cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B19: Inactivation of KLF4 in T cell acute lymphoblastic leukemia promotes the expansion of leukemia cells by activating the Map2k7/Jnk pathway.

Acute lymphoblastic leukemia is the most common hematological malignancy in pediatric patients, and disease relapse is the leading cause of cancer-associated death in children. Despite steadily improved outcomes in patients with newly diagnosed disease, little progress has been made to treat relapse leukemia and to reduce the incidence of relapse by increasing the cure rates of frontline therapy. Targeted therapy is currently not available for T-ALL and the development of novel agents requires a better understanding of how leukemia-initiating cells (LIC) are maintained. In contrast to normal blood cells, we found that the transcription factor KLF4 is significantly downregulated in pediatric T-ALL. Next-generation bisulfite sequencing revealed that the KLF4 promoter is hypermethylated in lymphoblasts from T-ALL patients but not in normal bone marrow cells, T cells, and pediatric B-ALL. Deletion of the Klf4-floxed gene with Vav-iCre transgene and transplantation of Klf4 Δ / Δ bone marrow cells transduced with the Notch1-L1601P-ΔP mutant resulted in a significant acceleration of T-ALL due to a 9-fold expansion of LIC and increased G1-S transition in leukemic T cells. A combined analysis of global gene expression and genome-wide binding revealed that KLF4 directly represses the dual specificity mitogen-activated protein kinase 7 (Map2k7) and thus Klf4 Δ / Δ T-ALL mice exhibit increased Map2k7 expression. Most remarkably, T-ALL cells from both mouse model and pediatric patients showed elevated levels of total and phosphorylated Map2k7 and subsequent activation of downstream targets JNK, c-Jun, and ATF2. Finally, we tested several JNK inhibitors in T-ALL cell lines, primary patient samples, and pre-clinical xenograft models of T-ALL and confirmed that JNK inhibition blocks ATF2 activation and controls expansion of leukemia cells, validating the Map2k7/Jnk pathway as a selective target for T-ALL therapy. Thus, KLF4 emerges as a novel tumor suppressor in T-ALL and Jnk inhibition as a novel therapeutic approach for adjunctive therapy in T-ALL patients with refractory or relapse disease. Citation Format: Ye Shen, Koramit Suppipat, Chun Shik Park, Toni-Ann Mistretta, Terzah Horton, Karen Rabin, Daniel Lacorazza. Inactivation of KLF4 in T cell acute lymphoblastic leukemia promotes the expansion of leukemia cells by activating the Map2k7/Jnk pathway.. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B19.
Survey and analysis of measles antibody level in children aged from 0 to 6 year-old in The 2nd Division of Xinjiang Production and Construction Corps

Objective To investigate measles antibody level among children aged from 0 to 6 year-old and to provide a scientific basis for formulating policy of control measles in The 2nd Division of Xinjiang Production and Construction Corps.Methods By random sampling surveys, 483 children of 0 to 6 year-old from 5 farms of the division were selected and their serum antibody levels were detected with ELISA method in 2012. Results The results showed that the measles antibody GMT was 748, with positive rate of 88.20%. Differences in positive rate of antibody and GMT between the male and female were of no statistical significance(χ2=3.56, F=3.72, P0.05), but of statistical significance(P0.01) among different ages(χ2=19.51, F=5.42), P0.01 and various areas(χ2=29.07, F=63.02). Conclusions The immune status in children aged from 0 to6 year-old was good to prevent epidemic of measles in short-term. In the future the routine immunization and supplementary immunization, especially in children over 1 year-old or floating children, should be strengthened.
From Nadir to Zenith: the Power to Detain in War

Who controls the detention of individuals on the battlefield? Assuming the President possesses some inherent authority to detain — as this article does — to what extent can Congress prescribe the President’s authority? Could Congress go so far as to direct the detention of a particular individual or class of individuals; or, conversely, could they prohibit the detention of the same? Though these questions involve fundamental constitutional issues and have been the focus of four Supreme Court rulings and more than 200 federal court opinions since 2001, the issue remains decidedly unsettled. This article argues that the President possesses some inherent power to detain, the breadth of which, relative to Congress, is a function of two factors: the location of detention (e.g., whether it occurs outside or inside the United States and its territories) and the nature of the detention (e.g., the intensity of the conflict in which the detention occurs).
The evolving story of new food allergies following liver transplantation.

