cssi/SciSciGPT-SciSciNet huggingface dataset:
Durable Molecular Remission in Two Acute Promyelocytic Leukemia (APL) Patients Treated with Arsenic Trioxide at First Molecular Relapse.

Background: The recurrent detection of the PML- RARα transcripts in APL patients in complete remission (CR) is predictive of clinical relapse. Intervention at the time of molecular relapse rather than at the time of overt clinical relapse may minimize the risks associated with the disease as well as treatment-related complications. Previous studies have shown that patients treated at molecular relapse had improved overall survival compared to patients treated at clinical relapse; however, the optimal approach to the treatment of molecular relapse has not yet been established. Arsenic trioxide is active as a single agent in APL patients who developed overt clinical relapse after treatment with ATRA and anthracycline chemotherapy. We evaluated the use of single agent arsenic trioxide in APL patients who are still in first hematological CR but have become RT-PCR positive. Methods: So far, 2 patients were studied, both females with the long form of RAR RARα (bcr1), aged 29 and 39 years. These patients had normal bone marrow morphology but were found to be RT-PCR positive twice in an interval of at least 2 months, while in first CR at 12 and 36 months, respectively. Arsenic trioxide, 0.15 mg/kg/dose, was administered intravenously for 5 days per week for 5 weeks (total of 25 doses) with a 3 to 6 week rest period between cycles up to a maximum of 4 cycles. Results: Both patients became PCR negative after the first cycle of arsenic trioxide. One patient completed four cycles of therapy. The second patient had a history of diabetes mellitus, received only 20 doses of the first cycle and was removed from the study because of grade III sensory neurotoxicity. The only other side effects were grade II headache in both patients and self-limited grade III liver toxicity in one patient. Both patients remain RT-PCR negative at 30 and 28 months after enrollment, respectively, without further therapy. Conclusions: Without treatment, these patients could be expected to have developed a clinical relapse within 4–10 months. Arsenic trioxide induced a durable second molecular relapse, extending disease-free survival and obviating the need for more intensive treatment, such as chemotherapy and stem cell transplantation.
Abstract 237: Retrospective Validation of Pre-Hospital Electrocardiogram with Zoll E-Series Monitoring System for Field Identification of ST Elevation Myocardial Infarction Patients

Background: Rapid reperfusion of ST elevation myocardial infarction (STEMI) patients with primary percutaneous coronary intervention (PCI) improves outcomes. Systems have been developed in many areas to identify STEMI patients in the field using pre-hospital electrocardiograms (ECGs). The Zoll E-Series (ES) is a defibrillator/monitoring system that utilizes the GE Medical Systems 12SL interpretive algorithm to assist with identification of STEMIs. There is a lack of significant data measuring the accuracy of the Zoll ES and its algorithm, especially in the setting of a large urban population. Methods: We retrospectively looked at 307 consecutive ECGs transmitted by one emergency medical service (EMS) provider to an urban primary PCI facility from October 2009 to January 2011. All transmissions were from Zoll ES monitors. Multiple ECG computer interpretations were screened and filtered out to those labeled \***|ACUTE MI\***|. A retrospective chart review was performed to determine the clinical outcome for each transmission in order to determine the performance of the interpretive algorithm in this population. Results: Overall, 307 ECGs were analyzed. A total of 7% (20 of 307) were confirmed STEMIs (Table 1). The computer reading shows a sensitivity of 95% (20 of 21) and specificity of 94% (268 of 286). There is a positive predictive value (PPV) of 53% (20 of 38). Conclusions: The initial data from this study shows that the Zoll ES has a remarkably high sensitivity of 95% but a poor PPV of 53%. This may be due to multiple confounders that result in STEMI “mimics.” The Zoll ES helps provide a pre-hospital ECG that serves as a powerful and life saving tool in the field. However, due to the low PPV, these findings reinforce that the pre-hospital ECG needs to be combined with an appropriate clinical history and additional human interpretation. Further studies analyzing a larger population of patients should be conducted to further assess the value of using this tool. ![Graphic][1] [1]: /embed/inline-graphic-1.gif
Causal search procedures for fMRI: review and suggestions

In this article, the most commonly used algorithms for causal search on fMRI data are reviewed and discussed, with particular attention paid to aspects of the algorithms useful for substantive neuroimaging researchers. Classic algorithms, such as PC and GES, as well as more contemporary algorithms, such as IMaGES–LOFS and GIMME, are compared and contrasted. One major difference between algorithms, the use of lagged variables to infer direction vs. the assumption of non-normality to infer direction is discussed, with eye on the impact those choices have on substantive findings. The algorithms share some commonalities as well as differences. For instance, some use lagged variables to assist in ascertaining directionality, whereas others rely on aspects of non-normality in the data to infer directionality. Attention is given to the impact of these choices on the reliability of results.
Advanced remote decontamination techniques reduce costs and radiation doses

