cssi/SciSciGPT-SciSciNet huggingface dataset:
Outpatient Prescription Expenditure of Social Medical Institutions in Chenzhou

Objective To analyze the outpatient prescription expenditure of social medical institutions and its influential factors.Methods Altogether 3139 prescriptions by 106 clinicians were randomly selected from 105 social medical institutions in Chenzhou,and were studied for the correlation between prescription expenditure and its influential factors with multiple linear regression analysis.Results The average outpatient prescription expenditure per day was 46.82 Yuan.Prescription expenditure was positively correlated with the kinds of drugs,the proportion of antibiotics and injection,the professional title of doctors and the age of patients.Meanwhile,there was a negative correlation between prescription expenditure and the proportion of basic drug.Nonprofit-making medical institutions cost slightly higher than profit ones.Conclusions In social medical institutions,usage of more drugs,high proportion of injection and antibiotics in a single prescription are the major causative factors for increased prescription expenditure.Therefore,we should strengthen supervision and management,correct improper use of medicine so as to ensure medical safety.
Abstract C163: Understanding the mechanism for synergistic anti-tumor activity of a meosthelin-targeted immunotoxin and taxanes

Recombinant immunotoxins (RITs) are antibody-based therapies that carry a bacterial toxin payload. RG7787 is a next generation RIT that targets the cancer antigen mesothelin (MSLN) to deliver a recombinantly engineered variant of Pseudomonas exotoxin A (PE) into the cell cytosol. PE irreversibly modifies elongation factor-2 (EF-2) by catalyzing addition of an ADP-ribose moiety. This causes EF-2 inactivation, inhibition of new protein synthesis, and a drop in the short-lived pro-survival factor mcl-1, triggering apoptosis. Combination of RG7787 with paclitaxel or nab-paclitaxel results in boosted anti-tumor efficacy in several mouse models. In the KLM1 pancreatic cancer xenograft model, either drug alone halts tumor growth while the combination produces complete regressions. Here, we show that enhanced efficacy is also seen using an identically structured RIT that targets the transferrin receptor instead of mesothelin (LMB-74), but is not seen when RIT is combined with gemcitabine, suggesting that the effect is specific to both taxane and PE. Further, we have found that the interaction of RG7787 and taxane can be modeled in vitro. Under these conditions, the interaction is dependent on the dose of RG7787, and cannot be replicated by a chemical inhibitor of protein synthesis. Co-treatment with taxane does not affect the depth, rate of onset or recovery of cells from RG7787-mediated protein synthesis inhibition. Tumor cell killing occurs over a delayed time course and is not associated with an early drop in mcl-1 levels as is seen when using a cytotoxic dose of RG7787 alone. Taken together, these data suggest that PE treatment sensitizes cancer cells to taxane-mediated killing. Citation Format: Christine Campo Alewine, Emily Kolyvas, Ira Pastan. Understanding the mechanism for synergistic anti-tumor activity of a meosthelin-targeted immunotoxin and taxanes. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C163.
The effect of the night float rotation on annual in-training examination performance.

Objective To assess whether night-float rotation affected resident performance on the Council on Resident Education in Obstetrics and Gynecology (CREOG) in-service examination. Study design Review of annual CREOG in-service examination scores standardized for postgraduate year level (2001-2009) compared scores for residents on night float rotation at time of examination to those on non-night float rotation. Data were analyzed by linear mixed effects model. Results Data were obtained for 72 residents, 20 of whom were on night float at time of at least one examination. One to four test scores were available for each resident (total 225 test scores). Average test score was 213 (SD = 20). The mean score for residents on night float was 214 (95% CI 207-221); the mean score for those on non-night float rotations was 212 (95% CI 208-216, p = 0.53). Sample size was sufficient to detect a difference of 12 points with 80% power. Conclusion Although night float rotations necessitate a complete reversal in sleep schedules, we found that night float service did not significantly affect scores On the annual in-service examination. To our knowledge, no studies have evaluated the impact of this schedule on test-taking ability.
Culture and Ecology: The Use of Biological Concepts

This chapter discusses culture and ecology using biological concepts. Cultural ecology is an academic category that is a relatively new effort put in cultural anthropology, and it will undergo great changes in the years to come. Characteristics stem from the methodological bent of cultural anthropology or ethnology. Pastoralism is one of the oldest topics in ethnology, which means the investment in herds rather than in land is the critical factor in pastoralism. The ecological explanation for pastoralism is nothing more than the environmental aspect of the description of pastoralism. Not only has cultural ecology tended to seek its problems in issues emanating from social and cultural topics, but elaborate schools of interpretation of culture–nature relations have developed for particular small portions of the earth's surface. If enough cultural ecologists study enough small agricultural localities, it is possible that a sample of sufficient representativeness to provide some relevant comment. When biological concepts are applied to data from social situations, there are obviously two possibilities. They can be applied (1) analogically, where the biological concepts and mathematical techniques are used to describe or simulate social phenomena, and (2) literally, in which case the actual biological or physical dimensions of the social phenomena would be identified and the same measurements performed on them.
Shift or Stasis| Al Jazeera’s Complex Legacy: Thresholds for an Unconventional Media Player from the Global South

