cssi/SciSciGPT-SciSciNet huggingface dataset:
Aetiology, microbiology and therapy of periapical lesions around oral implants: a retrospective analysis

Objective The aim of this study was: (i) to evaluate whether an endodontic pathology on the extracted tooth or adjacent teeth of an implant site has an influence on the emergence of a periapical lesion, (ii) to retrospectively analyse the outcome of different treatment strategies, (iii) to determine which bacteria were present in periapical lesions. Methods The endodontic status of the tooth at the implant site and the adjacent teeth was explored and linked to the periapical status of the implant. For all the lesions treated since 2000, their survival was assessed. Finally, microbial samples (culturing) from the periapical lesions, were analysed. Results If an endodontic treatment or a periapical lesion at the apex of a tooth is present, a periapical lesion around the implant can be detected in 8.2% up to 13.6% (OR 7.2). For periapical pathology at the adjacent teeth, the percentage rises to 25% (OR 8.0). The best treatment option could not be found. Bacteria were found in 9/21 lesions. The most prominent species was P. gingivalis. Conclusions When an endodontic pathology is present on the extracted or neighbouring teeth, it is significantly more likely that a periapical lesion will develop around a future implant.
Stereotype threat, mental arithmetic, and the mere effort account

Abstract The currently prevailing explanation for stereotype threat (ST) debilitation effects argues for working memory interference as the proximal mediator. Using mental arithmetic problems as the test bed, Beilock et al. (2007) have spelled out in greater detail exactly how this process might work. They propose that worries resulting from activation of the negative stereotype occupy the phonological loop, taking up capacity that could be used to remember the intermediate values produced when solving horizontal mental subtraction problems. In the current work, we test an alternative, motivational account for this effect, mere effort. The mere effort account argues that ST motivates stigmatized participants to want to perform well, potentiating the prepotent response on the given task. In Experiment 1 we identified a possible prepotent response for horizontal subtraction, termed the method of adjustment (e.g., adjust the second number to the nearest 10, subtract the two numbers, and then add the adjustment). Consistent with the mere effort account, Experiment 2 showed that ST potentiated the prepotent approach, the method of adjustment. Experiment 3 pitted the mere effort account against the working memory account. Working memory predicts debilitation effects on horizontal subtraction problems when participants need to use the phonological loop (i.e., entering answers from left-to-right), whereas mere effort predicts that the potentiated use of the method of adjustment should facilitate performance when answers must be entered from left-to-right. Results supported the mere effort account. Finally, Experiment 4 showed that when we control for the effect of the potentiated prepotent response, instead of performing more poorly, threatened participants perform better than no threat participants. Overall, these experiments support the mere effort account, which argues for motivation as a core process in producing ST effects.
Microearthquake study of the Elsinore Fault Zone, southern California

Microearthquakes along the Elsinore fault zone, southern California, were monitored during the summer and fall of 1972. Four arrays of at least five portable, high-gain, seismographs were operated for about 12 days each from the vicinity of Corona to just north of the Mexican border. Over 5,000 hr of noisefree records were accumulated and analyzed. The recorded rates of seismic activity show a marked increase going from north to south along the fault— 0.5 events per day in the vicinity of Lake Elsinore to 3.7 events per day in the south near Monument Peak. Fifty-three events located, assuming a four-layer crustal-velocity model, show considerable scatter along the fault and are generally very shallow, averaging 3.3 km below sea level. A signal duration ( D ) versus magnitude ( M ) relationship was found: M = −1.9+2.0 log D . First motions of the located earthquakes indicate a complex pattern of faulting along the Elsinore fault zone. In comparison to the San Jacinto Fault to the east, the Elsinore Fault shows very little strike-slip displacement and is a seismically quiet area except for a localized area of east-west faulting in the far south near Vallecito Mountain.
Ideals of Public Discourse

“Public discourse” signifies speeches, publications and other statements made in pursuit of the public good. If (as it is for republicans) the sole aim of government, laws and the state is to serve the common good of the people, then public discourse offers the primary practical technique for finding (or clarifying) what the laws should require. “Public discourse” (in this sense) regards public policy as distinguished from “private discourse” among citizens seeking to develop their own private friendships and interests. This line between “public” and “private” discourse may be difficult to draw, because it concerns the fundamental division of power within society and the state. Public discourse defines and limits the powers of the government, but also of individuals. That which is not public is private, and vice versa, but it is public discourse itself that must, in the end, decide the boundaries. The standards of behavior that should govern public discourse constitute “civility”. Many of these same standards also extend to private discourse, with some exceptions.
Separation and characterization of metallosupramolecular libraries by ion mobility mass spectrometry.

