In Ontological Terror Calvin L. Warren intervenes in Afro-pessimism, Heideggerian metaphysics, and black humanist philosophy by positing that the "Negro question" is intimately imbricated with questions of Being. Warren uses the figure of the antebellum free black as a philosophical paradigm for thinking through the tensions between blackness and Being. He illustrates how blacks embody a metaphysical nothing. This nothingness serves as a destabilizing presence and force as well as that which whiteness defines itself against. Thus, the function of blackness as giving form to nothing presents a terrifying problem for whites: they need blacks to affirm their existence, even as they despise the nothingness they represent. By pointing out how all humanism is based on investing blackness with nonbeing—a logic which reproduces antiblack violence and precludes any realization of equality, justice, and recognition for blacks—Warren urges the removal of the human from its metaphysical pedestal and the exploration of ways of existing that are not predicated on a grounding in being.
This paper discusses how the arrival of born-digital content into archives operating systems and complex digital collections, archives must build upon practices developed over recent decades in the handling of electronic records while also radically reconsidering the extent of acquisition and approaches to access. These changes are discussed within the context of the manuscripts and computers that comprise Salman Rushdie’s personal literary “papers,” which are housed in Emory University’s Manuscript, Archives, and Rare Book Library (MARBL). Early in the development of the Rushdie project, the library made a commitment to approach the material as holistically as possible, to prioritize the integration of paper and digital, and to balance the needs of donors with those of researchers. The paper will outline how the library developed researcher tools that allow concurrent exploration of the paper material and the born-digital material via emulation and item-level, database-driven searches.
Designed to meet the needs of all who play a role in the MR imaging process, this book first develops the very important concepts of the physical principles on which MR imaging is based and then builds an understanding of the various methods and techniques that are at the heart of each imaging procedure. It gives special emphasis to image quality and the associated issues of optimizing protocols. Safety concerns are addressed in order to have an informed staff who can take a realistic approach to reducing risk and increasing patient comfort and acceptance. People who know how to apply various imaging options to the wide range of clinical needs will continue to be a vital link in the total MR imaging process: the objective of this book is to help them obtain maximum performance and benefit from the sophisticated MR technology that is available today.
Beginning with his famous 1963 lecture on Foucault, Derrida repeatedly invokes a line from Kierkegaard, often translated from his French as ‘the instant of decision is madness,’ without ever giving a precise reference or subjecting that sentence to anything like a reading in the Derridean sense. This paper tracks some of the unsuspected complexities that emerge when that sentence is located in Kierkegaard and the Pauline tradition to which Kierkegaard is appealing. It is suggested that the singular functioning of this sentence in Derrida nonetheless, in its very failure to read, shows up something of the madness, folly or stupidity at play in Kierkegaard’s thinking, and thus performs in its repetitions something of the unreadability that opens the possibility of reading itself.
Based on Micah Vandegrift’s article What is digital humanities and what’s it doing in the library? and Stewart Varner’s response to that piece, this article offers an overview of the foundational ideals where libraries and digital humanities overlap. The authors lay out practical ways for libraries to involve themselves in this evolving area, especially focused on current strengths of many libraries including commitments to resource accessibility and project development. Finally, this article proposes that the role of the research librarian is evolving in order to effectively integrate the library as a partner in the scholarship of digital humanities.
Jahnke and Asher explore workflows and methodologies at a variety of academic data curation sites, and Keralis delves into the academic milieu of library and information schools that offer instruction in data curation. Their conclusions point to the urgent need for a reliable and increasingly sophisticated professional cohort to support data-intensive research in our colleges, universities, and research centers.
The incidence of obesity is rising with greater than 40% of the world’s population expected to be overweight or suffering from obesity by 2030. This is alarming because obesity increases mortality rates in patients with various cancer subtypes including leukemia. The survival differences between lean patients and patients with obesity are largely attributed to altered drug pharmacokinetics in patients receiving chemotherapy; whereas, the direct impact of an adipocyte-enriched microenvironment on cancer cells is rarely considered. Here we show that the adipocyte secretome upregulates the surface expression of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukemia cells (B-ALL) which promotes chemoresistance. Antibody-mediated targeting of GAL-9 on B-ALL cells induces DNA damage, alters cell cycle progression, and promotes apoptosis in vitro and significantly extends the survival of obese but not lean mice with aggressive B-ALL. Our studies reveal that adipocyte-mediated upregulation of GAL-9 on B-ALL cells can be targeted with antibody-based therapies to overcome obesity-induced chemoresistance.