The rise of Al Jazeera has left an indelible mark on Middle East politics, invigorated the region’s media landscape, and introduced new dynamics in global media flows and international communication. The recent unsettling developments in the Middle East, however, have altered the media dynamics on which Al Jazeera thrived all along. Taking heed of the ongoing transformation of the Arab media landscape and the geopolitical reconfigurations of the region in the aftermath of the Arab uprisings, this article explores growing tensions and conflictual pulls that are redefining the network and compelling it to change.
Development of the visual system

Abstract This chapter reviews theory and data concerning development of the human visual system. Visual development begins before birth, and young infants can direct their gaze toward important visual information such as motion and contrast, but developmental processes that yield an interpretation of objects as coherent, stable, and predictable involve learning and maturation over the first several months after birth.
Crimes Against Nature: Kincest, Cosmology, and Conservation in Southwest China

The post-Mao era (1976–present) has seen a number of great changes in China. Two of these – the revival of religion and the emergence of a nascent, but powerful environmental movement – have come t...
Fine Mapping, Transcriptome Analysis, and Marker Development for Y2, the Gene That Conditions β-Carotene Accumulation in Carrot (Daucus carota L.)

Domesticated carrots, Daucus carota subsp. sativus , are the richest source of β-carotene in the US diet, which, when consumed, is converted into vitamin A, an essential component of eye health and immunity. The Y 2 locus plays a significant role in beta-carotene accumulation in carrot roots, but a candidate gene has not been identified. To advance our understanding of this locus, the genetic basis of β-carotene accumulation was explored by utilizing an advanced mapping population, transcriptome analysis, and nucleotide diversity in diverse carrot accessions with varying levels of β-carotene. A single large effect Quantitative Trait Locus (QTL) on the distal arm of chromosome 7 overlapped with the previously identified β-carotene accumulation QTL, Y 2 . Fine mapping efforts reduced the genomic region of interest to 650 kb including 72 genes. Transcriptome analysis within this fine mapped region identified four genes differentially expressed at two developmental time points, and 13 genes differentially expressed at one time point. These differentially expressed genes included transcription factors and genes involved in light signaling and carotenoid flux, including a member of the Di19 gene family involved in Arabidopsis photomorphogenesis, and a homolog of the bHLH36 transcription factor involved in maize carotenoid metabolism. Analysis of nucleotide diversity in 25 resequenced carrot accessions revealed a drastic decrease in diversity of this fine-mapped region in orange cultivated accessions as compared to white and yellow cultivated and to white wild samples. The results presented in this study provide a foundation to identify and characterize the gene underlying β-carotene accumulation in carrot.
Abstract 14770: Secreted Frizzled Related Protein 2 Reduces Resident Cardiac Progenitor Cell Proliferation and Induces Cardiac Marker Expression

Introduction: Endogenous repair via activation of resident cardiac progenitor cells represents an attractive therapeutic approach for limiting cardiac remodeling and enhancing cardiac regeneration post infarction. Secreted Frizzled Related Protein 2 (Sfrp2) has been shown to reduce myocyte apoptosis and to affect infarct size in vivo , but its effect on resident cardiac progenitor cells has yet to be investigated. In this study, we examined the effects of Sfrp2 in the proliferation and differentiation of mouse resident cardiac progenitor cells (mCPCs). Methods: cKit+/Sca1+ mCPCs were isolated by magnetic beads and single cell clones were derived after plating cells by limiting dilutions. Expression of stem cell and mesenchymal markers was evaluated by FACS analysis and Sfrp s by qRT-PCR. To examine the effects of Sfrp2 on mCPC proliferation, cell cycle was assessed by BrdU incorporation and DNA content staining using FACS analysis and confirmed by BrdU ELISA. The effect of Sfrp2 on mCPC differentiation was evaluated by both qRT-PCR and immunofluorescent staining for cardiac markers Nkx2.5, Actinin, and α-MHC. Results: Isolated mCPC clones maintained expression of Sca1, CD44, CD105, CD29 and CD106 throughout the study. These cells expressed high levels of Sfrp1 and 3 . Sfrp2 was detectable but at significantly lower levels. Treatment of mCPCs with 1–100 nM recombinant Sfrp2 protein showed a dose dependent reduction in the percent of cells in S-phase (maximum reduction at 10 nM of 35–40%, P Conclusions: Our data suggests that Sfrp2 induces cell cycle arrest of mCPCs by specifically blocking progression of cells from the G0/G1 to S-phase without effecting cell division. This inhibition in proliferation is accompanied by induction of mCPC differentiation as evident by increased expression cardiac specific markers, such as Nkx2.5, but Sfrp2 failed to drive these cells to fully differentiate to mature cardiomyocytes.
Effect of oligonucleic acid (ONA) backbone features on assembly of ONA–star polymer conjugates: a coarse-grained molecular simulation study

