cssi/SciSciGPT-SciSciNet huggingface dataset:
Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period

Importance Chronic opioid use imposes a substantial burden in terms of morbidity and economic costs. Whether opioid-naive patients undergoing surgery are at increased risk for chronic opioid use is unknown, as are the potential risk factors for chronic opioid use following surgery. Objective To characterize the risk of chronic opioid use among opioid-naive patients following 1 of 11 surgical procedures compared with nonsurgical patients. Design, Setting, and Participants Retrospective analysis of administrative health claims to determine the association between chronic opioid use and surgery among privately insured patients between January 1, 2001, and December 31, 2013. The data concluded 11 surgical procedures (total knee arthroplasty [TKA], total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery [FESS], cataract surgery, transurethral prostate resection [TURP], and simple mastectomy). Multivariable logistic regression analysis was performed to control for possible confounders, including sex, age, preoperative history of depression, psychosis, drug or alcohol abuse, and preoperatice use of benzodiazepines, antipsychotics, and antidepressants. Exposures One of the 11 study surgical procedures. Main Outcomes and Measures Chronic opioid use, defined as having filled 10 or more prescriptions or more than 120 days’ supply of an opioid in the first year after surgery, excluding the first 90 postoperative days. For nonsurgical patients, chronic opioid use was defined as having filled 10 or more prescriptions or more than 120 days’ supply following a randomly assigned “surgery date.” Results The study included 641 941 opioid-naive surgical patients (169 666 men; mean [SD] age, 44.0 [12.8] years), and 18 011 137 opioid-naive nonsurgical patients (8 849 107 men; mean [SD] age, 42.4 [12.6] years). Among the surgical patients, the incidence of chronic opioid in the first preoperative year ranged from 0.119% for Cesarean delivery (95% CI, 0.104%-0.134%) to 1.41% for TKA (95% CI, 1.29%-1.53%) The baseline incidence of chronic opioid use among the nonsurgical patients was 0.136% (95% CI, 0.134%-0.137%). Except for cataract surgery, laparoscopic appendectomy, FESS, and TURP, all of the surgical procedures were associated with an increased risk of chronic opioid use, with odds ratios ranging from 1.28 (95% CI, 1.12-1.46) for cesarean delivery to 5.10 (95% CI, 4.67-5.58) for TKA. Male sex, age older than 50 years, and preoperative history of drug abuse, alcohol abuse, depression, benzodiazepine use, or antidepressant use were associated with chronic opioid use among surgical patients. Conclusions and Relevance In opioid-naive patients, many surgical procedures are associated with an increased risk of chronic opioid use in the postoperative period. A certain subset of patients (eg, men, elderly patients) may be particularly vulnerable.
Simple Kinetic Models of Sorting

In Chapter 3, the distribution of receptors and ligands in the endosome at equilibrium was examined and found to give a poorer separation than has been experimentally observed in several systems. In addition, this scheme does not allow for a variety of outcomes of the sorting process, as suggested by experimental data discussed later in this text (Chapters 5 and 6). Furthermore, it is not known whether the kinetics of ligand and receptor movement into tubules are rapid enough to allow an equilibrium distribution of molecules to be approached within the estimated sorting time. For these reasons, models of sorting which include the kinetics of receptor and ligand transport between the vesicle and tubules should next be examined.
Alternatives to Metformin for Patients with PCOS.

Compared with placebo, thiazolidinediones (TZDs) decrease systolic blood pressure and fasting blood glucose and insulin levels while improving menstrual irregularities in women with PCOS. Metformin and TZDs have similar effects on pregnancy rates, ovulation, and menstrual frequency, but TZDs can cause weight gain and lower free testosterone and dehydroepiandrosterone (DHEA) levels to a greater degree, whereas metformin reduces body mass index (BMI) and serum triglyceride levels to a greater degree.
Cognitive Remediation to Improve Functional Outcome

Abstract Cognitive dysfunction is common in psychotic disorders and significantly contributes to difficulty functioning in the home, and in therapeutic, social, educational, and occupational venues. Cognitive remediation is a behavioural treatment used to improve cognition, so people can function better in their life roles. In this chapter, we provide a brief overview of cognition in people with schizophrenia spectrum disorders, how cognition relates to their everyday functioning, and the approaches used in cognitive remediation to improve cognition. We focus on the literature supporting the impact of cognitive remediation on functional outcome, and examine the factors recognised to maximise therapeutic outcome. Finally, we consider some of the challenges and opportunities that arise when implementing cognitive remediation in mental health service settings.
African Religion and Colonial Rebellion: The Contestation of Power in Colonial Zimbabwe’s Chimurenga of 1896-1897

