bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV
Authors: Ebrahim Ismaeel , Maartens Gary , Wiesner Lubbe , Orrell Catherine , Smythe Wynand , McIlleron Helen
Published: December 2019

Background

Darunavir/ritonavir is better tolerated than lopinavir/ritonavir and has a higher genetic barrier to resistance. Co-administration with rifampicin has been contraindicated as a significant reduction in darunavir exposure is expected. This is a barrier to darunavir/ritonavir use where TB is endemic.

Objectives

To evaluate the safety and pharmacokinetic profile of adjusted doses of darunavir/ritonavir with rifampicin.

Methods

Virally suppressed participants on second-line lopinavir/ritonavir-based ART were switched to darunavir/ritonavir 800/100 mg q24h. In sequence: rifampicin was added; the dose of ritonavir was escalated; and darunavir was increased (darunavir/ritonavir 1600/200 mg q24h and 800/100 mg q12h were given in randomized sequence with rifampicin). Darunavir plasma concentrations were measured on the seventh/last day of each treatment period. To prevent viral rebound, dolutegravir (50 mg q12h) was added during rifampicin administration and for 1 week thereafter. Clinical events, ALT and bilirubin were monitored every 2–3 days during rifampicin administration.

Results

A total of 17/28 participants started study treatment. Six (35.3%) were withdrawn for symptomatic hepatitis with severe ALT elevations, developing after 9–11 days of rifampicin and 2–4 days of ritonavir 200 mg. The study was stopped prematurely due to this high rate of hepatotoxicity. Only four participants completed the study. All hepatotoxicity resolved on withdrawal of study treatment. All participants were successfully re-established on their lopinavir/ritonavir-based regimen. After doubling the darunavir/ritonavir doses on rifampicin, darunavir pre-dose concentrations approached those on standard doses without rifampicin for q12h doses, but not for q24h doses.

Conclusions

Adjusted doses of darunavir/ritonavir with rifampicin had unacceptable risk of hepatotoxicity. Darunavir trough concentrations were markedly reduced with the daily adjusted dose.
Research data management in health and biomedical citizen science: practices and prospects
Authors: Borda Ann , Gray Kathleen , Fu Yuqing
Published: December 2019

Background

Public engagement in health and biomedical research is being influenced by the paradigm of citizen science. However, conventional health and biomedical research relies on sophisticated research data management tools and methods. Considering these, what contribution can citizen science make in this field of research? How can it follow research protocols and produce reliable results?

Objective

The aim of this article is to analyze research data management practices in existing biomedical citizen science studies, so as to provide insights for members of the public and of the research community considering this approach to research.

Methods

A scoping review was conducted on this topic to determine data management characteristics of health and bio medical citizen science research. From this review and related web searching, we chose five online platforms and a specific research project associated with each, to understand their research data management approaches and enablers.

Results

Health and biomedical citizen science platforms and projects are diverse in terms of types of work with data and data management activities that in themselves may have scientific merit. However, consistent approaches in the use of research data management models or practices seem lacking, or at least are not prevalent in the review.

Conclusions

There is potential for important data collection and analysis activities to be opaque or irreproducible in health and biomedical citizen science initiatives without the implementation of a research data management model that is transparent and accessible to team members and to external audiences. This situation might be improved with participatory development of standards that can be applied to diverse projects and platforms, across the research data life cycle.
PSIV-3 Effect of winter-feeding system and roughage level in feedlot ration on subsequent spring grazing behavior and dry matter intake of beef growing heifers
Authors: Burjel María Victoria , Simeone Alvaro , Bentancur Oscar , Zabalveytia Natalia , Beretta Virginia
Published: December 2019

This study aimed to evaluate the effect of winter-feeding system (grazing, GFS vs. feedlot, FFS) and ration roughage level (RL), on subsequent spring grazing behavior and forage dry matter intake (DMI). Thirty-two Hereford female calves (149 ± 13 kg) were assigned to four winter dietary treatments (110 days) in a randomized block design (n = 2/treatment): three feedlot rations differing RL (Setaria italica) (0%, 35% or 70% DM) or oats grazing (5 kg DM/100 kg LW). In spring (84 days) all treatments grazed a mixed grass-legume pastures (4317 ± 1009 kg DM/ha; 6 kg DM/100 kg LW). During weeks 1, 3 and 5 after changing diets, diurnal behavior activity (effective/search grazing, rumination, idling or water intake) was visually recorded and DMI estimated from the in vivo DM digestibility (DMD) and fecal production. Data were analyzed according to a block design with repeated measures, with general model including block, treatment (T), week (W) and T×W effects. Means were compared through orthogonal contrasts (Table 1). Spring DMI varied with T (P = 0.0084) regardless of W effect (P = 0.1619), with higher values for GFS compared to FFS (1.55 vs. 1.16 kg/100 kg LW, P = 0.0034) and for 70RL compared to 35RL (P = 0.0286). DMD did not differ between treatments (P = 0.2488) but was lower on W1 than W5 (55 vs. 64 %, P = 0.0150). T×W was significant (P < 0.0001) for effective grazing, rumination and idling. On W1, heifers from GFS grazed less (0.40 vs. 0.49, P = 0.0268) but tended to ruminate more (0.26 vs. 0.18, P = 0.0591) than FFS. As pasture DMD improved (W5) GFS grazed more (0.64 vs. 0.51, P = 0.0020) but ruminated less (0.14 vs. 0.21, P = 0.0450) than FFS. Transition from FFS to spring grazing might reduce pasture DMI modifying animal ingestive behavior compare to animals from GFS. Impact could be higher when ration RL is below 70%.
PSXI-37 Differences in thermoregulation ability and genetic parameters of skin traits in Angus, Brahman and their Crossbreds
Authors: Dikmen Serdal , Mateescu Raluca G
Published: December 2019