A highly contaminated cell in the Pacific Northwest Laboratory's (PNL) 324 Building Radiochemical Engineering Facilities was recently decontaminated using a series of remote and contact techniques. The approach used in decontaminating the cell was very successful: It resulted in an 87% lower radiation dose to workers and a cost saving of 39% compared with a hands-on procedure used in another cell 2 yr earlier. Eight cycles of remote decontamination, combining use of an alkaline cleaner foam spray and pressurized water rinse, preceded manned entry. Initial radiation readings in cell C, averaging 50 rad/h, were first reduced to {lt} 200 mrad/h using remote techniques. Contact decontamination was then permissible using ultrahigh-pressure water at 270 MPa, further reducing the average radiation level in the cell to {lt} 86 mrem/h. The radiation dose and the costs to achieve a 244-fold reduction in radiation contamination were 17.8 mrem/m{sup 2} and $1033/m{sup 2} of cell surface area. This paper is part of a larger effort sponsored by the U.S. Department of Energy's Surplus Facilities Management Program to clean out six radioactive cells and to dismantle PNL's pilot-scale radioactive liquid-fed ceramic melter. In this program, numerous other advanced techniques are being developed and are proving valuable,more » particularly in lowering radiation doses.« less
AREM: A Novel Associative Regression Model Based on EM Algorithm

In recent years, there have been increasing efforts in applying association rule mining to build Associative Classification (AC) models. However, the similar area that applies association rule mining to build Associative Regression (AR) models has not been well explored. In this work, we fill this gap by presenting a novel regression model based on association rules called AREM. AREM starts with finding a set of regression rules by applying the instance based pruning strategy, in which the best rules for each instance are discovered and combined. Then a probabilistic model is trained by applying the EM algorithm, in which the right hand side of the rules and their importance weights are updated. The extensive experimental evaluation shows that our model can perform better than both the previously proposed AR model and some of the state of the art regression models, including Boosted Regression Trees, SVR, CART and Cubist, with the Mean Squared Error (MSE) being used as the performance metric.
Structural basis for specific ligation of the peroxisome proliferator-activated receptor δ

The peroxisome proliferator-activated receptor (PPAR) family comprises three subtypes: PPARα, PPARγ, and PPARδ. PPARδ transcriptionally modulates lipid metabolism and the control of energy homeostasis; therefore, PPARδ agonists are promising agents for treating a variety of metabolic disorders. In the present study, we develop a panel of rationally designed PPARδ agonists. The modular motif affords efficient syntheses using building blocks optimized for interactions with subtype-specific residues in the PPARδ ligand-binding domain (LBD). A combination of atomic-resolution protein X-ray crystallographic structures, ligand-dependent LBD stabilization assays, and cell-based transactivation measurements delineate structure–activity relationships (SARs) for PPARδ-selective targeting and structural modulation. We identify key ligand-induced conformational transitions of a conserved tryptophan side chain in the LBD that trigger reorganization of the H2′–H3 surface segment of PPARδ. The subtype-specific conservation of H2′–H3 sequences suggests that this architectural remodeling constitutes a previously unrecognized conformational switch accompanying ligand-dependent PPARδ transcriptional regulation.
Quantifying uncertainty in short-term traffic prediction and its application to optimal staffing plan development

Abstract In this paper, we aim to quantify uncertainty in short-term traffic volume prediction by enhancing a hybrid machine learning model based on Particle Swarm Optimization (PSO) and Extreme Learning Machine (ELM) neural network. Different from the previous studies, the PSO-ELM models require no statistical inference nor distribution assumption of the model parameters, but rather focus on generating the prediction intervals (PIs) that can minimize a multi-objective function which considers two criteria, reliability and interval sharpness. The improved PSO-ELM models are developed for an hourly border crossing traffic dataset and compared to: (1) the original PSO-ELMs; (2) two state of the art models proposed by Zhang et al. (2014) and Guo et al. (2014) separately; and (3) the traditional ARMA and Kalman filter models. The results show that the improved PSO-ELM can always keep the mean PI length the lowest, and guarantee that the PI coverage probability is higher than the corresponding PI nominal confidence, regardless of the confidence level assumed. The study also probes the reasons that led to a few points being not covered by the PIs of PSO-ELMs. Finally, the study proposes a comprehensive optimization framework to make staffing plans for border crossing authority based on bounds of PIs and point predictions. The results show that for holidays, the staffing plans based on PI upper bounds generated much lower total system costs, and that those plans derived from PI upper bounds of the improved PSO-ELM models, are capable of producing the lowest average waiting times at the border. For a weekday or a typical Monday, the workforce plans based on point predictions from Zhang et al. (2014) and Guo et al. (2014) models generated the smallest system costs with low border crossing delays. Moreover, for both holiday and normal Monday scenarios, if the border crossing authority lacked the required staff to implement the plans based on PI upper bounds or point predictions, the staffing plans based on PI lower bounds from the improved PSO-ELMs performed the best, with an acceptable level of service and total system costs close to the point prediction plans.
[Prevalence of human immunodeficiency virus and associated risk factors among men who have sex with men in the major regions of Pearl River Delta, from 2009 to 2013].