Understanding the impact of incorporating new physical and chemical features in oligomeric DNA mimics, termed generally as "oligonucleic acids" (ONAs), on their structure and thermodynamics will be beneficial in designing novel materials for a variety of applications. In this work, we conduct coarse-grained molecular simulations of ONA-star polymer conjugates with varying ONA backbone flexibility, ONA backbone charge, and number of arms in the star polymer at a constant ONA strand volume fraction to elucidate the effect of these design parameters on the thermodynamics and assembly of multi-arm ONA-star polymer conjugates. We quantify the thermo-reversible behavior of the ONA-star polymer conjugates by quantifying the hybridization of the ONA strands in the system as a function of temperature (i.e. melting curve). Additionally, we characterize the assembly of the ONA-star polymer conjugates by tracking cluster formation and percolation as a function of temperature, as well as cluster size distribution at temperatures near the assembly transition region. The key results are as follows. The melting temperature (Tm) of the ONA strands decreases upon going from a neutral to a charged ONA backbone and upon increasing flexibility of the ONA backbone. Similar behavior is seen for the assembly transition temperature (Ta) with varying ONA backbone charge and flexibility. While the number of arms in the ONA-star polymer conjugate has a negligible effect on the ONA Tm in these systems, as the number of ONA-star polymer arms increase, the assembly temperature Ta increases and local ordering in the assembled state improves. By understanding how factors like ONA backbone charge, backbone flexibility, and ONA-star polymer conjugate architecture impact the behavior of ONA-star polymer conjugate systems, we can better inform how the selection of ONA chemistry will influence resulting ONA-star polymer assembly.
Commit Yourself to Improvement of Student Learning

The word “assessment” may be the most dreaded word in higher education. Many faculty members associate assessment with institutional compliance and accreditation, which come with self-studies, site visits, and evaluative judgments. While assessment can take on many forms, it should always be
Information security policies and value conflict in multinational companies

The purpose of this paper is to examine challenges multinational companies face during the diffusion of their information security policies. Parent companies use these policies as their discourse for legitimization of their practices in subsidiaries, which leads to value conflicts in subsidiaries. The authors postulate that, when properly crafted, information security policies can also be used to reduce the very conflicts they are creating.,The proposed framework is conceptualized based on the review of literatures on multinational companies, information security policies and value conflict.,The authors identified three factors that may lead to value conflict in subsidiary companies: cultural distance, institutional distance and stickiness of knowledge. They offer three recommendations based on organizational discourse, ambidexterity and resource allocation to reduce value conflict.,The authors postulate that information security policies are the sources of value conflict in subsidiary companies. Yet, when crafted properly, these policies can also offer solutions to minimize value conflict.,The proposed framework can be used to increase policy diffusion success, minimize value conflict and, in turn, decrease information security risk.,The growing literature on information security policy literature is yet to examine the diffusion of policies within multinational companies. The authors argue that information security policies are the source of, and solution to, value conflict in multinational companies.
6S RNA, a Global Regulator of Transcription

6S RNA is a small RNA regulator of RNA polymerase (RNAP) that is present broadly throughout the bacterial kingdom. Initial functional studies in Escherichia coli revealed that 6S RNA forms a complex with RNAP resulting in regulation of transcription, and cells lacking 6S RNA have altered survival phenotypes. The last decade has focused on deepening the understanding of several aspects of 6S RNA activity, including (i) addressing questions of how broadly conserved 6S RNAs are in diverse organisms through continued identification and initial characterization of divergent 6S RNAs; (ii) the nature of the 6S RNA-RNAP interaction through examination of variant proteins and mutant RNAs, cross-linking approaches, and ultimately a cryo-electron microscopic structure; (iii) the physiological consequences of 6S RNA function through identification of the 6S RNA regulon and promoter features that determine 6S RNA sensitivity; and (iv) the mechanism and cellular impact of 6S RNA-directed synthesis of product RNAs (i.e., pRNA synthesis). Much has been learned about this unusual RNA, its mechanism of action, and how it is regulated; yet much still remains to be investigated, especially regarding potential differences in behavior of 6S RNAs in diverse bacteria.
Success is Not Guaranteed — Practical Matters for Direct Phase Determination in Electron Crystallography

The success of direct phasing methods for solving crystal structures from electron diffraction intensity data is not only determined by the adherence of the observed intensities to the single scattering approximation. While manipulation of experimental parameters such as crystal thickness (minimum) and electron wavelength (also minimum) are desirable goals, there have been successful determinations based on data collected at just 50 kV. The type of preparation also has a role to play in the collection of intensity data adequate for ab initio structure analyses. For example, is the area irradiated a 1 mm diameter instead of a 1 nm diameter? The former case might minimize some dynamical interactions due to averaging over many crystal orientations while the latter might emphasize the multiple scattering component if the effective sample is a perfect flat crystal.
Bilinear Forms and Quadratic Forms

This chapter discusses a useful way to classify quadratic forms and describes methods for simplifying them. It also discusses the bilinear forms. A bilinear form on a vector space V is a bilinear mapping V × V → F, where F is the field of scalars. The chapter describes the characteristic values of a real symmetric matrix as extrema of suitably defined functions. It also explains a rule called Lagrange's method of undetermined multiples, which finds out the stationary points a function whose variables are constrained by a side condition.
Chloride secretion across distal airway epithelium: relationship to submucosal gland distribution.

