cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of baroreceptor denervation on stimulation of drinking by angiotensin II in conscious dogs

Angiotensin II causes marked stimulation of drinking when it is injected centrally but is a relatively weak dipsogen when administered intravenously. However, it has been proposed that the dipsogenic action of systemically administered angiotensin II may be counteracted by the pressor action of the peptide. To test this hypothesis, the dipsogenic action of angiotensin II was investigated in dogs, in which low and high baroreceptor influences had been eliminated by denervation of the carotid sinus, aortic arch, and heart. In five sham-operated dogs, infusion of angiotensin II at 10 and 20 ng.kg-1.min-1 increased plasma angiotensin II concentration to 109.2 +/- 6.9 and 219.2 +/- 38.5 pg/ml and mean arterial pressure by 20 and 29 mmHg, respectively, but did not induce drinking. In four baroreceptor-denervated dogs, the angiotensin II infusions produced similar increases in plasma angiotensin II concentration and mean arterial pressure but, in contrast to the results in the sham-operated dogs, produced a dose-related stimulation of drinking. Water intake with the low and high doses of angiotensin II was 111 +/- 44 and 255 +/- 36 ml, respectively. The drinking responses to an increase in plasma osmolality produced by infusion of hypertonic sodium chloride were not different in the sham-operated and baroreceptor-denervated dogs. These results demonstrate that baroreceptor denervation increases the dipsogenic potency of intravenous angiotensin II and provides further support for the hypothesis that the dipsogenic action of intravenous angiotensin II is counteracted by the rise in blood pressure.
Exposure and Manipulation of Rectal Lesions

This article outlines the transanal and posterior anal proctotomy approaches to lesions considered to be benign. These procedures have been employed at the Ferguson Clinic with excellent results.
Liberty and crystal : two new U.S.-developed aroma hops

Liberty and Crystal, two triploid female half-sister selections with largely German Hallertauer mittelfruh ancestry were found to be suitable for commercial production in hop growing areas in Washi...
Rethinking imperial infrastructure: A bottom-up perspective on the Inca Road

Abstract The Inca road has been the iconic example of imperial infrastructure in the prehispanic Andes. However, scholarly attention to its role in expanding and consolidating the Inca domain has overshadowed analysis of how locals may have appropriated the Inca road for their own private benefit. Based on a full-coverage survey and excavations, this article presents the case of small mining communities along the Inca road and the use they made of it. I argue that they most likely leveraged on emerging imperial infrastructure, in order to expand their existing lapidary and pigment production and exchange in the Atacama desert. The Inca Road may thus have served as an unintended stimuli for local economic activities, since it improved transportation logistics, and served as a linear exchange nexus. I further demonstrate how the Inca Road was, to some extent, appropriated to serve local economic purposes. This provides a unique “bottom-up” perspective of how the Inca infrastructure could not be fully controlled by the elites. Thus, the “imperial landscape” created by the Inca Road was more permeable than what the Incas expected and scholars have assumed, despite the physical or ideological coercion elites may have enforced.
Platelet Transfusion Requirement during ASCT for Lymphoma Is a Powerful Prognostic Variable.

Current techniques of autologous stem cell transplantation (ASCT) yield neutrophil and platelet engraftment in approximately 10 to 13 days post transplant. During this thrombocytopenia nadir, almost all patients require multiple platelet transfusions. Infections, fevers, and other clinical events likely influence the number of platelet transfusions received. However, some patients require minimal transfusion support. We have anecdotally noted that these patients seem to have a favorable outcome. To further study this issue, we retrospectively reviewed 723 patients undergoing a single ASCT at the Cleveland Clinic from 1995–2006 fulfilling the following criteria: > 18 years of age; diagnosis of lymphoma (NHL or HD); and a busulfan-based chemotherapy only preparative regimen. Median age was 50; 79% had NHL; 29% received prior radiation therapy; median time from diagnosis to transplant was 17 months; 26% had an elevated LDH at the time transplant; 88% had disease that was sensitive to salvage chemotherapy; and all patients received peripheral stem cells (PSC) with the median CD34+ dose of 6.02x106/kg. Patients received platelet transfusion for platelet counts of less than 10,000 x 109/liter or for clinical bleeding. The median number of platelet transfusions received for the entire group was 4. Median time to platelet engraftment greater than 20,000 x109/liter was 13 days. A univariable analysis revealed that older age at transplant, more courses of prior chemotherapy, resistant disease, lower CD34+ cell dose, and NHL diagnosis were associated with more platelet transfusions. The finding that NHL patients required more transfusions was unexpected; HD patient had a median of 3 platelet transfusions vs. 4 in the NHL group (p=0.015). Patients receiving 0 to 1 platelet transfusions had 5 year survival of 83%, vs. 61% for patients receiving 2 to 4 platelet transfusions, and 47% for patient receiving 5 or more platelet transfusions (p<0.001). 5 year relapse free survival was 59% for patients receiving 0 to 1 platelet transfusion, 46% for patients receiving 2 to 4 platelet transfusions, and 37% for patients receiving 5 or more platelet transfusions, shown graphically below: Multivariable analysis revealed that older patient age, more courses of prior chemotherapy, resistant disease, and more platelet transfusions were associated with worse overall and relapse-free survival (p<0.001). Of note, total number of CD34+ cells was included in this multivariable analysis and was not prognostic for survival or for relapse-free survival. We conclude that patients who received fewer platelet transfusions during their transplant admission have a better overall survival and relapse free survival. The mechanism is unknown. Platelet transfusion requirement may be a surrogate marker for other prognostic variables. However, the fact that the number of platelet transfusions was significant in the multivariable analysis, which included other well known prognostic variables, is intriguing and warrants additional study. ![Figure][1] Figure [1]: pending:yes
A Multifaceted Career in Basic and Applied Vision Science