Thermoregulation is important for beef cattle but tends to be negatively correlated with production traits. The objective of this study was to determine the variation in core body temperature and to estimate genetic parameters of skin traits in Angus, Brahman, and different levels of crossbred heifers (n = 337) reared in hot and humid conditions. Core body temperature was recorded as vaginal temperature every 15 minutes for 5 consecutive days. Dry bulb temperature and relative humidity in the pasture were also measured every 15 min and used to calculate a temperature-humidity index (THI). Five mm skin biopsies were collected from the right side of sixth thoracic bone of each heifer. Cross-sections of biopsy samples with a thickness of 7 µm were stained with Hematoxilin–Eosin technique. The number and area of sweat and sebaceous glands, and the thickness of dermis and epidermis were determined using the ImageJ program. Data were analysed using PROC MIXED in SAS 9.4 with a model including the effect of breed, year, and their interaction. Genetic parameters were estimated using WOMBAT. Average core body temperature of Angus, 25%, 37.5%, 50%,75% and 100% Brahman were 39.50±0.05, 39.30±0.04, 39.15±0.05, 39.2±0.0, 39.03±0.05, 39.04±0.05, respectively. Brahman heifers had lower core body temperature compared to Angus heifers (P = 0.0006). Heifers with smaller and more numerous sweat glands had higher (P < 0.01) and more variable core body temperature (P < 0.0001). Heritability of core body temperature under high and low THI was 0.44±0.006 and 0.61±0.003, respectively. Dermis and epidermis thickness had the lowest heritability (0.231±0.002) and the highest heritability (0.75±0.007), respectively. Heritabilities for the number of sweat glands and total sweat gland area were 0.375±0.02 and 0.432±0.006, respectively. In conclusion, thermoregulation was highly correlated with breed composition, number of sweat glands and the average size of sweat glands.
PSIX-5 Effects of live yeast on functional attributes of rumen microbiota in beef cattle
Authors: Ogunade Ibukun M , Lay Jerusha , Andries Kenneth
Published: December 2019

This study applied whole-metagenomics shotgun sequencing to evaluate the effects of live yeast supplementation on functional potential of rumen microbiota in beef cattle. Eight rumen-cannulated Holstein steers were assigned randomly to 1 of 2 treatments in cross-over design with two 25-d experimental periods and a 10-d wash-out between the two periods. The steers were housed in individual pens and were fed 50% concentrate and 50% red clover hay ad libitum. Dietary treatments were (1) control (CON; basal diet) and (2) yeast (YEA; basal diet plus 15 g/d of yeast product; PMI, Arden Hills, MN, USA). Rumen fluid samples were collected at 3, 6 and 9 h after feeding on the last day of each period. Sequencing was done on an Illumina HiSeq 2500. Differences in the relative abundance of taxa at the species level were analyzed using the GLIMMIX procedure of SAS using a model that included the effects of treatment, period, and their interaction. Dietary yeast supplementation increased (P < 0.05) the relative abundance of carbohydrate-fermenting bacteria, such as Ruminococcus albus, R. champanellensis, R. bromii, and R. obeum, and lactate-utilizing bacteria, such as Megasphera elsdenii, Desulfovibrio desulfuricans, and D. vulgaris. A total of 154 differentially abundant microbial genes (DAGs) were obtained (false discovery rate < 0.01). Kyoto Encyclopedia of Genes and Genomes annotation analysis of the DAGs revealed that pathways involving amino sugar and nucleotide sugar metabolism, oxidative phosphorylation, pantothenate and CoA biosynthesis, beta-alanine metabolism, and polyketide sugar unit biosynthesis were enriched in steers fed YEA. Annotation of the DAGs in carbohydrate-active enzymes database revealed that genes coding for enzymes belonging to glycoside hydrolases, glycosyltransferases, and carbohydrate binding modules were enriched in steers fed YEA. These findings confirm the efficacy of live S. cerevisiae product at reducing redox potential and increasing cellulolytic and lactate-utilizing activities in the rumen.
Comparing Prophylactic Versus Threshold-Based Insecticide Programs for Striped Cucumber Beetle (Coleoptera: Chrysomelidae) Management in Watermelon
Authors: Ternest John J , Ingwell L L , Foster R E , Kaplan I
Published: December 2019

