cssi/SciSciGPT-SciSciNet huggingface dataset:
Early Recurrence and Omission of Adjuvant Therapy after Pancreaticoduodenectomy Argue against a Surgery-First Approach

Background Sequencing therapy for patients with periampullary malignancy is controversial. Clinical trial data report high rates of adjuvant therapy completion, though contemporary, real-world rates remain incomplete. We sought to identify patients who failed to receive adjuvant therapy and those at risk for early recurrence (ER) who might benefit most from neoadjuvant therapy (NT).
Abstract # 1783 Metabolic dysfunction, inflammation, and task-induced emotional stress reactivity: Neural and cognitive correlates in 331 middle-aged adults

Pre-diabetes and type 2 diabetes (T2D) etiology is characterized by insulin resistance (IR) and systemic inflammation. These factors can cause deficits in cognitive and affective processing, particularly psychological stress reactivity. The neural correlates of these deficits are unknown. We wished to determine how T2D, IR, and interleukin-6 (IL-6) were related to psychophysiological, behavioral, and hormonal measures of psychological stress reactivity and negative affect predisposition. Among 331 adults (36–84 years old) from the Midlife in the United States (MIDUS) study, we reviewed startle eye-blink response (EBR) to “unpleasant” versus “pleasant” international affect picture system (IAPS) stimuli. Using resting electroencephalography (EEG), we analyzed right frontal alpha asymmetry, a well-established biomarker of negative affect predisposition. Finally, cognitive performance and cortisol output were gauged during an arithmetic stressor task. Fasting glucose and insulin characterized T2D or the homeostatic model assessment of IR (HOMA-IR). High-sensitivity ELISA was used to derive IL-6. For EBR startle magnitude, higher HOMA-IR strongly corresponded to greater EBR for “unpleasant” versus “pleasant” stimuli [R2 = 0.218, p = .020]. For resting EEG, IL-6 [p = 0.030], or T2D showed greater right frontal alpha asymmetry [p = .011]. During the stressor task, participants with T2D scored 26 ± 2% worse than those with euglycemia [p = .040]. Surprisingly, cortisol output at baseline was lower in participants with T2D and pre-diabetes [p = .025]. These results suggest that dysmetabolism and inflammation may increase stress sensitization both at the neuronal and behavioral level.
Community Unemployment and Disaster-Related Stressors Shape Risk for Posttraumatic Stress in the Longer-Term Aftermath of Hurricane Sandy.

Persons living in communities with limited resources are at heightened risk of posttraumatic stress (PTS) after disasters, especially if they were highly exposed. The support deterrence desistence model and the conservation of resources theory suggest that this risk might increase in the longer-term aftermath of disasters. In the present study, we aimed to test this hypothesis. Two population-based samples of New York City residents in communities affected by Hurricane Sandy were surveyed at either 13–16 months (Time 1; n = 421) or 25–28 months (Time 2; n = 420) postdisaster. Participants reported on their exposure to disaster-related stressors and PTS. The percentage of residents who were unemployed in participants’ census tracts was collected from the 2008–2012 American Community Survey. Multilevel models found that disaster-related stressors were more strongly associated with PTS for participants living in communities with high unemployment, but only at Time 2 (Est. = .58, SE = .21, p = .006). Mapping of community unemployment and disaster-related stressors suggested that communities in southern Brooklyn and Queens, and northeastern Staten Island were at particularly high risk for PTS at Time 2. The results suggest the need for ongoing support to economically disadvantaged communities in which residents have endured disaster-related stressors.
Managing Pain in the Context of Unhealthy Alcohol Use

For the primary care clinician treating patients with unhealthy alcohol use, pain syndromes are frequently clinical issues that pose unique challenges relative to the management of low risk or non-alcohol users with pain. Unhealthy alcohol use and its consequences may impact both the assessment and management of pain. Such considerations are particularly important when prescribing medications that can interact with alcohol or alcohol-related comorbidities, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioid medications. Rather than a comprehensive review of general pain management, this chapter provides recommendations on how to approach the patient with unhealthy alcohol use and pain. Special attention is devoted to the safe and effective use of opioid analgesics, given the inherent risks of interactions and misuse, and that observational studies demonstrate that patients with current or past alcohol use disorders are at higher risk for subsequent prescription opioid misuse.
Two-zone tumor tolerance can arise from a simple immunological feedforward motif that estimates tumor growth rates

Since the early 1990s, many authors have independently suggested that self/nonself recognition by the immune system might be modulated by the rates of change of antigen challenges. This paper introduces an extremely simple and purely conceptual mathematical model that allows dynamic discrimination of immune challenges. The main component of the model is a motif which is ubiquitous in systems biology, the incoherent feedforward loop, which endows the system with the capability to estimate exponential growth exponents, a prediction which is consistent with experimental work showing that exponentially increasing antigen stimulation is a determinant of immune reactivity. Combined with a bistable system and a simple feedback repression mechanism, an interesting phenomenon emerges as a tumor growth rate increases: elimination, tolerance (tumor growth), again elimination, and finally a second zone of tolerance (tumor escape). This prediction from our model is analogous to the "two-zone tumor tolerance" phenomenon experimentally validated since the mid 1970s. Moreover, we provide a plausible biological instantiation of our circuit using combinations of regulatory and effector T cells.
Nietzsche and the Battle Over Being