Vengu Lakshminarayanan urged me to summarize my experiences as a vision scientist and issues confronted along the way. Here, I describe influences which have affected my scientific career, but I discuss only limited aspects of my administrative, organizational, and professional activities in the USA or abroad. And I do not discuss my research into the history of science.
Kinematic Magnetic Resonance Imaging of Peroneal Tendon Subluxation with Intraoperative Correlation

Magnetic resonance imaging (MRI) is a noninvasive modality of choice for the detection of static peroneal tendon pathologic features. The depiction of peroneal tendon subluxation using real-time kinematic MRI has not been previously reported. We describe the MRI and intraoperative correlation of peroneal tendon and retinacular pathologic findings, and the novel use of kinematic MRI in the illustration of peroneal tendon subluxation.
Are Perceived Differences for Junior and Senior Women Because of Struggle to Balance Career and Family

Because career stage is highly correlated with chronological age, junior women are more likely to face childbearing and caring issues and/or may be more likely to be trying to establish a satisfactory dual career situation in conjunction with their partner/spouse than are their senior colleagues. This chapter focuses on whether balancing career and family explains the perceived differences for junior and senior women. A quick interpretation of the responses might suggest that differences for junior and senior women scientists center on career-family balance. Closer examination reveals a more complex situation. Qualitative comments add the necessary dimension to understand that while balancing career and family contributes significantly to the perceived differences between junior and senior women, those are not the only issues that account for the differences.
Computational Design of a Model for the Platelet Integrin αIIbβ3.

Abstract Integrins, the principal receptors linking the cytoskeleton to extracellular ligands, are responsible, in large part, for platelet adhesion and aggregation. Like many membrane spanning proteins, the molecular structure of integrins has been difficult to determine, although crystal and NMR structures are available for water soluble portions of αVβ3 and αIIbβ3. In addition, models for the αIIb and β3 transmembrane (TM) heterodimer have been obtained using computational methods, but with conflicting results. Accordingly, we employed two different modeling strategies to distinguish between existing models. First, we used a Monte Carlo-simulated annealing (MCSA) protocol that features a selective advantage for structures that are consistent with previously characterized αIIb and β3 TM domain point mutations. During each step of the protocol, we calculated the effects of selected mutations and assigned a penalty to the step if it produced a structure that was inconsistent with experimental results. Second, we threaded the αIIb and β3 TM sequences onto a database of membrane helix dimers and rank-ordered the structures based on their calculated energies and their agreement with the cysteine crosslinking experiments reported by Luo et al (PLoS Biol 2:776–86, 2004). The MCSA and threaded TM models were similar with a root mean squared deviation (RMSD) of 1.5 A. Moreover, they differed from a model reported by Kay Gottschalk (Structure 13:703–12, 2005) most notably by an ~50° rotation of the αIIb TM helix about its helical axis. This positions αIIb residue Leu980 in the TM interface and in van der Waals contact with β3 residue Gly708, a result consistent with mutagenesis experiments. Further, the αIIb and β3 TM helices pack along conserved glycine residues (Gly972 and Gly976) in the GXXXG motif of αIIb with a right-handed crossing angle of −18°. To create a model for the full-length integrin, the N-termini of the TM model were connected to the crystal structure of the αVβ3 extracellular domain and its C-termini were connected to the corresponding NMR structures of the αIIb and β3 cytosolic domains. The model predicts an αIIb Arg995-β3 Asp723 salt bridge in the membrane proximal cytosolic domains and a change in the secondary structure of the extracellular domains from an extended to a helical conformation that occurs at Pro965 in αIIb and Pro693 in β3, just proximal to the TM domains. Finally, the full length model provides insight into distal interactions since its extracellular portion is held close to the membrane and is therefore sterically inaccessible to large ligands such as fibrinogen, whereas cytosolic regulatory sites such as the talin binding site in β3 are accessible and not sequestered by α/β interactions. In conclusion, we have modeled the αIIbβ3 TM heterodimer using two fundamentally different computational strategies, both of which converge upon similar structures that were used to construct a model for the full-length integrin.
Evaluating the Effect of the Changes in FDA Guidelines for Clozapine Monitoring

