cssi/SciSciGPT-SciSciNet huggingface dataset:
Plasma ApoA1 Associates with Age at Onset and Motor Severity in Early Parkinson Disease Patients (P6.068)

OBJECTIVE:To validate plasma Apolipoprotein A1 (ApoA1) as a marker of disease risk and motor severity in Parkinson disease (PD). BACKGROUND:The development of robust plasma-based biomarkers in Parkinson disease (PD) could lead to new approaches for identifying those at risk for PD and developing novel therapies. We previously identified ApoA1 as a candidate biomarker for PD risk, whereby lower ApoA1 levels were associated with earlier age at disease onset. DESIGN/METHODS:Plasma ApoA1 and HDL at baseline, six months, and 12 months were measured in 254 research volunteers [154 patients with PD and 100 normal controls (NC)] enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study. RESULTS: Lower baseline plasma ApoA1 levels associate with an earlier age at PD onset in early-stage, drug-naive PPMI PD patients (p=0.023). Moreover, lower baseline ApoA1 levels trend towards association with worse UPDRS-III score (motor severity) in PPMI PD patients (p=0.080). Over 12 months of follow-up, plasma ApoA1 levels do not predict motor decline in the PPMI PD cohort. Finally, a meta-analysis of five PD cohorts encompassing >1000 patients confirms significant association of lower plasma ApoA1 with earlier age at PD onset (p<0.001) and greater motor severity (p<0.001). CONCLUSIONS:Our results confirm the association of lower plasma ApoA1 levels with indicators of poorer dopaminergic system integrity in early-stage, drug-naive PD patients. This is the first report of a plasma-based biomarker evaluated in the PPMI study. Future investigations are warranted evaluating plasma ApoA1 as a longitudinal correlate of disease progression, and investigating the potential of ApoA1 as a therapeutic target in PD. Study Supported by: Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). Disclosure: Dr. Swanson has nothing to disclose. Dr. Berlyand has nothing to disclose. Dr. Xie has nothing to disclose. The NIH K02 NS080915. Parkinson9s Disease Foundation: research support. Smart Foundation: research support and the Michael J Fox foundation: research support through the L Dr. Chahine has nothing to disclose. Dr. Chen-Plotkin has nothing to disclose.
Can evolution be directional without being teleological

Convergent evolution reveals to us that the number of possibilities available for contingent events is limited, that historically contingent evolution is constrained to occur within a finite number of limited pathways, and that contingent evolution is thus probabilistic and predictable. That is, the phenomenon of convergence proves that truly contingent evolutionary processes can repeatedly produce the same, or very similar, organic designs in nature and that evolution is directional in these cases. For this reason it is argued in this paper that evolution can be directional without being teleological, and that the dichotomy that evolution must either be directionless and unpredictable or directional and predetermined (teleological) is false.
Operations Research in Solving a Marketing Problem

An Operations Research task group was assembled at the Sun Oil Company to consider future product policies. Possible courses of action were: (1) To retain the policy of marketing only a single grad...
Responses of Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) to Residues of Permethrin and Endosulfan

Tomato plants were sprayed to runoff with permethrin (0.112 kg [AI]/ha) or endosulfan (0.560 kg [AI]/ha). At selected days postspray (1 to 21), Heliothis zea (Boddie) eggs were attached to excised leaves of treated and control plants, and exposed to adults of Trichogramma pretiosum (Riley) within 3.8-liter laboratory containers. Permethrin residues caused significantly lower rates of parasitization by, and higher mortality of, T. pretiosum adults than those of the control for 21 days postspray. Conversely, endosulfan residues significantly reduced egg parasitism and increased adult mortality of T. pretiosum only on day 1 postspray, when compared with the control. Of H. zea host eggs parasitized by T. pretiosum on leaves treated with permethrin or endosulfan, no significant differences were noted in either the female-male ratio of progeny or the mean number of parasitoids produced per host egg.
Pyrolytic hydrocarbon growth from cyclopentadiene.

Aromatic hydrocarbon growth from cyclopentadiene (CPD) was studied using a laminar flow reactor operating in the temperature range 550−950 °C without oxygen. Benzene, indene, and naphthalene were the major products, which is in agreement with the previous computational studies on the reaction pathways from CPD. A crossover of indene and naphthalene yields around 775 °C was also observed, which further supports the results of the computational studies. Although the specific intermediates in the proposed pathways from CPD were not detected, the high selectivity of products and the observation of other methylindene and dihydronaphthalene intermediates suggest that the recombination of two CPDs via radical−molecule and/or radical−radical pathways to form indene and naphthalene is the dominant formation pathway. In addition to the products from the CPD−CPD reactions, the products from the reactions of CPD with indene, naphthalene, and acenaphthylene were also observed, which demonstrate the importance of CPD i...
Better medical office safety culture is not associated with better scores on quality measures.

ObjectiveA strong safety culture is an essential element of safe medical practice. Few studies, however, have studied the link between safety culture and clinical quality outcomes. In this study, we examined the association between safety culture and quality measures in primary care offices.SettingA
Is There a Place for Cross-cultural Contastive Rhetoric in English Academic Writing Courses?

