bluuebunny/crossref_metadata_2025 huggingface dataset:
Allele-specific suppression in Caenorhabditis elegans reveals details of EMS mutagenesis and a possible moonlighting interaction between the vesicular acetylcholine transporter and ERD2 receptors
Authors: Mathews Eleanor A , Stroud Dave , Mullen Gregory P , Gavriilidis Gavriil , Duerr Janet S , Rand James B , Hodgkin Jonathan
Published: April 2021

A missense mutant, unc-17(e245), which affects the Caenorhabditis elegans vesicular acetylcholine transporter UNC-17, has a severe uncoordinated phenotype, allowing efficient selection of dominant suppressors that revert this phenotype to wild-type. Such selections permitted isolation of numerous suppressors after EMS (ethyl methanesulfonate) mutagenesis, leading to demonstration of delays in mutation fixation after initial EMS treatment, as has been shown in T4 bacteriophage but not previously in eukaryotes. Three strong dominant extragenic suppressor loci have been defined, all of which act specifically on allele e245, which causes a G347R mutation in UNC-17. Two of the suppressors (sup-1 and sup-8/snb-1) have previously been shown to encode synaptic proteins able to interact directly with UNC-17. We found that the remaining suppressor, sup-2, corresponds to a mutation in erd-2.1, which encodes an endoplasmic reticulum retention protein; sup-2 causes a V186E missense mutation in transmembrane helix 7 of ERD-2.1. The same missense change introduced into the redundant paralogous gene erd-2.2 also suppressed unc-17(e245). Suppression presumably occurred by compensatory charge interactions between transmembrane helices of UNC-17 and ERD-2.1 or ERD-2.2, as previously proposed in work on suppression by SUP-1(G84E) or SUP-8(I97D)/synaptobrevin. erd-2.1(V186E) homozygotes were fully viable, but erd-2.1(V186E); erd-2.2(RNAi) exhibited synthetic lethality [like erd-2.1(RNAi); erd-2.2(RNAi)], indicating that the missense change in ERD-2.1 impairs its normal function in the secretory pathway but may allow it to adopt a novel moonlighting function as an unc-17 suppressor.
Magnetic fabric from Quaternary volcanic edifices in the extensional Bransfield Basin: internal structure of Penguin and Bridgeman islands (South Shetlands archipelago, Antarctica)
Authors: Oliva-Urcia B , López-Martínez J , Maestro A , Gil A , Schmid T , Lambán L J , Galé C , Ubide T , Lago M
Published: April 2021

