bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Accuracy of Assays Using Point-of-Care Testing or Dried Blood Spot Samples for the Determination of Hepatitis C Virus RNA: A Systematic Review
Authors: Catlett Beth , Hajarizadeh Behzad , Cunningham Evan , Wolfson-Stofko Brett , Wheeler Alice , Khandaker-Hussain Benazir , Feld Jordan J , Martró Elisa , Chevaliez Stéphane , Pawlotsky Jean Michel , Bharat Chrianna , Cunningham Philip H , Dore Gregory J , Applegate Tanya , Grebely Jason
Published: February 2022

Background

Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA.

Methods

Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates.

Results

Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%–99%) and 99% (95% CI, 94%–100%) and for HCV RNA quantification was 100% (95% CI, 93%–100%) and 100% (95% CI, 94%–100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%–11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%–98%) and 100% (95% CI, 98%–100%) and for HCV RNA quantification was 98% (95% CI, 96%–99%) and 100% (95% CI, 95%–100%).

Conclusions

Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.
Simple Eco-Friendly RP-LC Method for the Synchronous Separation of Six Widely Used Drugs in the Treatment of Cerebrovascular and Vestibular Disorders: Application for Analysis in Their Single and Combined Drug Products
Authors: El-Houssini Ola M , Mohammad Mohammad A
Published: February 2022

Background

Reverse phase liquid chromatography (RP-LC) is considered the most extensively used chromatographic technique in drug separation and quantification, yet its routine use shows increasing environmental challenges about energy consumption, solvent used, and waste engendered. From this perception, efforts for greening the developed RP-LC methods are focused on using green solvents and reducing the amount of solvent used and waste produced.

Objective

The target of this work is to develop an eco-friendly RP-LC method for the synchronous separation of six widely used drugs in the treatment of cerebrovascular and vestibular disorders, namely neurotropic piracetam, antihistamines dimenhydrinate, cinnarizine, and fluranizine, and vasodilators vincamine and vinpocetine.

Method

Separation and quantification are accomplished at ambient temperature by isocratic elution mode using acetonitrile–0.2% triethylamine (85:15 by volume) as a mobile phase at a flow rate of 1.5 mL/min on a Hypersil C18 column. UV detection and quantification are carried out at 225 nm.

Results

The method is fully validated per ICH guidelines, where all analytical parameters are within the acceptable range (r > 0.9999), accuracy (≥99.55%), and precision (0.02–0.97%).

Conclusions

The method is applied for the routine analysis of the cited drugs in their single and combined drug products, and it is considered excellent in terms of greenness with respect to Eco-Scale assessment.

Highlights

As the routine use of the RP-LC technique shows increasing environmental challenges, efforts for greening are attempted focusing on the use of green solvents and reducing the amount of solvent used and waste produced. A simple eco-friendly RP-LC method for the synchronous separation of six widely used drugs in the treatment of cerebrovascular and vestibular disorders is developed. The method is fully validated per ICH guidelines, where all analytical parameters are within the acceptable range. The method is applied for the routine analysis of the cited drugs in their single and combined drug products.
Survival Politics: Regime Security and Alliance Design on the Korean Peninsula
Authors: Kim Inwook , Woods Jackson
Published: February 2022

What determines states’ willingness to institutionalize alliances? Contrary to conventional emphasis on system-level conditions, we argue that states pay close attention to the domestic political consequences of institutionalizing alliances. This is particularly true for unequal allies. Client regimes are disproportionately sensitive to alliance design, as it affects patron allies’ ability to influence their military, distribute finance and arms, and legitimate preferred political groups. Two factors—power consolidation and political compatibility—determine whether the client views alliance institutionalization as complementary or conflictual with regime survival. The divergent alliance designs North and South Korea chose after the Korean War support our argument. An unresolved power consolidation process forced Kim Il-Sung to refuse formalizing the wartime alliance with the PRC, and Kim concluded a minimal treaty in 1961 after consolidating his power. In contrast, rapid consolidation left Rhee Syngman little to fear from continuing the highly institutionalized wartime alliance arrangement with the United States, which accepted his authority in the south. Our findings have important implications for alliance design, intra-alliance politics, and civil–military relations.