Aquest article es tracta d'un estudi dissenyat per investigar l'enfocament pedagogic d'emprar la retorica contrastiva i la comparacio entre cultures (cross-cultural contrastive rhetoric o CCCR en angles) en els cursos d'escriptura a nivell de postgrau. Dues classes de nivell avancat van ser reclutats per participar en aquest estudi: una classe va rebre instruccio CCCR i va participar en les discussions relacionats a l'enfocament CCCR, i l'altra classe no va rebre instruccio CCCR ni discussions. L'estudi va utilitzar investigacions quantitatives i qualitatives que van consistir en la classificacio dels resultats, el recompte de l'us de les clausules dependents i cohesio del text en les mostres d'escriptura dels estudiants; enquestes pre- i post-estudi, questionaris i entrevistes. Els resultats mostren que els estudiants que van rebre instruccions CCCR i van participar en les discussions CCCR van demostrar un us mes actiu dels connectius i van mostrar un augment de la metacognicio sobre les similituds i diferencies entre l'escriptura academica en la llengua meta (angles) i la L1 dels estudiants.
Rare Urologic Pathology Presenting as Abdominal Masses in Children

The key to correct diagnosis of abdominal masses in children is awareness of all the possibilities. Three children with abdominal masses of uncommon urologic origin are described. The lesions were adrenal cortical carcinoma, a pancake pelvic kidney and a non-functioning hydronephrotic segment of a horseshoe kidney. Management of these patients is discussed and the literature is reviewed.
Sexually Compulsive Behaviors: Implications for Attachment, Early Life Stressors, and Religiosity

ABSTRACTThe prevalence and rampant growth of sexually compulsive behaviors is recognized as a significant social problem affecting those who struggle with the behaviors, their romantic partners, their families, and other individuals in their social network. The current study investigated the role of attachment, early life stressors (ELS), age, and behavioral religiosity in sexually compulsive behaviors. Results suggested attachment anxiety, ELS, and behavioral religiosity were positively associated with sexually compulsive behaviors while age was negatively associated with sexually compulsive behaviors. Those participants high in sexually compulsive behaviors reported more attachment insecurity and ELS.
Predictability of Precipitation Over the Conterminous U.S. Based on the CMIP5 Multi-Model Ensemble.

Characterizing precipitation seasonality and variability in the face of future uncertainty is important for a well-informed climate change adaptation strategy. Using the Colwell index of predictability and monthly normalized precipitation data from the Coupled Model Intercomparison Project Phase 5 (CMIP5) multi-model ensembles, this study identifies spatial hotspots of changes in precipitation predictability in the United States under various climate scenarios. Over the historic period (1950–2005), the recurrent pattern of precipitation is highly predictable in the East and along the coastal Northwest, and is less so in the arid Southwest. Comparing the future (2040–2095) to the historic period, larger changes in precipitation predictability are observed under Representative Concentration Pathways (RCP) 8.5 than those under RCP 4.5. Finally, there are region-specific hotspots of future changes in precipitation predictability, and these hotspots often coincide with regions of little projected change in total precipitation, with exceptions along the wetter East and parts of the drier central West. Therefore, decision-makers are advised to not rely on future total precipitation as an indicator of water resources. Changes in precipitation predictability and the subsequent changes on seasonality and variability are equally, if not more, important factors to be included in future regional environmental assessment.
Real-time on-line network simulation

Abstract: The complexity and dynamics of the Internet is driving the demand for scalable and efficient network simulation. Yet, parallelizing network simulation at packet level does not work efficiently and therefore do not scale to large number of processors because of tight synchronization between network components. To overcome this problem we designed a method in which a large network is decomposed into parts and each part is simulated independently and concurrently with the others. These parts exchange information periodically about the packet delays and drop rates along the paths within each part. Each part iterates over the selected simulated time interval until the exchanged information changes less than the prescribed tolerance. Each decomposed part may represent a subnet or a subdomain of the entire network, thereby mirroring the network structure in the simulation design. The proposed method is independent of the specific simulator technique employed to run simulators of the parts of the decomposed network. Hence, it is a general method for efficient parallelization of network simulation based on convergence to the fixed point solution of inter-part traffic. The method can be used in all applications in which the speed of the simulation is of essence, such as: on-line network simulation, network management, ad-hoc network design, emergency network planning, large network simulation or network protocol verification under extreme conditions (large flows). The paper describes the method, its implementation based on ns simulator, and its performance for sample communication networks.
Integrative Approaches for the Identification and Localization of Specialized Metabolites in Tripterygium Roots

