bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitral valve thickness: A promising echocardiographic parameter for distinguishing between cardiac amyloidosis and Fabry disease
Authors: Mattig I , Steudel T , Barzen G , Frumkin D , Spethmann S , Romero Dorta E , Stangl K , Heidecker B , Landmesser U , Knebel F , Canaan-Kuehl S , Hahn K , Brand A
Published: June 2023

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): The study was financially supported by Alnylam Pharmaceuticals (Cambridge, MA, USA).

Background

Left ventricular (LV) "hypertrophy" is present in various cardiomyopathies, such as cardiac amyloidosis (CA) and Fabry disease (FD). To differentiate both, multiple echocardiographic characteristics have been evaluated, but diagnosis and treatment are still often delayed.

Purpose

We evaluated new diagnostic indices, including the thickness of the mitral valve leaflets (ML) and the ratio of PM to LV area (PM/LV ratio), to distinguish between CA and FD.

Methods

We retrospectively enrolled patients with diagnosed CA and genetically confirmed FD and measured (i) the thickness of the ML in mid-diastole in the parasternal long axis view and (ii) the PM/LV ratio at end-diastole in the parasternal short axis view, as described by Nieman et al. in an offline analysis (EchoPAC PC, GE Vingmed, Horton, Norway; Vivid E9 or E95, GE Vingmed, Horton, Norway, M5S[c] 1.5–4.5MHz transducer). Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of the measurements. The reproducibility of leaflet measurement was calculated using the intra-class correlation coefficient for intra-observer agreement and inter-observer agreement.

Results

A total of 129 patients with FD (n=49) and CA (n=80) were analyzed. The ML were significantly thicker, and the area of PM and LV were significantly larger in CA compared to FD patients (ML: 4±1 mm in CA vs. 3±1 mm in FD, p<0.001). This resulted in a comparable PM/LV ratio between the two groups (0.23 [0.20–0.26] in CA vs. 0.21 [0.14–0.28] in FD, p = 0.223). Specifically, the posteromedial PM and the LV area were significantly larger in CA patients, while the increase in anterolateral PM area did not reach statistical significance. The thickness of the ML showed the best diagnostic accuracy (area under the curve [AUC]: 0.75, 95% confidence interval [CI]: 0.65–0.85) for discriminating between CA and FD. The reproducibility of leaflet measurement had a good to excellent agreement (intra-class correlation coefficient for intra-observer agreement: 0.92 [95% CI 0.79–0.97] and inter-observer agreement:0.85 [95% CI 0.64–0.94]).

Conclusion

In contrast to previous studies, the PM/LV ratio did not differ between FD and CA. Nevertheless, the measurement of ML may be useful in routine clinical practice to differentiate between the two cardiomyopathies.
Supine ergometry induced changes of left ventricular function and pulmonary hypertension have an uneven prognostic relevance for asymptomatic aortic stenosis according to age and gender
Authors: Armenis I , Ritsatos K , Vartela V , Marinou M , Gonteva M , Kyrzopoulos S , Tsiapras D , Athanassopoulos G D
Published: June 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Risk stratification in the asymptomatic severe aortic stenosis (AS) remains a difficult task within the spectrum of its hemodynamic phenotypes, especially on aging demographics. Interplay of left ventricular function and AS hemodynamics may be studied using semisupine bicycle ergometry (SBE).

Purpose

Purpose of the study was to interrogate the prognostic relevance of SBE based evaluation of LV function and noninvasive hemodynamics in asymptomatic severe AS.

Methods

Seventy-eight asymptomatic severe AS patients (pts), followed up on valve clinic in a tertiary center (age 65±12 years, female 29), were referred for SBE. AS related cardiac events (independent decision for surgery, NYHA worsening) during a follow up of 33/21 months occurred in 25 pts (64% for age>65 vs 30% for age<65).

Workload (Watts) and % achieved target heart rate (%targetHR) were considered surrogates for SBE efficiency. The following parameters (mean±SD) were estimated at rest(R) and SBE (Ex): Biplane LV ejection fraction (EF) and stroke volume (SV), 2D strain (SR), tricuspid peak gradient (TRPG), transmitral E/e, HR, systolic blood pressure (SBP), HR*SBP product and their respective % changes.

Results

Event group had a decreased SBE efficiency in workload (Watts: 59±16 vs 78±20, p<0.001), similar %target heart rate (73±13 vs 73±9), with differences among the continuous variables only in EFex (59±8 vs 63±7, p = 0.04) and %dLVEF (6±10 vs 12±10, p = 0.02).

Categorical classification was performed for inadequate LV functional improvement at SBE, using the absolute cut off for <5% LVEF increase and the <3% for LVSR increase, as well as for an excessive increase in pulmonary hypertension at SBE, using the cut off for TRPG >55mmHg.

Respective distribution of cases was similar for age category > or <=65 years (dEX <5: 46% vs 45%, dSR <3: 62% vs 87%, TRPGEx >55mmHg: 38% vs 48%, all p = ns).

Kaplan Meier analysis for events using TRPG>55 was significant for females (log rank=3.2, p = 0.06/ figure1). Kaplan Meier analysis for events using dEF≥5 was significant for age <65 years (log rank =4.7, p = 0.03/figure2).

LVSR cut off did not provide any difference in outcome.

