cssi/SciSciGPT-SciSciNet huggingface dataset:
Reversibility of chronic kidney disease and outcomes following aortic valve replacement

OBJECTIVES: Chronic kidney disease (CKD) is prevalent in patients undergoing aortic valve replacement (AVR). We sought to evaluate the impact of AVR on estimated glomerular filtration rate (eGFR) levels and determine the impact of reversibility of CKD on postoperative outcomes. METHODS: We retrospectively reviewed 2169 patients who underwent isolated AVR between 2000 and 2012. eGFR was calculated using the CKD-EPI formula. Based on preoperative eGFR, patients were divided into three groups: NoCKD (eGFR >60, n= 1417), ModCKD (eGFR = 30–60, n= 619) and SevCKD (eGFR = 15–30, n= 86). End-stage renal disease patients (eGFR <15 and/or dialysis, n= 47) were excluded from the study. RESULTS: Before AVR, eGFR in the NoCKD, ModCKD and SevCKD groups was 81.3 ± 14.2, 48.9 ± 8.10 and 25.3 ± 4.12 ml/min/1.73 m 2 , respectively. NoCKD patients showed a decline in eGFR during the first month postoperatively; thereafter, eGFR remained stable over 1 year. ModCKD and SevCKD patients demonstrated an initial improvement in eGFR, which peaked at 1 week postoperatively. In ModCKD, eGFR stabilized at a slightly lower level thereafter out to 1-year follow-up. In SevCKD, eGFR declined slightly out to 6 months postoperatively. Regardlessly, eGFR in ModCKD at 1 year and in SevCKD at 6 months postoperatively demonstrated sustained improvement over baseline eGFR. Reversibility of CKD was associated with a better long-term survival in the ModCKD group (P< 0.001) and short-term survival in the SevCKD group (P= 0.018). CONCLUSIONS: AVR confers a marked initial improvement in eGFR, which is sustained in patients with ModCKD and SevCKD, and is associated with a better survival. The reversible nature of CKD in certain patients warrants careful consideration during preoperative risk scoring and stratification.
Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons

Proneural proteins of the class I/II basic-helix-loop-helix (bHLH) family are highly conserved transcription factors. Class I bHLH proteins are expressed in a broad number of tissues during development, whereas class II bHLH protein expression is more tissue restricted. Our understanding of the function of class I/II bHLH transcription factors in both invertebrate and vertebrate neurobiology is largely focused on their function as regulators of neurogenesis. Here, we show that the class I bHLH proteins Daughterless and Tcf4 are expressed in postmitotic neurons in Drosophila melanogaster and mice, respectively, where they function to restrict neurite branching and synapse formation. Our data indicate that Daughterless performs this function in part by restricting the expression of the cell adhesion molecule Neurexin. This suggests a role for these proteins outside of their established roles in neurogenesis.
Resistance to the Spotted Alfalfa Aphid (Homoptera: Aphididae) in Glandular-Haired Medicago Species

We evaluated glandular-haired Medicago species [perennial tetraploid M. sativa L. subsp. praefalcata (Sinskaya) C. R. Gunn, annual diploids M. blancheana Boiss., M. disciformis DC, and annual tetraploids, M. rugosa Desr., and M. scutellata (L.) Mill.] for resistance to the spotted alfalfa aphid, Therioaphis maculata (Buckton), in growth chambers. Resistant and susceptible perennial M. sativa clones were used for controls. In free-choice tests, the glandular-haired species and the resistant M. sativa control clone were less attractive than the susceptible control clone. Very few aphids reproduced on M. disciformis . Fewer aphids were on the annuals than on the perennial glandular-haired species. When the aphids' choices were limited to the annual species M. scutellata and M. disciformis , they departed from both and moved around the arena. Similarly, when only the resistant M. sativa clone and M. scutellata were available, the aphids chose the arena over the plants. In no-choice tests under three temperature regimes, resistance of M. disciformis and the resistant M. sativa clone was similar. Resistance of M. blancheana , M. rugosa , and M. scutellata was similar and lower than that of M. disciformis . Resistance of the glandular-haired M. sativa clone was low, but rate of aphid reproduction and total nymphs produced on it were lower than on the susceptible control clone under a constant temperature of 24°C or under 29°C day-16°C night temperature regimes.
Undiversion in Men Following Prior Cystoprostatectomy and Cutaneous Diversion. Is It Practical

AbstractThis report discusses the feasibility and functional outcome of conversion to an orthotopic Kock neobladder in 11 men (average age 58 years) who underwent cystoprostatectomy and cutaneous urinary diversion an average of 7.3 years previously are discussed. Cystectomy had been performed for bladder cancer in 9 men and for multiple failed bladder reconstructions in 2. No patient had any evidence of recurrent cancer. The reasons for conversion to a Kock neobladder included complications with the current form of diversion (stomal stenosis, leakage and so forth) and dislike of a cutaneous stoma. Average followup since neobladder conversion was 36 months.The exactness of the anastomosis to the urethra and the presence of a retained apex of the prostate were major factors in the technical success of the operation, degree of continence and satisfaction of the patients. All 4 patients who had some portion of retained prostate enjoy excellent continence without anastomotic stricture. In 2 of the early undive...
Effectively Transparent Front Contacts for Optoelectronic Devices