Objective To examine the HIV prevalence and associated risk factors among men who have sex with men (MSM) in the Pearl River Delta (PRD) region,in order to provide scientific basis for assessment on HIV prevention programs.Methods Surveillance projects on HIV infection status and risk factors were carried out among MSM in six prefectural PRD cities,based on the national sentinel surveillance program among MSM.Results A total of 8 770 MSM were recruited in the six PRD prefectural cities from 2009 to 2013.The overall prevalence rates of HIV among MSM during 2009 and 2013 were 4.7％,9.7％,10.6％,12.9％ and 11.4％,respectively,appeared an increasing trend.HIV related high-risk behaviors were commonly seen among MSM.The proportion of consistent condom use during anal sex in the last six months was 46.3％.Associated risk factors for HIV infection among MSM would include older age,being non-permenant residents,inconsistent condom use,history of having had sexually transmitted diseases and without having received intervention services in the last year.Conclusion High-risk behaviors were popular in the MSM population that causing the HIV transmission to expand among the MSM population in the major region of PRD.It seemed necessary to reinforce the publicity and education programs as well as effective behavior intervening measures among the MSM group. Key words: Men who have sex with men; HIV/AIDS; Sentinel surveillance; Influence factors
Neurocognition and Medication Adherence in HIV-Infected Adults

Pharmacological advances in the treatment of HIV infection have transformed what was once a terminal illness into a chronic illness. Although an increasing number of patients are being placed on antiretroviral therapy, poor adherence to treatment remains one of the leading causes of treatment failure. As such, research assessing factors that predict medication adherence to antiretroviral therapy is highly important from a public health perspective. This chapter will focus on the relationship between cognition and medication adherence among HIV-infected adults, with special emphasis on older HIV+ adults, one of the fasting growing subgroups in the HIV-infected populace. The chapter is intended to provide a broad overview of neuropsychological factors associated with medication adherence to antiretroviral therapy. We will begin with a brief review of some of the many methodological complexities important to consider in the study of medication adherence and cognition. The balance of the chapter will focus on key neurocognitive, psychiatric (including substance use), and psychosocial factors that are related to medication adherence in the HIV population.
Photon Scattering at Very High Energies — OR: How does the Photon Evolve?

In the framework of this Course on the Gauge Interaction, it is appropriate that we take a close look at the quantum of that basic gauge field which we believe to have a solid grip on, at the photon. The carrier of the electromagnetic field has, of course, been shown to be precisely described by Quantum Electrodynamics (QED) in its interactions with point-like leptons. The question of interest here is this: what have we gleaned from the manifestations of the photon in kinematical regimes where its coupling to heavier particles becomes intimately entangled with observables?
Monitoring a multivariate step process

The productivity of an industrial processing unit often depends on equipment that changes over time. These changes may not be consistent, and , in many cases, may appear to occur in stages. Although changes in the process levels within each stage may ap..
An Analysis and Correction of Polarization Induced Calibration Errors for the Cross-track Infrared Sounder (CrIS) Sensor

A model of the potential polarization induced calibration bias is presented for the CrIS instrument, along with details of the model parameter determination, and the predicted impact of the correction on the calibrated radiances.
Neurolymphomatosis: Clinical, Radiographic, and Pathologic Characteristics (S45.005)

Objective: To characterize the clinical, radiographic, pathologic findings and outcomes after therapy in biopsy-proven cases of primary and secondary neurolymphomatosis (NL). Background: NL is a rare presentation of lymphoma involving the nerve roots, plexus, or peripheral nerves. It can be primary NL or indicate progression of previously diagnosed lymphoma (secondary NL). The varied clinical presentation and overlap with other paraneoplastic and paraproteinemic neuropathic syndromes makes the diagnosis of NL difficult. This has implications for prognosis as the disease can progress over weeks to months if untreated. Design/Methods: We reviewed 49 patients evaluated at the Mayo Clinic in Rochester, MN with nerve-biopsy proven NL between 1992 and 2016. Results: Twenty-nine patients had primary NL (59%) and 20 patients had secondary NL (41%). The most common clinical presentations were an asymmetric, painful radiculoplexus neuropathy (37.5%), polyradiculoneuropathy (23%), or multiple/single mononeuropathies (18%). MRI better identified lymphoma than CT or PET (84 % vs. 46% vs. 58%). Diffuse large B-cell NHL represented most cases of primary and secondary NL (96%). Distal cutaneous (12) or proximal targeted fascicular biopsies (25) showed increased demyelination and empty nerve strands in both groups, with more prominent axonal degeneration in secondary NL (31% vs. 7%; p=0.005). Secondary NL had a less favorable response to treatment (33% vs. 62%, p=0.02) and higher mortality (60% vs. 24%, p=0.015). Conclusions: Peripheral nerve lymphoma should be considered in the setting of a subacute, painful peripheral nerve syndrome. MRI should be used in the evaluation, but nerve biopsy is necessary to confirm the diagnosis. The prominent axonal degeneration seen in secondary NL is likely a manifestation of more aggressive disease. The demyelinating features in both primary and secondary NL differ from what is seen in paraneoplastic and paraproteinemic syndromes. If there is clinical suspicion for primary or secondary NL, timely evaluation should be undertaken in order to expedite treatment. Disclosure: Dr. Martinez-Thompson has nothing to disclose. Dr. Suanprasert has nothing to disclose. Dr. King has nothing to disclose. Dr. Macon has nothing to disclose. Dr. Mauermann has nothing to disclose. Dr. Amrami has nothing to disclose. Dr. Spinner has nothing to disclose. Dr. Dyck has nothing to disclose. Dr. Dyck has nothing to disclose.
Heart rate variability in alcohol use: A review.