This article examines the unifying roles of the Mwari cult, the cultural symbol of land, and the authority of spirit mediums in the first anti-colonial socio-political and religious protest of Chimurenga of 1896-97 in colonial Zimbabwe. Using their spiritually and socially defined authority, spirit mediums (n’anga) served as movement intellectuals to the Chimurenga—they crafted strategies and inspiration for social protest. The shared values of the Mwari cult, the cultural symbol of land, and the office of mediums were further employed to mobilize masses into a social movement that sought to reverse rapid sociocultural and political changes brought about by colonialism. To make this case, the article problematizes religion within an African lifeworld. Aside from showing that African religions share many aspects with other world religions; the article rejects Eliade's, and Durkheim’s theory of ‘the sacred and the profane’. It argues that this separation is hard to establish in African traditional religions and cosmologies. Spirit mediums, for example, employed African sociology, spiritual beliefs and customs in their attempts to reject the colonial order. Besides, the implementation of ‘indirect rule’ and land grabs led to the contestation of power between colonial authorities, chiefs, and spirit mediums. This contestation is analyzed from a social movement perspective. Amidst contemporary social injustices, human rights abuses and corruption in post-colonial Africa, and without underestimating the role traditional religions play in African politics, the study challenges Christianity to follow the prophetic example of spirit mediums in the Chimurenga . Keywords : Religion, movement intellectuals, social movement, Chimurenga, indirect rule, spirit mediums, Mwari cult
Tritium and Fissile Fuel Exchange between Hybrids, Fission Power Reactors, and Tritium Production Reactors

A mathematical model extending work by Gordon and Harms is developed to describe the fissile fuel and tritium flows in a fusion-fission system consisting of a fusion hybrid reactor, a tritium production reactor, and several fission power reactors. The hybrid reactor plays the role of a fuel factory, providing the fission reactors and the tritium production reactor with their fissile fuel needs. The tritium production reactor ( a fission reactor) is devoted primarily to producing tritium for subsequent use in the hybrid. Different combinations of these systems are found by shifting the tritium breeding function among the various parts. At steady state, the total thermal power in fission reactors per unit of fusion power depends only on the total conversion ratio of the fission reactors and the hybrid. An economic analysis is required to determine which combination of systems will produce electricity at the lowest costs.
Addressing reverse inference in psychiatric neuroimaging: Meta-analyses of task-related brain activation in common mental disorders

Functional magnetic resonance imaging (fMRI) studies in psychiatry use various tasks to identify case-control differences in the patterns of task-related brain activation. Differently activated regions are often ascribed disorder-specific functions in an attempt to link disease expression and brain function. We undertook a systematic meta-analysis of data from task-fMRI studies to examine the effect of diagnosis and study design on the spatial distribution and direction of case-control differences on brain activation. We mapped to atlas regions coordinates of case-control differences derived from 537 task-fMRI studies in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder comprising observations derived from 21,427 participants. The fMRI tasks were classified according to the Research Domain Criteria (RDoC). We investigated whether diagnosis, RDoC domain or construct and use of regions-of-interest or whole-brain analyses influenced the neuroanatomical pattern of results. When considering all primary studies, we found an effect of diagnosis for the amygdala and caudate nucleus and an effect of RDoC domains and constructs for the amygdala, hippocampus, putamen and nucleus accumbens. In contrast, whole-brain studies did not identify any significant effect of diagnosis or RDoC domain or construct. These results resonate with prior reports of common brain structural and genetic underpinnings across these disorders and caution against attributing undue specificity to brain functional changes when forming explanatory models of psychiatric disorders. Hum Brain Mapp, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
A relevance ranking method for citation-based search results

A growing number of researchers are exploring the use of citation relationships such as direct citation, bibliographic coupling, and co-citation for information retrieval in scientific databases and digital libraries. In this paper, I propose a method of ranking the relevance of citation-based search results to a set of key, or seed, papers by measuring the number of citation relationships they share with those key papers. I tested the method against 23 published systematic reviews and found that the method retrieved 87% of the studies included in these reviews. The relevance ranking approach identified a subset of the citation search results that comprised 27% of the total documents retrieved by the method, and 7% of the documents retrieved by these reviews, but that contained 75% of the studies included in these reviews. Additional testing suggested that the method may be less appropriate for reviews that combine literature in ways that are not reflected in the literature itself. These results suggest that this ranking method could be useful in a range of information retrieval contexts.
Safety and outcomes of aspirin desensitization for aspirin-exacerbated respiratory disease: A single-center study.