Effectively transparent front contacts for optoelectronic devices achieve a measured transparency of up to 99.9% and a measured sheet resistance of 4.8 Ω sq^(−1). The 3D microscale triangular cross-section grid fingers redirect incoming photons efficiently to the active semiconductor area and can replace standard grid fingers as well as transparent conductive oxide layers in optoelectronic devices.
Excessive Daytime Somnolence in Women with Abnormal Respiratory Efforts During Sleep

An abnormal level of respiratory efforts, indicated by significant increase in peak negative esophageal pressure (Pes), can be associated with daytime somnolence in snoring pre-menopausal women. No drop in oxygen saturation (SaO2) or visual evidence of transient electroencephalographic (EEG) arousals can be found at repeat polysomnography. Nasal continuous positive airway pressure (CPAP) titrated on Pes measurements eliminates somnolence.
Were the May 2012 Emilia-Romagna earthquakes induced? A coupled flow-geomechanics modeling assessment

Seismicity induced by fluid injection and withdrawal has emerged as a central element of the scientific discussion around subsurface technologies that tap into water and energy resources. Here we present the application of coupled flow-geomechanics simulation technology to the post mortem analysis of a sequence of damaging earthquakes (Mw = 6.0 and 5.8) in May 2012 near the Cavone oil field, in northern Italy. This sequence raised the question of whether these earthquakes might have been triggered by activities due to oil and gas production. Our analysis strongly suggests that the combined effects of fluid production and injection from the Cavone field were not a driver for the observed seismicity. More generally, our study illustrates that computational modeling of coupled flow and geomechanics permits the integration of geologic, seismotectonic, well log, fluid pressure and flow rate, and geodetic data and provides a promising approach for assessing and managing hazards associated with induced seismicity.
Drivers of 30-Day Readmission in Elderly Patients (>65 Years Old) After Spine Surgery: An Analysis of 500 Consecutive Spine Surgery Patients

Background Early readmission after spine surgery is being used as a proxy for quality of care. One-fifth of patients are rehospitalized within 30 days after spine surgery, and more than one-third within 90 days; however, there is a paucity of data about the cause of early readmissions in elderly patients after elective spine surgery. Methods A total of 500 elderly patients (>65 years old) undergoing elective spine surgery at a major academic hospital were included in the study. We identified all unplanned readmissions within 30 days of discharge. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. Patient records were reviewed to determine the cause of readmission and the length of hospital stay. Results A total of 50 (10%) unplanned early readmissions were identified. The mean ± SD age was 72.54 ± 5.84 years. The mean ± SD number of days from discharge to readmission was 11.02 ± 7.25 days, and the average length of hospital stay for the readmissions was 7.7 days. The majority of patients that were readmitted presented to the emergency department from home (46%), whereas 38% were readmitted from a skilled nursing facility. The most common causes for readmission were infection or a concern for infection (42%) and pain (14%), with 32% of readmissions requiring a return to the operating room. Conclusion Our study suggests that in elderly patients undergoing elective spine surgery, infection or a concern for infection, pain, and altered mental status were the most common primary reasons for unplanned readmission.
Categorization of camera captured documents based on logo identification

In this paper, we present a methodology to categorize camera captured documents into pre-defined logo classes. Unlike scanned documents, camera captured documents suffer from intensity variations, partial occlusions, cluttering, and large scale variations. Furthermore, the existence of non-uniform folds and the lack of document being flat make this task more challenging. We present the selection of robust local features and the corresponding parameters by comparisons among SIFT, SURF, MSER, Hessian-affine, and Harris-affine. We evaluate the system not only with respect to amount of space required to store the local features information but also with respect to categorization accuracy. Moreover, the system handles the identification of multiple logos on the document at the same time. Experimental results on a challenging set of real images demonstrate the efficiency of our approach.
Ocular Dysfunctions Presenting in Tacrolimus-Induced Posterior Reversible Encephalopathy Syndrome: A Case Presentation.

Abstract The constellation of ocular symptoms known as Balint syndrome is a rare disorder seen in bilateral parieto-occipital lesions and is most frequently due to arterial occlusive disease or acute hypertension. Here we present the case of a patient with tacrolimus-induced posterior reversible encephalopathy syndrome (PRES) who presented with optic ataxia, simultanagnosia, and ocular apraxia. These ocular findings, consistent with Balint syndrome, are rarely the initial presentation of PRES. This case highlights the importance of early recognition of this unusual phenomenon, as well as the importance of an individualized rehabilitation plan to maximize functional independence in these patients. Level of Evidence V
Parents’ Influence on Infants’ Gender-Typed Toy Preferences

Gender socialization influences children at early ages, shaping their developing identities. The toys provided by parents deliver some of the earliest gender-based messages by encouraging children to engage in activities associated with, for example, dolls and trucks. In the current study, we measured the influence of parental socialization by assessing 5- and 12 ½-month-old infants' exposure to dolls and trucks and by experimentally manipulating parents' encouragement to play with these toys. We found that infants displayed gender-typical toy preferences at 12 ½, but not 5 months, a pattern characteristic of previous studies. However, brief encouragement by a parent to play with toys from each category was ineffective in altering infants' preferences. Rather, the types of toys present in the home predicted preferences, suggesting that at-home exposure to toys may be influential in the development of toy preferences. These findings reveal that socialization processes may indeed play a role in the formation of early gender-typical toy preferences and highlight the importance of equal toy exposure during infancy to ensure optimal development.
Reinforcement with multiple mating Response from Marshall, Arnold and Howard