Abstract Background Prior studies have shown that resting heart rate variability (HRV) is reduced in those with alcohol use disorders (AUD). However, HRV following an acute stressful stimulus (reactive HRV), and the relationship between resting or reactive HRV and drinking, craving and relapse in AUD have received less attention. Methods Studies using HRV in relationship to acute or chronic alcohol consumption were included in this review. Manuscripts that related to alcohol in the context of cardiovascular disease were excluded. Results Thirty-three articles were included and findings are presented in healthy social drinkers, moderate/heavy drinkers without AUD and individuals with AUD. Results on resting and reactive HRV were presented separately. Acute alcohol reduced resting HRV in healthy subjects but healthy controls had higher resting HRV then AUD subjects and moderate/heavy drinkers (in some studies). Resting HRV improved in AUD subjects only after at least 4 months of abstinence. AUD subjects had higher reactive HRV scores when compared to controls. In AUD subjects increased reactivity was related to more craving, faster relapse and more negative mood. Reactive HRV showed slower improvement with abstinence in AUD subjects. Conclusions Chronic, heavy alcohol has a negative effect on the autonomic nervous system and may be a sensitive biomarker of craving and relapse.
(189) Intersectional Health-Related Stigma and Poor Quality of Life in People Living with HIV and Chronic Pain

Intersectional health-related stigma (IHRS) refers to stigma that arises at the convergence of multiple health conditions. People living with HIV (PLWH) and chronic pain have two highly stigmatized health conditions, and thus may be at especially high risk for internalizing these stigmas and consequently experiencing reduced health-related quality of life (QOL). This study examined the intersectionality of internalized HIV and chronic pain stigma in relation to mental QOL and physical QOL in a sample of PLWH and chronic pain. Participants (N = 66) were recruited from an HIV clinic in the Southeastern United States. Chronic pain was defined as pain that has been present for at least three consecutive months, and that has been an ongoing problem for at least half the days in the past six months. All participants completed the HIV Stigma Mechanisms Scale, Internalized Chronic Pain Stigma Scale, and the Short Form 36 Health Survey (SF-36). An intersectional HIV and chronic pain stigma composite variable was created and participants were categorized as either high (29%), moderate (35%), or low (36%). Results from two unadjusted ANOVAs revealed that intersectional HIV and chronic pain stigma was significantly associated with poor mental QOL (F2,65 = 3.09, p = .05) and poor physical health QOL (F2,65 = 8.74, p
A Model of Causal Relationships Affecting the Effectiveness of Primary Schools under Khon Kaen Primary Education Service Area

The objectives of this research were 1) to examine the causal relationship model of factors affecting the effectiveness of primary schools which was developed through empirical data, 2) to study the factors that have direct, indirect and overall influence on the effectiveness of primary schools in Khon Kaen. The samples were 640 school administrators including teachers in Khon Kaen primary schools. The data were analyzed by program computer using the method of structural equation modeling (SEM). The research results indicated that the causal relationship model factors affecting the effectiveness of Khon Kaen primary schools consist of 5 latent variables or factors namely: 1) school vision, 2) academic leadership, 3) promotion of school climate and environment, 4) quality teaching, and 5) learned behavior of students. As for causal relationship model of factors affecting the effectiveness of the above-stated schools, it is found that the construct validity is in congruence with the empirical data. The indices of congruence are Chi-Square at 94.793, df = 87, P-value=0.2662, TLI= 0.998, CFI=0.999, SRMR=0.031, RMSEA=0.013, with statistical significance at .01. The factors that directly and positively affect were of statistical significance at .01, are 1) shared vision, 2) academic leadership, 3) teaching quality, respectively, The most indirect influential factors affecting the school effectiveness are 1) shared vision, having indirect influence in positive manner to climate and environment of the schools, affecting in positive manner to teachers’ teaching quality, and 3) academic leadership having indirect influence in positive manner on school climate and environment that affect students’ learning, respectively.
Tobacco Retail Licensing and Density 3 Years After License Regulations in Philadelphia, Pennsylvania (2012–2019)

