cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 745: Oncostatin M receptor activation leads to molecular targeted therapy resistance in non-small cell lung cancer

Background: The emergence of molecular targeted therapies against driver mutations and gene fusions has resulted in significant therapeutic advances within a subset of non-small cell lung cancer (NSCLC) patients. However, even when targeted therapy is effective, patients eventually develop resistance and better therapies in this setting are still being sought. Preliminary studies, from the ongoing BATTLE-2 clinical trial in chemo-refractory NSCLC, identified a number of molecular candidates portending to targeted therapy resistance, including the oncostatin M (OSM) and leukemia inhibitory factor (LIF) receptors (OSMR, LIFR), both co-localized on a frequently amplified chromosome 5p region. In this study, we investigated the functional contribution of the OSM pathway to targeted therapy resistance in NSCLC. Materials and Methods: We analyzed OSM, OSMR, LIFR, and associated downstream pathways in a panel of OSMR-LIFR amplified (10) and diploid (10) NSCLC cell lines, in both mono- and co-culture experiments using human normal and lung cancer-associated fibroblasts (CAFs). We assessed the effect of OSM pathway stimulation and blockade on sensitivity to a variety of molecularly targeted agents. Further, we performed correlative studies using the BATTLE-2 molecular dataset. Results: OSM stimulation activated cell proliferation and survival pathways (AKT-mediated) through OSMR and LIFR. In addition, a dramatic JAK1/STAT3 pathway activation was predominant in OSMR amplified cells and was associated with EMT features. Co-culture experiments suggested a preferential paracrine activation of the OSM-STAT3 pathway, underscoring the importance of the microenvironment. Interestingly, OSM stimulation protected cells from drug-induced apoptosis in a STAT3-dependent manner. In the BATTLE-2 translational analysis, we also found that OSMR upregulation was significantly associated to STAT3 upregulation and EMT-gene expression signatures. Conclusions: Our data suggest that the OSM-OSMR/LIFR-STAT3 pathway causes EMT and contributes to molecular targeted therapy resistance in oncogene-addicted NSCLC cells, suggesting that this pathway could be a therapeutic target in NSCLC. Ongoing experiments are assessing therapeutic vulnerabilities and refining the signaling functionally involved. Supported by NIH-NCI CA155196 & 2P50CA070907-16A1 Citation Format: Kazuhiko Shien, Vassiliki A. Papadimitrakopoulou, Dennis Ruder, Nana E. Hanson, Neda Kalhor, J. Jack Lee, Waun Ki Hong, Ximing Tang, Roy S. Herbst, Luc Girard, John D. Minna, Jonathan M. Kurie, Ignacio I. Wistuba, Julie G. Izzo. Oncostatin M receptor activation leads to molecular targeted therapy resistance in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 745. doi:10.1158/1538-7445.AM2015-745
Natural Orifice-Assisted Laparoscopic Meckel Diverticulectomy Incidentally Found During Para-Aortic Mass Resection.

Abstract Study Objective To show a surgical video in which an incidentally found Meckel diverticulum was resected with a natural orifice–assisted laparoscopic approach during para-aortic resection of a retroperitoneal schwannoma. Design Case report (Canadian Task Force classification III). Setting Tertiary referral center in New Haven, Connecticut. Interventions This is a step-by-step illustration for resection of a retroperitoneal para-aortic schwannoma and of an incidentally found Meckel diverticulum. The patient was a 39-year-old white woman diagnosed with stage IV choriocarcinoma with metastasis to the lungs and left para-aortic area. She received chemotherapy in the form of etoposide, methotrexate, actinomycin-D, cyclophosphamide, oncovine (EMA-CO) and had an excellent clinical response with resolution of all metastatic disease except for the para-aortic mass. Therefore, she was taken to the operating room for laparoscopic resection of the persistent left para-aortic mass. After placement of four 5-mm abdominal ports, the pelvis and abdomen were explored and revealed an incidental Meckel diverticulum as well as the 5 cm left para-aortic mass. The peritoneum overlying the para-aortic mass was incised and the retroperitoneum explored. Given the proximity to the mass, left ureterolysis was performed. The retroperitoneal attachments were resected, and the left para-aortic mass was removed without any complications. At this point attention was turned to the Meckel diverticulum. In order not to extend the abdominal incisions, a posterior colpotomy was performed in the cul-de-sac equidistant from the uterosacral ligaments. Endo-GIA (Covidien, New Haven CT) was introduced through the 10-mm port site at the posterior colpotomy. Meckel diverticulum was resected without narrowing the lumen of the distal ileum. The specimen was removed in a contained manner through posterior colpotomy. Measurements and Main Results The procedure was performed without any complications. The patient had an uneventful postoperative course and was discharged home on postoperative day 0. Pathology revealed a retroperitoneal schwannoma with negative margins and benign Meckel diverticulum without ectopic gastric or pancreatic tissue. The patient has been disease-free since the completion of surgery. Conclusion Laparoscopic resection of the retroperitoneal schwannoma and Meckel diverticulum were successfully performed in this patient with history of stage IV choriocarcinoma. To our knowledge, this is the first report describing a natural orifice–assisted laparoscopic approach for resection of Meckel diverticulum. Natural orifice–assisted laparoscopy should be considered when the surgeon needs to remove a large specimen and/or to introduce >5-mm diameter instruments into the peritoneal cavity without having to extend the abdominal incisions.
Unfolding the Folding Problem of the Cerebral Cortex: Movin’ and Groovin’

