bluuebunny/crossref_metadata_2025 huggingface dataset:
Neck lumps
Authors: Darr Adnan , Hakim Navid , Mummadi Sangha Mitra , Hobbs Christopher
Published: April 2018

Neck lumps are among the most common presentations to primary care. The majority of cases are of a benign aetiology, however, the morbidity associated with delayed referral or incorrect diagnosis can be catastrophic in cases of malignancy. It is, therefore, vital that clinicians have a sound approach to this important presentation. The aim of this article is to equip clinicians with an understanding of regional neck anatomy and pathology, a systematic approach to neck masses, and guidance to follow for appropriate investigations and referrals.
Epigenetic regulation of inflammation in stroke
Authors: Ng Gavin Yong-Quan , Lim Yun-An , Sobey Christopher G. , Dheen Thameem , Fann David Yang-Wei , Arumugam Thiruma V.
Published: April 2018

Despite extensive research, treatments for clinical stroke are still limited only to the administration of tissue plasminogen activator and the recent introduction of mechanical thrombectomy, which can be used in only a limited proportion of patients due to time constraints. A plethora of inflammatory events occur during stroke, arising in part due to the body’s immune response to brain injury. Neuroinflammation contributes significantly to neuronal cell death and the development of functional impairment and death in stroke patients. Therefore, elucidating the molecular and cellular mechanisms underlying inflammatory damage following stroke injury will be essential for the development of useful therapies. Research findings increasingly point to the likelihood that epigenetic mechanisms play a role in the pathophysiology of stroke. Epigenetics involves the differential regulation of gene expression, including those involved in brain inflammation and remodelling after stroke. Hence, it is conceivable that epigenetic mechanisms may contribute to differential interindividual vulnerability and injury responses to cerebral ischaemia. In this review, we summarize recent findings on the emerging role of epigenetics in the regulation of neuroinflammation in stroke. We also discuss potential epigenetic targets that may be assessed for the development of stroke therapies.
Evaluating strategies and outcomes following rotator cuff tears
Authors: Amoo-Achampong Kelms , Krill Michael K , Acheampong Derrick , Nwachukwu Benedict U , McCormick Frank
Published: April 2018

Introduction

Rotator cuff tear surgical repair techniques have significantly progressed. However, tendon retear following primary repair persistently occurs at high rates. Rehabilitation protocols, surgical fixation techniques, biologic therapy with scaffolds, platelet-rich plasma, and even stem cell applications are under study to promote adequate tendon healing.

Methods

A nonsystematic query of the PubMed database was conducted in July 2016 utilizing the search terms “rotator cuff repair,” “tear,” “rehabilitation,” “scaffold,” “platelet-rich plasma,” and “stem cell” to identify, analyze, and summarize relevant studies.

Conclusion

Individualized rehabilitation protocols may be the best approach for small to medium sized tears. Surgical fixation will continue to be debated as modifications to single-row technique and increases in suture number have improved tensile strength. Double-row repairs have been associated with higher costs. Transosseous equivalent technique exhibits comparable subjective and objective outcomes to single- and double-row repair at two-year follow-up. Biocompatible scaffold augmentation has showed inconsistent short-term results. Platelet-rich plasma has lacked uniformity in treatment preparation, administration, and outcome measurement with mixed results. Few human studies have suggested decreased retear rates and improved repair maintenance following bone marrow-derived mesenchymal stem cell augmentation. This review reiterated the necessity of additional high-quality, large-sample studies to develop any final verdict regarding efficacy.
External rotation bracing for first-time anterior dislocation of the shoulder: A discontinued randomised controlled trial comparing external rotation bracing with conventional sling
Authors: Chan Samuel KL , Bentick Kieran R , Kuiper Jan H , Kelly Cormac P
Published: April 2018

Introduction

Itoi et al. introduced the concept of bracing in abduction and external rotation to treat traumatic anterior shoulder dislocations. However, controversy remains as studies have reported variable results. Our study investigates whether there is a difference in outcomes between treatment with a conventional sling or external rotation brace.

Methods

A prospective, multi-centre randomised control trial was conducted between 2006 and 2010. The study was discontinued early with 72 (36 cases in each group) first-time anterior shoulder dislocations recruited.

Results

The re-dislocation rate over 24 months was comparable 30% (95% CI: 17–47) sling vs. 24% (95% CI: 13–41) external rotation bracing. Sixteen percent (95% CI: 7–32) of sling patients and 12% (95% CI: 5–27) of external rotation-bracing patients had shoulder stabilisation surgery within 24 months of the initial dislocation (p > 0.05). There was no difference in OSI scores at 24 months between the two treatment groups and intolerability of the external rotation brace was high.

