ResearchPad - research-article https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A pilot study of ex-vivo MRI-PDFF of donor livers for assessment of steatosis and predicting early graft dysfunction]]> https://www.researchpad.co/article/elastic_article_14544 The utility of ex vivo Magnetic resonance imaging proton density fat fraction (MRI-PDFF) in donor liver fat quantification is unknown.PurposeTo evaluate the diagnostic accuracy and utility in predicting early allograft dysfunction (EAD) of ex vivo MRI-PDFF measurement of fat in deceased donor livers using histology as the gold standard.MethodsWe performed Ex vivo, 1.5 Tesla MRI-PDFF on 33 human deceased donor livers before implantation, enroute to the operating room. After the exclusion of 4 images (technical errors), 29 MRI images were evaluable. Histology was evaluable in 27 of 29 patients. EAD was defined as a peak value of aminotransferase >2000 IU/mL during the first week or an INR of ≥1.6 or bilirubin ≥10 mg/dL at day 7.ResultsMRI-PDFF values showed a strong positive correlation (Pearson’s correlation coefficient) when histology (macro-steatosis) was included (r = 0.78, 95% confidence interval 0.57‐0.89, p<0.0001). The correlation appeared much stronger when macro plus micro-steatosis were included (r = 0.87, 95% confidence interval 0.72‐0.94, p<0.0001). EAD was noted in 7(25%) subjects. AUC (Area Under the Curve) for macro steatosis (histology) predicted EAD in 73% (95% CI: 48–99), micro plus macro steatosis in 76% (95% CI: 49–100). AUC for PDFF values predicted EAD in 67(35–98). Comparison of the ROC curves in a multivariate model revealed, adding MRI PDFF values to macro steatosis increased the ability of the model in predicting EAD (AUC: 79%, 95% CI: 59–99), and addition of macro plus micro steatosis based on histology predicted EAD even better (AUC: 90%: 79–100, P = 0.054).ConclusionIn this pilot study, MRI-PDFF imaging showed potential utility in quantifying hepatic steatosis ex-vivo donor liver evaluation and the ability to predict EAD related to severe allograft steatosis in the recipient. ]]> <![CDATA[Predicting the impact of patient and private provider behavior on diagnostic delay for pulmonary tuberculosis patients in India: A simulation modeling study]]> https://www.researchpad.co/article/elastic_article_14543 India contributes more than a quarter of the 10 million global tuberculosis (TB) cases every year.Several studies capture long, circuitous care pathways followed by TB patients until their diagnosis. However, these studies do not quantify the link between diagnostic delay and underlying patient and provider behavior characteristics.What did the researchers do and find?We developed a quantitative simulation model to estimate the impact of behavioral characteristics of patients and providers on diagnostic delay and estimated the parameters of this model using data from detailed interviews of 76 patients from Mumbai and 64 patients from Patna.We found that earlier test ordering by providers would yield a much larger reduction in diagnostic delay than increasing their diagnostic accuracy.What do these findings mean?Policy-makers and implementing agencies should encourage early test ordering behavior by providers to reduce diagnostic delay, and, consequently, to reduce disease transmission. ]]> <![CDATA[Effect of aging and body characteristics on facial sexual dimorphism in the Caucasian Population]]> https://www.researchpad.co/article/elastic_article_14542 The aim of this study was to quantify gender-specific facial characteristics in younger and older adults and to determine how aging and body characteristics, such as height and body-mass index (BMI), influence facial sexual dimorphism.MethodsThe cohort study included 90 younger adults of Caucasian origin (average age of 45 females 23.2 ± 1.9 and 45 males 23.7 ± 2.4 years) and 90 older adults (average age of 49 females 78.1 ± 8.1 and 41 males 74.5 ± 7.7 years). Three-dimensional facial scans were performed with an Artec MHT 3D scanner. The data were analyzed using the software package Rapidform®. The parameters to evaluate facial symmetry, height, width, profile, facial shape, nose, eyes and mouth characteristics were determined based on 39 facial landmarks. Student’s t-test was used to calculate the statistical differences between the genders in the younger and older adults and a multiple-linear-regression analysis was used to evaluate the impact of gender, age, body-mass index and body height.ResultsWe found that the female faces were more symmetrical than the male faces, and this was statistically significant in the older adults. The female facial shape was more rounded and their faces were smaller, after normalizing for body size. The males had wider mouths, longer upper lips, larger noses and more prominent lower foreheads. Surprisingly, we found that all the gender-dependent characteristics were even more pronounced in the older adults. Increased facial asymmetry, decreased facial convexity, increased forehead angle, narrower vermilions and longer inter-eye distances occurred in both genders during aging. An increased BMI was associated with wider faces, more concave facial profiles and wider noses, while greater body height correlated with increased facial heights and wider mouths.ConclusionFacial sexual dimorphism was confirmed by multiple parameters in our study, while the differences between the genders were more pronounced in the older adults. ]]> <![CDATA[Risk of recurrent venous thromboembolism in patients with HIV infection: A nationwide cohort study]]> https://www.researchpad.co/article/elastic_article_14541 The HIV pandemic affects approximately 40 million people and causes significant morbidity, including a markedly increased risk of a venous thromboembolism (VTE).The recurrence risk of VTE in people living with HIV (PWH) is unknown, although this risk drives the anticoagulant therapy duration after a first VTE.Our study determined the recurrent VTE risk in PWH compared to uninfected controls.What did the researchers do and find?We performed an observational cohort study using data from the national ATHENA PWH cohort (2003–2015) in the Netherlands and the Dutch Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) cohort (1999–2009) of HIV-uninfected controls with a first VTE.The recurrent VTE incidence rate per 100 person-years of follow-up (PYFU) was higher in PWH (5.2) compared to controls (3.1) yielding a 1.70 hazard ratio (HR; 95% CI 1.23–2.36). Incidence rates were consistently higher for PWH in subgroups stratified by sex or the cause of the first VTE.PWH with lower cluster of differentiation 4 (CD4)+ T-cell counts at their first VTE had fewer recurrent events, which was driven by PWH experiencing a better CD4+ T-cell recovery on HIV treatment prior to anticoagulant discontinuation.What do these findings mean?The risk of recurrent VTE is apparently increased in PWH but is ameliorated with better immune reconstitution.HIV-associated immunodeficiency reflects a reversible risk factor for VTE specific to PWH and is of relevance for decisions on anticoagulant therapy duration. ]]> <![CDATA[Sublethal and transgenerational effects of sulfoxaflor on the demography and feeding behaviour of the mirid bug <i>Apolygus lucorum</i>]]> https://www.researchpad.co/article/elastic_article_14540 Sulfoxaflor, the first commercially available sulfoximine insecticide, has been used for the control of sap-feeding insect pests such as plant bugs and aphids on a variety of crops. However, its sublethal effects on the mirid bug Apolygus lucorum, one of the key insect pests of Bt cotton and fruit trees in China, have not been fully examined. Here, we evaluated the demography and feeding behaviour of A. lucorum exposed to sulfoxaflor. The leaf-dipping bioassay showed that the LC10 and LC30 of sulfoxaflor against 3rd-instar nymphs of this insect were 1.23 and 8.37 mg L-1, respectively. The LC10 significantly extended the nymphal duration and decreased the oviposition period by 5.29 days and female fecundity by 56.99% in the parent generation (F0). The longer duration of egg, 5th-instar nymphs, preadult, and male adult longevity were observed in the F1 generation (F1) at LC10. At the LC30, the duration of egg and 1st-instar nymph, female adult longevity, and oviposition period of the F1 were significantly shorter, while the nymphal duration in the F0 and duration of 5th-instar nymphs, preadult survival rate, and male adult longevity in the F1 significantly increased. The net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) in the F1 were not significantly affected by these two concentrations, whereas the mean generation time (T) was lower at the LC30. Additionally, the probe counts and cells mixture feeding time were markedly lengthened by the LC10 and LC30, respectively, when A. lucorum nymphs exposed to sulfoxaflor fed on Bt cotton plants without insecticides. These results clearly indicate that sulfoxaflor causes sublethal effects on A. lucorum and the transgenerational effects depend on the tested concentrations.