In our recent article in TREE [1xReinforcement: the road not taken. Marshall, J.L. et al. Trends Ecol. Evol. 2002; 17: 558–563Abstract | Full Text | Full Text PDF | Scopus (79)See all References[1], we suggested that the cost of mating with a heterospecific, and thus the strength of selection against hybridization acting upon the individual, is reduced for those individuals that mate multiply and with at least one conspecific relative to individuals that mate once and with a heterospecific. Given the above and assuming that, in multiple mating systems, individuals always mate with at least one conspecific, we inferred that reinforcement would be less likely to occur in promiscuous systems than in monogamous systems. Under this scenario, our inferences about the role of multiple mating, per se, are correct.However, if the above assumption is removed and heterospecific matings are allowed to occur at a given frequency, as in Kisdi's model [2xReinforcement with multiple mating. Kisdi, E. Trends Ecol. Evol. 2003; See all References[2], then there is no a priori reason to predict that reinforcement would be less likely to occur in promiscuous systems. Nevertheless, the individual cost of mating with a heterospecific is reduced if it is preceded, or followed by a conspecific mating. Kisdi's model helps resolve the apparent disconnect between costs at the individual level and the spread of a ‘reinforcement’ allele (e.g. a preference or assortative mating allele) through a population.Kisdi's model and letter [2xReinforcement with multiple mating. Kisdi, E. Trends Ecol. Evol. 2003; See all References[2] also serve to underscore a major inference of our paper; that the interaction between the mating system and pattern of gamete utilization will influence the potential for reinforcement when there is selection against hybridization [1xReinforcement: the road not taken. Marshall, J.L. et al. Trends Ecol. Evol. 2002; 17: 558–563Abstract | Full Text | Full Text PDF | Scopus (79)See all References[1]. In particular, any deviation, regardless of how small, from equal utilization of gametes will affect the possibility of reinforcement under a multiple mating system. If conspecific gamete preference exists (the possibility explored in our paper [1xReinforcement: the road not taken. Marshall, J.L. et al. Trends Ecol. Evol. 2002; 17: 558–563Abstract | Full Text | Full Text PDF | Scopus (79)See all References[1]), reinforcement is less likely to occur. However, if hetero-population sperm precedence occurs (a possibility supported by recent experimental evidence [3xHeteropopulation males have a fertilization advantage during sperm competition in the yellow dung fly (Scatophaga stercoraria). Hosken, D.J. et al. Proc. R. Soc. Lond. Ser. B. 2002; 269: 1701–1707Crossref | PubMed | Scopus (43)See all References[3]), then reinforcement is more likely to occur.
Narratives of Migrant Mothers: Exploitation, Transience, Education, and Resilience

This narrative study provides new understanding about migrant farm worker families in Michigan. Mothers, in particular, are central to the family structure, providing continuity and stability in the migratory process. In 2016, we interviewed five migrant mothers working in Harbor County, Michigan. The women shared their struggles along with their hopes for the future. In this article, we focus our attention on the challenges faced by the women: family obligations, sexism, limited English proficiency, limited income, and work-related demands. In addition to their accounts of difficulties, the interviews also revealed the women’s great resilience and their belief in the power of education to change the future for their children. To conclude, we discuss the ways in which our schools and communities can support migrant students and their families.
Next-Generation Process Design for Monoclonal Antibody Purification

Abstract Monoclonal antibodies (mAbs) are among the fastest-growing therapeutics (see Chapter 3 ) and are being developed for a broad range of indications, from cancer to infectious diseases to cardiovascular diseases (Foltz et al. [1], Hansel et al. [2]). Owing to their efficacy in the clinic and ease of manufacturability, mAbs have emerged as one of the major recombinant protein therapeutic classes. The antibody expression/production has standardized over years using mammalian cells as a host system. The homologous protein sequence of humanized mAbs—the Fc region of mAbs—enables the use of Protein A chromatography for mAb capture, thereby, harmonizing the downstream manufacturing process with only minimal changes required from product to product. Manufacturing processes for mAbs have evolved tremendously over the last three decades since the first licensed mAb product (Kelley [5]). The advancements in cell culture productivity shifted the bioprocessing bottleneck from cell culture to downstream processing, primarily in form of facility constraints. Some of the challenges in downstream processing and continued improvements in downstream process technologies are discussed in this chapter. There is an increased focus on improved utilization of production facilities and reducing the manufacturing cost and footprint (Guldager [3]). We discuss several emerging technologies with improved productivity, including single-use disposable ones that enable the production of multiple products in a flexible manufacturing facility with deduced downtime and cleaning/validation cost.
Mating, Fertilization, and Ovum Viability in the Anovulatory, Persistent-Estrus Rat

