cssi/SciSciGPT-SciSciNet huggingface dataset:
Transforming growth factor-Beta binds reversibly in vitro to guglielmi detachable coils.

SUMMARY We determined the propensity for and reversibility of transforming growth factor-beta(TGFbeta) binding to uncoated Guglielmi Detachable Coils (GDC) and to GDC coated with extracellular matrix (ECM) proteins. Three 1.0 centimetre samples each of uncoated GDC-18 and of GDC-18 coated with either poly-L-lysine, laminin, type I collagen, type IV collagen, fibronectin, or poly-L-lysine and laminin were prepared. These samples were immersed briefly in a solution containing I(125)-labelled TGFbeta at a concentration of 0.225 mug/ml with initial specific activity of 123.3 mCi/mg (DuPont-NEN, Billerica, MA), and were counted using a scintillation counter. Each sample was then placed in a vial containing saline, shaken for 60 seconds, and counted again. Selected samples were immersed for varying periods within the TGFbeta solution and counted before and after saline rinse. Samples were rinsed one week after initial rinsing and counted again. The amount of binding between coil types was compared using the Student t test. For all samples initial binding of TGFbeta was in the order of 60-120 pg/cm. For the pre-rinse data there were no statistically significant differences between the amount bound to any single coil coating type relative to other coatings. Compared to the initial accumulations, the amount remaining after rinsing ranged from 40% (poly-L-lysine) to 63% (poly-L-lysine with laminin), with a mean of 55% among the seven coil types. After rinsing there was more growth factor remaining on uncoated coils than on poly-L-lysine-coated coils (p=0.05), fibronectin-coated coils (p=0.01), and type IV collagen-coated coils (p=0.04). There was a trend toward greater residual growth factor on coils coated with poly-L-lysine and laminin compared to coils coated with poly-L-lysine alone (p=0.10). Delayed, second rinsing of the samples one week after initial testing demonstrated only minor incremental loss of TGFbeta from the coil surfaces. After five minutes of immersion, accumulation was approximately 200% greater than that noted with brief submersion, but immersions lasting over five minutes did not yield increasing levels of TGFbeta binding. TGFbeta binds to GDC coils. Binding is not improved with ECM protein-coated coils compared to uncoated coils. The absolute amount of TGFbeta bound to the coil will likely result in local concentrations of growth factor in the order of those required for biological activity in vivo.
The predictive value of flow cytometric information in the clinical management of stage O (Ta) bladder cancer.

AbstractTwo blind retrospective flow cytometric studies were performed on archival stage O (Ta) papillary grades 1 to 2 transitional cell carcinomas of the bladder to learn whether deoxyribonucleic acid histogram patterns predict disease recurrence and progression. All patients with aneuploid histograms as predicted experienced recurrent disease. In 20 of 28 cases of recurrent disease the ploidy pattern changed during recurrence. Because of this finding we predicted disease progression if 2 or more histograms in the sequence were aneuploid. Two-thirds (8 of 12) of those having more than 1 aneuploid tumor incident experienced invasion, while only approximately a third (6 of 16) lacking repetitive aneuploidy had invasion. Furthermore, of the patients with 2 aneuploid lesions half had progression within 1 year and two-thirds within 2 years after the second aneuploid lesion. Therefore, it appears that in this disease deoxyribonucleic acid histograms can provide prognostic information beyond that obtained from...
Sex Differences in Binge Eating: Gonadal Hormone Effects Across Development

Eating disorders are highly sexually differentiated disorders that exhibit a female predominance in risk. Most theories focus on psychosocial explanations to the exclusion of biological/genetic influences. The purpose of this descriptive review is to evaluate evidence from animal and human studies in support of gonadal hormone effects on sex differences in binge eating. Although research is in its nascent stages, findings suggest that increased prenatal testosterone exposure in males appears to protect against binge eating. Although pubertal testosterone may exert additional protective effects, the prenatal period is likely critical for the decreased risk observed in males. By contrast, studies indicate that, in females, it is the lack of prenatal testosterone coupled with the organizational effects of pubertal ovarian hormones that may lead to increased binge eating. Finally, twin data suggest that changes in genetic risk may underlie these hormone influences on sex differences across development.
Mathematics & Economics: A Reality Check (Presentation Slides)

Economics (and by extension finance) is arguably one of the most mathematical fields of research. However, economists’ choice of math may be inadequate to model the complexity of social institutions. In a constructive spirit, this note offers some advice on how students could increase their chances of having a successful career in 21st century finance. Practitioners seeking to enhance their skill set may also draw some ideas.
Abstract 413: Lipoprotein SCARB1 Intronic Variant Associated With Increased Coronary Heart Disease Risk Affects Cardio-Protective Gene Networks