]]>
<![CDATA[Serological evidence for human exposure to <i>Bacillus cereus</i> biovar <i>anthracis</i> in the villages around Taï National Park, Côte d’Ivoire]]> https://www.researchpad.co/article/elastic_article_14539 Anthrax is a zoonotic disease transmitted from animals to humans and normally caused by B. anthracis mainly in savanna regions. However, untypical bacteria named Bacillus cereus biovar anthracis (Bcbva) were detected in a variety of wild animals in the rain forest region of the Taï National Park (TNP) in Côte d’Ivoire. No anthrax infections in humans living in the region around TNP were reported until now. Therefore, we assessed exposure to the pathogen by analysis of sera from human volunteers for the presence of antibodies against the protective antigen (PA), which is produced by B. anthracis and Bcbva, and against the Bcbva-specific protein pXO2-60. We found antibodies against PA in more than 20% of sera from humans living in the TNP region, and around 10% possessed also antibodies against pXO2-60, confirming exposure to Bcbva. As only Bcbva, but not classic B. anthracis was found in TNP, we assume that the majority of humans had contact with Bcbva and that pXO2-60 is less immunogenic than PA. Although most people reported animal contacts, there was no statistically significant correlation with the presence of antibodies against Bcbva. Nevertheless, our study confirmed that Bcbva represents a danger for humans living in the affected area.

