cssi/SciSciGPT-SciSciNet huggingface dataset:
Formation Enthalpies and Polymorphs of Nicotinamide–R-Mandelic Acid Co-Crystals

Co-crystals provide an opportunity to improve the properties of pharmaceuticals and other materials. We report a method for determining the formation enthalpies of co-crystals in which enthalpies of melting are measured for a co-crystal and the physical mixture of its component crystals. Because the two melting processes arrive at the same liquid, the difference of their enthalpy changes is the co-crystal’s formation enthalpy. For the system of nicotinamide (NIC) and R-mandelic acid (RMA), the formation enthalpy at 30 °C is −23 (3) J/g for polymorph 1 and −18 (3) J/g for polymorph 2. These values are comparable with the enthalpy of mixing for NIC and RMA liquids [−49 (4) J/g at 160 °C], indicating the need for correcting for nonideal mixing in calculating formation enthalpies of co-crystals via thermodynamic cycles. This correction is made automatically in our method by performing measurements with physical mixtures of component crystals, as opposed to pure component crystals. One of the NIC-RMA polymorph...
Magnetically inhomogeneous ground state below the first-order valence transition in ( Pr 1 − y Y y ) 0.7 Ca 0.3 Co O 3 − δ

Pr-based perovskite cobaltites, such as ${\mathrm{Pr}}_{0.5}{\mathrm{Ca}}_{0.5}\mathrm{Co}{\mathrm{O}}_{3\ensuremath{-}\ensuremath{\delta}}$ and (${\mathrm{Pr}}_{1\ensuremath{-}y}{\mathrm{Y}}_{y}{)}_{1\ensuremath{-}x}{\mathrm{Ca}}_{x}\mathrm{Co}{\mathrm{O}}_{3\ensuremath{-}\ensuremath{\delta}}$ have recently been discovered to undergo a first-order metal-insulator transition on cooling, thought to arise from an unusual shift in electron occupancy from Pr to hybridized Co-O orbitals. While this transition is known to generally suppress long-range ferromagnetic ordering, the true nature of the magnetic ground state remains unclear. In this work, we have performed structural, magnetic, transport, magnetotransport, and small-angle neutron scattering measurements on (${\mathrm{Pr}}_{1\ensuremath{-}y}{\mathrm{Y}}_{y}{)}_{0.7}{\mathrm{Ca}}_{0.3}\mathrm{Co}{\mathrm{O}}_{3\ensuremath{-}\ensuremath{\delta}}$ ($0.000\ensuremath{\le}y\ensuremath{\le}0.200$) in order to develop a complete microscopic picture of the ground state and a full appreciation of the evolution of the first-order transition with Y doping. Our magnetization and zero-field resistivity measurements confirm the presence of an abrupt temperature-dependent metal-insulator transition on cooling, accompanied by a sharp drop in magnetization, setting in between $y$ = 0.050 and 0.075. Small-angle neutron scattering measurements suggest the presence of critical ferromagnetic fluctuations above the metal-insulator transition for $y$ = 0.075, indicating that the system is poised to order ferromagnetically. This magnetic scattering is suppressed at the metal-insulator transition but reemerges at lower temperatures (below 40--50 K) due to the formation of a ferromagnetic cluster state. The clusters have a mean correlation length of \ensuremath{\sim}50 \AA{} at 4 K, although magnetic inhomogeneity occurs across a broad spectrum of length scales, evidencing a highly inhomogeneous ground state, which we relate to the numerous sources of chemical and structural disorder. Interestingly, the magnetically inhomogeneous state manifests an intercluster magnetoresistance effect and a strong field-cooling effect on the low-temperature transport. We interpret these results, quite generally, in terms of the electronic shift from Pr to Co driving the system from the ferromagnetic side of the generic perovskite cobaltite magnetic phase diagram to the insulating side (where ferromagnetic clusters are well known to exist). These results thus shed significant light on the formation of the magnetically inhomogenous ground state of Pr-based cobaltites undergoing a first-order metal-insulator transition and indeed provide clear and direct evidence of such.
LY53857, a 5HT2 receptor antagonist, delays occlusion and inhibits platelet aggregation in a rabbit model of carotid artery occlusion.