Among 188 female rats injected subcutaneously with either 50 mcg testosterone propionate (TP) or 150 mcg TP on Day 5 (Day 1 = birth) 93.6% had no corpora lutea at laparotomy 3 weeks following vaginal opening. These AF (androgenized females) showed vaginal estrus more than 90% of the time while ovulatory females showed vaginal diestrus more than 50% of the time. Among AF50 (AF given 50 mcg TP) AF250 and AF1250 placed with males for the first time fewer mated 60.6% 36.2% and 10.9% respectively than among mormal rats 83.6% (N.S. P< .001 respectively). Intraperitoneal injection of AF1250 with 10 mcg LH resulted in a higher mating response 34.3% than in untreated AF1250 (P < .025) perhaps due to steroid production of follicular ovaries. AF50 and AF250 autopsied at varying intervals after receiving LH at 4 PM showed ovulation occurred from 3 AM to 4 AM. This treatment also resulted in synchronization of mating. Of tubal ova recovered 9-15 hrs after ovulation from mated AF50 and AF250 given LH at 4 PM and from normal rats 75.8% and 71.2% respectively exhibited morphologically normal sperm penetration and pronuclear formation. Of Day 1 fertilized eggs transerred from normal rats AF50 and AF250 into the oviducts of normal Day 1 psuedopregnant females 50% 53.3% and 23.9% (different from controls p < .001) respectively developed into viable embryos at Day 18. The higher dose of TP may effect ovum viability by altering oocyte nuclear metabolism or indirectly by producing an adverse normal environment due to abnormal ovarian or adrenal steroid metabolism.
Comparative Effectiveness in Melanoma

The worldwide incidence of melanoma continues to rise. It is a leading cause of cancer death and the second leading cause of loss of productive years of life. Although the diagnosis of melanoma is straightforward, there remain many controversies regarding treatment and surveillance. This chapter addresses important questions in melanoma treatment such as sentinel lymph node biopsy, what to do with a positive sentinel lymph node, margins of resection for melanoma, radiation for primary, nodal and metastatic melanoma, and routine use imaging. Through this chapter, the evidence for these controversial subjects and the barriers to resolution will be elucidated.
A World of Uncertainty: Economics and the Globalization of Antitrust

This paper discusses some implications of the considerable uncertainty that, despite dramatic recent advances in the application and implementation of economics, surrounds antitrust analysis. During the past quarter century, increasingly rigorous economic models and econometric techniques have come to be employed in the identification and estimation of competitive effects. On the theory front we have witnessed a far greater appreciation of unilateral effects and increased use of game theory. On the empirical front the techniques for estimating demand elasticities have become ever more refined. There has also been growing use of merger simulation models to transform empirical estimates into predictions of competitive effects. The reliance upon microeconomic theory and advanced estimation techniques as a basis for antitrust analysis and decision-making has indeed been striking. It has not, however, eliminated the still-considerable uncertainty and imprecision involved in forming recommendations. One step toward grounding antitrust policy on a more economically sound, welfare-oriented path is to recognize more explicitly the uncertainty inherent in antitrust analysis and prediction, and to incorporate into the decision making process more information on the costs of making wrong decisions. In addition to analyzing the implications of uncertainty for efficient antitrust policy, this paper explores also the widely perceived differences in antitrust policy between the U.S. and the EU. These differences, it suggests, are not primarily a result of opposing views concerning either the relevance of economics or the ultimate goals of antitrust. Rather, they likely derive from the uncertainty inherent in antitrust decision-making and enforcement, along with different underlying views and presumptions concerning the scope for improvement by an imperfectly performing government over what may at times be an imperfectly performing marketplace.
SVM based on LMMSE for high-speed coded OFDM channel with normal and extended cyclic prefix

Abstract We propose in this article, a Linear Minimum Mean Squares Error-Support Vector Machine regression (LMMSE-SVR) method which is employed high-speed 3GPP Long Term Evolution (LTE) downlink coded channel estimation environment. LMMSE-SVR approach is applied to track and estimate the fast fluctuations caused by Doppler effect of a 3GPP realistic Extended Vehicular A model (EVA) channel. We integrate in this contribution both channel estimation at pilot symbols and interpolation at data symbols into the LMMSE-SVR process with and without turbo coding scheme. Bit Error Rate (BER) performance of our channel environment estimation proposal is validated via simulation of LTE downlink system for both coded and uncoded high-speed scenarios with normal and extended Cyclic Prefix (CP) modes.
Differences in pituitary-adrenal reactivity in Black and White men with and without alcohol use disorder.

Abstract Background Treatment-seeking men with alcohol use disorder (AUD) classically exhibit a blunted hypothalamic-pituitary-adrenal (HPA) axis response to pharmacologic and behavioral provocations during the early phases of abstinence from alcohol. Independent of alcohol, a significant muting of HPA axis reactivity is also observed among racial minority (e.g. Black) individuals. The effect of AUD upon the altered HPA axis response of racial minority individuals has not been explored. The current work represents a secondary analysis of race and AUD status among a sample of men. Methods Healthy male controls (17 White, 7 Black) and four-to six-week abstinent men with AUD (49 White, 13 Black) were administered a psychosocial stressor and two pharmacologic probes [ovine corticotropin releasing hormone (oCRH) and cosyntropin] to assess HPA axis reactivity. Plasma cortisol and adrenocorticotropin hormone (ACTH) were assessed at 10–20 min intervals prior to and following behavioral and pharmacological stimulation. Basal and net-integrated responses following provocations were analyzed to identify potential group differences. A measure of childhood adversity was also obtained to consider the implications of prior stressors upon HPA axis function. Results A three-fold increase in oCRH-induced ACTH was seen in Black men relative to White men regardless of AUD status. Adversity exerted a dampening effect on this pituitary sensitivity within Black controls only. Adjusted for adversity, a significant blunting effect of AUD status on ACTH reactivity was identified within White participants following oCRH. No group differences were present following cosyntropin administration. In response to the psychosocial stressor, White, but not Black, men with AUD experienced the expected blunting of cortisol reactivity relative to White controls. Rather, Black men with AUD exhibited greater cortisol reactivity relative to White men with AUD. Conclusions Differences in HPA axis reactivity associated with race were present in men with and without AUD. Explanatory biological mechanisms of the relationship between alcohol use and/or stress, in both healthy and unhealthy populations, may require a reassessment in different racial populations.
FYN tyrosine kinase, a downstream target of receptor tyrosine kinases, modulates anti-glioma immune responses