]]>
<![CDATA[Effect of public-private interface agency in Patna and Mumbai, India: Does it alter durations and delays in care seeking for drug-sensitive pulmonary tuberculosis?]]> https://www.researchpad.co/article/elastic_article_14532 Background: Public–private interface agency (PPIA) intervention models in Patna (E. India) and Mumbai (W. India) for pulmonary drug-sensitive (DS) tuberculosis (TB) patients were evaluated over 2 years after maturity to examine effect on reduction of patient pathways and retention.  The models engaged private providers, diagnostic facilities and pharmacies into an effective network providing free diagnostic tests and treatment.

Methods: A population-based retrospective study was undertaken to assess effectiveness of the PPIA model in care pathways of 64 (Patna) and 86 (Mumbai) patients through in-depth interviews conducted within 6 months of initiation treatments to identify types and facilities accessed, duration to diagnosis and treatment. Median durations based on facilities accessed were statistically analysed.  Comparisons were made with baseline values and endline pathways of patients accessing PPIA engaged/non-engaged facilities in private and public sectors.

Results: Compared to non-engaged facilities, persons accessing engaged facilities at first point-of-care had shorter pathways (Mumbai: 32 vs 43 days), (Patna: 15 vs 40 days).  Duration for first care-seeking was considerably shorter for patients accessing PPIA in Patna and for both engaged and non-engaged private facilities in Mumbai (4 days).  Whilst PPIA engaged facilities diagnosed more cases than others, the RNTCP in Mumbai provided diagnosis early.  There was good retention of patients by PPIA-engaged (1 st) facilities (90% post-diagnosis in Patna) but this was affected by the hub-spoke referral system in Mumbai (13%). Second diagnosis is a common feature in Mumbai.  The spoke-hub model in Mumbai contributed considerably to treatment delay; PPIA-engaged providers were better at retaining patients post treatment initiation 11/25 (44%).

Conclusion: PPIA-engaged facilities, accessed at onset, result in marked reduction in pathway durations.  Such initiatives should engage a critical mass of competent providers, proximal investigation facilities with enhanced disease awareness and literacy efforts amongst communities.  Patient movement should be minimized for early treatment and retention.