The self-assembly of ZnII ions and bis(terpyridine) (tpy) ligands carrying 120° or 180° angles between their metal binding sites was utilized to prepare metallosupramolecular libraries with the connectivity. These combinatorial libraries were separated and characterized by ion mobility mass spectrometry (IM MS) and tandem mass spectrometry (MS2). The 180°-angle building blocks generate exclusively linear complexes, which were used as standards to determine the architectures of the assemblies resulting from the 120°-angle ligands. The latter ligand geometry promotes the formation of macrocyclic hexamers, but other n-mers with smaller (n = 5) or larger ring sizes (n = 7–9) were identified as minor products, indicating that the angles in the bis(terpyridine) ligand and within the coordinative tpy–ZnII–tpy bonds are not as rigid, as previously believed. Macrocyclic and linear isomers were detected in penta- and heptameric assemblies; in the larger octa- and nonameric assemblies, ring-opened con...
A 29-year-old man with abnormal thyroid function tests.

The patient has elevated serum T4 and T3, but no symptoms of hyperthyroidism. What is the diagnosis?
Wrestling: Interaction of wrestling shoe and competition surface: effects on coefficient of friction with implications for injury

The purpose of this study was to determine whether there is a significant difference in the co‐efficient of friction (Fc) between old versus new wrestling shoes and mats and to investigate the effe...
A Systems Analysis Perspective for Managing Change in Clinical Laboratories

A host of external forces has prompted clinical laboratories to change in recent years. Prospective reimbursement, increasing competition, and societal demands for access to complex diagnostic services are just a few of the forces driving change. Inherent in the change process is a degree of resistance and uncertainty about the net impact of any change innovation. This article describes a systems analysis model to assist the laboratory manager in planning for and implementing change. From a systems analysis perspective, four distinct yet interactive components or dimensions make up the managerial setting: task, structure, technology, and people. The ability to predict how modifying one dimension of the system is likely to have an impact on other dimensions is the key to both designing adaptive change strategies and successful implementation. By viewing the laboratory setting from a holistic perspective, resistance to change can be minimized and results can be more accurately predicted.
Preventing Child Neglect and Physical Abuse: A Role for Pediatricians

1. Howard Dubowitz, MD, MS* 1. *Professor of Pediatrics, University of Maryland School of Medicine, Baltimore, Md After completing this article, readers should be able to: 1. Describe the importance of preventing child abuse and neglect. 2. Identify key risk and protective factors for child abuse and neglect. 3. Delineate useful principles and practical guidance for pediatricians on screening, brief assessment, and initial management of problems related to child abuse and neglect. Preventing child abuse and neglect spares a child pain and suffering, both physical and psychological. This is intuitively and morally preferable to intervening “after the fact.” Further, early intervention or prevention may be more effective than later intervention. For example, the time when a family has a new baby often is described as “a window of opportunity,” and early efforts to support the family and strengthen their parenting abilities may be particularly effective and cost-effective. Child maltreatment is not a rare phenomenon. Data from the 3rd National Incidence Study of Child Abuse and Neglect revealed that approximately 1% of children were identified as abused and 1.5% as neglected in 1993, and these rates are likely the “tip of the iceberg.” A number of studies have found that as many as one in four girls and one in ten boys has been sexually abused during childhood. Another reason for preventing child abuse and neglect is its immense morbidity and significant mortality rates. Research has documented the multiple physical, cognitive, behavioral, social, and emotional sequelae of child maltreatment. Brain damage, learning problems, aggression, juvenile delinquency and adult criminal behavior, depression, and parenting difficulties are a few of the potential long-term problems. The goal of preventing child maltreatment fits well with the goals and scope of pediatrics. “As physicians who assume a responsibility for children’s physical, mental, and emotional progress from conception to maturity, pediatricians must be concerned with social and environmental influences, which have a major impact on the health …
Dielectrics for DC and energy storage capacitors

Recent years have seen an incresase in the use of high power electronic equipment requiring larger bank capacity and higher joule content per unit for filter capacitors. A similar increase has been experienced in the energy storage field by the rapid increase in fusion research, wind tunnel test facilities, laser research and metals forming equipment. Here again an increase in joule content, performance and bank ratings has been demanded.
A Multimethod Study of Enterprise Social Media Implementation and Use: Mitigating the Gap between Theory and Practice

Enterprise social media ESM are web-based platforms dedicated to corporate-based communication and collaboration. Although the practitioner literature and industry reports have suggested the potential value of ESM for organizations, there has been limited research that focuses on employees' reactions to ESM implementation and their post-implementation use behaviors. The authors conducted a mixed methods study of a large-scale ESM implementation in a Fortune 500 manufacturing company and found that widely used IT adoption models and determinants failed to explain employees' ESM use. To help explain this paradoxical finding, the authors leveraged their qualitative data and found several major challenges, both internal and external, that the company faced during ESM implementation. Their findings have a number of generalizable lessons for practice as well as implications for research.
WE-AB-206-02: ACR Ultrasound Accreditation: Requirements and Pitfalls

The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: 1. Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging 2. dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools 3. Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.
Ureteral abnormalities in women with endometriosis

High-volume intravenous urography was performed in 63 women with surgically proven endometriosis. Subtle abnormalities were found in 15.9% of these women. No patient had urologic symptoms, and there was no evidence of hydroureter or ureteral obstruction on the IVP. Long-term follow-up study will be required to determine whether or not these lesions will progress and cause ureteral obstruction.
The CKD Classification System in the Precision Medicine Era.

“Tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes—and to give all of us access to the personalized information we need to keep ourselves and our families healthier” (President Barack Obama, State of the Union Address,
Political Economy and Social Justice in the US-Mexico Border Region

Political economy is the study of power in human affairs, including politics, economics, and ideology. Three border processes are examined in terms of these three elements. They are border crossing processes, border-reinforcing ones, and, a third category crucial to borders, uneven and combined relations. The latter involve both connections and also the maintenance or reinforcement of differentiation. The border is a subordinate region in the political economy of North America, though also a crucial point of production and exchange due to combined and uneven relations. This is explored through application of the concept of dependency to politics, economics, and ideas. Examples are taken from the domains of migration, smuggling, and industrialization, and the topic of regulated, unequal mobility is explored. Finally, the challenge and possibilities for social justice struggles of this highly unequal scenario of political economy are explored.
The frictional strength of talc gouge in high‐velocity shear experiments

Talc is present in several large-scale fault zones world-wide, and is mineralogically stable at temperature of the upper crust. It is therefore necessary to gain a better understanding of the frictional behavior of talc under a wide range of slip velocity conditions occurring during the seismic cycle. We analyzed the frictional and structural characteristics of room-dry and water-saturated talc gouge by shear experiments on a confined gouge layer at slip-velocity range of 0.002 – 0.66 m/s and normal stress up to 4.1 MPa. Room-dry talc showed a distinct slip-strengthening with the initial friction coefficient of μ ~ 0.4 increased systematically to μ ~ 1 at slip distance D > 1 m. Room-dry talc also displayed velocity-strengthening at slip-distances shorter than 1 m. The water-saturated talc gouge displayed systematic low frictional strength of μ = 0.1 - 0.3 for the entire experimental range, with clear velocity-strengthening behavior with positive (a-b) values (rate dependence parameter of rate- state- friction) of 0.01-0.04. The microstructural analyses revealed distributed shear and systematic dilation (up to 50%) for the room-dry talc, in contrast to the extreme slip localization and strong shear compaction for water-saturated talc. We propose that talc frictional strength is controlled by lubrication along cleavage surfaces that is facilitated by adsorbed water (room-dry) and surplus water (water-saturated). This mechanism can explain our experimental observations of slip-strengthening and velocity-strengthening for both types of talc gouge, as well as other clay minerals. It is thus expected that talc presence in fault-zones would enhance creep and inhibit unstable slip.
Gene-enhancer variants reveal diverse TCR-mediated differentiation

The transcription factor IRF4 acts as a 'rheostat' for TCR signaling. Discrete levels of IRF4 can activate distinct transcriptional programs in T cells due to binding sites of variable affinity in groups of target genes.
In-Hospital Breastfeeding Experiences Among Women with Gestational Diabetes

Abstract Background: In-hospital experiences among women with gestational diabetes mellitus (GDM) could impact breastfeeding success. We sought (1) to determine changes in the prevalence of hospital breastfeeding experiences between 2004–2008 and 2009–2011 among women with GDM and women without diabetes; (2) to determine whether GDM is associated with higher occurrence of experiencing Baby-Friendly hospital practices because of their known higher rates of breastfeeding difficulties. Materials and Methods: Data from the 2004 to 2011 Pregnancy Risk Assessment Monitoring System, a survey of women with a recent live birth from 16 states and New York City, were used based on inclusion of an optional survey question about hospital breastfeeding experiences. We examined the association of in-hospital experiences with GDM within each survey phase using chi-square tests. Weighted multivariable logistic regression was used to determine the association between GDM and hospital breastfeeding experiences. Results: Amo...
Biomarkers of disease can be detected in mice as early as 4 weeks after initiation of exposure to third-hand smoke levels equivalent to those found in homes of smokers

