Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconciling the evaluation of co-morbidities among HIV care patients in two large data systems: the Medical Monitoring Project and CFAR Network of Integrated Clinical Systems

ABSTRACT The estimated burden of chronic disease among people living with HIV (PLWH) varies considerably by data source, due to differences in case definitions, analytic approaches, and underlying patient populations. We evaluated the burden of diabetes (DM) and chronic kidney disease (CKD) in two large data systems that are commonly queried to evaluate health issues affecting HIV care patients: the Medical Monitoring Project (MMP), a nationally representative sample, and the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a clinical cohort. In order to reconcile these two data sources, we addressed issues common to observational data, including selection bias, missing data, and development of case definitions. The overall adjusted estimated prevalence of DM and CKD in MMP was 12.7% and 7.6%, respectively, and the overall prevalence of DM and CKD in CNICS was 9.9% and 8.3%, respectively; prevalence estimates increased with age in both data sources. After reconciling the approach to analyzing MMP and CNICS data, sub-group specific prevalence estimates of DM and CKD was generally similar in both data sources. Both data sources suggest a considerable burden of disease among older adults in HIV care. MMP and CNICS can provide reliable data to monitor HIV co-morbidities in the US.
Towards clinical outcome measures in myotonic dystrophy type 2: a systematic review

Purpose of review Myotonic dystrophies are the most frequent muscular dystrophies in adulthood; however, myotonic dystrophy type 2 (DM2) is by far less prevalent than myotonic dystrophy type 1 (DM1). Consequently, studies on large cohorts are lacking and disease-specific outcome measures have not been developed (see video abstract, Supplemental Digital Content 1, http://links.lww.com/CONR/A44). The aim of this review is to systematically evaluate the outcome measures applied in patients with DM2 and to identify tests adopted from other neuromuscular disorders potentially suitable for DM2. A systematic review of functional tests and patient reported outcomes (PROs) previously used in DM2 has been performed. In addition, we reviewed functional tests and PROs previously used in neuromuscular diseases (NMDs). Based on this approach, we propose a battery of tests to be validated in DM2. Recent findings: No outcome measures or PROs have been validated in DM2. The most used PROs in DM2 were INQoL, SF-36, MPQ, and BPI. It is not clear whether it is better to use MMT or QMT to assess muscle strength. The algometer seems to be a useful tool to assess myalgia. No currently adopted tests or PROs seem effective to assess the mild myotonia of DM2. Several outcome measures used in other NMDs (e.g. 6MWT, QMFT, GSGC) might be suitable for DM2; however, their disease-specific validity needs to be explored. Summary Although DM2 has a milder and more heterogeneous phenotype than DM1, there is an urgent need to develop validated outcome measures in DM2. The current lack of validated DM2 tests will delay the start of therapeutic trials.
The evolution of constitutive and induced defences to infectious disease

In response to infectious disease, hosts typically mount both constitutive and induced defences. Constitutive defence prevents infection in the first place, while induced defence typically shortens the infectious period. The two routes to defence, therefore, have very different implications not only to individuals but also to the epidemiology of the disease. Moreover, the costs of constitutive defences are likely to be paid even in the absence of disease, while induced defences are likely to incur the most substantial costs when they are used in response to infection. We examine theoretically the evolutionary implications of these fundamental differences. A key result is that high virulence in the parasite typically selects for higher induced defences even if they result in immunopathology leading to very high disease mortality. Disease impacts on fecundity are critical to the relative investment in constitutive and induced defence with important differences found when parasites castrate their hosts. The trade-off between constitutive and induced defence has been cited as a cause of the diversity in defence, but we show that the trade-off alone is unlikely to lead to diversity. Our models provide a framework to examine relative investment in different defence components both experimentally and in the field.
Relationship of vaginal discharge characteristics evaluated by Metricheck device to metabolic status in postpartum dairy cows

The relationship between vaginal discharge characteristics and metabolic status has been studied in postpartum dairy cows. Vaginal discharges at 2-6 weeks postpartum were scored weekly on a 1 (clear) to 5 (purulent material with stench) scale using the Metricheck device and classified into three groups as follows: Endometritis group (n = 19), greater than or equal to score 4 until 3 weeks postpartum; Delayed involution group (n = 9), score 2 or 3 after having score 1; Healthy group (n = 23), cows except those belonging to the Delayed involution and Endometritis groups. The uterus and cervix were assessed using ultrasonography. Blood samples were collected twice weekly from 1 to 6 weeks postpartum from all cows and were additionally obtained for 13,14-dihydro-15-keto-prostaglandin F2α (PGFM) measurements from multiparous cows. Cows with delayed involution had delayed onset of luteal activity (p < 0.05) and higher serum urea nitrogen (BUN) concentrations (p < 0.01) than healthy animals. Cows with endometritis had more peripartum diseases (p < 0.05), lower milk yield (p < 0.05), longer cervix diameter (p < 0.05), and lower serum albumin (p < 0.01), total cholesterol (p < 0.01), and magnesium (p < 0.01) concentrations, and higher aspartate aminotransferase levels (p < 0.05) than healthy cows. Plasma PGFM concentrations tended to be higher in the Delayed involution group (p = 0.083) and lower in the Endometritis group (p = 0.085) than in the Healthy group. In summary, delayed involution was shown to be associated with higher BUN concentration, and endometritis may have been caused by peripartum diseases and hepatic dysfunction.
Evidence for human-mediated range expansion and gene flow in an invasive grass