Background Concerns exist that clozapine is underutilized in the management of treatment-resistant schizophrenia. Although a 2015 change in the US Food and Drug Administration (FDA) monitoring recommendations lowered the threshold of the absolute neutrophil count for treatment interruption from 1,500/μL to 1,000/μL and removed white blood cell count thresholds from the monitoring algorithm, the implications of this policy change on clozapine interruptions remain unknown. Methods We analyzed outpatient prescribing records for antipsychotic medications in the Veterans Integrated Service Network 7 (VISN 7) database between 1999 and 2012 to assess the potential impact of the recent changes in FDA neutropenia monitoring recommendations on clozapine treatment discontinuation. We evaluated results of complete blood count monitoring to compare percentages of patients who developed or would have developed ≥ 1 hematologic event under the previous and current FDA guidelines in the first year following initiation of clozapine. Results From a cohort of 14,620 patients with schizophrenia (ICD-9-295.x), 246 patients received clozapine treatment (1.7%). No agranulocytosis was observed during the study period. Under the former recommendations, 5 patients in the clozapine initiation cohort (n = 160, 3.1%; 95% CI, 0.43-5.83) qualified for treatment interruption during the first year of clozapine treatment, while only 1 patient (0.6%) qualified under the current recommendations. Under the former recommendations, hematologic events occurred at a similar rate for individuals taking and not taking clozapine. Conclusions While clozapine remains an underused medication, the new FDA monitoring guidelines are likely to substantially reduce the percentage of patients who meet criteria for clozapine-associated hematologic events requiring treatment interruption. This decrease may reduce the clinical burden of managing patients on clozapine and therefore increase the number of individuals treated with this uniquely effective medication. However, prospective studies of individuals treated under the new guidelines are needed to fully assess safety of the FDA's change.
What’s the Story? The Impact of Race/Ethnicity on Crime Story Tone for Female Offenders

We examined how a female offender’s race/ethnicity influenced the tone of a crime story. Our thematic content analysis of front-page articles from four nationally available U.S. newspapers suggested that stories about minority female offenders were more likely to have negative tones, overall, than were stories about white female offenders. This finding held even after we considered the type of offense committed and the degree of front-page news coverage. The more negative depictions of minority females may explain their harsher treatment by the criminal justice system.
Time Off After Childbirth and Mothers’ Risk of Depression, Parenting Stress, and Parenting Practices:

There has been increased interest in U.S. parental leave policies, but relatively few studies have focused on how such policies may influence mothers’ well-being and parenting. This study addresses...
Sweetpotato Tolerance and Palmer Amaranth Control with Metribuzin and Oryzalin

Field studies were conducted in Clinton, NC in 2007 and 2009 to determine sweetpotato crop response and Palmer amaranth control with metribuzin and oryzalin. Treatments consisted of 140 and 202 g ai ha-1 metribuzin applied immediately after transplanting [0 wk after transplanting (WAP)] or 2 WAP, 560 and 1121 g ha-1 oryzalin 0 WAP, and tank mixes of metribuzin (140 or 202 g ha-1) and oryzalin (560 or 1,121 g ha-1) 0 WAP. At 2 WAP, metribuzin alone applied 0 WAP resulted in greater crop injury (33%) than oryzalin alone (1%), and the tank mix of metribuzin plus oryzalin resulted in greater crop injury (49%) than either herbicide applied alone. Greater crop injury occurred when metribuzin was applied at 202 g ha-1 (54%) than 140 g ha-1 (34%). Levels of injury were similar at 4 WAP (34, 8, and 52% for metribuzin, oryzalin, and the tank mix, respectively). At 4 WAP, injury from metribuzin was greater when it was applied 0 WAP (34%) compared to 2 WAP (18%). By 10 WAP, injury from metribuzin applied at 2 WAP was...
Clinical Manifestations of Sickle Cell Disease Across the Lifespan

Sickle cell disease (SCD) was the first “molecular” disease, but protean clinical manifestations belie simple molecular origins. The abnormal biophysical characteristics of sickle hemoglobin, which polymerizes in red blood cells and causes hemolysis and abnormal cellular interactions, result in a widespread vasculopathy that affects the central nervous system,the heart, lungs, liver, kidney, endocrine, and immune systems, as well as impairing bone and reproductive health. SCD causes lifelong episodes of acute and chronic pain, which are a major source of debility for patients, their families, and their communities. SCD afflicts approximately 100,000 Americans and millions of people worldwide, often in resource-limited settings. As health systems mature in these regions, childhood survival will improve, as it has in high-income countries over the past 40 years. However, absent a cure, the aging SCD population is facing multifaceted effects from acute-on-chronic vascular, inflammatory, and thrombotic injury, and life expectancy for adults with sickle cell anemia remains stubbornly stagnant in the fifth decade of life. Here, we review what is known about the clinical manifestations of SCD in the modern pediatric and enlarging adult populations.
Industry 4.0 Towards fabrication of mass-personalized parts on glass by Spark Assisted Chemical Engraving (SACE)