The development of reproducible folding in the gyrencephalic cerebral cortex is a topic of great interest to neuroscientists. In a recent paper in Cell, del Toro et al. (2017) show that changing the adhesive properties of neurons in the normally lissencephalic mouse cortex leads to the formation of stereotyped folding.
Drugs for the Management of Dystonia and Movement Disorders

Of all pharmacologic methods used to treat movement disorders following traumatic brain injury, none are without side effects. When deciding to treat a movement disorder, weigh the potential risks and benefits. If pharmacologic management is deemed necessary, an attempt should be made periodically to wean the patient from the medications, because a spontaneous remission may occur.
Atrioventricular Nodal Reentrant Tachycardia

Atrioventricular (AV) nodal reentrant tachycardia is a common cause of paroxysmal supraventricular tachycardia. Based on observations made in animal experiments, the mechanism of AV nodal reentrant tachycardia was postulated to be due to “longitudinal dissociation” of the AV node [1–5] in which two AV nodal pathways with different functional properties — fast and slow converge proximally and distally to form proximal and distal common pathways. An atrial or ventricular premature impulse may thus induce a reentrant phenomenon, utilizing one pathway for anterograde conduction and the other pathway for retrograde conduction (Figures 11-1 through 11-3) [6–11].
A Live Simulation-Based Investigation: Interactions with Clients and Their Effect on Audit Judgment and Professional Skepticism

SUMMARY Threats to professional skepticism are embedded in the social relationships and interactions between auditors and management. These can affect auditor skepticism and the extent of audit pro...
Taxonomic status of Parotia berlepschi Kleinschmidt, 1897 based on analysis of external appearance, voice and behavior (Aves: Paradisaeidae)

Described from trade-skins of unknown origins, Parotia berlepschi Kleinschmidt, 1897 was the subject of a longstanding ornithological mystery that remained unresolved for well over a century. With few specimens and no known wild population, most taxonomic assessments over the last century have treated P. berlepschi as a subspecies of Parotia carolae Meyer, 1894. Following discovery of its geographical home in 2005, most authorities returned to giving P. berlepschi full species status. However, evidence supporting the delineation of P. berlepschi from P. carolae has not yet been fully articulated in the literature. Here, we assess phenotypic differentiation and the taxonomic status of P. berlepschi relative to P. carolae based on specimens and recordings of wild birds. With regard to external appearance and voice, which are important intersexual signals among polygynous birds-of-paradise, our analysis confirms that P. berlepschi is well-differentiated from P. carolae and should be treated as specifically distinct. Evidence for differentiation in courtship behavior is inconclusive and requires further study.
Dynamical van der waals model of glassy behavior

A model fluid system whose intermolecular forces consist of the short range part characterizing usual stable fluid and the long range part of Kac-type is considered. When the ratio of the force ranges is large enough, the system can be described by regarding the system having only short range interactions as a reference fluid treated as a continuum, on which long range forces acting among tiny fluid elements are superimposed. We discuss the glassy behavior of this model relating it to the mode coupling theory and using real replica theory. These theories lead to the two equations for non-ergodicity parameter which are totally different from each other. We argue that our model can be a basis for examining nature of the drastic approximations entering derivations of the mode coupling equations. We further explore the possibility of developing the dynamical real replica approach for our model system with the hope of providing a framework to cope with different time scales characterizing complex glassy behavior.
Hand and Wrist Soft Tissue Conditions

Benign tumors, tendon conditions, sprains, and other soft tissue injuries of the hand and wrist occur commonly. Patients may seek evaluation due to discomfort or dysfunction caused by a wide range of disorders afflicting the tendons, ligaments, and other soft tissues. It is important for the healthcare provider to recognize and understand the pathways of care for a variety of clinical pathologies, in order to appropriately expedite diagnosis and management. This chapter aims to provide an overview of the most common soft tissue conditions affecting the hand and wrist to aid the treating practitioner in diagnosis and treatment.
E-government field force automation: promises, challenges, and stakeholders

With the growing pervasiveness and maturity of fully mobile and wirelessly connected technologies (FMWC), many organizations have begun to equip their field workforce with such information and communication technologies (ICT). The aim of these projects is to automate fieldwork operations, that is, to make them more effective, to improve field force responsiveness, and to speed up the field processes, while using resources and assets more efficiently. In both private and public sectors, such projects have been pursued, yet the specific promises and challenges are not deeply understood. We share early but already robust results from a multi-year research project, which studies the nature and interaction of organizational, social, technological, and human-actor related variables in local government field workforce automation, or short, field force automation (FFA). According to our findings, the ICT-based automation of fieldwork and field workforce appears as a far more demanding undertaking than other successful automation projects. However, the high potential for significant gains in productivity and fieldwork efficacy seem to justify a sumptuous and at times arduous adaptation process.
On the Various Statements of the Second Law of Thermodynamics