Cities and adjacent regions represent foci of intense human activity and provide unique opportunities for studying human-mediated dispersal and gene flow. We examined the effect of landscape features on gene flow in the invasive grass Brachypodium sylvaticum across an urban–rural interface at the edge of its expanding range. We used genome-wide single-nucleotide polymorphism surveys of individuals from 22 locations. Resistance surfaces were created for each landscape feature, using ResistanceGA to optimize resistance parameters. Our Structure analysis identified three distinct clusters, and diversity analyses support the existence of at least three local introductions. Multiple regression on distance matrices showed no evidence that development, roads, canopy cover or agriculture had a significant influence on genetic distance in B. sylvaticum. Geographical distance was a mediocre predictor of genetic distance and reflected geographical clustering. The model of rivers acting as a conduit explained a large portion of variation in genetic distance, but the lack of evidence of directional gene flow eliminated hydrochory as a dispersal mechanism. These results and observations of the distribution of populations in disturbed sites indicate that the influence of rivers on patterns of dispersal of B. sylvaticum probably reflects seed dispersal due to human recreational activity.
Media portrayal of Māori and bariatric surgery in Aotearoa/New Zealand.

AIM Media constructs in Aotearoa, New Zealand naturalise the dominant Western culture. Conversely, mainstream news about Māori is rare and prioritises negative stereotypical constructs that are often centred on Māori as economic threats via resource control and political activism. These narratives influence continued discrimination against Māori in New Zealand. Media representations of bariatric surgery in New Zealand are not widely understood. We explored the portrayal of Māori and bariatric surgery in print and online news media articles in New Zealand using an inductive approach to thematic analysis. METHOD An electronic search of two databases (Proquest Australia/ New Zealand Newsstream and Newztext) and two New Zealand news media websites (Stuff and the New Zealand Herald) was performed to retrieve news articles reporting stories, opinion pieces or editorials concerning Māori and bariatric surgery published between January 2007 to June 2017. Articles were scored using a five-point scale to assess the level of reporting as either very negative, negative, neutral, positive or very positive. Included articles were then subjected to inductive thematic analysis using the NVIVO 11 to identify and explore common themes surrounding Māori and bariatric surgery. RESULTS Of 246 articles related to bariatric surgery over the 10-year study period, 31 (13%) were representative of Māori. Articles were scored as 'neutral' to 'positive' with a mean reporting score of 3.7 (Kappa score of 0.72 [95% CI, 0.66-0.78, p<0.0001]). Five main themes were identified, these were: Attitudes towards bariatric surgery; complexity of obesity and weight loss; access to bariatric surgery; Māori advocacy and framing of Māori. Of the five themes, access to bariatric surgery and attitudes towards bariatric surgery were most prevalent. Māori advocacy was another common theme that arose largely due to the support of public funding of bariatric surgery championed by Dame Tariana Turia. Aside from this, narratives describing equity of bariatric surgery provision and equitable outcomes following bariatric surgery for Māori were sparse. CONCLUSION There was limited reporting on Māori health inequalities and equitable access to publicly funded bariatric surgery in New Zealand. We argue that this lack of coverage may work against addressing disparities in obesity prevalence and access to publicly funded bariatric surgery for Māori in New Zealand.
CD44 Facilitates Epithelial-to-Mesenchymal Transition Phenotypic Change at Acquisition of Resistance to EGFR Kinase Inhibitors in Lung Cancer