In cucurbit crops such as watermelon, implementation of integrated pest management (IPM) is important due to the high reliance on bees for fruit set, along with mounting evidence of the risks of insecticide use associated with pollinator health. Yet, IPM adoption, on-farm pesticide use behaviors, their costs, and impacts on the primary insect pest (striped cucumber beetle, Acalymma vittatum F.) are poorly known in one of the key watermelon-growing regions, the Midwestern United States. To better understand how to implement IPM into watermelon production, we assessed pest management practices on commercial watermelon farms using 30 field sites in Indiana and Illinois over 2 yr in 2017 and 2018. Across all sampling dates, beetles never crossed the economic threshold of five beetles/plant at any farm and most were maintained at densities far below this level (i.e., <1 beetle/plant). Moreover, we documented a wide range of insecticide inputs (mean ca. 5 applications per field per season; max. 10 applications) that were largely dominated by inexpensive foliar pyrethroid sprays; however, insecticide application frequency was poorly correlated with pest counts, suggesting that most of these applications were unnecessary. We calculated that the cost of the average insecticide program far exceeds the cost of scouting, and thus IPM is estimated to save growers ca. $1,000 per field under average conditions (i.e., field size, insecticide cost). These data strongly indicate that current management practices on commercial farms in the Midwest would benefit from implementing more threshold-based IPM programs with potential increases in both farm profitability and pollination services.
From discovery to delivery: public sector development of the rVSV-ZEBOV Ebola vaccine
Authors: Herder Matthew , Graham Janice E , Gold Richard
Published: December 2019

The discovery and development of the Ebola rVSV-ZEBOV vaccine challenge the common assumption that the research and development for innovative therapeutic products and vaccines is best carried out by the private sector. Using internal government documents obtained through an access to information request, we analyze the development of rVSV-ZEBOV by researchers at Canada’s National Microbiology Laboratory beyond its patenting and licensing to a biotech company in the United States in 2010. According to government documentation, the company failed to make any progress toward a phase 1 clinical trial until after the WHO Public Health Emergency of International Concern freed substantial donor and public funds for the vaccine’s further development. The development of rVSV-ZEBOV, from sponsoring early stage research through to carrying out clinical trials during the epidemic, was instead the result of the combined efforts of the Canadian government, its researchers, and other publicly funded institutions. This case study of rVSV-ZEBOV underscores the significant public contribution to the R&D of vaccines even under conditions of precarity, and suggests that an alternative approach to generating knowledge and developing interventions, such as open science, is required in order to fully realize the public sector’s contribution to improved global health.
Quantitative and Qualitative Costs of Autogeny in Phlebotomus papatasi (Diptera: Psychodidae) Sand Flies
Authors: Shymanovich Tatsiana , Hajhashemi Nima , Wasserberg Gideon
Published: December 2019

Most sand flies and mosquitoes require a bloodmeal for egg production, but when blood-sources are scarce, some of them can reproduce without it, so called facultative autogeny. The evolution of autogenous reproduction is thought to involve a trade-off between the benefit of reproducing in the absence of bloodmeal hosts versus the quantitative cost of reduced fecundity and/or or qualitative effect on reduced offspring development and survivorship. We blood-fed (BF) some Phlebotomous papatasi (Scopoli) sand fly females on mice while keeping others (from the same cohort) not BF. We then compared the fecundity of BF and non-blood-fed (NBF) females and also evaluated their egg mass and hatching rate, larval development rate and survivorship, pupa mass and eclosion rates, and progeny fecundity. Among NBF females, only 55% became gravid and produced three times less mature oocytes than BF ones. Autogenous females laid 3.5 and 5.7 times fewer eggs in individual and multi-female bioassays, respectively. Egg mass and hatching rate were not affected by blood-feeding. Individual-larvae bioassays suggested reduced survival during larval stages in the autogenous group. In multi-larvae bioassays, overall and especially pupae survival was significantly reduced in the autogenous group. Development rate was slower and pupal mass was reduced in progeny from autogenous mothers. These effects were particularly apparent at high larval density. Mothers’ blood-feeding history did not affect daughter’s fecundity. Studies on the costs of autogeny provides insights on the evolution of blood feeding. Moreover, it also provides insights regarding potential implications of autogeny to the emergence of vector-borne diseases.
Reduced Protumorigenic Tumor-Associated Macrophages With Statin Use in Premalignant Human Lung Adenocarcinoma
Authors: Al Dujaily Esraa , Baena Juvenal , Das Madhumita , Sereno Marco , Smith Claire , Kamata Tamihiro , Officer Leah , Pritchard Catrin , Le Quesne John
Published: December 2019

Background

Statins have anticancer properties by acting as competitive inhibitors of the mevalonate pathway. They also have anti-inflammatory activity, but their role in suppressing inflammation in a cancer context has not been investigated to date.

Methods

We have analyzed the relationship between statin use and tumor-associated macrophages (TAMs) in a cohort of 262 surgically resected primary human lung adenocarcinomas. TAMs were evaluated by multiplex immunostaining for the CD68 pan-TAM marker and the CD163 protumorigenic TAM marker followed by digital slide scanning and partially automated quantitation. Links between statin use and tumor stage, virulence, and cancer-specific survival were also investigated in a wider cohort of 958 lung adenocarcinoma cases. All statistical tests were two-sided.

Results

We found a statin dose-dependent reduction in protumorigenic TAMs (CD68+CD163+) in both stromal (P = .021) and parenchymal (P = .003) compartments within regions of in situ tumor growth, but this association was lost in invasive regions. No statistically significant relationship between statin use and tumor stage was observed, but there was a statin dose-dependent shift towards lower histological grade as assessed by growth pattern (P = .028). However, statin use was a predictor of slightly worse cancer-specific survival (P = .032), even after accounting for prognostic variables in a multivariable Cox proportional hazards survival model (hazard ratio = 1.38, 95% confidence interval = 1.04 to 1.84).