Food allergy has been increasingly reported in children who had orthotopic liver transplantation (OLT). We aimed to conduct a prospective study to investigate the prevalence of sensitizations and food allergy in pediatric OLT recipients. We also aimed to identify potential risk factors. The study group consisted of 28 children (14 male, 14 female, mean age 4.96 ± 0.76 yrs) who had OLT. Total eosinophil count (TEC), total IgE, and specific IgEs were studied before and 3, 6, 12 months after OLT. Six patients (21%) developed multiple food allergies. Mean age of six patients at OLT who developed food allergy was younger compared to the non-food allergy group (10.2 months vs. 68.9 months, p 0.05). Mean of TECs were significantly higher in food allergic group compared to non-food allergic group at each time point after OLT (p 0.05). These findings suggest that food allergy should be considered after OLT in patients who are younger than 1 yr of age, who developed hypereosinophilia, high total IgE levels or EBV viremia.
Hemangioma in the Wall of a Cyst

Two cases of hemangioma are reported. In the first case a hemangioma was found inside a benign renal cyst. The confusion of this unusual lesion with carcinoma is discussed. The second case is another example of the segmental radiographic sign that is useful in the preoperative diagnosis of hemangioma.
Sedimentology of the ~3.3Ga upper Mendon Formation, Barberton Greenstone Belt, South Africa

The Mendon Formation is the uppermost unit of the 3.5-3.26 Ga Onverwacht Group in the Barberton Greenstone Belt, South Africa. It consists of a cyclic stack of komatiitic volcanic units separated by thin cherty sedimentary layers. In most areas, the uppermost Mendon Formation is a sedimentary interval characterized by black chert, banded black-and-white chert, and banded ferruginous chert, although the detailed patterns of lithofacies in different sections are more complex. Previously reported zircon U/Pb ages suggest that Mendon deposition could represent more than 70 Myr of time between ∼3,334 Ma and ∼3,260 Ma. This study presents sedimentological and petrographic observations of the upper Mendon Formation from across the central part of the Barberton Greenstone Belt in order to investigate sediment sources, depositional processes, and environments of sedimentation. The dominant mode of sedimentation was quiet settling of carbonaceous grains and, in the deepest sections below storm wave base, fine ferruginous material, resulting in finely laminated black and grey chert. In situ carbonaceous laminations are rare, suggesting that benthic microbial mat growth had little direct influence on deposition. The hemipelagic background deposition was punctuated by occasional inputs of fine pyroclastic debris, formation and deposition of silica granules, and reworking by infrequent storm events. Storm deposits are represented by coarse-grained, poorly-sorted intraclast breccias, some of which include distinctive intraclasts sampling lithofacies that are not observed in situ. Despite considerable lateral variability, correlative temporal trends are resolvable in many Mendon sections: there is an upward-deepening of the overall depositional setting recorded in the oldest upper Mendon sections, consistent with the previous interpretation that Mendon time was characterized by rifting ( Lowe, 1994a; Lowe, 1999a). Younger Mendon cycles include thick, relatively ferruginous basal sections, interpreted to reflect the deepest water deposition. These sections are capped by black chert and silicified ashes with more evidence of disturbance and reworking by storms, reflecting gradual shoaling. This sedimentological analysis is broadly consistent with previous geochemical and tectonic analyses and provides a better picture of depositional patterns during uppermost Onverwacht time, before the distinct change in tectonic regime marked by impact spherule layer S2 and the onset of Fig Tree Group orogenesis and related siliciclastic deposition.
WE-AB-207B-04: A Preliminary Investigation of Indicators for Treatment Outcomes of CT Guided Cervical Cancer Brachytherapy

Purpose: To identify indicators for recurrence in cervical cancer patients treated with high-dose-rate brachytherapy (HDR-BT). Methods: A total of 37 biopsy proven uterine cervical cancer patients of stage IB-IVA treated between 2011 and 2015 were included in this study. All patients were treated with 37.8–52.2Gy of external beam radiotherapy (EBRT) plus 5 × 5.0–6.5Gy of HDR-BT. Patient age, standard deviation of high-risk clinical tumor volume (HR-CTVSD) collected throughout HDR-BT, and D90 (EQD2, α/β=10Gy) of the HR-CTV were investigated as potential indicators for local/distant recurrence using ROC analysis. The optimal cutoff value was identified through the Youden index and was subsequently used to obtain a group assignment for all patients. Another two comparing groups were defined per evidence of post-EBRT tumor shrinkage based on the pre-HDR MR scan. Kaplan-Meier curves were generated for recurrence-free proportions for comparing groups where time was measured from the final HDR treatment date to the date of the final follow-up exam and compared through Cox regression. Results: Patients had a median follow-up of 12 months, where 16% had local pelvic recurrence and 16% had distant recurrence. HR-CTVSD was identified as a statistically significant indicator for recurrence (AUC=0.802, p=0.007) compared to D90 (AUC=0.655, p=0.167) and patient age (AUC=0.683, p=0.103). HR-CTVSD of 6.26cc was chosen as the optimal cutoff value, which was used as the basis for patient group assignment. Patients with HR-CTVSD>6.26cc had a hazard ratio of 3.92 (95% CI-1.37, 11.24; p=0.011) for recurrence compared to HRCTVSD≤ 6.26cc. Patients without evidence of post-EBRT tumor shrinkage compared to those with had a hazard ratio of 4.28 (95% CI-1.14, 16.15; p=0.032) for recurrence. Conclusion: HR-CTVSD was identified as an indicator for recurrence and an optimal value of 6.26cc was established in our study. In addition, patients without evidence of post-EBRT tumor shrinkage demonstrated an increased recurrence rate.
The Art of Anselm Kiefer through the Lens of Martin Heidegger on Technology, Art, and Truth