Epithelial-to-mesenchymal transition (EMT) is one of the acquired resistance mechanisms to EGFR tyrosine kinase inhibitors (TKI) in lung cancers. Because EMT is related to tumor invasion, metastases, and resistance to various treatments, it is important to prevent the emergence of EMT. However, molecular mechanism(s) underlying EMT phenotypic changes, as well as biomarker(s) that predict the emergence of EMT in EGFR-mutated lung cancers, are unclear to date. Through the comparison of expression data between isogenic lung cancer cell lines that acquired resistance to EGFR-TKI(s), we identified that high CD44 expression is related to a mesenchymal phenotype and that shRNA-mediated knockdown of CD44 reversed the EMT change. High membranous CD44 expression was identified in lesions with mesenchymal phenotype that were obtained from lung cancer patients who developed acquired resistance to gefitinib or afatinib, whereas isogenic lesions without EMT change showed negative/weak staining for CD44. Immunohistochemistry for treatment-naïve lung cancer cell lines with EGFR mutations found those that acquire resistance to EGFR-TKIs via EMT (HCC4006 and H1975 cells) had strong membranous CD44 expression compared with non–EMT-transforming lines which demonstrated negative or weak staining (Fisher exact test P value = 0.036). shRNA-mediated CD44 knockdown in HCC4006 cells prevented the emergence of EMT after chronic exposure to osimertinib. These results suggest that upregulation of CD44 facilitates EMT-phenotypic change in lung cancers with EGFR mutations when treated with EGFR-TKIs. In addition, our results suggest that CD44 can be a useful biomarker to predict the emergence of EMT upon EGFR-TKI monotherapy. Mol Cancer Ther; 17(10); 2257–65. ©2018 AACR.
Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study

Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression. Trial Registration: ClinicalTrials.gov (NCT02391831).
Process Evaluation of an Early Care and Education Intervention: The California Childhood Obesity Research Demonstration Study (CA-CORD)

Given the widespread use of out-of-home child care in the United States, early care and education (ECE) providers offer ideal settings to promote health behaviors among Hispanic/Latino children whose obesity prevalence remains high. This study details the process evaluation of ECE intervention strategies of a childhood obesity research demonstration study (California Childhood Obesity Research Demonstration [CA-CORD]) to prevent and control obesity among Hispanic/Latino children aged 2 to 12 years. Participating ECE providers received the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) materials and action planning sessions with a trained interventionist; Sports, Play, and Active Recreation for Kids (SPARK) physical activity (PA), health behavior, and body mass index assessment trainings; and health behavior toolkit, cooking kit, water dispensers, and posters to promote healthy eating, PA, water consumption, and quality sleep. Intervention logs and director/lead teacher interviews evaluated how well 14 center-based and 9 private ECE providers implemented policy, system, and environmental changes. NAP SACC was implemented with higher fidelity than other strategies, and participation in SPARK trainings was lower than health behavior trainings. ECE directors/lead teachers reported that the intervention activities and materials helped them promote the targeted behaviors, especially PA. Results demonstrated that the use of NAP SACC, trainings, and toolkit had high fidelity and were potentially replicable for implementation in ECE settings among Hispanic/Latino communities.
Synaptic transmission may provide an evolutionary benefit to HIV through modulation of latency

Transmission of HIV is known to occur by two mechanisms in vivo: the free virus pathway, where viral particles bud off an infected cell before attaching to an uninfected cell, and the cell-cell pathway, where infected cells form virological synapses through close contact with an uninfected cell. It has also been shown that HIV replication includes a positive feedback loop controlled by the viral protein Tat, which may act as a stochastic switch in determining whether an infected cell enters latency. In this paper, we introduce a simple mathematical model of HIV replication containing both the free virus and cell-cell pathways. Using this model, we demonstrate that the high multiplicity of infection in cell-cell transmission results in a suppression of latent infection, and that this modulation of latency through balancing the two transmission mechanisms can provide an evolutionary benefit to the virus. This benefit increases with decreasing overall viral fitness, which may provide a within-host evolutionary pressure toward more cell-cell transmission in late-stage HIV infection.
Mobile elements contribute to the uniqueness of human genome with 15,000 human-specific insertions and 14 Mbp sequence increase

Abstract Mobile elements (MEs) collectively contribute to at least 50% of the human genome. Due to their past incremental accumulation and ongoing DNA transposition, MEs serve as a significant source for both inter- and intra-species genetic and phenotypic diversity during primate and human evolution. By making use of the most recent genome sequences for human and many other closely related primates and robust multi-way comparative genomic approach, we identified a total of 14,870 human-specific MEs (HS-MEs) with more than 8,000 being newly identified. Collectively, these HS-MEs contribute to a total of 14.2 Mbp net genome sequence increase. Several new observations were made based on these HS-MEs, including the finding of Y chromosome as a strikingly hot target for HS-MEs and a strong mutual preference for SINE-R/VNTR/Alu (SVAs). Furthermore, ∼8,000 of these HS-MEs were found to locate in the vicinity of ∼4,900 genes, and collectively they contribute to ∼84 kb sequences in the human reference transcriptome in association with over 300 genes, including protein-coding sequences for 40 genes. In conclusion, our results demonstrate that MEs made a significant contribution to the evolution of human genome by participating in gene function in a human-specific fashion.
Self-Incentives Uniquely Boost Cessation in Community-Based Stop Smoking Programs: Randomized Controlled Trial.