Conclusions

Statin use is associated with reduced numbers of protumorigenic TAMs within preinvasive lung adenocarcinoma and is related to reduced tumor invasiveness, suggesting a chemo-preventive effect in early tumor development. However, invasive disease is resistant to these effects, and no beneficial relationship between statin use and patient outcome is observed.
Stellar population properties of individual massive early-type galaxies at 1.4 < z < 2
Authors: Lonoce I , Maraston C , Thomas D , Longhetti M , Parikh T , Guarnieri P , Comparat J
Published: December 2019

We analyse publicly available, individual spectra of four massive ($M\gt 10^{11}\, \mathrm{M}_{\odot }$) early-type galaxies with redshifts in the range 1.4 ≤ z ≤ 2 to determine their stellar content, extending our previous work up to z ∼ 2. The wide wavelength range of the VLT/X-Shooter spectroscopic data in the UV–Optical–NIR arms along with the availability of spectro-photometry allows us to explore different techniques to obtain the stellar population properties, namely through age/metallicity-sensitive spectral indices, full spectral fitting, and broad-band photometric fitting. Moreover, together with the widely used optical Lick indices, we consider further indices in the UV rest frame, and demonstrate that UV indices significantly help the accuracy of the resulting population parameters. We find galaxy ages ranging from 0.2 to 4 Gyr, where the oldest galaxy is found at the lowest redshift, with an excellent agreement between ages determined via indices, full spectral fitting, or broad-band colours. These ages are in perfect agreement with ages of local galaxies at the same velocity dispersion when we assume pure passive evolution. Total metallicities derived from indices show some scatter (between less than half-solar to very high values, [Z/H] ∼ 0.6). We speculate on possible mechanisms explaining these values, but given the sample size and low S/N of the spectra no conclusion can be made. Indices in the UV rest frame generally lead to similar conclusions as optical indices. For the oldest galaxy (4 Gyr), we show that its UV indices can only be explained by stellar population models including a UV contribution from old stellar populations, suggesting that old, UV bright populations start to inhabit mature galaxies of a few Gyr of age. This is the highest redshift (z ∼ 1.4) detection of the UV upturn up to date.
Sardinia Radio Telescope observations of Local Group dwarf galaxies – I. The cases of NGC 6822, IC 1613, and WLM
Authors: Tarchi A , Castangia P , Surcis G , Brunthaler A , Henkel C , Pawlowski M , Menten K M , Melis A , Casu S , Murgia M , Trois A , Concu R , Darling J
Published: December 2019

Almost all dwarf galaxies in the Local Group (LG) that are not satellites of the Milky Way or M 31 belong to either one of two highly symmetric planes. It is still a matter of debate whether these planar structures are dynamically stable or whether they only represent a transient alignment. Proper motions, if they could be measured, could help to discriminate between these scenarios. Such motions could be determined with multi-epoch very long baseline interferometry (VLBI) of sources that show emission from water and methanol at frequencies of 22 and 6.7 GHz, respectively. We report searches for such masers. We have mapped three LG galaxies, NGC 6822, IC 1613, and WLM, in the bands covering the water vapour and methanol lines. These systems are members of the two above-mentioned planes of galaxies. We have produced deep radio continuum (RC) maps and spectral line cubes. The former have been used to identify star-forming regions and to derive global galactic star formation rates (SFRs). These SFRs turn out to be lower than those determined at other wavelengths in two of our sources. This indicates that dwarf galaxies may follow predictions on the RC–SFR relation only in individual regions of enhanced RC emission, but not when considering the entire optical body of the sources. No methanol or water maser emission has been confidently detected, down to line luminosity limits of ∼4 × 10−3 and 10 × 10−3 L⊙, respectively. This finding is consistent with the small sizes, low SFRs, and metallicities of these galaxies.
The Young Suns Exoplanet Survey: Detection of a wide-orbit planetary-mass companion to a solar-type Sco-Cen member
Authors: Bohn A J , Kenworthy M A , Ginski C , Manara C F , Pecaut M J , de Boer J , Keller C U , Mamajek E E , Meshkat T , Reggiani M , Todorov K O , Snik F
Published: December 2019

The Young Suns Exoplanet Survey consists of a homogeneous sample of 70 young, solar-mass stars located in the Lower Centaurus-Crux subgroup of the Scorpius-Centaurus association with an average age of 15 ± 3 Myr. We report the detection of a co-moving companion around the K3IV star TYC 8998-760-1 (2MASSJ13251211–6456207) that is located at a distance of 94.6 ± 0.3 pc using SPHERE/IRDIS on the VLT. Spectroscopic observations with VLT/X-SHOOTER constrain the mass of the star to $1.00\pm 0.02\, \mathrm{M}_{\odot }$ and an age of $16.7\pm 1.4\,$ Myr. The companion TYC 8998-760-1 b is detected at a projected separation of 1.71″, which implies a projected physical separation of 162 au. Photometric measurements ranging from Y to M band provide a mass estimate of $14\pm 3\, M_\mathrm{jup}$ by comparison to BT-Settl and AMES-dusty isochrones, corresponding to a mass ratio of q = 0.013 ± 0.003 with respect to the primary. We rule out additional companions to TYC 8998-760-1 that are more massive than $12\, M_\mathrm{jup}$ and farther than 12 au away from the host. Future polarimetric and spectroscopic observations of this system with ground and space based observatories will facilitate testing of formation and evolution scenarios shaping the architecture of the circumstellar environment around this ‘young Sun’.
The Hi-GAL catalogue of dusty filamentary structures in the Galactic plane
Authors: Schisano Eugenio , Molinari S , Elia D , Benedettini M , Olmi L , Pezzuto S , Traficante A , Brescia M , Cavuoti S , di Giorgio A M , Liu S J , Moore T J T , Noriega-Crespo A , Riccio G , Baldeschi A , Becciani U , Peretto N , Merello M , Vitello F , Zavagno A , Beltrán M T , Cambrésy L , Eden D J , Li Causi G , Molinaro M , Palmeirim P , Sciacca E , Testi L , Umana G , Whitworth A P
Published: December 2019