Studying the magnetic fabric in volcanic edifices, particularly lava flows from recent eruptions, allows us to understand the orientation distribution of the minerals related to the flow direction and properly characterize older and/or eroded flows. In this work, the magnetic fabric from recent (Quaternary) lava flows (slightly inclined in seven sites and plateau lavas in two sites), pyroclastic deposits (two sites from a scoria cone) and volcanic cones, domes and plugs (three sites) from Penguin and Bridgeman islands, located in the Bransfield backarc basin, are presented. The volcanism in the two islands is related to rifting occurring due to the opening of the Bransfield Strait, between the South Shetlands archipelago and the Antarctic Peninsula. The direction of flow of magmatic material is unknown. Rock magnetic analyses, low temperature measurements and electron microscope observations (back-scattered electron imaging and Energy Dispersive X-ray analyses) reveal a Ti-poor magnetite (and maghemite) as the main carrier of the magnetic fabric. Hematite may be present in some samples. Samples from the centre of the lavas reveal a magnetic lineation either parallel or imbricated with respect to the flow plane, whereas in the plateau lavas the magnetic lineation is contained within the subhorizontal plane except in vesicle-rich samples, where imbrication occurs. The magnetic lineation indicates a varied flow direction in Bridgeman Island with respect to the spreading Bransfield Basin axis. The flow direction in the plateau lavas on Penguin Island is deduced from the imbrication of the magnetic fabric in the more vesicular parts, suggesting a SE–NW flow. The volcanic domes are also imbricated with respect to an upward flow, and the bombs show scattered distribution.
TBN improves motor function and prolongs survival in a TDP-43M337V mouse model of ALS
Authors: Huang Chunhui , Li Jun , Zhang Guiliang , Lin Yingqi , Li Caijuan , Zheng Xiao , Song Xichen , Han Bofeng , Guo Baojian , Tu Zhuchi , Zhang Jun , Sun Yewei , Wang Yuqiang , Zhang Zaijun , Yan Sen
Published: April 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are serious neurodegenerative diseases. Although their pathogenesis is unclear, the abnormal accumulation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological feature that exists in almost all patients. Thus far, there is no drug that can cure ALS/FTLD. Tetramethylpyrazine nitrone (TBN) is a derivative of tetramethylapyrazine, derived from the traditional Chinese medicine Ligusticum chuanxiong, which has been widely proven to have therapeutic effects on models of various neurodegenerative diseases. TBN is currently under clinical investigation for several indications including a Phase II trial of ALS. Here, we explored the therapeutic effect of TBN in an ALS/FTLD mouse model. We injected the TDP-43 M337V virus into the striatum of mice unilaterally and bilaterally, and then administered 30 mg/kg TBN intragastrically to observe changes in behavior and survival rate of mice. The results showed that in mice with unilateral injection of TDP-43M337V into the striatum, TBN improved motor deficits and cognitive impairment in the early stages of disease progression. In mice with bilateral injection of TDP-43M337V into the striatum, TBN not only improved motor function but also prolonged survival rate. Moreover, we show that its therapeutic effect may be through activation of the Akt/mTOR/GSK-3β and AMPK/PGC-1α/Nrf2 signaling pathways. In summary, TBN is a promising agent for the treatment of ALS/FTLD.
Phenotypic recapitulation and correction of desmoglein-2-deficient cardiomyopathy using human-induced pluripotent stem cell-derived cardiomyocytes
Authors: Shiba Mikio , Higo Shuichiro , Kondo Takumi , Li Junjun , Liu Li , Ikeda Yoshihiko , Kohama Yasuaki , Kameda Satoshi , Tabata Tomoka , Inoue Hiroyuki , Nakamura Satoki , Takeda Maki , Ito Emiko , Takashima Seiji , Miyagawa Shigeru , Sawa Yoshiki , Hikoso Shungo , Sakata Yasushi
Published: April 2021

Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disk structures in the myocardium. Induced pluripotent stem cells (iPSCs) were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes [induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)]. Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not in HDR-iPSC-CMs. Micro-force testing of three-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provide evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.
Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models
Authors: Bai Dazhang , Yin Peng , Zhang Yiran , Sun Fengwei , Chen Laiqiang , Lin Li , Yan Sen , Li Shihua , Li Xiao-Jiang
Published: April 2021

Our previous work has established a huntingtin knock-in (KI) pig model that displays striatal neuronal loss, allowing us to examine if somatic CAG expansion in striatum accounts for the preferential neurodegeneration in Huntington disease (HD). We found that HD KI pigs do not display somatic CAG expansion in striatum as HD KI mice and that the majority of polyQ repeats in exon 1 HTT in the striatum of HD KI mice are fairly stable. We also found that striatal MSH2 and MLH3, which are involved in DNA repair, are more abundant in mouse brains than pig brains. Consistently inhibiting MSH2 and MLH3 reduced the somatic CAG expansion in HD KI mouse striatum with no influence on neuropathology. Our findings suggest that somatic CAG expansion is species-dependent, occurs in a small fraction of the HD gene in mice, and does not critically contribute to HD neuropathology.
Extension Theory for Braided-Enriched Fusion Categories
Authors: Jones Corey , Morrison Scott , Penneys David , Plavnik Julia
Published: April 2021