For Heidegger technology en-frames a world of manipulated objects and unleashes a one-dimensional subjectivity that blinds us to the essence of the object world. It is a distraction that promotes inauthentic living over confrontation with the finitude of our existence. Three themes tie Anselm Kiefer’s artistic commentary on technology to Heidegger’s philosophy. They are both interested in the essence of technology, Heidegger in its ontological aspects and Kiefer in its spiritual aspects. Both emphasize the ambiguity created by technology. Both point to a relation between earth and world. Kiefer’s art shows an earth and world relation that is fraught with peril, a relationship between earth and world where technology threatens, Being is in question, and no identity has been established between earth and world.
The Parallels between Mass Incarceration and Mass Deportation: An Intersectional Analysis of State Repression

In the spring of 2014, President Obama’s administration reached a landmark of over 2 million deportations—more in under six years than the sum total of all deportations prior to 1997. Mass deportation has not affected all communities equally: the vast majority of deportees are Latin American and Caribbean men. Today, nearly 90 percent of deportees are men, and over 97 percent of deportees are Latin American or Caribbean. This article explores the global context under which mass deportation has occurred and draws parallels with mass incarceration. Whereas other scholars have characterized mass deportation as a tool of social or migration control, this article argues that mass deportation is best understood as a racialized and gendered tool of state repression implemented in a time of crisis. I argue that the confluence of four factors has created the conditions of possibility for mass deportation from the United States: (1) nearly all deportees are Latin American and Caribbean men; (2) the rise of a politics of fear in the aftermath of the attacks of September 11th; (3) the global financial crisis; and (4) the utility of deportees
Retracing Homophobic Tendences in Two Central American Novels: Hector Tobar`s The Tattooed Soldier and Javier Payera's Ruido de fondo

Este articulo examina el heterosexismo y la homofobia en dos novelas centroamericanas –Ruido de fondo (2006) y The Tattooed Soldier (1995)– trazando sus origenes a la matriz colonial. El heterosexismo y la homofobia crecen de perspectivas sexistas de genero impuestas sobre las sociedades indigenas centroamericanas. Antes de la llegada de Colon a las Americas en 1492, organizaciones jerarquicas de los humanos no existian en la region. Sin embargo, despues de las conquistas militares espanolas, las sociedades indigenas fueron forzadas a adoptar ideales espanoles. Al poco tiempo, los espanoles usurparon los sistemas legales y penales en Centroamerica y gobernaron la moralidad en la region. A traves de su poder, los espanoles empezaron a borrar la cultura indigena y a cultivar normas jerarquicas, patriarcales y heterosexistas. Cuatro siglos despues, estas normas son analizadas en dos novelas contemporaneas centroamericanas, Ruido de fondo y The Tattooed Soldier. Estas novelas demuestran como representaciones difamatorias de homosexuales y la vigilancia de la masculinidad en la sociedad Centroamericana perpetuan y legitiman la violencia y el odio contra los homosexuales.
Sports fans, alcohol use, and violent behavior: a sociological review

This review makes four contributions to the sociological study of sports fans, alcohol use, and violent behavior. First, this article focuses explicitly on the relationship between alcohol use and violent behavior among sports fans. This is a worldwide social problem, yet it is quite understudied. Second, this article synthesizes the fragmented literature on alcohol use and violent behavior among sports fans. Third, this article identifies four broad sets of risk factors-sociocultural, event/venue, police, and crowd-that appear to be closely related to violent behavior among sports fans. Finally, to help explain the possible correlation between alcohol and violence among sports fans, this article draws upon the key understandings from the literature on alcohol and violence in wider society. The article concludes with suggestions for future research.
When Nature Becomes Culture: The National Register and Yosemite's Camp 4, A Case Study

For environmental advocates cultural analysis of natural sites opens the door to a universe of historic preservation laws originally designed to protect cultural resources. These can be used, as in the case of Camp 4, to protect significant areas that fail to meet the standards required for preservation purely on the basis of natural qualities.
Franchise Value, Competition and Insurer Risk Taking

Existing theory holds that high franchise value (HFV) firms are more prudent than low franchise value (LFV) firms because franchise value cannot be fully liquidated in the event of insolvency. This theory, however, does not consider the opportunity cost to HFV firms of being prudent, especially when confronted with intense competition. We develop a theoretical model in which the risk-constraining effect of franchise value is affected by the degree of competition, and then test it empirically using a sample of publicly traded stock property-casualty insurers. The results suggest that when competition is intense, HFV firms may have sufficient incentive to overcome the risk-constraining effects of franchise value.
104 - The Alcohol-related Problems Survey: Developing and Testing a Screening Measure for Older Adults