The recent data collected by Herschel have confirmed that interstellar structures with a filamentary shape are ubiquitously present in the Milky Way. Filaments are thought to be formed by several physical mechanisms acting from large Galactic scales down to subparsec fractions of molecular clouds, and they might represent a possible link between star formation and the large-scale structure of the Galaxy. In order to study this potential link, a statistically significant sample of filaments spread throughout the Galaxy is required. In this work, we present the first catalogue of 32 059 candidate filaments automatically identified in the Herschel Infrared Galactic plane Survey (Hi-GAL) of the entire Galactic plane. For these objects, we determined morphological (length la and geometrical shape) and physical (average column density $N_{\rm H_{2}}$ and average temperature T) properties. We identified filaments with a wide range of properties: 2 ≤ la ≤ 100 arcmin, $10^{20} \le N_{\rm H_{2}} \le 10^{23}$ cm−2 and 10 ≤ T ≤ 35 K. We discuss their association with the Hi-GAL compact sources, finding that the most tenuous (and stable) structures do not host any major condensation. We also assign a distance to ∼18 400 filaments, for which we determine mass, physical size, stability conditions and Galactic distribution. When compared with the spiral arms structure, we find no significant difference between the physical properties of on-arm and inter-arm filaments. We compare our sample with previous studies, finding that our Hi-GAL filament catalogue represents a significant extension in terms of Galactic coverage and sensitivity. This catalogue represents a unique and important tool for future studies devoted to understanding the filament life-cycle.
Galaxy interactions in IllustrisTNG-100, I: The power and limitations of visual identification
Authors: Blumenthal Kelly A , Moreno Jorge , Barnes Joshua E , Hernquist Lars , Torrey Paul , Claytor Zachary , Rodriguez-Gomez Vicente , Marinacci Federico , Vogelsberger Mark
Published: December 2019

We present a sample of 446 galaxy pairs constructed using the cosmological simulation IllustrisTNG-100 at z = 0, with M$_{\rm FoF,dm} = 10^{11}\!-\!10^{13.5}$ M⊙. We produce ideal mock SDSS g-band images of all pairs to test the reliability of visual classification schema employed to produce samples of interacting galaxies. We visually classify each image as interacting or not based on the presence of a close neighbour, the presence of stellar debris fields, disturbed discs, and/or tidal features. By inspecting the trajectories of the pairs, we determine that these indicators correctly identify interacting galaxies ∼45 per cent of the time. We subsequently split the sample into the visually identified interacting pairs (VIP; 38 pairs) and those which are interacting but are not visually identified (nonVIP; 47 pairs). We find that VIP have undergone a close passage nearly twice as recently as the non-VIP, and typically have higher stellar masses. Further, the VIP sit in dark matter haloes that are approximately 2.5 times as massive, in environments nearly 2 times as dense, and are almost a factor of 10 more affected by the tidal forces of their surroundings than the nonVIP. These factors conspire to increase the observability of tidal features and disturbed morphologies, making the VIP more likely to be identified. Thus, merger rate calculations which rely on stellar morphologies are likely to be significantly biased toward massive galaxy pairs which have recently undergone a close passage.
Differential expression of duplicated ribosomal protein genes modifies ribosome composition in response to stress
Authors: Ghulam Mustafa Malik , Catala Mathieu , Abou Elela Sherif
Published: December 2019

In Saccharomyces cerevisiae, most ribosomal proteins are synthesized from duplicated genes, increasing the potential for ribosome heterogeneity. However, the contribution of these duplicated genes to ribosome production and the mechanism determining their relative expression remain unclear. Here we demonstrate that in most cases, one of the two gene copies generate the bulk of the active ribosomes under normal growth conditions, while the other copy is favored only under stress. To understand the origin of these differences in paralog expression and their contribution to ribosome heterogeneity we used RNA polymerase II ChIP-Seq, RNA-seq, polyribosome association and peptide-based mass-spectrometry to compare their transcription potential, splicing, mRNA abundance, translation potential, protein abundance and incorporation into ribosomes. In normal conditions a post-transcriptional expression hierarchy of the duplicated ribosomal protein genes is the product of the efficient splicing, high stability and efficient translation of the major paralog mRNA. Exposure of the cell to stress modifies the expression ratio of the paralogs by repressing the expression of the major paralog and thus increasing the number of ribosomes carrying the minor paralog. Together the data indicate that duplicated ribosomal protein genes underlie a modular network permitting the modification of ribosome composition in response to changing growth conditions.
Managing pain and distress in children undergoing brief diagnostic and therapeutic procedures
Authors: Trottier Evelyne D , Doré-Bergeron Marie-Joëlle , Chauvin-Kimoff Laurel , Baerg Krista , Ali Samina
Published: December 2019