Third-hand smoke (THS) is a newly discovered environmental health hazard that results from accumulation and aging of second-hand smoke (SHS) toxins on surfaces where smoking has occurred. Our objective was to determine whether there is a time-dependent effect of THS exposure on health. Using an in vivo exposure mouse system that mimics exposure of humans to THS, we investigated its effects on biomarkers found in serum, and in liver and brain tissues. Mice were exposed to THS for 1, 2, 4, or 6 months and brain, liver, and serum were collected. We found that THS exposure, as early as 1 month, resulted in increased circulating inflammatory cytokines, tumor necrosis factor by an order of magnitude of 2 and granulocyte macrophage colony-stimulating factor by an order of magnitude of 1.5 and in increases in the stress hormone epinephrine and the liver damage biomarker aspartate aminotransferase (AST), increased in magnitude 1.5 and 2.5 times compared with controls, respectively. THS exposure for 2 months resulted in further damage and at 4 and 6 months, many factors related to oxidative stress were altered and caused molecular damage. We also found that the mice became hyperglycemic and hyperinsulinimic suggesting that insulin resistance (IR) may be a significant consequence of long-term exposure to THS. In conclusion, time-dependent THS exposure has a significant effect on health as early as 1 month after initiation of exposure and these alterations progressively worsen with time. Our studies are important because virtually nothing is known about the effects of increased THS exposure time, they can serve to educate the public on the dangers of THS, and the biomarkers we identified can be used in the clinic, once verified in exposed humans.
Solar Panel Tracking System

A newly developed solar tracking system is introduced with its adjustable orientation angle to track daily sunlight in 3D directions in order to receive the maximum solar energy via systematic photovoltaic arrays. The driving mechanisms designed with gear train unit in this solar tracking system can orientate solar system between east and west and a rotating table can orientate solar unit between north and south. The prototype of this new solar tracking system is depicted in Figs. 4.1 and 4.2.
Making space: Jennifer Camper, LGBTQ anthologies, and queer comics communities.

This article examines the career of lesbian cartoonist Jennifer Camper and how she has fostered queer community both in her comics and in real life. Archival research in LGBTQ archives and in Campe...
Why Judges Don't Recuse Themselves and Attorneys Don't Ask Them To: A Randomized Field Experiment Testing the Efficacy of Recusal and Disclosure

This Article reviews the two most prominent procedural approaches to addressing judicial conflicts of interest — judicial recusal and in-court disclosure — and contends that they fail to account for the legal and institutional dynamics that surround the relationship between judges and attorneys. It argues that judges do not recuse themselves, that attorneys will not ask them to, and that if we understand both the legal and extra-legal incentives at play in these decisions, this should not surprise us. The shortcomings of recusal and disclosure are particularly salient in the context of judicial campaign finance, where judges often face the acute dilemma of being assigned to preside over cases in which one of the parties or attorneys has contributed to their election campaign. To support these claims, this Article presents the results of a randomized field experiment in which we identify active Wisconsin and Texas civil cases that feature donor-attorneys and randomly assign a portion of the judges presiding over these cases to receive a letter from an NGO identifying the potential conflict and requesting recusal. The empirical findings support the growing skepticism surrounding judicial recusal and raise doubts that judicial disclosure is an efficacious remedy. Building on these results, the Article suggests that academics and policy makers spend fewer resources attempting to “fix” the current recusal regime, and it explores two potential remedies — one institutional and one procedural — that account for the realities of judicial conflicts of interest and the incentives of court actors.
Should Genetic Testing for Variants Associated with Influenza Infection Be Mandatory for Health Care Employees

Scientists are beginning to understand more about the role of host genetics in individuals' responses to influenza virus exposure. This fictional case addresses a situation in which a health care organization proposes requiring all health care practitioners with direct patient care responsibilities to undergo mandatory genetic testing for genetic variants used to (1) predict individuals' responses to the influenza vaccine, (2) determine individual susceptibility to influenza infection, and (3) identify individuals at increased risk for severe disease. This commentary will discuss ethical and legal issues associated with use of genetic test results to determine employee work assignments during an influenza pandemic.
The complex underpinnings of genetic background effects

Genetic interactions between mutations and standing polymorphisms can cause mutations to show distinct phenotypic effects in different individuals. To characterize the genetic architecture of these so-called background effects, we genotype 1411 wild-type and mutant yeast cross progeny and measure their growth in 10 environments. Using these data, we map 1086 interactions between segregating loci and 7 different gene knockouts. Each knockout exhibits between 73 and 543 interactions, with 89% of all interactions involving higher-order epistasis between a knockout and multiple loci. Identified loci interact with as few as one knockout and as many as all seven knockouts. In mutants, loci interacting with fewer and more knockouts tend to show enhanced and reduced phenotypic effects, respectively. Cross–environment analysis reveals that most interactions between the knockouts and segregating loci also involve the environment. These results illustrate the complicated interactions between mutations, standing polymorphisms, and the environment that cause background effects. Mutations often show distinct phenotypic effects across different genetic backgrounds. Here the authors describe the genetic basis of these so-called background effects using data on genotype and growth in 10 environments from 1411 segregants from a cross of two strains of budding yeast.
Relationships between the big five personality characteristics and performance on behavioral decision making tasks