]]>
<![CDATA[The fast and the frugal: Divergent locomotory strategies drive limb lengthening in theropod dinosaurs]]> https://www.researchpad.co/article/elastic_article_14509 Limb length, cursoriality and speed have long been areas of significant interest in theropod paleobiology, since locomotory capacity, especially running ability, is critical in the pursuit of prey and to avoid becoming prey. The impact of allometry on running ability, and the limiting effect of large body size, are aspects that are traditionally overlooked. Since several different non-avian theropod lineages have each independently evolved body sizes greater than any known terrestrial carnivorous mammal, ~1000kg or more, the effect that such large mass has on movement ability and energetics is an area with significant implications for Mesozoic paleoecology. Here, using expansive datasets that incorporate several different metrics to estimate body size, limb length and running speed, we calculate the effects of allometry on running ability. We test traditional metrics used to evaluate cursoriality in non-avian theropods such as distal limb length, relative hindlimb length, and compare the energetic cost savings of relative hindlimb elongation between members of the Tyrannosauridae and more basal megacarnivores such as Allosauroidea or Ceratosauridae. We find that once the limiting effects of body size increase is incorporated there is no significant correlation to top speed between any of the commonly used metrics, including the newly suggested distal limb index (Tibia + Metatarsus/ Femur length). The data also shows a significant split between large and small bodied theropods in terms of maximizing running potential suggesting two distinct strategies for promoting limb elongation based on the organisms’ size. For small and medium sized theropods increased leg length seems to correlate with a desire to increase top speed while amongst larger taxa it corresponds more closely to energetic efficiency and reducing foraging costs. We also find, using 3D volumetric mass estimates, that the Tyrannosauridae show significant cost of transport savings compared to more basal clades, indicating reduced energy expenditures during foraging and likely reduced need for hunting forays. This suggests that amongst theropods, hindlimb evolution was not dictated by one particular strategy. Amongst smaller bodied taxa the competing pressures of being both a predator and a prey item dominant while larger ones, freed from predation pressure, seek to maximize foraging ability. We also discuss the implications both for interactions amongst specific clades and Mesozoic paleobiology and paleoecological reconstructions as a whole.

]]>
<![CDATA[Two new sponge species (Demospongiae: Chalinidae and Suberitidae) isolated from hyperarid mangroves of Qatar with notes on their potential antibacterial bioactivity]]> https://www.researchpad.co/article/elastic_article_14508 This study presents the taxonomic description of two new sponge species that are intimately associated with the hyperarid mangrove ecosystem of Qatar. The study includes a preliminary evaluation of the sponges’ potential bioactivity against pathogens. Chalinula qatari sp. nov. is a fragile thinly encrusting sponge with a vivid maroon colour in life, often with oscular chimneys and commonly recorded on pneumatophores in the intertidal and shallow subtidal zone. Suberites luna sp. nov. is a massive globular-lobate sponge with a greenish-black colour externally and a yellowish orange colour internally, recorded on pneumatophores in the shallow subtidal zone, with large specimens near the seagrass ecosystem that surrounds the mangrove. For both species, a drug extraction protocol and an antibacterial experiment was performed. The extract of Suberites luna sp. nov. was found to be bioactive against recognized pathogens such as Staphylococcus epidermidis, Staphylococcus aureus and Enterococcus faecalis, but no bioactive activity was recorded for Chalinula qatari sp. nov. This study highlights the importance of increasing bioprospecting effort in hyperarid conditions and the importance of combining bioprospecting with taxonomic studies for the identification of novel marine drugs.

]]>
<![CDATA[<i>Escherichia coli</i> ST131 clones harbouring AggR and AAF/V fimbriae causing bacteremia in Mozambican children: Emergence of new variant of <i>fimH27</i> subclone]]> https://www.researchpad.co/article/elastic_article_14507 Escherichia coli ST131 has emerged as a globally disseminated multi-drug resistant clone associated with extra-intestinal infections acquired in the community or hospital. In Manhiça district, E. coli is among the top five leading bloodstream pathogens in children. We characterized E. coli strains causing bacteremia in young children in a rural hospital of Mozambique, providing novel information on the occurrence of a new subclone of ST131 harboring both ExPEC and EAEC related genes and belonging to commonly reported O25:H4 and other serotypes. These data suggest the need for further understanding of pathogenesis and clinical impact of this new entity to inform prompt recognition and appropriate treatment.

