Miracle-dz/UniFAR-FTUs huggingface dataset:
Healthcare providers' views and perceptions on post-mortem procedures for cause of death determination in Southern Mozambique

Background The minimally invasive autopsy (MIA) is being investigated as an alternative to the complete diagnostic autopsy (CDA), gold standard for CoD determination, in settings where CDA is unfeasible and/or unacceptable. We aimed to explore healthcare providers’ views and perceptions on theoretical and factual acceptability of the CDA and the MIA. Methods A qualitative study, combining ethnographic and grounded-theory approaches, was conducted within a project aiming to validate the MIA tool against the CDA for CoD investigation. We present data on in-depth and semi-structured interviews of 33 healthcare providers operating within the formal and informal health services in Southern Mozambique. MIA perception was analysed through the theory of diffusion of innovations. Results All participants considered CDA useful for CoD determination. CDA was perceived reliable, but the unpleasant nature of the procedure and its associated infection risk were the main perceived disadvantages. Participants considered the MIA simple, easy and quick to perform; likely to meet families’ expectations to know the CoD, and able to provide evidence-based knowledge for disease management. Concerns were raised on its reliability compared to the CDA. Family's emotional status and accessibility to decision-makers were mentioned as principal barriers for MIA performance. The main jeopardizing factors for MIA implementation were the shortage of required resources and the significant proportion of people dying at home. Key facilitators for MIA acceptance included the need for the support from community and religious leaders, provision of clear information to the community, and accompaniment to bereaved families. Conclusions Healthcare providers consider the MIAs potentially more acceptable and feasible than CDAs in places where the latter have shown significant implementation challenges. A clear understanding of healthcare provider’s perceived barriers and facilitators for conducting post-mortem procedures in general, and MIAs in particular, will shed light on their future field implementation for more robust mortality surveillance.
Finding Some Good in an Invasive Species: Introduction and Assessment of a Novel CURE to Improve Experimental Design in Undergraduate Biology Classrooms

Reports such as Vision and Change in Undergraduate Biology Education call for integration of course-based undergraduate research experiences (CUREs) into biology curricula and less emphasis on “cookbook” laboratories. CUREs, often characterized by a single open-ended research question, allow students to develop hypotheses, design experiments, and collaborate with peers. Conversely, “cookbook” labs incentivize task completion and have pre-determined experimental outcomes. While research comparing CUREs and “cookbook” labs is growing, there are fewer comparisons among CUREs. Here, we present a novel CURE built around an invasive grass, Bromus inermis. We evaluated this CURE’s effectiveness in improving students’ understanding of the Vision and Change competency relating to the application of the scientific process through development and testing of hypotheses. We did so by comparing changes in pre- and posttest scores on the Experimental Design Ability Test (EDAT) between Brome CURE students and students in a concurrent CURE, SEA-PHAGES. While students in both CUREs showed improvements at the end of the semester, Brome CURE students showed a greater increase in EDAT scores than did SEA-PHAGES CURE students. Additionally, Brome CURE students had significantly higher gains in 6 of the 10 EDAT criteria. We conclude that the Brome CURE is an effective ecological parallel to the SEA-PHAGES CURE and can help students gain a meaningful understanding of Vision and Change competencies. Journal of Microbiology & Biology Education
Behavioral Self-Regulation of Telework Locations: Interrupting Interruptions!

This study examines the impact of alternative telework strategies on professional and personal outcomes. The research design is a longitudinal betweenparticipants field experiment with two manipulated factors: satellite office space available (no, yes) and downtown office space available (no, yes). In all four conditions, participants could telework from home. The design incorporated a fifth (control) condition with no telework, reflecting current company policy. One hundred sixty medical coders from a large health care company participated in the experiment. Archival data recorded work locations, task interruptions, quality adjusted task performance, and employee retention, while the experience sampling method (ESM) captured cognitive and affective responses. The findings help to explain the social dynamics of work location autonomy in the rich ecological settings of employees’ organizational and per-
“I am not promiscuous enough!”: Exploring the low uptake of HIV testing by gay men and other men who have sex with men in Metro Manila, Philippines