ABSTRACT Background High grade gliomas are very aggressive and immunosuppressive brain tumors. Molecular mechanisms that regulate the inhibitory immune tumor microenvironment (TME) and glioma progression remain poorly understood. FYN tyrosine kinase is a downstream target of the oncogenic receptor tyrosine kinases pathway and is overexpressed in human gliomas. FYN’s role in vivo in glioma growth remains unknown. We aimed to study whether FYN regulates GBM growth and invasion. Methods We evaluated the role of FYN using genetically engineered mouse models (GEMM) of glioma. We also generated FYN knockdown stem cells to induce gliomas in immune-competent and immune-deficient mice (NSG and CD8−/−). We analyzed molecular mechanism by RNA-Seq and bioinformatics analysis. Flow cytometry was used to characterize immune cellular infiltrates in the FYN knockdown glioma TME. Results We show that FYN knockdown in diverse immune-competent GEMM of glioma reduced tumor progression and significantly increased survival. GSEA analysis of DE genes in WT vs. FYN knockdown gliomas showed enrichments of gene ontologies related to immune reactivity. However, in NSG and CD8−/− immune-deficient mice, FYN knockdown glioma failed to show difference in survival. These data suggest that the expression of FYN in glioma cells reduces anti-glioma immune activation. Examination of glioma immune infiltrates by flow-cytometry displayed reduction in the amount of immune inhibitory myeloid derived cells (MDSCs) in the FNY glioma TME. Conclusions Gliomas employ FYN mediated mechanisms to suppress the immune system and promote tumor progression. Selective inhibition of FYN within glioma cells could improve the efficacy of anti-glioma immunotherapies. Key points Inhibition of FYN tyrosine kinase in genetically engineered mouse glioma models delays tumor progression. The oncogenic effects of FYN in vivo are mediated by downregulation of anti-glioma immunity. Importance of the Study FYN is an effector of RTK signaling in glioma. However, its role in vivo remains unknown. Our study demonstrates that FYN tyrosine kinase is a novel regulator of the anti-glioma immune response. We show that FYN inactivation suppresses glioma growth, increases survival, and enhances anti-tumor immune reactivity. Our findings suggest that suppressing the expression of FYN in glioma cells could provide a novel therapeutic target.
Abstract P6-08-02: Developingin vitromodels of ductal carcinomain situfrom primary tissue

BACKGROUND: Because there are currently no reliable predictors for progression of ductal carcinoma in situ (DCIS) to invasive disease, nearly all patients receive aggressive therapy, leading to over-treatment in many cases. Few in vitro models for studying DCIS progression have been developed. We report here the successful culture and expansion of primary DCIS from surgical specimens using a conditional reprogramming protocol. MATERIALS AND METHODS: From 2/2014 to 4/2015, patients with percutaneous core needle biopsy demonstrating DCIS were enrolled in a tissue banking protocol after informed consent was received. Under supervision of the surgical pathologist, fresh tissue measuring between 5-15 mm in length was taken from lumpectomy or mastectomy specimens. Tissue was divided such that half was mechanically and enzymatically dissociated and then cultured in medium conditioned by irradiated mouse fibroblasts and supplemented with rho-associated protein kinase (ROCK) inhibitor, and the second half, known as the "mirror image" remained as part of the clinical specimen. RESULTS: Of 49 consented patients, mean age was 59 ± 10 years. 7 were excluded due to final pathology not consistent with DCIS: 4 upstaged to invasive ductal cancer, 2 had microinvasion and 1 showed pleomorphic lobular carcinoma in situ . Of the remaining 42, 9 were failures: 5 tissues were not received in lab and 4 cases were received, but no cells grew in culture. Of the remaining 33 cases of DCIS, 70% (n=23) and 27% (n=9) were nuclear grade 2 and 3 respectively. 91% (n=30) were ER-positive, with H-score ranging between 4 and 300. 19 (58%) were expanded in cell culture for up to two months in culture, and 14 were frozen immediately after mechanical dissociation for future growth. The 19 cell cultures could be cryopreserved and expanded. The cultures are almost exclusively composed of cytokeratin 8- and EpCAM-positive luminal cells and cytokeratin 14-, cytokeratin 5-, and p63-positive basal mammary epithelial cells, suggesting maintenance of heterogeneity in vitro . Furthermore, as assessed by luminal and basal marker expression, these cells retain their cellular identities both in the "conditionally reprogrammed" proliferative state and when conditioned media and ROCK inhibitor were withdrawn. When grown to 100% confluency, the cultures appear to organize into luminal and basal layers as well as luminal compartments surrounded by basal cells. CONCLUSION: Primary cultures of DCIS derived directly from patient tissues may serve as in vitro models for the study of DCIS. Citation Format: McAuliffe PF, Brown DD, Oesterreich S, Lee AV, Johnson RR, McGuire KP, Davidson NE, Brufsky AM, Dabbs DJ. Developing in vitro models of ductal carcinoma in situ from primary tissue. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-02.
Afterword: A Return to the Story