Background Aspirin desensitization is an effective treatment option for aspirin-exacerbated respiratory disease. Aspirin desensitization protocol modifications have improved the safety and efficiency of this procedure, yet some providers remain reluctant to perform it. Objective The primary objective of this study was to evaluate the safety and outcomes of outpatient aspirin desensitization procedures. A secondary objective was to assess clinical characteristics that might predict reaction severity during aspirin desensitization. Methods Two hundred seventy-five patients underwent aspirin desensitization at Scripps Clinic between January 2009 and August 2015. Baseline patient characteristics and reaction results were analyzed in the 167 patients who reacted during desensitization. Results All of the 167 reactors, including 23 who were classified as severe reactors, were successfully desensitized in the outpatient setting. The average desensitization duration among reactors was 1.67 days, and the average duration for gastrointestinal reactors was 2.29 days. The mean baseline Sino-Nasal Outcome Test score was higher in severe reactors compared with nonsevere reactors ( P = .05). Overall, patients receiving omalizumab had a similar reaction profile to those not receiving omalizumab. Conclusions Most patients undergoing aspirin desensitization will have symptoms. It remains difficult to predict the severity of these symptoms. However, desensitization can be done safely and efficiently in an appropriately equipped outpatient setting. This treatment option should be made available to all patients with aspirin-exacerbated respiratory disease. The Sino-Nasal Outcome Test score might be able to predict more severe reactions and merits further study. Eight of the 9 patients receiving omalizumab reacted during desensitization, suggesting that it does not block reactions during aspirin desensitization.
Serum vitamins, carotenoids, and angina pectoris: findings from the National Health and Nutrition Examination Survey III.

Abstract PURPOSE: Whether various vitamins and carotenoids can protect against ischemic heart disease remains an unsettled question. METHODS: We performed a cross-sectional analysis of data from National Health and Nutrition Examination Survey III (1988–1994) and examined the associations between serum vitamins A, C, E, and B12, serum folate, red blood cell folate, serum carotenoids, and angina pectoris in a representative population-based sample of 11,327 men and women aged 35–>90 years. RESULTS: After adjusting for age, sex, race or ethnicity, education, smoking status, systolic blood pressure, serum cholesterol, high-density lipoprotein cholesterol, history of diabetes mellitus, body mass index, and physical activity with multiple logistic regression analysis, no significant associations were present for any of the serum vitamin concentrations and angina pectoris. Significant linear trends were observed for serum concentrations of α-carotene (p CONCLUSIONS: These results provide little support for a cross-sectional association between angina pectoris and serum and red blood cell folate concentrations or concentrations of vitamins A, C, E, and B12. Several serum carotenoid concentrations were associated with a reduced risk for angina pectoris, however.
A Noise Prediction and Time-Domain Subtraction Approach to Deep Neural Network Based Speech Enhancement

Deep neural networks (DNNs) have recently been successfully applied to the speech enhancement task; however, the low signal-to-noise ratio (SNR) performance of DNN-based speech enhancement systems remains less than desirable. In this paper, we study an approach to DNN-based speech enhancement based on noise prediction. Three speech enhancement models based on noise prediction are proposed, and their performance is compared to that of conventional spectral-mapping models in seen and unseen noise tests. Objective test results show that the proposed noise prediction models perform well in enhancing speech quality in seen noise conditions and in enhancing high SNR speech signals. They also perform well in enhancing speech intelligibility in both seen and unseen noise conditions, but do not outperform the conventional models on quality metrics in unseen noise conditions. Further analysis of the enhanced speech signals is undertaken to explain the observed results.
Property Crime Clearance in Small Jurisdictions: Police and Community Factors

Research on the factors that influence crime clearance rates has primarily studied violent crimes in large cities. However, property crimes are among the most commonly occurring and least frequentl...
Effects of patch size and basal area on avian taxonomic and functional diversity in pine forests: Implication for the influence of habitat quality on the species-area relationship.

Relationships between avian diversity and habitat area are assumed to be positive; however, often little attention has given to how these relationships can be influenced by the habitat structure or quality. In addition, other components of biodiversity, such as functional diversity, are often overlooked in assessing habitat patch value. In the Sandhills Ecoregion of Georgia, USA, we investigated the relationship between avian species richness and functional diversity, forest basal area, and patch size in pine forests using basal area as a surrogate for overstory structure which in turn impacts vegetation structure and determines habitat quality within a patch. We conducted bird surveys in planted mature pine stands, during breeding season of 2011. We used three classes of stand basal area (BA): OS, overstocked (BA ≥ 23 m2/ha); FS, fully/densely stocked (13.8 m2/ha ≤ BA < 23 m2/ha); and MS, moderately stocked (2.3 m2/ha ≤ BA < 13.8 m2/ha). MS patches showed more structural diversity due to higher herbaceous vegetation cover than other two pine stocking classes of patches. Total species richness and functional richness increased with the size of MS patches, whereas functional divergence decreased with the size of OS patches (p < 0.05). Functional richness tended to be lower than expected as the size of OS patches increased. Greater richness of pine-grassland species was also found at MS patches. Percent cover of MS patches within a landscape influenced positively the richness of pine-grassland species (p < 0.05). Our results suggest that (a) avian species-habitat area relationship can be affected by habitat quality (structural diversity) and varies depending on diversity indices considered, and (b) it is important to maintain moderate or low levels of pine basal area and to preserve large-sized patches of the level of basal area to enhance both taxonomic and functional diversity in managed pine forests.
Story as Pedagogy: A Reflective Commentary