Members of the genus Tripterygium are known to contain an astonishing diversity of specialized metabolites. The lack of authentic standards has been an impediment to the rapid identification of such metabolites in extracts. We employed an approach that involves the searching of multiple, complementary chromatographic and spectroscopic data sets against the Spektraris database to speed up the metabolite identification process. Mass spectrometry-based imaging indicated a differential localization of triterpenoids to the periderm and sesquiterpene alkaloids to the cortex layer of Tripterygium roots. We further provide evidence that triterpenoids are accumulated to high levels in cells that contain suberized cell walls, which might indicate a mechanism for storage. To our knowledge, our data provide first insights into the cell type specificity of metabolite accumulation in Tripterygium and set the stage for furthering our understanding of the biological implications of specialized metabolites in this genus.
Short-Term Effects of Low-LET Radiation on the Endothelial Barrier: Uncoupling of PECAM-1 and the Production of Endothelial Microparticles

A significant target for radiation-induced effects is the microvascular system, which is critical to healthy tissue function and its pathology is linked to disrupted endothelial barrier function. Low-linear energy transfer (LET) ionizing radiation is a source of noncancer pathologies in humans and little is known about the early events that could initiate subsequent diseases. However, it is well known that gamma radiation causes a very early disruption of the endothelial barrier at doses below those required for cytotoxic effects. After irradiation of human umbilical vein endothelial cells (HUVECs) to doses as low as 2 Gy, transendothelial electrical resistance (TEER) is transiently reduced at 3 h, and the platelet-derived endothothelial cell adhesion molecule (PECAM-1 or CD31) is uncoupled from the cells along with the release of endothelial microparticles (EMPs). In this study, we measured TEER reduction as an indicator of barrier function loss, and specifically examined the shedding of EMPs from human endothelial barrier models after a variety of low-LET irradiations, including photons and charged particles. Our findings showed two TEER responses, dependent on radiation type and environmental conditions. The first response was diminishing oscillations of TEER, which occurred during the first 10 h postirradiation. This response occurred after a 5 Gy proton or helium-ion (1 GeV/n) dose in addition to a 5 Gy gamma or X radiation dose. This occurred only in the presence of multiple growth factors and did not show a dose response, nor was it associated with EMP release. The second response was a single acute drop in TEER at 3 h after photon irradiation. Dose response was observed and was associated with the shedding of EMPs in 2D barrier cultures and in 3D vessel models. In this case, helium-ion and proton irradiations did not induce a drop in TEER or shedding of EMPs. The photon radiation effects was observed both in serum-free media and in the presence of multiple growth factors, indicating that it occurs under a range of environmental conditions. These results show an acute response of the human endothelial barrier that is relevant to photon irradiation. Significantly, it involves the release of EMPs, which have recently attracted attention due to their emerging clinical importance.
Influence of Fatigue and Bending Strain on Critical Currents of Niobium Superconducting Flexible Cables Containing Ti and Cu Interfacial Layers

Niobium is a viable material for thin-film superconducting flexible microwave cables. To aid in the design of superconducting flexible cables using Nb, it is important to evaluate not only the superconductor electrical performance, but also mechanical reliability performance since these cables should be reasonably robust when flexed. In this paper, we performed fatigue and bending tests on Nb-only and Ti/Nb/Cu multilayer signal lines on flexible Kapton substrates and measured the change in critical current ( $I_c$ ) of these wires. From the fatigue tests, $I_c$ degradation of Nb-only cables occurred at a lower number of cycles than the Ti/Nb/Cu cables. After 250 fatigue cycles, Ti/Nb/Cu wires with the thickest Ti adhesion layer and Cu capping layer exhibited the lowest $I_c$ degradation of $\sim$ 1.2% and 0% in tensile and compressive cases, respectively. From bending tests, where the sample was held in an intentionally curved configuration during testing, $I_c$ degradation of the Nb-only cables was more severe than that of the Ti/Nb/Cu cables during tensile bending and the $I_c$ of Ti/Nb/Cu cables was minimally affected during compressive bending. These results demonstrate that a Ti adhesion layer and Cu capping layer provide reliability enhancement for superconducting Nb flex cables fabricated on Kapton.
Analysis of the 2005–2016 Earthquake Sequence in Northern Iran Using the Visibility Graph Method

We present an analysis of the seismicity of northern Iran in the period between 2005 and 2016 using a recently introduced method based on concepts of graph theory. The method relies on the inter-event visibility defined in terms of a connectivity degree parameter, k, which is correlated with the earthquake magnitude, M. Previous studies show that the slope m of the line fitting the k–M plot by the least squares method also observes a relationship with the b value from the Gutenberg–Richter law, thus rendering the graph analysis useful to examine the seismicity of a region. These correlations seem to hold for the analysis of relatively small sequences of earthquakes, offering the possibility of studying seismicity parameters in time. We apply this approach to the case of the seismicity of northern Iran, using an earthquake catalog for the tectonic seismic regions of Azerbaijan, Alborz, and Kopeh Dagh. We use results drawn for this region with the visibility graph approach in combination with results from other similar studies to further improve the universal relationship between m and b, and show that the visibility graph approach can be considered as a valid alternative for analyzing regional seismicity properties and earthquake sequences.
The Interaction Between Observer Sex and Sexual Identity on Attributions of Blame With a Heterosexual Female Victim.

This article examines the difference in blame attribution between men and women, heterosexuals and homosexuals, and heterosexual males, heterosexual females, gay males, and lesbians in response to ...
A bio-based pro-antimicrobial polymer network via degradable acetal linkages.