The contributors to this volume present us a provocative challenge. Reading between the lines of these bold essays, are we not asked to take a leap of faith into the nether world of ethnographic narratives through which ethnographers reconnect fully with human emotions? That leap takes us into the spaces between things, where we find the story and know it. When we embrace the story, we rediscover the field, reclaim our human emotions, and remember ourselves. That is a challenge worthy of our full attention.
Book Review: The Devil’s Music: How Christians Inspired, Condemned, and Embraced Rock ‘N’ Roll by Randall Stephens

Randall Stephens. The Devil’s Music: How Christians Inspired, Condemned, and Embraced Rock ‘N’ Roll . Cambridge: Harvard University Press, 2018. 344 pages. In my courses on religion and popular music, students typically have trouble offering concrete historical answers to two questions: How
Treatment of non-obstructive, non-struvite urolithiasis is effective in treatment of recurrent urinary tract infections.

To determine if treatment of non-obstructing urolithiasis is effective in management of recurrent UTI. A retrospective review was performed of patients undergoing elective management of non-struvite upper tract urinary calculi with recurrent UTI from 2009 to 2016. Recurrent UTI was defined at ≥ 3 UTI in 12 months, with symptoms and documented urine culture. Preoperative CT was performed in all patients to determine stone burden. All patients had postoperative imaging and ≥ 12 months of follow-up. Pre- and postoperative variables were between patients who had recurrent UTI after treatment versus those who did not. 46 patients met inclusion criteria. 42 (91.3%) were female. Median age was 63.7 years (IQR 49.1, 73.4) and median total stone burden was 20 mm (IQR 14–35). Within the cohort, 20 (43.5%) underwent ureteroscopy only, 26 (56.5%) underwent PCNL ± URS, and none underwent ESWL. Median postoperative follow-up was 2.9 years (IQR 2.0, 4.3). Only five patients (10.9%) had recurrent UTI after treatment. 80% were with the preoperative pathogen. The presence of residual stone was an independent risk factor for recurrent UTI after treatment (p < 0.046). Diabetes, hypertension, immunosuppression and chronic kidney disease were not. Stone removal for patients with recurrent UTIs was associated with a high rate of success (89.1%) in elimination of further recurrent UTIs. Residual fragments are independently associated with persistent recurrent UTIs and thus, complete stone removal is of paramount importance in treatment of this patient population.
Educational attainment and drinking behaviors: Mendelian randomization study in UK Biobank

Educational attainment has been associated with drinking behaviors in observation studies. We performed Mendelian randomization analysis to determine whether educational attainment causally affected drinking behaviors, including amount of alcohol intakes (in total and various types), drinking frequency, and drinking with or without meals among 334,507 white British participants from the UK Biobank cohort. We found that genetically instrumented higher education (1 additional year) was significantly related to higher total amount of alcohol intake (inverse-variance weighted method (IVW): beta = 0.44, 95% confidence interval (CI) 0.40–0.49, P = 1.57E−93). The causal relations with total amount and frequency of alcohol drinking were more evident among women. In analyses of different types of alcohol, higher educational attainment showed the strongest causal relation with more consumption of red wine (IVW beta = 0.34, 95% CI 0.32–0.36, P = 2.65E−247), followed by white wine/champagne, in a gender-specific manner. An inverse association was found for beer/cider and spirits. In addition, we found that 1 additional year of educational attainment was causally related to higher drinking frequency (IVW beta = 0.54, 95% CI 0.51–0.57, P = 4.87E−230) and a higher likelihood to take alcohol with meals (IVW: odds ratio (OR) = 3.10, 95% CI 2.93–3.29, P = 0.00E + 00). The results indicate causal relations of higher education with intake of more total alcohol especially red wine, and less beer/cider and spirits, more frequent drinking, and drinking with meals, suggesting the importance of improving drinking behaviors, especially among people with higher education.
Physician assistant utilization in U.S. emergency departments; 2010 to 2017.

Abstract Background Physician Assistants (PAs) are widely used in United States (US) Emergency Departments (EDs). We sought to characterize ED PA utilization and practice characteristics in US EDs 2010–2017. Methods A retrospective, secondary analysis of the 2010 to 2017 Center for Disease Control's National Hospital Ambulatory Medical Care Survey (NHAMCS) was performed. National estimates of ED visits involving PAs alone (PA), PAs with physician involvement (PA+), or physician only (PHYS) were analyzed for patient demographics and hospital characteristics. Results Between 2010 and 2017, an estimated 1 billion US ED visits occurred. 5.0% (95% confidence interval [CI] ±2.7%) of visits were seen by a PA, and 8.2% (±2.7%) by a PA+; 76.3% (±7.2%) by PHYS. No linear trends by year were identified in PA or PA+ visits. PA acuity was highest for semi-urgent/nonurgent (56.4%, ±10.7%). PA see the minority of ambulance arrival [5.8% (±1.3)] and admit less patients [1.7% (±0.7%)]. Less laboratory [53.3% (±10.2%) vs. 67.0% (±6.2%)] and radiographic [38.8% (±6.6%) vs. 51.6% (±4.6%) studies were performed during PA vs. PHYS visits. PA visits were most common for patients 25–44 years old (yo) (32.9%, ±6.2%) and 15–24 yo (19.2%, ±3.7%). Most PA visits result in a length of stay (LOS) between 1 and 1.9 h (32.9%, ±6.7%) compared to most PHYS visits resulting in a LOS >3 h (40.3%, ±3%). Conclusions From 2010 to 2017, no linear trends in US ED PA and PA+ utilization were identified. PHYS continue to see the majority of ED patients.
Role of Matrix Metalloproteinases in Colorectal Cancer