Diseño de alianzas y seguridad del régimen de la política de supervivencia en la península de Corea
AT2019azh: an unusually long-lived, radio-bright thermal tidal disruption event
Authors: Goodwin A J , van Velzen S , Miller-Jones J C A , Mummery A , Bietenholz M F , Wederfoort A , Hammerstein E , Bonnerot C , Hoffmann J , Yan L
Published: February 2022

Tidal disruption events (TDEs) occur when a star is destroyed by a supermassive black hole at the centre of a galaxy, temporarily increasing the accretion rate on to the black hole and producing a bright flare across the electromagnetic spectrum. Radio observations of TDEs trace outflows and jets that may be produced. Radio detections of the outflows from TDEs are uncommon, with only about one-third of TDEs discovered to date having published radio detections. Here, we present over 2 yr of comprehensive, multiradio frequency monitoring observations of the TDE AT2019azh taken with the Very Large Array and MeerKAT radio telescopes from approximately 10 d pre-optical peak to 810 d post-optical peak. AT2019azh shows unusual radio emission for a thermal TDE, as it brightened very slowly over 2 yr, and showed fluctuations in the synchrotron energy index of the optically thin synchrotron emission from 450 d post-disruption. Based on the radio properties, we deduce that the outflow in this event is likely non-relativistic and could be explained by a spherical outflow arising from self-stream intersections or a mildly collimated outflow from accretion on to the supermassive black hole. This data set provides a significant contribution to the observational data base of outflows from TDEs, including the earliest radio detection of a non-relativistic TDE to date, relative to the optical discovery.
The evolution of the heaviest supermassive black holes in jetted AGNs
Authors: Diana A , Caccianiga A , Ighina L , Belladitta S , Moretti A , Della Ceca R
Published: February 2022

We present the space density evolution, from z = 1.5 up to z = 5.5, of the most massive ($M \ge 10^9\, \mathrm{M}_{\odot }$) black holes hosted in jetted active galactic nuclei (AGNs). The analysis is based on a sample of 380 luminosity-selected (λL1350 ≥ 1046 erg s−1 and $P_{5\, \text{GHz}}\ge 10^{27}$ W Hz−1) flat spectrum radio quasars (FSRQs) obtained from the Cosmic Lens All Sky Survey (CLASS). These sources are known to be face-on jetted AGNs (i.e. blazars) and can be exploited to infer the abundance of all the (misaligned) jetted AGNs, using a geometrical argument. We then compare the space density of the most massive supermassive black holes hosted in jetted AGNs with those present in the total population (mostly composed by non-jetted AGNs). We find that the space density has a peak at z ∼ 3, which is significantly larger than the value observed in the total AGN population with similar optical/UV luminosities (z ∼ 2.2), but not as extreme as the value previously inferred from X-ray-selected blazars (z ≳ 4). The jetted fraction (jetted AGNs/total AGNs) is overall consistent with the estimates in the local Universe (10–20 per cent) and at high redshift, assuming Lorentz bulk factors Γ ≈ 5. Finally, we find a marginal decrease in the jetted fraction at high redshifts (by a factor of ∼2). All these evidences point towards a different evolutionary path in the jetted AGNs compared to the total AGN population.
PRAiSE: resolved spectral evolution in simulated radio sources
Authors: Yates-Jones Patrick M , Turner Ross J , Shabala Stanislav S , Krause Martin G H
Published: February 2022

We present a method for applying spatially resolved adiabatic and radiative loss processes to synthetic radio emission from hydrodynamic simulations of radio sources from active galactic nuclei (AGNs). Lagrangian tracer particles, each representing an ensemble of electrons, are injected into simulations and the position, grid pressure, and time since the last strong shock are recorded. These quantities are used to track the losses of the electron packet through the radio source in a manner similar to the Radio AGN in Semi-analytic Environments formalism, which uses global source properties to calculate the emissivity of each particle ex situ. Freedom in the choice of observing parameters, including redshift, is provided through the post-processing nature of this approach. We apply this framework to simulations of jets in different environments, including asymmetric ones. We find a strong dependence of radio source properties on frequency and redshift, in good agreement with observations and previous modelling work. There is a strong evolution of radio spectra with redshift due to the more prominent inverse-Compton losses at high redshift. Radio sources in denser environments have flatter spectral indices, suggesting that spectral index asymmetry may be a useful environment tracer. We simulate intermediate Mach number jets that disrupt before reaching the tip of the lobe, and find that these retain an edge-brightened Fanaroff–Riley Type II morphology, with the most prominent emission remaining near the tip of the lobes for all environments and redshifts we study.
Combined speciation analysis and elemental bioimaging provide new insight into gadolinium retention in kidney
Authors: Bücker Patrick , Funke Sabrina K I , Factor Cécile , Rasschaert Marlène , Robert Philippe , Sperling Michael , Karst Uwe
Published: February 2022