Abstract Although significant research exists of a relationship between impulsivity and performance on behavioral risky decision making tasks, relatively few studies examined performance on these tasks as a function of the big five personality characteristics. The present study sought to investigate relationships between the big five personality characteristics and performance on the Iowa Gambling Task (IGT), Balloon Analogue Risk Task (BART), Columbia Card Task (CCT), and Game of Dice Task (GDT). Two samples of undergraduate student participants (n = 318 Study 1; n = 531 Study 2) completed the IGT, BART, CCT, GDT, and assessment of the big five in a random order. Results of the two studies indicated minimal relationships between performance on the decision making tasks and neuroticism, extraversion, openness, and conscientiousness, but some evidence of a relationship between agreeableness and the CCT in Study 2 only. The present results are among the first examining relationships between the big five and performance on the CCT and GDT, and largely replicate findings of limited relationships between these personality characteristics and performance on the IGT and BART. Future research should further examine personality predictors of performance on these tasks, as they are increasingly used to differentiate patient and non-patient samples.
Pregnancy after cancer: Does timing of conception affect infant health?

Background The objective of this retrospective cohort study was to determine whether women who conceive soon after treatment for cancer have higher risks of adverse pregnancy outcomes. Methods Vital records data were linked to cancer registry diagnosis and treatment information in 3 US states. Women who conceived their first pregnancy after diagnosis between ages 20 and 45 years with any invasive cancer or ductal carcinoma in situ were eligible. Log-binomial models were used to compare risks in cancer survivors who conceived in each interval to the risks in matched comparison births to women without cancer. Results Women who conceived ≤1 year after starting chemotherapy for any cancer had higher risks of preterm birth than comparison women (chemotherapy alone: relative risk [RR], 1.9; 95% confidence interval [CI], 1.3-2.7; chemotherapy with radiation: RR, 2.4; 95% CI, 1.6-3.6); women who conceived ≥1 year after starting chemotherapy without radiation or ≥2 years after chemotherapy with radiation did not. In analyses imputing the treatment end date for breast cancer survivors, those who conceived ≥1 year after finishing chemotherapy with or without radiation had no higher risks than women without cancer. The risk of preterm birth in cervical cancer survivors largely persisted but was somewhat lower in pregnancies conceived after the first year (for pregnancies conceived ≤1 year after diagnosis: RR, 3.5; 95% CI, 2.2-5.4; for pregnancies conceived >1 year after diagnosis: RR, 2.4; 95% CI, 1.6-3.5). Conclusions In women who received chemotherapy, the higher risk of preterm birth was limited to those survivors who had short intervals between treatment and conception.Cancer 2018;124:000-000.
Chapter 8 – Liver and Gall Bladder

The liver represents a key target organ for toxicity. The recognition of the diverse patterns of liver injury following experimental or natural exposures to drug and chemical agents is an important step toward understanding the implications of toxicity. As such, characterizing the pattern of injury represents an important contribution of the toxicologic pathologist, who must then actively participate in the characterization of safety or risk, in collaboration with other scientists (toxicologists, molecular biologists, toxicokinetics and metabolism scientists, and clinicians). In many instances, acute responses may allow some prediction of chronic responses. This predictive process is optimal when a mechanism of action for the drug or chemical at the level of the hepatocyte can be inferred and ultimately extrapolated to various scenarios of exposure.
Fusing attributes predicted via conditional GANs for improved skin lesion classification (Conference Presentation)

Skin cancer is the most commonly diagnosed cancer worldwide. It is estimated that there are over 5 million cases of skin cancer are diagnosed in the United States every year. Although less than 5% of all diagnosed skin cancers are melanoma it accounts for over 70% of skin cancer-related deaths. In the past decade, the number of melanoma cancer cases has increased by 53%. Recently, there has been significant work on segmentation and classification of skin lesions via deep learning. However, there is limited work on identifying attributes and clinically-meaningful visual skin lesion patterns from dermoscopic images. In this work, we propose to use conditional GANs for skin lesion segmentation and attribute detection and use these attributes to improve skin lesion classification. The proposed conditional GAN framework can generate segmentation and attribute masks from RGB dermoscopic images. The adversarial-image-to-image translation style architecture forces the generator to learn both local and global features. The Markovian discriminator classifies pairs of image and segmentation labels as being real or fake. Unlike previous approaches, such an architecture not only learns the mapping from dermoscopic images image to segmentation and attribute masks but also learns an optimal loss function to train such a mapping. We demonstrate that the such an approach significantly improves the Jaccard index for segmentation (with a 0.65 threshold) up to 0.893. Fusing the lesion attributes for classification of lesions yields a higher accuracy compared to those without predicted attributes.
A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance.