Abstract With the fourth industrial revolution manufacturing industry faces new challenges. Small batches of personalized parts must be produced in an economically viable manner. In this study, we show the feasibility of an approach using Spark Assisted Chemical Engraving to achieve personalized parts of hard-to-machine materials like glass with a low-cost setup. Key is the use of low-cost rapid prototyping and in-situ fabrication of the needed tooling, eliminating high indirect costs and long lead times. This approach can be used for on-demand manufacturing of personalized high precision applications of glass such as smartphone covers, advanced medical devices or fiber optic telecommunications.
Development of the Brief Social Capital for Youth Sexual and Reproductive Health Scale: Exploratory and Confirmatory Factor Analysis

Social capital plays an important role in sexual and reproductive health among youth, yet few measures to assess this concept have been developed and tested for this population. We developed and examined the factor structure of the Brief Social Capital for Youth Sexual and Reproductive Health Scale. Drawing on the empirical literature, we identified item content to assess an overall construct of social capital in relationship to youth’s sexual and reproductive health, including condom self-efficacy, civic engagement, and adult and community support. We conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) with a sample of 200 youth, predominately low-income and ethnic minority in Denver, Colorado. EFA with geomax rotation yielded a three-factor solution. CFA provided an adequate model fit with acceptable standardized factor loadings. This study provides a validated measure for future research to further examine social capital and youth sexual and reproductive health.
Review of Unmanned Aerial System (UAS) applications in the built environment: Towards automated building inspection procedures using drones

Abstract Unmanned Aerial Systems (UAS – a.k.a. drones) have evolved over the past decade as both advanced military technology and off-the-shelf consumer devices. There is a gradual shift towards public use of drones, which presents opportunities for effective remote procedures that can disrupt a variety of built environment disciplines. UAS equipment with remote sensing gear present an opportunity for analysis and inspection of existing building stocks, where architects, engineers, building energy auditors as well as owners can document building performance, visualize heat transfer using infrared imaging and create digital models using 3D photogrammetry. This paper presents a comprehensive review of various literature that addresses this topic, followed by the identification of a standard procedures for operating a UAS for energy audit missions. The presented framework is then tested on the Syracuse University campus site based on the literature review to showcase: 1) pre-flight inspection procedure parameters and methodologies; 2) during-flight visually identified areas of thermal anomalies using a UAS equipped with Infrared (IR) cameras and; 3) 3D CAD modeling developed through data gathered using UAS. A discussion of the findings suggests refining procedure accuracy through further empirical experimentation, as well as study replication, as a step towards standardizing the automation of building envelope inspection.
Out of Season: Illness in Adolescent Fiction

The “young adult” novel is aimed at a carefully defined target market, often focused on a predictable range of issues. Where illness and death are the theme, the process of growing up is more dramatically defined. Young people who suffer or watch a family member suffer a serious illness find their “stages of moral development” disrupted, their values reorganized, and emerging sexual interests submerged under more insistent demands. The books discussed in this article are not formula novels, but complex tales with interesting subplots and characters. Notable features common to them are as follows: 1) strategies of normalization, 2) abandonment and alienation, 3) unexpected emotions, 4) extra-familial support, 5) other people's problems, and 6) God, meaning, and hope.
Inside the Partisan Judicial Mind: A Survey of Federal Judges Perspectives on Redistricting Litigation

How do federal judges view partisan information when considering a decision in redistricting cases? To what extent do federal judges believe their colleagues engage in partisan behavior in deciding redistricting cases? Relying on 2007-2008 mail survey consisting of a random sample of nearly 100 federal judges across 11 circuits, this study investigates how judges assess redistricting disputes that come before their courts. Recent evidence (McKenzie forthcoming) indicates that partisan influences are significant factors in judicial decisions on redistricting in the federal courts. A survey of judges allows us to gain more information from judges themselves on why partisanship may motivate their behavior. The survey also provides insight on judicial attitudes regarding their own colleagues and the practices of redistricting in the states. In short, the results from this survey provide a better picture of the motivations behind judicial decision making in redistricting. Though the focus of the study is on redistricting, the findings have important implications for understanding judicial behavior in other types of highly partisan political cases like Bush v. Gore.
Constraining sub-parsec binary supermassive black holes in quasars with multi-epoch spectroscopy – III. Candidates from continued radial velocity tests