Conclusion

Recruitment to this study was difficult, and lost-to-follow-up rates were high leading to early discontinuation of the study. The results suggest that ER bracing is unlikely to provide clinical benefit in traumatic first-time anterior shoulder dislocation.
Reflections on Race and Privilege in an Educational Leadership Course
Authors: Zarate Maria Estela , Mendoza Yoselinda
Published: April 2018

To be effective social justice leaders, school leaders need to gain critical understandings of their positionality and racial privilege and be prepared to engage in difficult conversations with others. This study examines how a peer-to-peer letter exchange assignment in a doctoral course allowed educational leadership doctoral students ( N = 27) to reflect on race and privilege with each other. The findings reveal how students examined racial privilege, positionality, and bias. The authors discuss how this assignment can be used in educational leadership programs to develop and grow the practice of critical reflection for self-examination of privilege.
The Relationship Between Nurses’ Sociotropy–Autonomy Personality Characteristics and Trait Anger: Anger Expression Styles
Authors: Kaya Nurten , Tosun Hale
Published: April 2018

The aim of the study is to determine the relationship between the nurses’ sociotropy–autonomy personality characteristics and trait anger–anger expression styles. This study was conducted in a cross-sectional design, and the sample included 776 nurses in a university hospital. The sample consisted of 370 nurses who were selected by stratified random sampling method in a university hospital. The Sociotropy–autonomy Scale and the State-Trait Anger Scale were used in data collection. The mean value of the Anger-In subscale was 16.24 point, the Anger-Out subscale was 15.38 point, and the Anger Control subscale was 22.86 point. The mean value of the sociotropy level of nurses was 66.71, and the mean value of the autonomy level of nurses was 75.41. Statistically significant relationships were observed between the Sociotropy–autonomy Scale and the Trait Anger–Anger Expression Scales scores. The higher the sociotropy–autonomy personality characteristics of the nurses are in an investigation, the higher the Trait Anger, Anger-In, and Anger-Out scores are. Furthermore, the anger control expression style was only related to the “Concern About Disapproval” in a negative way.
Agentic Engagement and Test Anxiety: The Mediatory Role of the Basic Psychological Needs
Authors: Mehdipour Maralani Farnaz , Shalbaf Azre , Gholamali Lavasani Masoud
Published: April 2018

Despite the role of agency in schools, few researchers have addressed the issue. The present study aims to analyze the relationship between agentic engagement, basic psychological needs, and test anxiety by using structural equation modeling. For this purpose, 289 female students in math-physics and basic sciences were selected as the samples by using multistage cluster sampling. Reeve and Tseng’s aspects of students’ engagement during learning activity, La Guardia’s et al. basic psychological needs, and Ahvaz test anxiety scale were used as data collection tools. The results of structural equation modeling indicated that agentic engagement positively influenced the basic psychological needs such as autonomy, competence, and relatedness while it could negatively affect test anxiety with the mediatory role of basic psychological needs. In conclusion, agentic engagement can be regarded as a critical variable in affecting the basic psychological needs and reducing test anxiety.
Romantic Relationship Status and Emerging Adult Well-Being: Accounting for Romantic Relationship Interest
Authors: Beckmeyer Jonathon J. , Cromwell Shannon
Published: April 2018

Using data from 744 unmarried emerging adults, we tested the associations between their romantic relationship status and well-being while accounting for single participants’ romantic relationship interest. Specifically, we compared the depressive symptoms, life satisfaction, and loneliness of those who were (1) romantically involved, (2) single not/slightly interested in a romantic relationship, and (3) single very interested in a romantic relationship. The single very interested group reported greater depressive symptoms than those in the other two groups, who did not differ from each other. Emerging adults in the romantically involved group reported greater life satisfaction than both groups of single participants who did not differ from one another. Those in the romantically involved group reported less loneliness than both groups of single emerging adults, and the single not/slightly interested group reported less loneliness than the single very interested group. Results are discussed within the context of emerging adult romantic development.
Preference for Subcutaneous Injection or Intravenous Infusion of Biological Therapy Among Italian Patients With SLE
Authors: Falanga Marina , Canzona Augusta , Mazzoni Davide
Published: April 2018

This article focuses on the patients’ acceptance of a subcutaneous injection device for patients with systemic lupus erythematosus, which in the upcoming years could be introduced beside the intravenous infusion of biological therapy. An online questionnaire was completed by 548 patients from different Italian regions. The preference for subcutaneous injection was 41.2%, for intravenous infusion was 36.9%, and 21.9% were uncertain. Patients with previous experience of biological therapies were less uncertain ( P = .001). The reported motivations for the preference were analyzed through a lexicometric approach with the software T-LAB. Results revealed that respondents who preferred subcutaneous injections reported motivations that were more related to convenience, avoiding the discomfort of reaching the hospital. Patients who preferred intravenous infusion emphasized the importance of safety feelings related to the presence of qualified assistance during the therapy administration. In conclusion, patients appreciated the convenience that characterizes subcutaneous injections but also emphasized the importance of feeling safe during the administration. The study suggests that the choice of prescribing subcutaneous injections or intravenous infusions should be shared with patients, discussing possible resistances and avoiding preconceptions about patients’ preferences.
Social Structures in Transition: Applications of Two Theories to Chiefdoms
Authors: Emanuelson Pamela , Willer David
Published: April 2018