This chapter describes the development and testing of the Alcohol-Related Problems Survey (ARPS), a screening measure specifically designed to meet the needs of older adults who drink and their primary care physicians. Older adults may experience unfavorable health effects from alcohol use at relatively low levels of consumption because of age-related physiological changes; and interactions among alcohol and declining health, medication-use and diminishing functional status. Physicians consistently fail to recognize alcohol-related risks and problems in this population. The ARPS is unique as it expands upon the traditional alcohol-use paradigm (which focuses on identification of persons who abuse or are dependent upon alcohol) to identify the much larger population of older adults who are at risk for or experiencing problems and those whose drinking is not problematic. The ARPS also provides clinical information describing the basis for determining risk status. The chapter also discusses the effectiveness of the Computerized ARPS (CARPS) in reducing hazardous and harmful drinking and sustaining nonhazardous drinking in older adults. The CARPS is an integrated screening and education system that provides patients and physicians with detailed reports of each patient's drinking patterns and targeted educational materials.
Examining the Heterogeneous Impact of Ridehailing Services on Public Transit Use

We examine the impact that ride-hailing services have had on the demand for different modes of public transit in the United States, with a particular focus on understanding heterogeneity in the effects. We assess these effects using a panel dataset that combines information on public transit utilization (from the Federal Transit Administration) with information on ride-hailing providers’ staggered arrival into different locations, based on public press-releases and newspaper reports. Our analysis indicates that, on average, ride-hailing services have led to significant reductions in the utilization of city bus services, while increasing utilization of commuter rail services. These average effects are also subject to a great deal of contextual heterogeneity, depending on the size of the local population, rates of violent crime, weather, gas prices, transit riders’ average trip distance and the quality of overall quality of public transit options. We demonstrate the robustness of our findings to alternative model specifications. Our findings contribute to the prior literature on technology substitution and complementarity and suggest explanations for contradictory findings that have been reported on ride-hailing’s influence upon public transit demand. We also offer useful insights for policymakers, highlighting the nuanced implications of ride-hailing services for different transit operators, depending on the local context.
Description and Codification of Miscanthus × giganteus Growth Stages for Phenological Assessment

Triploid Miscanthus × giganteus (Greef et Deu. ex Hodkinson et Renvoize) is a sterile, perennial grass used for biomass production in temperate environments. While M. × giganteus has been intensively researched, a scale standardizing description of M. × giganteus morphological stages has not been developed. Here we provide such a scale by adapting the widely-used Biologische Bundesanstalt, Bundessortenamt, CHemische Industrie (BBCH) scale and its corresponding numerical code to describe stages of morphological development in M. × giganteus using observations of the "Freedom" and "Illinois" clone in Iowa, USA. Descriptive keys with images are also presented. Because M. × giganteus plants overlap in the field, the scale was first applied to individual stems and then scaled up to assess plants or communities. Of the 10 principal growth stages in the BBCH system, eight were observed in M. × giganteus. Each principal stage was subdivided into secondary stages to enable a detailed description of developmental progression. While M. × giganteus does not have seed development stages, descriptions of those stages are provided to extend the scale to other Miscanthus genotypes. We present methods to use morphological development data to assess phenology by calculating the onset, duration, and abundance of each developmental stage. This scale has potential to harmonize previously described study-specific scales and standardize results across studies. Use of the precise staging presented here should more tightly constrain estimates of developmental parameters in crop models and increase the efficacy of timing-sensitive crop management practices like pest control and harvest.
Cortisol is More Important than Metanephrines in Driving Changes in Leukocyte Counts after Stroke.

Background There are notable changes in the number of white blood cells (WBCs) after stroke, but the primary mediators of these changes are unclear. In this study, we assessed the role of the neuroendocrine and sympathetic nervous systems in stroke-induced changes of WBCs within distinct leukocyte subsets, as well as the effect of these changes on stroke outcomes. Methods Patients were recruited within 72 hours after ischemic stroke; complete blood count with differential was obtained at set time points. The relationships among leukocyte numbers, cortisol, adrenocorticotropic hormone, interleukin-6, and metanephrines were assessed at 72 hours after stroke. Associations between abnormal leukocyte counts at 72 hours, poststroke infection, and 3-month outcomes were determined. Results A total of 114 subjects were enrolled. Severe stroke was associated with leukocytosis, neutrophilia, monocytosis, lymphopenia, and eosinopenia. At 72 hours after stroke, increased serum cortisol was independently associated with neutrophilia and lymphopenia. Abnormal leukocyte counts were not independently predictive of poststroke infection, but lymphopenia was associated with poor outcome (modified Rankin score >3) at 3 months after stroke (odds ratio = 22.86 [1.95, 267.65]; P = .01). Conclusions Increased serum cortisol is independently associated with neutrophilia and lymphopenia after stroke. Lymphopenia is not an independent predictor of infections but is independently associated with worse outcome.
Improving Environmental Quality Through Aid: An Experimental Analysis of Aid Structures With Heterogeneous Agents