Maternal obesity is correlated with cardiovascular disease in offspring, with a 1.3-fold increase in events observed in offspring of obese women. We have observed that obesity-exposed oocytes demon...
Acute Funisitis Correlates With the Risk of Early-Onset Sepsis in Term Newborns Assessed Using the Kaiser Sepsis Calculator

BackgroundThe risk of neonatal early-onset sepsis (EOS) is traditionally assessed on maternal signs of clinical chorioamnionitis. Recently, an online EOS risk calculator was developed by Kaiser Per...
Chirality Transfer from Carbon to Nitrogen to Carbon via Cyclic Ammonium Ylides

Cyclic ammonium salts 2 were prepared by diastereoselective quaternization of nitrogen in the corresponding proline or threonine derivatives. Upon treatment with base, salts 2 underwent [1,2]- or [2,3]-shift to 3 with moderate to complete stereospecificity. The overall process entails chirality transfer from the original α carbon to the neighboring nitrogen and then back to the carbon.
CGRP and Brain Functioning: Cautions for Migraine Treatment.

Background Calcitonin gene-related peptide has emerged as a therapeutic target in migraine. Monoclonal antibodies and small molecule receptor antagonists (gepants) directed against CGRP have been approved or are in Phase II or III clinical trials. For monitoring the long-term safety of these drugs, it is helpful to consider the role of CGRP in brain functioning. Methods Qualitative review of the preclinical literature on CGRP in brain physiology and pathophysiology. Results Within the brain, CGRP is upregulated by stresses such as ischemia, injury, hyperthermia, and seizure, and activates neuroprotective processes. Thus, CGRP buffers intracellular calcium, triggers antiapoptotic signaling, upregulates a number of neurotrophins (including insulin-like growth factor-1/IGF-1, basic fibroblast growth factor/bFGF, and nerve growth factor/NGF), reduces brain edema, and likely increases antioxidant defenses. When released outside the blood-brain barrier, CGRP likely protects the endothelium, upregulates growth factor signaling from the endothelium to the brain parenchyma, strengthens the blood-brain barrier, protects the immune privilege of the brain by inhibiting the movement of neutrophils and monocytes, and facilitates neurogenesis and angiogenesis at stem cell niches. Conclusions CGRP participates in a wide range of neuroprotective processes. In theory, migraineurs with comorbid brain pathology might be at increased risk from CGRP inhibition. However, the extent of compensating processes is unknown and will determine whether these risks materialize in practice.
The mechanisms and meteorological drivers of the summertime ozone–temperature relationship

Abstract. Surface ozone ( O3 ) pollution levels are strongly correlated with daytime surface temperatures, especially in highly polluted regions. This correlation is nonlinear and occurs through a variety of temperature-dependent mechanisms related to O3 precursor emissions, lifetimes, and reaction rates, making the reproduction of temperature sensitivities – and the projection of associated human health risks – a complex problem. Here we explore the summertime O3 –temperature relationship in the United States and Europe using the chemical transport model GEOS-Chem. We remove the temperature dependence of several mechanisms most frequently cited as causes of the O3 –temperature “climate penalty”, including PAN decomposition, soil NOx emissions, biogenic volatile organic compound (VOC) emissions, and dry deposition. We quantify the contribution of each mechanism to the overall correlation between O3 and temperature both individually and collectively. Through this analysis we find that the thermal decomposition of PAN can explain, on average, 20 % of the overall O3 –temperature correlation in the United States. The effect is weaker in Europe, explaining 9 % of the overall O3 –temperature relationship. The temperature dependence of biogenic emissions contributes 3 % and 9 % of the total O3 –temperature correlation in the United States and Europe on average, while temperature-dependent deposition (6 % and 1 %) and soil NOx emissions (10 % and 7 %) also contribute. Even considered collectively these mechanisms explain less than 46 % of the modeled O3 –temperature correlation in the United States and 36 % in Europe. We use commonality analysis to demonstrate that covariance with other meteorological phenomena such as stagnancy and humidity can explain the bulk of the remainder of the O3 –temperature correlation. Thus, we demonstrate that the statistical correlation between O3 and temperature alone may greatly overestimate the direct impacts of temperature on O3 , with implications for the interpretation of policy-relevant metrics such as climate penalty.
The γ-Na+,K+-ATPase subunit assembles selectively with α1/β1-Na+,K+-ATPase but not with the colonic H+,K+-ATPase

The γ-Na + ,K + -ATPase subunit assembles selectively with α 1 /β 1 -Na + ,K + -ATPase but not with the colonic H + ,K + -ATPase. Background The ubiquitous Na + -pump (Na + ,K + -ATPase) assembles as a heterodimer of composition α/β in some nephron segments, while in other segments it may exist as a heterotrimer of composition α/β/γ. The γ-subunit has been reported to increase the affinity of the Na + -pump for adenosine 5′-triphosphate (ATP), and decrease affinity for both Na + and K + . The α-subunit of the colonic H + ,K + -ATPase (cHK) shares 75% sequence similarity with α 1 -Na + ,K + -ATPase (α 1 ) and assembles with β 1 -Na + ,K + -ATPase (β 1 ) in distal colon and renal medulla. Differences in pharmacological properties have been ascribed to when heterologously expressed function has been compared to function in vitro. The purpose of this study was to determine if cHK might associate with the γ-subunit of the Na + ,K + -ATPase (γ) as a possible explanation for these variations in function. Methods An antibody specific for the γ was used in coimmunoprecipitation experiments to determine if the γ assembles stably in vitro with cHK and β 1 in rat renal medulla or distal colon. Results Our results demonstrate that the γ-subunit assembles specifically with the Na + -pump, but not with cHK. Furthermore, the γ-subunit assembly was specific for rat kidney and was not observed in distal colon. Conclusion Since the γ-subunit did not assemble with the cHK/β 1 , complex, γ-subunit assembly cannot explain those variations in ex vivo and in vitro pharmacologic properties ascribed to cHK.
Continuous-Time Multi-Armed Bandits with Controlled Restarts