Quasars whose broad emission lines show temporal, bulk radial velocity (RV) shifts have been proposed as candidate sub-parsec (sub-pc), binary supermassive black holes (BSBHs). We identified a sample of 16 BSBH candidates based on two-epoch spectroscopy among 52 quasars with significant RV shifts over a few rest-frame years. The candidates showed consistent velocity shifts independently measured from two broad lines (H$\beta$ and H$\alpha$ or Mg${\rm \,II}$) without significant changes in the broad-line profiles. Here in the third paper of the series, we present further third- and fourth-epoch spectroscopy for 12 of the 16 candidates for continued RV tests, spanning $\sim$5--15 yr in the quasars' rest frames. Cross-correlation analysis of the broad H$\beta$ calibrated against [O${\rm\,III}]\,\lambda 5007$ suggests that 5 of the 12 quasars remain valid as BSBH candidates. They show broad H$\beta$ RV curves that are consistent with binary orbital motion without significant changes in the broad line profiles. Their broad H$\alpha$ (or Mg${\rm \,II}$) lines display RV shifts that are either consistent with or smaller than those seen in broad H$\beta$. The RV shifts can be explained by a $\sim$0.05--0.1 pc BSBH with an orbital period of $\sim$40--130 yr, assuming a mass ratio of 0.5--2 and a circular orbit. However, the parameters are not well constrained given the few epochs that sample only a small portion of the hypothesized binary orbital cycle. The apparent occurrence rate of sub-pc BSBHs is $\lesssim$13$\pm$5% among all SDSS quasars, with no significant difference in the subsets with and without single-epoch broad line velocity offsets. Dedicated long-term spectroscopic monitoring is still needed to further confirm or reject these BSBH candidates.
Chapter 13 – C2

The second complement component C2 is a multidomain serine protease that provides catalytic activity to the C3 and C5 convertases of classical and lectin pathways of complement. Formation of these convertases requires the Mg-dependent binding of C2 to C4b and subsequent cleavage of C2 by C1s or mannose-binding lectin-associated serine protease 2, respectively.
A Holographic Quantum Code

Abstract: It was shown by [2] how bulk operators in the AdS/CFT correspondence can be represented on the boundary analogously to the way logical qubits are represented in an encoded subspace in quantum error correction. Then in [1] holographic tensor networks that serve as toy models of the bulk boundary. This paper reviews some of the developments of [1] and [2]. Then it is demonstrated explicitly how to construct perfect tensors, which are essential to the tensor networks mentioned in [2]. Lastly a new example of a holographic quantum error-correcting code based on an eight index perfect tensor is presented.
Integrative taxonomy: ghosts of past, present and future

Describing species has been a formal, intellectually rich and influential applied and basic area of study for many of the past 260 years. While formally described eukaryotic diversity still falls short of estimated eukaryotic species diversity by many hundreds of thousands of species, some recent accounts have suggested a growing number of taxonomists are within reach of describing all extant species. We present a case study that illustrates, to the contrary, a recent ‘taxonomic impediment’ in part attributable to derogation of taxonomy as a scientific discipline: contemporary practice has re-interpreted taxonomy largely as an endeavour in enumerating species. We argue that challenges lie in (1) a poor understanding of taxonomy's epistemology; (2) excessive displacement of interest toward ecological or molecular studies; (3) over-interpretation of the contributions of multiple authors describing a species; and (4) perspectives that are strongly influenced by well-known taxa. The historical and recent literature on scyphozoans reveal ghosts of taxonomy's past that persist in the present, but suggest also that a renaissance enabled by integrative taxonomy is possible in the (near) future.
Is ceramide signaling a target for vascular therapeutic intervention

Today's society is plagued by cardiovascular diseases such as hypertension and atherosclerosis. Research devoted to the study of these diseases has focused, in part, on physiological phenomena responsible for the development and progression of the disease. Peripheral vascular function is one such focal point of research, and identification of cellular mechanisms that regulate vascular contractility and/or cellular proliferation is crucial for the development of new therapeutic interventions to combat these diseases. This review evaluates a new signaling mechanism, the ceramide signaling pathway as a potential target for therapeutic intervention. Special attention is given ceramide signaling in the contexts of vascular reactivity and cell proliferation in the vasculature. While ceramide signaling is a nascent area of vascular research, a growing body of evidence from other physiological systems implicates this new pathway as a potential regulator of contractile and cell proliferative functions within the blood vessel wall.
Transcriptome clarifies mechanisms of lesion genesis versus progression in models of Ccm3 cerebral cavernous malformations

Cerebral cavernous malformations (CCMs) are dilated capillaries causing epilepsy and stroke. Inheritance of a heterozygous mutation in CCM3/PDCD10 is responsible for the most aggressive familial form of the disease. Here we studied the differences and commonalities between the transcriptomes of microdissected lesional neurovascular units (NVUs) from acute and chronic in vivo Ccm3/Pdcd10ECKO mice, and cultured brain microvascular endothelial cells (BMECs) Ccm3/Pdcd10ECKO. We identified 2409 differentially expressed genes (DEGs) in acute and 2962 in chronic in vivo NVUs compared to microdissected brain capillaries, as well as 121 in in vitro BMECs with and without Ccm3/Pdcd10 loss (fold change ≥ |2.0|; p < 0.05, false discovery rate corrected). A functional clustered dendrogram generated using the Euclidean distance showed that the DEGs identified only in acute in vivo NVUs were clustered in cellular proliferation gene ontology functions. The DEGs only identified in chronic in vivo NVUs were clustered in inflammation and immune response, permeability, and adhesion functions. In addition, 1225 DEGs were only identified in the in vivo NVUs but not in vitro BMECs, and these clustered within neuronal and glial functions. One miRNA mmu-miR-3472a was differentially expressed (FC = − 5.98; p = 0.07, FDR corrected) in the serum of Ccm3/Pdcd10+/− when compared to wild type mice, and this was functionally related as a putative target to Cand2 (cullin associated and neddylation dissociated 2), a DEG in acute and chronic lesional NVUs and in vitro BMECs. Our results suggest that the acute model is characterized by cell proliferation, while the chronic model showed inflammatory, adhesion and permeability processes. In addition, we highlight the importance of extra-endothelial structures in CCM disease, and potential role of circulating miRNAs as biomarkers of disease, interacting with DEGs. The extensive DEGs library of each model will serve as a validation tool for potential mechanistic, biomarker, and therapeutic targets.
Benzoyl peroxide use transiently decreases Cutibacterium acnes load on the shoulder