Conclusion

SBE induced changes on LV function and pulmonary hypertension have an uneven risk stratification relevance according to age and gender. Dedicated algorithms to gender and age have to be applied for the improvement of prognostication in severe AS based on SBE.
Body mass components affecting low-attenuation noncalcified coronary plaque burden
Authors: Henzel J , Kruk M , Kepka C , Makarewicz-Wujec M , Wardziak L , Trochimiuk P , Dabrowski R , Dzielinska Z , Demkow M
Published: June 2023

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology in Warsaw, Poland

Background

Weight control is a major risk modifier for coronary artery disease. However, the effect exerted by individual body mass components on coronary plaque may not be uniform. Low-attenuation noncalcified plaque (LAP) has been recently identified as an independent predictor of cardiovascular outcomes [1].

Purpose

To determine the relationship between changes in body mass composition and LAP burden.

Methods

89 participants of Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) were enrolled into the analysis (40% women, mean age 60±7.7 years). Patients with non-obstructive (stenosis<70%) coronary atherosclerosis confirmed in coronary computed tomography angiography (CCTA) and qualified to conservative treatment were randomized (1:1) to intensive diet and lifestyle intervention atop optimal medical therapy (OMT) versus OMT alone over 66.8±13.7 months [2]. Body mass (BM) and body mass components including total body fat (TBF), skeletal muscle mass (SMM), visceral cell mass (VCM), and extracellular mass (ECM) were measured at baseline and follow-up (InBody S10 analyser, South Korea). LAP burden was defined as the volume of coronary plaque <30 Hounsfield units divided by the vessel volume, and expressed in %. Changes in body components were compared with changes in LAP measured in serial CCTA scans (QAngioCT, Medis Medical Imaging Systems, the Netherlands).

Results

Reduction in BM was significantly higher in the experimental (∆BM=-3.6±4.9 kg) vs control arm (∆BM=-1.4±2.9 kg; p = 0.016) and so was the reduction in TBF (∆TBF=-4.2±5.3 kg vs ∆TBF=0.2±4.3 kg, respectively; p<0.001). SMM increased by 0.4±2.6 kg in the experimental arm and decreased by 1.0±2.1 kg in the control arm (p = 0.006). No significant interarm differences were observed for changes in VCM and ECM. Reduction in LAP was higher in the experimental vs control arm (∆LAP=-0.42±1.4% vs ∆LAP=-0.03±0.45%, respectively; p = 0.078).

In the entire study population, a significant positive correlation between LAP reduction and BM reduction was revealed (r=0.45, p<0.001). Multivariate regression model incorporating the investigated body mass components identified TBF as the only component associated with LAP reduction (table).

Conclusions

Body mass reduction may decrease LAP burden due to body fat reduction.
Assessment of intracardiac flow dynamics for the evaluation of patients with aortic stenosis
Authors: Leo I , Sabatino J , Strangio A , Canino G , Critelli C , Troilo F , Maglione M , Loliva G , Romano L R , Indolfi C , De Rosa S
Published: June 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Assessment of intracardiac flows has acquired increasing significance in the past few years, due to the development and introduction of technologies for non-invasive cardiovascular imaging. Recent studies have demonstrated abnormalities in cardiac function, which are related to pathological intracardiac vortical flows.

This study investigates the additional information provided by quantifying intracardiac flow dynamics for the evaluation of patients with aortic stenosis (AS), by using an advanced echocardiography vortex-based approach.

Methods

One hundred twenty patients with severe AS (65 females – 54%), 60 patients with concentric remodelling (VR) (7 females – 12%) and 100 healthy controls (CTRL) (32 females – 32%) were prospectively enrolled to undergo a non-invasive evaluation of intracardiac flow dynamics. Echocardiographic assessments were performed, and apical three chamber views were recorded by means of MyLab™ X8 Platform. The HyperDoppler software adapted to an Esaote echo-scanner without contrast injection was used to assess vortex properties in all the patients.

Results

Vortex depth, vortex length, vortex intensity and vortex area were all significantly increased in SAo compared to CTRL (p<0.001, p = 0.003, p<0.001 and p = 0,049, respectively). Only vortex depth and vortex intensity (p<0.001 and p = 0.013, respectively) were significantly increased in SAo compared with VR. The mean energy dissipation of SAo group was significantly increased compared to control group (p<0.001) and VR (p = 0.002). Finally, the ROC Curve, generated to assess the capability of vortex depth to discriminate patients with and without severe aortic stenosis, showed an AUC of 0.751 (cutoff value ≥ 0.354; sensitivity, 73%; specificity, 73%).

Conclusions

There is a significant change of vortex localization, vorticity and energy parameters in patients with Sao. In particular, vortex depth, vortex intensity and energy dissipation are all significantly increased in SAo compared to CTRL and vortex depth can independently differentiate patients with SAo to those with only concentric remodelling and to CTRLs with high accuracy.

These findings indicate that the assessment of intracardiac flow dynamics may provide complementary information to standard echocardiography, helping to distinguish within the heterogeneous population of patients with severe AS.
Health-economic modelling of cost savings due to the use of rezafungin based on a German cost-of-illness study of candidiasis
Authors: Jeck Julia , Jakobs Florian , Kurte Melina S , Cornely Oliver A , Kron Florian
Published: June 2023

Objective

Candida species are responsible for fungal diseases and the development of nosocomial bloodstream infections. Treatment is resource-intensive and economically challenging for healthcare systems. Cost analyses of drugs against candidiasis, such as rezafungin, are thus of great interest to healthcare payers.

Methods

We conducted a cost-of-illness study of patients with Candida infections based on real-word data of the Department I of Internal Medicine, University Hospital Cologne (Germany) between 2016 and 2021. Health-economic parameters were analysed to describe the economic impact of Candida infections. Potential cost savings due to the administration of rezafungin were modelled for patients with invasive candidiasis or candidaemia based on a 5 day reduction of ICU length of stay (LOS) shown by the STRIVE study.