Introduction: We previously reported a common intronic SCARB1 (12q24.31) variant, rs10846744, located in an enhancer region, to be significantly associated with coronary artery disease (CAD) in the Multi-Ethnic Study of Atherosclerosis (MESA). RNA-Seq showed expression of the immune checkpoint inhibitor lymphocyte activation gene 3 ( LAG3 , 12p13.31), to be 5-fold lower in carriers of the risk allele, while low plasma LAG3 protein levels were also significantly associated with increased CAD risk in MESA, after multivariate regression analysis. Hypothesis: That the SCARB1 rs10846744 variant disrupts long-range transcriptional regulation of LAG3 disturbing cardio-protective and anti-inflammatory gene networks to promote CAD. Methods and Results: Using functional genomics (HiC global chromatin capture, ChIP-Seq and RNA-Seq) in reference and risk EBV-transformed B lymphocytes to assess 3D chromatin architecture and gene-gene interactions at a 2.5kb resolution, we did not observe direct chromatin contacts between SCARB1 and LAG3. In the reference allele, an enhancer-rich intermediate contact (12q13.13) was found containing genes associated with cholesterol ( SOAT2 ) and NR2F2 signaling ( RARG ). This same 12q13.13 region was in direct contact with 22q12.3 ( APOLI) , an apoprotein associated with HDL and innate immunity. Micro-looping within the rs10846744 12q24.31 region showed direct contacts with other enhancers ( NCOR2 ) and cardiovascular loci ( TMEM132B ), while LAG3 micro-looping on 12p13.31 was associated with immune regulatory networks ( CD4 ). Loci associated with viral infection, cytokine production, heart failure and autoimmunity were also identified. NR2F2 disrupted contacts in the risk allele, implicating NR2F2 as a dysfunctional rs10846744 transcriptional repressor altering gene networks. The risk allele included contacts near PCSK9 , VLDLR and 2q33.1, a CAD locus. Conclusion: Functional genomics of the SCARB1 rs10846744 enhancer region identified a number of intra- and inter-chromosomal chromatin contacts in reference cells that were markedly disrupted in risk cells. Perturbing NR2F2 and/or genes disrupted in the SCARB1 -NR2F2 immuno-cardiovascular axis may protect against CAD in the rs10846744 risk population.
Expectant use of CIC in newborns with spinal dysraphism: Report of clinical outcomes.

PURPOSE Report urologic outcomes among newborns with spinal dysraphism managed within an expectant clean intermittent catheterization (CIC) program. METHODS Newborns were followed clinically and with serial ultrasound (US). Urodynamics (UD) and dimercaptosuccinic acid (DMSA) renal scan were obtained at 3-6 months, 1 year, 3 years, then as needed. Patients with initial evaluation after 6 months were excluded. RESULTS Median follow-up was 3.2 years. 11/102 began catheterization for continence (median 4.0 years) and 47/102 did not start CIC. Of these, 2/58 developed a DMSA abnormality. 44/102 began CIC early, often for elevated storage pressures and febrile urinary tract infection (UTI). Of these, 20/44 developed a DMSA abnormality including 9 who had abnormality detected prior to starting CIC. Being on CIC or starting immediately upon recognition of new hydronephrosis, reflux, elevated filling pressures, or febrile UTI was associated with lower chance of DMSA abnormalities (4/17, 24%) compared to delaying CIC (16/27, 60%) (p= 0.03). CONCLUSIONS CIC can be deferred until continence in select infants with a low risk of significant DMSA abnormality. However, immediate initiation of CIC upon recognition of risk factors is recommended as this was associated with fewer DMSA abnormalities than delaying CIC. Recommendations for expectantly-managed patients include close follow-up, serial US and UD, and prompt initiation of CIC upon recognition of new hydronephrosis, reflux, elevated storage pressures, or febrile UTIs.
Determination of the applicability of CERCLA's petroleum exclusion at contaminated sites – focus on metals

Areas impacted by petroleum refining and handling operations may become subject to CERCLA enforcement. Because of CERCLA's petroleum exclusion clause, determining whether contamination in a CERCLA Site originated from petroleum products or hazardous wastes becomes important. Because certain metals are typically enriched in wastes relative to petroleum products and background soils, knowledge of metal contents in these potential end member metal sources is an important step towards contaminant source identification in soils and sediments. In LNAPL plumes, metal content, particularly lead, may be claimed to be the result of wastes mishandling and not due only to the presence of leaded gasoline in the plume. Analysis of the percent gasoline in the plume and accounting for weathering are steps to determining whether the lead content in an LNAPL plume is within the historical lead concentration ranges in gasolines. In addition to metals analyses, understanding of operational parameters such as the hist...
Trajectories of Variables Related to Cardio-Metabolic Risk from Childhood to Young Adulthood

The Framingham Study which coined the term “risk factors” in middle-aged and older populations, provided the rationale for bridging the gap from youth to aging adults as part of the evolution of early natural history of cardiovascular (CV) diseases. This report details the time-course or trajectories of cardio-metabolic risk variables from childhood to adulthood in the Bogalusa Heart Study cohort. The observed adverse trajectories of body fatness, metabolic, and hemodynamic variables since childhood and the potential underlying mechanisms governing their interrelationships support a primary role of excess adiposity in the early natural histories of CV diseases, type 2 diabetes, and hypertension. These findings have implications for public health approaches to prevention.
Initiating value co-creation: Dealing with non-receptive customers