Objectives. To evaluate changes in licensed tobacco retailers and retailer density 5 years before and 3 years after novel tobacco retailer licensing regulations were implemented in a large, urban a...
Inter-organizational Ties, Community, And the Emergence of an Oyster Industry In New Hampshire

Through in-depth interviews with New Hampshire oyster farmers, this study examines how inter-organizational relations—in community form—can help emergent industries address challenges and collectively thrive. By examining the four main sources of uncertainty identified by the farmers, we are able to understand the way in which the farmers utilize their community to reduce those uncertainties. Their community functions as an inter-organizational network, where member participation is based on long-term, intangible benefits that complicate a simple instrumental exchange model. These benefits include open access to a pool of knowledge, sociopolitical legitimacy that enables regulatory influence, the existence of strong, community-wide norms that help to ensure high standards of quality and safety, and a buffering of opportunistic behavior in the event of a market fluctuation. Keywords: communities of practice, inter-organizational networks, uncertainty, risk management, aquaculture, oyster aquaculture
Guillain–Barré Syndrome

Guillain–Barre syndrome is an autoimmune nerve disease that presents with generalized weakness and sensory symptoms due to demyelination of the peripheral nerves. Diagnosis is usually supported by clinical findings of weakness with areflexia, electromyogram, and cerebrospinal fluid analysis. Most patients respond to immune-modulating therapies and recover with little to no residual weakness.
Outcomes assessment in intrahepatic cholangiocarcinoma using qualitative and quantitative imaging features

To assess the performance of imaging features, including radiomics texture features, in predicting histopathologic tumor grade, AJCC stage, and outcomes [time to recurrence (TTR) and overall survival (OS)] in patients with intrahepatic cholangiocarcinoma (ICC). Seventy-three patients (26 M/47F, mean age 63y) with pre-operative imaging (CT, n = 37; MRI, n = 21; CT and MRI, n = 15] within 6 months of resection were included in this retrospective study. Qualitative imaging traits were assessed by 2 observers. A 3rd observer measured tumor apparent diffusion coefficient (ADC), enhancement ratios (ERs), and Haralick texture features. Blood biomarkers and imaging features were compared with histopathology (tumor grade and AJCC stage) and outcomes (TTR and OS) using log-rank, generalized Wilcoxon, Cox proportional hazards regression, and Fisher exact tests. Median TTR and OS were 53.9 and 79.7 months. ICC recurred in 64.4% (47/73) of patients and 46.6% (34/73) of patients died. There was fair accuracy for some qualitative imaging features in the prediction of worse tumor grade (maximal AUC of 0.68 for biliary obstruction on MRI, p = 0.032, observer 1) and higher AJCC stage (maximal AUC of 0.73 for biliary obstruction on CT, p = 0.002, observer 2; and AUC of 0.73 for vascular involvement on MRI, p = 0.01, observer 2). Cox proportional hazards regression analysis showed that CA 19–9 [hazard ratio (HR) 2.44/95% confidence interval (CI) 1.31–4.57/p = 0.005)] and tumor size on imaging (HR 1.13/95% CI 1.04–1.22/p = 0.003) were significant predictors of TTR, while CA 19–9 (HR 4.08/95% CI 1.75–9.56, p = 0.001) and presence of metastatic lymph nodes at histopathology (HR 2.86/95% CI 1.35–6.07/p = 0.006) were significant predictors of OS. On multivariable analysis, satellite lesions on CT (HR 2.79/95%CI 1.01–7.15/p = 0.032, observer 2), vascular involvement on MRI (HR 0.10/95% CI 0.01–0.85/p = 0.032, observer 1), and texture feature MRI variance (HR 0.55/95% CI 0.31–0.97, p = 0.040) predicted TTR once adjusted for the independent predictors CA 19–9 and tumor size on imaging. Several qualitative and quantitative features demonstrated associations with TTR, OS, and AJCC stage at univariable analysis (range: HR 0.35–19; p 0.088). There was reasonable accuracy in predicting tumor grade and higher AJCC stage in ICC utilizing certain qualitative and quantitative imaging traits. Serum CA 19–9, tumor size, presence of metastatic lymph nodes, and qualitative imaging traits of satellite lesions and vascular involvement are predictors of patient outcomes, along with a promising predictive ability of certain quantitative texture features.
Subcutaneous sumatriptans for acute migraine attacks in adults.