To evaluate the possible relationship between submucosal glands and transepithelial Cl- secretion, we compared the bioelectric properties of two distal airway regions: bronchioles, which contain few submucosal glands, and small bronchi, which contain numerous glands. Intact distal bronchi were dissected from the lungs of 4-8 wk old pigs and cannulated with micropipettes and perfused. Transepithelial potential difference (PD), short-circuit current (Isc), and barrier resistance (Rm) in distal bronchi, determined by cable analysis, were -3.0 +/- 0.4 mV, 50.7 +/- 5.9 microA/cm2, and 59.6 +/- 5.9 omega.cm2, respectively (means +/- SE). Bumetanide (10 microM), which blocks Cl- secretion through inhibition of Na(+)-K(+)-2Cl- cotransport, reduced Isc in distal bronchi by 30.0 +/- 5.5 microA/cm2 (59.0% of the total Isc). By comparison, a previous study of porcine distal airways [S.T. Ballard and A.E. Taylor, Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L79-L84, 1994] determined that bumetamide-sensitive Isc in bronchioles was 2.6 +/- 1.4 microA/cm2 (only 9.0% of the total Isc). Submucosal gland duct openings to the luminal surface were identified microscopically and counted in representative fields. In eight bronchioles, 6.8 +/- 4.4 gland duct openings/cm2 of airway surface were observed, whereas seven distal bronchi contained 916.8 +/- 84.0 gland duct openings/cm2, over a 100-fold difference. These data suggest that a direct relationship may exist between the magnitude of active transepithelial Cl- secretion and the presence of submucosal glands in normal distal airways.
Structures and nonlinear optical properties of polar 2-amino-1,2,3-triazolequinone derivatives

A series of phenyldialkylamine, dimethoxyphenyl, and nitrothiophene derivatives of 2-amino-1,2,3-triazolequinones was characterized by NMR, IR, mass spectroscopy, cyclic voltammetry, and chemical analyses. The solvatochromic procedure was used to evaluate the potential of nine compounds for nonlinear optical applications, and the possible failure of this model is discussed. The crystal structures of seven compounds were determined: (4) P21/c, a = 15.430(3) A, b = 7.633(2) A, c = 15.940(3) A, β = 105.19(3)° (5) P21/c, a = 20.201(2) A, b = 9.6579(9) A , c = 18.517(2) A, β = 95.907(2)° (6) P-1, a = 7.769(2) A, b = 8.515(3) A, c = 17.312(5) A, α = 89.347(7)°, β = 83.219(6)°, γ = 86.001(7)° (7) P-1, a = 8.1365(7) A, b = 8.9605(8) A, c = 11.630(1) A, α = 79.553(2)°, β = 75.048(2)°, γ = 82.080(2)° (8) P-1, a = 8.298(3) A, b = 9.720(3) A, c = 10.033(3) A, α = 84.803(6)°, β = 83.735(6)°, γ = 77.659(5)° (10) P21/n, a = 8.4300(7) A, b = 13.980(1) A, c = 13.975(1) A, β = 106.590(2)° (12) P21/n, a = 7.715(2) A, b = 14.206(3) A, c = 12.758(3) A, β = 91.016(5)°.
The deviation potential of pH glass electrode

Change of the effective membrane surface area generates a deviation potential (Ed) from the conventional Nernst potential (E0). ThisEd is an exponential function of the fraction of the membrane surface area that is covered (b) as (1−e−2b). There is an isosbestic pH (pHiso) at which no deviation can be detected, even if the effective surface area of the membrane is reduced, and at this pH the conventional Nernst equation requires no modification. This is attributed to the isoelectric point of the glass membrane. An extended Nernst equation is proposed.
Mechanical Response and Damage Evolution of High-Strength Concrete Under Triaxial Loading

Current weapons effects modeling efforts rely heavily on quasi-static triaxial data sets. However, there are fundamental knowledge gaps in the current continuum modeling approach due to limited experimental data in the areas of dynamic effects and damage evolution. Arbitrary scalar values used for damage parameters have experimentally unverified mathematical forms that often do not scale to different geometries, stress states, or strain rates. Although some preliminary tests have been performed through dynamic triaxial compression experiments, the results are difficult to interpret due to changes in specimen diameter and length-to-diameter ratio. In this study, a high-strength concrete (f’c ∼130 MPa) was investigated under triaxial loading conditions at confining pressures up to 300 MPa. Three cylindrical specimen sizes were used to determine size effects, including 50 × 114 mm, 25 × 50 mm, and 25 × 13 mm. For a limited number of specimens, X-Ray Computed Microtomography (XCMT) scans were conducted. It was noted that size and length-to-diameter ratio have substantial effects on the experimental results that must be understood to determine dynamic effects based on specimen geometries used in dynamic triaxial compression experiments. Additionally, by quantifying pore crushing and crack development under a variety of triaxial loading conditions, future multi-scale modeling efforts will be able to incorporate systematically defined damage parameters that are founded on experimental results.
Chapter 23.3 Nucleic acids

This chapter covers the advances of our knowledge of nucleic acid duplexes, primarily from single-crystal X-ray diffraction, and the biological implications of this new knowledge. The focus is primarily on DNA because much more is known about it, but DNA/RNA hybrids and duplex RNA are also considered. Because the emphasis is on the geometry of the nucleic acid double helix, exotic structures, such as quadruplexes, hammerhead ribozymes and aptamers, are omitted, as are larger-scale structures such as tRNA. Keywords: A-tract bending; B-DNA; base pairing; DNA; glycosyl bond geometry; helix parameters; nucleic acids; sugar ring conformations; Watson–Crick Z-DNA
Relation between therapy-induced changes in natriuretic peptide levels and long-term therapeutic effects on mortality in patients with heart failure and reduced ejection fraction.