This chapter concerns the philosophy of Friedrich Nietzsche, in particular, a consideration of Nietzsche as a metaphysical thinker. This chapter is divided into three main sections: (1) a discussion of Nietzsche’s philosophy of science vis-a-vis his atheism, (2) a discussion of Nietzsche’s metaphysics through the lens of Martin Heidegger; and (3) a discussion of Nietzsche’s overcoming of metaphysics in the context of art. The goal of this chapter is to establish Nietzsche’s thinking on the materialist side of the Gigantomachy.
Efficient Energy Transfer from Near-Infrared Emitting Gold Nanoparticles to Pendant Ytterbium(III)

Here, we demonstrate efficient energy transfer from near-infrared-emitting ortho-mercaptobenzoic acid-capped gold nanoparticles (AuNPs) to pendant ytterbium(III) cations. These functional materials combine the high molar absorptivity (1.21 × 106 M–1 cm–1) and broad excitation features (throughout the UV and visible regions) of AuNPs with the narrow emissive properties of lanthanides. Interaction between the AuNP ligand shell and ytterbium is determined using both nuclear magnetic resonance and electron microscopy measurements. In order to identify the mechanism of this energy transfer process, the distance of the ytterbium(III) from the surface of the AuNPs is systematically modulated by changing the size of the ligand appended to the AuNP. By studying the energy transfer efficiency from the various AuNP conjugates to pendant ytterbium(III) cations, a Dexter-type energy transfer mechanism is suggested, which is an important consideration for applications ranging from catalysis to energy harvesting. Taken ...
The federal budget's core and periphery: patterns of budget outcomes

Cluster analysis on detailed federal outlay data from fiscal year (FY) 1962 to FY 1995 shows instead of being incremental or not, the budget is both. Spending is initially volatile but becomes incremental over time and with political entrenchment. The theory of incrementalism needs to be updated to reflect this complexity. Also, patterns show that most spending falls into three main groups, which do not correspond to traditional budgetary classifications, and none of the patterns show any major shifts in response to process upheaval. This suggests (1) rethinking how to analyze budget data, and (2) while processes and decision-makers have changed, the decisions have not.
Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia

Treatment of severe aplastic anemia with antithymocyte globulin (ATG) and cyclosporin leads to clinical remission in a large proportion of patients. As many as 10% to 57% of these patients, however, develop paroxysmal nocturnal hemoglobinuria (PNH). We and others have observed that this secondary PNH appears to be more indolent than classical PNH, which results from an acquired mutation in the PIG-A gene. In the present study, we compared PIG-A mRNA transcripts in affected cells from patients with secondary PNH and patients with classical PNH. All four of our aplastic patients who developed PNH had a negative Ham test at diagnosis. Two of the four showed a positive Ham test within 3 months after ATG/cyclosporin administration, one developed a positive test at 6 months, and another at 18 months after immunosuppressive therapy. All four patients remain transfusion-independent with no thrombotic episodes after a mean follow-up of 30 months (range, 6 to 63 months). Reverse transcription-polymerase chain reaction (RT-PCR) of PIG-A transcripts in DAF-/CD59- neutrophils or lymphocyte lines of the four patients showed PIG-A abnormalities in all cases. Transition of C163 to T was found in one, a 14-bp deletion (positions 1141 to 1154) was found in the second, deletion of C39 was found in the third, and two mutations, transition of C55 to T and transversion of T762 to A, were found in the fourth. These abnormalities compared with findings of abnormal RNA splicing causing a 133-bp deletion, a 4-bp insertion (between positions 578 and 579), loss of A767, and loss of C575 in four patients with primary PNH. We conclude that secondary PNH that evolves out of aplastic anemia, like classical PNH, is associated with mutations in the PIG-A gene. The apparent indolent nature of this disease probably reflects early detection.
Evidence-Based Therapies for Pharmacologic Prevention and Treatment of Acute Deep Vein Thrombosis and Pulmonary Embolism

Venous thromboembolism (VTE) remains a significant mortal and morbid disease. The major risks have not changed and many patients present with unprovoked VTE disease. Prevention of VTE in hospitalized patients depends on comprehensive risk factor assessment, with an individual risk score. Proper and timely prophylaxis with mechanical, pharmacologic, or both is then effective. Treatment of VTE with parenteral anticoagulation followed by either a direct oral anticoagulant or warfarin is standard to reduce risk of VTE recurrence and death. Selected cases of iliofemoral deep vein thrombosis may be treated by pharmacomechanical thrombolysis, but more data are needed before this is standard of care.
Treatment of malignant gliomas with nanoliposomal CPT-11 following both systemic administration or convection-enhanced delivery