This commentary seeks to encourage reflection upon learning and teaching through story. The authors illustrate ways they have used story in their teaching and what they perceive as the benefits of doing so. They explore how they learned through narrative as children and why they came to value it as a way of seeing and thinking. Then they consider how story disciplined their approaches to professional work before identifying specific narrative strategies used in teaching undergraduate and graduate students. The article concludes with suggestions about ways to better integrate narrative practices into teaching and learning.
NCX1: Mechanism of Transport

The plasma membrane Na+/Ca2+ exchanger (NCX) plays a critical role in the maintenance of Ca2+ homeostasis in a variety of tissues. NCX accomplishes this task by either lowering or increasing the intracellular Ca2+ concentration, a process which depends on electrochemical gradients. During each cycle, three Na+ are transported in the opposite direction to one Ca2+, resulting in an electrogenic transport that can be measured as an ionic current.
Acute inflammatory reaction after myocardial ischemic injury and reperfusion. Development and use of a neutrophil-specific antibody

Reperfusion of the infarcted canine myocardium after 1 hour of ischemia is associated with an acute inflammatory infiltrate at the border of the infarct. In this paper, we demonstrate that early margination and emigration of neutrophils originate in thin-walled (approximately 5 micrometers) venous cisterns that average 200 micrometers in length and vary from 10 to 70 micrometers in width and show strong constitutive expression of both ICAM-1 and P-selectin; this class of vessels (venous cisterns) appears to be a unique feature in heart. A monoclonal antibody (SG8H6) with specificity for canine neutrophils was developed that allowed much more sensitive immunohistochemical detection of neutrophils in tissue and allowed us to follow tissue infiltration with time. Samples from 1 hour of reperfusion revealed dense margination and substantial emigration of neutrophils associated with the venous cisterns and collecting venules. By 2 hours, there was intense local emigration to the extravascular space between cardiac myocytes. By 3 hours, the infiltrate extended deeper into the infarct, and there was a continuous border zone of neutrophil infiltration that overlapped a region where intact cardiac myocytes strongly expressed ICAM-1 mRNA and extended into the necrotic tissue. At later times, neutrophil migration into infarcted tissue continued to progress. Neutrophil transmigration into reperfused myocardium is more extensive than previously described, and its extravascular distribution during early reperfusion is primarily in the viable border zone of the myocardium where myocyte ICAM-1 mRNA is found. These data are compatible with the hypothesis that extravascular neutrophils may participate in reperfusion injury.
Palladium and Aluminum Thin Film Deposition on Thermally Sensitive Substrates From Organometallic Complexes

The ultraviolet decomposition of allylcyclopentadienyl palladium, [(η13-C3H5)(η5-C5H5)Pd], 1, has been used to deposit relatively pure (>95% palladium) metal films with submicrometer spatial resolution. The films deposited on polyimide resins were found to be porous with no apparent damage to the substrate from the ultraviolet photoassisted decomposition technique. The fabrication of palladium thin films from 1 is consistent with the known energetics of the ligand to metal bonds in the complex. The room temperature metallization of thermally sensitive substrates, such as plastics, was also achieved from the decomposition of the volatile aluminumborohydride complex, AIH2(BH4) ⋅ N(CH3)3, 2.. Films of thicknesses between 100 A and 2 μm have been prepared and characterized by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), laser microprobe mass analysis (LAMMA), X-ray diffraction (XRD), and energy dispersive X-ray analysis (EDXA).
Estimation of Sparse Directional Connectivity With Expectation Maximization

Motivated by the many applications associated with estimation of sparse multivariate models, the estimation of sparse directional connectivity between the imperfectly measured nodes of a network is studied. Node dynamics and interactions are assumed to follow a multivariate autoregressive model driven by noise, and the observations are a noisy linear combination of the underlying node activities. The corresponding maximum a posteriori (MAP) problem is derived to estimate system parameters. Due to the intractability of the MAP problem, the expectation maximization (EM) framework is used to iteratively implement the MAP estimation. To impose sparsity, the EM algorithm is augmented with an $\ell _1$ regularization of the connectivity matrix. Multiple techniques have been used to lower the computational complexity. Importantly, an efficient coordinate descent algorithm utilizing a closed-form solution is designed to solve the $\ell _1$ -regularized sub-problem of the EM. Cholesky factors of the unknown covariance matrices are used directly in the optimization process in order to impose positive definiteness and guarantee the functionality of the $\ell _1$ optimization. The algorithm is first applied to synthetic data to evaluate the estimation accuracy. A comparison with the previous work over an extensive set of configurations shows that our method is superior under moderate to high sparsity. Finally, the algorithm is applied to real temperature data obtained from 98 stations across the U.S. mainland to identify the predictive interactions between the time series.
Competitive Hydrogenation between Linear Alkenes and Aromatics on Close-Packed Late Transition Metal Surfaces