Aims To assess whether natriuretic peptides (NPs) can be used to reliably predict long-term therapeutic effect on clinical outcomes for patients with heart failure and reduced ejection fraction (HFrEF). Methods and results HFrEF intervention trials with mortality data were identified. Subsequently, we identified trials assessing therapy-induced changes in NPs. We assessed the correlation between the average short-term placebo-corrected drug or device effect on NPs and the longer-term therapeutic effect on clinical outcomes. Of 35 distinct therapies with an identifiable mortality result (n = 105 062 patients), 20 therapies had corresponding data on therapeutic effect on NPs. No correlation was observed between therapy-induced placebo-corrected change in brain natriuretic peptide or N-terminal pro-brain natriuretic peptide and therapeutic effect on all-cause mortality (ACM) (Spearman r = -0.32, P = 0.18 and r = -0.20, P = 0.47, respectively). There was no correlation between therapy-induced placebo-corrected per cent change in NP and intervention effect on ACM or ACM-heart failure hospitalizations (r = -0.30, P = 0.11 and r = 0.10, P = 0.75, respectively). Conclusions Short-term intervention-induced changes in NP levels are not reliable predictors of therapeutic long-term effect on mortality or morbidity outcomes for patients with HFrEF.
Iatrogenic withdrawal syndrome in specialty pediatric critical care

Abstract Aim To describe the occurrence of opioid and benzodiazepine withdrawal symptoms in a cohort of pediatric intensive care unit (PICU) patients, the characteristics of this group, and patterns of withdrawal scoring observed during medication weaning. Background Patients in the PICU are a complex and vulnerable population. Opioids and benzodiazepines are routinely administered in this setting. Providers must be equipped to recognize and assess symptoms of narcotic and benzodiazepine withdrawal. Methods A retrospective chart review was conducted to describe all patients admitted to the medical intensive care unit who received continuous infusions of morphine and midazolam during a one-year period. Patient demographics, diagnosis, and presence of co-morbidities were abstracted. The number of days on continuous infusions was measured, along with Withdrawal Assessment Tool-1 (WAT-1) scores and documented symptoms that could be associated with withdrawal. WAT-1 scoring ranges from 0 to 12, a WAT-1 score of 3 or higher is considered to indicate clinically significant withdrawal symptoms. Descriptive statistics were utilized to summarize demographic and clinical variables. Results Among 60 cases, patient ages ranged 5 weeks to 29 years (median 3.5 years). Eighty percent of patients had a primary respiratory diagnosis and 88.3% had one or more co-morbidities. Forty-four patients (73.3%) had symptoms consistent with withdrawal. Thirty-one percent of patients had a maximum WAT-1 score between 3 and 8. The majority of patients (55%) had a history of opioid and/or benzodiazepine exposure. Conclusions The information learned highlights the need for ongoing conversation and continued study of how best to assess and manage withdrawal syndrome in pediatric critical care environments.
Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma.

Brain tumors are the leading cause of cancer-related mortality in children and have distinct genomic and molecular features compared with adult glioma. However, the properties of immune cells in these tumors has been vastly understudied compared with their adult counterparts. We combined multiplex immunofluorescence immunohistochemistry coupled with machine learning and single-cell mass cytometry to evaluate T-cells infiltrating pediatric glial tumors. We show that low-grade tumors are characterized by greater T-cell density compared with high-grade glioma (HGG). However, even among low-grade tumors, T-cell infiltration can be highly variable and subtype-dependent, with greater T-cell density in pleomorphic xanthoastrocytoma and ganglioglioma. CD3+ T-cell infiltration correlates inversely with the expression of SOX2, an embryonal stem cell marker commonly expressed by glial tumors. T-cells within both HGG and low-grade glioma (LGG) exhibit phenotypic heterogeneity and tissue-resident memory T-cells consist of distinct subsets of CD103+ and TCF1+ cells that exhibit distinct spatial localization patterns. TCF1+ T-cells are located closer to the vessels while CD103+ resident T-cells reside within the tumor further away from the vasculature. Recurrent tumors are characterized by a decline in CD103+ tumor-infiltrating T-cells. BRAFV600E mutation is immunogenic in children with LGG and may serve as a target for immune therapy. These data provide several novel insights into the subtype-dependent and grade-dependent changes in immune architecture in pediatric gliomas and suggest that harnessing tumor-resident T-cells may be essential to improve immune control in glioma.
“We Could Do, Perhaps, More Good There Than Here”: Harriet Farley and the Transatlantic Audience of the Lowell Offering

This article argues that the Lowell Offering (1840–1845) should be read as a publication that actively cultivated a transatlantic readership by publishing increasingly English-focused content. It e...
High dose corticosteroids for treatment of vision loss due to indirect injury to the optic nerve.