This study uses a leaching approach in combination with elemental bioimaging and speciation analysis to obtain insight into the gadolinium species present in the kidney of rats that were treated with either a linear or a macrocyclic gadolinium-based contrast agent. Fresh frozen thin sections of the harvested kidneys were immersed halfway into water to wash out hydrophilic species and subsequently analyzed by laser ablation–inductively coupled plasma–mass spectrometry. The water-extracted gadolinium species were analyzed by means of hydrophilic interaction liquid chromatography–inductively coupled plasma–mass spectrometry. Information on the water-soluble species could not only be obtained from the full kidney, but also be traced back to its localization in the tissue. On longitudinal kidney sections treated with gadobutrol, it was found that water-insoluble, permanent Gd depositions were mainly located in the renal cortex, while water-soluble species were found in the medulla, which contains the intact contrast agent up to 1 year after injection. Moreover, kidney samples from gadodiamide-treated rats showed more water-insoluble Gd deposition in both the cortex and medulla, while the concentration of intact contrast agent in the water-soluble fraction was below the limit of detection after 12 months. In conclusion, this rapid approach allowed the spatially resolved differentiation between water-soluble and insoluble gadolinium deposition and is therefore capable of generating new insight into the retention and transportation behavior of gadolinium.
Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia
Authors: Chakraborty Kaustav , Kar Sumanta , Rai Bhawana , Bhagat Reshma , Naskar Nabanita , Seth Pankaj , Gupta Arnab , Bhattacharjee Ashima
Published: February 2022

Intracellular copper [Cu(I)] has been hypothesized to play role in the differentiation of the neurons. This necessitates understanding the role of Cu(I) not only in the neurons but also in the glia considering their anatomical proximity, contribution towards ion homeostasis, and neurodegeneration. In this study, we did a systematic investigation of the changes in the cellular copper homeostasis during neuronal and glial differentiation and the pathways triggered by them. Our study demonstrates increased mRNA for the plasma membrane copper transporter CTR1 leading to increased Cu(I) during the neuronal (PC-12) differentiation. ATP7A is retained in the trans-Golgi network (TGN) despite high Cu(I) demonstrating its utilization towards the neuronal differentiation. Intracellular copper triggers pathways essential for neurite generation and ERK1/2 activation during the neuronal differentiation. ERK1/2 activation also accompanies the differentiation of the foetal brain derived neuronal progenitor cells. The study demonstrates that ERK1/2 phosphorylation is essential for the viability of the neurons. In contrast, differentiated C-6 (glia) cells contain low intracellular copper and significant downregulation of the ERK1/2 phosphorylation demonstrating that ERK1/2 activation does not regulate the viability of the glia. But ATP7A shows vesicular localization despite low copper in the glia. In addition to the TGN, ATP7A localizes into RAB11 positive recycling endosomes in the glial neurites. Our study demonstrates the role of copper dependent ERK1/2 phosphorylation in the neuronal viability. Whereas glial differentiation largely involves sequestration of Cu(I) into the endosomes potentially (i) for ready release and (ii) rendering cytosolic copper unavailable for pathways like the ERK1/2 activation.
Physiologically relevant hCys concentrations mobilize MeHg from rabbit serum albumin to form MeHg–hCys complexes
Authors: Bridle Tristen G , Doroudian Maryam , White Wade , Gailer Jürgen
Published: February 2022

Methylmercury (MeHg) is one of the most potent neurotoxins to which humans are exposed via the consumption of fish, from which it is effectively absorbed via the gastrointestinal tract into the bloodstream. Its interactions with plasma proteins, small-molecular-weight (SMW) molecules, and red blood cells, however, are incompletely understood, but critical as they determine whether and how much MeHg reaches target organs. To better define the role that SMW thiols play in the delivery of MeHg to known transporters located at the placental and blood–brain barrier, we have employed size exclusion chromatography–inductively coupled plasma-atomic emission spectroscopy to analyze MeHg-spiked rabbit plasma in the absence and presence of SMW thiols dissolved in the phosphate-buffered saline buffer mobile phase. While 300 μM methionine did not affect the binding of MeHg to rabbit serum albumin (RSA), cysteine (Cys), homocysteine (hCys), and glutathione resulted in the elution of the main Hg peak in the SMW elution range. In addition, 50 μM of hCys or Cys in the mobile phase resulted in the mobilization of MeHg from RSA in rabbit plasma and from pure RSA in solution. The Hg peak that eluted in the SMW elution range (50 μM of hCys) was identified by electrospray ionization–mass spectrometry as an MeHg–hCys complex. Since l-type amino acid transporters are present at the blood–brain barrier (BBB), which facilitate the uptake of MeHg–Cys species into the brain, our results contribute to establish the bioinorganic mechanisms that deliver MeHg to the BBB, which is critical to predict organ-based adverse health effects.
A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis
Authors: Manley Harold J , Aweh Gideon , Frament Jill , Ladik Vladimir , Lacson Eduardo K
Published: February 2022

Background

Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known.

Methods

A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster.

Results

For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P < 0.0001). Series 2 (n = 1040) and booster (n = 2028) SP rates were similar between vaccines. Patients that received up to four HepB-CpG doses had higher SP rates compared with four doses of HepB (82.0% versus 62.9%, respectively; P < 0.0001).

