cssi/SciSciGPT-SciSciNet huggingface dataset:
Irreducible fracture-dislocation of the distal interphalangeal joint. A case report.

Advances in shoulder replacement surgery have allowed for the successful treatment of various shoulder conditions. As the elderly population increases and the surgical indications for shoulder replacement surgery continue to expand, the number of shoulder replacements performed annually will continue to increase. Accordingly, the number of complications also will be expected to increase. Successful shoulder replacement outcomes require surgeons to have a thorough understanding of the surgical indications, surgical technique, and potential complications of the procedure. By reviewing the key aspects of shoulder replacement surgery and focusing on the surgical technique and common complications for both anatomic and reverse total shoulder arthroplasty, surgeons can help improve outcomes and minimize complications.
In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin Analog

The aim of this research was to characterize the in vivo and in vitro properties of basal insulin peglispro (BIL), a new basal insulin, wherein insulin lispro was derivatized through the covalent and site-specific attachment of a 20-kDa polyethylene-glycol (PEG; specifically, methoxy-terminated) moiety to lysine B28. Addition of the PEG moiety increased the hydrodynamic size of the insulin lispro molecule. Studies show there is a prolonged duration of action and a reduction in clearance. Given the different physical properties of BIL, it was also important to assess the metabolic and mitogenic activity of the molecule. Streptozotocin (STZ)-treated diabetic rats were used to study the pharmacokinetic and pharmacodynamic characteristics of BIL. Binding affinity and functional characterization of BIL were compared with those of several therapeutic insulins, insulin AspB10, and insulin-like growth factor 1 (IGF-1). BIL exhibited a markedly longer time to maximum concentration after subcutaneous injection, a greater area under the concentration-time curve, and a longer duration of action in the STZ-treated diabetic rat than insulin lispro. BIL exhibited reduced binding affinity and functional potency as compared with insulin lispro and demonstrated greater selectivity for the human insulin receptor (hIR) as compared with the human insulin-like growth factor 1 receptor. Furthermore, BIL showed a more rapid rate of dephosphorylation following maximal hIR stimulation, and reduced mitogenic potential in an IGF-1 receptor–dominant cellular model. PEGylation of insulin lispro with a 20-kDa PEG moiety at lysine B28 alters the absorption, clearance, distribution, and activity profile receptor, but does not alter its selectivity and full agonist receptor properties.
Pott Disease in a 13-Month-Old: Case Report

Background and importance Tuberculosis (TB) is a common disease worldwide that is caused by Mycobacterium tuberculosis. TB of the spine is the most common site of bony infection and is often referred to as Pott disease. To the best of our knowledge, our case represents the youngest patient with naturally acquired Pott disease in the United States. Clinical presentation A 13-month-old boy presented with paraplegia and a known diagnosis of TB. His evaluation revealed a kyphotic gibbus deformity in the midthoracic region associated with severe spinal cord compression. The patient underwent urgent decompressive laminectomies, T2-T4 transpedicular corpectomies, placement of an anterior tibial strut graft, and posterior instrumentation with sublaminar wires and a Steinmann pin. At his 18-month follow-up, the patient was ambulating 5 steps at a time independently, and his kyphotic deformity showed no sign of progression. Conclusion Pott disease can occur in very young children and presents a unique challenge when a patient presents with a neurological deficit and unstable deformity requiring surgical intervention.
Comparison of Repeated and Non-Repeated Readings on the Reading Performances of Students With Emotional and Behavioral Disorders

This study used an alternating treatments design to compare the effects of three conditions on the reading fluency, errors, and comprehension of four, sixth-grade students with emotional and behavi...
Determination of kirenol from Xitong capsule in rat plasma by RP-HPLC

Objective To determine the content of kirenol in rat plasma after ig.administration of Xitong capsule(traditional Chinese medicines).Methods Forsythin was used as the internal standard.The plasma samples were prepared using a liquied-liquied extraction.A C18 column was used,with the mobile phase of acetonitrile-water(V∶V=28.5∶71.5)with the flow rate of 1.0 mL·min-1,at the detection wavelength of 215 nm and at the column temperature of 35 ℃.Results The calibration curve of kirenol was linear in the concentration range of 0.04-2.00 mg·L-1(r=0.998 4).The RSDs of inter-and intra-day were less than 15%.The average extraction recoveries were(83.4±3.6)%,(82.2±4.9)% and(80.5±2.5)% at concentrations of 0.08,0.40 and 1.60 mg·L-1,respectively.The main pharmacokinetic parameters:ke=(0.06±0.01)h-1,t1/2=(11.86±1.66)h,AUC0-24=(4.910±0.969)(mg·h·L-1).Conclusions This method is accurate and reliable,which can be available at the study of the pharmacokinetics of kirenol from Xitong capsule.
Effect of Herbal Decoction for Invigorating the Spleen to Dissolve Damp on Infantile Rotavirus Enteritis and on Myocardial Enzymes