Status characteristics theory and elementary theory are applied to explain developments through three structural forms that chiefdoms are known to take. Theoretic models find that downward mobility inherent in the first form, the status-lineage structure, destabilizes its system of privilege. As a consequence, high-status actors are motivated to find mechanisms to preserve and enhance privilege. By engaging in hostile relations with other chiefdoms, high-status actors offer protection to low-status others from real or imagined threats. Through that protection, they gain tribute and support. The result is structural change from influence based on status to power exercised through indirect coercion, the second structural form. In settled societies, accumulation through war and selective redistribution contribute to separation of warrior and commoner rankings. That separation leads to the third structural form, direct coercive chiefdom.
Evaluation of an E-Learning Course for Clubfoot Treatment in Tanzania: A Multicenter Study
Authors: Vaca Silvia D , Warstadt Nicholus M , Ngayomela Isidor H , Nungu Rachel , Kowero Emmanuel S , Srivastava Sakti
Published: April 2018

In total, 80% of clubfoot cases occur in low- and middle-income countries, where lack of clinical knowledge of the Ponseti method of treatment presents as a major barrier to treatment. This study aims to determine the effectiveness of an electronic learning course to teach clinicians in Tanzania Ponseti method theory. A total of 30 clinicians were recruited from clinics with high referral rates for clubfoot patients and invited to 1 of 3 training sites: Mbeya (n = 15), Zanzibar (n = 10), and Mwanza (n = 5). Baseline knowledge, measured through a pretest, was compared to performance on a posttest after e-learning course completion. Scores for Mbeya and Zanzibar participants improved from 44 ± 12.5 to 69.8 ± 16.5 ( P < .0001) and 44.3 ± 14.0 to 67.9 ± 21.4 ( P = .01), respectively. Our results suggest that an e-learning course may be an effective method of disseminating Ponseti method theory in Tanzania. Successful implementation requires an understanding of the device availability and technology literacy of the users.
The effect of carotid artery stenting on capillary transit time heterogeneity in patients with carotid artery stenosis
Authors: Arsava Ethem M , Hansen Mikkel B , Kaplan Berkan , Peker Ahmet , Gocmen Rahsan , Arat Anil , Oguz Kader K , Topcuoglu Mehmet A , Østergaard Leif , Dalkara Turgay
Published: April 2018

Introduction

Carotid revascularisation improves haemodynamic compromise in cerebral circulation as an additional benefit to the primary goal of reducing future thromboembolic risk. We determined the effect of carotid artery stenting on cerebral perfusion and oxygenation using a perfusion-weighted MRI algorithm that is based on assessment of capillary transit-time heterogeneity together with other perfusion and metabolism-related metrics.

Patients and methods

A consecutive series of 33 patients were evaluated by dynamic susceptibility contrast perfusion-weighted MRI prior to and within 24 h of the endovascular procedure. The level of relative change induced by stenting, and relationship of these changes with respect to baseline stenosis degree were analysed.

Results

Stenting led to significant increase in cerebral blood flow ( p < 0.001), and decrease in cerebral blood volume ( p = 0.001) and mean transit time ( p < 0.001); this was accompanied by reduction in oxygen extraction fraction ( p < 0.001) and capillary transit-time heterogeneity ( p < 0.001), but an overall increase in relative capillary transit-time heterogeneity (RTH: CTH divided by MTT; p = 0.008). No significant change was observed with respect to cerebral metabolic rate of oxygen. The median volume of tissue with MTT > 2s decreased from 24 ml to 12 ml ( p = 0.009), with CTH > 2s from 29 ml to 19 ml ( p = 0.041), and with RTH < 0.9 from 61 ml to 39 ml ( p = 0.037) following stenting. These changes were correlated with the baseline degree of stenosis. Discussion: Stenting improved the moderate stage of haemodynamic compromise at baseline in our cohort. The decreased relative transit-time heterogeneity, which increases following stenting, is probably a reflection of decreased functional capillary density secondary to chronic hypoperfusion induced by the proximal stenosis. Conclusion: Carotid artery stenting, is not only important for prophylaxis of future vascular events, but also is critical for restoration of microvascular function in the cerebral tissue.
Regenerative medicine in the retina: from stem cells to cell replacement therapy
Authors: Oswald Julia , Baranov Petr
Published: April 2018