Conclusions

SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.
The origin and evolution of a plant resistosome
Authors: Gong Zhen , Qi Jinfeng , Hu Meijuan , Bi Guozhi , Zhou Jian-Min , Han Guan-Zhu
Published: February 2022

The nucleotide-binding, leucine-rich receptor (NLR) protein HOPZ-ACTIVATED RESISTANCE 1 (ZAR1), an immune receptor, interacts with HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases (ZRKs) and AVRPPHB SUSCEPTIBLE 1-like proteins to form a pentameric resistosome, triggering immune responses. Here, we show that ZAR1 emerged through gene duplication and that ZRKs were derived from the cell surface immune receptors wall-associated protein kinases (WAKs) through the loss of the extracellular domain before the split of eudicots and monocots during the Jurassic period. Many angiosperm ZAR1 orthologs, but not ZAR1 paralogs, are capable of oligomerization in the presence of AtZRKs and triggering cell death, suggesting that the functional ZAR1 resistosome might have originated during the early evolution of angiosperms. Surprisingly, inter-specific pairing of ZAR1 and AtZRKs sometimes results in the formation of a resistosome in the absence of pathogen stimulation, suggesting within-species compatibility between ZAR1 and ZRKs as a result of co-evolution. Numerous concerted losses of ZAR1 and ZRKs occurred in angiosperms, further supporting the ancient co-evolution between ZAR1 and ZRKs. Our findings provide insights into the origin of new plant immune surveillance networks.
Hexose translocation mediated by SlSWEET5b is required for pollen maturation in Solanum lycopersicum
Authors: Ko Han-Yu , Tseng Hsuan-Wei , Ho Li-Hsuan , Wang Lu , Chang Tzu-Fang , Lin Annie , Ruan Yong-Ling , Neuhaus H Ekkehard , Guo Woei-Jiun
Published: February 2022

Pollen fertility is critical for successful fertilization and, accordingly, for crop yield. While sugar unloading affects the growth and development of all types of sink organs, the molecular nature of sugar import to tomato (Solanum lycopersicum) pollen is poorly understood. However, sugar will eventually be exported transporters (SWEETs) have been proposed to be involved in pollen development. Here, reverse transcription-quantitative polymerase chain reaction (PCR) revealed that SlSWEET5b was markedly expressed in flowers when compared to the remaining tomato SlSWEETs, particularly in the stamens of maturing flower buds undergoing mitosis. Distinct accumulation of SlSWEET5b-β-glucuronidase activities was present in mature flower buds, especially in anther vascular and inner cells, symplasmic isolated microspores (pollen grains), and styles. The demonstration that SlSWEET5b-GFP fusion proteins are located in the plasma membrane supports the idea that the SlSWEET5b carrier functions in apoplasmic sugar translocation during pollen maturation. This is consistent with data from yeast complementation experiments and radiotracer uptake, showing that SlSWEET5b operates as a low-affinity hexose-specific passive facilitator, with a Km of ∼36 mM. Most importantly, RNAi-mediated suppression of SlSWEET5b expression resulted in shrunken nucleus-less pollen cells, impaired germination, and low seed yield. Moreover, stamens from SlSWEET5b-silenced tomato mutants showed significantly lower amounts of sucrose (Suc) and increased invertase activity, indicating reduced carbon supply and perturbed Suc homeostasis in these tissues. Taken together, our findings reveal the essential role of SlSWEET5b in mediating apoplasmic hexose import into phloem unloading cells and into developing pollen cells to support pollen mitosis and maturation in tomato flowers.
The role of contractors in the uptake of precision farming—A spatial economic analysis
Authors: Wang Yanbing , Huber Robert , Finger Robert
Published: February 2022

Contractors will play a vital role in providing farms with access to new precision farming technologies, especially in small-scale farming systems. We investigate the impact of spatial competition among contractors on the uptake of precision farming and the effectiveness of policy interventions, considering alternative spatial price schedules. Conceptual analyses show that a lack of spatial competition among contractors hinders uptake of precision farming technology. The effectiveness of policy interventions to support precision farming also depends on the market structure and contractors’ price schedules. In addition, we illustrate the results in a Swiss case study based on a specific contractors’ service market of plant protection technologies.
Hidden Performance: Salary History Bans and the Gender Pay Gap
Authors: Davis Jesse , Ouimet Paige , Wang Xinxin
Published: February 2022

As of 2019, salary history bans were enacted by 17 states and Puerto Rico with the stated purpose of reducing the gender pay gap. We argue that salary history bans may negatively affect wages as employers lose an informative signal of worker productivity. We empirically evaluate these laws using a large panel dataset of disaggregated wages covering all public-sector employees in 36 states and find, on average, that salary history bans lead to a 3% decrease in new-hire wages. We find no decrease in the gender pay gap in the full sample and a modest 1.5% increase in the relative wages of women, as compared to men, among new hires most likely to have experienced gender discrimination historically.
Mortgage Debt, Hand-to-Mouth Households, and Monetary Policy Transmission
Authors: Agarwal Sumit , Deng Yongheng , Gu Quanlin , He Jia , Qian Wenlan , Ren Yuan
Published: February 2022