Ample research links mothers’ postpartum depression (PPD) to adverse interactions with their infants. However, most studies relied on general population samples, whereas a substantial number of women are at elevated depression risk. The purpose of this study was to describe mothers’ interactions with their 6- and 12-month-old infants among women at elevated risk, although with a range of symptom severity. We also identified higher-order factors that best characterized the interactions and tested longitudinal consistency of these factors from 6 to 12 months of infant age. We leveraged data from eight projects across the United States (n = 647), using standardized depression measures and an adaptation of the NICHD Mother-Infant Interaction Scales. Overall, these depression-vulnerable mothers showed high levels of sensitivity and positive regard and low levels of intrusiveness, detachment, and negative regard with their infants. Factor analyses of maternal behaviors identified two overarching factors—“positive engagement” and “negative intrusiveness” that were comparable at 6 and 12 months of infant age. Mothers’ ability to regulate depressed mood was a key behavior that defined “positive engagement” in factor loadings. An exceptionally strong loading of intrusiveness on the second factor suggested its central importance for women at elevated depression risk. Mothers with severe depressive symptoms had significantly more “negative intrusiveness” and less “positive engagement” with their 6-month-old infants than women with moderate or fewer depressive symptoms, suggesting a potential tipping point at which symptoms may interfere with the quality of care. Results provide the foundation for further research into predictors and moderators of women’s interactions with their infant among women at elevated risk for PPD. They also indicate a need for evidence-based interventions that can support more severely depressed women in providing optimal care.
Inflammation impacts basal ganglia motor circuitry in association with psychomotor retardation, a key symptom of major depression (MD). We previously reported associations between circulating protein inflammatory biomarkers and psychomotor slowing as measured by neuropsychological tests probing psychomotor speed in patients with MD. To discover novel transcriptional signatures in peripheral blood immune cells related to psychomotor slowing, microarray data were analyzed in a primary cohort of 88 medically-stable, unmedicated, ambulatory MD patients. Results were confirmed and extended in a second cohort of 57 patients with treatment resistant depression (TRD) before and after anti-inflammatory challenge with the tumor necrosis factor antagonist infliximab versus placebo. Composite scores reflecting pure motor and cognitive-motor processing speed were linearly associated with 403 and 266 gene transcripts in each cohort, respectively (|R| > 0.30, p < 0.01), that were enriched for cytokine signaling and glycolysis-related pathways (p < 0.05). Unsupervised clustering in the primary cohort revealed two psychomotor slowing-associated gene co-expression modules that were enriched for interferon, interleukin-6, aerobic glycolysis, and oxidative phosphorylation pathways (p < 0.05, q < 0.1). Transcripts were predominantly derived from monocytes, plasmacytoid dendritic cells, and natural killer cells (p’s < 0.05). In infliximab-treated TRD patients with high plasma C-reactive protein concentrations (>5 mg/L), two differential co-expression modules enriched for oxidative stress and mitochondrial degradation were associated with improvements in psychomotor reaction time (p < 0.05). These results indicate that inflammatory signaling and associated metabolic reprogramming in peripheral blood immune cells are associated with systemic inflammation in depression and may affect relevant brain circuits to promote psychomotor slowing.
by
Eric Sundberg;
M Garcia-Alija;
JJ Du;
I Ordonez;
A Diz-Vallenilla;
A Moraleda-Montoya;
N Sultana;
CG Huynh;
C Li;
TC Donahue;
L-X Wang;
B Trastoy;
ME Guerin
Bacteria produce a remarkably diverse range of glycoside hydrolases to metabolize glycans from the environment as a primary source of nutrients, and to promote the colonization and infection of a host. Here we focus on EndoE, a multi-modular glycoside hydrolase secreted by Enterococcus faecalis, one of the leading causes of healthcare-associated infections. We provide X-ray crystal structures of EndoE, which show an architecture composed of four domains, including GH18 and GH20 glycoside hydrolases connected by two consecutive three α-helical bundles. We determine that the GH20 domain is an exo-β-1,2-N-acetylglucosaminidase, whereas the GH18 domain is an endo-β-1,4-N-acetylglucosaminidase that exclusively processes the central core of complex-type or high-mannose-type N-glycans. Both glycoside hydrolase domains act in a concerted manner to process diverse N-glycans on glycoproteins, including therapeutic IgG antibodies. EndoE combines two enzyme domains with distinct functions and glycan specificities to play a dual role in glycan metabolism and immune evasion.
We developed a prognostic model for longer-term outcome prediction in traumatic brain injury (TBI) using an attention-based recurrent neural network (RNN). The model was trained on admission and time series data obtained from a multi-site, longitudinal, observational study of TBI patients. We included 110 clinical variables as model input and Glasgow Outcome Score Extended (GOSE) at six months after injury as the outcome variable. Designed to handle missing values in time series data, the RNN model was compared to an existing TBI prognostic model using 10-fold cross validation. The area under receiver operating characteristic curve (AUC) for the RNN model is 0.86 (95% CI 0.83-0.89) for binary outcomes, whereas the AUC of the comparison model is 0.69 (95% CI 0.67-0.71). We demonstrated that including time series data into prognostic models for TBI can boost the discriminative ability of prediction models with either binary or ordinal outcomes.