Objective To observe the effect of herbal decoction for invigorating the spleen to dissolve damp on infantile rotavirus enteritis (IRVE) and myocardial enzymes.Methods Eighty patients were randomized into a treated group and a control group.The former was treated with the herbal decoction which could invigorate the functions of spleen to dissolve damp,the latter treated with Smecta.The course of treatment for both groups was 3 days.The changes in the symptoms of diarrhea,vomiting,and fever were observed and the myocardial enzymes including aspartate aminotransferase (AST),lactic dehydrogenase (LDH),creatine phosphokinase (CK) and CK-MB were determined.Results The effect of the treated group in stopping diarrhea,relieving fever,and stopping vomiting was all superior to that of the contro1 group (P0.01).CK-MB,CK,and AST of both groups were significantly decreased after treatment (P0.01 or P0.05),and the decrease of CK-MB of the treated group was more than that of the control group (P0.05).LDH of both groups was not improved compared with before treatment (P0.05).Conclusion The herbal decoction for invigorating the spleen to dissolve damp in the treatment of IRVE functions to shorten the course of disease,improve the symptoms,and reduce the damage of cardiac muscles.
Spectral Changes Induced by Scattering From Space-Time Fluctuations

In the majority of theoretical studies dealing with the scattering of electromagnetic waves on random media one assumes that the incident field is monochromatic and that the density fluctuations of the medium may be described by equilibrium thermodynamics. In the last few years it was found that when these restrictions are removed, a number of interesting new phenomena are revealed. In this talk a review of these developments is presented. In particular an account is given of several recent investigations regarding spectral changes produced by scattering of light of any state of coherence and polarization and with arbitrary spectrum on a medium whose response is random both in space and in time, but is statistically homogeneous, isotropic and stationary, at least in the wide sense. It is shown that the spectrum of the radiation may be shifted towards the longer or towards the shorter wavelengths by the scattering process, thus inducing redshifts or blueshifts of spectral lines;2 and moreover, that conditions may be found which ensure that these shifts imitate the Doppler effect in its essential features, even though the source of the radiation, the scatterer and the observer are all at rest relative to each other.3,4 This possibility is of particular interest for astronomy.5
Cardiac Risk and Disordered Eating: Decreased R Wave Amplitude in Women with Bulimia Nervosa and Women with Subclinical Binge/Purge Symptoms.

The purpose of the present study was threefold. First, we examined whether women with bulimia nervosa (n = 12) and women with subthreshold binge/purge symptoms (n = 20) showed decreased mean R wave amplitude, an indicator of cardiac risk, on electrocardiograph compared to asymptomatic women (n = 20). Second, we examined whether this marker was pervasive across experimental paradigms, including before and after sympathetic challenge tasks. Third, we investigated behavioural predictors of this marker, including binge frequency and purge frequency assessed by subtype (dietary restriction, excessive exercise, self-induced vomiting, and laxative abuse). Results of a 3 (ED symptom status) × 5 (experimental condition) mixed factorial ANCOVA (covariates: body mass index, age) indicated women with bulimia nervosa and women with subclinical binge/purge symptoms demonstrated significantly reduced mean R wave amplitude compared to asymptomatic women; this effect was pervasive across experimental conditions. Multiple regression analyses showed binge and purge behaviours, most notably laxative abuse as a purge method, predicted decreased R wave amplitude across all experimental conditions. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.
Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly

ABSTRACT Giant tailed bacterial viruses, or phages, such as Pseudomonas aeruginosa phage ϕKZ, have long genomes packaged into large, atypical virions. Many aspects of ϕKZ and related phage biology are poorly understood, mostly due to the fact that the functions of the majority of their proteins are unknown. We hypothesized that the Salmonella enterica phage SPN3US could be a useful model phage to address this gap in knowledge. The 240-kb SPN3US genome shares a core set of 91 genes with ϕKZ and related phages, ∼61 of which are virion genes, consistent with the expectation that virion complexity is an ancient, conserved feature. Nucleotide sequencing of 18 mutants enabled assignment of 13 genes as essential, information which could not have been determined by sequence-based searches for 11 genes. Proteome analyses of two SPN3US virion protein mutants with knockouts in 64 and 241 provided new insight into the composition and assembly of giant phage heads. The 64 mutant analyses revealed all the genetic determinants required for assembly of the SPN3US head and a likely head-tail joining role for gp64, and its homologs in related phages, due to the tailless-particle phenotype produced. Analyses of the mutation in 241, which encodes an RNA polymerase β subunit, revealed that without this subunit, no other subunits are assembled into the head, and enabled identification of a “missing” β′ subunit domain. These findings support SPN3US as an excellent model for giant phage research, laying the groundwork for future analyses of their highly unusual virions, host interactions, and evolution. IMPORTANCE In recent years, there has been a paradigm shift in virology with the realization that extremely large viruses infecting prokaryotes (giant phages) can be found in many environments. A group of phages related to the prototype giant phage ϕKZ are of great interest due to their virions being among the most complex of prokaryotic viruses and their potential for biocontrol and phage therapy applications. Our understanding of the biology of these phages is limited, as a large proportion of their proteins have not been characterized and/or have been deemed putative without any experimental verification. In this study, we analyzed Salmonella phage SPN3US using a combination of genomics, genetics, and proteomics and in doing so revealed new information regarding giant phage head structure and assembly and virion RNA polymerase composition. Our findings demonstrate the suitability of SPN3US as a model phage for the growing group of phages related to ϕKZ.
Measurement-based analysis of the video characteristics of Twitch.tv