For a braided fusion category $\mathcal{V}$, a $\mathcal{V}$-fusion category is a fusion category $\mathcal{C}$ equipped with a braided monoidal functor $\mathcal{F}:\mathcal{V} \to Z(\mathcal{C})$. Given a fixed $\mathcal{V}$-fusion category $(\mathcal{C}, \mathcal{F})$ and a fixed $G$-graded extension $\mathcal{C}\subseteq \mathcal{D}$ as an ordinary fusion category, we characterize the enrichments $\widetilde{\mathcal{F}}:\mathcal{V} \to Z(\mathcal{D})$ of $\mathcal{D}$ that are compatible with the enrichment of $\mathcal{C}$. We show that G-crossed extensions of a braided fusion category $\mathcal{C}$ are G-extensions of the canonical enrichment of $\mathcal{C}$ over itself. As an application, we parameterize the set of $G$-crossed braidings on a fixed $G$-graded fusion category in terms of certain subcategories of its center, extending Nikshych’s classification of the braidings on a fusion category.
Semiclassical Resolvent Bounds for Long-Range Lipschitz Potentials
Authors: Galkowski Jeffrey , Shapiro Jacob
Published: April 2021

We give an elementary proof of weighted resolvent estimates for the semiclassical Schrödinger operator $-h^2 \Delta + V(x) - E$ in dimension $n \neq 2$, where $h, \, E> 0$. The potential is real valued and $V$ and $\partial _r V$ exhibit long-range decay at infinity and may grow like a sufficiently small negative power of $r$ as $r \to 0$. The resolvent norm grows exponentially in $h^{-1}$, but near infinity it grows linearly. When $V$ is compactly supported, we obtain linear growth if the resolvent is multiplied by weights supported outside a ball of radius $CE^{-1/2}$ for some $C> 0$. This $E$-dependence is sharp and answers a question of Datchev and Jin.
Development and Validation of RP-HPLC Method for Vicenin-2, Orientin, Cynaroside, Betulinic Acid, Genistein, and Major Eight Bioactive Constituents with LC-ESI-MS/MS Profiling in Ocimum Genus
Authors: Girme Aboli , Bhoj Prajkta , Saste Ganesh , Pawar Sandeep , Mirgal Amit , Raut Dipak , Chavan Machindra , Hingorani Lal
Published: April 2021

Background

Ocimum genus, known as Tulsi or Basil, is a prominent botanical class in Asian culture, especially in India. The leaves have immunomodulatory, antioxidant, stress-relieving, and adaptogenic roles in traditional and modern medicine, with prominent usage in herbal teas and nutraceuticals.

Objective

An high-performance liquid chromatography–photodiode array (HPLC-PDA) method was developed and validated for quantification of vicenin-2, orientin, cynaroside, betulinic acid, genistein with syringic acid, rosmarinic acid, eugenol, carnosic acid, oleanolic acid, ursolic acid, luteolin, and apigenin and was confirmed using a novel electrospray ionisation-mass spectrometry (ESI-MS/MS) method in the Ocimum genus samples.

Method

The methodology parameters were developed on an reverse phase (RP) C18 column with a gradient elution of 1 mL/min flow rate for 0.1% o-phosphoric acid and acetonitrile at 210 and 340 nm wavelengths.

Results

The validation data for 13 bioactive compounds showed good linearity (r2 > 0.99) with sensitive LOD (0.034–0.684 µg/mL) and LOQ (0.100–2.068 µg/mL) with recoveries (83.66–101.53%). The results of the quantification were found to be precise (RSD, <5.0%) and accurate (relative error (RE), -0.60–1.06). The method performance was verified by analyzing 10 samples of O. tenuiflorum from the 10 geographical states of India (RSD, <5.0%) and were found to be robust. This HPLC-PDA method with ESI-MS/MS confirmation was applicable to the 13 cultivars from O. thyrsiflorum, O. citriodorum, O. americanum, O. africanum, O. basilicum, O. gratissimum, and O. tenuiflorum species.