Common medical procedures to assess and treat patients can cause significant pain and distress. Clinicians should have a basic approach for minimizing pain and distress in children, particularly for frequently used diagnostic and therapeutic procedures. This statement focuses on infants (excluding care provided in the NICU), children, and youth who are undergoing common, minor but painful medical procedures. Simple, evidence-based strategies for managing pain and distress are reviewed, with guidance for integrating them into clinical practice as an essential part of health care. Health professionals are encouraged to use minimally invasive approaches and, when painful procedures are unavoidable, to combine simple pain and distress-minimizing strategies to improve the patient, parent, and health care provider experience. Health administrators are encouraged to create institutional policies, improve education and access to guidelines, create child- and youth-friendly environments, ensure availability of appropriate staff, equipment and pharmacological agents, and perform quality audits to ensure pain management is optimal.
Iron requirements in the first 2 years of life
Authors: Unger Sharon L , Fenton Tanis R , Jetty Radha , Critch Jeff N , O’connor Deborah L
Published: December 2019

Iron is an essential micronutrient required for hemoglobin synthesis, central nervous system development, and protection from infection. Early childhood is a time of vulnerability as iron deficiency in this period is associated with impaired neurodevelopment. Low socioeconomic status, preterm birth, and suboptimal diet are risk factors for iron deficiency. Due to a lack of iron excretory mechanism, the possibility of iron excess also exists. Appropriate iron intake in the first 2 years of life is critical.
Coping with the extremes: comparative osteology of the tepui-associated toad Oreophrynella and its bearing on the evolution of osteological novelties in the genus
Authors: Kok Philippe J R , van der Velden Milan A J , Means D Bruce , Ratz Sebastian , Josipovic Iván , Boone Matthieu , McDiarmid Roy W
Published: December 2019

The only study of the osteology of the toad genus Oreophrynella dates back to 1971 and was based on a single species. Here, we use high-resolution X-ray microcomputed tomography to analyse the osteology of all nine described Oreophrynella species, which are compared with representatives of other bufonid lineages. Oreophrynella is unique among bufonids in having opposable digits. Osteological synapomorphies confirmed for the genus are as follows: presence of parietal fontanelles and exposed frontoparietal fontanelle, absence of quadratojugal, five presacral vertebrae, distally enlarged terminal phalanges and urostyle greatly expanded into flanges. Ancestral character reconstruction indicates that arboreal habits in some Oreophrynella species are likely to have evolved after the evolution of opposable digits. Opposable digits, in combination with an extension of the interdigital integument and the relative length/orientation of the digits, are likely to be adaptations to facilitate life on rocky tepui summits and an exaptation to arboreality. Cranial simplification in Oreophrynella, in the form of cranial fontanelles and absence of the quadratojugal, is possibly driven by a reduction of developmental costs, increase in flexibility and reduction of body weight. Cranial simplification combined with the shortening of the vertebral column and the shift towards a partly firmisternal girdle might be adaptations to the peculiar tumbling behaviour displayed by Oreophrynella.
Cigarette smoke inhibits the NLRP3 inflammasome and leads to caspase‐1 activation via the TLR4‐TRIF‐caspase‐8 axis in human macrophages
Authors: Buscetta Marco , Di Vincenzo Serena , Miele Monica , Badami Ester , Pace Elisabetta , Cipollina Chiara
Published: December 2019

The NLRP3 inflammasome is formed by the sensor NLRP3, the adaptor ASC, and pro‐caspase‐1. Assembly and activation of the inflammasome trigger caspase‐1‐dependent cleavage of pro‐IL‐1β and pro‐IL‐18 into their secreted forms. Cigarette smoke is a risk factor for chronic inflammatory diseases and is associated with macrophage dysfunction. The impact of cigarette smoke on NLRP3‐dependent responses in macrophages is largely unknown. Herein, we investigated the effects of cigarette smoke extract (CSE) on the NLRP3 inflammasome in human monocyte‐derived macrophages (MDMs) and THP‐1 cells stimulated with lipopolysaccharide (LPS) and LPS plus the NLRP3 inflammasome activator ATP. We found that CSE inhibited the release of IL‐1β and IL‐18 as well as the expression of NLRP3 acting mainly at the transcriptional level. Interestingly, we found that CSE increased the caspase‐1 activity via an NLRP3‐independent and TLR4‐TRIF‐caspase‐8‐dependent pathway. Activation of caspase‐1 by CSE led to a reduction of the basal glycolytic flux and impaired glycolytic burst in response to LPS. Overall, our findings unveil novel pathways leading to immune‐metabolic alterations in human macrophages exposed to cigarette smoke. These mechanisms may contribute to macrophage dysfunction and increased risk of infection in smokers.
Ability of Thromboelastography to Detect Hypercoagulability: A Systematic Review and Meta-Analysis
Authors: Brown Wesley , Lunati Matthew , Maceroli Michael , Ernst Alexandra , Staley Christopher , Johnson Richard , Schenker Mara
Published: December 2019

Objective:

To review the current literature on the use of viscoelastic hemolytic assays, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), during the perioperative period of patients and determine the ability of TEG and ROTEM to detect hypercoagulability and identify increased risk of the development of venous thromboembolism (VTE).