Technology advances have brought a growth in live streaming, where users can broadcast real-time videos of the games they are playing to interested viewers. While characteristics of traditional video on demand sites are relatively well understood, live streaming has received comparatively less attention. A better understanding of such systems is needed to plan for future systems and architectures. This paper uses a crawler and stream analyzer to characterize Twitch.tv, the most popular live streaming system for games. Analysis of the data confirms live stream volume from previous research, while providing novel frame rate and bitrate analysis.
Immunotherapeutic Strategies Directed at the Trimolecular Complex

Publisher Summary This chapter discusses earlier experience in preventing the formation of the ternary complex and discusses some newer attempts to induce unresponsiveness in experimental animals. The three components of the complex serve as independent targets for development of strategies aimed at disrupting the trimolecular complex. The earliest attempts at immunotherapy targeting the T cell used anti-lymphocyte serum and monoclonal antibodies directed at the Thy-1 antigen, a marker for all T cells, to eliminate or downregulate T cell activation. The development of hybridoma technology made available reagents, which could target a specific cell population. The chapter discusses the use of antibodies directed at various proteins on the T cell surface in regulating T cell responses, examines T cells as effectors of immune regulation. This approach involves the use of antigen-specific T cell lines or clones as vaccinating agents to elicit “anti-idiotypic” regulator T cells capable of inhibiting the response of the antigen-specific T cell population. As opposed to passive administration of antibodies, this approach involves active participation of the individual's immune system in inducing a regulatory response to the immunizing cells. Among the potential immunotherapeutic strategies outlined in this chapter the most favored is the therapy that is most selective in turning off autoantigen-specific T cells while sparing the rest of the immune response.
ELMO proteins transduce G protein-coupled receptor signal to control reorganization of actin cytoskeleton in chemotaxis of eukaryotic cells

Chemotaxis, which is chemoattractant-guided directional cell migration, plays major roles in recruitment of neutrophils, the metastasis of cancer cells, and the development of the model organism Dictyostelium discoideum. These cells share remarkable similarities in the signaling pathways by which they control chemotaxis. They all use a G protein-coupled receptor (GPCR)-mediated signal transduction pathway to sense the chemotactic gradient to guide cell migration. Diverse chemokines activate Rac through conserved GPCR signaling pathways. ELMO proteins are an evolutionarily conserved, essential component of the ELMO/Dock complex, which functions as a guanine nucleotide exchange factor (GEF) for small G protein Rac activation. The linkages between the GPCR-initiated gradient sensing compass and the Rac-mediated migrating machinery have long been missing. Here, we summarize recent findings on ELMO proteins that directly interact with G protein and transduce GPCR signaling to control the reorganization of actin-based cytoskeleton through regulating Rac activation during chemotaxis, first in D. discoideum and then in mammalian cancer cells. This represents an evolutionarily conserved signaling shortcut from GPCR to the actin cytoskeleton.
Rehabilitation and Postoperative Management Practices After Osteochondral Allograft Transplants to the Distal Femur: A Report From the Metrics of Osteochondral Allografts (MOCA) Study Group 2016 Survey.

Context:We present the current spectrum of postoperative management practices for patients receiving distal femur osteochondral allograft (OCA) transplants.Evidence Acquisition:The Joint Restoratio...
Effect of chronic stress on running wheel activity in mice

Acute and chronic stress have been reported to have differing effects on physical activity in rodents, but no study has examined a chronic stress protocol that incorporates stressors often experienced by rodents throughout a day. To examine this, the effects of the Unpredictable Chronic Mild Stress (UCMS) protocol on voluntary running wheel activity at multiple time points, and/or in response to acute removal of chronic stress was determined. Twenty male Balb/c mice were given access and accustomed to running wheels for 4 weeks, after which they were randomized into 2 groups; exercise (EX, n = 10) and exercise with chronic stress using a modified UCMS protocol for 7 hours/day (8:00 a.m.-3:00p.m.), 5 days/week for 8 weeks (EXS, n = 10). All mice were given access to running wheels from approximately 3:30 p.m. to 7:30 a.m. during the weekday, however during weekends mice had full-time access to running wheels (a time period of no stress for the EXS group). Daily wheel running distance and time were recorded. The average running distance, running time, and work each weekday was significantly lower in EXS compared to EX mice, however, the largest effect was seen during week one. Voluntary wheel running deceased in all mice with increasing age; the pattern of decline appeared to be similar between groups. During the weekend (when no stress was applied), EXS maintained higher distance compared to EX, as well as higher daily distance, time, and work compared to their weekday values. These results indicate that mild chronic stress reduces total spontaneous wheel running in mice during the first week of the daily stress induction and maintains this reduced level for up to 8 consecutive weeks. However, following five days of UCMS, voluntary running wheel activity rebounds within 2-3 days.
Partisanship, Militarized International Conflict, and Electoral Support for the Incumbent:

Comparative politics scholarship often neglects to consider how militarized interstate disputes (MIDs) shape political behavior. In this project, we advance an argument that considers voter responses to international conflict at the individual level. In particular, we consider how the well-known conditioning effects of partisanship manifest in relation to militarized international conflict. Examining individual- and macro-level data across ninety-seven elections in forty-two countries over the 1996–2011 period, we find consistent evidence of militarized conflict impacting vote choice. This relationship is, however, moderated by partisanship, conflict side (initiator or target), and conflict hostility level. Among non-copartisan voters, the incumbent benefits the most electorally from initiating low-hostility MIDs or when the country is a target of a high-hostility MID; the opposite scenarios (initiator of a high-hostility MID or target of a low-hostility MID) lead to punishment among this voter group. Cop...
Krylov subspace based model order reduction of distribution networks

With the introduction of distributed energy resources there is increased use of power electronics to control and compensate distribution networks due to the occurrence of bi-directional power flows. This motivates the need for reduced order models of medium voltage distribution circuits for use in designing control systems and compensators. This work presents the use of shifted interpolation points as an option to further improve the accuracy of reduced order models. In this research, the IEEE 123 Node Test Feeder is reduced to 72- and 42-order. It is shown that the accuracy is not considerably improved between the 72-order and 42-order reduced systems. The accuracy of the reduced system was improved after performing the reduction by shifting the interpolation point from 0 to 5. Results are validated by evaluating the time domain and frequency domain responses. An application of the model is given by simulating the inclusion of a static synchronous series compensator.
Examination of approach and avoidance inclinations on the reinforcing value of alcohol.

Abstract Although behavioral economics tends to focus on environmental factors (i.e., price, availability) that act to influence valuation of alcohol, recent research has begun to address how motivational and cognitive factors influence an individual's demand for alcohol. Motivational states, including craving, are one possible mechanism underlying the value based decision making that demand represents. Using a multidimensional model of craving (Ambivalence Model of Craving), the current study examined the relationships between indices of alcohol demand (i.e., reinforcing value of alcohol) and craving (i.e., approach inclinations), and the ways in which competing desires moderate that relationship (i.e., avoidance inclinations). Individuals who reported consuming alcohol in the past month were recruited for the study using Amazon's Mechanical Turk. A total of 529 participants (mean age = 33.03 years, SD = 8.85) completed a series of surveys assessing their drinking behavior and other alcohol-related measures. Multiple regression analyses indicated that while approach significantly predicted intensity (i.e., consumption at zero cost), Omax (i.e., the maximum alcohol expenditure) and breakpoint (i.e., the first price that seizes consumption), avoidance moderated the relationship between approach and Omax and breakpoint. Specifically, follow up analyses demonstrated that higher avoidance inclinations attenuated the effect of approach inclinations on these demand indices. Finally, despite conceptual overlap between approach, avoidance, and alcohol demand, regression analyses indicated that these constructs account for unique variance in alcohol outcomes. These results illustrate the importance of considering the effects of both approach and avoidance inclinations on an individual's valuation of alcohol.
Post-translational modification of type IV collagen with 3-hydroxyproline affects its interactions with glycoprotein VI and nidogens 1 and 2

Type IV collagen is a major component of the basement membrane and interacts with numerous other basement membrane proteins. Many of these interactions are poorly characterized. Type IV collagen is abundantly post-translationally modified with 3-hydroxyproline (3-Hyp), but 3-Hyp's biochemical role in type IV collagen's interactions with other proteins is not well established. In this work, we present binding data consistent with a major role of 3-Hyp in interactions of collagen IV with glycoprotein VI and nidogens 1 and 2. The increased binding interaction between type IV collagen without 3-Hyp and glycoprotein VI has been the subject of some controversy, which we sought to explore, whereas the lack of binding of nidogens to type IV collagen without 3-Hyp is novel. Using tandem MS, we show that the putative glycoprotein VI-binding site is 3-Hyp-modified in WT PFHR-9 type IV collagen, but not in PFHR-9 cells in which prolyl-3-hydroxylase 2 (P3H2) has been knocked out (KO). Moreover, we observed altered 3-Hyp occupancy across many other sites. Using amino acid analysis of type IV collagen from the WT and P3H2 KO cell lines, we confirm that P3H2 is the major, but not the only 3-Hyp-modifying enzyme of type IV collagen. These findings underscore the importance of post-translational modifications of type IV collagen for interactions with other proteins.
Abstract 3012: Significant Genome Wide Association Identified Between the Glycine N-Methyltransferase Gene (GNMT) and Post-Methionine Load Test Homocysteine Levels in the Vitamin Intervention for Stroke Prevention (VISP) Cohort