Abstract Thirty-six patients with vision loss due to indirect injury to the optic nerve were retrospectively studied. Twenty-one had been acutely treated with high-dose intravenous dexamethasone and 15 had not. The visual acuity of 62% of the treated patients and of 33% of the untreated patients improved. This difference was not statistically significant. However, of those patients whose vision did improve, the vision of those on steroids began to improve earlier (P less than .05).
Carboxyhemoglobinemia in Critically Ill Coronavirus Disease 2019 Patients

Carboxyhemoglobinemia is a common but a serious disorder, defined as an increase in carboxyhemoglobin level. Unfortunately, there are few data on carboxyhemoglobinemia in coronavirus disease 2019 (COVID-19) patients. Therefore, our study aimed to evaluate the incidence and etiologies of carboxyhemoglobinemia in COVID-19 patients and determine any association between carboxyhemoglobinemia and novel coronavirus infection. A retrospective chart review was performed at an academic medical center for all inpatient COVID-19 cases with either single or serial carboxyhemoglobin (COHb) levels from March 2020 through August 2020.Our study demonstrates that carboxyhemoglobinemia in COVID-19 patients is due to sepsis, hemolysis, and cytokine storm, triggered by the novel coronavirus infection sequela and is not directly from the virulence of novel coronavirus. Given the coexisting illnesses in critically ill COVID-19 patients, it is impossible to establish if coronavirus virulence was the culprit of elevated COHb levels. Moreover, our study found a high incidence of carboxyhemoglobinemia in critically ill COVID-19 patients. The oxygen saturation measured by pulse oximetry can be inaccurate and unreliable; however, our study could not demonstrate any uniform results on the discrepancy between oxygen saturation measured by pulse oximetry and arterial blood gas. In this study, COHb levels were measured using a CO-oximeter. Therefore, we recommend monitoring the COHb level routinely in critically ill COVID-19 patients to allow more effective and prompt treatment.
Retarded ejaculation

Retarded ejaculation (RE) has a relatively low prevalence (<3%), yet this condition results in considerable distress, anxiety, and lack of sexual confidence for those suffering from it. Furthermore, men with partners often experience impairment of both the sexual and nonsexual aspects of their relationships, with such negative effects compounded when procreation is a consideration. The definition of RE is ambiguous, due to the variability and paucity of data regarding normal coital ejaculatory latency. RE is influenced by both biogenic and psychogenic components, which may vary over time both between and within individuals. While specific pathophysiology can often be identified, further elucidation of the biogenic components of this dysfunction will require greater understanding of the physiological mechanisms underlying ejaculation. Yet, the most useful strategies for understanding RE will integrate rather than isolate the various biogenic and psychogenic aspects of this dysfunction. Evidence based evaluation and treatment protocols for this disorder are lower than for other sexual dysfunctions, but reports suggest better treatment efficacy when the etiology is predominantly psychogenic. As with erectile dysfunction (ED) and premature ejaculation (PE), if safe and efficacious oral pharmaceuticals are eventually developed for this condition, the treatment algorithm is likely to undergo significant alteration. Even then, however, the most effective treatments are likely to result from a combination treatment that integrates sex coaching with pharmacotherapy.
Spike Protein NTD mutation G142D in SARS-CoV-2 Delta VOC lineages is associated with frequent back mutations, increased viral loads, and immune evasion

Abstract The significantly greater infectivity of the SARS-CoV-2 Delta variants of concern (VOC) is hypothesized to be driven by key mutations that result in increased transmissibility, viral load and/or evasion of host immune response. We surveyed the mutational profiles of Delta VOC genomes between September 2020 and mid-August 2021 and identified a previously unreported mutation pattern at amino acid position 142 in the N-terminal domain (NTD) of the spike protein which demonstrated multiple rounds of mutation from G142 to D142 and back. This pattern of frequent back mutations was observed at multiple time points and across Delta VOC sub-lineages. The etiology for these recurrent mutations is unclear but raises the possibility of host-directed editing of the SARS-CoV-2 genome. Within Delta VOC this mutation is associated with higher viral load, further enhanced in the presence of another NTD mutation (T95I) which was also frequently observed in these cases. Protein modeling of both mutations predicts alterations of the surface topography of the NTD by G142D, specifically disturbance of the ‘super site’ epitope that binds NTD-directed neutralizing antibodies (NAbs). The appearance of frequent and repeated G142D followed by D142G back mutations is previously unreported in SARS-CoV-2 and may represent viral adaptation to evolving host immunity characterized by increasing frequency of spike NAbs, from both prior infection and vaccine-based immunity. The emergence of alterations of the NTD in and around the main NAb epitope is a concerning development in the ongoing evolution of SARS-CoV-2 which may contribute to increased infectivity, immune evasion and ‘breakthrough infections’ characteristic of Delta VOC. Future vaccine and therapy development may benefit by recognizing the emergence of these novel spike NTD mutations and considering their impact on antibody recognition, viral neutralization, infectivity, replication, and viral load.
Applications of the Marcus cross relation to inner sphere O2 reduction: Implications in Small-Molecule Activation

The Marcus cross relation has been used for outer sphere electron transfer, proton transfer, hydride transfer, and proton-coupled electron transfer. This work shows that the same Marcus cross relation is useful in determining rate constants for inner sphere reduction of molecular oxygen. This has many implications in the field of small molecule activation in the form of catalyst design and as an indirect mechanistic probe.
CYP2C9 and 3A4 play opposing roles in bioactivation and detoxification of diphenylamine NSAIDs.