BACKGROUND Self-incentives offer a plausible alternative to paying smokers to quit but have not yet been tested in a randomized controlled trial. PURPOSE The present study tested whether, compared with a control group, prompting smokers explicitly to self-incentivize if they abstain from smoking for a week or a month encouraged sustained abstinence. METHOD One hundred and fifty-nine smokers were recruited from stop smoking clinics and randomized to an active control condition (asked to form a plan to quit, n = 65) or one of two intervention conditions in which they were asked to form implementation intentions designed to ensure that they incentivized themselves if they had not smoked at all by the end of (a) the week (n = 44) or (b) the month (n = 50). The main outcome measure was self-reported abstinence at 3- and 6-month follow-ups, which was biochemically verified at baseline and in a subsample at 3-month follow-up. RESULTS At 3-month follow-up, 34% (15/44; p < .05, d = 0.45) and 36% (18/50; p < .05, d = 0.49) of smokers abstained in the weekly and monthly self-incentivizing conditions respectively, compared with 15% (10/65) in the control. The same pattern of findings was observed at 6-month follow-up: 30% (13/44; p < .05, d = 0.35), 34% (17/50; p < .05, d = 0.45) and 15% (10/65) of smokers remained abstinent in the two intervention groups and control group, respectively. CONCLUSIONS Ensuring that smokers self-incentivized boosted significantly the effectiveness of the stop smoking program. Self-incentivizing implementation intentions could be implemented at low cost with high public health "reach" to change many health behaviors beyond smoking. TRIAL REGISTRATION ISRCTN11610200.
Assessment of food quality and microbial safety of brown macroalgae (Alaria esculenta and Saccharina latissima).

BACKGROUND There has been a rapid increase in the number of seaweed farms in the Western world, and it is crucial for these companies and their customers to have standardized methods for quality assessment and optimization. The aim of this study was to adapt known methods for food-quality determination for the analysis of seaweed quality, including color, texture, and microbiology, and to discuss optimal heat treatments for the popular macroalgae Saccharina latissima and Alaria esculenta. RESULTS The development of an attractive, green color during heating was highly specific to species, freezing history, and part of the thallus. Resilience and thermostability were also species dependent. Low microbial numbers (1-3 log cfu/g) for total aerobic count, psychrotrophic bacteria, and spore-forming bacteria were found, but Bacillus spp. were isolated. No enterococci, coliforms, pathogenic vibrios, or Listeria monocytogenes were detected. CONCLUSION The methods employed were able to describe clearly the physical and microbial qualities of A. esculenta and S. latissima, and quality changes during processing. Based on the results, optimal cooking for a minimum of 15 min at 95 °C was suggested for S. latissima. Fresh and frozen A. esculenta showed the greenest color after heating for 5-9 s at a high temperature (> 85 °C). If a higher heat load is needed to achieve safe and stable food products, using fresh and not frozen A. esculenta is highly recommended, as fresh specimens remain green even after 15 min at 95 °C. © 2018 Society of Chemical Industry.
Resistance exercise alone improves muscle strength in growth hormone deficient males in the transition phase

Abstract Background During the transition phase (TP), patients with growth hormone deficiency (GHD) exhibit decreased muscle strength. Studies assessing the effects of resistance exercise alone on muscle strength in these individuals are scarce. The objective of this study was to evaluate the effects of a program of resistance exercise (PRE) on parameters of muscle strength in subjects in the TP and with childhood-onset GHD treated with recombinant GH (rGH). Methods Sixteen male patients were enrolled and divided into two groups: GHD (n=9) and GH sufficiency (GHS, n=7). Patients with GHD underwent a 12-week PRE followed by another 12-week PRE plus rGH, while GHS patients underwent a 12-week PRE alone. Dynamic knee muscle strength was evaluated using an isokinetic dynamometer. Results Before PRE, there were significant differences between the groups regarding the results of flexor peak torque (FPT) normalized to body weight (BW-FPT) in the dominant (DO, p=0.008) and non-dominant (ND, p=0.01) limbs, and in the agonist/antagonist (A/A) ratio in the DO (p=0.02) and ND (p=0.006) limbs. After PRE in the GHD group, values of FPT and BW-FPT in both limbs increased significantly (p<0.001) and independently of rGH, while the A/A ratio value improved significantly (p<0.001) in the ND limb. Conclusions A short period of PRE alone was sufficient to improve parameters of muscle strength in young male adults with childhood-onset GHD.