According to the legend, Menelaus, on his return from Troy, surprised Proteus and held him fast through all his changes of form … The Century Dictionary and Cyclopedia , 1911
Are electronic nicotine delivery systems helping cigarette smokers quit? Evidence from a prospective cohort study of U.S. adult smokers, 2015-2016

Background The potential of electronic nicotine delivery systems (ENDS) to reduce the cardiovascular and other disease risks of smoking is of great interest. While many smokers report using ENDS for cessation, their impact under real-world use patterns and conditions on adult smokers’ quitting behavior is uncertain. The objective of this study was to generate more recent and comprehensive evidence on the effect of “real world” ENDS use on the population quit rates of adult smokers while taking account of frequency and duration of use, device type, e-liquid flavor, and reasons for use. Methods and findings We conducted a population-based, prospective cohort study of a random probability sample of 1284 U.S. adult smokers recruited in August/September 2015 and re-contacted one-year later (September 2016) from GfK’s KnowledgePanel, a national, probability-based web-panel designed to be representative of non-institutionalized U.S. adults. Among the 1081 baseline smokers who remained members of KnowledgePanel, 858 completed the follow-up survey. The primary outcome was smoking abstinence for at least 30 days prior to follow-up. Secondary outcomes were making a quit attempt during the 12-month study period and number of cigarettes smoked per day at follow-up. The adjusted odds of quitting smoking were lower for those that used ENDS at baseline (9.4%, 95% CI = 5.22%-16.38%; AOR = 0.30, 95% CI = 0.13–0.72) compared to smokers who did not use at ENDS (18.9%, 95% CI = 14.24%-24.68%). Smokers who used ENDS daily at some point during the study period were also less likely to quit smoking than nonusers (AOR = 0.17; 95% CI = 0.04–0.82). Limited ability to draw causal inferences from the observational design and a lack of biochemical verification of quitting smoking or ENDS use are limitations of this study. Conclusions We found no evidence that ENDS use, within context of the 2015–2016 US regulatory and tobacco/vaping market landscape, helped adult smokers quit at rates higher than smokers who did not use these products. Absent any meaningful changes, ENDS use among adult smokers is unlikely to be a sufficient solution to obtaining a meaningful increase in population quit rates. Additional research is needed to reconcile the divergent literature and monitor the impact of ENDS in an environment of rapidly evolving markets and regulatory policies.
Effects of Inhibitors on the Membrane Potential (Δψ) of Mung Bean Mitochondria

Safranine O was used to measure changes imposed on the membrane potential (Δψ) of mung bean mitochondria by different metabolic conditions and inhibitors. Changes in Δψ were correlated with simultaneously made measurements of O2 uptake. Δψ values of 129 ± 3 mV and 144 ± 4 mV were obtained under state 3 and state 4 conditions, respectively, during the oxidation of malate. At concentrations of electron transport inhibitors that maximally inhibited O2 utilization, Δψ was only partially collapsed. Under state 4 conditions, the collapse of Δψ to the Donnan potential by uncouplers correlated with the concentration at which state 4 respiration was stimulated maximally. Inhibition of O2 utilization by F0 inhibitors correlated with an increase in Δψ from the state 3 to the state 4 potential.
Glycerol 3-phosphate dehydrogenases in social bees.

Electrophoretic analysis of extracts of 12 bumblebee species revealed complex patterns of extramitochondrial diphosphopyridine nucleotide-dependent glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) variants. Most Bombus species show one pattern, while Bombus nevadensis has a second and Bombus occidentalis a third pattern. All three Psithyrus (i.e. parasitic bumblebee) species tested have a fourth pattern. All patterns share one feature, i.e. there is both a slow and fast migrating set of two to four bands each. The slow set, as a whole, stains more intensely than the fast set in flight muscle extracts, whereas the opposite is true for extracts of heads and abdomens. The slow sets have been termed "alar-muscular," the fast sets "omniregional." The major alar-muscular isozyme has been crystallized from thoraces of B. nevadensis. The omniregional isozymes of most, but not all, bumblebees utilize triphosphopyridine nucleotide, whereas none of the alarmuscular variants utilize this nucleotide. Electrophoretic experiments indicate that most, if not all, the variants differ in primary structure. In contrast to bumblebees, honeybees have only one form of glycerol 3-phosphate dehydrogenase. Rabbit antibodies directed against glycerol 3-phosphate dehydrogenase of honeybees and of B. nevadensis were prepared. Each of these antisera precipitated the honeybee enzyme and all of the bumblebee isozymes. Immunological experiments using the micro-complement fixation technique with anti-B. nevadensis glycerol 3-phosphate dehydrogenase reveal that thoracic extracts of all other bumblebees tested cross-reacted very strongly, with Bombus bifarius and B. occidentalis extracts showing slightly less reactivity than that of the other Bombus and Psithyrus species. Honeybee extracts cross-reacted much more weakly. Micro-complement fixation studies with anti-honeybee glycerol 3-phosphate dehydrogenase suggest that extracts of different bumblebee species are immunochemically indistinguishable from one another.
Language: Being Familiar