Using a representative sample of credit card holders from a leading Chinese commercial bank, we investigate how consumers respond to an unexpected interest rate decrease that automatically reduces interest expenses for all mortgage borrowers in the country and thereby generates significant positive disposable-income shocks. Our difference-in-differences analysis shows that compared with homeowners without mortgage obligations, mortgage borrowers increased their monthly credit card spending by 8.7% after the 230-bps mortgage rate reduction announced in September 2008. We find a significant spending response both immediately after the announcement and during the post-reset period. The credit card delinquency rate also decreased after the mortgage rate reset. Subsequent to an interest-rate increase episode, mortgage borrowers symmetrically reduced their credit card spending. Hand-to-mouth mortgage borrowers experienced a more pronounced spending increase. The debt-service channel plays an important role in transmitting monetary policy—our estimate implies a marginal propensity to consume 0.40–0.54 through credit card spending.
Full-Likelihood Genomic Analysis Clarifies a Complex History of Species Divergence and Introgression: The Example of theerato-saraGroup ofHeliconiusButterflies
Authors: Thawornwattana Yuttapong , Seixas Fernando A , Yang Ziheng , Mallet James
Published: February 2022

Introgressive hybridization plays a key role in adaptive evolution and species diversification in many groups of species. However, frequent hybridization and gene flow between species make estimation of the species phylogeny and key population parameters challenging. Here, we show that by accounting for phasing and using full-likelihood methods, introgression histories and population parameters can be estimated reliably from whole-genome sequence data. We employ the multispecies coalescent (MSC) model with and without gene flow to infer the species phylogeny and cross-species introgression events using genomic data from six members of the erato-sara clade of Heliconius butterflies. The methods naturally accommodate random fluctuations in genealogical history across the genome due to deep coalescence. To avoid heterozygote phasing errors in haploid sequences commonly produced by genome assembly methods, we process and compile unphased diploid sequence alignments and use analytical methods to average over uncertainties in heterozygote phase resolution. There is robust evidence for introgression across the genome, both among distantly related species deep in the phylogeny and between sister species in shallow parts of the tree. We obtain chromosome-specific estimates of key population parameters such as introgression directions, times and probabilities, as well as species divergence times and population sizes for modern and ancestral species. We confirm ancestral gene flow between the sara clade and an ancestral population of Heliconius telesiphe, a likely hybrid speciation origin for Heliconius hecalesia, and gene flow between the sister species Heliconius erato and Heliconius himera. Inferred introgression among ancestral species also explains the history of two chromosomal inversions deep in the phylogeny of the group. This study illustrates how a full-likelihood approach based on the MSC makes it possible to extract rich historical information of species divergence and gene flow from genomic data. [3s; bpp; gene flow; Heliconius; hybrid speciation; introgression; inversion; multispecies coalescent]
The Implications of Incongruence between Gene Tree and Species Tree Topologies for Divergence Time Estimation
Authors: Carruthers Tom , Sun Miao , Baker William J , Smith Stephen A , de Vos Jurriaan M , Eiserhardt Wolf L
Published: February 2022

Phylogenetic analyses are increasingly being performed with data sets that incorporate hundreds of loci. Due to incomplete lineage sorting, hybridization, and horizontal gene transfer, the gene trees for these loci may often have topologies that differ from each other and from the species tree. The effect of these topological incongruences on divergence time estimation has not been fully investigated. Using a series of simulation experiments and empirical analyses, we demonstrate that when topological incongruence between gene trees and the species tree is not accounted for, the temporal duration of branches in regions of the species tree that are affected by incongruence is underestimated, whilst the duration of other branches is considerably overestimated. This effect becomes more pronounced with higher levels of topological incongruence. We show that this pattern results from the erroneous estimation of the number of substitutions along branches in the species tree, although the effect is modulated by the assumptions inherent to divergence time estimation, such as those relating to the fossil record or among-branch-substitution-rate variation. By only analyzing loci with gene trees that are topologically congruent with the species tree, or only taking into account the branches from each gene tree that are topologically congruent with the species tree, we demonstrate that the effects of topological incongruence can be ameliorated. Nonetheless, even when topologically congruent gene trees or topologically congruent branches are selected, error in divergence time estimates remains. This stems from temporal incongruences between divergence times in species trees and divergence times in gene trees, and more importantly, the difficulty of incorporating necessary assumptions for divergence time estimation. [Divergence time estimation; gene trees; species tree; topological incongruence.]
The Effect of Cancer Rehabilitation on Functional Outcomes in a Patient With Stage IV Melanoma With Subsequent Brain Metastases: A Case Report
Authors: Bucio Daniela , Bertram Jessica
Published: February 2022

Background and Purpose:

Malignant melanoma has a high propensity to metastasize, specifically to the brain. Research has shown that incorporating oncology rehabilitation as part of the interdisciplinary care team promotes independence in functional mobility that leads to an improvement in a patient's quality of life.