Scholarly emphasis on the significance of integrating customer and supplier work processes to co-create customer value is increasingly important. While suppliers and customers working closely is imperative for the success of the value co-creation (VCC) process, customers’ reluctance at times to allow suppliers into their environments has not been fully explored. The present study is an expansive qualitative inquiry consisting of 114 in-depth interviews across 57 business-to-business evaluations that aims to understand both the nuanced nature of customer non-receptivity to specific VCC initiatives and those strategies suppliers may adopt to successfully manage it. Findings elicit three potential kinds of customer non-receptivity: apathy, ambivalence, and annoyance. Furthermore, conclusions propose six strategies suppliers may use to manage customer non-receptivity: intrinsic initiative, inspiration and implementation, complexity absorption, value alignment, credibility building, and objective centrality.
Liver X Receptor Agonist Therapy Prevents Diffuse Alveolar Hemorrhage in Murine Lupus by Repolarizing Macrophages.

The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-α (LXRα) is an oxysterol-regulated transcription factor that promotes reverse cholesterol transport and alternative (M2) macrophage activation. Conversely, hypoxia-inducible factor 1-α (HIF1α) promotes classical (M1) macrophage activation. The objective of this study was to see if lupus can be treated by enhancing the generation of M2-like macrophages using LXR agonists. Peritoneal macrophages from pristane-treated mice had an M1 phenotype, high HIFα regulated phosphofructokinase and TNFα expression (quantitative PCR, flow cytometry), and low expression of the LXR α regulated gene ATP binding cassette subfamily A member 1 (Abca1) and Il10 vs. mice treated with mineral oil, a control inflammatory oil that does not cause lupus. Glycolytic metabolism (extracellular flux assays) and HIF1a expression were higher in pristane-treated mice (M1-like) whereas oxidative metabolism and LXRα expression were higher in mineral oil-treated mice (M2-like). Similarly, lupus patients’ monocytes exhibited low LXRα/ABCA1 and high HIF1α vs. controls. The LXR agonist T0901317 inhibited type I interferon and increased ABCA1 in lupus patients’ monocytes and in murine peritoneal macrophages. In vivo, T0901317 induced M2-like macrophage polarization and protected mice from diffuse alveolar hemorrhage, an often fatal complication of lupus. We conclude that end-organ damage (diffuse alveolar hemorrhage) in murine lupus can be prevented using an LXR agonist to correct a macrophage differentiation abnormality characteristic of lupus. LXR agonists also decrease inflammatory cytokine production by human lupus monocytes, suggesting that these agents may be have a role in the pharmacotherapy of lupus
Multiple Origins of Neocortex: Contributions of the Dorsal Ventricular Ridge

The uniqueness of mammalian neocortex may ultimately only be clarified with improved understanding of the evolutionary origins of cortical structure and cortical functions. Comparative studies of the organization of the nonmammalian and mammalian telencephalon may provide valuable clues for understanding the evolution of neocortex. In the nonmammalian telencephalon, there are neuronal populations which correspond to cell groups in the neocortex of mammals in terms of connections, single unit-responses, and functions. Some of these populations lying within the dorsal ventricular ridge, however, are organized in a non-laminar, rather than laminar fashion. These observations suggest that the emergence of basic “cortical” circuit and laminar organization are distinct evolutionary events that can be differentiated and studied independently in order to understand each of their respective contributions to the cognitive functions of the neocortex. Moreover, in contrast to an argument that many cortical visual areas are derived from a single area by gene duplication (Allman, 1977, in press), the origins of neocortex can be separable into at least the precursors of non-laminar and laminar regions, and thus multiple evolutionary origins of neocortex are proposed.
Prospective, double blinded, comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke.

Abstract Background Our previous work in acute ischemic stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after embolic stroke in a rodent model. Methods Male Wistar rats were subjected to embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. Results Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p Conclusion Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after stroke.
Effects of angiotensin-II on brain endothelial cell permeability via PPARalpha regulation of para- and trans-cellular pathways

Angiotensin-II (Ang-II) is a key factor in hypertension, diabetes and aging, which are all primary risk factors for CNS disease. Furthermore, Ang-II may play under-appreciated roles in neurogenesis, angiogenesis and CNS remodeling. Therefore, any contemplated attempts for neurorestorative therapies in the CNS should consider the context of Ang-II signaling. Here, we investigate how Ang-II may regulate cerebral endothelial permeability, a key functional feature of the neurovascular unit. Exposure of human brain endothelial cell cultures to Ang-II increased its permeability to BSA-Alexa488 tracer. Immunocytochemistry and pulse-chase experiments suggested that both para-cellular as well as trans-cellular pathways were involved. Candesartan but not PD123319 blocked Ang-II permeability effects, suggesting that Ang-II effects may be mediated via type 1 receptor. Immunocytochemistry and western blots showed that Ang-II disrupted the membrane distributions of ZO-1 and VE-Cad, decreased total levels of JAM-A and Mfsd2a, and increased Cav1. These effects of Ang-II were accompanied by dephosphorylation of PPARalpha. Finally, Ang-II-induced increases in endothelial permeability were ameliorated by PPARalpha agonists. Taken together, these studies suggest that Ang-II may disrupt both para- and trans-cellular permeability in cerebral endothelium, and PPARalpha-related pathways may offer potential therapeutic targets for ameliorating these effects in cell-based regenerative medicine.
High-pressure nano-seismology: Use of micro-ring resonators for characterizing acoustic emissions