Selective hydrogenation of linear alkenes in the presence of aromatics is desired to prevent gum formation in pyrolysis gasoline (PYGAS) upgrading. To examine the competitive hydrogenation between linear alkenes and aromatics, we investigate ethylene and benzene competitive hydrogenation on different catalysts. Through density functional theory (DFT) calculations, we show the adsorption energies of benzene and ethylene correlate on monometallic close-packed surfaces, with benzene binding stronger for the same C to surface metal atom ratio. DFT calculations demonstrate Bronsted–Evans–Polanyi and scaling relationships hold, and these are fed into microkinetic modeling to predict the rate of ethylene and benzene hydrogenation with only ethylene and hydrogen binding energies as the surface descriptors. Due to stronger binding, benzene adsorption will dominate the surface. Higher barriers for benzene hydrogenation versus ethylene hydrogenation lead to benzene poisoning at temperatures at which ethylene hydroge...
Petrology and petrogenesis of the Mount Stuart batholith — Plutonic equivalent of the high-alumina basalt association?

The Mount Stuart batholith is a Late Cretaceous calc-alkaline pluton composed of rocks ranging in composition from two-pyroxene gabbro to granite. Quartz diorite is most abundant. This batholith may represent the plutonic counterpart of the high-alumina basalt association. A petrogenetic model is developed in which this intrusive series evolved from one batch of magnesian high-alumina basalt, represented by the oldest intrusive phase, by successive crystal fractionation of ascending residual magma. However, the possibility that this intrusive suite originated from an andesite (quartz diorite) parent by fractionation cannot be excluded.
Servant Leadership in Sports and Athletics

This chapter explores servant leadership in an athletic context and connects it to other concepts that are related to both servant leadership and sport. The connection between winning and servant leadership is discussed and while winning is important, servant leaders see it as a by-product of a process that enables others to be their best; selfless leadership and performance are not mutually exclusive. Power, a vital currency in athletics, and servant leadership are largely incompatible constructs but there are times when a servant leader will need to use power to support his or her followers such as in removing a coercive coach or leader. The idea that servant leadership represents a soft or weak approach is disputed in this section and examples are provided to support that claim. The benefits of a coach–athlete relationship built upon servant leadership are also explored and how existing athlete-centric models (e.g., Jowett’s 3 C’s +1, Cloud’s Four Corners) are best supported by servant leadership principles. Examples of prominent coaches displaying servant leadership tendencies are also shared. Ethics, sports, and servant leadership are discussed and the important role servant leaders can play in mitigating the ethical dilemmas including gender equity within athletics. Finally, growth mind-set research is connected to servant leadership and follower need satisfaction.
Pathophysiology and clinical presentation of lumbar stenosis

Abstract Originally described by Kirkaldy–Willis, the degenerative cascade leading to anatomic LSS occurs in a predictable pattern, beginning with altered biomechanics of the intervertebral disk (Yong-Hing and Kirkaldy-Willis, 1983). Further studies have elucidated several theorized mechanisms responsible for the varied clinical manifestations experienced by patients with similar radiographic evidence of LSS; however, a single explanation for these finding has yet to be identified (Olemarker et al., 1996; Rydevick et al., 1991; Pedowitz et al., 1992). Obtaining thorough patient history and performing a complete physical exam is critical to ensure an accurate diagnosis. Although neurogenic claudication symptoms are classic for LSS, patients frequently present with varied and often mixed symptomatology (Buckland et al, 2017; Lesher et al., 2008). Consistent screening for myelopathic symptoms, identifying “red-flag” symptoms suggesting systemic illness, and awareness of potential extraspinal pathology is necessary to improve patient outcomes (Devin et al, 2012; Golob et al, 2006; Berger et al, 2017).
TWEAK/Fn14 Is Overexpressed in Crohn’s Disease and Mediates Experimental Ileitis by Regulating Critical Innate and Adaptive Immune Pathways

Background & Aims Crohn’s disease (CD) is a debilitating inflammatory disorder that affects more than 1.6 million people in North America alone. Members of the tumor necrosis factor superfamily are key regulators of intestinal inflammation; specifically, tumor necrosis factor–like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor–inducible 14 (Fn14), are involved in normal and pathologic tissue remodeling. Our aim was to determine the role of TWEAK/Fn14 in CD and a murine model of CD-like ileitis (ie, SAMP1/YitFc [SAMP] strain). Methods SAMP mice deficient in Fn14 (SAMP × Fn14-/-) were developed and a detailed time-course study was performed evaluating ileal tissues by histology and stereomicroscopy, as well as quantitative polymerase chain reaction and NanoString technology (Seattle, WA). Reciprocal bone marrow chimeras were generated to assess the relevance of Fn14 in hematopoietic vs nonhematopoietic compartments. Surgically resected intestinal tissues and mucosal biopsy specimens from patients with CD, ulcerative colitis, and healthy controls were analyzed for the expression of TWEAK/Fn14 by quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. Results SAMP × Fn14-/- showed a marked decrease in ileitis severity at 20 weeks of age compared with SAMP WT controls. Bone marrow chimeras showed that Fn14 was required in both hematopoietic and nonhematopoietic compartments for ileitis to develop. Transcriptome data showed multiple cellular pathways regulated by Fn14 signaling. Finally, increased expression of TWEAK and Fn14 was observed in tissue lesions from CD patients compared with ulcerative colitis and healthy controls. Conclusions TWEAK/Fn14 are up-regulated in CD, and also mediate experimental CD-like ileitis, by regulation of multiple innate and adaptive cellular pathways. Therefore, TWEAK/Fn14 may represent a novel therapeutic target for the treatment of small intestinal inflammation in CD.
Fragile Future: The Human Cost of Conflict in Afghanistan