Abstract Environmental aid has grown significantly over the past decade with aid allocation mechanisms varying greatly and little guidance as to which should be preferred. To increase aid effectiveness, some have argued that potential recipients should compete for aid. We experimentally test this proposition against a baseline treatment where groups of heterogeneous agents receive aid by improving environmental quality. With the first mechanism, aid is allocated based on the improvement of environmental quality by each group with the potential of multiple groups receiving aid. In the second mechanism, aid is competitively allocated only to the single group that has initiated the greatest improvement of environmental quality. Surprisingly, the average level of environmental progress is lower in a competitive setting than in the setting with the potential for multiple recipients. Underscoring this result is our finding that environmental progress is stable in the baseline but begins high and falls quickly with repetitions in the competition. Although the initial level of progress is higher on average in the competitive setting, this mechanism generates the highest variance which could be catastrophic to sensitive ecosystems. These findings have direct implications on which mechanism the granting agency should use dependent upon their specific objectives.
A journey from blame to empathy in a family assessment of a mother and her sons.

Psychotherapists undertaking conjoint family treatment often feel stymied by the intensity and refractoriness of blaming among family members. Therapists feel drawn in as judges and referees, roles which do not seem to offer a possibility for constructive therapeutic activity. Embedded within the blameful exchanges, however, may be occasional moments of reflection by one or more members. Attending to these thoughtful experiences, rather than focusing on the angry exchange affords the therapist the opportunity of depending understanding and empathy among the family members. The family session described herein illustrates this evolution from blame to empathy. Language: en
Postscript I: What Exactly Are the Natural Numbers?

This postscript to Part I consists of philosophical and historical remarks concerning the nature of the natural numbers. It contrasts the absolutism absolutist approach requiring absolute constructions of individual natural numbers such as those given by Frege, G.Frege, Russell, B.Russell, Zermelo, E.Zermelo, and von Neumann, with Dedekind, R.Dedekind’s structuralism structuralist approach in which the natural numbers can be taken as members of any Dedekind–Peano system.
On no man’s (Is)land: futurities at the border

Focusing on communities that, displaced by riverbank erosion, relocate to the islands formed by silt sedimentation in the middle of the Ganga, along the stretch of the river that coincides with the...
A Decision Procedure for Univariate Polynomial Systems Based on Root Counting and Interval Subdivision.

This paper presents a formally verified decision procedure for determinining the satisfiability of a system of univariate polynomial relations over the real line. The procedure combines a root counting function, based on Sturm’s theorem, with an interval subdivision algorithm. Given a system of polynomial relations over the same variable, the decision procedure progressively subdivides the real interval into smaller intervals. The subdivision continues until the satisfiability of the system can be determined on each subinterval using Sturm’s theorem on a subset of the system’s polynomials. The decision procedure has been formally verified in the Prototype Verification System (PVS). In PVS, the decision procedure is specified as a computable Boolean function on a deep embedding of polynomial relations. This function is used to define a proof producing strategy for automatically proving existential and universal statements on polynomial systems. The soundness of the strategy solely depends on the internal logic of PVS.
Neurologic intensive care in patients with raised intracranial pressure

INTRODUCTION Intracranial hypertension is associated with a high mortality in patients with various encephalo-cranial disorders, so that it is important to recognize and treat the condition without delay. DEVELOPMENT The main factors interacting to maintain normal intracranial pressure are the cerebral blood flow, arteriolar radius, cerebral perfusion pressure and plasma viscosity. Current treatment of raised intracranial pressure is aimed to restore these factors to normal, so as to maintain equilibrium between encephalic mass, cerebro-spinal fluid and blood volume. As well as traditional measures such as hyperventilation, administration of mannitol and barbiturates, today there are also new treatments available to the intensive care neurologist: hypertonic saline solutions, hypothermia, craniectomies and neuroprotective agents.
Integrating Population Health Content into FNP Program Curriculum

In the current healthcare environment, the healthcare industry has become increasingly focused on population health concerns. While advanced practice registered nurses (APRNs) are well prepared to contribute to population health by delivering holistic healthcare to individuals, families, groups, communities, and populations, they are not engaged in initiatives to improve population health commensurate with their numbers, education, training, experience, and role as primary care providers and essential healthcare team leaders and members. This article discusses the rationale for integrating population health into APRN curricula, one program's approach to doing so, and preliminary lessons learned from this effort. The three main lessons learned include population health content should be integrated across the curriculum for all APRN cohorts, supplementary population health content should be considered, and opportunities for integrating didactic population health content should be included across the FNP curriculum.
Carbon monoxide sensitizes cisplatin-resistant ovarian cancer cell lines toward cisplatin via attenuation of levels of glutathione and nuclear metallothionein.