The present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 eM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 eM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 ± 16.7% inhibition), collagen (76.1 ± 15.9% inhibition) and U46619 (65.2 ± 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 ± 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 eg/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 eg/kg i.v. occlusion time extended to 164 ± 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 eg/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 eM) and serotonin (1 eM). These studies document the ability to obtain reproducible arterial occlusion in the rabbit and showed that intravenously administered LY53857 prolonged the time to carotid artery occlusion. Prolongation of carotid artery occlusion time was accompanied by inhibition of serotonin-amplified ADP-induced aggregation in rabbit platelets, an effect observed both in vitro and ex vivo. Thus, the rabbit is a useful model for studying the effectiveness of 5HT2 receptor antagonists in prolonging vascular occlusion induced by insult of the carotid artery.
Transient and Permanent Link Errors Co-Management

Transient and permanent errors can be co-managed at the network layer. Ali et al. use end-to-end error detection and retransmission to deal with transient errors; they utilize deterministic rerouting to avoid broken links [1]. Sanusi et al. apply single-error correction and multiple-error detection to packets at the destination, and request flooding if permanent errors are detected [2]. Handling all errors in the network layer increases the burden of that layer.
Clarifying the unique associations among intolerance of uncertainty, anxiety, and depression.

Increasing evidence suggests that intolerance of uncertainty (IU) may be a transdiagnostic factor across the anxiety disorders, and to a lesser extent, unipolar depression. Whereas anxiety inherently involves uncertainty regarding threat, depression has traditionally been associated with certainty (e.g. the hopelessness theory of depression). Some theorists posit that the observed relationship between depression and IU may be due to the relationship between depression and anxiety and the relationship between anxiety and IU. The present study sought to elucidate the unique relationships among trait anxiety, depression, and IU in undergraduate (N = 554) and clinical (generalized anxiety disorder; N = 43) samples. Findings suggest that IU may play a larger role in anxiety than depression, although some evidence indicates that inhibitory IU and depression may have a modest but independent relationship.
TCT-7 Trends and outcomes of percutaneous coronary intervention for ventricular tachycardia or fibrillation cardiac arrest: analysis from nationwide inpatient sample

The decision to perform cardiac catheterization and percutaneous coronary intervention (PCI) in resuscitated patients with sudden cardiac death remains controversial. Prior data suggest a potential benefit from percutaneous revascularization. Using the Nationwide Inpatient Sample, we identified
Initial Characterization of the Pig Skin Bacteriome and Its Effect on In Vitro Models of Wound Healing

Elucidating the roles and composition of the human skin microbiome has revealed a delicate interplay between resident microbes and wound healing. Evolutionarily speaking, normal cutaneous flora likely has been selected for because it potentiates or, at minimum, does not impede wound healing. While pigs are the gold standard model for wound healing studies, the porcine skin microbiome has not been studied in detail. Herein, we performed 16S rDNA sequencing to characterize the pig skin bacteriome at several anatomical locations. Additionally, we used bacterial conditioned-media with in vitro techniques to examine the paracrine effects of bacterial-derived proteins on human keratinocytes (NHEK) and fibroblasts (NHDF). We found that at the phyla level, the pig skin bacteriome is similar to that of humans and largely consists of Firmicutes (55.6%), Bacteroidetes (20.8%), Actinobacteria (13.3%), and Proteobacteria (5.1%) however species-level differences between anatomical locations exist. Studies of bacterial supernatant revealed location-dependent effects on NHDF migration and NHEK apoptosis and growth factor release. These results expand the limited knowledge of the cutaneous bacteriome of healthy swine, and suggest that naturally occurring bacterial flora affects wound healing differentially depending on anatomical location. Ultimately, the pig might be considered the best surrogate for not only wound healing studies but also the cutaneous microbiome. This would not only facilitate investigations into the microbiome’s role in recovery from injury, but also provide microbial targets for enhancing or accelerating wound healing.
Fast, Deep Detection and Tracking of Birds and Nests

We present a visual object detector based on a deep convolutional neural network that quickly outputs bounding box hypotheses without a separate proposal generation stage [1]. We modify the network for better performance, specialize it for a robotic application involving “bird” and “nest” categories (including the creation of a new dataset for the latter), and extend it to enforce temporal continuity for tracking. The system exhibits very competitive detection accuracy and speed, as well as robust, high-speed tracking on several difficult sequences.
Probabilistic Tests with Polynomials

In this lecture, we give a useful probabilistic technique for testing properties that are equivalent to the vanishing of some polynomial of low degree. This technique has many interesting applications, not only in algebraic algorithms, but also in graph theory and combinatorics. Several examples of its use will be given later.
Chapter 34 – Gastrointestinal Drugs

The Side Effects of Drugs Annuals is a series of volumes describing the adverse effects and adverse reactions of drugs. The series supplements the content of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January–December 2015 publications addresses adverse reactions to gastrointestinal-related drugs: acid-impacting, anticonstipation, prokinetic, antidiarrheal, antispasmodic, antiemetic, and anti-inflammatory agents. Materials surveyed included systematic reviews, clinical trials, observational studies, meta-analyses, and case reports with the additional filters of adverse drug reactions, drug-interactions, adverse events, clinical controversies, newly approved drugs/labeling, and pharmacogenomics.
Impact of Metabolic Factors on Screening, Early Detection, and Management of Prostate Cancer