The Vitamin Intervention for Stroke Prevention (VISP) trial was a multi-center, controlled, double blinded clinical trial, designed to determine whether the daily intake of high dose folic acid, vitamins B6 and B12 reduced recurrent cerebral infarction. Baseline post-methionine load homocysteine levels were predictive of recurrent stroke risk in VISP. We have conducted a genome-wide association study (GWAS), investigating 2100 VISP stroke cases required to have homocysteine levels greater than the 25th percentile at enrolment. Using imputation with 1000 genomes and principal component analysis, we were able to detect an association of p≤6.70x10-17 for SNPs within, or flanking, the glycine N-methyltransferase (GNMT) gene and post-methionine load test homocysteine level. Change in homocysteine levels pre and post-methionine load test also resulted in significant GWAS scores in the chromosome 6 region (p = 2.54x10-23, rs7760250). GNMT catalyzes the conversion of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine and sarcosine via the folate one-carbon metabolism pathway. In addition to being an essential component in the conversion of methionine to homocysteine, GNMT plays a significant role in the global epigenetic state as homocysteine is an important methyl donor. This region displays significant linkage disequilibrium, warranting close analysis of the entire GNMT locus in search of both rare and common variants. Cases who carry the minor allele haplotype at associated loci had a higher level of post-methionine load homocysteine (37.69µM/L) than those who carry the major allele haplotype (27.33µM/L), inferring functional differences due to GNMT variants. Taken together these data suggest a clear and important role for GNMT in post-methionine load test homocysteine level, epigenetic state and stroke risk.
Implications of Revenue Changes for the Persistence and Valuation of Earnings

This study extends the capital markets literature for the returns-earnings relation by suggesting that revenue declines are temporary and do not necessarily result in like changes for earnings. The study hypothesizes that investors respond asymmetrically to earnings for negative and positive revenue changes. A general sample of Compustat firms produces results that are consistent with the hypothesized asymmetric market response. The result is incremental to the effects of non-recurring items, losses, positive earnings changes, and growth opportunities. An industry analysis is also consistent with the hypothesis. The results suggest future avenues for earnings management research.
A New HPLC Immunoaffinity Assay for Intact Hepatitis A Virus: Applications in Vaccine Process Development

An 8 minute HPLC immunoaffinity assay for hepatitis A intact virus (HAV) was developed using an activated aldehyde perfusive support and a purified monoclonal antibody. The assay is linear, reproducible, and sensitive for the evaluation of HAV in crude process streams over the range of 0.35 to 3.8 g of HAV injected. It presents an attractive alternative to ELISA methods for process monitoring applications.
Humor as Redemption in the Pessimistic Philosophy of Julius Bahnsen

Is humor an antidote for pessimism? One philosopher who saw humor as the only redemption in a world filled with suffering and sorrow was Julius Bahnsen (1830–81), one of the most radical pessimists of the German pessimistic tradition (1860–1900). After a brief account of the life of Bahnsen, I sketch his tragic philosophy of life, according to which life is filled with inevitable and irresolvable contradictions. The only respite from the suffering created by these contradictions, he taught, came with humor. Against his contemporary Nietzsche, Bahnsen held that art could not serve as a source of redemption from the tragedy of life. True art revealed suffering and did not try to conceal it; and true redemption came only after utter honesty, recognizing the horrors of life while still laughing at them.
HPV-Related Cancer Prevention and Control Programs at Community-Based HIV/AIDS Service Organizations: Implications for Future Engagement