1489 We have developed a stable nanoliposomal formulation of the topoisomerase I inhibitor CPT-11 / irinotecan (nLs-CPT-11) for treatment of brain tumors. Two modes of administration were evaluated in rat intracranial U87 xenografts: bolus i.v. injection (systemic) and convection-enhanced delivery (CED) (local-regional). Following i.v. injection, tissue PK of free CPT-11 or nLs-CPT-11 (both at 50 mg/ml) reveal similar brain tissue Cmax of 10.2 μg/g and 11.8 μg/g respectively. However, tumor AUC for nLs-CPT-11 was 13-fold greater than free CPT-11 demonstrating extended tumor exposure. Additionally, nLs-CPT-11 showed significantly higher tumor t 1/2 and MRT (5.6-fold and 5.5-fold greater, respectively) than free CPT-11. Tumor selectivity was demonstrated for free CPT-11 and nLs-CPT-11, as the maximum drug concentration was >12 fold higher in the tumor than surrounding healthy striatum for both formulations following i.v. injection. CED of nLs-CPT-11 was associated with dose-dependent clearance in healthy rat brains, with doses of 60 μg, 0.8 mg, and 1.6 mg resulting in tissue t 1/2 of 6.7, 10.7, and 19.7 d, respectively. CED of 0.8 mg nLs-CPT-11 resulted in tumor t 1/2 of 43 d indicating even greater retention in tumors. At equivalent CED doses of 60 μg, nLs-CPT-11 increased healthy brain tissue AUC by 25-fold and tissue t 1/2 by 22-fold over free CPT-11. MTD for CED of free CPT-11 was 60 μg while no MTD was reached with nLs-CPT-11 at the highest tested dose of 1.6 mg. Preliminary efficacy data following i.v. treatment with nLs-CPT-11 was collected in the intracranial U87 tumor model. 50 mg/kg of nLs-CPT-11 administered on days 5, 8, 11, and 14 post-tumor implantation resulted in a 66 d median survival, and 3 of 6 rats surviving until study end at day 100. Rats in the control group all reach terminal morbidity at 19-22 d (median = 20 d, p = 100 d) as compared to CED of control liposomes (19.5 d, p =
Epilepsy in Older Adults

A 75-year-old female is seen in the emergency department (ED) due to a subacute onset of severe back pain. The pain is centered in the mid-thoracic area of the back without radiation and is easily exacerbated by movement. She is an established patient and has a history of localization-related epilepsy with recurrent focal seizures. The seizures were caused by a previous stroke that occurred almost a decade ago. The typical seizure manifests as a generalized convulsion. In the past, they had been sporadic and had occurred in both the day and nighttime. The patient also reports persistent imbalance and a feeling of chronic dizziness. She has been adherent to her current dosage of phenytoin taken as directed by her neurologist. She is taking 300 mg per day with a recent serum level of 10 mg/dl. The patient had been on a higher dose of phenytoin in the past but complained that she experienced significant problems with her balance. In the ED, following clinical assessment, a radiograph of the thoracic spine was performed. The interpretation suggested a compression deformity in the appropriate area. An MRI is performed and reveals the following (Fig. 18.1):
Isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and hyperthermia in the treatment of localized and metastatic cancer.

Tumor necrosis factor (TNF)-α is a central molecule in both immune and metabolic networks. It is secreted as a 17-kDa protein which has an amino acid sequence which is highly conserved among numerous species (Spriggs 1991). TNF-α was initially described as an agent causing hemorrhagic necrosis of transplanted murine sarcomas and as a protein associated with chronic wasting disorders and sepsis (cachectin). These two functions were found to be caused by the same molecule after the cloning and sequencing of cachectin in 1985 (Beutler et al. 1985). Oncologic applications have been based on its ability to induce rapid hemorrhagic necrosis in a wide variety of transplanted murine tumors of many histologic types. This in vivo antitumor effect does not appear to correlate with either the expression of TNF receptors (widely expressed in a variety of tissues and tumors) or in vitro tumor cytolysis by TNF (which only occurs in a limited number of cultured tumor lines). Although the dramatic antitumor effects of TNF in animal models are well documented, initial clinical trials with TNF in patients with cancer were disappointing. Numerous clinical trials administering TNF systemically failed to show significant clinical activity despite administering TNF doses at maximally tolerated levels (MTD; Creaven et al. 1989; Alexander and Rosenberg 1991). The MTD of approximately 300–400μg/m2 by intravenous bolus induced symptoms of septic shock in patients without evidence of tumor necrosis.
Can rule-based indexing support concept-based multimedia retrieval in digital libraries? some experimental results

The emerging conception of a "digital library" as an information environment in which distributed information sources are made available in an integrated way implies new requirements for indexing and retrieval methods. Therefore, one important research topic in the field of digital libraries is the design of task-specific methods for very precise searching. In addition, we have to anticipate highly dynamic information bases which change continually. This paper outlines an approach which addresses both problems. Rule-based indexing can be used to support highly precise searches in dynamic information bases. The method enables users to perform conceptual searches in image collections, thus going far beyond contemporary content-based retrieval methods for pictorial material. The paper concludes with a discussion of the empirical results obtained so far.
Moving Toward Third-Space: Reflections on the Tensions with/in Qualitative Research / Vers le troisième espace : réflexions sur les tensions en recherche qualitative