Following the fast pace of the growing field of stem cell research, retinal cell replacement is finally emerging as a feasible mean to be explored for clinical application. Although neuroprotective treatments are able to slow the progression of retinal degeneration caused by diseases such as age-related macular degeneration and glaucoma, they are insufficient to fully halt disease progression and unable to recover previously lost vision. Comprehensive, technological and intellectual advances over the past years, including the in vitro differentiation of retinal cells at manufacturing scale from embryonic stem (ES) cell and induced pluripotent stem (iPS) cell cultures, progress within the area of retinal disease modeling, and the first clinical trials have started to shape the way towards addressing this treatment gap and translating retinal cell replacement to the clinic. Here, summarize the most recent advances within retinal cell replacement from both a scientific and clinical perspective, and discuss the remaining challenges towards the delivery of the first retinal cell products.
Nocturnal cerebral hypoxia in obstructive sleep apnoea: a randomised controlled trial
Authors: Schwarz Esther I. , Furian Michael , Schlatzer Christian , Stradling John R. , Kohler Malcolm , Bloch Konrad E.
Published: April 2018

Cerebral hypoxia may promote cerebral damage in patients with obstructive sleep apnoea (OSA). We investigated whether OSA patients experience nocturnal cerebral hypoxia that is prevented by continuous positive airway pressure (CPAP).

OSA patients using CPAP underwent sleep studies including pulse oximetry (arterial oxygen saturation (SpO2)) and near-infrared spectroscopy to monitor cerebral tissue oxygenation (CTO) at baseline and after 2 weeks on either subtherapeutic or therapeutic CPAP according to randomised allocation. Changes in oxygenation at end of the 2-week intervention were compared between groups.

Among 21 patients (mean apnoea/hypopnoea index 50.3 events·h−1), OSA recurred in all nine patients using subtherapeutic CPAP and in none of the patients using therapeutic CPAP: mean (95% CI) between-group differences in changes of oxygen desaturation index from baseline to 2 weeks +40.7 (31.1–50.4) events·h−1forSpO2and +37.0 (25.3–48.7) events·h−1for CTO (both p<0.001). Mean nocturnalSpO2and CTO decreased more in patients using subtherapeuticversustherapeutic CPAP: −2.4 (−3.4–−1.1)% and −3.8 (−7.4–−0.1)%, respectively; both p<0.03. Severe CTO drops ≥13% associated with cerebral dysfunction in previous studies occurred in four out of nine patients using subtherapeutic CPAP, but in none out of 12 patients using therapeutic CPAP (p=0.01).

In patients with OSA, CPAP withdrawal resulted in nocturnal cerebral deoxygenation, suggesting a role of cerebral hypoxia in predisposing untreated OSA patients to cerebral damage.
Lung cancer staging: a concise update
Authors: Rami-Porta Ramón , Call Sergi , Dooms Christophe , Obiols Carme , Sánchez Marcelo , Travis William D. , Vollmer Ivan
Published: April 2018

Diagnosis and clinical staging of lung cancer are fundamental to planning therapy. The techniques for clinical staging,i.e. anatomic and metabolic imaging, endoscopies and minimally invasive surgical procedures, should be performed sequentially and with an increasing degree of invasiveness. Intraoperative staging, assessing the magnitude of the primary tumour, the involved structures, and the loco-regional lymphatic spread by means of systematic nodal dissection, is essential in order to achieve a complete resection. In resected tumours, pathological staging, with the systematic study of the resected specimens, is the strongest prognostic indicator and is essential to make further decisions on therapy. In the present decade, the guidelines on lung cancer staging of the American College of Chest Physicians and the European Society of Thoracic Surgeons are based on the best available evidence and are widely followed. Recent advances in the classification of the adenocarcinoma of the lung, with the definition of adenocarcinomain situ, minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma, and the publication of the eighth edition of the tumour, node and metastasis classification of lung cancer, have to be integrated into the staging process. The present review complements the latest guidelines on lung cancer staging by providing an update of all these issues.
In vitro,in silicoandin vivostudy challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss
Authors: Chernyavsky Igor L. , Russell Richard J. , Saunders Ruth M. , Morris Gavin E. , Berair Rachid , Singapuri Amisha , Chachi Latifa , Mansur Adel H. , Howarth Peter H. , Dennison Patrick , Chaudhuri Rekha , Bicknell Stephen , Rose Felicity R.A.J. , Siddiqui Salman , Brook Bindi S. , Brightling Christopher E.
Published: April 2018

Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival.

Airway smooth muscle and bronchial epithelial cells were exposed to media (37–70°C) for 10 s to mimic thermoplasty.In silicowe developed a mathematical model of airway heat distribution post-thermoplasty.In vivowe determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma.

In vitroairway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to ≥65°C.In silicosimulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼4 mm.In vivoat 6 weeks post-thermoplasty, there was an improvement in asthma control (measuredviaAsthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1–1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0–10; p=0.03) and epithelial integrity increased (14%, IQR 6–29; p=0.007). Neither of the latter two outcomes was related to improved asthma control.

