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.
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.
Cell motility drives many biological processes, including immune responses and embryonic development. In the brain, microglia are immune cells that survey and scavenge brain tissue using elaborate motile processes. Motility of these processes is guided by local release of chemoattractants. However, most microglial processes retract during prolonged brain injury or disease. This hallmark of brain inflammation remains unexplained. Here we identified a molecular pathway in mouse and human microglia that converts ATP-driven process extension into process retraction during inflammation. This chemotactic reversal was driven by upregulation of the A2A adenosine receptor coincident with P2Y12 downregulation. Thus, A2A receptor stimulation by adenosine, a breakdown product of extracellular ATP, caused activated microglia to assume their characteristic amoeboid morphology during brain inflammation. Our results indicate that purine nucleotides provide an opportunity for context-dependent shifts in receptor signaling. Thus, we reveal an unexpected chemotactic switch that generates a hallmark feature of CNS inflammation.
Background
This study determined the reliability of topographic motor cortical maps and MEP characteristics in the extensor digitorum communis (EDC) evoked by single-pulse TMS among patients with chronic stroke.
Methods
Each of ten patients was studied on three occasions. Measures included location of the EDC hotspot and center of gravity (COG), threshold of activation and average amplitude of the hotspot, number of active sites, map volume, and recruitment curve (RC) slope.
Results
Consistent intrahemispheric measurements were obtained for the three TMS mapping sessions for all measured variables. No statistically significant difference was observed between hemispheres for the number of active sites, COG distance or the RC slope. The magnitude and range of COG movement between sessions were similar to those reported previously with this muscle in able-bodied individuals. The average COG movement over three sessions in both hemispheres was 0.90 cm. The average COG movement in the affected hemisphere was 1.13 (± 0.08) cm, and 0.68 (± 0.04) cm) for the less affected hemisphere. However, significant interhemispheric variability was seen for the average MEP amplitude, normalized map volume, and resting motor threshold.
Conclusion
The physiologic variability in some TMS measurements of EDC suggest that interpretation of TMS mapping data derived from hemiparetic patients in the chronic stage following stroke should be undertaken cautiously. Irrespective of the muscle, potential causes of variability should be resolved to accurately assess the impact of pharmacological or physical interventions on cortical organization as measured by TMS among patients with stroke.
An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer–relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.001), as well as for the subset of 42 Gleason score 7 patients (P < 0.001). We performed an independent validation analysis on 40 samples and found that the biomarker panel was also significant at prediction of biochemical recurrence for all cases (P = 0.013) and for a subset of 19 Gleason score 7 cases (P = 0.010), both of which were adjusted for relevant clinical information including T-stage, prostate-specific antigen, and Gleason score. Importantly, these biomarkers could significantly predict clinical recurrence for Gleason score 7 patients. These biomarkers may increase the accuracy of prognostication following radical prostatectomy using formalin-fixed specimens.
In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site’s mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development.
by
James J Kohler;
Seyed H. Hosseini;
Elgin Green;
Amy Hoying-Brandt;
Ioan Cucoranu;
Chad P. Haase;
Rodney Russ;
Jaya Srivastava;
Kristopher Ivey;
Tomika Ludaway;
Victor Kapoor;
Allison Abuin;
Alexsey Shapoval;
Robert Santoianni;
Ann Saada;
Orly Elpeleg;
William Lewis
Mitochondrial (mt) DNA biogenesis is critical to cardiac contractility. DNA polymerase gamma (pol γ) replicates mtDNA, whereas thymidine kinase 2 (TK2) monophosphorylates pyrimidines intramitochondrially. Point mutations in POLG and TK2 result in clinical diseases associated with mtDNA depletion and organ dysfunction. Pyrimidine analogs (NRTIs) inhibit Pol γ and mtDNA replication. Cardiac “dominant negative” murine transgenes (TGs; Pol γ Y955G, and TK2 H121N or I212N) defined the role of each in the heart. mtDNA abundance, histopathological features, histochemistry, mitochondrial protein abundance, morphometry, and echocardiography were determined for TGs in “2 × 2” studies with or without pyrimidine analogs. Cardiac mtDNA abundance decreased in Y955C TGs (∼50%) but increased in H121N and I212N TGs (20-70%). Succinate dehydrogenase (SDH) increased in hearts of all mutants. Ultrastructural changes occurred in Y955C and H121N TGs. Histopathology demonstrated hypertrophy in H121N, LV dilation in I212N, and both hypertrophy and dilation in Y955C TGs. Antiretrovirals increased LV mass (≈50%) for all three TGs which combined with dilation indicates cardiomyopathy. Taken together, these studies demonstrate three manifestations of cardiac dysfunction that depend on the nature of the specific mutation and antiretroviral treatment. Mutations in genes for mtDNA biogenesis increase risk for defective mtDNA replication, leading to LV hypertrophy.