Conclusions

The validated HPLC-PDA and LC-ESI-MS/MS method was found to be selective and suitable for analyzing 13 compounds in O. tenuiflorum and 12 cultivars from the Ocimum genus as a quality control tool. This method can be used in routine analysis as an inexpensive alternative to advanced techniques.

Highlights

This work is the first to report for vicenin-2, orientin, cynaroside, betulinic acid, and genistein, with simultaneous analysis of eight bioactive compounds in the Ocimum genus.
Assessment of a Nondestructive Method for Rapid Discrimination of Moroccan Date Palm Varieties via Mid-Infrared Spectroscopy Combined with Chemometric Models
Authors: Elhamdaoui Omar , El Orche Aimen , Cheikh Amine , Karrouchi Khalid , Laarej Khalid , Bouatia Mustapha
Published: April 2021

Background

Morocco is an important world producer and consumer of several varieties of date palm. In fact, the discrimination between varieties remains difficult and requires the use of complex and high-cost techniques.

Objective

We evaluated in this work the potential of mid-IR (MIR) spectroscopy and chemometric models to discriminate eight date palm varieties.

Method

Four chemometric models were applied for the analysis of the spectral data, including principal-component analysis (PCA), support-vector machine discriminant analysis (SVM-DA), linear discriminant analysis (LDA), and partial-least-squares (PLS) analysis. MIR spectroscopic data were recorded from the wavenumber range 4000–600 cm−1, with a spectral resolution of 4 cm−1.

Results

The discriminant analysis was performed by LDA and SVM-DA with a 100% correct classification rate for the date mesocarp. PLS analysis was applied as a complementary chemometric tool aimed at quantifying moisture content; the validation of this model shows a good predictive capacity with a regression coefficient of 84% and a root-mean-square error of cross-validation of 0.50.

Conclusions

The present study clearly demonstrates that MIR spectroscopy combined with chemometric approaches constitutes a promising analytical method to classify date palms according to their varietal origin and to establish a regression model for predicting moisture content.

Highlights

An alternative analytical method to discriminate date palm cultivars by FTIR-attenuated total reflection spectroscopy coupled with chemometric approaches is described.
A geometrical description for interplanetary propagation of Earth-directed CMEs based on radiative proxies
Authors: Salas-Matamoros C , Sanchez-Guevara J
Published: April 2021

We present a 3D geometrical model to describe the propagation and expansion of coronal mass ejections (CMEs) in the interplanetary space based on radiative proxies to be implemented in previous procedures that use SXR and microwave emissions to estimate the Earth-directed CME propagation speed. We carefully selected a sample of 45 well-defined CME-ICME events to evaluate our model. We computed this 3D geometrical model for each event as a tool to improve the arrival time predictions based on radiative proxies. We conducted a different analysis for each radiative proxy: SXR emission and microwave emission at 9 GHz, and we compared the results separately with the observations by the Wind spacecraft. In general, the results showed that the implementation of our 3D geometrical model improves the predictions and provides an important complement to the arrival time prediction method based on radiative proxies, especially for CME events whose source origin were located at helio longitudes far from the central meridian at least 10°. Improvements for this tool based on observations by Parker Solar Probe and Solar Orbiter must be developed in the future work.
AstroSat observation of the HBL 1ES 1959+650 during its October 2017 flaring
Authors: Shah Zahir , Ezhikode Savithri H , Misra Ranjeev , Rajalakshmi T R
Published: April 2021