Results

We found 724 cases (652 patients) with Candida infections, of which 61% received ICU treatment (n = 442) and 29% were mechanically ventilated (n = 207). Twenty-six percent died during hospitalization (n = 185). Median LOS was 25 and 15 days, on normal wards and ICU, respectively. Median total treatment costs per case accounted for €22 820. Based on the ICU LOS reduction, the retrospective model showed a median cost-saving potential of €7175 per hospital case with invasive candidiasis or candidaemia. Accumulated cost savings for 37 patients of €283 335 were found.

Conclusions

Treatment of candidiasis is cost intensive due to increased hospital LOS. The ICU LOS reduction rezafungin showed in STRIVE would lead to sustainable cost savings.
Semi-automated technique for bovine skeletal muscle fiber cross-sectional area and myosin heavy chain determination
Authors: Fuerniss Luke K , Johnson Bradley J
Published: June 2023

Myosin heavy chain (MyHC) type and muscle fiber size are informative but time-consuming variables of interest for livestock growth, muscle biology, and meat science. The objective of this study was to validate a semi-automated protocol for determining MyHC type and size of muscle fibers. Muscle fibers obtained from the longissimus and semitendinosus of fed beef carcasses were embedded and frozen within 45 min of harvest. Immunohistochemistry was used to distinguish MyHC type I, IIA, and IIX proteins, dystrophin, and nuclei in transverse sections of frozen muscle samples. Stained muscle cross sections were imaged and analyzed using two workflows: 1) Nikon workflow which used Nikon Eclipse inverted microscope and NIS Elements software and 2) Cytation5 workflow consisting of Agilent BioTek Cytation5 imaging reader and Gen5 software. With the Cytation5 workflow, approximately six times more muscle fibers were evaluated compared to the Nikon workflow within both the longissimus (P < 0.01; 768 vs. 129 fibers evaluated) and semitendinosus (P < 0.01; 593 vs. 96 fibers evaluated). Combined imaging and analysis took approximately 1 h per sample with the Nikon workflow and 10 min with the Cytation5 workflow. When muscle fibers were evaluated by the objective thresholds of the Cytation5 workflow, a greater proportion of fibers were classified as glycolytic MyHC types, regardless of muscle (P < 0.01). Overall mean myofiber cross-sectional area was 14% smaller (P < 0.01; 3,248 vs. 3,780) when determined by Cytation5 workflow than when determined by Nikon workflow. Regardless, Pearson correlation of mean muscle fiber cross-sectional areas determined by Nikon and Cytation5 workflows was 0.73 (P < 0.01). In both workflows cross-sectional area of MyHC type I fibers was the smallest and area of MyHC type IIX fibers was the largest. These results validated the Cytation5 workflow as an efficient and biologically relevant tool to expedite data capture of muscle fiber characteristics while using objective thresholds for muscle fiber classification.
A Diagnostic Dilemma: New Enhancing Suspicious Findings on Breast MRI Following Neoadjuvant Chemotherapy
Authors: LaRoy Jennifer R , Tadros Audree B , Sevilimedu Varadan , Mango Victoria L
Published: June 2023

Objective

Evaluate the incidence and outcome of new enhancing findings on breast MRI after neoadjuvant chemotherapy (NAC).

Methods

This IRB-approved retrospective review included women with breast cancer undergoing MRI to evaluate NAC response at our institution from January 1, 1998 to March 3, 2021. Post-NAC MRIs given BI-RADS 4 or 5 with new enhancing findings were identified. Patients were excluded if they lacked pretreatment MRI or insufficient follow-up, or if the finding was a satellite of the primary tumor. Medical records and imaging studies were reviewed to identify patients and to find characteristics and outcomes.

Results

Over the study period, 2880 post-NAC breast MRIs were performed. Of 128 post-NAC MRIs given BI-RADS 4 or 5 (4.4%), 35 new suspicious findings were found on 32 MRIs, incidence rate 1.1% (32/2880). Most were characterized as nonmass enhancement (17/35, 49%), followed by mass (11/35, 31%), and then focus (7/35, 20%), with an average maximum dimension of 1.3 cm (range 0.3–7.1 cm). New findings were ipsilateral to the index cancer in 20/35 (57%) of cases. Of the 35 suspicious findings, 22 underwent image-guided biopsy (62%), 1 was surgically excised (3%), 7 underwent mastectomy (20%), 5 were stable or resolved on follow-up (8%), and none were malignant. Thirty-three were benign (94%), and two were benign high-risk lesions (atypical ductal hyperplasia, radial scar) (6%).

Conclusion

New suspicious breast MRI findings after NAC are uncommon with a low likelihood of malignancy. Further study is warranted using multi-institutional data for this low incidence finding.
Establishment and impacts of emerald ash borer (Coleoptera: Buprestidae) parasitoids released at early- and post-invasion sites
Authors: Morris Timothy D , Gould Juli R , Fierke Melissa K
Published: June 2023