Radiology reports are a rich resource for advancing deep learning applications for medical images, facilitating the generation of large-scale annotated image databases. Although the ambiguity and subtlety of natural language poses a significant challenge to information extraction from radiology reports. Thyroid Imaging Reporting and Data Systems (TI-RADS) has been proposed as a system to standardize ultrasound imaging reports for thyroid cancer screening and diagnosis, through the implementation of structured templates and a standardized thyroid nodule malignancy risk scoring system; however there remains significant variation in radiologist practice when it comes to diagnostic thyroid ultrasound interpretation and reporting. In this work, we propose a computerized approach using a contextual embedding and fusion strategy for the large-scale inference of TI-RADS final assessment categories from narrative ultrasound (US) reports. The proposed model has achieved high accuracy on an internal data set, and high performance scores on an external validation dataset.
Objective
To identify distinctly regulated gene markers and enriched gene sets in breast tissue of cynomolgus monkeys (Macaca fascicularis) treated for six months with either conjugated equine estrogens (CEE) or estradiol (E2) by analysis of corresponding mRNA levels of genes associated with breast development, carcinogenesis, apoptosis and immune regulation. Additionally, translation of three nuclear markers was analyzed.
Methods
RNA from breast biopsies and necropsies was isolated from two independent study trials from Ethun et al. (CEE) and Foth et al. (E2) after 6 month of treatment duration. RNA was subjected to qRT-PCR and MicroArray analysis. Immunohistochemical stainings were performed for the estrogen receptor alpha subunit (ERa), the progesterone receptor (PGR) and the proliferation marker Ki67.
Results
We identified a total of 36 distinctly enriched gene sets. Thirty-one were found in the CEE treatment group and five were found in the E2 treatment group, with no overlap. Furthermore, two individual genes IGFBP1 and SGK493 were upregulated in CEE treated animals. Additional targeted qRT-PCR analysis of ten specific estrogen-related genes showed upregulation of three genes (TFF1, PGR and GREB1) after CEE treatment, respectively one gene (TFF1) after E2 treatment. Immunohistochemical stains of breast biopsies showed a significant increase in expression of the PGR marker after CEE treatment.
Conclusions
In this study we identified enriched gene sets possibly induced by CEE or E2 treatment in various processes associated with cancer biology and immunology. This preliminary translational data supports the concept that different estrogen types have different effects on healthy breast tissue and may help generate hypotheses for future research.
by
Alvaro Alonso;
A Alam;
H Kamel;
V Subbian;
J Qian;
E Boerwinkle;
M Cicek;
CR Clark;
EG Cohn;
KA Gebo;
R Loperena-Cortes;
KR Mayo;
S Mockrin;
L Ohno-Machado;
SD Schully;
AH Ramirez;
P Greenland
Background The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described. Methods We analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR. Results At enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF. Conclusion The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.
by
Jonathan Sevransky;
H Meissen;
MN Gong;
A-KI Wong;
JJ Zimmerman;
N Nadkarni;
SL Kane-Gil;
J Amador-Castaneda;
H Bailey;
SM Brown;
AD DePriest;
I Mary Eche;
M Narayan;
JJ Provencio;
NO Sederstrom;
J Tremper;
RA Aslakson
While technological innovations are the invariable crux of speculation about the future of critical care, they cannot replace the clinician at the bedside. This article summarizes the work of the Society of Critical Care Medicine-appointed multiprofessional task for the Future of Critical Care. The Task Force notes that critical care practice will be transformed by novel technologies, integration of artificial intelligence decision support algorithms, and advances in seamless data operationalization across diverse healthcare systems and geographic regions and within federated datasets. Yet, new technologies will be relevant and meaningful only if they improve the very human endeavor of caring for someone who is critically ill.
by
Elisabeth Binder;
EW Tobi;
DL Juvinao-Quintero;
J Ronkainen;
R Ott;
R Alfano;
M Canouil;
ML Geurtsen;
A Khamis;
LK Küpers;
IY Lim;
P Perron;
G Pesce;
J Tuhkanen;
AP Starling;
T Andrew;
R Caiazzo;
JKY Chan;
R Gaillard;
PD Gluckman;
E Keikkala;
N Karnani;
S Mustaniemi;
TS Nawrot;
F Pattou;
M Plusquin;
V Raverdy;
KH Tan;
E Tzala;
K Raikkonen;
C Winkler;
AG Ziegler;
I Annesi-Maesano;
L Bouchard;
YS Chong;
D Dabelea;
JF Felix;
B Heude;
VWV Jaddoe;
J Lahti;
B Reimann;
M Vääräsmäki;
A Bonnefond;
P Froguel;
S Hummel;
E Kajantie;
MR Jarvelin;
RPM Steegers-Theunissen;
CG Howe;
MF Hivert;
S Sebert
OBJECTIVE: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. RESEARCH DESIGN AND METHODS: To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). We performed lookup analyses for identified cytosine-guanine dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression. RESULTS: Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β [SE] -0.013 [2.1 × 10-3], P value corrected for false discovery rate [PFDR] = 5.1 × 10-3) and cg02988288 (β [SE]-0.013 [2.3 × 10-3], PFDR = 0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm. CONCLUSIONS: Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent lookup analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.