Abstract Cisplatin resistance remains a major impediment to effective treatment of ovarian cancer. Despite initial platinum responsiveness, thiol-containing peptides and proteins, glutathione (GSH) and metallothionein (MT), bind and inactivate cisplatin in cancer cells. Indeed, high levels of GSH and MT in ovarian cancers impart cisplatin resistance and are predictive of poor prognosis. Cystathionine β-synthase (CBS), an enzyme involved in sulfur metabolism, is overexpressed in ovarian cancer tissues and is itself associated with cisplatin resistance. Treatment with exogenous carbon monoxide (CO), a known inhibitor of CBS, may mitigate cisplatin resistance in ovarian cancer cells by attenuation of GSH and MT levels. Using a photo-activated CO-releasing molecule (photoCORM), [Mn(CO)3(phen)(PTA)]CF3SO3 (phen = 1,10-phenanthroline, PTA = 1,3,5-triza-7-phosphaadamantane) we assessed the ability of CO to sensitize established cisplatin-resistant ovarian cancer cell lines to cisplatin. Cisplatin-resistant cells, treated with both cisplatin and CO, exhibited significantly lower cell viability and increased poly (ADP-ribose) polymerase (PARP) cleavage versus those treated with cisplatin alone. These cisplatin-resistant cell lines overexpressed CBS and had increased steady state levels of GSH and expression of nuclear MT. Both CO treatment and lentiviral-mediated silencing of CBS attenuated GSH and nuclear MT expression in cisplatin resistant cells. We have demonstrated that CO, delivered from a photoCORM, sensitizes established cisplatin-resistant cell lines to cisplatin. Furthermore, we have presented strong evidence that the effects of CO in circumventing chemotherapeutic drug resistance is at least in part mediated by the inactivation of endogenous CBS.
Effect of Histone Lysine Methylation on DNA Lesion Reactivity in Nucleosome Core Particles.

Lysine methylation is a common post-translational histone modification that regulates transcription and gene expression. The lysine residues in the histone tail also react with damaged nucleotides in chromatin, including abasic sites and N7-methyl-2'-deoxyguanosine, the major product of DNA methylating agents. Lysine monomethylation transforms the e-amine into a secondary amine, which could be more nucleophilic and/or basic than the e-amine in lysine, and therefore more reactive with damaged DNA. The effect of lysine methylation on the reactivity with abasic sites and N7-methyl-2'-deoxyguanosine was examined in nucleosome core particles using a methylated lysine analogue derived from cysteine. e-Amine methylation increases the rate constant for abasic site reaction within nucleosome core particles. Reactivity at the two positions examined increased less than twofold. Mechanistic experiments indicate that faster β-elimination from an intermediate iminium ion accounts for accelerated abasic reactivity. The rate constants for nucleophilic attack (Schiff base/iminium ion formation) by the lysine and methylated lysine analogues are indistinguishable. Similarly, the rate constants describing nucleophilic attack by the lysine and methylated lysine analogues on β-2'-fluoro-N7-methyl-2'-deoxyguanosine to form DNA-protein cross-links are also within experimental error of one another. These data indicate that abasic site containing DNA will be destabilized by lysine methylation. However, these experiments do not indicate that DNA-protein cross-link formation, a recently discovered form of damage resulting from N7-guanine methylation, will be affected by this post-translational modification.
Hematology/Oncology in Noonan Syndrome

Abstract Since the first hematological abnormalities in Noonan syndrome were first described in 1980, we provide a brief contemporary review of the hematologic and oncologic associations unique to patients with Noonan syndrome. This review highlights the more common associations you are likely to encounter in caring for patients with Noonan syndrome.
Rapid Sequence Intubation Standardization and Improvement Process in the Pediatric Emergency Department

Background: Rapid Sequence Intubation (RSI) is the standard definitive airway management in the pediatric emergency department (PED). There are limited data describing time to intubation (TTI), adverse events (AE), and process variation for RSI in the PED. Prior studies demonstrate the first pass intubation success rate (FPISR) is between 26-85% and, the RSI-associated AE rate is between 20-61% in this setting. We report a low cost, multidisciplinary initiative to improve the safety of RSI in the PED. Methods: We conducted a single center quality improvement initiative (QII) at a tertiary care academic PED from 12/31/2015-1/31/2017. …
Cellular Reprogramming Approaches to Engineer Cardiac Pacemakers

The goal of this paper is to review present knowledge regarding biological pacemakers created by somatic reprogramming as a platform for mechanistic and metabolic understanding of the rare subpopulation of pacemaker cells, with the ultimate goal of creating biological alternatives to electronic pacing devices. Somatic reprogramming of cardiomyocytes by reexpression of embryonic transcription factor T-box 18 (TBX18) converts them into pacemaker-like. Recent studies take advantage of this model to gain insight into the electromechanical, metabolic, and architectural intricacies of the cardiac pacemaker cell across various models, including a surgical model of complete atrioventricular block (CAVB) in adult rats. The studies reviewed here reinforce the potential utility of TBX18-induced pacemaker myocytes (iPMS) as a minimally invasive treatment for heart block. Several challenges which must be overcome to develop a viable therapeutic intervention based on these observations are discussed.
Unraveling the Invisible but Harmful Impact of COVID-19 on Deaf Older Adults and Older Adults with Hearing Loss.