Forest stands infested by emerald ash borer (EAB), Agrilus planipennis Fairmaire, experience extensive mortality of mature ash trees. Post-invasion woodlands commonly have a small contingent of mature lingering ash, an orphaned cohort of seedlings/saplings, and low EAB densities. To protect regenerating ash against rebounding EAB populations, a suite of biocontrol agents are being reared and released. USDA APHIS guidelines currently recommend the release of parasitoids into forests prior to overstory ash mortality at sites containing a variety of ash size classes and low to moderate but building EAB densities. To understand if biocontrol establishment and control of EAB is feasible in post-invasion sites, we assessed the establishment of parasitoids in 6 post-invasion forest stands in 2 regions of NY and compared EAB mortality in these stands to 2 regions where releases were conducted during the early-invasion phase. Results of parasitoid trapping indicates Tetrastichus planipennisi Yang established under both release strategies. Spathius galinae Belokobylskij & Strazanac was only released in post-invasion stands, where it was established successfully. Artificial EAB cohorts were established and life tables were constructed at 3 sites per region. EAB mortality due to T. planipennisi parasitism was similar under both release strategies 2 yr after release in post-invasion stands versus 8 yr after release in early-invasion stands. Combined mortality from T. planipennisi and woodpecker predation resulted in consistently low EAB reproductive rates. Future biocontrol releases could target forests identified as economically or ecologically important, regardless of whether EAB populations are increasing or have collapsed following initial invasion.
Identification and functional analysis of isopentenyl pyrophosphate isomerase genes in the whiteflies Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Yang Zhifang , Wang Kui , Liu Shunxiao , Li Xiang , Wang Hongliang , Wang Liuhao , Zhang Hongwei , Yu Hao
Published: June 2023

The juvenile hormone (JH) plays a vital role in the regulation of a number of physiological processes, including development, reproduction, and ovarian maturation. Isopentenyl pyrophosphate isomerase (IPPI) is a key enzyme in the biosynthetic pathway of JH. In this study, we identified an isopentenyl pyrophosphate isomerase protein from Bemisia tabaci and named it BtabIPPI. The open reading frame (ORF) of BtabIPPI is 768 bp and encodes a protein of 255 amino acids that contains a conserved domain of the Nudix family. The temporal and spatial expression profiles showed that BtabIPPI was highly expressed in the female adults.RNA interference (RNAi)-mediated silencing of BtabIPPI reduced JH titers and the relative expression of vitellogenin receptor (VgR) and JH signaling pathway genes, resulting in a dramatic reduction in fecundity and hatchability. These results indicate that the BtabIPPI gene plays an important role in the female fecundity of B. tabaci. This study will broaden our understanding of the function of IPPI in regulating insect reproduction and provide a theoretical basis for targeting IPPI for pest control in the future.
Factors that affect long-distance movements of small rodents and shrews in the Ural taiga: disentangling dispersal from excursion movements
Authors: Tolkachev Oleg , Maklakov Kirill , Malkova Ekaterina
Published: June 2023

Long-distance movements (LDMs) of small mammals (SMs) are complex phenomena that cover both dispersals and excursions occurring outside the home ranges of individuals. Owing to methodological difficulties, there are a lack of data on LDMs for SMs. In this study, we aimed to determine the factors that influence the LDMs of different mouse-sized rodents and shrews in the Ural taiga (Sverdlovsk region, Russia). We conducted a field experiment in a boreal forest using individual- (capture–marking–recapture [CMR]) and group- (biomarkers: tetracycline and rhodamine B) marking methods, in conjunction with additional feeding. The species, sex, maturity, plot ID, additional food supply, species abundance indices, individuals/100 trap-nights indices in the capture plot, and body weight of each animal were analyzed as predictors of LDMs. We identified 89 individuals from six species that moved at distances of 250, 350, and 500 m. LDMs varied with the particular species and its population abundance. Most of the observed movements were excursions and not dispersal events. Applying mathematical simulations to the obtained empirical data facilitated estimation of the intensity of the excursion activity for different species. We present the 1st excursion data on Sylvaemus uralensis (Pallas, 1811), Microtus arvalis (Pallas, 1778), and Sorex caecutiens (Laxmann, 1788). The detected excursion distance (250 m) for Myodes glareolus (Schreber, 1780) is the maximum excursion distance known for this species. We demonstrate that with comparable labor and time costs, the use of biomarkers makes it possible to detect many more LDMs than CMR allows.
Shedding light on the controversial taxonomic status of Culicoides jamaicensis and Culicoides paolae (Diptera: Ceratopogonidae): an overseas trip among continents
Authors: Bravo-Barriga Daniel , González Mikel Alexander , Parreira Ricardo , Frontera Eva , Huerta Herón , Alarcón-Elbal Pedro María
Published: June 2023

Culicoides biting midges (Diptera: Ceratopogonidae) are small bloodsucking flies that act as vectors for various pathogens of medical and veterinary importance. This study aimed to examine, using a comprehensive approach, the controversial taxonomic status of 2 Culicoides species that are currently distributed in the Neotropical (Culicoides jamaicensis Edwards) and Palearctic (Culicoides paolae Boorman) areas and possess unique and distinctive features. Previous investigations based on morphological analysis have suggested that these 2 species may be synonyms. Our work updated the current geographical distribution of both species and analyzed new specimens from different geographic origins, together with publicly available sequences. We used 2 universal genetic markers (COI and 28S) to test this hypothesis. Our study reveals evidence that C. paolae and C. jamaicensis belong to the same species due to the following statements: (i) similar morphological features; (ii) low interspecific genetic variation; (iii) association with a single genetic cluster; (iv) inclusion within the subgenus Drymodesmyia, which has only been recorded in the New World; and (v) occurrence in habitats with moderate temperatures. We recommend that European and African specimens of C. paolae be considered from now on as C. jamaicensis. Our comprehensive approach shed new light on the taxonomic status of these 2 Culicoides species and has implications for future studies on their biology and ecology.
Highly efficient production and characterization of the exopolysaccharides from a thermotolerant Bacillus sp.
Authors: Ma Jing , Zhao Xiangying , Rong Zhangbo , Liu Liping , Zhang Jiaxiang , Li Qingshuai , Han Mo , Liu Jianjun
Published: June 2023