Background Cutibacterium acnes is the most common pathogen in shoulder prosthetic joint infections. Short-contact benzoyl peroxide (BPO) solutions effectively reduce C acnes loads on the shoulder preoperatively. It is unknown how long the effect of BPO lasts. We evaluated C acnes counts 1 week after BPO application. We hypothesized that BPO would decrease C acnes burden with a rebound after 1 week. Methods Screening of 102 healthy volunteers with no history of shoulder surgery or C acnes infection was performed to establish bacterial counts. Thirty-four participants were selected based on an established threshold. Each was given BPO 5% for 3 consecutive days of application on either the left or right shoulder as indicated by a random number generator. Deep sebaceous gland cultures were obtained with a detergent scrub technique before BPO application, after 3 days of use, and 1 week after BPO treatment commenced. Results The differences between the logarithmic reduction and the logarithmic rebound at the anterior, lateral, and posterior sites were statistically significant. Anteriorly, the average log reduction was −0.44 and the average log rebound was 0.69 (P = .003). Laterally, reduction was −0.64 and rebound was 0.74 (P = .003). Posteriorly, reduction was −0.63 and rebound was 0.78 (P = .008). At the axilla, reduction was −0.40 and rebound was 0.31 (P = .10). The differences in C acnes burden between pretreatment and 1-week counts at all sites were not statistically significant. Conclusion A significant decrease in C acnes burden occurred after BPO application but was not permanent. Significant rebound occurred just 1 week later.
Increased mitochondrial apoptotic priming with targeted therapy predicts clinical response to re‐induction chemotherapy

Most patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) do not benefit from current re-induction or approved targeted therapies. In the absence of targetable genetic mutations, there is minimal guidance on optimal treatment selection particularly in the R/R setting highlighting an unmet need for clinically useful functional biomarkers. Blood and bone marrow samples from patients treated on two clinical trials were used to test the combination of lenalidomide (LEN) and MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy in R/R AML patients. The bone marrow samples were available to test the clinical utility of the mitochondrial apoptotic BH3 and dynamic BH3 profiling (DBP) assays in predicting response, as there was no clear genetic biomarker identifying responders. To test whether LEN-induced mitochondrial priming predicted clinical response to LEN-MEC therapy, we performed DBP on patient myeloblasts. We found that short-term ex vivo treatment with lenalidomide discriminated clinical responders from non-responders based on drug-induced change in priming (delta priming). Using paired patient samples collected before and after clinical LEN treatment (prior to MEC dosing), we confirmed LEN-induced increased apoptotic priming in vivo, suggesting LEN enhanced vulnerability of myeloblasts to cytotoxic MEC chemotherapy. This is the first study demonstrating the potential role of DBP in predicting clinical response to a combination regimen. Our findings demonstrate that functional properties of relapsed AML can identify active therapies.
Documentary and disability: edited by Catalin Brylla and Helen Hughes, London, Palgrave Macmillan, 2017, 299 pp., $139.99 (hardcover), ISBN: 9781137598936

Documentary and Disability is edited by Catalin Brylla and Helen Hughes, senior lecturers in film and film studies (respectively) whose areas of interest illustrate the interdisciplinarity of both ...
Adapting rapid assessment procedures for implementation research using a team-based approach to analysis: a case example of patient quality and safety interventions in the ICU.