Case Description:

A 70-year-old man presented with recurrent melanoma to the brain 10 years after initial diagnosis. Multiple brain metastases led to left hemiparesis of the arm and leg. Left-sided weakness affected his ability to perform activities of daily living and exercise regularly. The confounding impairments in balance resulted in multiple falls at home.

Interventions:

Interventions included balance training on various surfaces, core and proximal lower extremity strengthening, aerobic conditioning, and implementation of a home exercise program.

Outcomes:

The patient attended outpatient cancer rehabilitation for 19 weeks and discharged from physical therapy with a reported 47.7% improvement in global physical health and 26.7% improvement in global mental health on the PROMIS tool. At discharge, performance on the Five Times Sit to Stand Test, Timed Up and Go Test, and Dynamic Gait Index was below cutoff scores, indicating the patient was no longer a high risk for falls at home.

Discussion:

Physical therapy specifically tailored for the oncology patient allows for a customized rehabilitation approach that incorporates oncologic medical history and treatment into the episode of care, with the ultimate goal of improving quality of life and function throughout the patient's cancer journey.
Access to Physical Rehabilitation for a Range of Adverse Physical Effects Following Different Types of Breast Cancer Surgery
Authors: McGhee Deirdre E. , Steele Julie R.
Published: February 2022

Purpose:

To investigate the access to physical rehabilitation for a range of adverse physical effects following different types of breast cancer surgery.

Methods:

Online survey of 632 Australian women (mean age = 59.8 years, SD = 9.6) grouped according to their breast cancer surgery, (i) breast-conserving surgery (BCS; n = 228), (ii) mastectomy (MAST; n = 208), (iii) breast reconstruction (BRS; n = 196), who retrospectively reported whether they received any physical rehabilitation for 6 adverse physical effects. Fisher's exact tests were used to compare the frequency of respondents who received physical rehabilitation for each adverse physical effect among the 3 groups. The percentage of the entire cohort of respondents (n = 632) who had lymph nodes removed, postoperative complications, or preexisting musculoskeletal issues who received physical rehabilitation was also tabulated.

Results:

No significant difference was found among the 3 groups in the percentage of respondents who received physical rehabilitation for most adverse physical effects (scar: P = .27; shoulder: P = .11; torso: P = .76; physical discomfort disturbing sleep: P = .74), except lymphedema (P = .001) and breast support issues (P = .01), which were significantly less for the BRS and BCS groups. Less than 50% of respondents following all types of breast cancer surgery received physical rehabilitation for issues associated with scars, the torso, and physical discomfort disturbing sleep, whereas more than 70% received physical rehabilitation for shoulder issues and lymphedema.

Conclusion:

Access to physical rehabilitation was similar following the different types of breast cancer surgery; however, gaps were identified for adverse physical effects associated with scars, torso, and physical discomfort disturbing sleep, where access was less than that for shoulder issues and lymphedema.
Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients
Authors: Li Chun , Zuo Yu , Zhang Song , Makris Una E. , Karp David R. , Li Zhanguo
Published: February 2022

Background:

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers.

Methods:

This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients.

Results:

Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408–15.637, P 
= 0.0001), hypertension (OR = 2.368, 95% CI = 1.249–4.491, P 
= 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387–8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681–12.553, P 
= 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355–11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407–7.744, P 
= 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients’ sera have more pronounced NET release compared with those treated with aPL carriers’ sera without underlying autoimmune diseases.

Conclusion:

We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.
Dominant role of CACNA1D exon mutations for blood pressure regulation
Authors: Wang Huan , Zhu Jing-Kang , Cheng Lan , Mao Gaowei , Chen Hong , Wu Xiaoying , Hong Huiwu , Wang Canwang , Lin Pengcheng , Chen Jie , Maboh Rene Nfornah , Chen Hui
Published: February 2022

Background:

CACNA1D gene, which encodes the α1 subunit of the Cav1.3 L-type calcium channel effectively regulates intracellular Ca2+ stability. In recent years, clinical studies have shown that the CACNA1D polymorphisms were associated with hypertension.

Objective:

The purpose of this study was to evaluate the effects of CACNA1D exon mutation on blood pressure (BP) in Sprague–Dawley rats.

Methods:

The rats with CACNA1D p.D307G, CACNA1D p.V936I or CACNA1D p.R1516Q were constructed using CRISPR-Cas9 technology. SBP measurements of rats were taken for 32 weeks. Tissue morphology of rats and vasoactive substances in serum was tested. Furthermore, the effects of L-type calcium channel blocker isradipine and endothelin-1 (ET-1) inhibitor BQ-123 on BP of double mutation rats (CACNA1D p.D307G/p.R1516Q) were tested. Then we examined the effects of CACNA1D gene mutation on gene expression in human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs).

