bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive model to predict mitotic division in budding yeasts
Authors: Sutradhar Sabyasachi , Yadav Vikas , Sridhar Shreyas , Sreekumar Lakshmi , Bhattacharyya Dibyendu , Ghosh Santanu Kumar , Paul Raja , Sanyal Kaustuv
Published: August 2015

High-fidelity chromosome segregation during cell division depends on a series of concerted interdependent interactions. Using a systems biology approach, we built a robust minimal computational model to comprehend mitotic events in dividing budding yeasts of two major phyla: Ascomycota and Basidiomycota. This model accurately reproduces experimental observations related to spindle alignment, nuclear migration, and microtubule (MT) dynamics during cell division in these yeasts. The model converges to the conclusion that biased nucleation of cytoplasmic microtubules (cMTs) is essential for directional nuclear migration. Two distinct pathways, based on the population of cMTs and cortical dyneins, differentiate nuclear migration and spindle orientation in these two phyla. In addition, the model accurately predicts the contribution of specific classes of MTs in chromosome segregation. Thus we present a model that offers a wider applicability to simulate the effects of perturbation of an event on the concerted process of the mitotic cell division.
Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis
Authors: Goldstein Jill , Roth Eve , Roberts Natalie , Zwick Rachel , Lin Samantha , Fletcher Sean , Tadeu Ana , Wu Christine , Beck Amanda , Zeiss Caroline , Suárez-Fariñas Mayte , Horsley Valerie
Published: August 2015

Immunosuppressive therapies using calcineurin inhibitors, such as cyclosporine A, are associated with a higher incidence of squamous cell carcinoma formation in mice and humans. Calcineurin is believed to suppress tumorigenesis in part through Nfatc1, a transcription factor expressed primarily in hair follicle bulge stem cells in mice. However, mice overexpressing a constitutively active Nfatc1 isoform in the skin epithelium developed increased spontaneous skin squamous cell carcinomas. Because follicular stem cells can contribute to skin tumorigenesis, whether the endogenous expression of Nfatc1 inhibits or enhances skin tumorigenesis is unclear. Here we show that loss of the endogenous expression of Nfatc1 suppresses the rate of DMBA/TPA-induced skin tumorigenesis. Inducible deletion of Nfatc1 in follicular stem cells before tumor initiation significantly reduces the rate of tumorigenesis and the contribution of follicular stem cells to skin tumors. We find that skin tumors from mice lacking Nfatc1 display reduced Hras codon 61 mutations. Furthermore, Nfatc1 enhances the expression of genes involved in DMBA metabolism and increases DMBA-induced DNA damage in keratinocytes. Together these data implicate Nfatc1 in the regulation of skin stem cell–initiated tumorigenesis via the regulation of DMBA metabolism.
Early science with the Large Millimeter Telescope: dust constraints in a z ∼ 9.6 galaxy
Authors: Zavala J. A. , Michałowski M. J. , Aretxaga I. , Wilson G. W. , Hughes D. H. , Montaña A. , Dunlop J. S. , Pope A. , Sánchez-Argüelles D. , Yun M. S. , Zeballos M.
Published: August 2015

Recent observations with the GISMO (Goddard-IRAM Superconducting 2 Millimeter Observer) 2 mm camera revealed a detection 8 arcsec away from the lensed galaxy MACS1149-JD1 at z = 9.6. Within the 17.5 arcsec FWHM GISMO beam, this detection is consistent with the position of the high-redshift galaxy and therefore, if confirmed, this object could be claimed to be the youngest galaxy producing significant quantities of dust. We present higher resolution (8.5 arcsec) observations of this system taken with the AzTEC 1.1 mm camera mounted on the Large Millimeter Telescope Alfonso Serrano. Dust continuum emission at the position of MACS1149-JD1 is not detected with an r.m.s. of 0.17 mJy/beam. However, we find a detection ∼11 arcsec away from MACS1149-JD1, still within the GISMO beam which is consistent with an association to the GISMO source. Combining the AzTEC and GISMO photometry, together with Herschel ancillary data, we derive a zphot = 0.7–1.6 for the dusty galaxy. We conclude therefore that the GISMO and AzTEC detections are not associated with MACS1149-JD1. From the non-detection of MACS1149-JD1 we derive the following (3σ) upper limits corrected for gravitational lensing magnification and for cosmic microwave background effects: dust mass <1.6 × 107 M⊙, IR luminosity <8 × 1010 L⊙, star formation rate <14 M⊙ yr−1, and UV attenuation <2.7 mag. These limits are comparable to those derived for other high-redshift galaxies from deep Atacama Large Millimeter/submillimeter Array observations.
Intracranial hemorrhage in setting of glioblastoma with venous
thromboembolism
Authors: Khoury Michael Nabil , Missios Symeon , Edwin Natasha , Sakruti Susmita , Barnett Gene , Stevens Glen , Peereboom David M. , Khorana Alok A. , Ahluwalia Manmeet S.
Published: August 2015

Background

Venous thromboembolism (VTE) is a complication of glioblastoma. Anticoagulating patients with glioblastoma carries a theoretical risk of intracranial hemorrhage (ICH).

