Miracle-dz/UniFAR-FTUs huggingface dataset:
Rey Auditory Verbal Learning Test and Rey–Osterrieth Complex Figure Test performance validity indices in a VA Polytrauma sample

Abstract Objective: Performance validity assessment is a crucial component of any neuropsychological evaluation, particularly in settings where potential exaggeration of complaints and deficits is heightened. Standalone performance validity measures can be time-consuming, so many investigations have explored embedded indices within existing measures. The Rey Auditory Verbal Learning Test (RAVLT) and the Rey–Osterrieth Complex Figure Test (ROCF) each have a number of available embedded performance validity tests (PVTs). This investigation sought to evaluate several of these indices and to identify the most effective within a VA mild traumatic brain injury (mTBI)/Polytrauma sample. Method: A sample of 100 U.S. military veterans underwent clinical neuropsychological evaluation. There were 37 individuals whose test results were considered invalid based on failure of 2 or more independent PVTs, 47 whose results were valid, and 16 whose results were equivocal (failure on one PVT). The classification accuracies of published PVTs from the RAVLT and ROCF were evaluated. Results: Several indices had sensitivity values above 50% and strong positive predictive power with specificity held over 90%. Conclusions: The results demonstrated that there are multiple effective RAVLT & ROCF PVTs available for use in mTBI evaluations with veterans.
Function is Dissociated From Activation-Related Immunophenotype on Phagocytes From Patients With Sirs/Sepsis Syndrome.

Sepsis is a life-threatening condition associated with failure of at least one organ in the presence of infection. Along with SIRS, the acute systemic inflammatory syndrome without documented infection, sepsis represents a main health problem in intensive care units around the world. Hypercytokinemia and overexpression of activation-markers on leukocytes are frequently reported in SIRS/sepsis. Leukocyte functions including antibody mediated-phagocytosis, pathogen recognition and migration appear to be disabled in SIRS/septic patients. Our aim was to evaluate the so-called activation immunophenotype and functions related to infection contention in phagocytes from patients with sepsis. We analyzed blood samples from 44 patients with SIRS/sepsis and 14 healthy volunteers. CD16, CD69, CD64, CCR7, and TREM-1 levels were determined on the surface of neutrophils and monocytes. Phagosome maturation and p38, STAT3, and STAT5 phosphorylation were evaluated in these phagocytes. As expected, sepsis and SIRS patients had increased serological levels of pro- and anti-inflammatory cytokines. E. coli internalization was not increased in monocytes from patients with SIRS/sepsis, despite increased numbers of circulating neutrophils and monocytes (p < 0.05) and overexpression of CD64 and CD69 in neutrophils (p < 0.05), TREM-1 (p < 0.01), CD69 (p < 0.001), and CCR7 (p < 0.05). Moreover, phagosome maturation was decreased in phagocytes from patients with SIRS/sepsis syndrome (p < 0.00001). Furthermore, p38 and STAT-3 phosphorylation elicited by LPS or IL-10 (respectively) was diminished in neutrophils and monocytes from patients (p < 0.05). Our results indicate that "activation markers" may not reflect higher functionality, so a more profound analysis should be made before assuming that the activated immunophenotype means increased phagocyte responses.
Iron Deficiency: The Problem and Approaches to its Solution

Anaemia is associated with increased perinatal mortality, increased child morbidity and mortality, behavioural changes and impaired mental development, decreased work performance, increased susceptibility to lead poisoning, and impaired immune competence. Iron-deficiency anaemia is an intractable problem, as indicated by the goal set by world leaders of reducing nutritional anaemia to one-third of 1990 levels by the year 2000, compared with the goals of virtually eliminating deficiencies of vitamin A and of iodine during the same period. To a large extent, this is because intake is less associated with status for iron than for iodine and vitamin A. The demand for iron varies throughout the life cycle, and the bioavailability of iron varies over a wide range because of a number of factors, such as the species of iron compound, the molecular linkage, the amount of nutrient consumed in a meal, the matrix in which the nutrient is incorporated, the absorption modifiers, the nutrient status of the host, genetic factors, other host-related factors, and interactions among factors.
Genes wide open: Data sharing and the social gradient of genomic privacy