Abstract The synthesis of a fully degradable, bio-based, sustained release, pro-antimicrobial polymer network comprised of degradable acetals (PANDA) is reported. The active antimicrobial agent – p-anisaldehyde (pA) (an extract from star anise) – was converted into a UV curable acetal containing pro-antimicrobial monomer and subsequently photopolymerized into a homogenous thiol-ene network. Under neutral to acidic conditions (pH Statement of Significance With the increasing number of patients prescribed immunosuppressants coupled with the rise in antibiotic resistance – life-threatening microbial infections are a looming global threat. With limited success within the antibiotic pipeline, nature-based essential oils (EOs) are being investigated for their multimodal effectiveness against microbes. Despite the promising potential of EOs, difficulties in their encapsulation, limited water solubility, and high volatility limit their use. Various studies have shown that covalent attachment of these EO derivatives to polymers can mitigate these limitations. The current study presents the synthesis of a fully-degradable, sustained release, cytocompatible, pro-antimicrobial acetal network derived from p-anisaldehyde. This polymer network design provides a pathway toward application-specific EO releasing materials with quantitative encapsulation efficiencies, sustained release, and broad-spectrum antimicrobial activity.
Sensory adaptation to electrical stimulation of the somatosensory nerves.

Objective. Sensory systems adapt their sensitivity to ambient stimulation levels to improve their responsiveness to changes in stimulation. The sense of touch is also subject to adaptation, as evidenced by the desensitization produced by prolonged vibratory stimulation of the skin. Electrical stimulation of nerves elicits tactile sensations that can convey feedback for bionic limbs. In this study, we investigate whether artificial touch is also subject to adaptation, despite the fact that the peripheral mechanotransducers are bypassed. Approach. Using well-established psychophysical paradigms, we characterize the time course and magnitude of sensory adaptation caused by extended electrical stimulation of the residual somatosensory nerves in three human amputees implanted with cuff electrodes. Main results. We find that electrical stimulation of the nerve also induces perceptual adaptation that recovers after cessation of the stimulus. The time course and magnitude of electrically-induced adaptation are equivalent to their mechanically-induced counterparts. Significance. We conclude that, in natural touch, the process of mechanotransduction is not required for adaptation, and artificial touch naturally experiences adaptation-induced adjustments of the dynamic range of sensations. Further, as it does for native hands, adaptation confers to bionic hands enhanced sensitivity to changes in stimulation and thus a more natural sensory experience.
Circadian clock neurons mediate time-of-day dependent responses to light

Circadian (~24 h) rhythms influence nearly all aspects of physiology, including sleep/wake, metabolism, and hormone release. The suprachiasmatic nucleus (SCN) synchronizes these daily rhythms to the external light cycle, but the mechanisms by which this occurs is unclear. The neuropeptide vasoactive intestinal peptide (VIP) is the predominant contributor to synchrony within the SCN and is important for circadian light responses, but the role of VIP neurons themselves is unclear. Thus, we tested the hypothesis that rhythmic SCN VIP neurons mediate circadian light responses. Using in vivo fiber photometry recording of SCN VIP neurons we found daily rhythms in spontaneous calcium events that peaked during the subjective day and in light-evoked calcium events that exhibited the greatest response around subjective dusk. These rhythms were correlated with spontaneous and NMDA-evoked VIP release from SCN VIP neurons in vitro. Finally, in vivo hyperpolarization of VIP neurons attenuated light-induced shifts of daily rhythms in locomotion. We conclude that SCN VIP neurons are circadian and depolarize to light to modulate entrainment of daily rhythms in the SCN and behavior.
A technique for proving lower bounds on the size of sweeping automata

A sweeping automaton is a two-way deterministic finite automaton which makes turns only at the endmarkers. Sipser [12] has proved that one-way nondeterministic finite automata can be exponentially more succinct in sizes than sweeping automata. In this paper, we propose a technique based on the work in [6] for establishing lower bounds on the size of sweeping automata. We show that Sipser's technique is a special case of our method. In addition, we prove two lower bound results with the new technique.
Towards the use of HIFU, in Conjunction with Surgery, in the Treatment of Malignant Brain Tumors

The first medical response to the presence of a brain tumor is often its resection, both to alleviate mass effect, and to obtain tissue for diagnosis, itself necessary for guiding adjunctive therapy. Malignant brain tumors typically recur at the tumor resection margin. Most current chemotherapy and radiotherapy strategies target local recurrence with limited success. Here we review a new strategy for delivering chemotherapeutics for brain tumor recurrence. It uses intra‐operative high‐intensity focused ultrasound (HIFU) to transiently open the blood‐brain barrier (BBB) over a significantly large volume of brain at and near the resection margin to enhance the subsequent delivery of systemically delivered chemotherapeutic agents into the region of tumor recurrence.
Dummett, Realism and Other Minds

The traditional problem of other minds has surfaced in Michael Dummett’s work as an occasion to develop his deep-going critique of the realist view of linguistic meaning.
Distribution and Targeting Mechanisms of Voltage Activated Ca2+ Channels