Methods

We performed a retrospective cohort study of consecutive glioblastoma patients (2007–2013) diagnosed with VTE.

Results

The study population comprised of 523 glioblastoma patients of whom 173 (33%) had VTE events. Seventeen (10%) had ICH: 6 (35%) subdural hematomas and 11 (65%) intratumoral hemorrhages. In total, 4 patients with ICH required neurosurgical intervention. Enhancement in the area of subsequent intratumoral hemorrhage was noted in 9 of 10 with available pre-ICH scans. Multivariable regression did not show associations between ICH and tumor enhancement diameter or use of vascular-endothelial-growth-factor inhibitor. Fifteen (16%) patients receiving anticoagulation had ICH compared with 2 (2.6%) not receiving anticoagulation (P = .005). The method of anticoagulation was not associated with development of ICH. Median survival times from nondistal VTE diagnosis to death were 8.0 and 3.5 months (P = .05) in patients receiving anticoagulation and those not on anticoagulation, respectively.

Conclusion

Patients with glioblastoma and VTE on anticoagulation have increased incidence of ICH. However, development of ICH was not associated with lower median survival from time of VTE. Intratumoral hemorrhage occurred within the enhancing portion of tumor; however, no relationship was identified between the development of ICH and (i) the median diameter of enhancement or (ii) type of anticoagulant used. However, patients with absence of enhancing tumor did not have intratumoral bleed, suggesting gross total resection may limit this adverse outcome. It is appropriate to initiate anticoagulation in glioblastoma patients with VTEs.
Development of genu valgum after removal of osteochondromas from the proximal tibia
Authors: Denduluri Sahitya K. , Lu Min , Bielski Robert J.
Published: August 2015

Genu valgum is a well-documented deformity secondary to hereditary multiple exostoses about the knee. Post-traumatic tibia valgus is also a well-described phenomenon that occurs in children who sustain an incomplete fracture of the proximal tibia. The finding is considered to be secondary to asymmetric blood flow to the proximal tibial physis. The existing literature only describes genu valgum as a sequela of the hereditary multiple exostoses disorder itself and does not address genu valgum occurring as a postoperative consequence of mass excision. In this paper, we report on three pediatric patients who developed unilateral genu valgum after removal of osteochondromas from the medial proximal tibia. Chart and radiographic data were retrospectively reviewed for a series of three patients. Three patients developed genu valgum after medial proximal tibial osteochondroma excision. The maximum tibiofemoral angle varied from 17 to 23°. One case resolved spontaneously with observation, one was addressed surgically with guided growth correction, and another was advised to undergo operative correction, but declined. We conclude that genu valgum can arise secondary to osteochondroma excision when the mass is resected near the proximal tibial physis. Surgeons should counsel patients on the possibility of postoperative angular growth deformity and monitor closely for its development.
Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women
Authors: Kabat Geoffrey C. , Salazar Christian R. , Zaslavsky Oleg , Lane Dorothy S. , Rohan Thomas E.
Published: August 2015

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women’s Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.
Length but not transverse diameter of the excision specimen for high-grade cervical intraepithelial neoplasia (CIN 2–3) is a predictor of pregnancy outcome
Authors: Liverani Carlo A. , Di Giuseppe Jacopo , Clemente Nicolò , Delli Carpini Giovanni , Monti Ermelinda , Fanetti Fabiana , Bolis Giorgio , Ciavattini Andrea
Published: August 2015

The objective of this study was to analyze the impact of cone characteristics (depth, transverse diameter, and volume) on subsequent pregnancies after the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN 2–3). Pregnancy outcomes (preterm birth, gestational age at birth, mode of delivery, and birth weight) of 501 women with singleton gestations and no previous preterm birth or history of late miscarriage, who had previously undergone a single LEEP for CIN 2–3, were retrospectively analyzed with respect to length, transverse diameter, and volume of the excision specimen. The overall incidence of preterm birth was 2.4%. The rate of preterm birth in women with length greater than 20 mm or volume greater than 2.5 cm3 was significantly higher than that in women with length between 15 and 19 mm (15.6 vs. 3.9%, P=0.02) or women with volume between 2.0 and 2.4 cm3 (5.8 vs. 1.6%, P=0.04). A linear inverse correlation (r=−0.3, P<0.001) between gestational age at birth and length, but not volume (r=0.0, P=0.9) or transverse diameter (r=0.2, P<0.0001), emerged. The mode of delivery was not affected by cone characteristics. Length, but not transverse diameter and volume, of the excised specimen seems to be related to a lower gestational age at birth. When excisions are performed under strict colposcopic guidance, with a correct modulation of cone length, the risk for preterm birth and cesarean delivery in subsequent pregnancies is not increased.
The Effect of Cumulative Dissipated Energy on Changes in Intraocular Pressure After Uncomplicated Cataract Surgery by Phacoemulsification
Authors: Lee Roland Y. , Chen Rebecca I. , Kasuga Toshimitsu , Cui Qi N. , Porco Travis C. , Lin Shan C.
Published: August 2015

Purpose:

To investigate the association between ultrasound energy, expressed as cumulative dissipated energy (CDE), and changes in intraocular pressure (IOP) after uncomplicated cataract surgery by phacoemulsification.