To inform your audience, you have to use language that your audience understands. When you have an audience outside your area of expertise, it is often difficult to find familiar language. Why? Scientists and engineers work on particular crooks of particular ridges of particular mountains, and each mountain has its own special set of terms. These terms may be words or abbreviations: Plasma Physics: glow discharge MHD Hemodynamics: immunodeficiency B cells Spectroscopy: gas chromatography GC/MS
Race, Structural Predictors, and Police Shootings: Are There Differences Across Official and “Unofficial” Accounts of Lethal Force?:

Police shootings have received considerable attention recently. While official data have often been used to capture police use of lethal force, “unofficial” databases have been developed to document lethal force patterns throughout the United States. Thus, it is now possible to systematically compare databases, exploring racial differences and potential causes, which is important given longstanding criticisms of official records. Here, we examine police shootings using Mapping Police Violence and Supplemental Homicide Reports data and investigate the impact of commonly used structural predictors on race-specific police shootings. Significant differences are revealed across official and unofficial databases, particularly by race. We conclude that the data used to estimate police shootings matter, which has key implications for future work on this important topic.
Learning from bacterial competition in the host to develop antimicrobials

In recent years, the alarming increase of antibiotic resistance, compounded by the simultaneous decrease in development of new antibiotics, has created serious concerns for public health. Moreover, current antibiotics also target the beneficial commensal microbes (microbiota) that inhabit our body, sometimes with significant health consequences. The answer to the antibiotic crisis thus involves broad, creative efforts to develop new treatments for infectious agents. Here I discuss what can be learned from investigating microbial competition in vivo and how this knowledge can be utilized to devise new narrow-spectrum therapeutics that target bacterial pathogens while minimizing deleterious effects to the microbiota.
EEG predictors of dreaming outside of REM sleep.

The stream of human consciousness persists during sleep, albeit in altered form. Disconnected from external input, the mind and brain remain active, at times creating the bizarre sequences of thought and imagery that comprise "dreaming." Yet despite substantial effort toward understanding this unique state of consciousness, no reliable neurophysiological indicator of dreaming has been discovered. Here, we identified electroencephalographic (EEG) correlates of dreaming using a within-subjects design to characterize the EEG preceding awakenings from sleep onset, REM (rapid eye movement) sleep, and N2 (NREM Stage 2) sleep from which participants were asked to report their mental experience. During the transition into sleep, compared to periods during which participants reported thinking, emergence of dream imagery was associated with increased absolute power below 7 Hz. During later N2, dreaming conversely occurred during periods of decreased relative power below 1 Hz, accompanied by an increase in relative power above 4 Hz. No EEG predictors of dreaming were identified during REM. These observations suggest an inverted-U relationship between dreaming and the prevalence of low-frequency EEG rhythms, such that dreaming first emerges in concert with EEG slowing during the sleep-wake transition, but then disappears as high-amplitude slow oscillations come to dominate the recording during later N2 sleep.
An Evaluation of Communication Methods for Community Outreach in Patients with Diabetes

Research Objectives To prevent health complications, patients with type 2 diabetes mellitus should be regularly seen by their medical provider and routinely checked for hemoglobin A1c levels. However, many patients do not return for routine visits. The objective was to evaluate the efficacy of two communication modalities in scheduling patient appointments. Study Design/Methods Patients with a hemoglobin A1c > 9.0 not seen in clinic in >6 months were randomly assigned to a control or experimental group. All participants received an initial text message offering help with scheduling an appointment. The control group was contacted via a second text message and the experimental group was contacted via phone call. Additionally, the experimental group was asked to identify perceived healthcare barriers. In addition to the reported barriers, data included patients who scheduled and kept appointments in each group when data was available. Chi-squared test (p-value of <0.001) was performed. Principal Findings and Quantitative Results The total number of patients with an HbA1c greater than 9.0% was 416. A total of 156 were contacted with 34 (21.8%) participating. Twenty-five (16.0%) were lost to follow-up. Sixteen patients (47.1%) responded to voice and 18 (52.9%) to text. A chi-squared test with a value of 49.67 (p-value of <0.001) determined our findings significant. Ten (6.4%) were scheduled for follow-up. A larger proportion of patients received an appointment via voice (6 of 16, 37.5%) than text (4 of 18, 22.2%) with a chi-squared value of 118.56 (p-value of <0.0001). Conclusions/Impact on Health Centers The study demonstrated that combined use of text messaging and phone calls could lead to higher rates of scheduled appointments. Future studies could address whether appointments made with this method of contact are kept. One factor that limited scheduled appointments was that 16% of patients indicated they were no longer being seen at El Rio. This suggests the need for an additional feature to be placed in NextGen where staff can indicate that patients are no longer being followed. Results of our research will be presented at El Rio Research Fair in May 2019.
On the Basis of Sex (2018)

Focused on a relatively brief period in Ruth Bader Ginsburg’s career, “On the Basis of Sex” is a standard-issue biopic that conveys what she achieved in the fight for gender equality, and why it ma...
A Response to Núñez et al.'s (2019) “What Happened to Cognitive Science?”