In this chapter, we review the influence of energy imbalance on prostate cancer screening, diagnosis, and management. The influence of obesity on prostate cancer screening, diagnosis, and management is substantial and complex. Obese men have lower serum PSA, a tool to used to screen for prostate cancer, and larger prostate volume, which may lead to a reduced likelihood that an extant, but occult tumor without lethal potential is ever detected, while that same delay may lead to more advanced stages of disease at diagnosis and corresponding increases in prostate cancer mortality. Obesity can adversely affect the efficacy and safety of the treatment of prostate cancer with surgery or radiation. Development of an optimal framework to guide decision-making for prostate cancer screening, risk stratification, and management in obese men is needed.
Leveraging the Knorr Pyrazole Synthesis for the Facile Generation of Thioester Surrogates for use in Native Chemical Ligation

Facile synthesis of C-terminal thioesters is integral to native chemical ligation (NCL) strategies for chemical protein synthesis. We introduce a new method of mild peptide activation, which leverages solid-phase peptide synthesis (SPPS) on an established resin linker and classical heterocyclic chemistry to convert C-terminal peptide hydrazides into their corresponding thioesters via an acyl pyrazole intermediate. Peptide hydrazides, synthesized on established trityl chloride resins, can be activated in solution with stoichiometric acetyl acetone (acac), readily proceed to the peptide acyl pyrazoles. Acyl pyrazoles are mild acylating agents and are efficiently exchanged with an aryl thiol, which can then be directly utilized in NCL. The mild, chemoselective, and stoichiometric activating conditions allow this method to be utilized through multiple sequential ligations without intermediate purification steps.
Impact of the Discordance Between the American College of Cardiology/American Heart Association and American Diabetes Association Recommendations on Hypertension in Patients With Diabetes Mellitus in the United States

Hypertension is common in patients with diabetes mellitus,1,2 and coexistence of hypertension and diabetes mellitus significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD).3 In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) published the new guideline for hypertension,2 and the American Diabetes Association (ADA) also published a position statement for hypertension and diabetes mellitus.4 The ACC/AHA recommended 130/80 mm Hg as the blood pressure (BP) threshold to define hypertension, whereas the ADA recommended 140/90 mm Hg. The authors of the ADA position statement emphasized the importance of an individualized approach to treat hypertension in patients with diabetes mellitus rather than changing the BP threshold.5 Because of the difference between the 2 recommendations and lack of quality evidence to determine a precise BP threshold/target in patients with diabetes mellitus,5 uncertainty still remains in this population. Because the clinical impact of this difference has never been studied, we investigated the prevalence and characteristics of diabetic patients with hypertension and discordant population in the United States according to the ACC/AHA and ADA recommendations. We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2014, a cross-sectional survey representing the noninstitutionalized civilian population in the United States. It was conducted by the National Center for Health Statistics using a stratified, multistage probability sample design. Anonymized data are publicly available at the Centers for Disease Control and Prevention website and can be accessed at https://www.cdc.gov/nchs/nhanes/index.htm. Between 2005 and 2014, the overall response rates ranged from 68.5% to 77.5%. NHANES was approved by the National Center for Health Statistics Research Ethics Review Board. All participants provided written informed consent. Among 28 461 adults aged ≥20 years from the NHANES 2005 to 2014, we firstly excluded participants without 3 BP measurements (n=3483) or data …
FGFR3 Antibodies in Neuropathy. What to do with them? (P1.463)

Objective: To describe the variability of fibroblast growth factor receptor 3 (FGFR3) antibody titers in a series of patients with neuropathy. Background: FGFR3 antibodies have been reported in sensory neuropathy, in the context of autoimmune diseases, using ELISA test as screening method and cell-based assay as confirmatory test. Currently available commercial testing only utilizes ELISA testing. Design/Methods: We performed a retrospective chart review of neuropathy patients with initial positive FGFR3 levels. All FGFR3 antibody testing was performed at the same commercial laboratory. Results: We report five patients with positive FGFR3 antibodies, three women and two men, aged 44 – 74 years. Repeat testing revealed absent antibody titers in two and a significant drop in one patient. High titers (18,000 – 65,000) were present in 4 patients, and low titers in one patient who had no repeat testing. Symptom onset was sudden in 3 and slowly progressive in 2 patients. Four patients reported neuropathic pain; one reported autonomic symptoms. Clinical examination ranged from normal large fiber sensation to mild/moderate predominantly sensory neuropathy; one exhibited sensory ataxia. Four patients showed mild worsening on follow-up examination. NIS-LL scores ranged from 2 to 28. Additional antibodies included: trisulfated disaccharide IdoA2S-GlcNS-6S in two patients, and anti-histone H3 antibodies in 1 patient. One patient had paraproteinemia. Concomitant diseases include polycythemia vera, sarcoidosis, and diabetes mellitus. Electrodiagnostic testing revealed: normal large fiber function (2), severe demyelinating polyneuropathy with axonal features (1). mild/moderate sensorimotor peripheral neuropathy with mixed features (2). No immunotherapy was employed between visits or antibody testing. Conclusions: Our case series highlights the variability and inconsistency in FGFR3 antibody titers by ELISA testing methodology. These antibody titers should be interpreted with caution and clinicians should consider repeat testing or confirmatory testing prior to initiating immunotherapy. Disclosure: Dr. Samara has nothing to disclose. Dr. Sampson has nothing to disclose. Dr. Muppidi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Lundbeck.
Investigate Performance of Expected Maximization on the Knowledge Tracing Model