Methods:

In this prospective study, nonglaucomatous subjects underwent cataract surgery by phacoemulsification. IOP was compared by clustered linear regression at 4 separate time-points: preoperative, 1 day, 1 month, and 3 months after cataract surgery. Changes in the IOP were evaluated as a function of CDE using univariate and multivariate clustered linear regression models, which adjusted for sex, ethnicity, age, axial length, spherical equivalent, mean preoperative Shaffer gonioscopy grade of all 4 quadrants, cataract grade, preoperative IOP, central corneal thickness, and use of both eyes in the same subject.

Results:

One hundred sixty-one eyes (89 Asian, 49 white, 12 African, and 11 Hispanic) from 116 nonglaucomatous subjects were analyzed. The 161 eyes included 81 right and 80 left eyes. The 89 Asian eyes included 46 Chinese, 35 Filipino, and 8 Vietnamese. Preoperative IOP was 14.9±3.2 mm Hg. Postoperative IOP significantly increased to 16.0±4.9 mm Hg at 1 day (P=0.037) and decreased to 12.4±3.1 and 12.3±3.0 mm Hg at 1 and 3 months, respectively (both P<0.0001). IOP changes at 1 day, 1 month, and 3 months did not demonstrate significant associations with CDE measurements in either univariate or multivariate clustered linear regression analyses (all P>0.05).

Conclusions:

The amount of ultrasound energy delivered to the eye during phacoemulsification, expressed as CDE, was not associated with postoperative changes in IOP.
Hybridization Capture Using RAD Probes (hyRAD), a New Tool for Performing Genomic Analyses on Collection Specimens
Authors: Suchan Tomasz , Pitteloud Camille , Gerasimova Nadezhda S. , Kostikova Anna , Schmid Sarah , Arrigo Nils , Pajkovic Mila , Ronikier Michał , Alvarez Nadir
Published: August 2015

In the recent years, many protocols aimed at reproducibly sequencing reduced-genome subsets in non-model organisms have been published. Among them, RAD-sequencing is one of the most widely used. It relies on digesting DNA with specific restriction enzymes and performing size selection on the resulting fragments. Despite its acknowledged utility, this method is of limited use with degraded DNA samples, such as those isolated from museum specimens, as these samples are less likely to harbor fragments long enough to comprise two restriction sites making possible ligation of the adapter sequences (in the case of double-digest RAD) or performing size selection of the resulting fragments (in the case of single-digest RAD). Here, we address these limitations by presenting a novel method called hybridization RAD (hyRAD). In this approach, biotinylated RAD fragments, covering a random fraction of the genome, are used as baits for capturing homologous fragments from genomic shotgun sequencing libraries. This simple and cost-effective approach allows sequencing of orthologous loci even from highly degraded DNA samples, opening new avenues of research in the field of museum genomics. Not relying on the restriction site presence, it improves among-sample loci coverage. In a trial study, hyRAD allowed us to obtain a large set of orthologous loci from fresh and museum samples from a non-model butterfly species, with a high proportion of single nucleotide polymorphisms present in all eight analyzed specimens, including 58-year-old museum samples. The utility of the method was further validated using 49 museum and fresh samples of a Palearctic grasshopper species for which the spatial genetic structure was previously assessed using mtDNA amplicons. The application of the method is eventually discussed in a wider context. As it does not rely on the restriction site presence, it is therefore not sensitive to among-sample loci polymorphisms in the restriction sites that usually causes loci dropout. This should enable the application of hyRAD to analyses at broader evolutionary scales.
Determinants of RNA metabolism in theSchizosaccharomyces pombegenome
Authors: Eser Philipp , Wachutka Leonhard , Maier Kerstin C. , Demel Carina , Boroni Mariana , Iyer Srignanakshi , Cramer Patrick , Gagneur Julien
Published: August 2015

To decrypt the regulatory code of the genome, sequence elements must be defined that determine the kinetics of RNA metabolism and thus gene expression. Here we attempt such decryption in an eukaryotic model organism, the fission yeastS. pombe. We first derive an improved genome annotation that redefines borders of 36% of expressed mRNAs and adds 487 non-coding RNAs (ncRNAs). We then combine RNA labelingin vivowith mathematical modeling to obtain rates of RNA synthesis and degradation for 5,484 expressed RNAs and splicing rates for 4,958 introns. We identify functional sequence elements in DNA and RNA that control RNA metabolic rates, and quantify the contributions of individual nucleotides to RNA synthesis, splicing, and degradation. Our approach reveals distinct kinetics of mRNA and ncRNA metabolism, separates antisense regulation by transcription interference from RNA interference, and provides a general tool for studying the regulatory code of genomes.
Tax fraud: a socially acceptable financial crime in France?
Authors: Compin Frederic
Published: August 2015

Purpose

– The purpose of this paper is to point out that tax fraud, recognized as a scourge by both governments and responsible tax-payers, hits public finances hard with an inevitable knock-on effect on general welfare. Based on this observation, key players interviewed for this paper, including magistrates, a trade unionist and a high-ranking official, will attempt to provide some possible solutions to help understand why significant sections of public opinion consider this very particular form of financial crime to be legitimate, largely inspired by the notion that tax fraud and evasion are socially acceptable and even seen as a national sport in certain countries.