Nunez et al.'s (2019) negative assessment of the field of cognitive science derives from evaluation criteria that fail to reflect the true nature of the field. In reality, the field is thriving on both the research and educational fronts, and it shows great promise for the future.
Teaching NeuroImages: Autoimmune glial fibrillary acidic protein meningoencephalomyelitis

A 73-year-old woman with myelodysplastic syndrome presented with 2 months of decline in cognition and mobility, accompanied by headache and weight loss. Examination revealed a somnolent woman with symmetric cogwheel rigidity, bradykinesia, arm myoclonus, and hyperreflexia. Brain MRI showed leptomeningeal, linear/stippled parenchymal, and ependymal enhancement (figure 1). Spine MRI demonstrated nonenhancing cervicothoracic cord signal change and circumferential enhancement of conus medullaris with central canal enhancement (figure 2). CSF was inflammatory with glial fibrillary acidic protein (GFAP)–immunoglobulin G (IgG). The patient responded promptly to IV methylprednisolone. GFAP-IgG identifies a severe but highly corticosteroid-responsive autoimmune meningoencephalomyelitis with distinctive MRI findings.1,2
Associations of accelerometer-measured physical activity and physical activity-related cancer incidence in older women: results from the WHI OPACH Study.

We examined the associations between accelerometry-measured physical activity (PA) and incidence of 13 cancers among a cohort of postmenopausal women. In this prospective study, 6382 women wore ActiGraph GT3X+ accelerometers at the hip for up to 7 days during 2012–2013, and were followed over a median of 4.7 years for diagnosis of 13 invasive cancers. Calibrated intensity cut points were used to define minutes per day of total, light and moderate-to-vigorous PA. We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles, and one-standard deviation (SD) unit increments of PA exposures in relation to cancer incidence. We examined effect measure modification by age, race/ethnicity, body mass index and smoking history. The highest (vs. lowest) tertiles of total, light and moderate-to-vigorous PA were associated with covariate-adjusted HRs of 0.72 (95% CI = 0.53–0.97), 0.81 (95% CI = 0.60–1.09) and 0.66 (95% CI = 0.48–0.91), respectively. In age-stratified analyses, HRs for total PA were lower among women <80 years (HRper one-SD = 0.75, 95% CI = 0.63–0.90) than among women ≥80 years (HRper one-SD = 0.99, 95% CI = 0.82–1.18) (PInteraction = 0.03). Race/ethnicity, BMI and smoking did not strongly modify these associations. Engaging in physical activity may play a beneficial role in the prevention of certain cancers in older women.
Introductory Lecture The Dopamine Vascular Receptor: Agonists and Antagonists

This paper describes the research which led to the discovery of the renal vasodilating action of dopamine (DA) and the subsequent evidence indicating that the phenomenon was due to action on a specific vascular receptor. The structure activity relationship of agonists and lists of specific antagonists of this receptor will be presented and compared with agonists and antagonists reported to be active on other DA receptors. Physiological and clinical implications of these findings will be discussed.
NMR spectroscopy: the swiss army knife of drug discovery

Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool within drug discovery over the last two decades. While traditionally being used by medicinal chemists for small molecule structure elucidation, it can also be a valuable tool for the identification of small molecules that bind to drug targets, for the characterization of target-ligand interactions and for hit-to-lead optimization. Here, we describe how NMR spectroscopy is integrated into the Pfizer drug discovery pipeline and how we utilize this approach to identify and validate initial hits and generate leads.
Preparation and Drug Entrapment Properties of Asymmetric Liposomes Containing Cationic and Anionic Lipids

We have developed cyclodextrin-catalyzed lipid exchange methods to prepare large unilamellar vesicles (LUVs) with asymmetric charge distributions, i.e., with different net charges on the lipids in the inner and outer leaflets. LUVs contained a mixture of a zwitterionic lipid (phosphatidylcholine), cholesterol, and various cationic lipids (O-ethyl phosphatidylcholine or dioleoyl-3-trimethylammonium propane) or anionic lipids (phosphatidylglycerol, phosphatidylserine, or phosphatidic acid). Symmetric and asymmetric LUVs with a wide variety of lipid combinations were prepared. The asymmetric LUVs contained cationic or anionic outer leaflets and inner leaflets that had either the opposite charge or were uncharged. The behavior of symmetric LUVs prepared with zwitterionic, anionic, or cationic leaflets was compared to those of asymmetric LUVs. Lipid exchange was confirmed by quantitative thin-layer chromatography, and lipid asymmetry by a novel assay measuring binding of a cationic fluorescent probe to the LUV outer leaflet. For both symmetric and asymmetric LUVs, the level of entrapment of the cationic drug doxorubicin was controlled by the charge on the inner leaflet, with the greatest entrapment and slowest leakage in vesicles with an anionic inner leaflet. This shows that it is possible to choose inner leaflet lipids to maximize liposomal loading of charged drugs independently of the identity of outer-leaflet lipids. This implies that it should also be possible to independently vary outer-leaflet lipids to, for example, impart favorable bioavailability and biodistribution properties to lipid vesicles.
Stochastic Geometry‐Based Performance Analysis of Drone Cellular Networks