One thermotolerant Bacillus strain SFLV-ZM107 which could produce large amounts of extracellular polysaccharides (EPS) at 50°C was identified as Bacillus licheniformis by 16S rDNA sequencing and physiological and biochemical experiments. The EPS was identified as levan fructan by monosaccharides determination, NMR, and FTIR. Strain SFLV-ZM107 can be grown in the range of 35–55°C and it is efficient to produce levan from 400 to 500 g l−1 of sucrose. The production of levan can reach 158 g l−1 in a 5 L tank fermentation with an initial sucrose concentration of 450 g l−1 at 50°C for 12 hours with a maximum productivity of 13.17 g l−1 h−1. To the best of our knowledge, the strains obtained in this study are the most productive and efficient, which has great prospects for industrial application.
Genetic variants underlying developmental arrests in human preimplantation embryos
Authors: Ozturk Saffet
Published: June 2023

Developmental arrest in preimplantation embryos is one of the major causes of assisted reproduction failure. It is briefly defined as a delay or a failure of embryonic development in producing viable embryos during ART cycles. Permanent or partial developmental arrest can be observed in the human embryos from one-cell to blastocyst stages. These arrests mainly arise from different molecular biological defects, including epigenetic disturbances, ART processes, and genetic variants. Embryonic arrests were found to be associated with a number of variants in the genes playing key roles in embryonic genome activation, mitotic divisions, subcortical maternal complex formation, maternal mRNA clearance, repairing DNA damage, transcriptional, and translational controls. In this review, the biological impacts of these variants are comprehensively evaluated in the light of existing studies. The creation of diagnostic gene panels and potential ways of preventing developmental arrests to obtain competent embryos are also discussed.
Translation initiation with exotic amino acids using EF-P-responsive artificial initiator tRNA
Authors: Katoh Takayuki , Suga Hiroaki
Published: June 2023

Translation initiation using noncanonical initiator substrates with poor peptidyl donor activities, such as N-acetyl-l-proline (AcPro), induces the N-terminal drop-off-reinitiation event. Thereby, the initiator tRNA drops-off from the ribosome and the translation reinitiates from the second amino acid to yield a truncated peptide lacking the N-terminal initiator substrate. In order to suppress this event for the synthesis of full-length peptides, here we have devised a chimeric initiator tRNA, referred to as tRNAiniP, whose D-arm comprises a recognition motif for EF-P, an elongation factor that accelerates peptide bond formation. We have shown that the use of tRNAiniP and EF-P enhances the incorporation of not only AcPro but also d-amino, β-amino and γ-amino acids at the N-terminus. By optimizing the translation conditions, e.g. concentrations of translation factors, codon sequence and Shine-Dalgarno sequence, we could achieve complete suppression of the N-terminal drop-off-reinitiation for the exotic amino acids and enhance the expression level of full-length peptide up to 1000-fold compared with the use of the ordinary translation conditions.
Demographic history and distinct selection signatures of two domestication genes in mungbean
Authors: Lin Ya-Ping , Chen Hung-Wei , Yeh Pei-Min , Anand Shashi S , Lin Jiunn , Li Juan , Noble Thomas , Nair Ramakrishnan , Schafleitner Roland , Samsononova Maria , Bishop-von-Wettberg Eric , Nuzhdin Sergey , Ting Chau-Ti , Lawn Robert J , Lee Cheng-Ruei
Published: June 2023

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome resequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying 2 key traits representing different stages of domestication. Mungbean originated in Asia, and the Southeast Asian wild population migrated to Australia about 50 thousand generations ago. Later in Asia, the cultivated form diverged from the wild progenitor. We identified the gene associated with the pod shattering resistance trait, VrMYB26a, with lower expression across cultivars and reduced polymorphism in the promoter region, reflecting a hard selective sweep. On the other hand, the stem determinacy trait was associated with VrDet1. We found that 2 ancient haplotypes of this gene have lower gene expression and exhibited intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in a soft selective sweep. In mungbean, contrasting signatures of selection were identified from the detailed dissection of 2 important domestication traits. The results suggest complex genetic architecture underlying the seemingly simple process of directional artificial selection and highlight the limitations of genome-scan methods relying on hard selective sweeps.
Consumers pay attention to ingredients on the front of a label: an eye tracking study
Authors: Lowry Mark , Julian Anne K , Tribby Calvin , Perna Frank
Published: June 2023

Sunscreen is an important part of skin cancer prevention. The Food and Drug Administration (FDA) proposed numerous changes to sunscreen labeling including adding active ingredients to the front of a label. The purpose of the study was to identify and describe differences in attention between current label formatting and the proposed label formatting. Forty-seven participants were interviewed. Participants were presented with mock sunscreen labels that resembled current labeling or labeling based on the proposed FDA rule. While reading the labels, eye movements were recorded. Participants spent 12.3 s longer looking at the front of the proposed rule-compliant label than they did on the front of the current label. They spent the longest time reading the directions (13–14 seconds) compared with other areas. Placing active ingredients on the front of a label in relatively large font makes it more likely consumers will look at the information.
Plasma exosomes and contained MiRNAs affect the reproductive phenotype in polycystic ovary syndrome
Authors: Jiang Xiao , Zhang Zhirong , Hou Min , Yang Xiaohe , Cui Linlin
Published: June 2023