Design/methodology/approach

– The survey was carried out among 20 tax officials, a trade unionist, two magistrates and a high-ranking civil servant. The interviewees were carefully chosen for their ability to provide valuable insights into the reasons behind the lenient treatment of fraudsters by a state lacking the necessary means and structures to fight this crime.

Findings

– The fight against tax fraud has clearly sparked numerous controversies around evaluation, scope, criminal perpetrators and cooperation between services.

Social implications

– Tax fraud, an offence committed with the aim of avoiding taxation or reducing the amount of tax to be paid, ranges from low-level illegal activity, such as undeclared work to make ends meet, to more serious offences, such as value-added tax carousel fraud. All the unpaid tax resulting from such blatant flouting of the law represent a serious loss of revenue for the state and local authorities.

Originality/value

– The fight against tax fraud is crucial in determining taxpayers’ acceptance of the contribution required for state expenditure and investment. In a country such as France, where tax fraud is almost a national sport, combating this scourge will help restore the state’s budgetary sovereignty by making it central to people’s concerns about redistributive justice, tax equality and fair access to public goods.
Amending UN drug treaties to allow member states self-determination
Authors: Vanni Domitilla
Published: August 2015

Purpose

– This paper aims to analyse the fundamental principles of the main international conventions against use of drug and to verify if it would be preferable to let European Member States adopt specific measures according to own needs at a national level.

Design/methodology/approach

– The research uses a comparative approach by examining the different national legislations in respect of the discipline of the international conventions for finding analogies and differences between them.

Findings

– The research has discovered a wide variation in the criteria for triggering a legislative response and in the penalties for non-compliance. Nevertheless, there seems to be a trend towards countries focusing on penalising supply rather than possession of these substances.

Research limitations/implications

– To maintain a common international level in fighting against the use and commerce of drug to enforce the effectiveness of national regulations.

Practical implications

– The achievement of a high level of health protection, well-being and social cohesion to prevent and reduce drug use, dependence and drug-related damage to health and society.

Social implications

– To ensure a high level of security for the general public by taking action against drug production, cross-border trafficking in drugs and the diversion of chemical precursors used in drug production, as well as by intensifying preventive action against drug-related crime through effective cooperation, embedded in a joint approach.

Originality/value

– This is a fast-moving area of law, which continues to evolve for the different new substances being introduced in international drug traffic, so different solutions to the problem can be found by national legislators who need to be coordinated at an international level.
Power, dependence and frustration
Authors: Stone Gerard
Published: August 2015

Purpose

– This study aims to explore the existence and strength of power through focussing on the manner in which accountants exercise power in their advisory relationship with small business.

Design/methodology/approach

– Interviews provided insights into accountants’ power-related perceptions, experiences and use of power in the advisory relationship. A questionnaire accessed evidence from small business owner-managers (SBOMs). Power theoretical perspectives informed the analysis of the findings.

Findings

– Accountants’ expert and information power is a consequence of SBOMs’ dependence on their accountants’ expertise and knowledge. Accountants construct advisor roles and exercise power in a manner indicating that they attempt to manage rather than exploit power imbalances to the detriment of dependent SBOMs. However, outbreaks of frustration and conflict in the relationship illustrate the difficulties in managing the dysfunctional consequences of power imbalances.

Research limitations/implications

– While the findings are restricted to the Australian accountant–small business advisory relationship, they offer a basis for research into the effect of power on the relationship in other national contexts. Research which includes the views of managers of failed small businesses would also extend this work.

Practical implications

– The study’s focus on accountants’ experiences can assist practitioners endeavouring to develop advisory relationships with small business and designers of professional development programmes seeking to optimise the value of the advisory relationship.

Originality/value

– The paper extends the study of power to the under-researched yet important accountant–small business advisory area. Its findings are of interest to accountants and accounting policymakers who envisage a broadening of accountants’ small business advisory role.
The effects of fair trade on coffee growers: a framework and analysis
Authors: Omidvar Vahid , Giannakas Konstantinos
Published: August 2015

The world coffee market has undergone a significant transformation in the past couple of decades resulting in declining farm prices despite the fact that coffee demand has been strong and consumer prices have been soaring. Fair Trade organizations have tried to address this price imbalance by providing an alternative method of trading aimed at increasing the prices received by coffee growers. Despite their noble objectives, Fair Trade movements have had limited success in improving coffee growers’ welfare, however. This paper utilizes a novel framework of heterogeneous producers and relevant market information to provide insights on the market and welfare impacts of the Fair Trade regime when important idiosyncrasies of Fair Trade production and marketing are included in the analysis.
Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study
Authors: Cheng C.‐M. , Wu Y.‐H. , Tsai S.‐J. , Bai Y.‐M. , Hsu J.‐W. , Huang K.‐L. , Su T.‐P. , Li C.‐T. , Tsai C.‐F. , Yang A. C. , Lin W.‐C. , Pan T.‐L. , Chang W.‐H. , Chen T.‐J. , Chen M.‐H.
Published: August 2015

Background

A cross‐sectional retrospective study suggested a link between allergic diseases and Parkinson's disease. However, the temporal association between asthma and Parkinson's disease remains unknown.