The Philippines faces a severe HIV epidemic among gay and other men who have sex with men (MSM). HIV testing uptake remains low. A case series of 12 men from Metro Manila were interviewed to explore barriers to uptake of HIV testing services. Most did not see the need to get tested for HIV despite significant risk, based on the misconception they were feeling well or showed no symptoms. Being of a higher socioeconomic class, feeling morally superior to other gay men, distance of the testing facility, fear of what will happen once infected, fear of HIV- and sexual stigma, fear of side effects of antiretroviral drugs and fear of high health care expenses after testing positive for HIV were key reasons why MSM kept postponing their test. Misconceptions about HIV risk, disease, and treatment and care need to be addressed in order to increase uptake of HIV services in this population.
Isotype-Switched Autoantibodies Are Necessary To Facilitate Central Nervous System Autoimmune Disease in Aicda−/− and Ung−/− Mice

B cell–depleting therapies have been shown to ameliorate symptoms in multiple sclerosis (MS) patients; however, the mechanism of action remains unclear. Following priming with Ag, B cells undergo secondary diversification of their BCR, including BCR class-switch recombination (CSR) and somatic hypermutation (SHM), with both processes requiring the enzyme activation-induced (cytidine) deaminase. We previously reported that activation-induced (cytidine) deaminase is required for full clinical manifestation of disease in an animal model of MS (experimental autoimmune encephalomyelitis; EAE) provoked by immunization with the extracellular domain of recombinant human myelin oligodendrocyte glycoprotein (hMOG). In this study, we investigated the role of CSR versus SHM in the pathogenesis of EAE. We found that passive transfer of class-switched anti-MOG IgG1 Abs into hMOG-primed Aicda−/− mice is sufficient to fully rescue EAE disease. In addition, we found that the nature of the Ag is an important determinant of EAE severity in Aicda−/− mice because the lack of a diversified BCR does not affect the induction of EAE when immunized with the extracellular domain of rat MOG. To discriminate the effect of either CSR or SHM, we induced EAE in uracil DNA glycosylase–deficient mice (Ung−/−) that exhibit a defect primarily in CSR. We observed that Ung−/− mice exhibit milder clinical disease compared with control mice, concomitant with a reduced amount of anti-MOG IgG1 class-switched Abs that preserved normal affinity. Collectively, these results indicate that CSR plays an important role in governing the incidence and severity of EAE induced with hMOG but not rat MOG.
ERP correlates of cognitive control in children prenatally exposed to methadone or buprenorphine

ABSTRACT Much is still unknown about the potential long-term effects of prenatal methadone and buprenorphine exposure. We examined neural correlates of cognitive control in 19 prenatally methadone and buprenorphine exposed and 21 nondrug exposed children, aged 9-11 years. Children performed a modified version of the Eriksen Flanker task, which taps into selective attention, conflict response, and response inhibition mechanisms. We investigated behavioral responses and the ERP components N1, P2, N2, P3, and the late positive component (LPC). Children in the exposed group showed normal cognitive control function. However, an atypical ERP response related to perceptual and attention allocation processes was found in the exposed group.
“Okay, We Get It. You Vape”: An Analysis of Geocoded Content, Context, and Sentiment regarding E-Cigarettes on Twitter

The current study examined conversations on Twitter related to use and perceptions of e-cigarettes in the United States. We employed the Social Media Analytic and Research Testbed (SMART) dashboard, which was used to identify and download (via a public API) e-cigarette-related geocoded tweets. E-cigarette-related tweets were collected continuously using customized geo-targeted Twitter APIs. A total of 193,051 tweets were collected between October 2015 and February 2016. Of these tweets, a random sample of 973 geocoded tweets were selected and manually coded for information regarding source, context, and message characteristics. Our findings reveal that although over half of tweets were positive, a sizeable portion was negative or neutral. We also found that, among those tweets mentioning a stigma of e-cigarettes, most confirmed that a stigma does exist. Conversely, among tweets mentioning the harmfulness of e-cigarettes, most denied that e-cigarettes were a health hazard. These results suggest that current efforts have left the public with ambiguity regarding the potential dangers of e-cigarettes. Consequently, it is critical to communicate the public health stance on this issue to inform the public and provide counterarguments to the positive sentiments presently dominating conversations about e-cigarettes on social media. The lack of awareness and need to voice a public health position on e-cigarettes represents a vital opportunity to continue winning gains for tobacco control and prevention efforts through health communication interventions targeting e-cigarettes.
A funder-imposed data publication requirement seldom inspired data sharing