The invisible but deleterious impact of COVID-19 on health increases previously accumulated health disparities among older adults. Compared to hearing older adults, deaf older adults and older adults with hearing loss may be at higher risk for adverse COVID-related outcomes. This may be largely due to the intersection of low health literacy and knowledge about COVID-19, lack of access to public information regarding COVID-19, higher prevalence of chronic diseases, unintended negative consequences of using masks, and inaccessible health-care services (including COVID-19 testing). Therefore, social workers should develop and implement efficacious interventions aimed at reducing adverse COVID-19 outcomes in Deaf older adults and older adults with hearing loss.
ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment.

Although immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment, many patients do not respond or develop resistance to ICB. N6 -methylation of adenosine (m6A) in RNA regulates many pathophysiological processes. Here, we show that deletion of the m6A demethylase Alkbh5 sensitized tumors to cancer immunotherapy. Alkbh5 has effects on m6A density and splicing events in tumors during ICB. Alkbh5 modulates Mct4/Slc16a3 expression and lactate content of the tumor microenvironment and the composition of tumor-infiltrating Treg and myeloid-derived suppressor cells. Importantly, a small-molecule Alkbh5 inhibitor enhanced the efficacy of cancer immunotherapy. Notably, the ALKBH5 gene mutation and expression status of melanoma patients correlate with their response to immunotherapy. Our results suggest that m6A demethylases in tumor cells contribute to the efficacy of immunotherapy and identify ALKBH5 as a potential therapeutic target to enhance immunotherapy outcome in melanoma, colorectal, and potentially other cancers.
Self-Presentation on Social Media: When Self-Enhancement Confronts Self-Verification

Social media affords users the ability to control how they present themselves to their audience. People generally choose to show an ideal self-image on social media. However, this may be dependent ...
Football (soccer)-related spinal cord injury-reported cases from 1976 to 2020.

STUDY DESIGN An analysis of reported cases. OBJECTIVES To analyze the existing data on soccer (international football)-related spinal cord injury (SCI). SETTING Cases of soccer (international football)-related SCI that were reported globally. METHODS PubMed/MEDLINE, EMBASE, and online news publication databases were searched. RESULTS Fourteen cases of football-related SCI that occurred between 1976 and 2020 were found. Average age at the time of injury was 19 and 86% of individuals were males. Eight of 14 individuals had vertebral fracture/dislocation, whereas two individuals had concomitant traumatic brain injury. Neurologically, 54% had tetraplegia, 39% had paraplegia, and 8% each suffered from hemiplegia and sensory deficit. Two cases could regain ability to walk with orthosis and four had full mobility with "Return to Play" (RTP). The mortality was 14%. CONCLUSIONS Younger males were most commonly affected. The most common etiology, vertebral level of injury, and neurological manifestation was fall, cervical spine, and tetraplegia respectively. More than 50% of the individuals with football-related SCI were able to walk or RTP after rehabilitation. Further studies are required to establish universal RTP criteria and formulate preventive measures.
EM Lifetime Constrained Optimization for Multi-Segment Power Grid Networks

This chapter provides techniques for power grid network sizing while considering electromigration reliability. Starting with power grid network and electromigration (EM) fundamentals. Specifically the concerns here are EM immortality and aging effects used as EM constraints when formulating the optimization problems. The chapter first shows that the new power/ground (P/G) optimization problem, subject to the voltage IR drop and new EM constraints, can still be formulated as an efficient sequence of linear programming (SLP) problem, where the optimization is carried out in two linear programming phases in each iteration. The new optimization will ensure that none of the wires fails if all the constraints are satisfied. However, requiring all the wires to be EM immortal can be over-constrained. To mitigate this problem, the improvement is to consider the aging effects of interconnect wires in P/G networks. The idea is to allow some short-lifetime wires to fail and optimize the rest of the wires while considering the additional resistance caused by the failed wire segments. In this way, the resulting P/G networks can be optimized such that the target lifetime of the whole P/G networks can be ensured and will become more robust and aging-aware over the expected lifetime of the chip.
Discovering intimate partner violence from web search history

Abstract Intimate partner violence is a public health problem with increasing prevalence and harmful influence to both individuals and society. Automated screening for intimate partner violence is still an unsolved problem in academic research and practical applications. Current detection methods use self-reporting scales and in-person interviews, which are laborious, expensive, and often lack precision and sensitivity, making it essential to develop new approaches. This paper proposes a scalable and lightweight ubiquitous screening technique, validated via ground truth data collected through self assessment survey, for detecting signs of intimate partner violence by analyzing individual-level Google search histories. Initial analysis shows that there are temporal, textual, contextual differences in search behavior between individuals who have/haven't experienced intimate partner violence. Using these differentiating signals, we were able to build a model that can detect violence in intimate relationships with an F1 score of 0.80. Though preliminary, we hope our findings pave the way for the AI community to address this important public health problem.
Nonlinear elastic response of pan based carbon fiber to tensile loading and relations to microstructure