Time-constrained decision processes have been ubiquitous in many fundamental applications in physics, biology and computer science. Recently, restart strategies have gained significant attention for boosting the efficiency of time-constrained processes by expediting the completion times. In this work, we investigate the bandit problem with controlled restarts for time-constrained decision processes, and develop provably good learning algorithms. In particular, we consider a bandit setting where each decision takes a random completion time, and yields a random and correlated reward at the end, with unknown values at the time of decision. The goal of the decision-maker is to maximize the expected total reward subject to a time constraint $\tau$. As an additional control, we allow the decision-maker to interrupt an ongoing task and forgo its reward for a potentially more rewarding alternative. For this problem, we develop efficient online learning algorithms with $O(\log(\tau))$ and $O(\sqrt{\tau\log(\tau)})$ regret in a finite and continuous action space of restart strategies, respectively. We demonstrate an applicability of our algorithm by using it to boost the performance of SAT solvers.
Abstract IA11: Reversal of immunotherapy resistance through hypoxia reduction

Across multiple cancers, we find that T cells fail to accumulate in regions of hypoxia that can occupy as much as 50% of the volume of some solid tumors. In mouse models of both prostate cancer and head and neck cancer, we find that the hypoxia-activated prodrug TH-302 (evofosfamide) can reduce hypoxia by triggering a tissue-remodeling process that culminates in revascularization with organized, functional vessels. In the TRAMP-C2 model of prostate cancer, combining TH-302 with blockade of the T-cell immune checkpoint receptors CTLA-4 and PD-1 cures nearly all mice of 7-day established tumors and the majority of larger, 2-week established malignancy. TRAMP transgenic mice, which do not respond at all to immunotherapy alone, treated with the combination of TH-302 and either CTLA-4 and PD-1 blockade or CTLA-4 blockade and 4-1BB agonist show exceptional tumor control at 36 weeks of age. Mechanistically, hypoxia favors accumulation of myeloid-derived suppressor cells (MDSC), and reduction of hypoxia using TH-302 significantly decreases both their frequency and density in prostate tumors. In addition, the capacity of MDSC from mice receiving hypoxia reduction and checkpoint blockade to suppress T-cell proliferation is significantly diminished. Tumor-infiltrating T cells benefit both directly and indirectly from hypoxia reduction as evidenced by increased proliferation, cytotoxicity, effector cytokine production, and survival. Immunofluorescence reveals a lack of T-cell infiltration of hypoxic zones even in the context of CTLA-4 and PD-1 blockade. In contrast, coadministration of TH-302 with checkpoint blockade promotes nearly equivalent T-cell densities across normoxic and hypoxic tumor areas. Clinically, we are evaluating the combination of TH-302 and ipilimumab in patients with checkpoint refractory melanoma, HPV- head and neck cancer, metastatic prostate cancer, and pancreatic cancer (NCT03098160). Correlative studies in these patients reveal advantageous skewing of the tumor immune microenvironment in tumors where hypoxia is reduced on therapy. Further studies of the response of patient cancers to this therapy are ongoing. In addition, we seek to understand the molecular mechanisms linking hypoxia to impaired suppression in stromal myeloid and fibroblast compartments, and to identify additional pharmacologic interventions capable of disrupting hypoxia. Citation Format: Priyamvada Jayaprakash, Midan Ai, Michael A. Curran. Reversal of immunotherapy resistance through hypoxia reduction [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA11.
Treatment admissions for opioids, cocaine, and methamphetamines among adolescents and emerging adults after legalization of recreational marijuana.