Growth of the open science movement has drawn significant attention to data sharing and availability across the scientific community. In this study, we tested the ability to recover data collected under a particular funder-imposed requirement of public availability. We assessed overall data recovery success, tested whether characteristics of the data or data creator were indicators of recovery success, and identified hurdles to data recovery. Overall the majority of data were not recovered (26% recovery of 315 data projects), a similar result to journal-driven efforts to recover data. Field of research was the most important indicator of recovery success, but neither home agency sector nor age of data were determinants of recovery. While we did not find a relationship between recovery of data and age of data, age did predict whether we could find contact information for the grantee. The main hurdles to data recovery included those associated with communication with the researcher; loss of contact with the data creator accounted for half (50%) of unrecoverable datasets, and unavailability of contact information accounted for 35% of unrecoverable datasets. Overall, our results suggest that funding agencies and journals face similar challenges to enforcement of data requirements. We advocate that funding agencies could improve the availability of the data they fund by dedicating more resources to enforcing compliance with data requirements, providing data-sharing tools and technical support to awardees, and administering stricter consequences for those who ignore data sharing preconditions.
Binding of Dickkopf-3 to CXCR7 Enhances Vascular Progenitor Cell Migration and Degradable Graft Regeneration

Rationale: Vascular progenitor cells play key roles in physiological and pathological vascular remodeling—a process that is crucial for the regeneration of acellular biodegradable scaffolds engineered as vital strategies against the limited availability of healthy autologous vessels for bypass grafting. Therefore, understanding the mechanisms driving vascular progenitor cells recruitment and differentiation could help the development of new strategies to improve tissue-engineered vessel grafts and design drug-targeted therapy for vessel regeneration. Objective: In this study, we sought to investigate the role of Dkk3 (dickkopf-3), recently identified as a cytokine promotor of endothelial repair and smooth muscle cell differentiation, on vascular progenitor cells cell migration and vascular regeneration and to identify its functional receptor that remains unknown. Methods and Results: Vascular stem/progenitor cells were isolated from murine aortic adventitia and selected for the Sca-1 (stem cell antigen-1) marker. Dkk3 induced the chemotaxis of Sca-1+ cells in vitro in transwell and wound healing assays and ex vivo in the aortic ring assay. Functional studies to identify Dkk3 receptor revealed that overexpression or knockdown of chemokine receptor CXCR7 (C-X-C chemokine receptor type 7) in Sca-1+ cells resulted in alterations in cell migration. Coimmunoprecipitation experiments using Sca-1+ cell extracts treated with Dkk3 showed the physical interaction between DKK3 and CXCR7, and specific saturation binding assays identified a high-affinity Dkk3-CXCR7 binding with a dissociation constant of 14.14 nmol/L. Binding of CXCR7 by Dkk3 triggered the subsequent activation of ERK1/2 (extracellular signal-regulated kinases 1/2)-, PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)-, Rac1 (Ras-related C3 botulinum toxin substrate 1)-, and RhoA (Ras homolog gene family, member A)-signaling pathways involved in Sca-1+ cell migration. Tissue-engineered vessel grafts were fabricated with or without Dkk3 and implanted to replace the rat abdominal aorta. Dkk3-loaded tissue-engineered vessel grafts showed efficient endothelization and recruitment of vascular progenitor cells, which had acquired characteristics of mature smooth muscle cells. CXCR7 blocking using specific antibodies in this vessel graft model hampered stem/progenitor cell recruitment into the vessel wall, thus compromising vascular remodeling. Conclusions: We provide a novel and solid evidence that CXCR7 serves as Dkk3 receptor, which mediates Dkk3-induced vascular progenitor migration in vitro and in tissue-engineered vessels, hence harnessing patent grafts resembling native blood vessels.
Anticonvulsants and the risk of perinatal bleeding complications