Migraines are common and most often described as painful pulsatile headaches with nausea and sensory sensitivities. Sumatriptan is one of many medications available for treatment of acute migraine attacks.
Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial

ABSTRACT Background Older patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19. Objective To evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic ≥40 years-old COVID-19 patients. Design A randomized, double-blind, placebo-controlled clinical trial. Setting Outpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020. Participants Out of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephone-based recruitment, but only 34 subjects were able to be randomized. Interventions Hydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days. Measurements The primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia. Results The median time to release from quarantine for HCQ-treated vs. placebo-treated participants was 8 days (range 4-19 days) vs. 11 days (4-18 days); z-score +0.58, p=n.s. This did not meet the pre-specified criteria for early termination, however, this study was terminated early due to lack of feasibility. There was no mortality in either study arm. Limitation Since this study was terminated early due to a lack of feasibility, no conclusion can be made about the efficacy of hydroxychloroquine as a treatment for COVID-19 patients 40 years of age or older quarantined at home. Conclusion The design of this remotely conducted study could guide testing of other more promising agents during the COVID-19 pandemic. Trial registration Clinicaltrials.gov identifier: NCT04329923
Peptides Derived from In Vitro and In Vivo Digestion of Human Milk Are Immunomodulatory in THP-1 Human Macrophages.

BACKGROUND Milk proteins contain many encrypted bioactive peptides. Whether these bioactive peptides are released in the infant intestine and exert immunomodulatory activity remains unknown. OBJECTIVE This study examined in vitro immunomodulatory activities of peptides from in vitro- and in vivo-digested human milk. METHODS Peptides were extracted from in vitro-digested human milk and pooled intestinal samples from eight infants fed human milk. Peptides extracted from in vitro-digested samples were fractionated. The in vitro effects of these peptides and fractions on the secretion of TNFα and IL-8 in LPS-treated human immune THP-1 macrophages were evaluated. The significance of differences between in vitro peptide fraction treatment and control on cytokine production were analyzed by t-test. LC-MS/MS-based peptidomics was conducted to identify the peptides. The peptides were screened for potential bioactivity using a sequence homology search against Milk Bioactive Peptide Database (MBPDB). RESULTS Six fractions of the peptide mixture extracted from the in vitro-digested human milk significantly inhibited TNFα production by LPS-challenged THP-1 macrophages. Fractions F4, F8, F11, F14, and F17 attenuated IL-8 secretion, and F6/7 and F18 increased IL-8 secretion. Peptides extracted from the pooled in vivo intestinal samples attenuated both TNFα and IL-8 secretion. There were 266 and 418 peptides identified in the in vitro and in vivo samples, respectively. Among the peptides, 34 and 50 in the in vitro and in vivo samples, respectively, had > 80% sequence similarity to bioactive peptides in the MBPDB. CONCLUSIONS Peptides released by in vitro and in vivo infant digestion of human milk were immunomodulatory in human immune cells, fractions F4, F8, and F11 were anti-inflammatory, and F6/7 and F18 were pro-inflammatory. Thirteen peptides were present in all fractions with anti-inflammatory activity, and 38 peptides were present in all fractions with pro-inflammatory activity. These peptides potentially contributed to the observed immunomodulatory activity of the peptide mixtures.
Government Speech, Distorted Science, and the First Amendment

Throughout the COVID-19 pandemic, Americans have had to confront an extraordinary speech phenomenon: an onslaught of misinformation and recurring lies from government officials, including the former President and his top health officials, about the pandemic. This phenomenon intersects in potentially novel ways with enduring questions about the regulation of government speech. Ordinarily, the government is free to articulate its own message to the exclusion of others. It can be pro-democracy or anti-tobacco without running afoul of the First Amendment. Whereas the requirement of content neutrality applies when the government polices the public speech of non-governmental actors, neither the government nor government officials are required to be neutral in their own messaging. Nor would we want them to be neutral regarding scientific and factual issues. Rather, we expect that government health agencies, such as the CDC or FDA and their officials, express only one side – the side best supported by science. In this sense, we have traditionally treated government speech relating to health, safety and scientific matters as a particular form of expert speech. The expectation of content neutrality also does not apply to non-governmental experts, such as physicians and other health professionals. They are expected to ground the information they offer in the best science available. But unlike government officials, they are subject to malpractice law when they are offering advice to particular patients and clients. Government speakers have traditionally faced no such consequences for giving bad advice to the public. The torts of public health malpractice or public official informational fraud are not recognized. That raises the critical question: should they be? Or, do First Amendment values demand that government speakers have free reign, even when they deliberately distort scientific information related to the health of the citizenry? In this Article, we engage with such questions. We begin by offering a typology that disaggregates speakers and types of speech through the lens of the range of misinformation that officials have offered during the COVID-19 pandemic. We distinguish among government speakers who echo experts, government experts who speak outside of their realm of expertise, and government speakers who lack expertise and issue official statements contra to expertise. We then explore the First Amendment’s relationship to government health misinformation, and consider whether private law should play a similar demarcation between protected and unprotected speech for government health officials as it does for privately practicing health professionals. We then argue that given the strong similarities between certain types of official health-related misinformation and professional speech, the legal regime that applies to the latter, more specifically malpractice law, provides a helpful model for thinking about and potentially policing the former.
Targeted drug combinations: avant-garde oncology