Integratedin vitroandin silicomodelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.
Dissemination of blaNDM-5 gene via an IncX3-type plasmid among non-clonal Escherichia coli in China
Authors: Li Xi , Fu Ying , Shen Mengyuan , Huang Danyan , Du Xiaoxing , Hu Qingfeng , Zhou Yonglie , Wang Dairong , Yu Yunsong
Published: April 2018

Background

The emergence and spread of New Delhi metallo-β-lactamase-producing Enterobacteriaceae has been a serious challenge to manage in the clinic due to its rapid dissemination of multi-drug resistance worldwide. As one main type of carbapenemases, New Delhi metallo-β-lactamase (NDM)is able to confer resistance to almost all β-lactams, including carbapenems, in Enterobacteriaceae. Recently, New Delhi metallo-β-lactamase-5 attracted extensive attention because of increased resistance to carbapenems and widespread dissemination. However, the dissemination mechanism of blaNDM-5 gene remains unclear.

Methods

A total of 224 carbapenem-resistant Enterobacteriaceae isolates (CRE) were collected from different hospitals in Zhejiang province. NDM-5-positive isolates were identified and subjected to genotyping, susceptibility testing, and clinical data analysis. We established the genetic location of blaNDM-5 with southern blot hybridisation, and analysed plasmids containing blaNDM-5 with filter mating and DNA sequencing.

Results

Eleven New Delhi metallo-β-lactamase-5 (NDM-5)-producing strains were identified, including 9 Escherichia coli strains, 1 Klebsiella pneumoniae strain, and 1 Citrobacter freundii strain. No epidemiological links for E. coli isolates were identified by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). S1-PFGE and southern blot suggested that the blaNDM-5 gene was located on a 46-kb IncX3-type plasmid in all isolates. Nine of the 11 isolates (81.8%) tested could successfully transfer their carbapenem-resistant phenotype to E. coli strain C600. Moreover, sequence analysis further showed that this plasmid possessed high sequence similarity to most of previously reported blaNDM-5-habouring plasmids in China.

Conclusion

The present data in this study showed the IncX3 type plasmid played an important role in the dissemination of blaNDM-5 in Enterobacteriaceae. In addition, to the best of our knowledge, this report is the first to isolate both E. coli and C. freundii strains carrying blaNDM-5 from one single patient, which further indicated the possibility of blaNDM-5 transmission among diverse species. Close surveillance is urgently needed to monitor the further dissemination of NDM-5-producing isolates.
Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis
Authors: Kim Kang Ho , Choi Jong Min , Li Feng , Arizpe Armando , Wooton-Kee Clavia Ruth , Anakk Sayeepriyadarshini , Jung Sung Yun , Finegold Milton J , Moore David D
Published: April 2018

Progressive familial intrahepatic cholestasis (PFIC) is a genetically heterogeneous disorder of bile flow disruption due to abnormal canalicular transport or impaired bile acid (BA) metabolism, causing excess BA accumulation and liver failure. We previously reported an intrahepatic cholestasis mouse model based on loss of function of both farnesoid X receptor (FXR; NR1H4) and a small heterodimer partner (SHP; NR0B2) [double knockout (DKO)], which has strong similarities to human PFIC5. We compared the pathogenesis of DKO livers with that of another intrahepatic cholestasis model,Bsep−/−, which represents human PFIC2. Both models exhibit severe hepatomegaly and hepatic BA accumulation, but DKO showed greater circulating BA and liver injury, andBsep−/− had milder phenotypes. Molecular profiling of BAs uncovered specific enrichment of cholic acid (CA)–derived BAs in DKO livers but chenodeoxycholate-derived BAs inBsep−/− livers. Transcriptomic and proteomic analysis revealed specific activation of CA synthesis and alternative basolateral BA transport in DKO but increased chenodeoxycholic acid synthesis and canalicular transport inBsep−/−. The constitutive androstane receptor (CAR)/pregnane X receptor (PXR)–CYP2B/CYP2C axis is activated in DKO livers but not in other cholestasis models. Loss of this axis inFxr:Shp:Car:Pxr quadruple knockouts blockedCyp2b/Cyp2c gene induction, impaired bilirubin conjugation/elimination, and increased liver injury. Differential CYP2B expression in DKO andBsep−/− was recapitulated in human PFIC5 and PFIC2 livers. In conclusion, loss of FXR/SHP results in distinct molecular pathogenesis and CAR/PXR activation, which promotesCyp2b/Cyp2c gene transcription and bilirubin clearance. CAR/PXR activation was not observed inBsep−/− mice or PFIC2 patients. These findings provide a deeper understanding of the heterogeneity of intrahepatic cholestasis.
Contrast thresholds reveal different visual masking functions in humans and praying mantises
Authors: Tarawneh Ghaith , Nityananda Vivek , Rosner Ronny , Errington Steven , Herbert William , Arranz-Paraíso Sandra , Busby Natalie , Tampin Jimmy , Read Jenny , Serrano-Pedraza Ignacio
Published: April 2018

