95% confidence interval (CI), 0.80-1.0], 91% (95% CI, 0.80-1.0), and 91.0% (95% CI, 0.80-1.0) at 6 months, and 86% (95% CI, 0.73-1.0), 82% (95% CI, 0.67-1.0), and 82.0% (95% CI, 0.67-1.0) at 12 months. The success rate of an IOP≤16 mm Hg without medications did not depend on age [hazard ratios (HR) 1.02; 95% CI, 0.85-1.12; P=0.74], preoperative IOP (HR 0.97; 95% CI, 0.83-1.23; P=0.89), and mean visual defect (HR 1.05; 95% CI, 0.72-1.27; P=0.76). Laser goniopuncture was performed on 2 eyes (9%) 4.1 months postoperatively; the mean IOP was 19.5 mm Hg before and 13.6 mm Hg after goniopuncture. The number of medications dropped from 2.9±0.6 before surgery to 0.05±0.2 after surgery (P<0.001). The postoperative best-corrected visual acuity at last visit (0.12±0.09; range, 0 to 0.39) was comparable to preoperative values (mean±SD, 0.16±0.10; range, 0 to 0.39) (P=0.35). Minor intraoperative or postoperative complications included microhyphema (8 eyes) and transient elevated IOP (steroid responder; 2 eyes).

Conclusions:
Implantation of the Stegmann Canal Expander in canaloplasty lowered IOP significantly in POAG without complications related to the device in this 1-year observation period.