Methods

From the Taiwan National Health Insurance Research Database, 10 455 patients who were diagnosed with asthma between 1998 and 2008 and aged ≥45 years and 41 820 age‐ and sex‐matched controls were selected for our study and observed until the end of 2011. Those who developed Parkinson's disease during the follow‐up period were identified. We also examined the asthma severity, as indicated by the frequency of admission (times per year) for asthma exacerbation, and the risk of subsequent Parkinson's disease.

Results

Patients with asthma had an increased risk of developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval [CI]: 2.20–4.36) after we adjusted for demographic data, health system use, medical comorbidities, and medication use. Sensitivity tests yielded consistent findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04–4.13) and first 3 years (HR: 2.46, 95% CI: 1.64–3.69). Patients with asthma who had more frequent admissions (times per year) during the follow‐up period exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95% CI: 5.88–45.91; 1‐2: 12.69, 95% CI: 5.03–31.71; 0‐1: HR: 2.92, 95% CI: 1.91–4.49).

Conclusion

Patients with asthma had an elevated risk of developing Parkinson's disease later in life, and we observed a dose‐dependent relationship between greater asthma severity and a higher risk of subsequent Parkinson's disease.
The effect of pars plana vitrectomy and nuclear cataract on oxygen saturation in retinal vessels, diabetic and non‐diabetic patients compared
Authors: Šín Martin , Chrapek Oldřich , Karhanová Marta , Šínová Irena , Špačková Kareřina , Langová Kateřina , Řehák Jiří
Published: August 2015

Purpose

To determine the effect of pars plana vitrectomy (PPV) on oxygen saturation in retinal vessels in patients with diabetes and non‐diabetes after a 1‐year follow‐up.

Methods

This was a prospective consecutive interventional case series in 82 eyes in 82 patients. The sample consisted of 25 patients with non‐proliferative diabetic retinopathy with macular oedema based on vitreoretinal traction or epiretinal membrane (ERM) and 57 non‐diabetic patients with macular hole and ERM. Automatic retinal oximetry (Oxymap Inc.) was used on all patients 24 hr prior to PPV, and it was also used 7 and 52 weeks after PPV (classic 20G or sutureless 23G). We analysed the data according to subgroup diagnosis and lens status.

Results

Arterial saturation increased significantly from 96.4 ± 2.9% at baseline to 96.6 ± 3.4% at week 7 and 97.3 ± 3.4% at week 52 (p < 0.0001; Friedman test). Vein saturation also increased significantly from 63.5 ± 7.9% at baseline to 66.1 ± 7.7% and 67.0 ± 7.2% at weeks 7 and 52 (p < 0.0001; Friedman test). The value of the arteriovenous (A‐V) difference decreased significantly after vitrectomy from 32.8 ± 7.5% at baseline to 30.5 ± 7.5% and 30.3 ± 7.0% at weeks 7 and 52 (p < 0.0001; Friedman test). The subgroup analysis revealed that in patients with diabetes, there were no statistically significant changes in oxygen saturation in blood vessels or in the A‐V difference after PPV. After vitrectomy, retinal vessel diameter reduced by about 3.5% in both groups of patients. Further, the analysis revealed that opacification of the lens leads to a decrease in oxygen saturation in contrast to a clear lens and pseudophakic IOLs.

Conclusion

Oxygen saturation is higher in the retinal veins and arteries after PPV in patients with non‐diabetes, and this lasts for at least 52 weeks. In contrast, in patients with diabetes, there is no increase in oxygen saturation in the retinal vessels after vitrectomy. After vitrectomy, retinal vessel diameter reduced in both groups of patients. Further, the nuclear cataract progression has substantial effect on oximetry results. Patients with nuclear cataract exhibited an increase in saturation in both arteries and veins, but the A‐V difference remained the same.
Long‐Term Pharmacotherapy of Adults With Attention Deficit Hyperactivity Disorder: A Literature Review and Clinical Study
Authors: Fredriksen Mats , Peleikis Dawn E.
Published: August 2015