Recently, we showed a novel property of the Hassenstein–Reichardt detector, namely that insect motion detection can be masked by ‘undetectable’ noise, i.e. visual noise presented at spatial frequencies at which coherently moving gratings do not elicit a response (Tarawneh et al., 2017). That study compared the responses of human and insect motion detectors using different ways of quantifying masking (contrast threshold in humans and masking tuning function in insects). In addition, some adjustments in experimental procedure, such as presenting the stimulus at a short viewing distance, were necessary to elicit a response in insects. These differences offer alternative explanations for the observed difference between human and insect responses to visual motion noise. Here, we report the results of new masking experiments in which we test whether differences in experimental paradigm and stimulus presentation between humans and insects can account for the undetectable noise effect reported earlier. We obtained contrast thresholds at two signal and two noise frequencies in both humans and praying mantises (Sphodromantis lineola), and compared contrast threshold differences when noise has the same versus different spatial frequency as the signal. Furthermore, we investigated whether differences in viewing geometry had any qualitative impact on the results. Consistent with our earlier finding, differences in contrast threshold show that visual noise masks much more effectively when presented at signal spatial frequency in humans (compared to a lower or higher spatial frequency), while in insects, noise is roughly equivalently effective when presented at either the signal spatial frequency or lower (compared to a higher spatial frequency). The characteristic difference between human and insect responses was unaffected by correcting for the stimulus distortion caused by short viewing distances in insects. These findings constitute stronger evidence that the undetectable noise effect reported earlier is a genuine difference between human and insect motion processing, and not an artefact caused by differences in experimental paradigms.
Loss of PTEN promotes formation of signaling-capable clathrin-coated pits
Authors: Rosselli-Murai Luciana K. , Yates Joel A. , Yoshida Sei , Bourg Julia , Ho Kenneth K. Y. , White Megan , Prisby Julia , Tan Xinyu , Altemus Megan , Bao Liwei , Wu Zhi-Fen , Veatch Sarah L. , Swanson Joel A. , Merajver Sofia D. , Liu Allen P.
Published: April 2018

Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs. The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], which is dephosphorylated by phosphatase and tensin homolog (PTEN), is a potent tumorigenic signaling lipid. By using total internal reflection fluorescence microscopy and automated tracking and detection of CCPs, we found that EGF-bound EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that correspond with clathrin-dependent EGF-induced signaling. We demonstrated that PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased PI(3,4,5)P3 resulted in higher proportion of short-lived CCPs, an effect that recapitulates PTEN deletion. Altogether, our findings provide evidence for the existence of short-lived ‘signaling-capable’ CCPs.
Multiple roles of epithelial heparan sulfate in stomach morphogenesis
Authors: Huang Meina , He Hua , Belenkaya Tatyana , Lin Xinhua
Published: April 2018

Heparan sulfate proteoglycans (HSPGs) have been shown to regulate various developmental processes. However, the function of heparan sulfate (HS) during the development of mammalian stomach has not been characterized yet. Here, we investigate the role of epithelial HS in embryonic stomach by examining mice deficient in the glycosyltransferase gene Ext1. We show that HS exhibits a specific and dynamic expression pattern in mouse embryonic stomach. Depletion of the epithelial HS leads to stomach hypoplasia, with phenotypic differences in the gastric mucosa between the forestomach and hindstomach. In the posterior stomach, HS depletion disrupts glandular stomach patterning and cytodifferentiation via attenuation of Fgf signaling activity. Inhibition of Fgf signaling in vitro recapitulates the patterning defect. Ligand and carbohydrate engagement assay (LACE) reveals a diminished assembly of Fgf10 and Fgfr2b in the mutant. In the anterior stomach, loss of epithelial HS leads to stratification and differentiation defects of the multilayered squamous epithelium, along with reduced Hh and Bmp signaling activity. Our data demonstrate that epithelial HS plays multiple roles in regulating mammalian stomach morphogenesis in a regional-specific manner.
Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems
Authors: Alzaid Abdullah , Kim Jin-Hyoung , Devlin Robert H. , Martin Samuel A. M. , Macqueen Daniel J.
Published: April 2018

Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system, an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterizing muscle immune responses in size-matched coho salmon (Oncorhynchus kisutch) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth, a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30h post-injection with PBS (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared to wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation.
Fiscal Centralization: Theory and Evidence from the Great Depression
Authors: Coen-Pirani Daniele , Wooley Michael
Published: April 2018