Colorectal cancer or CRC is amongst the top three leading causes of cancer related fatalities in the US. Advanced stages of CRC have very restricted treatment options. Matrix metalloproteinases (MMPs) are vital to maintain extracellular homeostasis, however, they play an important in CRC invasion and progression. Activities of MMP1, MMP2, MMP3, MMP7, MMP9, MMP13, and MT1-MMP are overexpressed in CRC and associated with worse results, whereas activities of MMP12 is known to be protective. Therefore, MMPs have become an important therapeutic target. Earlier clinical trials by broad-spectrum inhibitors of MMP have proven to be unsuccessful due to off-target toxicity as well as lack of efficiency. Currently, safe and selective inhibitors have transformed its therapeutic ability to target MMPs.
Improved recovery of cell-cycle gene expression in Saccharomyces cerevisiae from regulatory interactions in multiple omics data

Gene expression is regulated by DNA-binding transcription factors (TFs). Together with their target genes, these factors and their interactions collectively form a gene regulatory network (GRN), which is responsible for producing patterns of transcription, including cyclical processes such as genome replication and cell division. However, identifying how this network regulates the timing of these patterns, including important interactions and regulatory motifs, remains a challenging task. We employed four in vivo and in vitro regulatory data sets to investigate the regulatory basis of expression timing and phase-specific patterns cell-cycle expression in Saccharomyces cerevisiae. Specifically, we considered interactions based on direct binding between TF and target gene, indirect effects of TF deletion on gene expression, and computational inference. We found that the source of regulatory information significantly impacts the accuracy and completeness of recovering known cell-cycle expressed genes. The best approach involved combining TF-target and TF-TF interactions features from multiple datasets in a single model. In addition, TFs important to multiple phases of cell-cycle expression also have the greatest impact on individual phases. Important TFs regulating a cell-cycle phase also tend to form modules in the GRN, including two sub-modules composed entirely of unannotated cell-cycle regulators (STE12-TEC1 and RAP1-HAP1-MSN4). Our findings illustrate the importance of integrating both multiple omics data and regulatory motifs in order to understand the significance regulatory interactions involved in timing gene expression. This integrated approached allowed us to recover both known cell-cycles interactions and the overall pattern of phase-specific expression across the cell-cycle better than any single data set. Likewise, by looking at regulatory motifs in the form of TF-TF interactions, we identified sets of TFs whose co-regulation of target genes was important for cell-cycle expression, even when regulation by individual TFs was not. Overall, this demonstrates the power of integrating multiple data sets and models of interaction in order to understand the regulatory basis of established biological processes and their associated gene regulatory networks.
A 10 $\mu \mathrm{W}-74.6\mathrm{dB}$ THD Arterial Pulse Waveform Sensing System with Automatic Bridge-Offset Calibration and Super Class-AB Output Stage

This paper presents a power-efficient, highly-linear sensing system for arterial pulse waveform (APW) acquisition. The system consists of a front-end circuit connected to a packaged silicone-coated resistive-bridge pressure sensor for detecting APW through direct skin contact in a non-invasive manner. Compared to other pulse sensing approaches, the proposed front-end only requires an instrumentation amplifier (IA) and a low-pass filtering analog-to-digital converter (LPF-ADC), and consumes a total power of 10 $\mu \mathrm{W}$ . An automatic calibration circuit is proposed to compensate for the resistive-bridge offset and can reduce such offset down to 1 mV. High linearity in the IA is provided through the use of a super class-AB output stage. A LPF-ADC architecture is employed to extract and digitize the APW in a 100 Hz bandwidth, saving 90 % of the passives area. The front-end provides a measured input-referred noise of 7.2 $\mu \mathbf{Vrms}$ with a gain of 32–40 dB, and a THD of -74.6 dB. Together with an on-chip low dropout regulator (LDO) and a buffer stage, the prototype fabricated in 0.18 $\mu \mathrm{m}$ CMOS technology has an active area of 0.52 mm2.
Multiple Non-Linear Epitopes of ADAMTS13 Were Targeted by Anti- ADAMTS13 IgG in Patients with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura

Abstract Most patients with idiopathic thrombotic thrombocytopenic purpura (TTP) are caused by acquired autoantibodies that bind and inhibit proteolytic activity of ADAMTS13, a metalloprotease that cleaves von Willebrand factor (vWF). However, the binding epitopes of these anti-ADAMTS13 autoantibodies in many cases have not been fully defined. The limited data in the literature were largely from studies of small sample size, using less desirable recombinant ADAMTS13 fragments expressed in E. coli bacteria or insect cells or employing a non-physiological technique for detection. The results were therefore either inconclusive or controversial. To overcome these pitfalls, the full-length ADAMTS13 and various fragments of ADAMTS13 were expressed in human embryonic kidney (HEK293) cells. The recombinant proteins were purified by a combination of anion exchange chromatography and Ni-NTA affinity column. The antibody and antigen reactions were all performed in phosphate-buffered saline at pH 7.4. The immune complexes were collected by incubation with protein A/G Sepharose. After electrophoresis under denatured and reduced conditions, the antigens (ADAMTS13 and fragments) were then detected by Western blot with anti-V5 IgG, which recognizes the carboxyl terminal V5- His epitopes of the recombinant proteins. We showed that IgGs from 67 patients with acquired idiopathic TTP all interacted with full-length ADAMTS13 (construct FL-AD13) and the CUB domainless variant (construct delCUB). Approximately 97% (65/67) of IgGs in TTP patients bound the variant truncated after the spacer domain (construct MDTCS). However, a removal of the Cys-rich and spacer domains (construct MDT) reduced its reactivity with IgGs from TTP patients by 88%, suggesting the important contribution of these domains to the antibody binding epitopes. Unexpectedly, a fragment consisting of a disintegrin domain, the first TSP1 repeat, the Cys-rich and spacer domains (construct DTCS) reacted with IgGs from only 52% of TTP patients, indicating the additional contribution of the metalloprotease domain to these non-linear binding epitopes. Moreover, approximately 31%, 37%, and 46% of patients' IgGs targeted against the carboxyl terminal CUB domains, TSP1 2–8, and TSP1 5-8CUB, respectively. Low platelet count was observed at the time of admission in patients with the IgGs that reacted with the TSP1 2–8 and CUB domains of ADAMTS13, suggesting that the autoantibodies with the specificity toward more distal carboxyl-terminal domains of ADAMTS13 may impair ADAMTS13 function in vivo. We conclude that while the Cys-rich and spacer domains of ADAMTS13 contain the core epitopes, other adjacent functional domains may also contribute to the non-linear binding epitopes that are recognized by anti-ADAMTS13 IgGs. The data further support the role of autoantibodies against the middle and distal carboxyl terminal domains of ADAMTS13 in pathogenesis of TTP. Our findings provide novel insight into the mechanism of autoimmune-mediated TTP.
Assessment of Critical Experiment Benchmark Applicability to a Large-Capacity HALEU Transportation Package Concept

This work presents an assessment of the applicability of existing benchmark critical experiments to the criticality safety code validation for a large-capacity high-assay low-enriched uranium (HALE...
Research on Active Current Suppression Control Strategy of Photovoltaic Generation System

With the proportion of DC-connected photovoltaic (PV) power supply to the power supply capacity of the grid is increasing, its impact on the grid is also gradually increasing. In this paper, inter-pole short circuit fault and pole-to-ground short circuit fault of the PV generation system in the micro-grid are studied. Firstly, the inter-pole and monopolar short circuit fault characteristics in the DC micro-grid are analyzed. Secondly, the fault state detection method is improved by combining the fault characteristics. It is proposed to control the power electronic element IGBT in the converter to keep it on during faults, so as to shunt the current provided by PV cell, and finally achieve the purpose of suppressor the fault current. The proposed scheme is verified, and the simulation results prove that the control strategy can effectively suppress the fault current of the PV generation system.
Caspase-8 mutations associated with head and neck cancer differentially retain functional properties related to TRAIL-induced apoptosis and cytokine induction

The cysteine protease, caspase-8, undergoes dimerization, processing, and activation following stimulation of cells with death ligands such as TRAIL, and mediates TRAIL induction of the extrinsic apoptosis pathway. In addition, caspase-8 mediates TRAIL-induced activation of NF-κB and upregulation of immunosuppressive chemokines/cytokines, via a mechanism independent of caspase-8 catalytic activity. The gene encoding procaspase-8 is mutated in 10% of human head and neck squamous cell carcinomas (HNSCCs). Despite a paucity of experimental evidence, HNSCC-associated caspase-8 mutations are commonly assumed to be loss of function. To investigate their functional properties and phenotypic effects, 18 HNSCC-associated caspase-8 mutants were expressed in doxycycline-inducible fashion in cell line models wherein the endogenous wild-type caspase-8 was deleted. We observed that 5/8 mutants in the amino-terminal prodomain, but 0/10 mutants in the carboxyl-terminal catalytic region, retained an ability to mediate TRAIL-induced apoptosis. Caspase-8 proteins with mutations in the prodomain were defective in dimerization, whereas all ten of the catalytic region mutants efficiently dimerized, revealing an inverse relationship between dimerization and apoptosis induction for the mutant proteins. Roughly half (3/8) of the prodomain mutants and 9/10 of the catalytic region mutants retained the ability to mediate TRAIL induction of immunosuppressive CXCL1, IL-6, or IL-8. Doxycycline-induced expression of wild-type caspase-8 or a representative mutant led to an increased percentage of T and NKT cells in syngeneic HNSCC xenograft tumors. These findings demonstrate that HNSCC-associated caspase-8 mutants retain properties that may influence TRAIL-mediated apoptosis and cytokine induction, as well as the composition of the tumor microenvironment.