Objective: To correlate the pathologic findings of temporal artery biopsies in patients clinically defined as positive, presumed, or negative for giant cell arteritis (GCA).
Design: Retrospective case series.
Participants and Controls: Patients evaluated for giant cell arteritis.
Methods: Temporal artery biopsies examined between 1989 and 2007 were studied. Clinical information and residual tissue for immunohistochemical staining was identified in 107 patients. Clinical information was used in order to make a diagnosis of “positive”, “presumed”, or “negative” GCA. The biopsies were reviewed in a masked fashion and classified as “positive”, “indeterminate”, or “negative” based on published, classic pathologic diagnosis (CPD) criteria. All biopsies were immunostained for CD3 and CD68 and graded as “negative”, “mildly” (+), “moderately” (++), or “markedly” (+++) positive. Clinical and pathologic results were correlated and a modified pathologic diagnosis classification (MPD) scheme was developed. The modified scheme was compared in a masked fashion with the final clinical diagnosis and positive and negative predictive values (PVs) were calculated.
Main Outcome Measures: Pathologic diagnosis and final clinical diagnosis.
Results: Using the MPD classification, there were 25%, 16% and 61% positive, indeterminate, and negative biopsies, respectively. There was excellent correlation between the modified pathologic criteria and final clinical diagnosis (correlation coefficient 0.997, p value <0.0001, kappa 0.81). The positive predictive values (PVs) for CPD and MPD were 85% and 96%, respectively. The negative PVs for CPD and MPD were 64% and 61%, respectively. Positive and negative biopsies strongly correlated with clinical diagnoses of positive and negative for GCA, respectively whereas indeterminate cases moderately correlated with presumed GCA. The diagnosis did not change from the original biopsy in 11 patients who had a second biopsy. Immunostaining for CD 68 was helpful in several indeterminate cases.
Conclusions: We recommend using the modified histologic classification of temporal artery biopsies. There are indeterminate cases that cannot be further defined using current pathologic classification criteria. A second biopsy has very limited value. Immunostaining for CD68 stain may be helpful in indeterminate cases, although the diagnosis in these cases is based on clinical judgement.
by
Marisa Young;
RC Bailey;
I Nyaboke;
ME Mackesy-Amiti;
E Okello;
V Pengo;
B Ochomo;
ME Auma;
S Were;
S Ojuok;
E Adoyo;
M Adhiambo;
RM Plank;
FO Otieno
Objectives
This case study showcases an academic health sciences library's experience with designing comprehensive search strategies for a given grant number. Through our research impact and analysis services, we assist with annual progress reports and funding renewals. Key to this is the identification of recent citations to specific grant support. Award administrators also seek to supplement self-reporting with robust search-strategy alerts.
Methods
Using a research center grant awarded by the NIH (P30 grant) as a case study, we will discuss the search strategies developed for the PubMed and Web of Science databases as well as the different indexing practices and result variations. Of particular importance are the common author mistakes in award citations (confusion of letters and numbers, transpositions, missing zeros, etc.) and how each database responds to such scenarios. Since the example center grant covers over 200 associated researchers, the documentation and careful inclusion of common variations is an important element of comprehensive searching. Final search results were compared against NIH RePORTER records (https://projectreporter.nih.gov/reporter.cfm) to determine extant of coverage in each databases under the finalized search strategies and the effect of author reporting variations on publication-grant linking.