Data Sources:

PubMed, EMBASE, and Cochrane online databases were queried through February 11, 2018, by pairing the terms “thromboelastography,” “viscoelastic hemostatic assays,” and “rotational thromboelastometry” with “venous thromboembolism,” “deep vein thrombosis,” “pulmonary embolism,” and “hypercoagulability.”

Study Selection:

Inclusion and exclusion criteria were established to determine relevance and quality of data, of which 2.54% of initially identified studies met.

Data Extraction and Synthesis:

Articles and citations were reviewed for relevance by 2 independent individuals following PRISMA guidelines as well as a quality assessment of data as established by Zaza et al. In studies that separated patients postoperatively by VTE development or no VTE development, data were pooled utilizing a modified DerSimmion and Laird random effects model.

Results:

One thousand eight hundred ninety-three articles were assessed for eligibility, yielding 370 abstracts. Of the 370 abstracts, 35 studies were included, and of these, only 5 were included in the meta-analysis. Studies included postsurgical patients in a variety of surgical fields, encompassing a total of 8939 patients, with 717 thrombotic events reported. Elevated maximum amplitude (MA) was a statistically significant indicator of hypercoagulability across at least 1 perioperative time point in 17 (50%) of the articles reviewed, consisting of 6348 (72%) patients. The pooled mean MA value for defining hypercoagulability was greater than 66.70 mm. Using a prepublished value for hypercoagulability of 65 mm, the combined effect of MA on the development of VTE in postsurgical patients was determined to be 1.31 (95% confidence, 0.74–2.34, P = 0.175) and was 46% sensitive and 62% specific in predicting a postoperative VTE.

Conclusions:

Only 1 parameter, MA, was consistently used to both define hypercoagulability and be predictive of VTE after traumatic injury and surgical intervention; however, there remains a broad variability in the definition of hypercoagulability as determined by MA and thus limits its predictive ability. In addition, when hypercoagulability was measured throughout the perioperative period, TEG consistently demonstrated hypercoagulability starting on post-op day 1 (POD1).

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Update on oncogenesis and therapy for Kaposi sarcoma
Authors: Dupin Nicolas
Published: December 2019

Purpose of review

This review is an update of the recent findings on pathophysiology of Kaposi sarcoma, the role of HHV-8 in Kaposi sarcoma pathogenesis and to summarize the recent advances in the treatment of Kaposi sarcoma and the role of immunity to control the disease.

Recent findings

The causal agent of Kaposi sarcoma is HHV-8 and the mechanism by which HHV-8 drives the tumor development is unique. HHV-8 is not a classic oncogenic virus and the disease is an opportunistic tumor responding to immune restoration when it is possible.

Five epidemiologic types of Kaposi are recognized and HHV-8 is associated to all epidemiologic forms of Kaposi. HHV-8 is a virus favoring both angiogenesis and cellular proliferation, which are the two main histological features of Kaposi sarcoma. Although in many cases, treatment of Kaposi sarcoma is not necessary, specific chemotherapy, immunomodulation and immune stimulation are the tools for treating Kaposi sarcoma. Monochemotherapy has been shown to be as efficient as polychemotherapy and less toxic. Immune checkpoint inhibitors gave some promising results, which should be confirmed by prospective studies.
Physical Therapy as a Force Multiplier: Population Health Perspectives to Address Short-Term Readiness and Long-Term Health of Military Service Members
Authors: Fraser John J. , Schmied Emily , Rosenthal Michael D. , Davenport Todd E.
Published: December 2019

Neuromusculoskeletal (NMSK) injuries are ubiquitous in the United States Armed Forces and pose a substantial threat to operational readiness. Many service members who sustain an NMSK injury progress to develop chronic conditions that may result in substantial decrease in function and physical activity across a lifetime. Both social and psychological factors may drive care-seeking and treatment compliance in service members following NMSK injury, contribute to the chronification of injury, which likely result in long-term cardiovascular consequences that contribute to morbidity and mortality. The decision to seek care following NMSK injury is ultimately related to the knowledge, beliefs, attitudes, and values of individual service members that are influenced by the military culture in which they serve. In this clinical perspective, the authors provided a theoretical framework on how psychosocial determinants of care-seeking may contribute to chronification of NMSK conditions and how this may influence long-term cardiovascular health. Cultural shifts and changes in health care delivery in the military may help to mitigate barriers to care and promote care-seeking with the clinician being viewed as a “force multiplier” or optimizer of readiness. Because there are substantial gaps still remaining in the evidence, the authors hope that this perspective will facilitate future research related to this topic.
Roles for Physical Therapists to Address Health Literacy as a Social Determinant of Cardiovascular Disease: A Clinical Perspective
Authors: Griech Sean F. , Skrzat Julie M.
Published: December 2019