]]>
<![CDATA[A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase]]> https://www.researchpad.co/article/elastic_article_14506 The function of a protein is often dictated by a single defined fold, which in turn is determined by its amino acid sequences. However, multiple global conformations can be utilized by a protein to fulfill distinct functions under different circumstances. The flavivirus NS5 protein, a natural fusion of an N-terminal methyltransferase (MTase) and a C-terminal RNA-dependent RNA polymerase (RdRP), may be such an example. Previously reported NS5 crystal structures exhibit two apparently different global conformations. In this work, we demonstrate that both conformations are conserved in the flaviviruses and important for virus proliferation, but only one of them is clearly relevant to RdRP catalysis, in particular at the early stages of the RNA synthesis.

]]>
<![CDATA[Inference on dengue epidemics with Bayesian regime switching models]]> https://www.researchpad.co/article/elastic_article_14505 Dengue, a mosquito-borne infectious disease caused by the dengue viruses, is present in many parts of the tropical and subtropical regions of the world. All four serotypes of dengue viruses are endemic in Singapore, an equatorial city-state. Frequent outbreaks occur, sometimes leading to national epidemics. However, few studies have attempted to characterize breakpoints which precede large rises in dengue case counts. In this paper, Bayesian regime switching (BRS) models were employed to infer epidemic and endemic regimes of dengue transmissions, each containing regime specific processes which drive the growth and decline of dengue cases, estimated using a custom built multi-move Gibbs sampling algorithm. Assessments against various baseline showed that BRS performs better in characterizing dengue transmissions. The dengue regimes estimated by BRS are characterized by their persistent nature. Next, climate analysis showed no short nor long term associations between classified regimes with climate. Lastly, fitting BRS to simulated disease data generated from a mechanistic model, we showed links between disease infectivity and regimes classified using BRS. The model proposed could be applied to other localities and diseases under minimal data requirements where transmission counts over time are collected.

]]>
<![CDATA[Interplay between axonal Wnt5-Vang and dendritic Wnt5-Drl/Ryk signaling controls glomerular patterning in the <i>Drosophila</i> antennal lobe]]> https://www.researchpad.co/article/elastic_article_14504 During brain development, the processes of nerve cells, axons and dendrites, grow over long distances to find and connect with each other to form synapses in precise locations. Understanding the mechanisms that control the growth of these neurites is important for understanding normal brain functions like neuronal plasticity and neural diseases like autism. Although much progress has been made by studying the development of axons and dendrites separately, the mechanisms that guide neuronal processes to their final locations are still incompletely understood. In particular, careful observation of converging pre- and postsynaptic processes suggests that their targeting may be coordinated. Whether the final targeting of axons and dendrites are functionally linked and what molecular mechanisms may be involved are unknown. In this paper we show that, in the developing Drosophila olfactory circuit, coalescing axons and dendrites respond to the extracellular Wnt5 signal in a codependent manner. We demonstrate that the converging axons and dendrites contribute different signaling components to the Wnt5 pathway, the Vang Gogh and Derailed transmembrane receptors respectively, which allow Wnt5 to coordinately guide the targeting of the neurites. Our work thus reveals a novel mechanism of neural circuit patterning and the molecular mechanism that controls it.