Results
Our results found a total of 15 unique grant variations in Web of Science indexed funding results and 13 unique grant citation variations in PubMed. These variations returned 549 publication results in Web of Science and 851 publication results in PubMed. NIH RePROTER listed 685 publication results linked to our grant of interest. All of the NIH RePORTER listings were returned by the PubMed variations. However, both Web of Science and PubMed returned unique results when compared to the NIH RePORTER listings as well as to each other. Excluding the most current year (2016) approximately 20% of grant citing publications were not captured in NIH RePORTER. For those publications not in NIH RePORTER, 99.9% had PMCIDs so any reasons for exclusion have yet to be determined.
Conclusions
Once the citation variations for a given grant have been determined, PubMed offers the best coverage of citing publications. Results should be supplemented with a Web of Science search to capture additional unique articles. Robust analysis of variation possibilities may be needed periodically to ensure that PubMed and/or Web of Science searches or alerts still contain relevant citation variations.
by
Kimberly A. Dowd;
Christina R. DeMaso;
Rebecca S. Pelc;
Scott D. Speer;
Alexander R. Y. Smith;
Leslie Goo;
Derek J. Platt;
John R. Mascola;
Barney S. Graham;
Mark Mulligan;
Michael S. Diamond;
Julie E. Ledgerwood;
Theodore C. Pierson
Recent epidemics of Zika virus (ZIKV) have been associated with congenital malformation during pregnancy and Guillain-Barré syndrome. There are two ZIKV lineages (African and Asian) that share >95% amino acid identity. Little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. We investigated the breadth of the neutralizing antibody response following ZIKV infection by measuring the sensitivity of six ZIKV strains to neutralization by ZIKV-confirmed convalescent human serum or plasma samples. Contemporary Asian and early African ZIKV strains were similarly sensitive to neutralization regardless of the cellular source of virus. Furthermore, mouse immune serum generated after infection with African or Asian ZIKV strains was capable of neutralizing homologous and heterologous ZIKV strains equivalently. As our study defines only a single ZIKV serotype, vaccine candidates eliciting robust neutralizing antibody responses should inhibit infection of both ZIKV lineages, including strains circulating in the Americas.
by
Mitsunori Odagiri;
Alexander Schriewer;
Miles E. Daniels;
Stefan Wuertz;
Woutrina A. Smith;
Thomas Clasen;
Wolf-Peter Schmidt;
Yujie Jin;
Belen Torondel;
Pravas R. Misra;
Pinaki Panigrahi;
Marion W. Jenkins
Efforts to eradicate open defecation and improve sanitation access are unlikely to achieve health benefits unless interventions reduce microbial exposures. This study assessed human fecal contamination and pathogen exposures in rural India, and the effect of increased sanitation coverage on contamination and exposure rates. In a cross-sectional study of 60 villages of a cluster-randomized controlled sanitation trial in Odisha, India, human and domestic animal fecal contamination was measured in community tubewells and ponds (n = 301) and via exposure pathways in homes (n = 354), using Bacteroidales microbial source tracking fecal markers validated in India. Community water sources were further tested for diarrheal pathogens (rotavirus, adenovirus and Vibrio cholerae by quantitative PCR; pathogenic Escherichia coli by multiplex PCR; Cryptosporidium and Giardia by immunomagnetic separation and direct fluorescent antibody microscopy). Exposure pathways in intervention and control villages were compared and relationships with child diarrhea examined. Human fecal markers were rarely detected in tubewells (2.4%, 95%CI: 0.3-4.5%) and ponds (5.6%, 95%CI: 0.8-10.3%), compared to homes (35.4%, 95%CI: 30.4-40.4%). In tubewells, V. cholerae was the most frequently detected pathogen (19.8%, 95%CI: 14.4-25.2%), followed by Giardia (14.8%, 95%CI: 10.0-19.7%). In ponds, Giardia was most often detected (74.5%, 95%CI: 65.7-83.3%), followed by pathogenic E. coli (48.1%, 95%CI: 34.8-61.5%) and rotavirus (44.4%, 95%CI: 34.2-54.7%). At village-level, prevalence of fecal pathogen detection in community drinking water sources was associated with elevated prevalence of child diarrhea within 6 weeks of testing (RR 2.13, 95%CI: 1.25-3.63) while within homes, higher levels of human and animal fecal