Objective To examine the risk of postpartum hemorrhage (PPH) and neonatal bleeding complications associated with late-pregnancy exposure to anticonvulsant drugs (ACDs) that induce cytochrome P450 enzymes (ACDi) and alter the metabolism of vitamin K compared to other ACDs. Methods We used a population-based cohort study stemming from a nationwide sample of publicly insured pregnant women with a liveborn infant from the 2000 to 2010 Medicaid Analytic eXtract. ACDi (carbamazepine, phenobarbital, phenytoin, oxcarbazepine, topiramate) were compared to other ACDs dispensed during the last month of pregnancy. Relative risks (RRs) and 95% confidence intervals (CIs) of PPH and neonatal bleeding complications were estimated using generalized linear models with fine stratification on the propensity score to control for indication and other potential confounders. Results Among 11,572 women with an ACD prescription overlapping delivery, 2.6% (135/5,109) in the ACDi group and 3.6% (231/6,463) in the other ACDs group had a diagnosis of PPH: unadjusted RR 0.74 (95% CI 0.60–0.91), adjusted RR 0.77 (95% CI 0.58–1.00). The prevalence of neonatal bleeding complications was 3.1% (157/5,109) in the ACDi group and 3.5% (229/6,463) in the other ACDs group: unadjusted RR 0.87 (95% CI 0.71–1.06), adjusted RR 0.83 (95% CI 0.64–1.08). Conclusions Evidence from this large observational study suggests that use of ACDi near delivery does not increase the risk of bleeding complications compared to other ACDs in clinical settings where neonatal intramuscular or oral vitamin K administration is considered standard of care. These findings provide reassurance for clinicians and pregnant women successfully treated with ACDi.
Factors associated with advance directives completion among patients with advance care planning communication in Taipei, Taiwan

Background Although advance directives (AD) have been implemented for years in western countries, the concept of AD is not promoted extensively in eastern countries. In this study we evaluate a program to systematically conduct advance care planning (ACP) communication for hospitalized patients in Taiwan and identify the factors associated with AD completion. Methods In this retrospective evaluation of a clinical ACP program, we identified adult patients with chronic life-limiting illness admitted to Taipei City Hospital between April 2015 and January 2016. Trained healthcare providers held an ACP meeting to discuss patients’ preference regarding end-of-life care and AD completion. A multiple logistic regression was performed to determine the factors associated with the AD completion. Results A total of 2878 patients were determined to be eligible for ACP during the study, among which 1798 (62.5%) completed ACP and data was available for 1411 patients (49.1%). Of the 1411 patients who received ACP communication with complete data, the rate of AD completion was 82.6%. The overall mean (SD) age was 78.2 (14.4) years. Adjusting for other variables, AD completion was associated with patients aged ≥ 85 years [adjusted odds ratio (AOR) = 1.80, 95% CI 1.21–2.67], critical illness (AOR = 1.17, 95% CI 1.06–1.30), and social workers participating in ACP meetings (AOR = 1.74, 95% CI 1.24–2.45). Conclusion The majority of inpatients with chronic life-limiting illness had ACP communication as part of this ACP program and over 80% completed an AD. Our study demonstrates the feasibility of implementing ACP discussion in East Asia and suggests that social workers may be an important component of ACP communication with patients.
Survival from childhood cancers in Eastern Africa: A population‐based registry study

Cancers occurring in children in Africa are often underdiagnosed, or at best diagnosed late. As a result, survival is poor, even for cancers considered ‘curable’. With limited population‐level data, understanding the actual burden and survival from childhood cancers in Africa is difficult. In this study, we aimed at providing survival estimates for the most common types of cancers affecting children aged 0–14 years, in three population‐based Eastern African registries; Harare, Zimbabwe (Kaposi sarcoma, Wilms tumour (WT), non‐Hodgkin lymphoma (NHL), retinoblastoma, and acute lymphocytic leukaemia (ALL)), Kampala, Uganda (Burkitt lymphoma, Kaposi sarcoma, WT, and retinoblastoma), and Nairobi, Kenya (ALL, retinoblastoma, WT, Burkitt lymphoma, and Hodgkin lymphoma). We included cases diagnosed within the years 1998–2009 and followed up till the end of 2011. We estimated the observed and relative survival at 1, 3, and 5 years after diagnosis. We studied 627 individual patient records. Median follow‐up ranged from 2.2 months for children with Kaposi sarcoma in Harare to 30.2 months for children with ALL in Nairobi. The proportion of children lost to follow‐up was highest in the first year after diagnosis. In Harare and Kampala, the 5‐year relative survival was <46% for all cancer types. The 5‐year relative survival was best for children in Nairobi, though with wider confidence intervals. Survival from childhood cancers in Africa is still poor, even for cancers with good prognosis and potential for cure. Supporting cancer detection, treatment, and registration activities could help improve survival chances for children with cancers in Africa.
Molecular Imaging of Radiolabeled Bispecific T-Cell Engager 89Zr-AMG211 Targeting CEA-Positive Tumors