Abstract Diphenylamine NSAIDs are taken frequently for chronic pain conditions, yet their use may potentiate hepatotoxicity risks through poorly characterized metabolic mechanisms. Our previous work revealed that seven marketed or withdrawn diphenylamine NSAIDs undergo bioactivation into quinone-species metabolites, whose reaction specificities depended on halogenation and the type of acidic group on the diphenylamine. Herein, we identified cytochromes P450 responsible for those bioactivations, determined reaction specificities, and estimated relative contributions of enzymes to overall hepatic bioactivations and detoxifications. A qualitative activity screen revealed CYP2C8, 2C9, 2C19, and 3A4 played roles in drug bioactivation. Subsequent steady-state studies with recombinant CYPs recapitulated the importance of halogenation and acidic group type on bioactivations but importantly, showed patterns unique to each CYP. CYP2C9, 2C19 and 3A4 bioactivated all NSAIDs with CYP2C9 dominating all possible bioactivation pathways and their specificities. For each CYP, specificities for overall oxidative metabolism were not impacted significantly by differences in NSAID structures but the values themselves differed among the enzymes such that CYP2C9 and 3A4 were more efficient than others. When considering hepatic CYP abundance, CYP2C9 almost exclusively accounted for diphenylamine NSAID bioactivations, whereas CYP3A4 provided a critical counterbalance favoring their overall detoxification. Preference for either outcome would depend on molecular structures favoring metabolism by the CYPs as well as the influence of clinical factors altering their expression and/or activity. While focused on NSAIDs, these findings have broader implications on bioactivation risks given the expansion of the diphenylamine scaffold to other drug classes such as targeted cancer therapeutics.
Forest Dieback/Decline: A Regional Response to Excessive Air Pollution Exposure

Healthy forests are the rule and diseased forests the exception. Whenever forest trees become visibly symptomatic or die in large numbers and over widespread areas the phenomenon is dramatic and distressing to human managers and observers. The latter part of the twentieth century has seen numerous examples of forest dieback/decline in temperate and tropical latitudes. What is the role of atmospheric deposition in these forest dieback/decline phenomena?
The Robustness of Price Elasticity Estimates: A Revisit of Various Methodologies Used To Estimate Demand for Cigarettes

Although the price elasticity of cigarettes has been estimated using a variety of models and methods, few studies apply these methods to the same dataset and compare the estimates from alternative approaches. This paper employs the National Longitudinal Survey of Youth 1997 to provide the first comprehensive study that addresses most methodology limitations found in the previous literature and compares cigarette price elasticity estimated from many approaches. We estimate the elasticity by allowing the addictiveness to differ by non-addictive, myopic and rational smoking. We account for the state-level anti-smoking sentiment using its time-invariant and time-variant measures. We control for the heterogeneity of smoking behavior among population using the two-part model in a cross-sectional approach and the two-way error component model in a longitudinal approach. The estimates of elasticity are significant in almost all specifications and strikingly close in magnitude. The price elasticity of smoking participation ranges from -0.08 to -0.24 with an average of -0.16, and the price elasticity of cigarette consumption rages from -0.07 to -0.24 with an average of -0.14. This indicates that when estimated using the same panel dataset with a relative long time span, the elasticity is likely to be estimated consistently regardless of approach.
Computer-Managed Instruction for Prospective Health Teachers.

(1972). Computer-Managed Instruction for Prospective Health Teachers. School Health Review: Vol. 3, No. 3, pp. 16-18.
Human pulmonary surfactant protein (SP-A), a protein structurally homologous to C1q, can enhance FcR- and CR1-mediated phagocytosis.

C1q, a subunit of the first component (C1) of the classical complement pathway, and the pulmonary surfactant protein SP-A are structurally homologous molecules, each having an extended collagen-like domain contiguous with a non-collagenous domain. It is the collagen-like region of C1q that binds to mononuclear phagocytes and mediates the enhancement of phagocytosis of opsonized particles by these cells. Because SP-A enhances the endocytosis of phospholipids by alveolar type II cells and alveolar macrophages, we examined whether these two molecules were functionally interchangeable. The phagocytosis of sheep erythrocytes opsonized with IgG or with IgM and complement was enhanced by the adherence of monocytes or macrophages, respectively, to SP-A. The enhanced response was dependent on the concentration of SP-A used for coating the surfaces, similar to that seen when monocytes were adhered to C1q-coated surfaces. Both the percentage of cells ingesting the opsonized targets and the number of targets ingested per cell increased with increasing concentrations of SP-A. No such enhancement was seen with cells adhered to albumin, iron-saturated transferrin, or uncoated surfaces. However, SP-A did not substitute for C1q in the formation of hemolytically active C1. C1q did not stimulate lipid uptake by alveolar type II cells or alveolar macrophages and had only a slight inhibitory effect on the binding of SP-A to alveolar type II cells. Thus, these results suggested that a function which requires interactions of both the collagenous and the non-collagenous regions (i.e. initiation of the classic complement cascade) could not be mimicked by a protein sharing structural macromolecular similarity but lacking sequence homology in the non-collagen-like region. However, SP-A could substitute for C1q in stimulating a function previously shown to be mediated by the collagen-like domains of the C1q molecule.
Scarred states in strongly coupled quantum systems