marker detection were associated with increased risks of subsequent child diarrhea (P = 0.044 and 0.013, respectively). There was no evidence that the intervention, which increased functional latrine coverage and use by 27 percentage points, reduced human fecal contamination in any tested pathway, nor the prevalence of pathogens in water sources. In conclusion, the study demonstrates that (1) improved sanitation alone may be insufficient and further interventions needed in the domestic domain to reduce widespread human and animal fecal contamination observed in homes, (2) pathogens detected in tubewells indicate these sources are microbiologically unsafe for drinking and were associated with child diarrhea, (3) domestic use of ponds heavily contaminated with multiple pathogens presents an under-recognized health risk, and (4) a 27 percentage point increase in improved sanitation access at village-level did not reduce detectable human fecal and pathogen contamination in this setting.
Purpose We expanded the clinical usefulness of EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice) by evaluating its responsiveness to health related quality of life changes, defining the minimally important differences for an individual patient change in each domain and applying it to a sexual outcome prediction model. Materials and Methods In 1,201 subjects from a previously described multicenter longitudinal cohort we modeled the EPIC-CP domain scores of each treatment group before treatment, and at short-term and long-term followup. We considered a posttreatment domain score change from pretreatment of 0.5 SD or greater clinically significant and p ≤0.01 statistically significant. We determined the domain minimally important differences using the pooled 0.5 SD of the 2, 6, 12 and 24-month posttreatment changes from pretreatment values. We then recalibrated an EPIC-CP based nomogram model predicting 2-year post-prostatectomy functional erection from that developed using EPIC-26. Results For each health related quality of life domain EPIC-CP was sensitive to similar posttreatment health related quality of life changes with time, as was observed using EPIC-26. The EPIC-CP minimally important differences in changes in the urinary incontinence, urinary irritation/obstruction, bowel, sexual and vitality/hormonal domains were 1.0, 1.3, 1.2, 1.6 and 1.0, respectively. The EPIC-CP based sexual prediction model performed well (AUC 0.76). It showed robust agreement with its EPIC-26 based counterpart with 10% or less predicted probability differences between models in 95% of individuals and a mean ± SD difference of 0.0 ± 0.05 across all individuals. Conclusions EPIC-CP is responsive to health related quality of life changes during convalescence and it can be used to predict 2-year post-prostatectomy sexual outcomes. It can facilitate shared medical decision making and patient centered care.
This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37±0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications.
Purpose. This study examines the prevalence of alcohol-related problems, the factors underlying these problems, and whether or not there is evidence of syndemic effects in a community population of southern, urban African American women. Methods. Questionnaire-based interviews were conducted with 817 women, all African American, from 80 targeted census block groups in Atlanta, Georgia. Results. Most of the alcohol users (67.8%) experienced at least one problem as a result of their alcohol (ab)use, with most women experiencing two or more such problems. Eight factors were found to be associated with experiencing more alcohol problems: being aged 30 or older, having had no recent health insurance, lower levels of educational attainment, self-identifying as lesbian or bisexual, experiencing greater amounts of childhood maltreatment, greater impulsivity, perceiving one’s local community or neighborhood to be unsafe, and having a larger number of criminally involved friends. Conclusions. Drinking-related problems were prevalent in this population. Numerous factors underlie the extent to which African American women experienced problems resulting from their alcohol use. There is strong evidence of syndemic-type effects influencing drinking problems in this population, and future efforts to reduce the negative impact of alcohol (ab)use ought to consider the adoption of programs using a syndemics’ theory approach.