We present the results of the X-ray flaring activity of 1ES 1959+650 during 2017 October 25–26 using AstroSat observations. The source was variable in the X-ray. We investigated the evolution of the X-ray spectral properties of the source by dividing the total observation period (∼130 ks) into time segments of 5 ks, and fitting the Soft X-ray focusing Telescope and Large Area X-ray Proportional Counter spectra for each segment. Synchrotron emission of a broken power-law particle density model provided a better fit than the log-parabola one. The X-ray flux and the normalized particle density at an energy less than the break one were found to anticorrelate with the index before the break. However, a stronger correlation between the density and index was obtained when a delay of ∼60 ks was introduced. The amplitude of the normalized particle density variation |Δnγ/nγ| ∼ 0.1 was found to be less than that of the index ΔΓ ∼ 0.5. We model the amplitudes and the time delay in a scenario where the particle acceleration time-scale varies on a time-scale comparable to itself. In this framework, the rest-frame acceleration time-scale is estimated to be ∼1.97 × 105 s and the emission region size to be ∼6.73 × 1015 cm.
Deciphering balanced translocations in infertile males by next-generation sequencing to identify candidate genes for spermatogenesis disorders
Authors: Yammine T , Reynaud N , Lejeune H , Diguet F , Rollat-Farnier P A , Labalme A , Plotton I , Farra C , Sanlaville D , Chouery E , Schluth-Bolard C
Published: April 2021

Male infertility affects about 7% of the general male population. Balanced structural chromosomal rearrangements are observed in 0.4–1.4% of infertile males and are considered as a well-established cause of infertility. However, underlying pathophysiological mechanisms still need to be clarified. A strategy combining standard and high throughput cytogenetic and molecular technologies was applied in order to identify the candidate genes that might be implicated in the spermatogenesis defect in three male carriers of different balanced translocations. Fluorescence in situ hybridization (FISH) and whole-genome paired-end sequencing were used to characterize translocation breakpoints at the molecular level while exome sequencing was performed in order to exclude the presence of any molecular event independent from the chromosomal rearrangement in the patients. All translocation breakpoints were characterized in the three patients. We identified four variants: a position effect on LACTB2 gene in Patient 1, a heterozygous CTDP1 gene disruption in Patient 2, two single-nucleotide variations (SNVs) in DNAH5 gene and a heterozygous 17q12 deletion in Patient 3. The variants identified in this study need further validation to assess their roles in male infertility. This study shows that beside the mechanical effect of structural rearrangement on meiosis, breakpoints could result in additional alterations such as gene disruption or position effect. Moreover, additional SNVs or copy number variations may be fortuitously present and could explain the variable impact of chromosomal rearrangements on spermatogenesis. In conclusion, this study confirms the relevance of combining different cytogenetic and molecular techniques to investigate patients with spermatogenesis disorders and structural rearrangements on genomic scale.
Prey utilization by Neptunea arthritica (Caenogastropoda: Buccinidae): predation on gastropods and size-related variation
Authors: Yamakami Ryusei , Wada Satoshi
Published: April 2021

The whelk Neptunea arthritica (Buccinidae) is a common fishery species in Hokkaido, northern Japan. Although ecological information is needed for fisheries management, there is only one paper examining the foraging ecology of this species and it reported that N. arthritica preyed mainly on the invasive mussel Mytilus galloprovincialis. To date, no studies have examined utilization of native prey species by this whelk. Here, we report the findings of a study on the native prey utilization by N. arthritica in an area where M. galloprovincialis is not present. We conducted line transect sampling every month from May 2018 to May 2019 on the western coast of Hakodate Bay, southwestern Hokkaido, Japan. Prey items were composed mostly of gastropods (72%), followed by bivalves (24%) and only a small amount of carrion (<4%). Overlapping spatial distributions were observed among size classes of N. arthritica, while the prey utilization varied with body size. Small individuals (<30 mm in shell height) preyed mainly on the small colloniid gastropod Homalopoma sangarense, while larger individuals (>40 mm) preyed mainly on two tegulid gastropods (Chlorostoma lischkei and Omphalius rusticus) and two venerid bivalves (Protothaca euglypta and Ruditapes philippinarum). There were positive size relationships between whelk body size and prey size for prey categories (Vetigastropoda, Caenogastropoda and Bivalvia) and even for the same prey species (H. sangarense, O. rusticus and P. euglypta). These results suggest that N. arthritica is a predator of mobile gastropods, especially during its early life stage, in areas without the invasive Mediterranean mussel. It is possible that the foraging strategy of N. arthritica may differ quite markedly between areas with and without the invasive mussel.
AnnotSV and knotAnnotSV: a web server for human structural variations annotations, ranking and analysis
Authors: Geoffroy Véronique , Guignard Thomas , Kress Arnaud , Gaillard Jean-Baptiste , Solli-Nowlan Tor , Schalk Audrey , Gatinois Vincent , Dollfus Hélène , Scheidecker Sophie , Muller Jean
Published: April 2021