Purpose: AMG 211, a bispecific T-cell engager (BiTE) antibody construct, targets carcinoembryonic antigen (CEA) and the CD3 epsilon subunit of the human T-cell receptor. AMG 211 was labeled with zirconium-89 (89Zr) or fluorescent dye to evaluate the tumor-targeting properties. Experimental Design: 89Zr-AMG211 was administered to mice bearing CEA-positive xenograft tumors of LS174T colorectal adenocarcinoma or BT474 breast cancer cells, as well as CEA-negative HL-60 promyelocytic leukemia xenografts. Biodistribution studies with 2- to 10-μg 89Zr-AMG211 supplemented with unlabeled AMG 211 up to 500-μg protein dose were performed. A BiTE that does not bind CEA, 89Zr-Mec14, served as a negative control. 89Zr-AMG211 integrity was determined in tumor lysates ex vivo. Intratumoral distribution was studied with IRDye800CW-AMG211. Moreover, 89Zr-AMG211 was manufactured according to Good Manufacturing Practice (GMP) guidelines for clinical trial NCT02760199. Results: 89Zr-AMG211 demonstrated dose-dependent tumor uptake at 6 hours. The highest tumor uptake was observed with a 2-μg dose, and the lowest tumor uptake was observed with a 500-μg dose. After 24 hours, higher uptake of 10-μg 89Zr-AMG211 occurred in CEA-positive xenografts, compared with CEA-negative xenografts. Although the blood half-life of 89Zr-AMG211 was approximately 1 hour, tumor retention persisted for at least 24 hours. 89Zr-Mec14 showed no tumor accumulation beyond background level. Ex vivo autoradiography revealed time-dependent disintegration of 89Zr-AMG211. 800CW-AMG211 was specifically localized in CEA-expressing viable tumor tissue. GMP-manufactured 89Zr-AMG211 fulfilled release specifications. Conclusions: 89Zr-AMG211 showed dose-dependent CEA-specific tumor targeting and localization in viable tumor tissue. Our data enabled its use to clinically evaluate AMG 211 in vivo behavior. Clin Cancer Res; 24(20); 4988–96. ©2018 AACR.
CHIP E3 ligase mediates proteasomal degradation of the proliferation regulatory protein ALDH1L1 during the transition of NIH3T3 fibroblasts from G0/G1 to S-phase

ALDH1L1 is a folate-metabolizing enzyme abundant in liver and several other tissues. In human cancers and cell lines derived from malignant tumors, the ALDH1L1 gene is commonly silenced through the promoter methylation. It was suggested that ALDH1L1 limits proliferation capacity of the cell and thus functions as putative tumor suppressor. In contrast to cancer cells, mouse cell lines NIH3T3 and AML12 do express the ALDH1L1 protein. In the present study, we show that the levels of ALDH1L1 in these cell lines fluctuate throughout the cell cycle. During S-phase, ALDH1L1 is markedly down regulated at the protein level. As the cell cultures become confluent and cells experience increased contact inhibition, ALDH1L1 accumulates in the cells. In agreement with this finding, NIH3T3 cells arrested in G1/S-phase by a thymidine block completely lose the ALDH1L1 protein. Treatment with the proteasome inhibitor MG-132 prevents such loss in proliferating NIH3T3 cells, suggesting the proteasomal degradation of the ALDH1L1 protein. The co-localization of ALDH1L1 with proteasomes, demonstrated by confocal microscopy, supports this mechanism. We further show that ALDH1L1 interacts with the chaperone-dependent E3 ligase CHIP, which plays a key role in the ALDH1L1 ubiquitination and degradation. In NIH3T3 cells, silencing of CHIP by siRNA halts, while transient expression of CHIP promotes, the ALDH1L1 loss. The downregulation of ALDH1L1 is associated with the accumulation of the ALDH1L1 substrate 10-formyltetrahydrofolate, which is required for de novo purine biosynthesis, a key pathway activated in S-phase. Overall, our data indicate that CHIP-mediated proteasomal degradation of ALDH1L1 facilitates cellular proliferation.