Microring resonator (MRR) ultrasound detectors provide orders of magnitude greater sensitivity and frequency range (to < 10 Pa, from DC to 100 s of MHz) than previously achieved in recording acoustic emissions from materials at high pressures. We characterize acoustic emissions from crystal-structural phase transitions in Si to pressures of 50 GPa, well beyond the brittle-ductile transition at room temperature, and find that the number of events increases nearly tenfold for each decade reduction in the duration of recorded events. The shortest-duration events arrive in clusters, suggestive of a self-propagating, transformation-catalyzed process.
Belonging and boundaries in Little Guyana: Conflict, culture, and identity in Richmond Hill, New York:

Research on the assimilation of contemporary second-generation Americans has shown that ethnic enclaves are saturated with several cultural, religious, and transnational amenities that facilitate t...
Patterns of Pediatric Firearm-Related Ocular Trauma in the United States.

Importance Gun violence represents a substantial public health issue, and firearm-related injuries rank second among the causes of injury-related deaths in children aged 0 to 17 years in the United States. Ocular trauma from firearm-related injuries can lead to devastating vision loss, but little is known to date about the specific demographics and characteristics of such injuries in children. Objective To evaluate the epidemiologic pattern of pediatric firearm-related ocular injuries. Design, Setting, and Participants This retrospective analysis used deidentified data from the National Trauma Data Bank, the largest national registry of hospitalized trauma cases in the United States. The firearm-related ocular injuries (n = 1972) of pediatric patients (defined as those younger than 21 years) hospitalized between January 1, 2008, and December 31, 2014, were analyzed. Statistical analyses were conducted from July 15, 2017, to June 15, 2019. Exposure Firearm-related ocular trauma. Main Outcomes and Measures Pediatric patients with firearm-related ocular injuries were identified usingInternational Classification of Diseases, Ninth Revision, Clinical Modificationcodes and external causes of injury codes. Patient demographics (age, sex, and race/ethnicity), type of ocular injury, injury intent, geographic location, length of hospital admission, health insurance status, disposition at discharge, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were collected. Results A total of 8715 firearm-related ocular injuries were identified. Of these injuries, 1972 (22.6%) occurred in pediatric patients, most of whom were male (1678 [85.1%]) and adolescents (1037 [52.6%]), with a mean (SD) age of 15.2 (5) years. Common locations of injury were home (761 [38.6%]) and street (490 [24.8%]). Mean (SD) hospital length of stay was 7.6 (12) days, ISS was 16 (13.1), and GCS score was 11 (5.1). The most common types of firearm-related ocular injuries were open wound of the eyeball (820 [41.6%]) and ocular adnexa (502 [25.5%]), orbital injuries or fractures (591 [30.0%]), and contusion of the eye or adnexa (417 [21.1%]). Patients aged 0 to 3 years had greater odds of unintentional injuries (odds ratio [OR], 4.41; 95% CI, 2.51-7.75;P Conclusions and Relevance This study found that pediatric firearm-related ocular injuries from 2008 through 2014 were predominantly sight-threatening and associated with traumatic brain injury. If the possible risk factors, including sex, age, race/ethnicity, and injury intention, can be confirmed for 2015 through 2019, these findings may be useful in developing strategies to prevent pediatric firearm-related ocular injuries.
Prophylactic arterial ligation following transoral robotic surgery: A systematic review and meta‐analysis

Prophylactic arterial ligation has been proposed to reduce the severity of postoperative hemorrhage following transoral robotic surgery (TORS). Previous studies have shown a trend toward a reduction in major and severe bleeding. Search strategies were implemented in multiple databases and completed in August 2018. Inclusion and exclusion criteria were designed to capture studies examining adults undergoing TORS for oropharyngeal cancer. Four retrospective studies were selected appropriate for analysis by two reviewers who independently extracted data. PRISMA guidelines were followed. A random-effects model was used for meta-analysis. Meta-analysis of 619 patients in four retrospective reviews showed that the pooled RR of major and severe bleeding events was significantly lower in prophylactically ligated patients (RR, 0.28; 95% CI, 0.08-0.92; I2 = 0). Prophylactic arterial ligation of external carotid artery branches is associated with a decreased risk of major and severe bleeding events, although confounding factors remain incompletely analyzed.
Climate effects of aerosols reduce economic inequality