This context analysis examines the humanitarian, political, societal, and economic dimensions that make the protracted conflict in Afghanistan intractable and precarious for civilian populations. The report is based on field visits to numerous regions in Afghanistan in July 2018 — which included interviews and consultations with a variety of actors, including political stakeholders, humanitarian agencies, and populations affected by conflict — as well as a review of recent and relevant literature. The purpose of this analysis is to (1) provide a current assessment of the conflict, drawing from field interviews and an in- depth assemblage of various reports and resources, (2) examine the interconnected and interdependent interests fueling the conflict, and (3) suggest that if these dynamics persist in the way they have for decades, recent elections and peace talks will represent yet another setback for Afghan communities and a peaceful future for the country.
Self-Assembling Scaffolds Supported Long-Term Growth of Human Primed Embryonic Stem Cells and Upregulated Core and Naïve Pluripotent Markers.

The maintenance and expansion of human embryonic stem cells (ESCs) in two-dimensional (2-D) culture is technically challenging, requiring routine manipulation and passaging. We developed three-dimensional (3-D) scaffolds to mimic the in vivo microenvironment for stem cell proliferation. The scaffolds were made of two 8-arm polyethylene glycol (PEG) polymers functionalized with thiol (PEG-8-SH) and acrylate (PEG-8-Acr) end groups, which self-assembled via a Michael addition reaction. When primed ESCs (H9 cells) were mixed with PEG polymers, they were encapsulated and grew for an extended period, while maintaining their viability, self-renewal, and differentiation potential both in vitro and in vivo. Three-dimensional (3-D) self-assembling scaffold-grown cells displayed an upregulation of core pluripotency genes, OCT4, NANOG, and SOX2. In addition, the expression of primed markers decreased, while the expression of naive markers substantially increased. Interestingly, the expression of mechanosensitive genes, YAP and TAZ, was also upregulated. YAP inhibition by Verteporfin abrogated the increased expression of YAP/TAZ as well as core and naive pluripotent markers. Evidently, the 3-D culture conditions induced the upregulation of makers associated with a naive state of pluripotency in the primed cells. Overall, our 3-D culture system supported the expansion of a homogenous population of ESCs and should be helpful in advancing their use for cell therapy and regenerative medicine.
Real-Time Thermoacoustic Imaging and Thermometry during Focused Microwave Heating in Multilayer Breast Phantom

This study describes real-time thermoacoustic imaging (TAI) and thermometry (TAT) for feedback during thermal therapies. The system uses a linear ultrasound array and imaging system to noninvasively estimate temperature. The system was validated in gel phantoms, muscle and fat tissue samples. A mean error between 10 and 20% per degree was observed for estimating temperature. A TAT system using a single element ultrasound probe was also integrated with a focused microwave therapy (FMT) setup for generating local heating, leading to a mean error of 1.18±0.87 °C compared to thermocouples placed near the region of interest. The results support the long-term goal of developing a closed-loop platform for image-guided ablation therapy for breast cancer.
(Curcumin+sildenafil) enhances the efficacy of 5FU and anti-PD1 therapies in vivo

We have extended our analyses of (curcumin+sildenafil) biology. The drug combination caused vascularization and degradation of mutant K-RAS that correlated with reduced phosphorylation of ERK1/2, AKT T308, mTORC1, mTORC2, ULK1 S757, STAT3, STAT5, and NFκB and increased phosphorylation of eIF2α, ATM, AMPKα, ULK1 S317; all concomitant with elevated ATG13 S318 phosphorylation and autophagosome formation. Prior studies with drug combinations utilizing sildenafil have delineated an ATM-AMPK-ULK1 S317 pathway and an AKT-mTOR-ULK1 S757 pathway as modules which control ATG S318 phosphorylation and autophagosome formation. The knockdown of PKG reduced cell killing as well as reducing drug-enhanced phosphorylation of ATM, AMPKα, and ATG13. In the absence of PKG, no significant increase in ULK1 S317 phosphorylation was observed. In a Beclin1-dependent fashion, the drug combination reduced the expression of multiple histone deacetylase (HDAC) proteins, including HDAC2 and HDAC3. Molecular knockdown of HDAC2, HDAC3, and especially (HDAC2+HDAC3) significantly reduced the expression of PD-L1 and elevated expression of Class I human major histocompatibility complex. In vivo, (curcumin+sildenafil) enhanced the efficacy of 5-flurouracil against CT26 colorectal tumors. Prior exposure of established CT26 tumors to (curcumin+sildenafil) significantly enhanced the efficacy of a subsequently administered anti-PD-1 antibody. Collectively our data argue that (curcumin+sildenafil) has the potential in several settings to be an efficacious neoadjuvant therapy for colon cancer.
A Bibliometric Review of Artificial Extracellular Matrices Based on Tissue Engineering Technology Literature: 1990 through 2019