Voltage dependent Ca^* channels control critical parameters of cell function. Their involvement in excitation contraction (EC)-coupling in muscle, their role in secretion in pancreas, their involvement in the acrosome reaction in sperm and their function in fast and slow signal transduction in brain predicts a variety of different Ca^* channel complexes with defined biophysical properties. Since all these actions occur within specialized subcellular structures like the triad in muscle cells or the presynaptic terminal in neurons, Ca^* channel complexes have to be targeted to their specific site of action. Thus mechanisms have to exist to control for subunit assembly and transport of the Ca^* channel complex. The human genome predicts more than 20 different Ca^* channel subunits, which may assemble to a large variety of channel combinations. Functional Ca * channels consists of three to four subunits designated tti, p, a2-8 and y. The tti subunit is the pore forming subunit consisting of four channel domains, which are connected via intracellular protein or peptide bridges. The ancillary subunits p, a2-6 and y interact with the intracellular, extracellular and transmembrane regions of the OLi subunit and modulate the channel function. Three large Ca * channel families can be distinguished according to their sequence homology of the ai subunit and their electrophysiological and pharmacological differences. These families are L-type chan­ nels, P/Q/N/R-type channels and T-type channels. Further characterization of the predicted Ca * channel types obtained from genome projects will likely extend each subgroup and may define new Ca * channel types. We will first describe the distribution of these different families in brain and periphety and will then discuss what we know about the transport mechanisms to the subcellular destiny of the Ca^^ channel subunit. Distribution of Ca^* Channel Types Specified by Their Pore Forming ai Subunit Voltage dependent Ca^* channels appear already in the most primitive animals like the single cell ciliate Paramecium where they trigger regenerative Ca * action potential necessaty for environment sensing. ^'^ In mammals Ca^* channels are expressed in almost evety cell throughout all tissues and organs such as brain, muscle, pancreas and testis. Distribution of L-Type Channels CapI.I and Ca^lA L-type channels are encoded by the Cayl.l, Cavl.2, Cavl.3 and Cavl.4 OL\ subunits. L-type channels were first identified in large diameter muscle fibers of crab leg.^ Due to its high concentration in the T-tubular system of skeletal muscle it was the first Ca^* channel complex purified. This complex consists of the CayLl OL\, pia, CLx-^i and yi subunit.^ The CavLl ttisubunit contains the DHP binding site and together with the other channel subunits are
Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of Cholesterol Molecules

Abstract Cholesterol is a major regulator of multiple types of ion channels, but the specific mechanisms and the dynamics of its interactions with the channels are not well understood. Kir2 channels were shown to be sensitive to cholesterol through direct interactions with “cholesterol-sensitive” regions on the channel protein. In this work, we used Martini coarse-grained simulations to analyze the long (μs) timescale dynamics of cholesterol with Kir2.2 channels embedded into a model membrane containing POPC phospholipid with 30 mol% cholesterol. This approach allows us to simulate the dynamic, unbiased migration of cholesterol molecules from the lipid membrane environment to the protein surface of Kir2.2 and explore the favorability of cholesterol interactions at both surface sites and recessed pockets of the channel. We found that the cholesterol environment surrounding Kir channels forms a complex milieu of different short- and long-term interactions, with multiple cholesterol molecules concurrently interacting with the channel. Furthermore, utilizing principles from network theory, we identified four discrete cholesterol-binding sites within the previously identified cholesterol-sensitive region that exist depending on the conformational state of the channel—open or closed. We also discovered that a twofold decrease in the cholesterol level of the membrane, which we found earlier to increase Kir2 activity, results in a site-specific decrease of cholesterol occupancy at these sites in both the open and closed states: cholesterol molecules at the deepest of these discrete sites shows no change in occupancy at different cholesterol levels, whereas the remaining sites showed a marked decrease in occupancy.
The temporal relationship between pain intensity and pain interference and incident dementia

Background Chronic pain is common among older adults and is associated with cognitive dysfunction based on cross-sectional studies. However, the longitudinal association between chronic pain and incident dementia in community-based samples is unknown. Objective We aimed to evaluate the association of pain intensity and pain interference with incident dementia in a community-based sample of older adults. Methods Participants were 1,114 individuals 70 years of age or older from Einstein Aging Study (EAS), a longitudinal cohort study of community-dwelling older adults in the Bronx County, NY. The primary outcome measure was incident dementia, diagnosed using DSM-IV criteria. Pain intensity and interference in the month prior to first annual visit were measured using items from the SF-36 questionnaire. Pain intensity and pain interference were assessed as predictors of time to incident dementia using Cox proportionate hazards models while controlling for potential confounders. Results Among participants, 114 individuals developed dementia over an average 4.4 years (SD=3.1) of follow-up. Models showed that pain intensity had no significant effect on time to developing dementia, whereas higher levels of pain interference were associated with a higher risk of dementia. In the model that included both pain intensity and interference as predictors of incident dementia, pain interference had a significant effect on incident dementia, and pain intensity remained non-significant. Conclusion As a potential remediable risk factor, the mechanisms linking pain interference to cognitive decline merit further exploration.
The atypical antipsychotic quetiapine induces hyperlipidemia by activating intestinal PXR signaling