Abstract This study reports on 13 semistructured in-depth interviews to qualitatively explore the experiences of individuals who publicly shared their direct-to-consumer genetic testing results on the platform openSNP. In particular, we focused on interviewees’ understanding of privacy. Participants reported that the likelihood and the magnitude of privacy harms depend on gender, ethnicity, sexual orientation, the stigma associated with certain clinical conditions, the existence of adequate legislation, and the nature of national health care systems. Some participants expressed the view that those who enjoy higher socioeconomic status or are better protected by their country’s legislation have a responsibility to share their genetic data. Our study shows that people who share their genetic data publicly online—far from being insensitive to privacy risks—have a complex understanding of the social, relational, and contextual nature of genetic privacy.
The dose-response effect in routinely delivered psychological therapies: A systematic review

Abstract The dose-response effect refers to the relationship between the dose (e.g., length, frequency) of treatment and the subsequent probability of improvement. This systematic review aimed to synthesize the literature on the dose-response effect in routine psychological therapies delivered to adult patients with mental health problems. Twenty-six studies were eligible for inclusion. Different methodological approaches have been used to examine the dose-response effect; including survival analysis, multilevel modelling and descriptive cluster analyses. Replicated and consistent support was found for a curvilinear (log-linear or cubic) relationship between treatment length and outcomes, with few exceptions such as eating disorders and severe psychiatric populations. Optimal doses of psychotherapy in routine settings range between 4 and 26 sessions (4–6 for low intensity guided self-help) and vary according to setting, clinical population and outcome measures. Weekly therapy appears to accelerate the rate of improvement compared to less frequent schedules. Most of the reviewed evidence is from university counselling centres and outpatient psychotherapy clinics for common mental health problems. There is scarce and inconclusive evidence in clinical samples with chronic and severe mental disorders.
Adverse events in radiation oncology: A case series from wake up safe, the pediatric anesthesia quality improvement initiative

Radiation therapy in pediatric patients often requires anesthesia and poses environmental challenges. Monitoring must be done remotely to limit radiation exposure to the provider. Airway access can be limited by masks or frames. Care is often delivered in relatively inaccessible locations in the hospital. While individual institutions have reported their outcomes, this case series aims to review a multicenter registry of significant adverse events and make recommendations for improved care.
Land cover impacts on storm flow suspended solid and nutrient concentrations in southwest Ohio streams

Impacts between urban and agricultural land cover on storm flow water quality are poorly understood for the Eastern Corn Belt Ecoregion in SW Ohio. Storm flow water samples were collected from May 2017 to October 2017 across seven SW Ohio watersheds which ranged in urban land cover from 6% to 92% and in agricultural land cover from 4% to 70%. Two watersheds contained water resource recovery facilities (WRRFs). Percent agricultural land cover in a watershed and storm magnitude were primary explanatory variables for total suspended solid and total phosphorus concentrations. Total nitrogen, nitrate, and phosphate concentrations were primarily explained by the presence of WRRFs and percent agricultural land cover. Increased dissolved nutrient concentrations in watersheds with WRRFs indicate that WRRFs in the study area are ineffectively removing nitrate and phosphate from effluent. Results suggest that to improve water quality during storm flows, additional management efforts need to be focused on agricultural watersheds and WRRFs.
The Crotalaria juncea metal transporter CjNRAMP1 has a high Fe uptake activity, even in an environment with high Cd contamination

Abstract Large quantities of Fe and Cd accumulate in the leaves of the metal-accumulating leguminous plant, Crotalaria juncea. A member of the metal transporter NRAMP family was cloned from C. juncea. The amino acid sequence of this clone, designated CjNRAMP1, was similar to the sequence of Arabidopsis AtNRAMP1, which is involved in Fe and Cd transport. Organ-specific analysis showed that CjNRAMP1 mRNA was expressed mainly in the leaves of C. juncea plants, as well as in stems and roots. Use of green fluorescent protein fused to CjNRAMP1 suggested its localization to the plasma membranes of plant cells. Complementation experiments using yeast strains with impaired metal transport systems showed that CjNRAMP1 transported both Fe and Cd in an inward direction within the cells. Transgenic Arabidopsis plants overexpressing CjNRAMP1 showed high tolerance to Cd, with Cd translocation from roots to leaves being substantially greater in transgenic than in wild-type plants. Overexpression of CjNRAMP1 resulted in a greater accumulation of Fe in shoots and roots, suggesting that CjNRAMP1 recognizes Fe and Cd as substrates and that the high Cd tolerance of CjNRAMP1 is due to its strong Fe uptake activity, even in the presence of high Cd concentrations in the rhizosphere.
Understanding the role of chondrocytes in osteoarthritis: utilizing proteomics