Twenty years after they were first introduced, quantum wavefunctions scarred on classically unstable structures continue to appear in new and surprising contexts. Starting from the photoelectric effect in ultra-strong fields, the manuscript briefly reviews some of these and suggests a motivation for a more general understanding of this quantum phenomenon.
Sedimentary architecture and genesis of Holocene shallow-water mud-mounds, northern Belize

Cangrejo and Bulkhead Shoals are areally extensive, Holocene biodetrital mud-mounds in northern Belize. They encompass areas of 20 km2 and 35 km2 in distal and proximal positions, respectively, on a wide and shallow-water, microtidal carbonate shelf where storms are the major process affecting sediment dynamics. Sediments at each mound are primarily biodetrital and comprise part of a eustatically forced, dominantly subtidal cycle with a recognizable deepening-upward transgressive systems tract, condensed section and shallowing-upward highstand systems tract. Antecedent topographic relief on Pleistocene limestone bedrock also provided marine accommodation space for deposition of sediments that are a maximum of 7·6 m thick at Cangrejo and 4·5 m thick at Bulkhead. Despite differences in energy levels and location, facies and internal sedimentological architectures of the mud-mounds are similar. On top of Pleistocene limestone or buried soil developed on it are mangrove peat and overlying to laterally correlative shelly gravels. Deposition of these basal transgressive, premound facies tracked the rapid rate of sea-level rise from about 6400–6500 years BP to 4500 years BP, and the thin basal sedimentation unit of the overlying mound-core appears to be a condensed section. Following this, the thick and complex facies mosaic comprising mound-cores represents highstand systems tract sediments deposited in the last ≈ 4500 years during slow and decelerating sea-level rise. Within these sections, there is an early phase of progradationally offlapping catch-up deposition and a later (and current) phase of aggradational keep-up deposition. The mound-cores comprise stacked storm-deposited autogenic sedimentation units, the upper bounding surfaces of which are mostly eroded former sediment–water interfaces below which depositional textures have largely been overprinted by biogenic processes associated with Thalassia-colonized surfaces. Vertical stacking of these units imparts a quasi-cyclic architecture to the section that superficially mimics metre-scale parasequences in ancient rocks. The locations of the mud-mounds and the tidal channels transecting them have apparently been stable over the last 50 years. Characteristics that might distinguish these mud-mounds and those mudbanks deposited in more restricted settings such as Florida Bay are their broad areal extent, high proportion of sand-size sediment fractions and relatively abundant biotic particles derived from adjoining open shelf areas.
Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium

Using confocal scanning laser microscopy of viable tissue sections, we have demonstrated organized lymphoid aggregates (LA), that have a unique structure, in the stratum basalis of uterine endometrium. These LA consist of a core of B cells surrounded by more numerous T cells and an outer halo of monocytes/ macrophages. The T cells in the LA were almost exclusively CD8+CD4-. These CD8+ LA, in terms of both their T cell and B cell components, were either small or absent during the early proliferative stage of the menstrual cycle, significantly larger in size at mid-cycle and during the secretory phase, and absent in post-menopausal women, suggesting that their development is hormonally influenced. This new finding of a menstrual cycle-dependent, phenotypically unique, organized immune cell structure may lead to new insights into the mechanisms by which the endometrium accepts a semiallogeneic graft while providing resistance to infectious organisms.
Population Pharmacokinetic Analysis of Orally‐Administered Ruxolitinib (INCB018424 Phosphate) in Patients With Primary Myelofibrosis (PMF), Post‐Polycythemia Vera Myelofibrosis (PPV‐MF) or Post‐Essential Thrombocythemia Myelofibrosis (PET MF)

Ruxolitinib is a selective inhibitor of Janus kinase 1 and 2, which is approved to treat intermediate or high-risk myelofibrosis. The population pharmacokinetics for ruxolitinib were characterized by a modeling dataset of 272 subjects from a Phase 2 and a Phase 3 study and validated by an external validation dataset of 142 subjects from a second Phase 3 study. The PK of ruxolitinib was adequately described by a two-compartment disposition model with first-order absorption and linear elimination. All model parameters were estimated with good precision. Gender and body weight were identified as covariates for oral clearance (CL/F) and volume of distribution for central compartment (Vc/F), respectively. Apparent oral clearance was 22.1 and 17.7 L/h for a typical male and female subject, respectively, with 39.1% unexplained inter-individual variability (IIV). The typical Vc /F for a subject with a median weight of 72.9 kg was estimated to be 58.6 L, with 28% unexplained IIV. The model predictive performance was validated by visual predictive check (VPC) and the external validation dataset. This analysis suggests that effects of gender and body weight on ruxolitinib PK are not clinically significant and hence no dose adjustment is needed based on gender and weight.