Background: People living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and, men who have sex with men (MSM) are disproportionately affected by genital warts and cancers caused by human papillomavirus (HPV). We assessed community-based HIV/AIDS service organizations' (ASOs) staff awareness, knowledge, attitudes, and beliefs about HPV and effective cancer prevention tools, namely HPV vaccination, Pap, and HPV tests. The potential engagement of ASO staff in future efforts to reduce the disproportionate burden of genital warts and HPV-related cancers among HIV-positive women and MSM was explored. Methods: In May-June 2016, staff were recruited from three ASOs located in the South United States Census region-a geographical area disproportionately affected by HIV/AIDS. Participants completed a 30-min self-administered, 118-item paper and pencil survey about HPV and cancer. Data analysis was conducted using Stata/SE 14.2. Results: ASO staff (n = 30) were 83% non-Hispanic Black, 40% lesbian/gay, and worked with people living with HIV for an average of 11.4 ± 7.7 years. All reported hearing of HPV and 77% had heard of the HPV vaccine (n = 23). While all knew HPV can cause cervical cancer, only 67% knew HPV can cause anal cancer. Most (61%) thought the HPV vaccine could prevent cervical cancer. Fewer (39-48%) thought the HPV vaccine could prevent anal, oral, penile, vaginal, and vulvar cancers. All were willing to encourage MSM and female clients to talk to a healthcare provider about HPV vaccination. Almost all were willing to promote HPV vaccination to clients (91-95%) and navigate clients to adult safety net HPV vaccine providers (86-95%). More than half (59-67%) thought they could positively influence their MSM and female clients' HPV vaccine decision-making. Conclusion: HPV vaccination and the Pap and HPV tests are effective cancer prevention tools that can reduce the disproportionate burden of genital warts and HPV-related cancers among HIV-positive women and MSM. Engaging ASO staff in cancer prevention efforts may increase HPV vaccination rates and early detection of HPV-related cancers among HIV-positive women and MSM. Exploring ASOs as community-based settings for promoting effective cancer prevention tools may foster opportunities to reduce the disproportionate burden of genital warts and HPV-related cancers among HIV-positive women and MSM.
Phosphatidate-mediated regulation of lipid synthesis at the nuclear/endoplasmic reticulum membrane

In yeast and higher eukaryotes, phospholipids and triacylglycerol are derived from phosphatidate at the nuclear/endoplasmic reticulum membrane. In de novo biosynthetic pathways, phosphatidate is channeled into membrane phospholipids via its conversion to CDP-diacylglycerol. Its dephosphorylation to diacylglycerol is required for the synthesis of triacylglycerol as well as for the synthesis of phosphatidylcholine and phosphatidylethanolamine via the Kennedy pathway. In addition to the role of phosphatidate as a precursor, it is a regulatory molecule in the transcriptional control of phospholipid synthesis genes via the Henry regulatory circuit. Pah1 phosphatidate phosphatase and Dgk1 diacylglycerol kinase are key players that function counteractively in the control of the phosphatidate level at the nuclear/endoplasmic reticulum membrane. Loss of Pah1 phosphatidate phosphatase activity not only affects triacylglycerol synthesis but also disturbs the balance of the phosphatidate level, resulting in the alteration of lipid synthesis and related cellular defects. The pah1Δ phenotypes requiring Dgk1 diacylglycerol kinase exemplify the importance of the phosphatidate level in the misregulation of cellular processes. The catalytic function of Pah1 requires its translocation from the cytoplasm to the nuclear/endoplasmic reticulum membrane, which is regulated through its phosphorylation in the cytoplasm by multiple protein kinases as well as through its dephosphorylation by the membrane-associated Nem1-Spo7 protein phosphatase complex. This article is part of a Special Issue entitled Endoplasmic reticulum platforms for lipid dynamics edited by Shamshad Cockcroft and Christopher Stefan.
Extracorporeal Membrane Oxygenation as a Bridge to Initial Medical Therapy in a Patient With Decompensated Pulmonary Arterial Hypertension Presenting With Biventricular Failure.

Extracorporeal membrane oxygenation (ECMO) can be used as a bridge to medical therapy in decompensated right heart failure due to pulmonary arterial hypertension (PAH). A middle-aged man with previously undiagnosed pulmonary hypertension was successfully bridged to intravenous prostanoid therapy with venoarterial ECMO support after presenting with cardiogenic shock and hypoxemic respiratory failure. Although the patient initially had biventricular failure, PAH was suspected due to underlying mixed connective tissue disease and disproportionate right ventricular dysfunction. On occasion, patients with PAH may present with biventricular failure. A high index of suspicion for PAH and serial reassessment of left ventricular function following correction of shock may demonstrate improvement in left ventricular function, allowing for initiation of pulmonary vasodilator therapy. J Med Cases. 2019;10(9):260-263 doi: https://doi.org/10.14740/jmc3327
Effects of Under-Resolved Convective Dynamics on the Evolution of a Squall Line

AbstractSimulations of a squall line observed on 20 May 2011 during the Midlatitude Continental Convective Clouds Experiment (MC3E) using 750- and 250-m horizontal grid spacing are performed. The h...
Antagonisms of Adaptation: Climate Change Adaptation Measures in New Orleans and New York City

This chapter identifies climate change adaptation measures implemented in post-Sandy New York City and post-Katrina New Orleans and examines their conflictual and contradictory dynamics and impacts. Climate change adaption measures aim to reduce existing and future climate change risks and enhance adaptive capacity. The chapter begins with an introduction to the concepts of risk, resilience, mitigation, and adaptation. We then use a comparative-sociological approach to examine similarities and variation in adaptation dynamics in the two cities. We develop a dual argument that the decentralized and fragmented structure of policy-making and implementation in the United States both (1) frustrates and discourages the formulation and implementation of comprehensive climate change adaptation measures and (2) fosters spatially distinct locations for different types of climate change adaptation measures, a condition that buttresses local distinctiveness and innovation. The chapter focuses attention on the social structural challenges of reducing climate change risks, the various policy options in the two cities, and the facilitative and contradictory roles of the federal government in the local implementation of climate change adaptation measures.
Novel Immunotherapy Combinations