The Knowledge Tracing model is broadly used in various intelligent tutoring systems. As it estimates the knowledge of the student, it is important to get an accurate estimate. The most common approach for fitting the model is Expected Maximization (EM), which normally stops iterating when there is minimal model improvement as measured by log-likelihood. Even though the model’s predictive accuracy has converged, EM may not have come up with the right parameters when it stops, because the convergence of the log-likelihood value does not necessarily mean the convergence of the parameters. In this work, we examine the model fitting process in more depth and answer the research question: when should EM stop, specifically for the Knowledge Tracing model. While typically EM runs for approximately 7 iterations, in this work we forced EM to run for 50 iterations for a simulated dataset and a real dataset. By recording the parameter values and convergence states at each iteration, we found that stopping EM earlier leads to problems, as the parameter estimates continue to noticeably change after the convergence of the log-likelihood scores.
Using Samples-of-Opportunity to Assess Gender Bias in Principal Evaluations of Teachers: A Cautionary Tale

This paper uses two “samples-of-opportunity” datasets to examine whether principal evaluations of teachers differ systematically across genders after controlling for arguably gender unbiased measures of teacher productivity---namely value-added student test scores calculated relative to other teachers in the same grade/school (where teachers are randomly allocated to classrooms within the same grade/school). While the two datasets appear to be quite similar in nature, both were samples-of-opportunity in that they were not representative of any particular population. Our findings differ substantially across datasets. This exercise reveals how results in the education and discrimination literature may be sensitive to the sample used.
Effects of an Affective Drug Abuse Prevention Program on Inner City Black Youth

With the goal of reinforcing the drug-free experi­ence, this program offered an affective approach to drug abuse prevention intended for teenagers from an inner city minority population. Through informal seminars including films and discussion, youngsters were led to explore their feelings and goals for the future, and the possible effects of drug use on these goals. About 80 teenagers from lower socioeconomic areas of Boston took part in the six-week pro­gram during the summer of 1977. Almost all the participants were black.
Associations Between Social Anxiety and Nonverbal Processing Skill in Preadolescent Boys and Girls

This study was designed to investigate the potential association between social anxiety and children's ability to decode nonverbal emotional cues. Participants were 62 children between 8 and 10 years of age, who completed self-report measures of social anxiety, depressive symptomatology, and nonspecific anxious symptomatology, as well as nonverbal decoding tasks assessing accuracy at identifying emotion in facial expressions and vocal tones. Data were analyzed with multiple regression analyses controlling for generalized cognitive ability, and nonspecific anxious and depressive symptomatology. Results provided partial support for the hypothesis that social anxiety would relate to nonverbal decoding accuracy. Difficulty identifying emotions conveyed in children's and adults' voices was associated with general social avoidance and distress. At higher levels of social anxiety, children more frequently mislabeled fearful voices as sad. Possible explanations for the obtained results are explored.
2.14 – On-line Water Quality Monitoring for Drinking Water Contamination

Monitoring for changes in drinking water quality using online sensors has focused on improving the water delivered to consumers. However, recent research has focused on using sensors as one facet of a holistic contamination warning system or simply monitoring for unusual changes that could indicate contamination. This chapter focuses on the following areas: (1) Results on the change of online water quality parameters to contamination in drinking water. Total organic carbon and free/total chlorine (in chlorinated/chloraminated water, respectively) are often presented as the most effective online-monitoring parameters, so the benefits and gaps of these parameters are discussed; (2) The role that event detection software and algorithms play in analyzing online water quality data for unusual changes; (3) The challenge of high operational and maintenance costs for online sensors within a water distribution network; and (4) The future of online water quality monitoring.
Protestant Perspectives on Organ Donation

My assigned task is to examine Protestant perspectives on organ retrieval, particularly organ donation, with some attention to brain death. Because of the diverse traditions and denominations that are labeled Protestant, I cannot hope to be comprehensive. Instead, I will offer some rough generalizations about perspectives that can legitimately be considered Protestant, while raising more general issues as well.
Superconducting transition widths in applied magnetic fields