Results:

Elevated SBP and increased circulating ET-1 was observed in CACNA1D p.D307G mutant rats. Morphological assessments showed that the vascular, cardiac and renal remodeling could also be observed in rats with p.D307G mutant. Cav1.3 protein expression and calcineurin phosphatase activity in VSMCs of rats with CACNA1D p.D307G were increased in vitro, and the vascular ring tension test of mesenteric grade 3 arteries in CACNA1D p.D307G rats were increased in vivo. Furthermore, ET-1 expression were increased in isolated primary aortic endothelial cells in p.D307G mutant rats and transfected p.D307G mutant HUVECs. Finally, double heterozygosity rats with CACNA1D p.D307G/p.R1516Q or CACNA1D p.D307G/p.V936I further accelerated the rise of SBP compared with p.D307G mutation rats, and isradipine and BQ-123 reduced BP to the same extent in CACNA1D p.D307G/p.R1516Q rats.

Conclusion:

CACNA1D gene is key players in the regulation of blood pressure. CACNA1D mutation rat may be a new hypertension animal model.
Genotypes and phenotypes characterization of 17 Iranian patients with inherited factor X deficiency: identification of a novel mutation: Leu487Phe
Authors: Fallah Aysan , Shams Mahmood , Agi Elnaz , Jazebi Mohammad , Baghaipoor Mohammad R. , Naderi Tohid , Rezvany Mohammad R.
Published: February 2022

Factor X deficiency is a rare bleeding disorder that affects almost 1 : 1000 000 people worldwide. It derives from multiple mutational changes in the factor X gene (F10). The main objective of the present study was to determine a consistent correlation between the clinical presentations and causative genotype. The phenotype and genotype of 17 Iranian patients with reduced factor X activity (FX:C) from 14 unrelated families were analyzed to screen factor X gene expression for any possible mutations and function alteration. Analysis of the sequencing results led to the identification of eight different mutations besides a single nucleotide variation. One of the mutations was novel (Leu487Phe) as studied by means of online analysis programs and molecular modeling. Eight patients were homozygote; three were heterozygote, while six out of 17 patients were symptomatic cases without any mutations. The Arg40Thr missense mutation was detected in three patients including two siblings and was associated with severe bleeding symptoms. Also, two patients were identified with Gly262Asp missense mutation which commonly presented with bleeding disorder. Each of the other patients was associated with a unique missense mutation including one novel mutation in which the tentative relation of the mutation to bleeding symptoms is reported. Mutations leading to a FX:C of less than 1% are associated with severe bleeding symptoms confirming the strong correlation between clinical severity and FX:C. The novel Leu487Phe mutation with FX:C of 13% may have possible negative effects on factor X protein function resulting in minor clinical manifestation.
Liver trauma in the intensive care unit
Authors: Hetherington Alexandra , Cardoso Filipe S. , Lester Erica L.W. , Karvellas Constantine J.
Published: February 2022

Purpose of review

To review the surgical and critical care management of liver trauma; one of the most common abdominal injuries sustained due to its size and location.

Recent findings

Hepatic injuries range from negligible to life threatening: in the acute phase, the most common cause of morbidity and mortality is hemorrhage; however, severe traumatic hepatic injuries can also lead to biochemical abnormalities, altered coagulation, and ultimately liver failure. This brief review will review the classification of traumatic liver injuries by mechanism, grade, and severity. Most Grades I–III injuries can be managed nonoperatively, whereas the majority of Grades IV–VI injuries require operative management. Therapeutic strategies for traumatic liver injury including nonoperative, operative, radiologic will be described. The primary goal of liver trauma management in the acute setting is hemorrhage control, then the management of secondary factors such as bile leaks. The rapid restoration of homeostasis may prevent further damage to the liver and allow for deferred nonoperative management, which has been shown to be associated with good clinical outcomes.

A multidisciplinary approach to the care of these patients at an experienced liver surgery center is warranted.
Underdetection of pre-existing HIV/AIDS during psychiatric hospitalizations
Authors: Mangurian Christina , Dahiya Priya , Goldman Matthew L. , Corbeil Tom , Wall Melanie M. , Essock Susan M. , Dixon Lisa B. , Tang Fei , Frimpong Eric , Mascayano Franco , Radigan Marleen , Wang Rui , Olfson Mark , Smith Thomas E.
Published: February 2022

Objectives:

People with severe mental illness are 10 times more likely to have HIV/ AIDS than the general population, yet little is known about the characteristics and frequency of recognition of pre-existing HIV/AIDS diagnoses among inpatients with severe mental illness. This study examines documentation rates of pre-existing HIV/ AIDS among inpatients within psychiatric hospitals in New York State.

Design:

Retrospective cohort study to examine recognition of pre-existing HIV/AIDS among psychiatric inpatients.

Methods:

Patient-level Medicaid claims records were linked with hospital and regional data for people admitted to psychiatric inpatient units in New York State. Presence of HIV/AIDS diagnoses prior to psychiatric hospitalization was coded for each inpatient (n = 14 602). Adjusted odds ratios of undocumented HIV/AIDS diagnoses at the time of discharge were calculated using logistic regression analyses.