To leverage the numerous benefits offered by drone cellular networks, the third generation partnership project (3GPP) has recently included the support for drone base stations (DBSs) communications as part of the fifth generation standard. This chapter focuses on a 3GPP‐inspired drone mobility model in which the initial locations of DBSs are modeled as a homogeneous 2D Poisson point process at a constant height from the ground and each DBS moves along a straight line in a random direction, independently of the other DBSs. Given the irregularity in the locations of DBSs and user equipment (UE), the use of tools from stochastic geometry is a natural choice for modeling and analysis of aerial communication networks. The chapter characterizes the point process of the interfering DBSs for service models, using which we derive the average received rate at the typical UE. It also characterizes the handover probability for the service models.
Pregnancy and Scleroderma

The management of scleroderma during pregnancy varies significantly by organ system involvement, medication use, and the development of new complications, such as renal crisis. Overall, women with scleroderma do well, with similar rates of miscarriages, and only slightly increased rates of premature birth and small for gestational age newborns. Pregnancies in women with pulmonary hypertension have high rates of maternal and fetal mortality, and should be avoided. Pregnancy may also be recommended against in women with significant interstitial lung disease or renal insufficiency, as they may not be able to safely adapt to the normal physiologic changes of pregnancy. Scleroderma renal crisis during pregnancy is an emergency that requires immediate administration of an ACE inhibitor, despite the teratogenic nature of this class of medication. Pregnancy should be avoided in those at highest risk for renal crisis, including those with 5 years or less of diffuse skin disease and those with antibodies to RNA polymerase III. Many anti-rheumatic medications used in scleroderma are teratogenic, and should be discontinued prior to conception.
Association between vision impairment and cognitive decline in older adults with stroke: Health and Retirement Study

Stroke survivors may experience multiple residual symptoms post-stroke, including vision impairment (VI) and cognitive decline. Prior studies have shown that VI is associated with cognitive decline, but have not evaluated the contribution of VI to post-stroke cognitive changes. We used data from four waves (2010–2016) of the Health and Retirement Study to investigate the cognitive trajectories of stroke survivors with and without VI. Vision (excellent–very good[ref], good, fair–poor) and stroke diagnosis were self-reported. Cognition was defined using the Telephone Interview for Cognitive Status. Regression was used to model the association between vision and change in cognitive function, adjusting for confounders. The final sample included 1,439 stroke survivors and the average follow-up time was 4.1 years. Fair–poor overall (B = −1.30, p < 0.01), near (B = −1.53, p < 0.001), and distance (B = −1.27, p < 0.001) vision were associated with significantly lower baseline cognitive function. VI was not associated with the rate of cognitive decline. Future research should determine whether specific types of VI potentiate the risk of cognitive impairment and dementia in stroke survivors.
The Language That Drives Engagement: A Systematic Large-scale Analysis of Headline Experiments.

We use a large-scale dataset of thousands of field experiments conducted on Upworthy.com, an online media platform, to investigate the informational, cognitive, linguistic, and affective factors implementable in messages to motivate people to engage with online content. We map from textual cues measured with Natural Language Processing tools to constructs implied to be relevant by a broad range of prior research literatures. We then test which constructs drive click- through to articles when implemented in headlines. Our findings suggest that the use of textual cues identified in previous research does impact the effectiveness of headlines overall, but the prior research does not provide useful guidance as to the direction of the effects. We identify the specific textual characteristics that make headlines most effective at motivating engagement.
Elevated salivary cortisol predicts response to adjunctive immune modulation in treatment-resistant bipolar depression

Abstract Background Adjunctive inflammatory treatments improve response and remission rates in treatment-resistant bipolar depression (TRBDD), but underlying mechanisms remain unclear. Given the association between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and treatment-resistant depression, we investigated the pre-treatment HPA-axis profile in relation to treatment response. Methods This is a secondary analysis of 31 TRBDD patients with moderately severe depression scores as assessed with the Hamilton Depression Rating Scale 17 (HAMD17), who were randomized to receive either escitalopram (ESC) (10–40 mg daily) + celecoxib (CBX) (200 mg twice daily), or ESC (10–40 mg daily) + placebo (PBO) (twice daily). Salivary cortisol was measured at baseline. A multivariate linear regression model was applied to evaluate whether depression scores at Week 8 were related to CBX and baseline salivary cortisol, adjusting for sex, age, BMI, and baseline depression scores. We utilized the HAMD17 and Montgomery-Asberg Depression Rating Scale (MADRS). Results Coefficient of determination (R2) for week 8 MADRS and HAMD17 scores were 0.907 and 0.624 (both p-value Conclusions /* Increased salivary cortisol levels at baseline diurnal timepoints independently predicted posttreatment depression scores in TRBDD patients treated with either with antidepressant monotherapy or combined CBX therapy.
Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer’s disease risk variant p.S1038C in the TTC3 gene