This MiniReview reports and discusses the main findings of the author's thesis including a literature study of long‐term pharmacological treatment of adults with attention deficit hyperactivity disorder (ADHD), and a clinical study of 1‐year medication. Electronic databases were systematically reviewed for original studies on pharmacotherapy of the defined duration, 24 weeks or more. Although few trials were found with limitations such as excluding comorbidities, treatment with stimulants and atomoxetine was reported tolerated and effective compared to non‐treatment. The clinical study of the thesis was conducted on 250 medication‐naïve patients with ADHD referred to a specialized outpatient clinic. Comorbid psychiatric disorders were diagnosed among 75% of the patients. About 56% had not completed secondary school, and 51% had been unable to work the preceding year. Persisting inattentive symptoms and comorbid mental disorders in adulthood were related to long‐term work disability. In the prospective observational study of the thesis, patients were treated with methylphenidate as first‐line drug and atomoxetine or dexamphetamine as second‐line drugs, according to current treatment guidelines. At 12‐month follow‐up, 232 patients completed evaluation and 70% persisted on medication. About 80% of these used methylphenidate. Sustained improvement of symptoms and functioning was related to continued medication. Comorbid mental disorders and side effects were related to lower effectiveness and adherence, and 12% stopped medication due to side effects. Summing up the MiniReview, treatment with stimulants and atomoxetine of adults with ADHD has long‐term beneficial effects and is tolerated but more longitudinal studies should be performed. With stated limitations, the findings of the thesis should contribute to a relevant guidance for clinical practice.
Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro
Authors: Cai Jie , Dai Da‐Peng , Geng Pei‐Wu , Wang Shuang‐Hu , Wang Hao , Zhan Yun‐Yun , Huang Xiang‐Xin , Hu Guo‐Xin , Cai Jian‐Ping
Published: August 2015

Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that metabolizes a large number of therapeutic drugs. To date, more than 100 CYP2D6 allelic variants have been reported. Among these variants, we recently identified 22 novel variants in the Chinese population. The aim of this study was to functionally characterize the enzymatic activity of these variants in vitro. A baculovirus‐mediated expression system was used to express wild‐type CYP2D6.1 and other variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) at high levels. Then, the insect microsomes containing expressed CYP2D6 proteins were incubated with bufuralol or dextromethorphan at 37°C for 20 or 25 min., respectively. After termination, the metabolites were extracted and used for the detection with high‐performance liquid chromatography. Among the 24 CYP2D6 variants tested, two variants (CYP2D6.92 and CYP2D6.96) were found to be catalytically inactive. The remaining 22 variants exhibited significantly decreased intrinsic clearance values for bufuralol 1′‐hydroxylation and 20 variants showed significantly lower intrinsic clearance values for dextromethorphan O‐demethylation than those of the wild‐type CYP2D6.1. Our in vitro results suggest that most of the variants exhibit significantly reduced catalytic activities compared with the wild‐type, and these data provide valuable information for personalized medicine in Chinese and other Asian populations.
Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group
Authors: Bröckelmann Paul J. , Goergen Helen , Fuchs Michael , Kriz Jan , Semrau Robert , Baues Christian , Kobe Carsten , Behringer Karolin , Eichenauer Dennis A. , von Tresckow Bastian , Klimm Beate , Halbsguth Teresa , Wongso Diana , Plütschow Annette , Haverkamp Heinz , Dietlein Markus , Eich Hans T. , Stein Harald , Diehl Volker , Borchmann Peter , Engert Andreas
Published: August 2015

Accurate clinical staging is crucial for adequate risk‐adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under‐ or over‐treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re‐evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first‐line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte‐predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk‐adapted first‐line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice.
Environmental carcinogenesis – 100th anniversary of creating cancer
Authors: Imai Misa , Hino Okio
Published: August 2015

Asbestos is an environmental carcinogen, and asbestos‐related diseases represent a global‐scale environmental issue. Mesothelioma is an aggressive, malignant tumor that initially progresses along the surfaces of the pleura and peritoneum that is chiefly attributed to asbestos exposure. X‐rays are commonly used for tumor screening in populations at risk for developing this cancer. We previously reported that the N‐terminal of mesothelin may be a useful blood marker for early diagnosis method for mesothelioma and since then developed an N‐terminal of mesothelin ELISA kit in collaboration with IBL Co., Ltd. and confirmed its utility as a diagnostic system for mesothelioma. Recently, we performed a large‐scale research screening for mesothelioma and showed that it is a good model for early diagnosis in at‐risk populations. The year 2015 is the 100th anniversary of Yamagiwa's great work on coaltar‐induced carcinogenesis by formative stimulation in 1915 and the 10th year since 2005, “Kubota shock”, people recognized that asbestos induces mesothelioma. We dedicate this review to this memorial year for environmental carcinogenesis.
Suppressive effects of the NADPH oxidase inhibitor apocynin on intestinal tumorigenesis in obese KK‐Ay and Apc mutant Min mice
Authors: Komiya Masami , Fujii Gen , Miyamoto Shingo , Takahashi Mami , Ishigamori Rikako , Onuma Wakana , Ishino Kousuke , Totsuka Yukari , Fujimoto Kyoko , Mutoh Michihiro
Published: August 2015