The width of superconducting-normal transitions for inhomogeneous ellipsoidal superconductors in an applied magnetic field is calculated. A simple model is used for the variation in transition temperature with position and the range of this variation is assumed to be larger than the Landau-Ginzburg coherence length. It is found that the decrease in transition width with increasing applied magnetic fields at low fields occurs because the boundaries between superconducting and normal regions begin to be determined less by the inhomogeneities and more by the loss of condensation energy between domains, and by sample surface effects. At higher fields, the transition width increases with applied field because of the finite demagnetization coefficient.
Efficacy of transversus abdominis plane (TAP) block in pain management after laparoscopic sleeve gastrectomy (LSG): A double-blind randomized controlled trial

Abstract Background The aim of this randomized controlled trial was to assess the effectiveness of transversus abdominis plane (TAP) block in post-operative pain management in patients undergoing laparoscopic sleeve gastrectomy (LSG). Methods Ninety consecutive patients undergoing LSG were randomly assigned to three groups: placebo, TAP block with 0.25% bupivacaine (40mL total), and TAP block with 0.25% bupivacaine + 1/100,000 epinephrine (40mL total). Pain and nausea/vomiting scores were evaluated at varying times until discharge. Other parameters included, additional analgesia required, time to ambulation, length of stay and time required for return to work after discharge. Results There was decrease in post-operative pain 3 hours after surgery between the placebo group and the bupivacaine group and between the placebo group and the bupivacaine with epinephrine group, however, no difference in 1, 6, 12 and every 6 hours after. There was no significant difference in post-operative analgesia requirements, nausea/vomiting scores, time to ambulation, hospital length of stay, or time to return to work after discharge. Conclusion The efficacy of TAP block is not apparent likely due to the ERAS protocol set in place for bariatric surgery, which already targets early postoperative pain control and mobility.
Consumer preferences of antifungal products for treatment and prevention of tinea pedis

Tinea pedis is a common condition seen in clinical practice and has a significant impact on quality of life. Recommendations of over-the-counter antifungal products based on consumer preferences may guide dermatologists in treating patients with tinea pedis and preventing onychomycosis recurrences. Our study aimed to determine consumer preferences of antifungal products for tinea pedis, focusing on features that may guide purchases and usage. A search was performed for antifungal products used to treat athlete's foot on Amazon.com as of 2018, and the top one percentile of over-the-counter products were sorted by rating and number of reviews. Functionality was the most cited positive feature (42% of comments) followed by cosmetic characteristics (14%). The median price of all products was $1.80 (range $0.33-$95.42), with solutions and balms associated with higher costs and soaks being the least expensive. Our study showed that the range of antifungal products available online for treatment and prevention of tinea pedis is large and variable in terms of type/vehicle, price, and ingredients. Physicians must counsel patients on the efficacy and Food and Drug Administration approval of listed ingredients, especially for those products associated with numerous supplementary claims.
Five‐Membered Ring Systems: Pyrroles and Benzo Analogues

Review: synthesis and reactivity of pyrroles, indoles and related fused ring systems rported during 2012; 341 refs.
A Review of the Totality of Evidence Supporting the Development of the First Adalimumab Biosimilar ABP 501

ABP 501 [United States: AMJEVITA™ (adalimumab-atto); European Union: AMGEVITA® (adalimumab)] is the first approved biosimilar to adalimumab [reference product (RP)], a monoclonal antibody (mAb) targeting tumor necrosis factor-alfa (TNF-α). ABP 501 has received approval for use in indications that adalimumab RP is approved for, except those protected by regulatory exclusivity. A systematic step-wise totality of evidence (TOE) approach formed the basis of approval of ABP 501; this involved methodical accumulation of scientifically robust comparative data supporting similarity in analytical, preclinical, and clinical [pharmacokinetics (PK)], efficacy, safety and immunogenicity) evaluations. As a foundational first step, comprehensive analytical assessments demonstrated that ABP 501 is structurally and functionally similar to adalimumab RP in critical quality attributes. Preclinical assessments confirmed similar activity in assessing mechanisms of action and toxicology. Clinical evaluation included a phase 1 PK equivalence study in healthy subjects and two comparative phase 3 studies that evaluated ABP 501 and adalimumab RP in two sensitive patient populations, plaque psoriasis (PsO) and rheumatoid arthritis (RA). The PK profiles of ABP 501 and adalimumab RP were similar in healthy subjects as well as patients with PsO and RA. The pivotal phase 3 study in patients with PsO demonstrated that ABP 501 was clinically similar to adalimumab RP in terms of efficacy, safety and immunogenicity in both the primary and transition phases. The pivotal phase 3 study in patients with RA also established clinical similarity between ABP 501 and adalimumab RP; an open-label extension of this study demonstrated sustained efficacy over an additional 72 weeks, with no new safety or immunogenicity concerns with ABP 501 treatment. Overall, the TOE supported the conclusion that ABP 501 is highly similar to adalimumab RP and provided scientific justification for extrapolation to all the approved indications of adalimumab RP not protected by exclusivities. Funding: Amgen Inc.
Uncovering Lymphatic Transport Abnormalities in Patients with Primary Lipedema