The UMi028-A-2 human induced pluripotent stem cell line carries a homozygous mutation (rs377155188, C>G, p.S1038C) in the tetratricopeptide repeat domain 3 (TTC3) gene that was introduced via CRISPR/Cas9 genome editing. The line was originally derived from a neurologically normal male and has been thoroughly characterized following editing. The p.S1038C variant has been shown to potentially contribute to the risk of late onset Alzheimer's disease and is a resource to further investigate the consequences of TTC3 and this alteration in disease pathology.
Communicative and Discursive Perspectives on the Medication Experience

Taking the ‘medication experience’ in the broad sense of what individuals hear and say about their medication, as well as how they experience it, this paper explores diverse research on medication information available to patients and their modes and capacities for interaction, including personal circles, doctors and pharmacists, labeling and promotion, websites, and the patient’s own inner conversations and self-expression. The goal is to illustrate, for nonspecialists in communication, how the actors, messages, mediums, genres, and contextual factors within a standard ethnographic and social semiotic model of discourse and communication are operating, not always effectively or beneficially, to mediate or construct a patient’s medication experience. We also suggest how disparate insights can be integrated through such a model and might generate new research questions.
Initial Management of Youth with Type 1 Diabetes

The Yale T1D Treatment Program has utilized traditional, twice a day injections of insulin as initial treatment of youth with type 1 diabetes (T1D). Moreover, almost all of our newly diagnosed patients are admitted to the hospital when first diagnosed with T1D. While the limitations of twice a day insulin injections become more apparent over time, it is very effective during the initial treatment of T1D, since most youngsters go through a honeymoon period of increased endogenous insulin secretion during the first 6 months of diabetes. We refer to this approach as “The Bridge to Pump Treatment,” since most of our patients transition to pump therapy when metabolic control of diabetes because more difficult during the second half of the first year of treatment.
Osmotic tubulopathy in a patient with COVID-19 treated with remdesivir.

Coronavirus Disease 2019 (COVID-19) has posed unique challenges to nephrology. COVID-19–associated acute kidney injury occurs in as high as 36.6% of patients,S1 with the most common etiology being acute tubular injury due to hemodynamic changes and a proinflammatory milieu. In addition to acute tubular injury, patients with COVID-19 can also develop a variety of glomerular pathologies, including primary podocytopathies and immune-mediated glomerular diseases (membranous nephropathy, lupus nephritis, anti–glomerular basement membrane disease).1 Here, we report another pattern of tubular pathology related to COVID-19, osmotic injury associated with antiviral therapy.
Self-identified Race and COVID-19-Associated Acute Kidney Injury and Inflammation: a Retrospective Cohort Study of Hospitalized Inner-City COVID-19 Patients.

Black individuals have been disproportionately affected by the coronavirus disease 2019 (COVID-19). However, it remains unclear whether there are any biological factors that predispose Black patients to COVID-19-related morbidity and mortality. To compare in-hospital morbidity, mortality, and inflammatory marker levels between Black and White hospitalized COVID-19 patients. This single-center retrospective cohort study analyzed data for Black and White patients aged ≥18 years hospitalized with a positive SARS-CoV-2 PCR test between March 1, 2020, and August 4, 2020. The exposure was self-identified race documented in the medical record. The primary outcome of was in-hospital death. Secondary outcomes included intensive care unit admission, hospital morbidities, and inflammatory marker levels. A total of 1,424 Black and White patients were identified. The mean ± SD age was 56.1 ± 17.4 years, and 663 (44.5%) were female. There were 683 (48.0%) Black and 741 (52.0%) White patients. In the univariate analysis, Black patients had longer hospital stays (8.1 ± 10.2 vs. 6.7 ± 8.3 days, p = 0.011) and tended to have higher rates of in-hospital death (11.0% vs. 7.3%), myocardial infarction (6.9% vs. 4.5%), pulmonary embolism (PE; 5.0% vs. 2.3%), and acute kidney injury (AKI; 39.4% vs. 23.1%) than White patients (p <0.05). However, after adjusting for potential confounders, only PE (adjusted odds ratio [aOR] 2.07, 95% CI, 1.13–3.79) and AKI (aOR 2.16, 95% CI, 1.57–2.97) were statistically significantly associated with Black race. In comparison with White patients, Black patients had statistically significantly higher peak plasma D-dimer (standardized β = 0.10), erythrocyte sedimentation rate (standardized β = 0.13), ferritin (standardized β = 0.09), and lactate dehydrogenase (standardized β = 0.11), after adjusting for potential confounders (p<0.05). Black hospitalized COVID-19 patients had increased risks of developing PE and AKI and higher inflammatory marker levels compared with White patients. This observation may be explained by differences in the prevalence and severity of underlying comorbidities and other unmeasured biologic risk factors between Black and White patients. Future research is needed to investigate the mechanism of these observed differences in outcomes of severe COVID-19 infection in Black versus White patients.
Best Practices for Building a High-Tech Law School [book]

Written for all those involved in a new building or renovation process for law school classes, this state-of-the-art book explains the entire building construction process, the roles and responsibilities of the stakeholders involved in the project, and the technology options and ramifications that each choice holds. Substantive chapters each include a checklist as an appendix. Topics include: preparation and planning, using technology design consultants, space and adjacency requirements, classroom technology and design, courtroom technology, clinic technology, and building accents.
Biomarker testing in patients (pts) with metastatic colorectal cancer (mCRC): Survey of U.S. oncologists (ONC) in rural areas and urban clusters.