Anovulation is the main feature of infertile women with polycystic ovary syndrome (PCOS), and there is very limited understanding of the role of plasma exosomes and miRNAs in it. To identify the effect of PCOS patients' plasma exosomes and exosomal miRNAs, we isolated plasma exosomes of PCOS patients and normal women and injected into 8‐week‐old ICR female mice via tail vein. The changes in estrus cycle, serum hormone levels, and ovarian morphology were observed. KGN cells were cultured and transfected with mimics and inhibitors of differentially expressed exosomal miRNAs (miR‐18a‐3p, miR‐20b‐5p, miR‐106a‐5p, miR‐126‐3p, and miR‐146a‐5p) and then tested for steroid hormone synthesis, proliferation, and apoptosis. The results showed that female ICR mice injected with plasma exosomes from PCOS patients presented ovarian oligo‐cyclicity. Hormone synthesis and proliferation of granulosa cells were affected by differentially expressed PCOS plasma‐derived exosomal miRNAs, of which miR‐126‐3p having the most evident effect. MiR‐126‐3p affected the proliferation of granulosa cells by inhibiting PDGFRβ and its downstream PI3K‐AKT pathway. Our results demonstrated plasma exosomes and contained miRNAs in PCOS patients affect the estrus cycle of mice, hormone secretion, and proliferation of granulosa cells. This study provides a novel understanding about the function of plasma exosomes and exosomal miRNAs in PCOS.
Experiences and Perceptions of Using Smartphone Ecological Momentary Assessment for Reporting Knee Osteoarthritis Pain and Symptoms
Authors: Overton Mark , Swain Nicola , Falling Carrie , Gwynne-Jones David , Fillingim Roger , Mani Ramakrishnan
Published: June 2023

Background:

Knee osteoarthritis (OA) is a prevalent, painful, and disabling musculoskeletal condition. One method that could more accurately monitor the pain associated with knee OA is ecological momentary assessment (EMA) using a smartphone.

Objectives:

The aim of this study was to explore participant experiences and perceptions of using smartphone EMA as a way of communicating knee OA pain and symptoms following participating in a 2-week smartphone EMA study.

Materials and Methods:

Using a maximum variation sampling method, participants were invited to share their thoughts and opinions in semistructured focus group interviews. Interviews were recorded and transcribed verbatim before thematic analysis using the general inductive approach.

Results:

A total of 20 participants participated in 6 focus groups. Three themes and 7 subthemes were identified from the data. Identified themes included: user experience of smartphone EMA, data quality of smartphone EMA, and practical aspects of smartphone EMA.

Discussion:

Overall, smartphone EMA was deemed as being an acceptable method for monitoring pain and symptoms associated with knee OA. These findings will assist researchers in designing future EMA studies alongside clinicians implementing smartphone EMA into practice.

Perspective:

This study highlights that smartphone EMA is an acceptable method for capturing pain-related symptoms and experiences of those expereiencing knee OA. Future EMA studies should ensure design features are considered that reduce missing data and limit the responder burden to improve data quality.
Emergence of resistance-associated variants during sofosbuvir treatment in chronically infected hepatitis E patients
Authors: Gömer André , Klöhn Mara , Jagst Michelle , Nocke Maximilian K. , Pischke Sven , Horvatits Thomas , Schulze zur Wiesch Julian , Müller Tobias , Hardtke Svenja , Cornberg Markus , Wedemeyer Heiner , Behrendt Patrick , Steinmann Eike , Todt Daniel
Published: June 2023

Background and Aims:

Chronic HEV infections remain a serious problem in immunocompromised patients, as specifically approved antiviral drugs are unavailable. In 2020, a 24-week multicenter phase II pilot trial was carried out, evaluating the nucleotide analog sofosbuvir by treating nine chronically HEV-infected patients with sofosbuvir (Trial Number NCT03282474). During the study, antiviral therapy reduced virus RNA levels initially but did not lead to a sustained virologic response. Here, we characterize the changes in HEV intrahost populations during sofosbuvir treatment to identify the emergence of treatment-associated variants.

Approach and Results:

We performed high-throughput sequencing on RNA-dependent RNA polymerase sequences to characterize viral population dynamics in study participants. Subsequently, we used an HEV-based reporter replicon system to investigate sofosbuvir sensitivity in high-frequency variants. Most patients had heterogenous HEV populations, suggesting high adaptability to treatment-related selection pressures. We identified numerous amino acid alterations emerging during treatment and found that the EC50 of patient-derived replicon constructs was up to ~12-fold higher than the wild-type control, suggesting that variants associated with lower drug sensitivity were selected during sofosbuvir treatment. In particular, a single amino acid substitution (A1343V) in the finger domain of ORF1 could reduce susceptibility to sofosbuvir significantly in 8 of 9 patients.