Background Although lipedema is often clinically distinguished from lymphedema, there is considerable overlap between the two entities. The purpose of this study was to evaluate lymphoscintigraphic findings in patients with lipedema to better characterize lymphatic flow in this patient population. Methods Patients with lipedema receiving lymphoscintigraphy between January 2015 and October 2017 were included. Patient demographics, clinical characteristics, and lymphoscintigraphic findings were extracted. Klienhan's transport index (TI) was utilized to assess lymphatic flow in patient's lower extremities (LEs).Scores ranged from 0 to 45, with values > 10 denoting pathologic lymphatic transport. Results A total of 19 total patients with lipedema underwent lymphoscintigraphic evaluation. Mean age was 54.8 years and mean body mass index was 35.9 kg/m2. Severity of lipedema was classified as stage 1 in five patients (26.3%), stage 2 in four patients (21.1%), stage 3 in four patients (21.1%), and stage 4 in six patients (31.6%). The mean TI for all extremities was 12.5; 24 (63.2%) LEs had a pathologic TI, including 7 LEs with stage 1 (29.2%), 3 LEs with stage 2 (12.5%), 6 LEs with stage 3 (25.0%), and 8 LEs with stage 4 lipedema (33.3%). The mean TI was significantly greater for extremities with severe (stage 3/4) lipedema than those with mild or moderate (stage 1/2) lipedema (15.1 vs. 9.7, p = 0.049). Mean difference in TI scores between each LE for individual patients was 6.43 (standard deviation +7.96). Conclusion Our results suggest that patients with lipedema have impaired lymphatic transport, and more severe lipedema may be associated with greater lymphatic transport abnormalities.
Assessment of primary liver carcinomas other than hepatocellular carcinoma (HCC) with LI-RADS v2018: comparison of the LI-RADS target population to patients without LI-RADS-defined HCC risk factors

To determine whether the LI-RADS imaging features of primary liver carcinomas (PLCs) other than hepatocellular carcinoma (non-HCC PLCs) differ between patients considered high risk (RF+) versus not high risk (RF−) for HCC and to compare rates of miscategorization as probable or definite HCC between the RF+ and RF− populations. This retrospective study included all pathology-proven non-HCC PLCs imaged with liver-protocol CT or MRI from 2007 to 2017 at two liver transplant centers. Patients were defined per LI-RADS v2018 criteria as RF+ or RF−. Two independent, blinded readers (R1, R2) categorized 265 lesions using LI-RADS v2018. Logistic regression was utilized to assess for differences in imaging feature frequencies between RF+ and RF− patients. Fisher’s exact test was used to assess for differences in miscategorization rates. Non-HCC PLCs were significantly more likely to exhibit nonrim arterial phase hyperenhancement (R1: OR = 2.94; R2: OR = 7.09) and nonperipheral “washout” (R1: OR = 3.65; R2: OR = 7.69) but significantly less likely to exhibit peripheral “washout” (R1: OR = 0.30; R2: OR = 0.10) and delayed central enhancement (R1: OR = 0.18; R2: OR = 0.25) in RF+ patients relative to RF− patients. Consequently, non-HCC PLCs were more often miscategorized as probable or definite HCC in RF+ versus RF− patients (R1: 23.3% vs. 3.6%, p < 0.001; R2: 11.0% vs. 2.6%, p = 0.009). Non-HCC PLCs are more likely to mimic HCCs on CT and MRI in the LI-RADS target population than in patients without LI-RADS-defined HCC risk factors. • The presence of LI-RADS-defined risk factors for HCC tends to alter the imaging appearances of non-HCC PLCs, resulting in higher frequencies of major features and lower frequencies of LR-M features. • Non-HCC PLCs are more likely to be miscategorized as probable or definite HCC in the LI-RADS target population than in patients without LI-RADS-defined HCC risk factors.
Exploring oral paleopathology in the Central Andes: A review

Abstract This targeted review of oral paleopathology in the Central Andes explores research that focuses on a set of interrelated, multifactorial processes: dental caries, macrowear, alveolar abscess, antemortem tooth loss (AMTL), periodontal disease, and the presence of dental calculus. These conditions help characterize oral health because they result from the culturally mediated interaction of individuals’ oral cavity with their external environment. To better understand how osteologists working in the Central Andes have interpreted the frequencies of these conditions, I review the etiology of each, as well as discuss the important issues in their analyses. I then highlight studies that integrate of a number of oral paleopathological conditions, that examine associations between oral conditions and other skeletal indicators of health, or that use multivariate statistical techniques to analyze conditions. In the Central Andes, these proxies for oral health have generally focused on several key research themes including the introduction of domesticated foods may have occurred earlier than expected, but that populations may have maintained mixed subsistence strategies for a significant period. Researchers have also identified that changes accompanying Inca imperialism were likely not as detrimental to local populations as was Spanish colonialism. Finally, the long-practiced, culturally important, activity of chewing coca has been shown to create an identifiable pattern of oral paleopathological conditions.
Online Searching and Social Media to Detect Alcohol Use Risk at Population Scale.