In this year’s most prominent oncology conferences, an emerging theme amongst leading abstracts was the increasing use of combination targeted therapy. Spurred by a presidential call for precision medicine, leading researchers are now exploring the use of a combination of targeted agents to simultaneously attack multiple cancer pathways. This strategy has been most exemplified in the case of cancer immunotherapy, as a number of groundbreaking studies in the clinical arena have demonstrated the promise and superiority of combination therapy.
Atomistic Potentials for Polymers and Organic Materials

Accurate representation of the potential energy lies at the heart of all simulations of real materials. Accurate potentials are required for molecular simulations to accurately predict the behavior and properties of materials, and even qualitative conclusions drawn from simulations employing inaccurate or unvalidated potentials are problematic. Various forms of classical potentials (force fields) for polymers and organic materials can be found in the literature [1, 2, 3]. The most appropriate form of the potential depends largely upon the properties of interest to the simulator. When interest lies in reproducing the static, thermodynamic and dynamic (transport and relaxational) properties of non-reactive organic materials, the potential must accurately represent the molecular geometry, nonbonded interactions, and conformational energetics of the materials of interest. The relatively simple representation of the classical potential energy discussed below has been found to work remarkable well for these properties. More complicated potentials that can handle chemical reactions [4] or are designed to very accurately reproduce vibrational spectra [5] can be found in the literature. The form of the force field considered here has the advantages of being more easily parameterized than more complicated forms. Parameterization of even simple potentials is a challenging task, however, as discussed below.
Preliminary Validation of a ‘Calf Side’ Test for Measurement of Serum IgG in Dairy Calves

The importance of adequate passive transfer (APT, IgG ≥ 10 mg/mL at 24-48 h) of immunoglobulin (lg) for newborn calves is widely known in the dairy industry. Failure of passive transfer (FPT) is associated with increased risk of morbidity, mortality, reduced growth rate, and decreased production at first lactation. The gold standard test is measurement of serum IgG concentrations in an accredited veterinary laboratory using either RID or turbidimetric immunoassay (TIA) methods. Laboratory measures are accurate but expensive ($6 to $12 per sample), plus take time to ship samples and wait for results. A common on-farm test is to measure serum total protein (TP) concentrations using a hand held refractometer to indirectly predict serum IgG concentrations. This approach is inexpensive and rapid but is less accurate than direct IgG measurement in a laboratory. Calloway and others (2002) reported that serum TP concentrations of 5.0 g/dL had a sensitivity and specificity of 0.89 and 0.84, respectively, in detecting calves with FPT. Ideally, the industry would have available an accurate, rapid, convenient, and inexpensive calf-side test to measure serum IgG concentrations. The Midland BioProducts QTII™ Bovine Serum IgG test is a portable hand-held chemistry analyzer that works on the principle of a TIA method (Midland BioProducts Inc., Boone, IA). The chemistry analyzer weighs about 2 lb (0.91 kg), is about the size of a 1 L bottle and costs $1,950.00 as a one time purchase. Test kits are available in sets of 5 at approx. $7 .50 per test for the bovine species IgG. Test kits are also available for other bovine analytes including serum albumin, total protein, calcium, magnesium and phosphorus. It takes approx. six minutes to run one test. The objective of this study was to describe the test characteristics of the MBC QTII™ Bovine Serum IgG test.
Microscopic and Macroscopic Phase Transitions in Polyelectroyte-Micelle Systems

1. ABSTRACT Polyelectrolytes interact with oppositely charged surfactant to micelles to form either soluble complexes, precipitates or coacervates. These interactions occur abruptly upon increase of micelle surface charge density σ or decrease in ionic strength I, thus resembling phase transitions. This paper presents three aspects of complex formation. The simple phenomenological relationship observed between σ and I is discussed in terms of the energetics of polyelectrolyte-micelle interaction. Structural features of soluble complexes deduced primarily from scattering measurements are described. Presented last is a summary of current understanding of the nature of liquid-liquid phase separation and the structure of the resultant coacervates.
Physician–patient discussions of controversial cancer screening tests

Abstract Background: Screening mammography for younger women and prostate-specific antigen (PSA) measurement have controversial benefits and known potential adverse consequences. While providing informed consent and eliciting patient preference have been advocated for these tests, little is known about how often these discussions take place or about barriers to these discussions. Methods: We administered a survey to medical house staff and attending physicians practicing primary care. The survey examined physicians’ likelihood of discussing screening mammography and PSA testing, and factors influencing the frequency and quality of these discussions. Results: For the three scenarios, 16% to 34% of physicians stated that they do not discuss the screening tests. The likelihood of having a discussion was significantly associated with house staff physicians’ belief that PSA screening is advantageous; house staff and attending physicians’ intention to order a PSA test, and attending physicians’ intention to order a mammogram; and a controversial indication for screening. The most commonly identified barriers to discussions were lack of time, the complexity of the topic, and a language barrier. Conclusions: Physicians report they often do not discuss cancer screening tests with their patients. Our finding that physicians’ beliefs and intention to order the tests, and extraneous factors such as time constraints and a language barrier, are associated with discussions indicates that some patients may be inappropriately denied the opportunity to choose whether to screen for breast and prostate cancer.
Ultrastructure of phloem in palms