]]>
<![CDATA[An Out-of-Patagonia migration explains the worldwide diversity and distribution of <i>Saccharomyces eubayanus</i> lineages]]> https://www.researchpad.co/article/elastic_article_14503 Lager yeast history has intrigued scientists for decades. The recent isolation of S. eubayanus, the lager yeast ancestor, represents an unprecedented opportunity to extend our knowledge on yeast phylogeography and the origins of the S. pastorianus lager hybrid. However, the genetic, phenotypic and evolutionary history of this species remains poorly known. Our work demonstrates that S. eubayanus isolates from Patagonia have the greatest genetic diversity, comprising the largest number of lineages within a single geographic region and experienced ancestral and recent admixture between lineages, likely suggesting co-occurrence in Patagonia. Importantly, some isolates exhibited significant phenotypic differences for traits such as high temperature and ethanol tolerance, together with fermentation performance, demonstrating their potential in the brewing industry for the generation of new styles of lager beers. Furthermore, our results support the idea of colonization from peripheral glacial refugia from the South, as responsible for the high genetic diversity observed in southern Chilean Patagonia. Our results allow hypothesizing a successful physiological adjustment of the species to the local conditions in Patagonia, explaining its wide distribution in the southern hemisphere.

]]>
<![CDATA[Identification and detection of a novel point mutation in the Chitin Synthase gene of <i>Culex pipiens</i> associated with diflubenzuron resistance]]> https://www.researchpad.co/article/elastic_article_14502 Diflubenzuron is one of the main larvicides used for the control of the West Nile Virus vector Culex pipiens in the Mediterranean. However, the efficiency of control is now under threat due to the selection of insecticide resistance. Two point mutations were previously identified at the Chitin synthase and shown to confer low and high levels of resistance and a diagnostic was developed to monitor the trait. This study reports the identification of a third mutation associated with high levels of diflubenzuron resistance in Italy. This mutation was also detected in France, whereas no resistance mutations were found in Cx. pipiens mosquitoes sampled from Greece, Portugal and Israel. The findings are of major concern for mosquito control programs in S. Europe, which rely on the use of a limited number of larvicides.

]]>
<![CDATA[Distribution pattern of Tugai forests species diversity and their relationship to environmental factors in an arid area of China]]> https://www.researchpad.co/article/elastic_article_14501 Ecological restoration of degraded riparian Tugai forests is a key driver to combat desertification in arid regions. Previous studies have focused mainly on changes in groundwater as the underlying mechanisms of Tugai forest’s decline. We evaluated species composition and diversity of Tugai forest and their relationship to groundwater, soil salinity, and soil nutrient. Using 73 quadrats (100 m × 100 m) from 13 transects located perpendicularly to river in the upper reaches of the Tarim River. Eighteen plant species belonging to sixteen genera and eight families were recorded, and the dominant species included Populus euphratica, Phragmites communis, and Tamarix ramosissima. Three P. euphratica stand ages were detected: young stand, mature stand, and old stand. There were significant differences in species diversity, groundwater depth, groundwater salinity, distance from the quadrat to the river channel, soil moisture content, pH, electrical conductivity, total salt, Cl, SO42−, Ca2−, Mg2+, Na+, K+, soil organic carbon, and soil organic matter across the stand ages. Seven species were identified as indicators of the three stand ages. Redundancy analysis indicated that the Tugai forest diversity indices were negatively correlated with groundwater depth, groundwater salinity, and distance from the river, and positively associated with electrical conductivity, total salt, pH, Cl, SO42−, CO32−, soil organic matter, soil organic carbon, and soil moisture content. Plant diversity was the highest at 3–6 m groundwater depth, followed by 0–3 m and then 6–9 m, with the lowest recorded at > 9 m. The appropriate groundwater depth for herbs was about 1–4 m, whereas the depth for trees and shrubs was about 3–6 m. The groundwater depth < 6 m was deemed suitable for the growth of desert riparian forests. This results provide a scientific reference for the ecological restoration and protection for Tugai forests in arid areas.