Quetiapine, one of the most prescribed atypical antipsychotics, has been associated with hyperlipidemia and an increased risk for cardiovascular disease in patients, but the underlying mechanisms remain unknown. Here, we identified quetiapine as a potent and selective agonist for pregnane X receptor (PXR), a key nuclear receptor that regulates xenobiotic metabolism in the liver and intestine. Recent studies have indicated that PXR also plays an important role in lipid homeostasis. We generated potentially novel tissue-specific PXR-KO mice and demonstrated that quetiapine induced hyperlipidemia by activating intestinal PXR signaling. Quetiapine-mediated PXR activation stimulated the intestinal expression of cholesterol transporter Niemann-Pick C1-Like 1 (NPC1L1) and microsomal triglyceride transfer protein (MTP), leading to increased intestinal lipid absorption. While NPC1L1 is a known PXR target gene, we identified a DR-1-type PXR-response element in the MTP promoter and established MTP as a potentially novel transcriptional target of PXR. Quetiapine's effects on PXR-mediated gene expression and cholesterol uptake were also confirmed in cultured murine enteroids and human intestinal cells. Our findings suggest a potential role of PXR in mediating adverse effects of quetiapine in humans and provide mechanistic insights for certain atypical antipsychotic-associated dyslipidemia.
mRNA-to-protein translation in hypoxia

Cells respond to hypoxia by shifting cellular processes from general housekeeping functions to activating specialized hypoxia-response pathways. Oxygen plays an important role in generating ATP to maintain a productive rate of protein synthesis in normoxia. In hypoxia, the rate of the canonical protein synthesis pathway is significantly slowed and impaired due to limited ATP availability, necessitating an alternative mechanism to mediate protein synthesis and facilitate adaptation. Hypoxia adaptation is largely mediated by hypoxia-inducible factors (HIFs). While HIFs are well known for their transcriptional functions, they also play imperative roles in translation to mediate hypoxic protein synthesis. Such adaptations to hypoxia are often hyperactive in solid tumors, contributing to the expression of cancer hallmarks, including treatment resistance. The current literature on protein synthesis in hypoxia is reviewed here, inclusive of hypoxia-specific mRNA selection to translation termination. Current HIF targeting therapies are also discussed as are the opportunities involved with targeting hypoxia specific protein synthesis pathways.
Metabolomic Investigations of the Temporal Effects of Exposure to Pharmaceuticals and Personal Care Products and Their Mixture in the Eastern Oyster (Crassostrea virginica).

The eastern oyster (Crassostrea virginica) supports a large aquaculture industry and is a keystone species along the Atlantic seaboard. Native oysters are routinely exposed to a complex mixture of contaminants that increasingly includes pharmaceuticals and personal care products (PPCPs). Unfortunately, the biological effects of chemical mixtures on oysters are poorly understood. Untargeted gas chromatography-mass spectrometry metabolomics was utilized to quantify the response of oysters exposed to fluoxetine, N,N-diethyl-meta-toluamide, 17α-ethynylestradiol, diphenhydramine, and their mixture. Oysters were exposed to 1 µg/L of each chemical or mixture for 10 d, followed by an 8-d depuration period. Adductor muscle (n = 14/treatment) was sampled at days 0, 1, 5, 10, and 18. Trajectory analysis illustrated that metabolic effects and class separation of the treatments varied at each time point and that, overall, the oysters were only able to partially recover from these exposures post-depuration. Altered metabolites were associated with cellular energetics (i.e., Krebs cycle intermediates), as well as amino acid metabolism and fatty acids. Exposure to these PPCPs also affected metabolic pathways associated with anaerobic metabolism, osmotic stress, and oxidative stress, in addition to the physiological effects of each chemical's postulated mechanism of action. Following depuration, fewer metabolites were altered, but none of the treatments returned them to their initial control values, indicating that metabolic disruptions were long-lasting. Interestingly, the mixture did not directly cluster with individual treatments in the scores plot from partial least squares discriminant analysis, and many of its affected metabolic pathways were not well predicted from the individual treatments. The present study highlights the utility of untargeted metabolomics in developing exposure biomarkers for compounds with different modes of action in bivalves. Environ Toxicol Chem 2020;39:419-436. © 2019 SETAC.
Response to requests for contraception in one direct-to-consumer telemedicine service.