Obesity is a risk factor for colorectal cancer. The accumulation of abdominal fat tissue causes abundant reactive oxygen species production through the activation of NADPH oxidase due to excessive insulin stimulation. The enzyme NADPH oxidase catalyzes the production of reactive oxygen species and evokes the initiation and progression of tumorigenesis. Apocynin is an NADPH oxidase inhibitor that blocks the formation of the NADPH oxidase complex (active form). In this study, we investigated the effects of apocynin on the development of azoxymethane‐induced colonic aberrant crypt foci in obese KK‐Ay mice and on the development of intestinal polyps in Apc mutant Min mice. Six‐week‐old KK‐Ay mice were injected with azoxymethane (200 μg/mouse once per week for 3 weeks) and given 250 mg/L apocynin or 500 mg/L apocynin in their drinking water for 7 weeks. Six‐week‐old Min mice were also treated with 500 mg/L apocynin for 6 weeks. Treatment with apocynin reduced the number of colorectal aberrant crypt foci in KK‐Ay mice by 21% and the number of intestinal polyps in Min mice by 40% compared with untreated mice. Both groups of mice tended to show improved oxidation of serum low‐density lipoprotein and 8‐oxo‐2′‐deoxyguanosine adducts in their adipose tissues. In addition, the inducible nitric oxide synthase mRNA levels in polyp tissues decreased. Moreover, apocynin was shown to suppress nuclear factor‐κB transcriptional activity in vitro. These results suggest that apocynin and other NADPH oxidase inhibitors may be effective colorectal cancer chemopreventive agents.
Retinoid X receptor α enhances human cholangiocarcinoma growth through simultaneous activation of Wnt/β‐catenin and nuclear factor‐κB pathways
Authors: Huang Gui‐Li , Zhang Wei , Ren Hong‐Yue , Shen Xue‐Ying , Chen Qing‐Xi , Shen Dong‐Yan
Published: August 2015

Retinoid X receptor α (RXRα) plays important roles in the malignancy of several cancers such as human prostate tumor, breast cancer, and thyroid tumor. However, its exact functions and molecular mechanisms in cholangiocarcinoma (CCA), a chemoresistant carcinoma with poor prognosis, remain unclear. In this study we found that RXRα was frequently overexpressed in human CCA tissues and CCA cell lines. Downregulation of RXRα led to decreased expression of mitosis‐promoting factors including cyclin D1and cyclin E, and the proliferating cell nuclear antigen, as well as increased expression of cell cycle inhibitor p21, resulting in inhibition of CCA cell proliferation. Furthermore, RXRα knockdown attenuated the expression of cyclin D1 through suppression of Wnt/β‐catenin signaling. Retinoid X receptor α upregulated proliferating cell nuclear antigen expression through nuclear factor‐κB (NF‐κB) pathways, paralleled with downregulation of p21. Thus, the Wnt/β‐catenin and NF‐κB pathways account for the inhibition of CCA cell growth induced by RXRα downregulation. Retinoid X receptor α plays an important role in proliferation of CCA through simultaneous activation of Wnt/β‐catenin and NF‐κB pathways, indicating that RXRα might serve as a potential molecular target for CCA treatment.
The case for an autoimmune aetiology of type 1 diabetes
Authors: Mannering S I , Pathiraja V , Kay T W H
Published: August 2015

Type 1 diabetes (T1D) develops when there are insufficient insulin-producing beta cells to maintain glucose homeostasis. The prevailing view has been that T1D is caused by immune-mediated destruction of the pancreatic beta cells. However, several recent papers have challenged the long-standing paradigm describing T1D as a tissue-specific autoimmune disease. These authors have highlighted the gaps in our knowledge and understanding of the aetiology of T1D in humans. Here we review the evidence and argue the case for the autoimmune basis of human T1D. In particular, recent analysis of human islet-infiltrating T cells brings important new evidence to this question. Further data in support of the autoimmune basis of T1D from many fields, including genetics, experimental therapies and immunology, is discussed. Finally, we highlight some of the persistent questions relating to the pathogenesis of human type 1 diabetes that remain to be answered.
Reframing the concept of alternative livelihoods
Authors: Wright Juliet H. , Hill Nicholas A. O. , Roe Dilys , Rowcliffe J. Marcus , Kümpel Noëlle F. , Day Mike , Booker Francesca , Milner‐Gulland E. J.
Published: August 2015