Abstract: This reflective essay examines some of the dialectical tensions that can emerge within qualitative research and that can result in internal and external conflicts and a wide range of emotions and feelings for researchers. It is important to notice and examine these tensions as many art educators use qualitative research methods. Subsequently, more attention is needed to recognizing research as an emotional, and conflicted journey. The Japanese aesthetic of wabi-sabi and paradox theory offers applicable insights into the qualitative research process. Approaches to ‘qualitative thinking’ and artistic and contemplative methods are explored with the aim of reflexivity and disrupting dialectical thinking in qualitative research. Keywords: Qualitative research; Dialectical tensions; Third Space; Rhizomatic thinking. Resume : Ce compte rendu reflexif se penche sur certaines des tensions dialectiques susceptibles d’apparaitre en recherche qualitative, de mener a des conflits internes et externes et de susciter chez le chercheur une vaste gamme d’emotions et de sentiments. Il importe de prendre note de ces tensions et de s’y attarder car de nombreux educateurs emploient concepts et methodes de recherche qualitative. Il faut par consequent se preoccuper davantage de la recherche qualitative en tant que processus emotionnel et souvent conflictuel. Cette enquete se base sur les travaux de chercheurs multidisciplinaires selon lesquels le concept « d’entre-deux » et de « troisieme espace » perturbe fondamentalement la pensee binaire. D’autres strategies sont par ailleurs introduites pour appuyer la pensee rationnelle dans le domaine de la recherche qualitative et la creation de cultures de recherche rhizomatiques. Mots-cles : recherche qualitative, tensions dialectiques, troisieme espace, pensee rhizomatique.
Venous Thromboprophylaxis in Spine Surgery.

Study Design:Review article.Objective:A review of the literature on postoperative initiation of thrombophylactic agents following spine surgery.Methods:A review of the literature and synthesis of t...
Toward an understanding of phyllosilicate mineralogy in the outer main asteroid belt

Abstract Proposed mineralogical linkages between CM/CI carbonaceous chondrites and outer Main Belt asteroids remain uncertain due to a dearth of diagnostic absorptions in visible and near-infrared (∼0.4–2.5 μm) spectra of the two sets of objects. Absorptions near 3 μm in both sets hold promise for illuminating the potential linkages. Spectral comparisons of meteorites and asteroids have been challenging because meteorite spectra have usually been acquired in ambient terrestrial environments, and hence were contaminated by atmospheric water. In this study, we compare near-infrared spectra of chondrites measured in the laboratory under asteroid-like conditions (Takir, D. et al. [2013]. Meteorit. Planet. Sci. 48, 1618–1637) and spectra of asteroids measured with the long-wavelength cross-dispersed (LXD: 1.9–4.2-μm) mode of the SpeX spectrograph/imager at the NASA Infrared Telescope Facility (IRTF) (Takir, D., Emery, J.P. [2012]. Icarus 219, 641–654). Using the 3-μm band shape, we find that spectral Group 2 CM and CI (Ivuna) chondrites are possible meteorite analogs for asteroids with the sharp 3-μm features, which are predominately located in the 2.5 a a
Poetry as a Key to the Unlocking of the Self.

In a series of brief narratives, the author demonstrates poetry’s self-explanatory and self-expressive powers. He includes experiences with emotionally disturbed preschoolers, hospitalized schizophrenic children, brain-injured and autistic preadolescents, adolescent victims of advanced cerebral palsy and dystonia muscularum deformans, adult schizophrenics both hospitalized and in halfway houses, withdrawn elderly, and a woman terminally ill. Examples of their creative work underscore the dramatic process of self-liberation that occurred in each instance.
Stability of KKT systems and superlinear convergence of the SQP method under parabolic regularity

This paper pursues a two-fold goal. Firstly, we aim to derive novel second-order characterizations of important robust stability properties of perturbed Karush-Kuhn-Tucker systems for a broadclass of constrained optimization problems generated by parabolically regular sets. Secondly, the obtained characterizations are applied to establish well-posedness and superlinear convergence of the basic sequential quadratic programming method to solve parabolically regular constrained optimization problems.
The Unique Effects of Hope, Optimism, and Self-Efficacy on Subjective Well-Being and Depression in German Adults

Positive thinking is a source of mental health. Hope, optimism, and generalized self-efficacy (GSE) are three factors of positive thinking that are strongly correlated but theoretically distinct. Specifically, these positive thinking factors covary with subjective well-being (composed of positive affect, negative affect, and satisfaction with life; SWB) and depression. However, the distinctiveness of hope, optimism, and GSE and their independent contributions to predicting SWB and depression is not well documented empirically. The present study used confirmatory factor analysis and structural equation modeling in a large (n = 6077), older (M = 62.49, SD = 11.63), German sample. The sample was 51.3% male with no statistically significant differences in the predictors based on gender. We found the following results. First, the three factors of hope, optimism, and GSE better accounted for their individual items than a single overarching factor of positive thinking. However, because hope and GSE were not identifiable as distinct latent constructs in this sample (r = .98), they were modeled as one construct in subsequent analyses. Second, combined hope/GSE and optimism had a strong positive relationship (r = .74) among themselves and a weak to moderate positive relationship with higher SWB (positive affect, r = .70; negative affect, r = −.42; satisfaction with life, r = .68) and lower depression (r = −.44). Third, hope/GSE and optimism in the same model had unique weak to moderate latent effects on SWB and depression. The fact that hope and GSE were not distinguishable in this sample ran contrary to the existing literature. Overall, the positive thinking factors were highly correlated with each other and were found to be significant predictors of higher well-being and lower depression in this sample. Further investigation of the lack of distinctiveness of positive thinking in this sample is warranted given these unexpected findings.
CASSCF with Extremely Large Active Spaces Using the Adaptive Sampling Configuration Interaction Method