The climate effects of anthropogenic aerosols have masked some of the warming induced by GHGs1 along with some impacts of that warming2. These temperature effects may be beneficial but are almost certainly overwhelmed by aerosols’ negative health impacts3. Recent analyses of economic impacts have concluded that warming harms economies in warm climates, but provides economic benefits in cold climates4. Here we investigate whether aerosol-induced cooling would have a positive effect on less wealthy economies in hotter regions and a negative effect on wealthier economies in colder regions. Climate simulations over the historical period both with and without anthropogenic aerosol emissions, using a fully coupled ocean and atmosphere climate model, indicate that in year 2010 anthropogenic aerosol emissions were cooling the Earth by 0.72 ± 0.02 °C relative to a scenario without such emissions. Due to opposing economic impacts in different regions, the net economic impact of aerosol-induced cooling is likely to be small at the global scale. However, these results suggest that the cooling effects of anthropogenic aerosols benefit developing tropical economies while harming developed high-latitude economies, and thus the temperature effects of past aerosol emissions have probably diminished global economic inequality. Anthropogenic aerosols mask some greenhouse warming via radiation scattering and cloud interactions. Research suggests the economic impact of this aerosol-induced cooling was small globally, although it benefitted developing countries in warm climates and harmed high-latitude developed countries.
Differences in human milk peptide release along the gastrointestinal tract between preterm and term infants.

Summary Background & aims Preterm infants are born with a gastrointestinal tract insufficiently developed to digesting large quantities of human milk proteins. Peptides released from the digestion of human milk proteins have been identified with bioactivities that may be beneficial to the developing infant. However, it is unknown how prematurity affects total and bioactive peptide release along the gastrointestinal tract. The aim of this study was to compare milk peptide release from milk to stomach to stool between preterm and term infants. Methods Milk, gastric, and stool samples were collected from preterm infants as early collection (days 8 and 9 of life) and late collection (days 21 and 22 of life), and from term infants as early collection. Milk peptides were extracted from the samples and identified using Orbitrap mass spectrometry. Peptide abundance and count were compared across digestion and between the three infant groups at each stage of digestion. Results Total milk peptide count and abundance increased from milk to stomach then decreased in stool. Total peptide release was similar among the three infant groups for milk and stool samples. In the stomach, preterm early collection had significantly higher peptide abundance and count than the other two groups. Patterns for peptide release from individual milk proteins were distinct from total peptide release both across digestion and among the infant groups. When analyzing single peptides, term early collection gastric samples had significantly higher peptide abundance than preterm early collection for a known antimicrobial peptide, QELLLNPTHQIYPVTQPLAPVHNPISV. Conclusions Preterm and term infants digest milk proteins differently along their gastrointestinal tracts. While preterm infants released more total peptides in the stomach, term infants released specific bioactive peptides at higher abundance. We identified a region at the C-terminus of β-casein that is conserved from milk through stool and from which are released known and potential antimicrobial peptides.
LAS FILOSOFÍAS DE LA CIENCIA DE THOMAS KUHN: DEL CICLO REVOLUCIONARIO AL ÁRBOL EVOLUTIVO

En este articulo exploro la transicion en el pensamiento de Kuhn hacia una filosofia evolutiva de la ciencia a partir de una filosofia historica de la ciencia. Esta primera filosofia de la ciencia de Kuhn se ha representado repetidas veces como un proceso ciclico en el que una antigua ciencia normal da lugar a un nueva ciencia normal a traves de una revolucion cientifica o un cambio de paradigma. Mas tarde en su carrera Kuhn rechaza la filosofia historica de la ciencia y se vuelca hacia una filosofia evolutiva. En lugar de entender el progreso cientifico como un levantamiento revolucionario, lo concibe ahora como la creciente especializacion de las disciplinas cientificas. De ahi que, en contraste con un ciclo revolucionario, un arbol evolutivo representa mejor la filosofia de la ciencia madura de Kuhn acerca de como progresa de la ciencia.
A challenging case of alpha-fetoprotein-result discrepancies in a patient with chronic hepatitis B.

Alpha-fetoprotein (AFP) is the most abundant serum protein found in the human fetus, produced by the yolk sac and the liver [1]. The levels of maternal serum AFP reach a peak value at ∼28–32 weeks of gestation and decrease rapidly after birth and usually drop to the normal at 8–12 months of age. The normal serum AFP level for an adult is <20 ng/mL [2]. In contrast, liver-tumor cells usually synthesize and secrete an increased level of AFP. Abdominal ultrasound and AFP are generally recommended as the screening modality for HCC for patients at risk for development of hepatocellular carcinoma (HCC) [1]. AFP-L3, an isoform of AFP that binds Lens culinaris agglutinin, can be particularly useful in the early identification of aggressive HCC [2]. These assays, however, can generate false-positive and false-negative AFP values. Of patients with advanced HCC, ∼20% had normal AFP levels, whereas some patients with liver diseases had significant AFP elevation without liver cancer in long-term surveillance [3]. Elevated AFP levels could be associated with active liver diseases with hepatocyte regeneration [4, 5]. In that setting, the AFP level will decline with improvement of the underlying liver condition. Our case illustrated the dilemma and uncertainties as a result of persistent abnormal AFP values after extensive clinical investigations.
Network meta-analysis comparing the effectiveness of anticoccidial drugs and anticoccidial vaccination in broiler chickens