Results:

About 5.1% (741/14 602) of unique psychiatric inpatients had pre-existing HIV/AIDS diagnoses. Of these inpatients, 58.3% (432/741) were not coded as having HIV/AIDS upon discharge. Higher rates of missed detection were associated with younger age, non-Hispanic white race/ethnicity, shorter length of stay, more distal coding of an HIV/AIDS diagnosis, and fewer HIV/AIDS-related Medicaid claims in the past year. Hospitals with higher readmission rates also had higher rates of undetected HIV/AIDS diagnoses.

Conclusion:

Over half of inpatients previously diagnosed with HIV/AIDS did not have their HIV-positive status noted upon discharge from psychiatric hospitalization. This finding underscores how frequently clinically significant medical comorbidities fail to be incorporated into psychiatric treatment and treatment planning. Inpatient clinicians are missing important opportunities to optimize HIV/AIDS treatment and reduce morbidity and mortality.
Radioiodine-Avid Paravertebral Bronchogenic Cyst Mimicking Neurofibroma
Authors: Shah Mohammadi Mohammad Reza , Norouzi Ghazal , Pirayesh Elahe
Published: February 2022

The whole-body postablation scan of a 38-year-old man, with history of papillary thyroid cancer, revealed a focus of intense 131I accumulation about the lower thoracic vertebrae. SPECT/CT revealing a soft tissue lesion adjacent the T9 to T10 vertebrae, which was reported as neurofibroma on the subsequently performed MRI. However, the lesion was confirmed as a bronchogenic cyst on biopsy. Respecting that unlike neurofibroma, immunohistochemistry studies have confirmed Na-I symporter expression in bronchogenic epithelium; our case highlights that, although rare, paravertebral bronchogenic cysts should be considered in differential diagnosis of radioiodine-avid paravertebral lesions.
Management of Mandibular Subcondylar Fracture Through an Intraoral Approach Using a Trans-Buccal Trocar With Ramus Buccal Decortication
Authors: Jeon Mina , Park Jin-Young , Choi Na-Rae , Chen Chun-Ming , Shriya Jaiswal M. , Hwang Dae-Seok
Published: February 2022

Purpose:

The aim of this study was to review retrospectively the functional recoveries of subcondylar fracture patients that underwent open reduction surgery using an extraoral approach or an intraoral approach using a trans-buccal trocar and involving ramus buccal decortication.

Materials and Methods:

Of 47 patients with mandibular condyle fracture who visited Pusan National University Dental Hospital Department of Oral and Maxillofacial Surgery between May 2015 and November 2020, 38 patients underwent open reduction and were classified according to the surgical method used. Preauricular, submandibular, and retro-mandibular approaches were all classified as extraoral approaches condyle fractures were classified as described by Spiessl and Schroll (1972). Distances between bone fragments on panorama radiographs before and after surgery were measured.

Results:

Thirty-eight patients were included in this study, 9 patients received subcondylar fracture surgery. Open reduction surgery using an extraoral approach had a greater mean operation time than the intraoral approach using a trocar. Of the 17 patients treated with an intraoral approach, the average distance between bone fragments right after surgery was 1.27 ± 1.41mm, which was significantly greater than that of the extraoral approach (0.72 ± 0.35 mm).

Conclusions:

Favorable results can be obtained by mandibular condylar fracture surgery through an intraoral approach using a trans-buccal trocar with ramus buccal decortication. This technique minimizes scarring, secures accessibility using a trocar, and sufficiently secures the field of view through buccal cortical bone reduction.
Computer-Aided Autogenous Coronoid Process Graft Combined With Median and Unilateral Sagittal Split Osteotomy for Late Reconstruction of Condylar Fracture and Occlusion after Trauma
Authors: Zhao Hanjiang , Li Xiaojie , Jiang Tengfei , Zhang Jianfei , Yu Hongbo
Published: February 2022

Purpose:

This study proposes a high-precision surgical technique that combines both computer-aided design/computer-aided manufacturing (CAD/CAM) and the screw-track transfer technique for condylar and occlusal reconstruction.

Materials and methods:

A 43-year-old male patient with facial asymmetry, limited mouth opening, and malocclusion underwent condylar and occlusal reconstruction surgery. An autogenous cor-onoid process graft was performed by combining CAD/CAM and the screw-track transfer technique.

Results:

The surgical plan was transformed successfully from preoperative virtual surgical planning to actual surgery; this was confirmed by merging the postoperative computed tomography images with the preoperative three-dimensional surgical design. The patient recovered well and had better occlusion and facial symmetry, as well as an increased degree of mouth opening post-surgery. No complications were observed.

Conclusions:

CAD/CAM combined with the screw-track transfer technique is a precise and feasible method that can be applied to autogenous coronoid process grafts. This approach can be used to reconstruct the condylar process and achieve a good occlusal relationship.