The complete active space self-consistent field (CASSCF) method is the principal approach employed for studying strongly correlated systems. However, exact CASSCF can only be performed on small active spaces of ∼20 electrons in ∼20 orbitals due to exponential growth in the computational cost. We show that employing the Adaptive Sampling Configuration Interaction (ASCI) method as an approximate Full CI solver in the active space allows CASSCF-like calculations within chemical accuracy (<1 kcal/mol for relative energies) in active spaces with more than ∼50 active electrons in ∼50 active orbitals, significantly increasing the sizes of systems amenable to accurate multiconfigurational treatment. The main challenge with using any selected CI-based approximate CASSCF is the orbital optimization problem; they tend to exhibit large numbers of local minima in orbital space due to their lack of invariance to active-active rotations (in addition to the local minima that exist in exact CASSCF). We highlight methods that can avoid spurious local extrema as a practical solution to the orbital optimization problem. We employ ASCI-SCF to demonstrate a lack of polyradical character in moderately sized periacenes with up to 52 correlated electrons and compare against heat-bath CI on an iron porphyrin system with more than 40 correlated electrons.
Incidence of Bacterial Chondronecrosis with Osteomyelitis (Femoral Head Necrosis) Induced by a Model of Skeletal Stress and its Correlation with Subclinical Necrotic Enteritis.

Bacterial chondronecrosis with osteomyelitis (BCO) is a septic necrosis of the skeletal system of unknown origin and an important cause of lameness in broiler chickens. Epithelial inflammation has been proposed as an avenue for bacterial translocation leading to BCO. We evaluated the effect of subclinical necrotic enteritis (SNE), an intestinal inflammatory event, with the development of BCO. In each of two experiments, chickens were divided into three treatments: (1) SNE challenge, including both dietary (wheat- and fish-based diet) and intestinal pathogenic challenges (Eimeria maxima and Clostridium perfringens), (2) dietary challenge only, and (3) control diet (corn-and soy-based diet). Floor ramps were introduced as part of an established method for increasing the frequency of BCO. The efficacy of the SNE challenge was corroborated by necropsy evaluation of a representative sample of the population. At the end of each experiment, all birds were evaluated for BCO. A high incidence of BCO was found, even in birds with no external signs of lameness. However, the incidence of BCO was not correlated with the intestinal challenge. Conclusions: under the conditions used in these studies, a treatment that is associated with severe damage to the intestinal mucosa does not change the incidence of BCO in broiler chickens.
Field Carcinogenesis in Cancer Evolution: What the Cell Is Going On?

Field carcinogenesis describes the prevalence of tumor-related alterations in normal-appearing tissues. Here we summarize recent efforts in profiling field molecular dynamics for resolving early events in cancer evolution. We also highlight gaps in our knowledge of the molecular and cellular heterogeneity of field carcinogenesis and propose directions to tackle these voids using single cell-based approaches and unique tissue sampling models. By interrogating both the mutagenized epithelium and its microenvironment, we surmise that single cell-guided studies will help chart the spatiotemporal molecular and cellular "atlas" of field carcinogenesis, will further delineate preneoplastic initiation and progression, and will help identify cancer prevention and early intervention targets.
Thermal Runaway Pressures of Iron Phosphate Lithium-Ion Cells as a Function of Free Space Within Sealed Enclosures

Mining vehicle manufacturers are developing lithium-ion (Li-ion) battery electric vehicles as an alternative to diesel-powered vehicles. In gassy underground mines, explosion-proof (XP) enclosures are commonly used to enclose electrical ignition sources to prevent propagation of an internal methane (CH4) air explosion to a surrounding explosive atmosphere. Li-ion batteries can create pressurized explosions within sealed enclosures due to thermal runaway (TR). Researchers at the National Institute for Occupational Safety and Health (NIOSH) measured TR pressures of lithium iron phosphate (LFP) cells as a function of free space within sealed enclosures and observed an inverse power relationship. A well-confined cell produced 294 bar (4260 psia) of pressure during a TR, far exceeding minimum pressure containment specifications for conventional XP enclosures. Results indicate that adding enough free space surrounding LFP cells can reduce TR pressures to levels below that expected for CH4-air ignitions. Measured TR temperatures were below the minimum autoignition temperature of CH4-air.
Inequities in neurology amplified by the COVID-19 pandemic.

This year, the COVID-19 pandemic has altered neurological care in many ways. However, evidence indicates that people from marginalized ethnic and socioeconomic groups have been affected by these changes more than others, highlighting and amplifying existing health-care disparities.
Anosmia in COVID-19: What Care Providers Need to Know.