Innovations to improve quality and safety in healthcare are increasingly complex, targeting multiple disciplines and organizational levels, and often requiring significant behavior change by those delivering care. Learning health systems must tackle the crucial task of understanding the implementation and effectiveness of complex interventions, but may be hampered in their efforts by limitations in study design imposed by business-cycle timelines and implementation into fast-paced clinical environments. Rapid assessment procedures are a pragmatic option for producing timely, contextually rich evaluative information about complex interventions implemented into dynamic clinical settings. We describe our adaptation of rapid assessment procedures and introduce a rapid team-based analysis process using an example of an evaluation of an intensive care unit (ICU) redesign initiative aimed at improving patient safety in four academic medical centers across the USA. Steps in our approach included (1) iteratively working with stakeholders to develop evaluation questions; (2) integration of implementation science frameworks into field guides and analytic tools; (3) selecting and training a multidisciplinary site visit team; (4) preparation and trust building for 2-day site visits; (5) engaging sites in a participatory approach to data collection; (6) rapid team analysis and triangulation of data sources and methods using a priori charts derived from implementation frameworks; and (7) validation of findings with sites. We used the rapid assessment approach at each of the four ICU sites to evaluate the implementation of the sites’ innovations. Though the ICU projects all included three common components, they were individually developed to suit the local context and had mixed implementation outcomes. We generated in-depth case summaries describing the overall implementation process for each site; implementation barriers and facilitators for all four sites are presented. One of the site case summaries is presented as an example of findings generated using the method. A rapid team-based approach to qualitative analysis using charts and team discussion using validation techniques, such as member-checking, can be included as part of rapid assessment procedures. Our work demonstrates the value of including rapid assessment procedures for implementation research when time and resources are limited.
Does Formal Training in Medical Education and Professional Development Lead to Better Career Outcomes for Clinician Educators

OBJECTIVES Medical school and residency training programs rely on skilled clinician-educators to provide high-quality educational experiences. In 2002, the University of Pittsburgh's Institute for Clinical Research Education created a master's-level degree-granting program in medical education, which now has more than a decade of graduates. METHODS All graduates between 2004 and 2014 were invited to complete an anonymous electronic survey regarding their experiences with the program and their perception of whether the master's program adequately prepared them in domains pertinent to medical educators. Participants also were asked to upload their current curricula vitae (CV) to assess objective measures of academic productivity among program graduates. RESULTS More than 75% of surveys were completed (47/60) and 75% of CVs were submitted (45/60). Demographics of respondents showed that 66% were woman. The racial demographics of respondents revealed 13% Hispanic/Latino, 28% Asian, and 59% white, respectively. More than 90% of respondents agreed that because they completed the program, they were competent in multiple teaching and learning domains; 94% of respondents believed that they were more effective educators than peers who did not complete this degree. CV abstraction revealed that 98% of respondents currently held academic positions. Number of publications and number of years since program graduation were used to determine the rate of productivity of the graduates. Twenty-six graduates (58%) successfully published at least one peer-reviewed article per year since they graduated. This equated to approximately 3.77 publications per year for these 26 respondents and 2.27 publications per year for the entire cohort. CONCLUSIONS Program graduates attributed their competence in several key domains that are crucial to excellence as a clinician-educator to their participation in the degree-granting program. The results of this study suggest that receipt of a graduate-level degree in medical education develops and enhances teaching skills and academic productivity among clinician-educators.
Limit theorems for process-level Betti numbers for sparse and critical regimes

The objective of this study is to examine the asymptotic behavior of Betti numbers of Cech complexes treated as stochastic processes and formed from random points in the d-dimensional Euclidean space . We consider the case where the points of the Cech complex are generated by a Poisson process with intensity nf for a probability density f. We look at the cases where the behavior of the connectivity radius of the Cech complex causes simplices of dimension greater than to vanish in probability, the so-called sparse regime, as well when the connectivity radius is of the order of , the critical regime. We establish limit theorems in the aforementioned regimes: central limit theorems for the sparse and critical regimes, and a Poisson limit theorem for the sparse regime. When the connectivity radius of the Cech complex is , i.e. the sparse regime, we can decompose the limiting processes into a time-changed Brownian motion or a time-changed homogeneous Poisson process respectively. In the critical regime, the limiting process is a centered Gaussian process but has a much more complicated representation, because the Cech complex becomes highly connected with many topological holes of any dimension.
Initial Validation of a Math Progress Monitoring Measure for Prekindergarten Students.