]]>
<![CDATA[Ontogenetic changes in energetic reserves, digestive enzymes, amino acid and energy content of <i>Lithodes santolla</i> (Anomura: Lithodidae): Baseline for culture]]> https://www.researchpad.co/article/elastic_article_14500 The southern king crab (SKC) Lithodes santolla is an important commercial species in southern South America. Fishing pressure has caused the deterioration of its stocks. Currently, culture techniques are being developed for producing SKC juveniles to enhance the natural population and to recover the fishing stock. Therefore, it is necessary to know about physiology, energetic and nutritional requirements for SKC maintenance in hatchery. Thus, this study aims to evaluate the biochemical and physiological changes in the midgut gland, muscle and hemolymph of juveniles, pre-adults and adults of wild SKC. The energetic reserves, digestive enzymes activity, amino acid profile and energy were quantified in twelve juveniles, ten pre-adult, and ten adult crabs. Juveniles showed high glycogen and low lipids in the midgut gland, and low proteins and low lactate in muscle. In the hemolymph, juveniles had high lipids. Pre-adults had high glycogen and lipids in the midgut gland, and both high protein and lactate in muscle. In the hemolymph, pre-adults had high lipids. Adults had low glycogen and high lipids in midgut gland, and both high proteins and high lactate in muscle. In hemolymph, adults had high glucose and lactate. Juveniles and pre-adults had high proteinase activity, whereas adults had high lipase activity. Major essential amino acids of SKC were arginine, methionine, and tryptophan, and the non-essential amino acids were glycine, aspartic acid and glutamic acid. On another hand, SKC had similar energy in the midgut gland and muscle, regardless of the ontogenetic stage. Moreover, we demonstrated that the biochemical energy calculation underestimates the actual measured values by a calorimeter. Thus, our results help to understand the physiological changes, energetic and nutritional requirements of L. santolla, and this study is a baseline for research on diet formulation for maintaining this species under culture conditions.

]]>
<![CDATA[Dialysis timing may be deferred toward very late initiation: An observational study]]> https://www.researchpad.co/article/elastic_article_14499 The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0–30 days before dialysis initiation [DI]) and control (90–120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18–90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0–2 uremic indicators), late (3–5 indicators), and very late (6–7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76–1.24) and 0.83 (0.61–1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

]]>
<![CDATA[The degradation-promoting roles of deubiquitinases Ubp6 and Ubp3 in cytosolic and ER protein quality control]]> https://www.researchpad.co/article/elastic_article_14498 The quality control of intracellular proteins is achieved by degrading misfolded proteins which cannot be refolded by molecular chaperones. In eukaryotes, such degradation is handled primarily by the ubiquitin-proteasome system. However, it remained unclear whether and how protein quality control deploys various deubiquitinases. To address this question, we screened deletions or mutation of the 20 deubiquitinase genes in Saccharomyces cerevisiae and discovered that almost half of the mutations slowed the removal of misfolded proteins whereas none of the remaining mutations accelerated this process significantly. Further characterization revealed that Ubp6 maintains the level of free ubiquitin to promote the elimination of misfolded cytosolic proteins, while Ubp3 supports the degradation of misfolded cytosolic and ER luminal proteins by different mechanisms.

]]>
<![CDATA[A content analysis-based approach to explore simulation verification and identify its current challenges]]> https://www.researchpad.co/article/elastic_article_14497 Verification is a crucial process to facilitate the identification and removal of errors within simulations. This study explores semantic changes to the concept of simulation verification over the past six decades using a data-supported, automated content analysis approach. We collect and utilize a corpus of 4,047 peer-reviewed Modeling and Simulation (M&S) publications dealing with a wide range of studies of simulation verification from 1963 to 2015. We group the selected papers by decade of publication to provide insights and explore the corpus from four perspectives: (i) the positioning of prominent concepts across the corpus as a whole; (ii) a comparison of the prominence of verification, validation, and Verification and Validation (V&V) as separate concepts; (iii) the positioning of the concepts specifically associated with verification; and (iv) an evaluation of verification’s defining characteristics within each decade. Our analysis reveals unique characterizations of verification in each decade. The insights gathered helped to identify and discuss three categories of verification challenges as avenues of future research, awareness, and understanding for researchers, students, and practitioners. These categories include conveying confidence and maintaining ease of use; techniques’ coverage abilities for handling increasing simulation complexities; and new ways to provide error feedback to model users.

]]>