With the trend to organic production and concerns about using antibiotic feed additives, the control of infections with Eimeria spp. in broiler flocks has become more difficult. Vaccination against coccidia is an alternative, but there are concerns that the live vaccines used might have negative effects on production parameters and intestinal health. Reports of experiments directly comparing anticoccidial drugs and anticoccidial vaccines are rare. This network meta-analysis (NMA) identified and analyzed 61 articles reporting 63 experiments testing anticoccidial drugs and anticoccidial vaccines under conditions resembling commercial broiler production. The effect sizes were mean differences in body weight/body weight gain (BW/BWG) and feed conversion rate (FCR) between the 175 included groups. The results show that groups vaccinated against coccidia have a similar BW/BWG and FCR at processing age compared to groups given anticoccidial drugs. However, the results tended to be more favorable for anticoccidial drugs than for vaccines. The analysis of eight subsets, containing only groups (1) groups that had not received an AGP in addition to an anticoccidial drug, (2) groups that had not received ionophores, (3) groups that had not received chemicals, (4) groups that had not received an attenuated vaccine, (5) groups that had not received a fully virulent vaccine, (6) groups that were not additionally challenged with bacteria or not challenged, (7) groups that had received a severe challenge as defined by a total infection dose of more than 100,000 oocysts or were not challenged, (8) groups that were challenged on day 15 or earlier or not challenged brought similar results and confirmed the robustness of the NMA. In addition, the analysis exposes unnecessary, as well as inherent, problems with data quality, which every researcher working with coccidia should carefully consider, and identifies under-researched areas that should be addressed in future research.
Context of reception, daily-linguistic biculturalism, and depressive symptoms among Hispanic college students

Abstract Daily diary studies allow for examining the day-to-day dynamic experiences of biculturalism. The present study used a 12-day daily diary dataset collected with 873 Hispanic college students. Our goal was to (a) identify two distinct forms of dynamic daily processes of linguistic biculturalism (bicultural levels and bicultural fluctuations) and (b) examine the mediating role of bicultural levels and bicultural fluctuations in the association between negative context of reception and depressive symptoms. Results indicated that bicultural levels did not emerge as a construct, because daily levels of English and Spanish language use were not sufficiently intercorrelated. Bicultural fluctuations did emerge at the intersection of English and Spanish language use fluctuations. English language use and bicultural fluctuations mediated the association between negative context of reception and depressive symptoms. Implications for theory and intervention are discussed.
B Cells Selectively Induce CD8+ MAIT Cell Effector Functions: Implications for Multiple Sclerosis (5355)

Objective: To study potential disease-relevant interactions between B cells and both CD8 MAIT and non-MAIT T cells in multiple sclerosis (MS) Background: B-cell depletion with anti-CD20 antibodies is highly effective in limiting new MS relapses, in part attributed to attenuation of CD4 T-cell responses, reflecting the well-recognized disease-implicated interactions between B cells and CD4 T cells. Curiously, B-cell depletion also attenuates CD8 T-cell responses, suggesting a role for B cell:CD8 T cell interactions in vivo. Both mucosal associated invariant T (MAIT) CD8 and non-MAIT (conventional) CD8 T cells have been implicated in MS. Design/Methods: Effects of differentially-activated B cells on CD8 T-cell subsets were initially assessed using in vitro co-cultures within whole peripheral blood mononuclear cells (PBMC) and using purified cell subsets from healthy controls. T cell proliferation, cytotoxicity and cytokine production were assessed by multiparametric flow-cytometry. Validated flow cytometry panels were applied in batch to cryopreserved PBMC from treatment-naive MS patients prior to and after in vivo anti-CD20 antibody therapy. Results: B cells suppress proliferation of non-MAIT CD8+ T cells yet significantly promote MAIT cell expansion in vitro. The differential impact on CD8+ T cell subsets is influenced by the B cell differentiation stage and mediated by B-cell secreted products. B cells also differentially impact CD8+ T-cell subset cytotoxicity and pro-inflammatory cytokine responses. In vivo, treatment with anti-CD20 selectively reduces frequencies and pro-inflammatory responses of MAIT cells, including diminished proliferation, cytotoxicity and pro-inflammatory cytokine production, that mirrors in vitro findings. Conclusions: Our findings implicate disease-relevant in vivo interactions between B cells and CD8+ T cells in MS. B cells differentially impact distinct CD8+ T cell subsets, selectively inducing of multiple effector responses of CD8+ MAIT cells. Selective decreases in CD8+ MAIT cell pro-inflammatory functions may contribute to the therapeutic mode of action of anti-CD20 therapy. Disclosure: Dr. Rezk has nothing to disclose. Dr. Shinoda has nothing to disclose. Dr. Li has nothing to disclose. Amit Bar-Or has participated as a speaker in meetings sponsored by, and received consulting fees from, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, Janssen/Actelion, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. Grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme.
Proteoform-selective imaging of tissues using mass spectrometry

Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Top-down proteomics is a powerful tool, which has been used for the identification of thousands of proteoforms in biological samples. Herein, we present a first spatially resolved top-down proteomics analysis of biological tissues using nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI). Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS). Proof-of-concept experiments demonstrate that the nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of thin tissue sections. Using rat brain tissue as a model system, we provide the first evidence of the differential proteoform expression in different regions of the brain.
Maximizing Step-Normalized Increases in Molecular Complexity: Formal [4+2+2+2] Photoinduced Cyclization Cascade to Access Polyheterocycles Possessing Privileged Substructures.

A new complexity building photoinduced cascade which amounts to an unprecedented formal [4+2+2+2] cycloaddition topology is developed to access complex nitrogen polyheterocycles. This photocascade is initiated by the excited state intramolecular proton transfer (ESIPT) in aromatic amino ketones with tethered dual unsaturated pendants, i.e. pyrrole and alkenic moieties, resulting in the formation of four σ-bonds and setting six new stereogenic centers in a single experimentally simple photochemical step with up to 220 mcbit complexity increases.
STRING TOPOLOGY AND THE BASED LOOP SPACE

For M a closed, connected, oriented manifold, we obtain the Batalin-Vilkovisky (BV) algebra of its string topology through homotopy-theoretic constructions on its based loop space. In particular, we show that the Hochschild cohomology of the chain algebra C WM carries a BV algebra structure isomorphic to that of the loop homology H (LM). Furthermore, this BV algebra structure is compatible with the usual cup product and Ger- stenhaber bracket on Hochschild cohomology. To produce this isomorphism, we use a derived form of Poincarduality with C WM-modules as local coefficient systems, and a related version of Atiyah duality for parametrized spectra connects the algebraic construc- tions to the Chas-Sullivan loop product.
Further considerations of two-dimensional condensation drop profiles and departure sizes

The problem of the equilibrium shape and departure size of two-dimensional dropwise condensation drops on a vertical surface, presented in an earlier work, is extended to include advancing contact angles to 180°. The equation of the surface of the drop is obtained by minimizing (for a given volume) the total energy of the drop, consisting of surface and gravitational energy, using the techniques of variational calculus. The solution is tractable once the advancing contact angle is known, and is taken as an approximation to the axial meridian profile of a threedimensional drop. The receding contact angle is obtained as part of the solution.
Predictors of Victimization Experiences of Adolescents with Disabilities in Transition

This study explored predictors of victimization experiences on a sample of adolescents with disabilities while in school and 1 year after leaving school, through phone interviews of students and parents. Logistic regression analyses revealed that people with serious emotional disturbance who demonstrated low personal/social achievement skills were more likely to experience victimization sometime in their school career than were people with other disabilities and higher personal/social skills. Variables affecting victimization rates 1 year out of school included prior victimization (while in school), gender (females were more likely to be victimized), and arrest record of people with serious emotional disturbance after leaving school.
Prevalence and nature of early glaucomatous defects in the central 10° of the visual field.

Importance The macula is essential for visual functioning and is known to be affected even in early glaucoma. However, little is currently understood about the prevalence and nature of central vision loss in early glaucoma. Objective To determine the prevalence and characteristics of visual field (VF) defects in the central 10° in glaucoma suspects and patients with mild glaucoma using a prospective design. Design, Setting, and Participants This prospective observational cohort study was conducted at an outpatient glaucoma specialty clinic. One hundred eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF with mean deviation better than −6 dB were prospectively studied and tested with a 10-2 test. Main Outcomes and Measures Reliable VF hemifields were classified as abnormal based on a cluster criterion, and abnormal 10-2 VFs were categorized based on the pattern of abnormal points: arcuatelike, widespread, or other. In addition, at each point of the 10-2 VF, the total deviation values were averaged across eyes and the number of abnormal points with total deviation values below a specific criterion level were calculated. Results There appeared to be as many abnormal 10-2 hemifields (53%) as abnormal 24-2 hemifields (59%). Of the eyes with normal 24-2 hemifields, 16% were classified as abnormal when the 10-2 test was used. Of the abnormal 10-2 hemifields, 68%, 8%, and 25% were arcuatelike, widespread, and other, respectively. The average total deviation values and number of abnormal points plots revealed superior VF defects that were deeper and closer to fixation than those in the inferior VF. Conclusions and Relevance The 10-2 VF was abnormal in nearly as many hemifields as was the 24-2 VF, including some with normal 24-2 VF, suggesting that the 24-2 test is not optimal for detecting early damage of the macula. The pattern of the defects was in agreement with a recent model of macular damage.
Genetic counseling in Alzheimer's disease