Given the importance of math in today’s society, it is critical that children who are at risk for math difficulty are identified early. We developed and validated a prekindergarten math subtest (i....
Abstract 2757: Analysis of stromal myofibroblasts identifies secreted proteins that promote pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most incurable types of cancer. Cancer that develops in the acinar cells of the pancreas is typically not diagnosed until later stages, such as stage 3 or 4. As such, this form of cancer is particularly lethal with only 9% of patients reaching 5-year survival. PDAC is known to have a particularly dense extracellular matrix composed of fibroblasts, which have been previously shown to play an important role in promoting resistance to drug therapy. Characterization of the stromal networks involved in PDAC tumor development as well as protein markers of fibroblast subpopulations within the tumor stroma are critical to developing new fibroblast-targeted therapeutic approaches as well as understanding key signaling molecules that ultimately promote tumor progression and drug resistance. Single-cell RNA sequencing (scRNAseq) was utilized to analyze cancer-associated fibroblasts (CAFs) from KPC mouse-derived, MT3 subcutaneous murine allografts along with two fibroblast lines derived from human PDAC tumors: CRC-811 and IA-1340. Single cell gene expression profiling and subsequent analysis of MT3-derived CAFs resulted in the identification of three CAF subpopulations including a myofibroblast subpopulation that expressed high levels of smooth muscle actin (Acta2), which was also observed in both human samples. Fibroblast subpopulations enriched in Acta2 expression, expressed high levels of Wnt5a along with several other secreted factors including Tgfb1, Tgfb2 and Ctgf. Wnt5a is a secreted protein that activates non-canonical Wnt signaling pathways and is known to regulate normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However Wnt5a is not natively expressed in MT3 cancer cells derived from syngeneic tumors, but potentially in the stroma. We hypothesize it is exclusively derived from fibroblasts. Previously it has been shown that Wnt5a inhibition suppressed gastric cancer metastasis, therefore further validation of the role of myofibroblast-derived Wnt5a on PDAC disease progression is warranted. This study received funding by LDRD 19-SI-003. This work was conducted under the auspices of the USDOE by LLNL (DE-AC52-07NA27344). IM Release Number: LLNL-ABS-798442. Citation Format: Kelly A. Martin, Aimy Sebastian, Nicholas R. Hum, Stephen Byers, Elizabeth K. Wheeler, Matthew A. Coleman, Gabriela G. Loots. Analysis of stromal myofibroblasts identifies secreted proteins that promote pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2757.
STOCHASTIC CONTEXT-FREE GRAMMARS FOR MODELLING RNA

Stochastic context-free grammars (SCFGs) are applied to the problems of folding, aligning and modeling families of homologous RNA sequences. These models capture the common primary and secondary structure of the sequences with a context-free grammar, much like those used to define the syntax of programming languages. SDFGs generalize the hidden Markov models used in related work on protein and DNA sequences. The novel aspect of this work is that the SCFGs developed here are learned automatically from initially unaligned and unfolded training sequences. To do this, a new generalization of the forward- backward algorithm, commonly used to train hidden Markov models, is introduced. This algorithm is based on tree grammars, and is more efficient than the inside-outside algorithm, which was previously proposed to train SCFGs. This method is tested on the family of transfer RNA (tRNA) sequences. The results show that the model is able to reliably discriminate tRNA sequences from other RNA sequences of similar length, that it can reliably determine the secondary structure of new tRNA sequences, and that it can produce accurate multiple alignments of large collections of tRNA sequences. The model is also extended to handle introns present in tRNA genes.
Thirlwall's law is not a tautology, but some empirical tests of it nearly are

This article examines the charge that Thirlwall's law is a theoretical tautology. It shows that a certain approach to empirical testing of that law can sometimes â€“ under conditions analysed here â€“ result in econometric estimates that reflect an approximate identity or 'near-tautology'. Nevertheless, other methods of empirically testing the law are not subject to the near-tautology critique, and hence the theory itself is not a tautology. Econometric estimates for the US and Mexico reveal that the near-tautology critique applies to data for the former but not the latter; the difference in these results is explained by exactly the reasons discussed here. The article offers an alternative interpretation of Thirlwall's law as implying a benchmark for analysing whether national income, rather than relative prices, is the main adjusting factor in response to current-account imbalances in the long run.
Effect of Parenteral Nutrition and Albumin in Oxygen Escalation/De-Escalation in SARS-CoV-2 Infected Patients Who are Pre-Intubation: A Multicenter, Observational Study in NYC

Background: SARS-CoV-2 infection includes a variety of gastrointestinal manifestations along with the usual viral symptoms of malaise and myalgias. The objective of this study was to determine if intravenous parenteral nutrition (PN) affected the risk of intubation in SARS-CoV-2 patients who were dependent on CPAP or BiPAP. This was the first study to investigate the role of nutrition in patients with severe SARS-CoV-2 infection. Methods: Retrospective, multicenter case-control study which analyzed oxygen requirements for 1974 adults with SARS-CoV-2, who were admitted to the NYCHHC system between March 1 and May 17, 2020. The exposure of interest was PN. Relevant baseline biomarkers were studied over 5 days. The main outcome was an escalation or de-escalation of oxygen requirements. Findings: 111 patients received PN while on CPAP/BiPAP. In the PN and control groups, there was a significant change between days 0-1 of oxygen requirements, suggesting changes within 24 hours after initiation on CPAP/BiPAP is suggestive for escalation or de-escalation of oxygen requirements. Day 0 albumin level was the only predictive marker for oxygen escalation in both the PN group (p<0.001) and the control group (p<0.001). Interpretation: Initiating PN in the setting of non-invasive ventilation of SARS-CoV-2 infected patients was significantly associated with a decrease in oxygen requirements over the initial 24 hours. Day 0 serum albumin level was predictive for oxygen escalation/de-escalation with marked improvement noted in patients who received PN. PN does not exacerbate oxygen requirements in SARS-CoV-2 infected pre-intubated patients. Funding: NYCHHC Office of Population Health. Conflict of Interest: None to declare. Ethical Approval: The protocol was approved by the Biomedical Research Alliance of New York (BRANY) via the NYCHHC institutional review board and sponsored by NYCHHC’s Office of Population Health.