Artificial extracellular matrices (aECMs) are an extension of biomaterials that were developed as in-vitro model environments for tissue cells that mimic the native in vivo target tissues' structure. This bibliometric analysis evaluated the research productivity regarding aECM based on tissue engineering technology. The Web of Science citation index was examined for articles published from 1990 through 2019 using three distinct aECM‑related topic sets. Data were also visualized using network analyses (VOSviewer). Terms related to in-vitro, scaffolds, collagen, hydrogels, and differentiation were reoccurring in the aECM‑related literature over time. Publications with terms related to a clinical direction (wound healing, stem cells, artificial skin, in‑vivo, and bone regeneration) have steadily increased, as have the number of countries and institutions involved in the artificial extracellular matrix. As progress with 3D scaffolds continues to advance, it will become the most promising technology to provide a therapeutic option to repair or replace damaged tissue.
Quantum element method for quantum eigenvalue problems derived from projection-based model order reduction

An effective multi-element simulation methodology for quantum eigenvalue problems is investigated. The approach is derived from a reduced-order model based on a data-driven learning algorithm, together with the concept of domain decomposition. The approach partitions the simulation domain of a quantum eigenvalue problem into smaller subdomains that, referred to as elements, could be the building blocks for quantum structures of interest. In this quantum element method (QEM), each element is projected onto a functional space represented by a set of basis functions (or modes) that are generated from proper orthogonal decomposition (POD). To construct a POD model for a large domain, these projected elements can be combined together, and the interior penalty discontinuous Galerkin method is applied to achieve the interface continuity and stabilize the numerical solution. The POD is able to optimize the basis functions specifically tailored to the geometry and parametric variations of the problem and can therefore substantially reduce the degree of freedom (DoF) needed to solve the Schrodinger equation. To understand the fundamental issues of the QEM, demonstrations in this study focus on examining the accuracy and DoF of the QEM influenced by the training settings for generation of POD modes, selection of the penalty number, suppression of interface discontinuities, structure size and complexity, etc. It has been shown that the QEM is able to achieve a substantial reduction in the DoF with a high accuracy even beyond the training conditions for the POD modes if the penalty number is selected within an appropriate range.
Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer's Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals

Background This study evaluated whether the apolipoprotein ɛ4 (APOE4) allele, a genetic marker associated with increased risk of developing late-onset Alzheimer's disease (AD), was associated with differences in evoked pain responsiveness in cognitively healthy subjects. Objective The aim was to determine whether individuals at increased risk of late-onset AD based on APOE allele genotype differ phenotypically in their response to experimentally-induced painful stimuli compared to those who do not have at least one copy of the ɛ4 allele. Methods Forty-nine cognitively healthy subjects aged 30-89 years old with the APOE4 allele (n = 12) and without (n = 37) were assessed for group differences in pain thresholds and affective (unpleasantness) responses to experimentally-induced thermal pain stimuli. Results Statistically significant main effects of APOE4 status were observed for both the temperature at which three different pain intensity percepts were reached (p = 0.040) and the level of unpleasantness associated with each (p = 0.014). APOE4 positive participants displayed lower overall pain sensitivity than those who were APOE4 negative and also greater overall levels of pain unpleasantness regardless of intensity level. Conclusion Cognitively healthy APOE4 carriers at increased risk of late-onset AD demonstrated reduced thermal pain sensitivity but greater unpleasantness to thermal pain stimuli relative to individuals at lower risk of late-onset AD. These results suggest that altered evoked pain perception could potentially be used as a phenotypic biomarker of late-onset AD risk prior to disease onset. Additional studies of this issue may be warranted.
Abstract PR004: Multi-dimensional biomarker analyses identify pembrolizumab responders in advanced stage, high grade endometrial cancer