Conclusions:

In conclusion, viral population dynamics played a critical role during antiviral treatment. High population diversity during sofosbuvir treatment led to the selection of variants (especially A1343V) with lower sensitivity to the drug, uncovering a novel mechanism of resistance-associated variants during sofosbuvir treatment.
The Effects of Yoga and Stabilization Exercises in Patients With Chronic Low Back Pain
Authors: Ulger Ozlem , Oz Muzeyyen , Ozel Asliyuce Yasemin
Published: June 2023

This study aimed to assess the effectiveness of yoga and stabilization exercises in patients with chronic low back pain. Thirty-five female patients were randomly assigned to the stabilization exercise group or the yoga group. Outcome measures were the visual analog scale (VAS), Oswestry Disability Index (ODI) and Back Performance Scale (BPS), 6-minute walk test (6MWT), Fear-Avoidance Beliefs Questionnaire (FABQ), and Pittsburgh Sleep Quality Index (PSQI). The scores of the VAS, ODI, BPS, 6MWT, and PSQI improved significantly after both interventions (P < .05). Improvements in the stabilization program were higher on the transversus abdominis activation (P < .05). Both interventions had no effect on kinesiophobia (P > .05). Both exercise approaches were found to be similarly effective on pain, function, metabolic capacity, and sleep quality.
Elevated Serum Tau and UCHL-1 Concentrations Within 12 Months of Injury Predict Neurobehavioral Functioning 2 or More Years Following Traumatic Brain Injury: A Longitudinal Study
Authors: Lange Rael T. , Gill Jessica M. , Lippa Sara M. , Hungerford Lars , Walker Thomas , Kennedy Jan , Brickell Tracey A. , French Louis M.
Published: June 2023

Objective:

Blood-based biomarkers have received considerable attention for their diagnostic and prognostic value in the acute and postacute period following traumatic brain injury (TBI). The purpose of this study was to examine whether blood-based biomarker concentrations within the first 12 months of TBI can predict neurobehavioral outcome in the chronic phase of the recovery trajectory.

Setting:

Inpatient and outpatient wards from 3 military medical treatment facilities.

Participants:

A total of 161 service members and veterans classified into 3 groups: (a) uncomplicated mild TBI (MTBI; n = 37), (b) complicated mild, moderate, severe, penetrating TBI combined (STBI; n = 46), and (c) controls (CTRL; n = 78).

Design:

Prospective longitudinal.

Main Measures:

Participants completed 6 scales from the Traumatic Brain Injury Quality of Life (ie, Anger, Anxiety, Depression, Fatigue, Headaches, and Cognitive Concerns) within 12 months (baseline) and at 2 or more years (follow-up) post-injury. Serum concentrations of tau, neurofilament light, glial fibrillary acidic protein, and UCHL-1 at baseline were measured using SIMOA.

Results:

Baseline tau was associated with worse anger, anxiety, and depression in the STBI group at follow-up (R
2 = 0.101-0.127), and worse anxiety in the MTBI group (R
2 = 0.210). Baseline ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) was associated with worse anxiety and depression at follow-up in both the MTBI and STBI groups (R
2Δ = 0.143-0.207), and worse cognitive concerns in the MTBI group (R
2Δ = 0.223).

Conclusions:

A blood-based panel including these biomarkers could be a useful tool for identifying individuals at risk of poor outcome following TBI.
Trajectories of Daily Postconcussion Symptoms in Children
Authors: Sullivan Lindsay , Xu Menglin , Yeates Keith Owen , Alshaikh Enas , Taylor H. Gerry , Pommering Thomas , Yang Jingzhen
Published: June 2023

Objectives:

To identify trajectories of daily postconcussion symptoms (PCS) from the acute postinjury period to symptom resolution among concussed children and examine demographic factors and acute PCS associated with the identified symptom trajectories.

Setting and Participants:

Seventy-nine participants with a concussion were enrolled within 72 hours of injury and completed a daily survey that assessed PCS from enrollment until symptom resolution.

Design:

This was a prospective cohort study among concussed children aged 11–17 years.

Main Measures:

Children rated their concussion symptoms daily using the Post-Concussion Symptom Scale. Symptom duration was assessed using participants' date of symptom resolution and coded as a dichotomous variable: (1) PCS duration 14 days or less or (2) PCS duration longer than 14 days.

Results:

Of the 79 participants, most were male (n = 53, 67%), injured during a sporting activity (n = 67, 85%), or had PCS that persisted for more than 14 days post-injury (n = 41, 52%). Group-based trajectory modeling yielded 4 trajectory groups: (1) low acute/resolved PCS (n = 39, 49%), (2) moderate/persistent PCS (n = 19, 24%), (3) high acute/persistent PCS (n = 13, 16%), and (4) high acute/resolved PCS (n = 8, 10%). No significant associations were found between demographic factors and the trajectory group. A higher symptom burden at injury was associated with an increased odds of being in the high acute/resolved or high acute/persistent recovery groups than being in the low acute/resolved group (odds ratio [OR] 1.39, 95% CI = 1.11-1.74; OR = 1.33, 95% CI = 1.11-1.60, respectively), as was a higher symptom severity at injury (OR = 1.09, 95% CI = 1.03-1.15; OR = 1.06, 95% CI = 1.02-1.11, respectively).

Conclusion:

Our findings may help clinicians identify concussed children on slower recovery trajectories, and implement early, individualized treatment plans that foster optimal recovery for concussed children.
Associations of Prior Head Injury With Mild Behavioral Impairment Domains
Authors: Richey Lisa N. , Daneshvari Nicholas O. , Young Lisa , Bray Michael J. C. , Gottesman Rebecca F. , Mosley Thomas , Walker Keenan A. , Peters Matthew E. , Schneider Andrea L. C.
Published: June 2023

Objective:

This study investigated associations of prior head injury and number of prior head injuries with mild behavioral impairment (MBI) domains.

Setting:

The Atherosclerosis Risk in Communities (ARIC) Study.

Participants:

A total of 2534 community-dwelling older adults who took part in the ARIC Neurocognitive Study stage 2 examination were included.

Design:

This was a prospective cohort study. Head injury was defined using self-reported and International Classification of Diseases, Ninth Revision (ICD-9) code data. MBI domains were defined using the Neuropsychiatric Inventory Questionnaire (NPI-Q) via an established algorithm mapping noncognitive neuropsychiatric symptoms to the 6 domains of decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content.