Abstract Objective To describe real-world care seeking and contraception provision in one direct to consumer telemedicine platform. Study design We described encounters with reproductive age female patients between July 2016 and July 2018 seeking contraception on the American Well telemedicine platform. Results Of 126,712 total encounters with reproductive age women, 682 were with women seeking contraception, and 83% received it. The mean encounter length was 4.4 min versus 5.0 min for non-contraceptive visits. Insurance information was provided for 78% of contraceptive encounters versus 85% of non-contraceptive encounters, p Conclusion Direct to consumer telemedicine may increase access to contraceptives, yet overall use was uncommon. Most women seeking contraception via direct to consumer telemedicine on this platform received it. Three women who requested emergency contraception did not receive it, yet reasons for this are unknown.
P111 A Content and Thematic Analysis of Lunch Shaming in the News Media

Background Lunch shaming is the stigmatization of students that are unable to pay for their school meals. The phenomenon of lunch shaming is frequently highlighted in the media. Objective The purpose of this study was to perform a content analysis on news sources covering the topic of lunch shaming in order to see trends in the media. Study Design, Setting, Participants A content analysis of national, international, and local online, print, and broadcast news was conducted to examine news stories that covered lunch shaming across the US. News stories were retrieved from 5 news media databases using predetermined search terms. Two trained coders analyzed the news stories for common themes and classified each story by state and type of news source. Measurable Outcome/Analysis Frequencies were summarized for the content analysis and articles were coded for themes. Results Of the 355 news stories analyzed, the majority came from local print newspapers (73.5%). The highest percentage of news stories covered incidences of lunch shaming in Pennsylvania (18.3%). Most stories mentioned state or national policies on lunch shaming (54.9%). For example, “New Mexico has passed a law said to be the first of its kind, banning lunch shaming.” Stories highlighted barriers (eg, poverty, language) that parents face while paying for school meals. Other themes included instances of individuals donating money to settle debt, specific shaming tactics used, and referring parents to Child Protective Services. Conclusions Lunch shaming remains a major problem and strategies need to be considered to remedy this phenomenon. Awareness of how the media is portraying the phenomenon of lunch shaming may provide insight into how school districts and foodservice directors can target their communication and education about this issue.
The Production, Efficacy, and Safety of Machine-Generated Bicarbonate Solution for Continuous Venovenous Hemodialysis (CVVHD): The Cleveland Clinic Method

Rationale & Objective Since 1994, the Nephrology and Hypertension Department at the Cleveland Clinic has prepared and used bicarbonate-based solution for continuous venovenous hemodialysis (CVVHD) using a standard volumetric hemodialysis machine rather than purchasing from a commercial vendor. This report describes the process of producing Cleveland Clinic UltraPure Solution (CCUPS), quality and safety monitoring, economic costs, and clinical outcomes. Study Design Retrospective study. Setting & Participants CVVHD experience at Cleveland Clinic, focusing on dialysate production, institutional factors, and patients requiring continuous kidney replacement therapy. Production is shown at www.youtube.com/watch?v=WGQgephMEwA. Outcomes Feasibility, safety , and cost. Results Of 6,426 patients treated between 2011 and 2019 with continuous kidney replacement therapy, 59% were men, 71% were White, 40% had diabetes mellitus, and 74% presented with acute kidney injury. 98% of patients were treated with CVVHD using CCUPS, while the remaining 2% were treated with either continuous venovenous hemofiltration or continuous venovenous hemodiafiltration using commercial solution. The prescribed and delivered effluent doses were 24.8 (IQR) versus 20.7 mL/kg/h (IQR), respectively. CCUPS was as effective in restoring electrolyte and serum bicarbonate levels and reducing phosphate, creatinine, and serum urea nitrogen levels as compared with packaged commercial solution over a 3-day period following initiation of dialysis, with a comparable effluent dose. Among those with acute kidney injury, mortality was similar to that predicted with the 60-day acute kidney injury predicted mortality score (r = 0.997; CI: 0.989-0.999). At our institution, the cost of production for 1 L of CCUPS is $0.67, which is considerably less than the cost of commercially purchased fluid. Limitations Observational design without a rigorous control group. Conclusions CVVHD using locally generated dialysate is safe and cost-effective.
Monitoring and correcting: why women read and men comment online

Using a probability sample of online news commenters and comment readers from the United States, we investigate gender differences in online commenting. We focus on two distinct behaviors in these ...
Time and the Moment in Victorian Literature and Society: Dickens’s peripatetic novels

It is well known that Charles Dickens was a walker. It’s also well known that walking was central to his stories and novels and to the myths of how they came to be written. G. K. Chesterton consolidated the myth, declaring that Dickens’s “earth was the stones of the street; his stars were the lamps of the street; his hero was the man in the street.” Walter Benjamin was drawn into the myth, and quotes Chesterton as well as Edmund Jaloux’s version of Chesterton’s thesis: Dickens needed “the immense labyrinth of London streets where he could prowl about continuously.” Dickens’s letters and biographies amply support the idea that he was a writer hooked on urban perambulation. Writing from Switzerland, he pines for London: I can’t express how much I want these streets … It seems as if they supplied something to my brain, which it cannot bear, when busy, to lose. For a week or a fortnight I can write prodigiously in a retired place … and a day in London sets me up again and starts me. It’s an alluring image – the writer whose imagination lives in symbiosis with walking. And given the wealth of criticism on the subject, it hardly seems to need more consideration. I take it up here because it is an important stage in the development of narrative aesthetics, specifically as it links embodiment to temporality. This chapter pursues the topic heuristically. The method seems called for by both the subject matter (walking) and the premise – that insofar as Dickens’s novels are process-oriented, they are misrepresented by thesis-driven treatments. I am proceeding with the following hypothesis: Dickens’s moments are junctures of accumulated energy and release in paced narratives, and pacing is methodological shorthand for the kinesthetic connections between walking, storytelling, and experiments in humanism. In all this, Dickens flirts with the promise of momentary figures to create narrative presentification – flirts, but often retreats. What we need to understand is how Dickens can be both an extravagant master of the moment of literary sensation, and yet something of a disappointment when it comes to making momentary figures deliver answers to the questions set in motion by his stories.
Somatic Cell Hybridization in Cytogenetic Analysis