A familiar image during the past year is a patient with COVID-19 on a ventilator in an intensive care unit, cared for by nurses swathed in protective equipment. Becoming more familiar now is the im...
PPARa agonist fenofibrate enhances cancer vaccine efficacy

Reducing metabolic stress within the tumor microenvironment (TME) could be essential for improving the efficacy of cancer immunotherapy. Using a mouse model of melanoma, we show here that appropriately timed treatment with the PPARα agonist fenofibrate improves the ability of a T cell–inducing cancer vaccine to delay tumor progression. Fenofibrate reduced the use of glucose by tumor and stromal cells in the TME and promoted the use of fatty acids for their metabolic needs. The glucose within the TME was in turn available for use by vaccine-induced tumor-infiltrating CD8+ T cells, which improved their ability to slow tumor progression. Early fenofibrate treatment 3 days after vaccination improved functions of circulating CD8+ T cells but failed to significantly affect tumor-infiltrating lymphocyte (TIL) metabolism or decrease tumor progression. In contrast, delaying treatment until day 5 after vaccination modified TIL metabolism and augmented the vaccine9s ability to slow tumor progression. In summary, our findings reveal that a PPARα agonist can increase the efficacy of a cancer vaccine by reprogramming cells within tumors to increase fatty acid metabolism, providing T cells access to glucose in the TME. Significance: These findings suggest that metabolic manipulations using already approved drugs may offer an easy pathway to increase the efficacy of vaccines against solid tumors.
Hepatic expression of redox factor-1 and thioredoxin-1: effects of aging and environmental heat stress

Aging is associated with reduced tolerance to physiological stressors such as hyperthermia. In animal models, heat stress is associated with increased oxidative DNA damage in the livers of old rats. In this study, we evaluated the expression of redox factor-1 (Ref-1), a DNA repair enzyme, and thioredoxin-1 (Trx-1), an antioxidant protein. We hypothesized that these proteins would be induced by heat stress in young animals, and that aging would attenuate this response. Young (6 mo) and old (24 mo) male Fischer 344 rats were exposed to a two-heat stress protocol, and livers were harvested at several time points after the second heat stress. Ref-1 and Trx-1 were evaluated by immunoblot and immunohistochemistry. In young rats, Ref-1 was induced immediately (0 h) after heat stress, and returned to control levels at 2h. We observed no heat-induced elevation of Ref-1 in old rats; however, Ref-1 was increased ~2-fold in old, compared to young rats at all time points. At 2h after heat stress, Trx-1 was increased i...
Learning to program by examining and modifying cases

Abstract This paper describes a system called TA, which learns how to program by maintaining a case base of previously encountered programs and modifying those cases in attempts to solve new programming problems. TA uses three case bases: one for programs, one for patches to code, and one for bugs that have been encountered in previous programming sessions. As TA writes correct programs, they are added to the program case base. If bugs are encountered in the process of arriving at a correct program, these (and the patches that TA uses to fix the buggy code) are added to the appropriate case bases. Thus, as TA writes more programs, its skill at finding similar programs increases, as does its ability to find and fix bugs.
Mycoplasma arthritidis-induced ocular inflammatory disease.

Abstract Mycoplasma arthritidis was demonstrated to incite experimental conjunctivitis and uveitis in Swiss Webster mice which have a known susceptibility to the arthritis customarily associated with infection by this mycoplasma. The initial symptom of ocular involvement was conjunctivitis, which appeared as early as 1 day after intravenous injection with viable culture concentrates of M. arthritidis. By day 2, histological analysis showed intraocular localized inflammatory reactions that were confined primarily to the anterior portion of the uvea and produced results which were compatible with those seen in iridocyclitis. Serological assays of the titer and the class of antibodies involved in the early humoral immune response to infection confirmed the predominance of immunoglobulin G (IgG) concentrations over IgM concentrations that was described by others (Cole et al., Infect. Immun. 4:431-440, 1971) and revealed significant titers of the IgG2a and IgG2b subclasses of complement-fixing antibodies. The rapid onset of acute conjunctivitis, together with the early appearance of immunoglobulins of the IgG class, suggests that the M. arthritidis-infected Swiss Webster mice may have experienced an anamnestic response to the mycoplasma antigens. These observations introduce a new animal model for the study of mycoplasma-induced experimental uveitis and conjunctivitis, which are demonstrated here to accompany a disseminated systemic disease process.
Ultrafast terahertz probes of interacting dark excitons in chirality-specific single-walled carbon nanotubes

Ultrafast terahertz intra-excitonic transition ∼6 meV reveals stable quasi-1D many-exciton states that evolve uniquely from a predominant dark exciton population to complex phasespace filling of both dark and bright pair states in (6,5) SWNTs.
Usability evaluation of two smart glass systems

Wearable computing has long been in development but "smart glasses" have just recently emerged as a viable platform for the personal and industrial sectors. Two recent implementations, Google Glass and the Vuzix M100 both contain an internetenabled computer, battery, speaker, camera, and voice and touch controls in an eyeglass form factor. The user can capture and see images, capture and play videos, capture and listen to audio, and connect to the internet via the small heads-up display mounted in front of one of the user's eyes. We developed a generic voice-controlled Android tutorial application for these devices that can be loaded with training content as needed for multi-step, complex processes. We found that neither Glass nor the M100 is ready for "prime time". Glass suffers from overheating, awkward placement of the on/off switch, toggling of voice navigation, and a fixed camera placement while the M100 has a burdensome hardware design, obstruction of view in the display eye, and lack of an expansive library for voice recognition. Despite these shortcomings, smart glasses show great promise as a means for delivering hands-free training content. We predict that the hands-free, personalized functionality of future models will accelerate learning of complex multistep processes and allow for real-time access of vital information in sterile or roving environments. As such, recommendations are made for the features of the ideal smart glass platform.
First-Principles Prediction of Enthalpies of Formation for Polycyclic Aromatic Hydrocarbons and Derivatives