The last decade witnessed an explosion in immunotherapeutic agent approvals for various malignancies. The success of immune checkpoint inhibitors (CTLA-4 and PD-1/PD-L1) in melanoma quickly sprung to other cancer types and are considered the emerging face of oncology. Antibodies to CTLA-4 were first to enter the field, quickly followed by PD-1/PD-L1 inhibitors. Combination anti-CTLA4 and anti-PD-1/PD-L1 therapies were investigated, and after demonstrating improved responses, rapidly gained approval. Certain tumor types previously considered non-immunogenic also demonstrated durable responses which has been a remarkable discovery. However, not all tumor types respond to immunotherapies and it is widely recognized that tumor-specific immune inflammatory status predicts the best responders. Ongoing translational work indicates specific upregulation in additional immune checkpoints that circumvent response to anti-CTLA4 and anti-PD-1/PD-L1 antibodies. Here, we provide a comprehensive review of promising therapies on the horizon with unique combinations designed to overcome resistance or expand the pool of treatment responders.
NKG2A Represents an Important Immune Checkpoint for Human Cytokine-Induced Memory-like NK Cells in Patients with AML

Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell anti-leukemia potential is unclear. Paradigm-shifting reports have shown that NK cells exhibit "memory-like" properties following hapten exposure, virus infection, or combined cytokine pre-activation. We and others have established that human cytokine-induced memory-like NK cells display enhanced re-stimulation responses to numerous activating stimuli, including tumor target cells. We have translated this finding into a potential cellular therapy for rel/ref AML patients, and have completed the dose escalation of a phase 1/2 study. We demonstrated that donor memory-like NK cells expand in patients9 blood and bone marrow and retain enhanced functionality ex vivo. Further, of the 11 evaluable AML patients, we have observed 7 clinical responses, including 6 patients with CR/CRi. Since NK cell recognition depends on signals from multiple activating and inhibitory receptors, we developed mass cytometry panels to immunophenotype and track the diversity and effector functions of these human in vivo-differentiated memory-like NK cells. Mass cytometry revealed that in vivo-differentiated memory-like (ML) NK cells were distinct from baseline (BL) NK cells from the same donor, as well as NK cells from normal donor PBMC. Multidimensional analyses revealed a memory-like phenotype: CD56hi CD11blo CD62L+ NKG2Ahi NKp30hi Ki-67+ (baseline: 2.7% ± 0.45% v memory-like: 87.4% ± 5.3%, mean ± SEM within memory-like gate). Furthermore, Citrus analyses revealed that higher NKG2A expression was significantly correlated with treatment failure [TF median NKG2A= 89.2 ± 25.0; responder median NKG2A= 8.1 ± 2.9 (mean ± SEM); p = 0.007, n = 5 each group; SAM FDR In order to interrogate the role NKG2A may play in limiting cytokine-induced memory-like NK cell responses, we stimulated in vitro-differentiated ML cells with the K562 AML tumor line displaying forced expression of HLA-E (K562-E) in the presence of isotype or anti-NKG2A blocking antibody. Increased IFN-γ (p = 0.02) and TNF (p = 0.05) production by NKG2A-blocked ML NK cells was detected, compared to isotype-treated ML NK cells. We performed a similar stimulation assay using primary AML blasts as targets, which express a variable level of HLA-E. Again, ML NK cells treated with NKG2A blockade produced significantly more IFN-γ than isotype-treated ML NK cells (p = 0.001). Studies examining NKG2A checkpoint blockade on in vivo-differentiated ML NK cells from AML patients are ongoing. In conclusion, in vivo-differentiated cytokine-induced memory-like NK cells are phenotypically distinct from conventional NK cells. Further, targeting NKG2A expressed on ML NK cells in vivo has the potential to enhance the clinical efficacy of memory-like NK cell therapy for patients. Disclosures No relevant conflicts of interest to declare.
Impact of a case-based collaborative learning curriculum on knowledge and learning preferences of dermatology residents