Introduction Harnessing engagement in online searching and social media may provide complementary information for monitoring alcohol use, informing prevention and policy evaluation, and extending knowledge available from national surveys. Methods Relative search volumes for 7 alcohol-related keywords were estimated from Google Trends (data, 2014–2017), and the proportion of alcohol use–related Twitter posts (data, 2014–2015) was estimated using natural language processing. Searching/posting measures were created for all 50 U.S. states plus Washington, D.C. Survey reports of alcohol use and summaries of state alcohol policies were obtained from the Behavioral Risk Factor Surveillance System (data, 2014–2016) and the Alcohol Policy Scale. In 2018–2019, associations among searching/posting measures and same state/year Behavioral Risk Factor Surveillance System reports of recent (past-30-day) alcohol use and maximum number of drinks consumed on an occasion were estimated using logistic and linear regression, adjusting for sociodemographics and Internet use, with moderation tested in regressions that included interactions of select searching/posting measures and the Alcohol Policy Scale. Results Recent alcohol use was reported by 52.93% of 1,297,168 Behavioral Risk Factor Surveillance System respondents, which was associated with all state-level searching/posting measures in unadjusted and adjusted models (p Conclusions Strong associations were found among individual alcohol use and state-level alcohol-related searching/posting measures, which were moderated by the strength of state alcohol policies. Findings support using novel personally generated data to monitor alcohol use and possibly evaluate effects of alcohol control policies.
Mechanisms of immune evasion in bladder cancer.

With the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.
Outcomes and Predictive Value of Post-adjuvant Therapy PET/CT for Locally Advanced Oral Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS For locally advanced oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant therapy, consensus has yet to be reached on whether the optimal time to initiate surveillance positron emission tomography/computed tomography (PET/CT) scan is before or after adjuvant therapy. In this study, we characterize the utility of PET/CT scans obtained 3 months after adjuvant therapy. STUDY DESIGN PET/CT scans were obtained for 220 patients with stage III, IVA, or IVB OSCC who underwent resection followed by adjuvant radiotherapy or chemoradiotherapy. METHODS Using the Neck Imaging Reporting and Data System, PET/CT scans were dichotomized as suspicious (primary or neck category ≥3, or distant lesion present) versus nonsuspicious. We then computed differences in locoregional progression, distant progression, and overall survival; positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity; and success rate of salvage. RESULTS Sixty-seven patients (30%) had suspicious PET/CT scans, which were significantly associated with local failure (hazard ratio [HR] 14.0, 95% confidence interval [CI] 7.3-26.6), distant failure (HR 18.4, 95% CI 9.6-35.3), and poorer overall survival (HR 9.5, 95% CI 5.0-17.9). Overall PPV, locoregional PPV, NPV, sensitivity, and specificity were 85%, 79%, 73%, 58%, and 92%, respectively. Among those with biopsy-confirmed progression, 37 patients (65%) underwent salvage therapy; four (11%) were without evidence of disease at last follow-up. CONCLUSIONS For locally advanced OSCC, PET/CT scan 3 months after adjuvant therapy is strongly predictive of disease recurrence and survival, demonstrating improved performance over postoperative imaging in previous studies. Following a suspicious post-adjuvant therapy PET/CT scan, cure of locoregional recurrence is possible but unlikely. LEVEL OF EVIDENCE 4 Laryngoscope, 2020.
Are we missing opioid-related deaths among people with HIV?