Abstract In assessing genetic risk for Alzheimer's Disease, it is important to recognize the incomplete state of knowledge concerning the causes of this condition. Along with the phenomenon of delayed onset, which reduces the portion of risk actually experienced by relatives in most instances, genetic heterogeneity must be considered. Differences in published findings may result from methodology, diagnostic techniques, or most likely the presence of several genetic and non-genetic entities within the rubric of Alzheimer's Disease. Genetic counselors should therefore be cautious in assessment of risks to relatives.
A clinical evaluation of a bioresorbable barrier with and without decalcified freeze‐dried bone allograft in the treatment of molar furcations

Abstract This study evaluated a bioresorbable barrier with and without decalcified freeze-dried bone allograft (DFDBA) in the treatment of human molar furcations. 14 subjects with paired class II mandibular molar furcation defects participated in the study (8 male and 6 female). The class-II furcation defects were randomly treated with either the resorbable barrier alone or resorbable barrier in combination with decalcified freeze-dried bone allograft (DFDBA). Gingival recession, probing depth, clinical attachment, and bone fill were measured. 6 months post-treatment measurements were repeated and each site was surgically re-entered. When the resorbable barrier alone was compared to resorbable barrier in combination with DFDBA. probing depth reduction was significantly (p<0.01) in favor of the combination therapy. Vertical bone gain was significant with the combination treatment demonstrating more bone fill (p<0.02). Smoking was also a variable examined in this study. When compared to smokers, non-smokers for both treatment groups revealed greater probing depth reduction, vertical bone gain, and horizontal bone gain. Within the non-smoking group, probing depth reduction was also significantly higher for the resorbable barrier and DFDBA group than the resorbable alone group (p<0.02). These results illustrate that the probing depth reduction is better in the non-smoker and the best in the non-smoker with the combination therapy of resorbable barrier and DFDBA than with resorbable barrier alone.
Differences in TIMI frame count following successful reperfusion with stenting or percutaneous transluminal coronary angioplasty for acute myocardial infarction.

The Thrombolysis In Myocardial Infarction (TIMI) flow grade achieved in the infarct-related artery (IRA) during reperfusion therapy for acute myocardial infarction (AMI) is directly related to myocardial salvage. Recently, several series have demonstrated the safety of stenting in AMI and documented a larger postprocedure luminal diameter than that found at angioplasty, although no study has compared the effect of PTCA and stenting in AMI on flow characteristics of the IRA. The residual stenosis and the number of frames required to opacify standardized angiographic landmarks normalized for vessel length (corrected TIMI frame count) or compared with flow in a corresponding normal coronary artery (TIMI frame count index) were determined for the IRA of 39 patients who underwent angioplasty or stenting for AMI. Baseline characteristics were similar for the 20 patients who underwent stenting and the 19 patients who underwent percutaneous transluminal coronary angioplasty. After intervention, the luminal diameter was greater (3.24 vs 2.09 mm, p <0.0001) and the residual stenosis was less (−9.4% vs. 26.7%, p <0.0001) after stenting than after percutaneous transluminal coronary angioplasty. These changes in vessel geometry were associated with a lower corrected TIMI frame count (16.1 vs 30.7, p <0.002) and a lower TIMI frame count index (0.68 vs 1.3, p <0.002). Thus, stenting in AMI is associated with a greater postprocedure luminal diameter and improvement in coronary blood flow as measured by the TIMI frame count method.
Aspartyl phosphates in the regulatory control of bacterial response

Acyl phosphates represent a mixed anhydride class of compounds whose lability allows the phosphorylation of an aspartyl carboxyl contained in a protein to reversibly induce changes in structure that may have biological significance, particularly in prokaryotic systems. In this report the phosphorelay system that regulates sporulation inBacillus subtilis is described briefly and its analogy to other regulatory systems is outlined. The structural properties of the aspartate containing second component of the phosphorelay system SpoOF is examined by multidimensional NMR techniques and comparison is made with a known sequence analog, CheY. Distinct differences are apparent that are reflected by the extended half life of phosphorylated SpoOF relative to the CheY analog. It is probable that in a general way the distinct half life characteristics may be related to the differing functions of the various regulatory aspartate containing proteins in the cell.
Control-system design for minimum bandwidth

THIS digest discusses a method of designing feedback control systems so that for a specified performance their bandwidth is a minimum. Not infrequently, engineers have designed control systems with the objective of minimizing errors; with attention focused on the problem of minimizing errors there is a tendency to use bandwidth inefficiently so that he manufactures increased difficulties. He may open up the bandwidth of the control system to the point where he has undue transmission of noise. In the case of mechanical systems, he may increase the bandwidth to the point where elastances in gear boxes and supporting structure will cause severe stability problems. As the result of large bandwidth, he may encounter a saturation problem in one of the components toward the output end that would not otherwise exist. Expanding the bandwidth of a control system may require him to use more expensive components than are really necessary. For these and many other reasons he should strive to keep the bandwidth requirements of a feedback control system as low as possible.