ABSTRACT Introduction: Proteomic analyses have been acknowledged to carry a significant prospective in elucidating the pathogenesis of several diseases, including osteoarthritis (OA). But it has not been an easy road: major technical issues, mainly derived from the complex and rigid nature of the cartilage tissue, had to be faced; an obstacle that led to the development of different approaches. Areas covered: In this review, we categorized the proteomic studies undertaken (proteomic analyses of the cartilage, cartilage explants, cultured chondrocytes, and chondrocytes’ secretome) as part of the different strategies developed in order to overcome tissue and disease-specific challenges. Essentially these approaches aimed at identifying differences in the proteome of healthy vs diseased tissue. Our aim was to point out the novel players that have emerged from these analyses and highlight the associated mechanism(s) suggested to play a role in the pathogenesis of OA. Expert commentary: The identified factors indicate the implication of age-associated mechanisms, such as metabolic deregulation, inflammation, and redox imbalance, in OA onset and/or progression. Taken together these results outline the causal network of the disease and place chondrocytes’ senescence at the center of the emerging aetiopathological atlas.
Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow‐up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex‐differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.
Poor diet quality in pregnancy is associated with increased risk of excess fetal growth: a prospective multi-racial/ethnic cohort study.

Background Nutritional perturbations during pregnancy may impact fetal and long-term childhood growth, although there are limited data on overall diet quality. We investigated whether diet quality, measured by the Healthy Eating Index-2010 (HEI-2010), during pregnancy was related to birthweight z-score (BWZ) and the clinically relevant birth outcomes of large- and small-for-gestational age (LGA and SGA). Methods In a prospective cohort of 2269 multi-racial/ethnic women from the Pregnancy Environment and Lifestyle Study (2014-2017), dietary intake was assessed by a food frequency questionnaire during early pregnancy. Offspring BWZ and LGA or SGA were derived based on gestational age-, sex-, and racial/ethnic-specific birthweight distributions. Multivariable linear and Poisson regression with robust standard errors were used. Results About 80% of women did not achieve good diet quality (HEI-2010 < 80). After adjusting for covariates, infants born to women in the lowest vs highest quartile of HEI-2010 (37.5-64.4 vs 78.7-94.2) had a 0.12 standard-deviation [95% confidence interval (CI) 0.01-0.23, P-for-trend = 0.023] greater BWZ and 1.76-fold (1.08-2.87, P-for-trend = 0.037) increased risk of LGA. No association was observed between HEI-2010 and SGA. Per-5-point substitution of the reversely coded empty calories component score with the whole grains component score in the HEI-2010 was related to a 25% (95% CI 0.66-0.86) lower risk of LGA. Conclusions Poor diet quality in pregnancy was associated with higher birthweight and increased risk of LGA independent of maternal obesity and other covariates. Substitution of empty calories with whole grains may mitigate the risk of excess fetal growth. Our findings may inform potential prevention strategies and dietary guidelines for pregnant women.
Co-Circulation and Excretion Dynamics of Diverse Rubula- and Related Viruses in Egyptian Rousette Bats from South Africa