In this article, the first-principles prediction of enthalpies of formation is demonstrated for 669 polycyclic aromatic hydrocarbon (PAH) compounds and a number of related functionalized molecules. It is shown that by extrapolating density functional theory calculations to a large basis set limit and then applying a group based correction scheme that good results may be obtained. Specifically, a mean unsigned deviation and root mean squared deviation from the experimental enthalpies of formation data of 5.0 and 6.4 kJ/mol, respectively, are obtained using this scheme. This computational scheme is economical to compute and straightforward to apply, while yielding results of reasonable reliability. The results are also compared for a smaller set of molecules to the predictions given by the G3B3 and G3MP2B3 variants of the Gaussian-3 model chemistry with a mean unsigned deviation and root mean squared deviation from the experimental enthalpies of formation of 4.5 and 4.8 kJ/mol, respectively.
Computer-Aided Detection of Rare Tumor Populations in Flow Cytometry

Objectives Diagnosing classical Hodgkin lymphoma (cHL) by flow cytometry (FC) relies on an observer gating rare populations of Hodgkin/Reed Sternberg (HRS) cells. Here, we apply machine-learning methods to aid in the detection of rare tumor cell populations using data derived from clinical FC analysis of cHL as a model disease. Methods FC data from 144 clinical cases using a nine-color FC reagent panel were analyzed using Python 2.7 and the “scikit-learn” module. Results Seventy-eight 50 × 50 two-dimensional histograms were generated from routine FC data and a reciprocal power function applied to favor rare events. Data were classified by support vector machine (SVM), gradient boosting, and random forest classifiers. All three classifiers showed no statistical difference in performance, with 89%–92% accuracy on cross-validation. Nearly all classifiers misclassified the same set of cases, with more false-positive than false-negative cases. Dimensionality reduction by ensemble methods selected for data points in a CD5+/ CD40+/CD64– region. Conclusions All classifiers provide probabilistic confidences for each result, and diagnostic cutoffs can be chosen to minimize false negatives and serve as a screening tool. Computational exclusion of manually gated HRS cells had little impact on the overall performance of selected support vectors in SVM or dimensionality reduction, suggesting that features of the immune response in cHL may dictate the method accuracy. We hypothesize there are distinct inflammatory cells that suggest cHL.
Ultrasensitive time-resolved linear dichroism spectral measurements using near-crossed linear polarizers

Abstract A simple and sensitive technique is introduced to measure time-resolved linear dichroism of spectral transitions. This technique uses the fact that a linear dichroic sample rotates the polarization plane of linearly polarized light. The theoretical basis of the technique is presented using Mueller calculus and a detailed signal analysis is given to account for the effects of various optical imperfections. The results of this analysis are confirmed with the application of the technique to the time-resolved linear dichroism of bacteriorhodopsin in membrane patches (purple membrane) during its photocycle. These experimental results demonstrate the sentivity of the technique.
Surgical Management of Familial Adenomatous Polyposis

Familial adenomatous polyposis is an autosomal-dominant disease caused by a germline mutation of the adenomatous polyposis coli ( APC ) gene. It is characterized by the progressive development of hundreds to thousands of polyps in the colorectum. There are also associated extracolonic manifestations. The average age of colorectal carcinoma in these patients is 39 years. Surgery is the only effective treatment available to prevent the development of colorectal carcinoma. In the era of ileoanal pouch surgery, there are several surgical options available to patients. We review the current literature's support for the various surgical options available at this time and the respective postoperative follow-up.
Blast and Construction Vibration Monitoring and Control: Thirty-Five-Year Perspective

Developing trends in important aspects of blast and construction vibration monitoring and control are identified through consideration of research and consulting experiences during the last 35 years . This retrospective view is written to identify strong currents in a large river of progress rather than to present a comprehensive state of the art survey. Specific case studies set the stage for the following discussion of trends, which in turn set the stage for the prediction of future developments.
Relative abundances in the low-metallicity dwarf irregular galaxy UGC 4483

UGC 4483 is a dwarf irregular galaxy in the M 81 group. Narrow-band optical imaging has revealed an H II region in UGC 4483 with an H-alpha flux of about 2 x 10 to the -13th erg/sq cm per A per s. Optical, UV and NIR spectroscopy of this H II region yield He, C, N, O, Ne, and S abundances for the ISM in this galaxy. With an oxygen abundance of 0.000021 12 + log(O/H) = 7.3, this galaxy is among the most metal-poor dwarf irregulars known to date. A comparison of the S/O abundance ratio in this galaxy with that in I Zw 18 supports the claim by Garnett (1990) that the S/O ratio is consistent with the solar ratio for low-metallicity dwarf irregulars. The C/O ratio in UGC 4483 is lower than that derived for I Zw 18 and, therefore, more in line with the trend seen in higher metallicity H II regions. The derived helium abundance is He/H = 0.075, which converts to a He mass fraction of 0.23, consistent with earlier determinations of the primordial He abundance.
Theory, Design, and Calibration of a uv Spectrophotopolarimeter