Alternative livelihood project (ALP) is a widely used term for interventions that aim to reduce the prevalence of activities deemed to be environmentally damaging by substituting them with lower impact livelihood activities that provide at least equivalent benefits. ALPs are widely implemented in conservation, but in 2012, an International Union for Conservation of Nature resolution called for a critical review of such projects based on concern that their effectiveness was unproven. We focused on the conceptual design of ALPs by considering their underlying assumptions. We placed ALPs within a broad category of livelihood‐focused interventions to better understand their role in conservation and their intended impacts. We dissected 3 flawed assumptions about ALPs based on the notions of substitution, the homogenous community, and impact scalability. Interventions based on flawed assumptions about people's needs, aspirations, and the factors that influence livelihood choice are unlikely to achieve conservation objectives. We therefore recommend use of a sustainable livelihoods approach to understand the role and function of environmentally damaging behaviors within livelihood strategies; differentiate between households in a community that have the greatest environmental impact and those most vulnerable to resource access restrictions to improve intervention targeting; and learn more about the social–ecological system within which household livelihood strategies are embedded. Rather than using livelihood‐focused interventions as a direct behavior‐change tool, it may be more appropriate to focus on either enhancing the existing livelihood strategies of those most vulnerable to conservation‐imposed resource access restrictions or on use of livelihood‐focused interventions that establish a clear link to conservation as a means of building good community relations. However, we recommend that the term ALP be replaced by the broader term livelihood‐focused intervention. This avoids the implicit assumption that alternatives can fully substitute for natural resource‐based livelihood activities.
THE RISK OF FIRE SALES IN THE TRI‐PARTY REPO MARKET
Authors: Begalle Brian , Martin Antoine , McAndrews James , McLaughlin Susan
Published: August 2015

This paper studies the risk of “fire sales” in the tri‐party repo market, a large and important market where securities dealers find short‐term funding for a substantial portion of their own and their clients' assets. We distinguish between fire sales of assets by a dealer who, facing a run that could lead to default, sells securities to generate liquidity, and fire sales of assets by repo investors after a dealer's default has occurred. While fire sales do cause damage no matter how they arise, the tools available to lessen the harm from the two types of fire sales are different. We find that limited tools are available to mitigate the risk of predefault fire sales and that no established tools currently exist to mitigate the risk of postdefault sales. (JEL G01, G18)
Custom‐Fitted EVA Mouthguards: what is the ideal thickness? a dynamic finite element impact study
Authors: Verissimo Crisnicaw , Costa Paulo Victor Moura , Santos‐Filho Paulo Cesar Freitas , Tantbirojn Daranee , Versluis Antheunis , Soares Carlos José
Published: August 2015

Background/Aim

The aim of this study was to evaluate the tooth stresses and strains, shock absorption, and displacement during impact of custom‐fitted mouthguards with different thicknesses.

Methods

Six bar‐shaped specimens of the EVA were made and subjected to tensile test for elastic modulus assessment. Two‐dimensional plane‐strain models of a human maxillary central incisor, periodontal ligament, bone support, soft tissue, and mouthguard (MTG) were created. The mouthguards were modeled in five different thicknesses (2, 3, 4, 5, and 6 mm). One model was created without mouthguard. A nonlinear dynamic impact analysis was performed in which a rigid object hit the model at 1 m s−1. Strain and stress (von Mises and Critical modified von Mises) distributions were evaluated, and the displacement of the mouthguard with respect to the tooth was calculated.

Results

The mean [SD] for the EVA elastic modulus was 18.075 [0.457] MPa. The model without mouthguard showed the highest stress values at the enamel and dentin structures in the tooth crown during the impact. For the MTG models, the location of the stress concentrations changed to the root, regardless of the MTG thickness, but maximum stresses in the enamel and dentin were lower compared with the model without MTG. Increasing the mouthguard thickness did not notably decrease the stress‐strain values.

Conclusion

It was concluded that the use of a mouthguard promoted lower stresses and strains in teeth during an impact with a rigid object. There was no substantial difference in peak stresses and strains and in shock absorption among the different mouthguard thicknesses.
miR‐124 exerts tumor suppressive functions on the cell proliferation, motility and angiogenesis of bladder cancer by fine‐tuning UHRF1
Authors: Wang Xinsheng , Wu Qiaoli , Xu Bin , Wang Pengfei , Fan Weijia , Cai Ying , Gu Xinquan , Meng Fanping
Published: August 2015

UHRF1, an epigenetic factor, is implicated in various cellular processes of tumorigenesis. However, the modulation of UHRF1 expression in human bladder cancer at post‐transcriptional levels remains unclear. Here, we report that miR‐124 suppresses expression of UHRF1 to affect the progression of human bladder cancer through competitive binding of the same region of its 3′‐UTR. We show that compared with corresponding normal tissues, UHRF1 is upregulated and miR‐124 is downregulated in bladder cancer tissues, demonstrating an inverse correlation of miR‐124 and UHRF1. Quantitative PCR and western blot assay demonstrated that over‐expression of miR‐124 resulted in the suppression of UHRF1. Furthermore, luciferase assay revealed that miR‐124 could control the fate of target gene UHRF1 mRNA by binding 3′‐UTR. The rescue experiment confirmed that miR‐124 exerted its biological functions by targeting UHRF1. miR‐124 over‐expression significantly attenuated cellular proliferation, migration, invasion and vasculogenic mimicry in vitro, and tumor growth in vivo. UHRF1 siRNA showed significant inhibitory effects on bladder cancer cells. Collectively, our study demonstrates that miR‐124 can impair the proliferation or metastasis of human bladder cancer cells by down‐regulation of UHRF1.