Objectives: The recent FDA approval of pembrolizumab for the treatment of recurrent, tissue agnostic cancers with Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) has led to the treatment of a selected cohort of endometrial cancer (EC) patients. Methods: We designed a study to ascertain tumor immune modulatory effects of pembrolizumab in the front-line setting for advanced stage III/IV surgically-resectable endometrial cancers regardless of MSI-H or dMMR status. The primary objectives were to determine the safety of treatment with pembrolizumab by radiographic imaging and to determine progression-free survival at 6 months. Exploratory objective was to compare the immune response before and after treatment. In an open label, single-arm Phase I trial, 8 EC patients were treated with 2 doses of preoperative pembrolizumab IV prior to surgery followed by carboplatin and paclitaxel and 4 doses of pembrolizumab 200mg/kg q3 weeks IV. Peripheral blood was collected from EC patients at baseline level before treatment and post 2 doses of pembrolizumab treatment. Blood from healthy controls (HC) was also collected. Both were processed for high-dimensional single-cell mass cytometry (CyTOF) using an optimized lymphoid and myeloid panel. Results: Patients who responded to therapy showed lower frequency of circulating CD8+ naive T cells but higher frequency of CD8+ effector T cells after the treatment than the poor responders. We observed post-therapy expansion of populations of CD8+ and CD4+ T cells expressing co-stimulatory receptor ICOS in responders but not in poor responders. Granzyme+CD8+ and Granzyme+CD4+ T cell populations were expanded after pembrolizumab treatment in responders but were decreased in poor responders. Higher frequency of CD27+Fas- CD4+ T cells at baseline and increased frequency of CD27-Fas+CD4+ T cells post-treatment were observed in responders but not in the poor responders. Furthermore, we identified that circulating MDSCs were reduced after pembrolizumab treatment in responders. Conclusions: Our results suggest that peripheral blood analysis may provide valuable insights into responses to anti-PD-1-targeted therapies in patients with endometrial cancers. Citation Format: Katherine Fuh, Elena Lomonosova, Russell Pachynski, Olga Malkova, Stephen Oh, Andrea Hagemann, Carolyn McCourt, Matthew Powell, Wendy Fantl, Premal Thaker. Multi-dimensional biomarker analyses identify pembrolizumab responders in advanced stage, high grade endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PR004.
The Impact of Frailty on Outcomes of Sling Surgery With and without Prolapse Repair. Reply.

Purpose:Frailty has emerged as a significant predictor of morbidity in urological surgery, but its impact on outcomes of sling surgery for stress incontinence remains unclear. The purpose of this s...
Skew-slit collimator for small animal SPECT

664 Objectives: We design a novel skew-slit collimator for small animal SPECT. Methods: The state-of-the-art small animal SPECT is a multipinhole imaging. A pinhole provides a cone-beam geometry, which magnifies the image so that the detection sensitivity and spatial resolution can be increased. The cone-beam geometry has a drawback of incomplete data measurement when using a circular detector rotation trajectory. The multipinhole method not only mitigates the incomplete-data sampling problem but also increases the detection sensitivity and uniformity. However, the multipinhole system may have multiplexing problems, that reduce the tomographic information content in the data. The data-incompletion artifacts worsen if the image magnification becomes large in the axial direction. We propose a novel skew-slit system that provides a relative small magnification in the axial direction and relatively large magnification in the transaxial direction. A skew-slit collimator consists of two tungsten plates, both parallel to the axis of detector rotation. The plate close to the object contains a slit parallel to the axis of rotation, while the other plate contains multiple slits perpendicular to the axis of rotation. If these two plates are touching each other, the skew-slit collimator reduces to a multipinhole collimator. For a spherical object, its pinhole projection image is a circle; its skew-slit projection image is an ellipse, with a longer axis perpendicular to the axis of rotation. Results: In the following way, a multipinhole collimator can be replaced by a skew-slit collimator. Given a satisfactory multipinhole pattern design, the equivalent skew-slit design will have the same axial magnification as the multipinhole system, and will have the maximum possible magnification in the transaxial direction (be sure that the projections are not truncated). The spacing between the multiple slits is chosen so that the projection data have no or very little overlap. In order to match the same detection sensitivity, more pinholes are required in the equivalent multipinhole system. One advantage of the skew-slit system over the multipinhole system is its better transaxial resolution due to a larger image magnification in the transaxial direction. Another advantage is its easy design. Still another advantage is the regular positioning of the projection images on the detector, making it possible to develop analytical reconstruction algorithms, while the only reconstruction algorithms for multipinhole are iterative ones. Conclusions: The proposed skew-slit collimator can be considered as a generalized multipinhole collimator. The skew-slit system provides an imaging geometry between cone-beam and fan-beam, allowing a larger magnification in the transaxial direction without introducing artifacts. The regular separation of the projection images makes analytical reconstruction possible.
Current Structure and Nonideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

[1] The Poincare index indicates that the Cluster spacecraft tetrahedron entraps a number of 3-D magnetic nulls during an encounter with the turbulent magnetosheath. Previous researchers have found evidence for reconnection at one of the many filamentary current layers observed by Cluster in this region. We find that many of the entrained nulls are also associated with strong currents. We dissect the current structure of a pair of spiral nulls that may be topologically connected. At both nulls, we find a strong current along the spine, accompanied by a somewhat more modest current perpendicular to the spine that tilts the fan toward the axis of the spine. The current along the fan is comparable to the that along the spine. At least one of the nulls manifests a rotational flow pattern in the fan plane that is consistent with torsional spine reconnection as predicted by theory. These results emphasize the importance of examining the magnetic topology in interpreting the nature of currents and reconnection in 3-D turbulence.