For many years, human geneticists dreamed of finding a way to study segregation and recombination in somatic cells, in order to overcome the difficulties of genetic analysis with small families, few genetic markers, limited availability of meiotic material, and no experimental matings. Somatic cell genetics became a powerful way to do this, with the discovery of preferential loss (segregation) of human chromosomes in interspecific human-rodent somatic cell hybrids. The analysis of such hybrids has made it possible to correlate the loss or retention of a specific chromosome or chromosome segment with the loss or retention of a specific gene product or gene, allowing the gene to be mapped to that chromosome or segment. Enormous strides have been made using this approach. It is still one of the most widely used methods for mapping genes and for demonstrating multiple genetic causes of a disease phenotype (genetic heterogeneity). Somatic cell hybrids have many other uses in cytogenetic analysis. It is therefore helpful to understand somatic cell hybridization and how it is achieved experimentally.
Accident/Incident Prevention Techniques

Section 1: Structuring the Foundation of the Prevention Process 1. Introduction 2. Safety and Health Programs 3. Accident/Incident Investigation 4. Hazard Recognition and Avoidance. Section 2: Human Elements of Accident Prevention 5. Accountability and Responsibility 6. Motivating Safety and Health. Section 3: Analysing Accident/Incidents 7. Accident/Incident Analysis 8. Root Cause Analysis 9. Causal Factor Analysis 10. Change Analysis 11. Barrier Analysis. Section 4: Accident Prevention Techniques 12. Job Safety/Hazard Analysis 13. Safe Operating Procedures 14. Job Safety Observations 15. Workplace Audits 16. Fleet Safety 17. Preventative Maintenance Programs 18. Special Emphasis Programs 19. Using Consultants or Engineers 20. Training 21. Tracking Progress. Section 5: Hazard Specific Accident Prevention 22. Using OSHA Regulations 23. Health Related Hazards 24. Controls and Personal Protective Equipment 25. Safety Related Hazards 26. Resources and Information 27. Summary and Future Considerations.
Should Chloral Hydrate Be Banned

Objective. Current federal regulations of potentially carcinogenic environmental chemicals are based on the assumption that risks for humans can be extrapolated from the effects of chronic high-dose exposure of rodents. It is assumed that all chemicals induce cancer by a genotoxic mechanism (direct interaction with DNA) and that humans metabolize chemicals by the same pathways as the test rodents. Trichloroethylene, a former medicine, is now regulated because of rodent studies. Its major metabolite, chloral hydrate, widely used as a sedative in both adults and children, is in danger of being banned by comparable studies. This paper assesses the safety of chloral hydrate. Design. Analysis of the literature regarding the metabolic, toxicologic, and epidemiologic data on trichloroethylene and chloral hydrate. Results. The dose-response relationship for carcinogenesis of chioral hydrate and other chemicals in its metabolic breakdown pathway is nonlinear in rodents: very high doses given chronically, sufficient to cause cellular necrosis, are necessary for induction of malignancies. In addition, epidemiologic data on people exposed to substantial amounts of trichloroethylene (which is metabolized to chloral hydrate) show no increase in mortality or cancers. Conclusions. The assumptions underlying current regulatory practices for environmental chemicals are not applicable to the medicinal use of chloral hydrate. Instead, a threshold model is appropriate. The data do not suggest the need to ban chloral hydrate as a medicine; however, possible modifications in its use are suggested.
Bilattices in logic programming

Bilattices are a family of multiple-valued logics. Those meeting certain natural conditions have provided the basis for the semantics of a family of logic programming languages. Consideration is given to further restrictions on bilattices in order to narrow things down to logic programming languages that can, at least in principle, be implemented. Appropriate bilattice background information is presented, so the work is relatively self-contained. The backgrounds of logic programming and bilattices are given. Logic programming syntax is discussed, along with fixpoint semantics. Smullyan-style propositional rules are discussed. >
Behavioral effects of disrupted direct pathway signal flow caused by dopamine depletion

Figure 1 All data points are from the subjects in both the naive and hemi-parkinsonian state. PPR is shown with blue markers and number of rears is shown with red. PPR was significantly correlated with motor time (t-test: p < 0.001). The blue line indicates the linear relationship between the two found via regression. Number of rears was significantly negatively correlated with motor time (t-test: p < 0.05) and the red line is found via linear regression.