The Great Depression produced a profound and lasting influence on the structure of US government. This paper studies theoretically and empirically the increased centralization of revenues and expenditures by the states relative to local governments during this period. A model of property and sales taxation and tax delinquency is introduced. In the model, the income decline of the Depression causes a rise in property tax delinquency and leads to a shift toward sales taxation and fiscal centralization by the states. Empirical evidence based on cross-state variation in the severity of the Depression is consistent with the model's key predictions. (JEL E32, H25, H71, H72, H77, N12, N42)
How Do Changes in Housing Voucher Design Affect Rent and Neighborhood Quality?
Authors: Collinson Robert , Ganong Peter
Published: April 2018

US housing voucher holders pay their landlord a fraction of household income and the government pays the rest, up to a rent ceiling. We study how two types of changes to the rent ceiling affect landlords and tenants. A policy that makes vouchers more generous across a metro area benefits landlords through increased rents, with minimal impact on neighborhood and unit quality. A second policy that indexes rent ceilings to neighborhood rents leads voucher holders to move into higher quality neighborhoods with lower crime, poverty, and unemployment. (JEL I38, R23, R31, R38)
The Fall of Coal: Joint Impacts of Fuel Prices and Renewables on Generation and Emissions
Authors: Fell Harrison , Kaffine Daniel T.
Published: April 2018

Since 2007, US coal-fired electricity generation has declined by a stunning 25 percent. Detailed daily unit-level data is used to examine the joint impact of natural gas prices and wind generation on coal-fired generation and emissions, with a focus on the interaction between gas prices and wind. This interaction is found to be significant. Marginal responses of coal-fired generation to natural gas prices (wind) in 2013 were larger, sometimes much larger, than the counterfactual with 2008 wind generation (gas prices). Additionally, these factors jointly account for the vast majority of the observed decline in generation and emissions. (JEL L94, L95, Q35, Q38, Q42, Q53)
Selection and Market Reallocation: Productivity Gains from Multinational Production
Authors: Alfaro Laura , Chen Maggie X.
Published: April 2018

Assessing productivity gains from multinational production has been a vital topic of economic research and policy debate. Positive productivity gains are often attributed to productivity spillovers; however, an alternative, much less emphasized channel is selection and market reallocation, whereby competition leads to factor and revenue reallocation within and between domestic firms and exits of the least productive firms. We investigate the roles of these different mechanisms in determining aggregate-productivity gains using a unifying framework that explores the mechanisms' distinct predictions on the distributions of domestic firms: within-firm productivity improvement shifts rightward or reshapes the productivity distribution, while selection and market reallocation move the revenue and employment distributions leftward and raise left truncations. Using a rich cross-country firm-level panel dataset, we find significant evidence of both mechanisms and effects of competition in product, technology, and labor space. However, selection and market reallocation account for the majority of aggregate-productivity gains, suggesting ignoring this channel could lead to substantial bias in understanding the nature of productivity gains from multinational production. (JEL D22, D24, F14, F23, G32, O47)
Cash-on-Hand and College Enrollment: Evidence from Population Tax Data and the Earned Income Tax Credit
Authors: Manoli Day , Turner Nicholas
Published: April 2018

We estimate causal effects of cash-on-hand on college enrollment decisions of students from low-income families. Using population-level, administrative data from US income tax returns, we exploit variation in tax refunds received in the spring of the high school senior year. The variation in tax refunds results from the kink point between the phase-in and maximum credit portions of the Earned Income Tax Credit schedule. The results suggest tax refunds received in the spring of the high school senior year have meaningful effects on college enrollment. (JEL D14, H24, I22, I23, I24)
Non-HDL cholesterol is better than LDL-c at predicting atherosclerotic cardiovascular disease risk factors clustering, even in subjects with near-to-normal triglycerides: A report from a Venezuelan population
Authors: Bermúdez Valmore , Torres Wheeler , Salazar Juan , Martínez María Sofía , Rojas Edward , Olivar Luis Carlos , Lameda Victor , Ortega Ángel , Ramírez Paola , Rojas Milagros , Rastogi Sheena , D’Addosio Rosanna , Hoedebecke Kyle , Graterol Modesto , Graterol Resemily , Wilches Sandra , de Bravo Mayela Cabrera , Rojas-Quintero Joselyn
Published: April 2018

Background: Non-high density lipoprotein cholesterol (non-HDL-c) has emerged as an important tool in primary prevention of atherosclerotic cardiovascular disease (ASCVD), especially among those at high risk. The main objective of this study was to evaluate the predictive value of non-HDL-c for the coexistence aggregation of multiple ASCVD risk factors and compare this with LDL-c in general subjects with normal or near normal triglycerides from Maracaibo city in Venezuela.