The Egyptian rousette bat (Rousettus aegyptiacus) has previously been implicated as the natural host of a zoonotic rubulavirus; however, its association with rubulaviruses has been studied to a limited extent. Urine, spleen, and other organs collected from the R. aegyptiacus population within South Africa were tested with a hemi-nested RT-PCR assay targeting a partial polymerase gene region of viruses from the Avula- and Rubulavirus genera. Urine was collected over a 14-month period to study the temporal dynamics of viral excretion. Diverse rubulaviruses, including viruses related to human mumps and parainfluenza virus 2, were detected. Active excretion was identified during two peak periods coinciding with the host reproductive cycle. Analysis of additional organs indicated co-infection of individual bats with a number of different putative rubulaviruses, highlighting the limitations of using a single sample type when determining viral presence and diversity. Our findings suggest that R. aegyptiacus can harbor a range of Rubula- and related viruses, some of which are related to known human pathogens. The observed peaks in viral excretion represents potential periods of a higher risk of virus transmission and zoonotic disease spill-over.
SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

Significance Endothelial cells (EC) subjected to laminar shear stress exhibit a specialized EC membrane architecture that promotes a nonpermeable barrier to constituents of blood. Emerging data support long-noncoding RNAs (lncRNAs) as regulators of EC phenotype. Here, levels of the lncRNA SENCR are induced with laminar shear stress in cultured EC as well as aortic EC of humanized mice. SENCR binds a new noncanonical RNA-binding protein called CKAP4. Upon knockdown of SENCR, a pool of CKAP4 binds CDH5 triggering CDH5 internalization, leading to perturbed adherens junctions, defective membrane integrity, and heightened EC permeability. These results support a function of SENCR in the maintenance of EC membrane homeostasis through CKAP4 binding and the proper localization of CDH5 at the cell membrane. SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure–function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR. Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.
A prospective, randomized trial of intravenous hydroxocobalamin versus noradrenaline or saline for treatment of lipopolysaccharide‐induced hypotension in a swine model

Early, non‐clinical studies support the use of hydroxocobalamin to treat sepsis‐induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45–55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log‐rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.
Creating Effective and Efficient Pediatric-Specific CME Content: More than Just Checking a Box

Abstract: States dictate the type of continuing medical education (CME) required for licensing; however, CME providers are not mandated to create content relevant to all specialties. This often forces pediatricians to engage in educational activities that are irrelevant to their practice. This is contrary to what constitutes effective CME. The goal was to develop pediatric content using adult learning theory that aligns with effective CME principles while simultaneously satisfying state licensure requirements. A targeted needs assessment of pediatric providers revealed that pediatric-specific CME activities satisfying the state's requirement for pain management and end-of-life issues were lacking. Webinars adhering to adult learning principles were created in consultation with content experts. Five hundred ninety-seven learners across 30 states successfully completed the webinars and received CME credit. To satisfy ongoing state licensing requirements, 44% of learners had completed similar activities in the past, but 72% of those learners participated in activities focused on adult medicine due to the lack of available pediatric modules. Until states and regulators allow for more flexibility in satisfying licensing requirements, it will be incumbent on those who create CME to develop educational activities that satisfy state requirements while aligning with the principles of effective CME. With strategic planning, this is possible and will hopefully empower physicians to engage in CME without resorting to “checking a box. ”
The crystal structure of amyloid precursor‐like protein 2 E2 domain completes the amyloid precursor protein family

The amyloid precursor–like protein 2 (APLP2) molecule is a type I transmembrane protein that is crucial for survival, cell‐cell adhesion, neuronal development, myelination, cancer metastasis, modulation of metal, and glucose and insulin homeostasis. Moreover, the importance of the amyloid precursor protein (APP) family in biology and disease is very well known because of its central role in Alzheimer disease. In this study, we determined the crystal structure of the independently folded E2 domain of APLP2 and compared that with its paralogues APP and APLP2, demonstrating high overall structural similarities. The crystal structure of APLP2 E2 was solved as an antiparallel dimer, and analysis of the protein interfaces revealed a distinct mode of dimerization that differs from the previously reported dimerization of either APP or APLP1. Analysis of the APLP2 E2 metal binding sites suggested it binds zinc and copper in a similar manner to APP and APLP1. The structure of this key protein might suggest a relationship between the distinct mode of dimerization and its biologic functions. —Roisman, L. C. , Han, S. , Chuei, M. J., Connor, A. R. , Cappai, R. The crystal structure of amyloid precursor‐like protein 2 E2 domain completes the amyloid precursor protein family. FASEB J. 33, 5076–5081 (2019). www.fasebj. org