Abstract Background A public health concern stemming from recreational marijuana legalization (RML) is the idea that marijuana may act as a “gateway” drug among youth and young adults, where growing marijuana use will lead to increasing substance use disorder (SUD) for “harder” illicit drugs. This study investigates whether SUD treatment admissions for cocaine, opioids, and methamphetamines increased following RML enactment in Colorado and Washington for adolescents and emerging adults. Methods We entered annual 2008–2017 treatment admissions data from the SAMHSA Treatment Episode Dataset – Admissions (TEDS-A) into difference-in-differences models to investigate whether the difference in treatment admissions for cocaine, opioids, and methamphetamines among adolescents (12–17), early emerging adults (18–20), and late emerging adults (21–24) before versus after RML enactment differed between Colorado and Washington and states without RML. Results There was no significant difference (p Conclusion RML in Washington and Colorado was not associated with an increase in adolescent or emerging adult SUD treatment admissions for opioids, cocaine, or methamphetamines. Future studies should extend this research to other states, other substances, for older adults, and over longer time periods; and consider how the effects of drug policies may differ across different jurisdictions.
Delayed Diagnosis of Congenital Hypothyroidism in a Child with Trisomy 21 and Biotinidase Deficiency and Successful Use of Levothyroxine Sodium Oral Solution.

Endocrine disorders are more common and appear earlier in people with trisomy 21 (T21) than in the general population, with thyroid dysfunction being the most common, including both congenital and acquired hypothyroidism. The treatment for biotinidase deficiency, a condition that occurs in approximately 1 : 110,000 people, is with biotin (vitamin B7) supplementation. However, biotin can interfere with endocrine laboratory assays and cause falsely low thyroid-stimulating hormone (TSH) and elevated free thyroxine (FT4) levels. This can interfere with the timely diagnosis and subsequent treatment of congenital hypothyroidism (CH). This case report describes an infant with partial biotinidase deficiency that was confirmed on day 10 of life. Routine screening erroneously reported "normal" TSH that caused delayed diagnosis of CH due to interference with the TSH assay from concurrent biotin use. Once the biotin treatment was withheld for 4 days and the thyroid function tests repeated, an elevated TSH became apparent. Treatment with tablet levothyroxine (L-T4) was started and subsequently changed to L-T4 oral solution (Tirosint®-SOL) to overcome treatment administration difficulties encountered with the tablet form. This resulted in improved TSH control due to more accurate and consistent dosing compared with the tablet formulation. This is the first report of the use of L-T4 oral solution in an infant with T21 and biotinidase deficiency.
DUOX1 in mammalian disease pathophysiology

Dual oxidase 1 (DUOX1) is a member of the protein family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. DUOX1 has several normal physiological, immunological, and biochemical functions in different parts of the body. Dysregulated oxidative metabolism interferes with various disease pathologies and numerous therapeutic options are based on targeting cellular redox pathways. DUOX1 forms an important enzymatic source of biological oxidants, and DUOX1 expression is frequently dysregulated in various diseases. While this review shortly addresses the biochemical and cellular properties and proposed physiological roles of DUOX1, its main purpose is to summarize the current knowledge with respect to the potential role of DUOX1 enzyme in disease pathology, especially in mammalian organisms. Although DUOX1 is normally prominently expressed in epithelial lineages, it is frequently silenced in epithelial-derived cancers by epigenetic mechanisms. While an abundance of information is available on DUOX1 transcription in different diseases, an increasing number of mechanistic studies indicate a causative relationship between DUOX1 function and disease pathophysiology. Additionally, specific functions of the DUOX1 maturation factor, DUOXA1, will also be addressed. Lastly, urgent and outstanding questions on the field of DUOX1 will be discussed that could provide valuable new diagnostic tools and novel therapeutic options.
Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Enteritidis ODA 99-30581-13, a Heat-Resistant Strain Isolated from Shell Eggs.

ABSTRACT Salmonella enterica serovar Enteritidis ODA 99‐30581‐13 is a relatively heat-resistant strain isolated from shell eggs. The strain has a 4,777,965-bp genome sequence (52.1% GC content) that was predicted to encode 4,455 proteins, including heat stress response proteins and stress response regulators; these may be involved in its heat resistance.
A systematic review of firsthand experiences and supports for students with autism spectrum disorder in higher education

Abstract Background As students with autism spectrum disorder (ASD) are increasingly enrolling at institutions of higher education, their new experiences and offered supports impact their success in this realm. The current review extends previous syntheses of literature related to support systems for students with ASD in higher education, as well as their first-hand experiences. Method This review systematically considered experiences of students with ASD in higher education and supports offered to them in both academic and non-academic realms as reported by students themselves. Of the 2,354 screened studies, 24 met inclusion criteria for review. Results Students with ASD experience high rates of mental health issues, sensory challenges, and social, academic, and communication difficulties. Academic supports, which were infrequently reported, include tutoring, accommodations, and coursework modifications. Non-academic supports included social skills training, peer-mediated interventions, counseling, and other university disability services. Although available, these supports may not be fully utilized due to students’ nondisclosure of their ASD diagnosis. Conclusions Non-academic supports for students with ASD are increasing along with this population’s enrollment in higher education, yet the development of academic supports appears to be less prevalent. These findings suggest institutions of higher education focus on the development and accessibility of academic supports, and additionally, provide faculty and staff with effective professional development to address the stigmatization of seeking out and utilizing available support systems.