Abstract Objective Case-based collaborative learning (CBCL) models that incorporate learner-guided content review, structured preparatory assessment, and interactive case-based classroom sessions have been shown to promote content mastery among medical students. However, limited research has explored the viability of CBCL in resident populations, particularly in dermatology. We therefore sought to investigate the impact of a CBCL curriculum covering complex medical dermatology topics on resident knowledge and learning preferences. Methods This prospective cohort study included dermatology and combined internal medicine-dermatology resident trainees of all levels (postgraduate years 2–5) in a single residency program in Boston, Massachusetts. Four CBCL sessions covering complex medical dermatology topics were delivered to program residents between March and April 2019. Preparatory material for each session included a 20-minute concept video and a multiple-choice readiness assessment. During the sessions, residents applied their nascent understanding to newly introduced clinical vignettes and cases covering the preassigned materials. To assess knowledge and learner preferences, 15-question surveys were administered before and immediately after curriculum delivery. Changes in knowledge and learner preferences were determined using Student t tests to compare means and χ2 tests to compare proportions. Results Of the 30 residents, 29 (96.7%) completed the precurriculum survey and 17 (56.7%) completed the postcurriculum survey. Mean content scores improved significantly (p Conclusion In this single-center prospective cohort study, resident knowledge improved significantly after CBCL curriculum delivery. Most resident learners viewed the curriculum as worthwhile and preferred it to traditional lecture-based didactics. Collectively, our findings suggest that CBCL models can be feasibly implemented and durably convey complex content to resident learners.
On Content Uniformity for Beliefs and Desires

The view that dominates the literature on intentional attitudes holds that beliefs and desires both have propositional content. A commitment to what I call “content uniformity” underlies this view. According to content uniformity, beliefs and desires are but different psychological modes having a uniform kind of content. Prima facie, the modes don’t place any constraint on the kinds of content the attitude can have. I challenge this consensus by pointing out an asymmetry between belief contents and desire contents which shows content uniformity to be mistaken. I do this by revisiting the arguments of Richard (Philosophical Studies, 39(1): 1–13, 1981), and show that arguments which purport to show the temporal specificity of belief contents yield the opposite results for desire contents. I defend this preliminary conclusion from various strategies to neutralize the asymmetry claim. My defense provides occasions to respond to objections by Brogaard (2012) and Recanati (2007) to the Richard argument, and to get clearer on the role of temporal adjuncts in desire ascriptions. Finally, I consider whether the construal of attitude content as centered propositions (as in Lewis Philosophical Review, 88(4): 513–543, 1979) can be invoked to vindicate content uniformity. My conclusion is that while the framework itself doesn’t vindicate content uniformity, it could, but only if it availed itself of a further, substantive thesis about desire, which itself is in need of defense.
Evidence-based smoking cessation treatment: a comparison by healthcare system.

A systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited. We surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017–2019. Of 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3–14.4; p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC, p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHC p = 0.001). VHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems’ prioritization of and investment in smoking cessation treatment is critical to improving providers’ adherence to guidelines.
Prolonged grief disorder: Course, diagnosis, assessment, and treatment

Losing a loved one is one of life's greatest stressors. Although most bereaved individuals navigate through a period of intense acute grief that lessens with time, approximately 10% will develop a prolonged grief condition. This review provides an overview of the course of grief and describes risk factors for developing prolonged grief disorder. The evolution of the prolonged grief disorder diagnosis, including the latest criteria sets for ICD-11 and DSM-5, as well as common comorbid conditions and differential diagnosis are discussed. Clinically useful self-report and clinician-rated measures for assessing symptom constructs and overall prolonged grief disorder severity, evidence-based psychotherapies (such as complicated grief treatment), as well as evidence about pharmacologic approaches are presented. Finally, the authors discuss important future directions, including a potential increase in prolonged grief disorder cases due to the COVID-19 pandemic.
Structure-activity and mechanistic studies of non-peptidic inhibitors of the PLK1 polo box domain identified through REPLACE.

Abstract Polo-like kinase 1 (PLK1) is a serine/threonine-protein kinase involved in cell cycle regulation and mitotic progression. Studies have shown that PLK1 is upregulated in many tumors and high levels are adversely related to a poor prognosis. Knocking down or inhibiting PLK1 results in synthetic lethality in PTEN deficient prostate tumors and Kras mutant colorectal tumors, further validating PLK1 as an oncotarget. Substrate recognition by PLK1 occurs through the Polo-Box Domain (PBD), which is a phospho-peptide binding site also responsible for subcellular localization. Much effort has been directed to target this kinase therapeutically through the ATP-binding site, and a few such inhibitors have advanced to clinical trials however with limited clinical efficacy. Moreover, it has been shown that a point mutation in PLK1 (C67V) confers dramatic cellular resistance to catalytic site inhibitors. An alternative approach to target PLK1 potently and selectively is through the PBD to block its protein-protein interactions. Through the REPLACE strategy, for converting peptide inhibitors into more drug-like non peptidic compounds, a PBD targeting compound series (“ABBAs”), has been identified and the key determinants of potency and selectivity elucidated through structure-activity relationship studies. In cellular experiments, the ABBAs were shown to lead to profound effects on the cell cycle, to inhibit tumor proliferation and overcome resistance of cells expressing the PLK1 C67V mutant to ATP-based inhibitors. These non-ATP competitive inhibitors of PLK1 were also used chemical biology probes to investigate the gene regulatory effects of PLK1, known to act on transcription factors such as p53.