A balloon-borne ultraviolet Ebert-Fastie spectrometer with a Sekera-type polarimeter is developed mathematically. The basic representation of polarized light by Stokes vector and the utilization of Mueller calculus to predict the performance of the spectrophotopolarimeter is discussed. The Stokes vector of the incident light is determined by a Fourier analysis of a light beam which is modulated by a rotating retardation plate. The effect of imperfect optical elements in the train is discussed, and an elegant, although simple, method of calibration which utilizes only nonperfect optical elements is developed. It is possible to calibrate satisfactorily the entire optical system in only one step as long as the optical elements in the train have some resemblance to their designed function.
A Right of Rebellion in the Mengzi

Mengzi believed that tyrannical rulers can be justifiably deposed, and many contemporary scholars see this as grounding a right of popular rebellion. I argue that the text of the Mengzi reveals a more mixed view, and does so in two respects. First, it suggests that the people are sometimes permitted to participate in a rebellion but not permitted to decide for themselves when rebellion is warranted. Second, it gives appropriate moral weight not to the people’s judgments about the justifiability of rebelling, but rather to certain affections and behaviors that closely track their life satisfaction. I contend that in both respects the permissions Mengzi grants the people fall short of a proper right of rebellion. I conclude that the more historical account of Mengzi’s “just revolt theory” suggests an intriguing division of deliberative labor, and note some of the advantages of this account.
Use of para-aminosalicylic acid in chronic pulmonary tuberculosis.

The serum of patients and normal individuals after ingestion of 2 to 4 gms. of para-aminosalicylic acid produces a definite inhibition of the growth of the tubercle bacillus in Dubos media. This has been demonstrated with the H37Rv strain as well as with strains recovered from patients with active pulmonary tuberculosis. Para-aminosalicylic acid was administered to twelve patients with advanced chronic pulmonary tuberculosis. The dosage employed was 10 to 11 gms. daily in courses of three weeks, with a free interval of one week. In seven patients in whom the symptoms of active infection were sufficiently marked to permit judgment of the effectiveness of drug, observable clinical improvement took place in all. In three patients recurrence of symptoms on cessation of treatment took place. Three patients who suffered from fever and signs of acute exudative tuberculosis were much improved and in good general condition after treatment, but without arrest of their disease. The characteristic effects of administration of para-aminosalicylic acid were prompt reduction in cough and expectoration, and decrease in fever when present. These favorable results were generally manifested within the first week of treatment. The side effects of the drug were intermittent nausea, vomiting and looseness of the bowels. In three of the twelve patients these symptoms were sufficiently severe to force discontinuance of the drug. The favorable clinical results of treatment with para-aminosalicylic acid in chronic pulmonary tuberculosis suggests that this drug is a useful agent in the treatment of acute exacerbation of the disease. The possibility that administration of para-aminosalicylic acid with other antibiotics, such as promizole and streptomycin, would appear to deserve investigation.
7-oxo-DHEA and Raynaud’s phenomenon

Patients with Raynaud's phenomenon have abnormal digital vasoconstriction in response to cold. The pathogenesis remains unknown but may involve a local neurovascular defect leading to vasoconstriction. Diagnosis of primary Raynaud's phenomenon is based on typical symptomatology coupled with normal physical examination, normal laboratory studies and lack of observable pathology by nail fold capillaroscopy. Secondary Raynaud's phenomenon is known to occur associated with several connective tissue diseases, vascular injury due to repeated vibrational trauma, and other causes which produce demonstrable vascular and microcirculatory damage. Treatment of Raynaud's symptoms is conservative and aimed at prevention of attacks. Patients are advised to remain warm and, if possible, to live in warm climates. We suggest that an ergogenic (thermogenic) steroid, 7-oxo-DHEA (3-acetoxyandrost-5-ene-7,17-dione), which is available without prescription as the trademarked 7-keto DHEA, may be very helpful in prevention of primary Raynaud's attacks by increasing the basal metabolic rate and inhibiting vasospasm.
FAS-MEDIATED CYTOTOXICITY REMAINS INTACT IN PERFORIN AND GRANZYME B ANTISENSE TRANSFECTANTS OF A HUMAN NK-LIKE CELL LINE

Cell-mediated cytotoxicity (CMC) has traditionally been thought to involve the release of granule components, including perforin and granzymes, from the effector cell (EC) onto the target cell (TC) membrane. Recently, a granule-independent cytolytic mechanism involving the interaction of Fas antigen (CD95) with Fas ligand has been described. We have generated antisense perforin (YT-xP1) and granzyme B (YT-xGrB) transfectants of the human NK-like cell line YT-INDY. These transfectants have greatly reduced cytolytic ability when compared to the vector-transfected control cell line (YT-neo). In this study, however, we demonstrate that the antisense transfectants retain the ability to lyse Fas+ TC. Fas-mediated lysis is Ca(2+)-independent and is inhibited by a monoclonal anti-Fas blocking Ab, M3. By RT-PCR, we detect message for FasL in unstimulated YT-xP1 and YT-xGrB transfectants, as well as in unstimulated YT-neo. By flow cytometry, we show that YT-neo, YT-xGrB, and YT-xP1 constitutively express surface FasL. These data indicate that in a human NK-like cell line, similar to the murine system, the granule and Fas pathways of cytotoxicity function independently of one another. At least with the TC tested, our data also indicate that the granule and Fas pathways together account for nearly 100% of the cytolytic ability of YT-INDY.