108Background: In the US, rural areas have higher cancer mortality rates than urban areas. Clinical practice guidelines recommend testing for BRAF and RAS mutations, and deficient mismatch repair (...
Pediatric Providers' Knowledge, Attitudes, Practice, and Barriers to Firearms Safety Counseling.

Objectives Firearms-related injuries and deaths are a leading cause of death in children and young adults ages 5 to 24 years. This study evaluated the counseling practices and barriers to providing safe firearms storage education by pediatricians and advance practice providers. Methods An online survey was sent to 296 pediatric outpatient providers in Houston, Texas. Pediatric providers were asked about demographics, knowledge, attitudes, and current practices regarding firearms safety counseling. Descriptive and comparative analyses were performed. Results Survey respondents (N = 76) were 86% women and 87% physicians. Most (86%) agree that they should discuss firearms safety with parents, whereas only 32% report routine counseling. The most frequent barrier to providing education was insufficient time (63%), followed by unfamiliarity with guns (26%). Conclusions Pediatric providers are interested in firearms safety counseling, but few incorporate it into their practice. Addressing barriers of time and comfort level around firearms are potential first steps to curbing a leading cause of injury death among children. Further research is needed to develop counseling methods that are time efficient and culturally competent for the pediatric office.
Preparing the Critically Ill or Injured Child for Surgery

The identification and assessment of perioperative risk factors in the critically ill child requiring surgery is important, because targeting these risk factors allows the creation of care plans that can significantly improve outcomes. This chapter provides an overview of the preoperative assessment and preparation of these patients for surgery. It reviews fasting guidelines, provides a systems-approach to the preoperative assessment, administration of preoperative medications, and determination of which preoperative laboratory or radiological data to attain. Appropriate access and monitoring, risk involved in the transportation process, reducing surgical site infections in the pediatric patient, and the importance of effective multidisciplinary communication and communication with patients and their families is also addressed.
Why Can’t I Be More Like My Brother? The Role and Correlates of Sibling Social Comparison Orientation

Siblings play an important role in relational and individual development throughout adolescence and beyond through several mechanisms. Central to this role and the mechanisms of sibling influence is the notion that siblings provide a constant and meaningful frame of reference for social comparison. This study examined the role of sibling social comparison orientation, or the tendency of siblings to compare themselves to one another, on youths' depressive symptoms and family relationships, both directly and by moderating links with parental differential treatment. Participants included 338 youth (M age = 18.34, SD = 1.03; 52 % female). Using hierarchical ordinary least squares regression, we found that a higher sibling social comparison orientation was linked with more depressive symptoms, warmer sibling relationships, and more sibling conflict. Additionally, sibling social comparison orientation moderated links of parental differential treatment with depressive symptoms and prosocial behavior toward family members such that effects were more salient for those with a high comparison orientation. The discussion focuses on the role of sibling comparison in the ways that siblings influence one another's development.
Media & Minorities: The Politics of Race in News and Entertainment, by Stephanie Greco Larson

Stephanie Greco Larson, a professor of political science at Dickinson College, has assumed the weighty responsibility of bringing some coherence to a multidimensional area of political communicatio...
The Law of Peoples, Distributive Justice, and Migrations

When at the end of the eighteenth century Kant penned his reflections on cosmopolitan right, the expansion of western imperialist ventures into the Americas had been underway for several centuries, since the late 1400s, while in the same period the Dutch, the Portuguese, the Spanish, and the British imperial navies had been vying with each other for dominance in the Indian Ocean, Southeast Asia, and the Far East. The right to hospitality was articulated against the background of such western colonial and expansionist ambitions. Kant's extensive references to the opening of Japan and China to western travelers and merchants in the “Perpetual Peace” essay give us a very lively sense of this historical context (Kant [1795] 1923, 444–446; see also Wischke 2002, 227). Arendt's reflections on statelessness emerge against a different historical background: the collapse of the multinational and multiethnic empires in Europe in the period between two world wars. The extensive use of denaturalization – that is, revocation of citizenship rights – to deal with unwanted minorities and refugees on the part of the European nation-states emerges in this context. A most brilliant, even if not fully explored, insight on Arendt's part is that the experiences gained by western powers during the colonization of Africa inform and even historically inspire the treatment of minorities in continental Europe. Overseas imperialism and continental imperialism are related. Despite these observations, missing from Kant's as well as Arendt's considerations is an explicit recognition of the economic interdependence of peoples in a world society.