Methods: This is a descriptive, cross-sectional study with a randomized multistage sampling. 2026 subjects were selected for this study, all were adults ≥18 years old of both genders and inhabitants of Maracaibo city, Venezuela. A complete history and physical medical assessment was performed. A multivariate logistic regression model was used to determine the odds ratio (CI95%) for the coexistence of multiple risk factors for ASCVD.

Results: The median (p25-p75) of non-HDL-c was 143 mg/dL (114-174 mg/dL). 52.1% (n=1056) of the sample were women, with a median of 144 mg/dL (115-174 mg/dL) among women and 143 mg/dL (114-17 4mg/dL) among men; p=0.740. Individuals ≥50 years old, smokers, those with hypertension, obesity, diabetes, high waist circumference and elevated hs-C Reactive Protein, all had higher levels of non-HDL-c. A lower median was observed among those <30 years of age with elevated physical activity levels in their leisure time. Non-HDL-c between 130-159 mg/dL (OR=2.44; CI 95%=1.48-4.02; p<0.001) and ≥160 mg/dL (OR=3.28; CI 95%=1.72-6.23; p<0.001) was associated with greater risk of coexistent multiple risk factors for ASCVD, albeit LDL-c was not significant in the multivariate model.

Conclusions: Elevated non-HDL-c was associated with conglomeration of multiple risk factors for ASCVD. This suggests evaluation of non-HDL-c may be of better utility in primary care for early identification of subjects for high risk of ASCVD. Future research might focus on the influence of non-HDL-c in cardiovascular mortality.
TDG regulates cell cycle progression in human neural progenitors
Authors: Germanguz Igal , Park Jenny C. , Cinkornpumin Jessica , Solomon Aryeh , Ohashi Minori , Lowry William E.
Published: April 2018

Background: As cells divide, they must both replicate their DNA and generate a new set of histone proteins.  The newly synthesized daughter strands and histones are unmodified, and must therefore be covalently modified to allow for transmission of important epigenetic marks to daughter cells.  Human pluripotent stem cells (hPSCs) display a unique cell cycle profile, and control of the cell cycle is known to be critical for their proper differentiation and survival.  A major unresolved question is how hPSCs regulate their DNA methylation status through the cell cycle, namely how passive and active demethylation work to maintain a stable genome. Thymine-DNA glycosylase (TDG), an embryonic essential gene, has been recently implicated as a major enzyme involved in demethylation.

Methods: We use human pluripotent stem cells and their derivatives to investigate the role of TDG in differentiation and proliferation.  To perform loss of function of TDG, RNA Interference was used.  To study the cell cyle, we engineered human pluripotent stem cells to express the FUCCI tool which marks cells at various stages of the cell cycle with distinct patterns of fluorescent proteins.  We also used cell cycle profiling by FACS, and DNA methylation analysis to probe a connection between DNA demethylation and cell cycle.

Results: Here we present data showing that TDG regulates cell cycle dynamics in human neural progenitors (NPCs) derived from hPSCs, leading to changes in  cell cycle related gene expression and neural differentiation capacity.  These data show that loss of TDG function can block differentiation by driving proliferation of neural progenitors.  We also identify specific cell cycle related genes whose expression changes upon loss of TDG expression.

Conclusions: These observations suggest that TDG and active demethylation play an important role in hPSC cell cycle regulation and differentiation.
Preliminary investigation of deoxyoligonucleotide binding to ribonuclease A using mass spectrometry: An attempt to develop a lab experience for undergraduates
Authors: Clark Daniel D.
Published: April 2018

Deoxyoligonucleotide binding to bovine pancreatic ribonuclease A (RNase A) was investigated using electrospray ionization ion-trap mass spectrometry (ESI-IT-MS). Deoxyoligonucleotides included CCCCC (dC5) and CCACC (dC2AC2).  This work was an attempt to develop a biochemistry lab experience that would introduce undergraduates to the use of mass spectrometry for the analysis of protein-ligand interactions.  Titration experiments were performed using a fixed RNase A concentration and variable deoxyoligonucleotide concentrations.  Samples at equilibrium were infused directly into the mass spectrometer under native conditions.  For each deoxyoligonucleotide, mass spectra showed one-to-one binding stoichiometry, with marked increases in the total ion abundance of ligand-bound RNase A complexes as a function of concentration, but the accurate determination of dC5and dC2AC2dissociation constants was problematic.
Case Report: Exome sequencing reveals recurrent RETSAT mutations and a loss-of-function POLDIP2 mutation in a rare undifferentiated tongue sarcoma
Authors: Chan Jason Y. K. , Poon Peony Hiu Yan , Zhang Yong , Ng Cherrie W. K. , Piao Wen Ying , Ma Meng , Yip Kevin Y. , Chan Amy B. W. , Lui Vivian Wai Yan
Published: April 2018

Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namelyPOLDIP2(DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation geneRETSAT(retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations toPOLDIP2, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 andNOTCH1germline mutations of the patient’s blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.