Abstract Background Ascertainment of unnatural and overdose death may be unreliable among individuals with life-limiting conditions such as HIV infection. We sought to determine whether the relationship between opioid use and unnatural death differs among decedents with HIV (DWH) and those without. Methods Decedents in the Veterans Aging Cohort Study (VACS) from 2002 to 14 were linked to the National Death Index cause of death file. Deaths were classified as unnatural, overdose (a subset of unnatural), or other. We defined opioid use as self-reported illicit use or receipt of prescribed opioids. Treating unnatural and overdose deaths as outcomes, we calculated odds ratios for opioid exposure by HIV status, with and without adjustment for disease severity using VACS Index. Results Among 561 decedents without HIV (DWOH) and 884 DWH, 11 % and 8 % respectively were classified as unnatural deaths and 4 % and 2 % were classified as overdose deaths. Among DWOH, opioid use was associated with 2-fold greater odds of unnatural (OR 2.3; 95 % CI 1.3–4.0) and 4-fold greater odds of overdose death (OR 4.5; 95 % CI 1.5–13.7); in adjusted analyses, opioid use was associated with unnatural death (OR 2.6; 95 % CI 1.3–4.9) and with overdose (OR 4.2; 95 % CI 1.4–12.7). Opioid use was not associated with unnatural or overdose death among DWH. Conclusion Opioid use was strongly associated with unnatural and overdose death among DWOH but not among DWH suggesting potential differential misclassification. Caution should be used in interpreting prevalence, incidence and risk factors for unnatural and overdose cause of death among patients with life-limiting conditions such as HIV.
The Economics of AI-Based Technologies: A Framework and an Application to Europe

First, this paper discusses how AI-based technologies that are powering the “Fourth Industrial Revolution” are similar in their speed, effects and prerequisites to general purpose technologies (GPTs) that came before and how they are different. AI-based technologies are similar to the steam engine, electric power, and information technology in that (a) they change the nature of work but do not reduce it in aggregate; (b) they increase productivity when accompanied by innovations in business process and investment in human capital; and (c) they leave little room for leapfrogging because profitable adoption of new techniques requires having adapted to previous rounds. AI is different from earlier GPTs mainly in that the speed of its spread is likely to be faster. Second, it provides an economic classification of these technologies based on the channels through which they reduce costs, distinguishing between transactional, informational, and operational technologies. This distinction is relevant because they differ in their structural, social and spatial effects. Third, the paper provides a framework that brings together the economic consequences of AI-based technologies and common policy goals: competitiveness, cohesion and convergence. Finally, it illustrates how this framework can be applied to the European Union. EU member states do least well in transactional platforms where scale matters a lot, they do somewhat better in informational technologies where both market size and regulations matter, and some of them are global leaders in the development and use of AI-based operational technologies such as robots. As with earlier waves of technical change, creation and adoption of AI-based technologies will require good education and well-designed R&D incentives, regulatory capacity, and robust tax-and-transfer systems.
Performance analysis of elliptic curves for VoIP audio encryption using a softphone

The usage of online media streaming has become an essential part of our daily lives due to COVID-19 pandemic. The security issues have gained in importance as well with the proliferative use of real-time media. Usually, symmetric key encryption schemes are used for encrypting real-time media, which are transmitted as Real-time Transport Protocol (RTP) payload. RTP uses the Secure RTP (SRTP) to secure its payload. Several issues exist in the existing SRTP media protection scheme that can be solved by applying lightweight asymmetric key cryptography such as Elliptic Key Cryptography (ECC). We have proposed some suitable Elliptic Curves for real-time audio encryption, which do not compromise the quality of the audio calls.
Impact of Position Errors on Synthetic Aperture DOA Convergence Based on Swarming UAV s

This paper reports on the direction-of-arrival (DOA) estimation using micro-UAV swarm-based (MUSB) arrays in the presence of location errors. The MUSB array is a virtually three-dimensional (3-D) random time-varying array reconstructed from swarming UAVs (unmanned aerial vehicle). In practice, the sensor position errors cannot be omitted and will impact the DOA estimation performance. The goal of this work is to evaluate the impact of the position errors in the proposed MUSB array and study the convergence under low snapshot conditions using the iterative Multiple Signal Classification (iterative- MUSIC) algorithm. Measurements on a thirty location test platform are provided to benchmark the performance with expectations.
Heartbeat: principles for excellence in development of clinical guidelines

Clinical guidelines have become a core element in optimising care for patients with cardiovascular disease. However, the quality of guidelines depends on a rigorous unbiased process that integrates the clinical evidence with input from a range of stakeholders. In this issue of Heart , Garbi1 summarises the National Institute for Health and Care Excellence (NICE) principles and processes for development of clinical guidelines in England. The discussion is divided into four key areas: (1) Guideline development by an independent advisory committee includes aligning recommendations with national health policies, and involvement of patients, patient-advocates, and the public as well as healthcare professionals. (2) Recommendations should be based on relevant, reliable and robust evidence and should include consideration of cost-effectiveness and population benefit. (3) Guidelines should support innovation and reduce healthcare inequalities. (4) Finally, ensuring guideline implementation and providing regular updates are essential. In the accompanying editorial, Otto, Kudenchuk and Newby2 compare the NICE methodology with the current approach of our cardiovascular professional societies, as well as to established reporting criteria for clinical practice guidelines (figure 1).3 They propose several areas for improvement including cooperative development of a common evidence database; a rigorous transparent process based on established standards; a more diverse group of stakeholders; minimising conflicts of interest; support by information specialists, medical writers and other relevant experts; regular updates; adaptation for regional …