Main Measures:

The primary outcome was the presence of impairment in MBI domains.

Results:

Participants were a mean age of 76 years, with a median time from first head injury to NPI-Q administration of 32 years. The age-adjusted prevalence of symptoms in any 1+ MBI domains was significantly higher among individuals with versus without prior head injury (31.3% vs 26.0%, P = .027). In adjusted models, a history of 2+ head injuries, but not 1 prior head injury, was associated with increased odds of impairment in affective dysregulation and impulse dyscontrol domains, compared with no history of head injury (odds ratio [OR] = 1.83, 95% CI = 1.13-2.98, and OR = 1.74, 95% CI = 1.08-2.78, respectively). Prior head injury was not associated with symptoms in MBI domains of decreased motivation, social inappropriateness, and abnormal perception/thought content (all P > .05).

Conclusion:

Prior head injury in older adults was associated with greater MBI domain symptoms, specifically affective dysregulation and impulse dyscontrol. Our results suggest that the construct of MBI can be used to systematically examine the noncognitive neuropsychiatric sequelae of head injury; further studies are needed to examine whether the systematic identification and rapid treatment of neuropsychiatric symptoms after head injury is associated with improved outcomes.
Risk of Adverse Outcomes Among Veterans Who Screen Positive for Traumatic Brain Injury in the Veterans Health Administration But Do Not Complete a Comprehensive Evaluation: A LIMBIC-CENC Study
Authors: Pogoda Terri K. , Adams Rachel Sayko , Carlson Kathleen F. , Dismuke-Greer Clara E. , Amuan Megan , Pugh Mary Jo
Published: June 2023

Objective:

To examine whether post-9/11 veterans who screened positive for mild traumatic brain injury (mTBI) but did not complete a Comprehensive TBI Evaluation (CTBIE) were at higher risk of subsequent adverse events compared with veterans who screened positive and completed a CTBIE. Upon CTBIE completion, information assessed by a trained TBI clinician indicates whether there is mTBI history (mTBI+) or not (mTBI−).

Setting:

Veterans Health Administration (VHA) outpatient services.

Participants:

A total of 52 700 post-9/11 veterans who screened positive for TBI were included. The follow-up review period was between fiscal years 2008 and 2019. The 3 groups studied based on CTBIE completion and mTBI status were: (1) mTBI+ (48.6%), (2) mTBI− (17.8%), and (3) no CTBIE (33.7%).

Design:

This was a retrospective cohort study. Log binomial and Poisson regression models adjusting for demographic, military, pre-TBI screening health, and VHA covariates examined risk ratios of incident outcomes based on CTBIE completion and mTBI status.

Main Measures:

Incident substance use disorders (SUDs), alcohol use disorder (AUD), opioid use disorder (OUD), overdose, and homelessness documented in VHA administrative records, and mortality as documented in the National Death Index, 3 years post-TBI screen. VHA outpatient utilization was also examined.

Results:

Compared with the no CTBIE group, the mTBI+ group had 1.28 to 1.31 times the risk of incident SUD, AUD, and overdose, but 0.73 times the risk of death 3 years following TBI screening. The mTBI− group had 0.70 times the risk of OUD compared with the no CTBIE group within the same period. The no CTBIE group also had the lowest VHA utilization.

Conclusions:

There were mixed findings on risk of adverse events for the no CTBIE group relative to the mTBI+ and mTBI− groups. Future research is needed to explore the observed differences, including health conditions and healthcare utilization, documented outside VHA among veterans who screen positive for TBI.
Prognostic factors in young patients with ST-segment elevation myocardial infarction
Authors: Zhang Zhanshuai , Qin Shaoqiang , Wang Rui , Wang Yaling , Fang Zhiqin
Published: June 2023

Objective

The prognostic factors of young patients aged ≤40 years with ST-segment elevation myocardial infarction (STEMI) remain unclear. This study explored risk factors that may affect the 1-year prognosis of young STEMI patients by analyzing patient data of baseline, clinical regimen, and secondary prevention.

Methods

Baseline and clinical data were collected from 420 STEMI patients aged ≤40 years. One year of follow-up was performed to record and compare the differences in data between patients with and without adverse events. Binary logistic regression analysis with controls for confounding factors was used to evaluate prognosis-related independent factors.

Results

The overall incidence of cardiovascular adverse events was 15.95%. Comparison of the subgroups revealed that regardless of adjustment for confounding factors, prognoses of the patients were affected by the following factors: BMI, marital status, serum apolipoprotein(a) (ApoA) levels, number of diseased vessels, treatment regimen, compliance of secondary prevention, improvement of lifestyle, and adjusted comorbidities (P < 0.05). Independent analysis of adverse events revealed that BMI, number of diseased vessels, and compliance of secondary prevention were independent factors of recurrent acute myocardial infarction in patients. Serum ApoA level, treatment regimen, and compliance of secondary prevention were independent influence factors of heart failure in patients. Marital status and serum ApoA level were independent factors of malignant arrhythmias in patients. BMI, compliance of secondary prevention, and improvement of lifestyle were independent factors of cardiac death in patients.

Conclusion

This study determined the influential factors for the prognosis of STEMI patients aged ≤40 years as follows: BMI, marital status, comorbidities, number of diseased vessels, regimen, compliance of secondary prevention, and improvement of lifestyle. The risk of cardiovascular adverse events may be reduced by modulating the influential factors.