Ultrastructure of mature phloem was studied from eighteen species in eleven genera of palms. Mature sieve elements are typically devoid of nuclei and contain only a thin layer of parietal cytoplasm. Plastids and mitochondria are present in various stages of degeneration depending on the age of the sieve element. Tubular structures apparently unrelated to P-protein are present in close association with the ER in many mature sieve elements. Membranous material comparable to the ER traverses the sieve-plate pores of mature protophloem elements in some smaller roots. However, sieve-plate pores of mature metaphloem elements are normally free of ER. Sieve-plate pores contain variable amounts of callose and P-protein-like filaments in most sieve elements of material that was cut into small slivers prior to fixation. However, sieve elements located near the middle of long slivers of material often have sieve-plate pores that are free of filaments after fixation. Sieve elements estimated to be several decades old are basically similar in structure to recently matured sieve elements except for the apparent decrease in the amount of ER, and increased degeneration of mitochondria and plastids in the older elements. Structural similarities and differences of sieve elements in palms are compared with those of other angiosperms.
Global systematics of mid-ocean ridge morphology

Global mid-ocean ridge morphology is characterized by a dichotomy in which slow spreading centers have discontinuous axial valleys and rugged flanking morphology while fast spreading centers have more continuous axial rises and smoother flanking morphology. This study investigates the relationship between axial and flanking morphology and the nature of the dichotomy. Both axial and flanking morphology show similar variations with spreading rate but the transition between axial valley and axial rise morphology suggests that the amplitude of the axial morphology is not the sole determinant of flanking roughness. At slower spreading rates, ridge flank roughness is moderately correlated with axial valley relief, but at intermediate spreading rates significant seafloor deformation can occur without the formation of an axial rise or axial valley. At faster spreading rates, well developed axial rises have smoother flanking morphology and show no correlation between axial relief and flanking roughness. This reflects a fundamental difference in the mechanisms of lithospheric deformation as well as the importance of extrusive volcanism at high spreading rates and thermal environments where an axial magma chamber can be maintained. Axial valley spreading centers exhibit a spreading rate dependence in both amplitude and variability of axial relief, asymmetry, flanking roughness and depth but spreading centers'with axial rises show much less variability and no spreading rate dependence for any observable above intermediate (∼70 km/Ma) spreading rates. The variability of axial valley environments at a given spreading rate results primarily from intrasegment structure but may also reflect temporal episodicity of magmatic emplacement and extension. The dichotomy, which is also manifest in the subsurface structure of spreading centers, suggests a transition from episodicity and rate dependence at slow spreading rates to a metastable mode of lithospheric accretion at faster spreading rates. The most plausible mechanism for the transition is a stabilization of mid-ocean ridge thermal structure above a critical spreading rate.
Why some papers have long citation lifetimes

When scientists publish their results they wonder whether their papers will be remembered for many years, as some are, or quickly forgotten. Here we show why the average lifetimes of papers in various scientific disciplines differ so much. We find that both the length of the paper and the speed of growth of the field are crucial in determining the duration and number of citations it receives.
A Floating NAV for Money Market Funds: Fix or Fantasy?

The announcement by the Reserve Primary Fund, in September 2008, that it was “breaking the buck,” triggered a widespread withdrawal of assets from other money market funds and led the U.S. Government to adopt emergency measures to maintain the stability of the short term credit markets. In light of these events, the SEC heightened the regulatory requirements to which money market funds - a three trillion dollar industry - are subject. Regulators and commentators continue to press for further regulatory change, however. The most controversial reform proposal would eliminate the ability of money market funds to purchase and sell shares at a stable $1/share price.This article argues that the debate over a floating NAV is misguided. First, under current law, money market funds can maintain a $1 share price only under limited conditions. Second, a floating NAV would not achieve the goals claimed by its proponents. Third, and most important, a stable share price is critical to the existence of the money market funds industry. A required floating NAV would eliminate the fundamental attraction of money market funds for investors and, as a result, jeopardize the availability of short term capital.The more important regulatory question, on which existing commentary has not focused, is what happens if an MMF breaks the buck. This article takes the position that this event should neither require the fund to be liquidated nor permit the board unfettered discretion in suspending redemptions. Instead the article proposes two procedural reforms designed to provide flexibility and predictability in these circumstances by allowing a money market fund to convert to a floating NAV and allowing investors to redeem most of their shares without awaiting completion of a fund’s liquidation. In conjunction with a modest amendment requiring improved fund disclosure about the circumstances under which a fund may be unable to maintain a stable share price, these changes will increase liquidity, address the pressures that may lead to a “run,” preserve the economic viability of money market funds, and allow them to respond to the preferences of investors.