Health literacy (HL) has been defined as “the capacity of individuals to obtain, process, and understand basic health information and services needed to make appropriate health decisions.” Despite its importance, 90 million individuals in the United States have less than adequate levels of HL. This is concerning, especially for patients with chronic conditions requiring daily disease management, such as cardiovascular disease (CVD). With 70 million Americans suffering from CVD, there is a high likelihood of HL and CVD overlapping, which can greatly impact physical therapy management and ultimately patient outcomes. Health literacy should be viewed as a specific form of education—a social determinant of health—that has important implications for wellbeing. To achieve the American Physical Therapy Association's vision of “Transforming society by optimizing movement to improve the human experience,” physical therapists must improve their understanding of HL to maximize their interventions. The purpose of this perspective is to discuss HL and its intersectional relationship with the Social Determinants of Health in patients with CVD. This perspective will then culminate in recommendations for physical therapists to reduce health inequities related to limited HL.
Administration of Interleukin-15 Peptide Improves Cardiac Function in a Mouse Model of Myocardial Infarction
Authors: Ameri Kurosh , Bayardorj Dulguun , Samurkashian Raffi , Fredkin Maxwell , Fuh Eric , Nguyen Vien , Yeghiazarians Yerem
Published: December 2019

Interleukin-15 is a pleotropic factor, capable of modulating metabolism, survival, proliferation, and differentiation in many different cell types. The rationale behind this study relates to previous work demonstrating that IL-15 is a major factor present in stem cell extracts, which protects cardiomyocytes subjected to hypoxic stress in vitro. The objective of this current study was to assess whether administration of IL-15 peptide will also show protective effects in vivo. The data indicate that administration of IL-15 reduces cell death, increases vascularity, decreases scar size, and significantly improves left ventricular ejection fraction in a mouse model of myocardial infarction.
Mechanisms of PARP inhibitor resistance in ovarian cancer
Authors: Kubalanza Kari , Konecny Gottfried E.
Published: December 2019

Purpose of review

To summarize recently discovered PARP inhibitor resistance mechanisms and highlight the clinical relevance of these findings to date.

Recent findings

A predominant mechanism of acquired PARP inhibitor resistance in homologous recombination-deficient cancers is the acquisition of homologous recombination proficiency as a consequence of secondary genetic or epigenetic events, such as secondary mutations in BRCA1 or BRCA2, or reversal of BRCA1 promoter methylation that restores homologous recombination and leads to PARP inhibitor resistance. Multiple other potential mechanisms of acquired resistance to PARP inhibitors including loss of DNA end resection inhibition (53BP1/REV7/RIF1/Sheldin) or DNA replication fork protection (PTIP/EZH2), but also increased drug efflux or induction of a reversible senescent or mesenchymal cell state have been described in ovarian cancer models. However, only few of these mechanisms have been identified in clinical samples.

Multiple adaptive responses following PARP inhibitor treatment have been identified. Further research is needed to better understand what role these mechanisms play for clinical PARP inhibitor resistance and how these mechanisms may render ovarian cancer cells susceptible to subsequent novel combination therapies.
Surgical Technique, Indications, and Outcomes of BIOM-Assisted Transvitreal Biopsy for Uveal Melanoma
Authors: Snyder Laura L. , Daniels Anthony B.
Published: December 2019

Purpose:

Controversy exists regarding the best method for biopsy of uveal melanoma. We describe our transvitreal technique and evaluate the safety of this technique as well as the efficacy for obtaining sample for prognostic genetic profiling.

Methods:

Description of surgical technique and retrospective case series. Medical records for uveal melanoma patients who underwent transvitreal biopsy using our described technique were analyzed for tumor size, location, primary treatment, method of biopsy, and any complications thereof. Characteristics of tumors that underwent transvitreal biopsy were noted including tumor size, location, or presence of subretinal fluid, to see whether these affected surgeon preference for biopsy modality. A cohort of contemporaneous uveal melanoma patients who underwent biopsy through a transscleral technique served as a comparator group for these patient, tumor, and complication factors.

Results:

A total of 27 patients aged 27.2 to 88.6 years (mean 64.8) underwent transvitreal biopsy using our described technique between 2013 and 2016. There were 15 small, 10 medium, and 2 large tumors at diagnosis with the majority (n = 17) posterior to the equator. Intraoperative complications included a clot or small trickle of blood at the biopsy site in 20 (74.1%) of patients, small localized subretinal hemorrhage in 8 (29.6%), small vitreous hemorrhage in 4 (14.8%), and small transient choroidal detachments in 1 patient (3.6%). When subretinal hemorrhage occurred, it was almost always into a pre-existing pocket of subretinal fluid (P = 0.0093). However, the presence of subretinal fluid was not associated with the decision to proceed with any biopsy (P = 0.36) or transvitreal biopsy specifically (P = 1.00). By 3 months, subretinal and/or vitreous hemorrhage resolved in essentially all cases. There were no cases of iatrogenic retinal detachment or extraocular tumor spread over a mean follow-up of 41.7 (range: 20–62.1) months. Adequate tissue for gene expression profiling was obtained from each biopsy. The comparator group of patients undergoing transscleral biopsy including 21 uveal melanomas in 20 patients (one eye had two melanomas). Transvitreal biopsies were more common in patients with small (n = 15; P < 0.0001), posterior (n = 17; P < 0.0001) tumors, compared with patients who underwent transscleral biopsy during the same period.

Conclusion:

This technique can be used for small or posterior tumors or for small anterior tumors where a transscleral approach would risk tumor perforation. Complications were minor, transient, and self-limited. Biopsy yields for molecular prognosis were adequate in all cases. The presence of subretinal fluid may be considered a relative contraindication because it may lead to subretinal hemorrhage in the fluid pocket but did not dissuade us from using this transvitreal technique for patients who would benefit from it.