Abstract In this study, wide- and small-angle scattering (WAXS, SAXS) are used to analyze the structure of polyacrylonitrile (PAN) carbon fiber. Wide angle scattering is used to identify lattice parameters such as d-spacings, stacking height of crystalline planes (Lc), average crystallize size (Lc), and various other features (void content, degree of graphitization). Small angle scattering results show orientation and size distributions of pores/amorphous regions. Several analysis techniques were applied to small angle scattering results to ensure accuracy. XRD Data collected is correlated to single fiber mechanical properties and a fiber model is developed. Fiber modulus is heavily related to crystallite dimensions and orientation as well as pore structure. Authors hypothesize that the non-linear elasticity observed in the fiber direction of carbon fibers arises from elastic planar motion within turbostratic carbon. As crystalline regions grow and expand, the lattice structure improves lowering the barriers for (002) quasi-graphene plane motion. This miniscule elastic planar motion can lead to a large nonlinear response to tensile loading especially for high crystallinity carbon fibers and underlying deformation mechanics is addressed considering transverse-isotropy of turbostatic graphite crystals.
Robust Global Tracking Control for a Quadrotor Based on Uncertainty and Disturbance Estimator

Abstract In this paper, an uncertainty and disturbance estimator (UDE)-based robust global tracking control strategy for a quadrotor is presented. Utilizing the quaternion framework, the attitude and position controllers are developed to achieve the global singularity-free and computational efficient quadrotor control while the UDE is adopted to deal with model uncertainties and external disturbances. In order to handle the highly nonlinear quaternion-based quadrotor dynamics, the backstepping technique is utilized for the attitude controller derivation. The thrust-vectoring approach is employed for the position controller derivation. The effectiveness of the proposed approach is demonstrated using the attitude recovery experiment with large angle initial conditions.
Development of a compressive failure model for carbon fiber composites and associated uncertainties

Abstract An approach to increase the value of carbon fiber for wind turbines blades, and other compressive strength driven designs, is to identify pathways to increase its cost-specific compressive strength. A finite element model has been developed to evaluate the predictiveness of current finite element methods and to lay groundwork for future studies that focus on improving the cost-specific compressive strength. Parametric studies are conducted to understand which uncertainties in the model inputs have the greatest impact on compressive strength predictions. A statistical approach is also presented that enables the micromechanical model, which is deterministic, to efficiently account for statistical variability in the fiber misalignment present in composite materials; especially if the results from the hexagonal and square pack models are averaged. The model was found to agree well with experimental results for a Zoltek PX-35 pultrusion. The sensitivity studies suggest that the fiber packing and the interface shear strength have the greatest impact on compressive strength prediction for the fiber reinforced polymer studied here. Based on the performance of the modeling approach presented in this work, it is deemed sufficient for future work which will seek to identify carbon fiber composites with improved cost-specific compressive strength.
Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis.

Importance Two mRNA-based vaccines against coronavirus disease 2019 (COVID-19) were found to be highly efficacious in phase 3 clinical trials in the US. However, patients with chronic illnesses, including cirrhosis, were excluded from clinical trials. Patients with cirrhosis have immune dysregulation that is associated with vaccine hyporesponsiveness. Objective To study the association of receipt of the Pfizer BNT162b2 mRNA or the Moderna mRNA-1273 vaccines in patients with cirrhosis compared with a propensity-matched control group of patients at similar risk of infection and severe disease from COVID-19. Design, Setting, and Participants We performed a retrospective cohort study of patients with cirrhosis who received at least 1 dose of a COVID-19 mRNA vaccine at the Veterans Health Administration. Patients who received at least 1 dose of the vaccine (n = 20 037) were propensity matched with 20 037 controls to assess the associations of vaccination with new COVID-19 infection and COVID-19 hospitalization and death. Exposures Receipt of at least 1 dose of the BNT162b2 mRNA or the mRNA-1273 vaccines between December 18, 2020, and March 17, 2021. Main Outcomes and Measures COVID-19 infection as documented by a positive result for COVID-19 by polymerase chain reaction, hospitalization, and death due to COVID-19 infection. Results The median (interquartile range) age of the vaccinated individuals in the study cohort was 69.1 (8.4) years and 19 465 (97.2%) of the participants in each of the vaccinated and unvaccinated groups were male, consistent with a US veteran population. The mRNA-1273 vaccine was administered in 10 236 (51%) and the BNT162b2 mRNA in 9801 (49%) patients. Approximately 99.7% of patients who received the first dose of either vaccine with a follow-up of 42 days or more received a second dose. The number of COVID-19 infections in the vaccine recipients was similar to the control group in days 0 to 7, 7 to 14, 14 to 21, and 21 to 28 after the first dose. After 28 days, receipt of 1 dose of an mRNA vaccine was associated with a 64.8% reduction in COVID-19 infections and 100% protection against hospitalization or death due to COVID-19 infection. The association of reduced COVID-19 infections after the first dose was lower among patients with decompensated (50.3%) compared with compensated cirrhosis (66.8%). Receipt of a second dose was associated with a 78.6% reduction in COVID-19 infections and 100% reduction in COVID-19–related hospitalization or death after 7 days. Conclusions and Relevance This cohort study of US veterans found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19–related hospitalization or death in patients with cirrhosis.