With the dramatic increase of pangenomic analysis, Human geneticists have generated large amount of genomic data including millions of small variants (SNV/indel) but also thousands of structural variations (SV) mainly from next-generation sequencing and array-based techniques. While the identification of the complete SV repertoire of a patient is getting possible, the interpretation of each SV remains challenging. To help identifying human pathogenic SV, we have developed a web server dedicated to their annotation and ranking (AnnotSV) as well as their visualization and interpretation (knotAnnotSV) freely available at the following address: https://www.lbgi.fr/AnnotSV/. A large amount of annotations from >20 sources is integrated in our web server including among others genes, haploinsufficiency, triplosensitivity, regulatory elements, known pathogenic or benign genomic regions, phenotypic data. An ACMG/ClinGen compliant prioritization module allows the scoring and the ranking of SV into 5 SV classes from pathogenic to benign. Finally, the visualization interface displays the annotated SV in an interactive way including popups, search fields, filtering options, advanced colouring to highlight pathogenic SV and hyperlinks to the UCSC genome browser or other public databases. This web server is designed for diagnostic and research analysis by providing important resources to the user.
Load-Sharing Classification Score as Supplemental Grading System in the Decision-Making Process for Patients With Thoracolumbar Injury Classification and Severity 4
Authors: Alan Nima , Donohue Joseph , Ozpinar Alp , Agarwal Nitin , Kanter Adam S , Okonkwo David O , Hamilton D Kojo
Published: April 2021

BACKGROUND

Patients with Thoracolumbar Injury Classification and Severity (TLICS) score of 4 fall into a gray zone between surgical and conservative management. The integrity of posterior ligamentous complex (PLC) evaluated by magnetic resonance imaging (MRI) contributes to surgical decision-making. Load-sharing classification (LSC) may provide a modifier to further guide decision-making in these patients.

OBJECTIVE

To evaluate associations between LSC score and MRI acquisition, compromise of PLC on MRI, and surgical intervention in TLICS 4 patients.

METHODS

A cohort of 111 neurologically intact patients with isolated thoracolumbar burst fracture with TLICS 4 was evaluated. LSC score was determined based on degree of comminution (1-3), apposition (1-3), and kyphosis (1-3), total composite score of 3 to 9.

RESULTS

Overall, 44 patients underwent MRI, 15 had PLC injury, and 32 (28.8%) underwent surgery. LSC score was higher in patients who had an MRI (median 6 vs 3, P < .001) and patients who had surgery (median 7 vs 4, P < .001). In univariate logistic regression, LSC score was associated with MRI acquisition (odds ratio [OR] 1.7; 1.32-2.12; P < .001), presence of PLC injury on MRI (OR 1.5; 1.2-2.0; P = .002) and, in multivariate logistic regression, undergoing surgical intervention (OR 3.7; 2.3-5.9; P < .001), independent of MRI or PLC injury.

CONCLUSION

LSC score in neurologically intact patients with isolated thoracolumbar burst fracture with TLICS 4 was independently associated with operative intervention. The application of LSC may further guide decision-making in this patient group.
Non-Hodgkin lymphoma of bone of the femur and humerus: a case report and review of the literature
Authors: Mremi Alex , Pyuza Jeremia J , Ahmad Bilal , Andongolile Alice A , Sadiq Adnan , Yahaya James J , Szuhai Karoly , Hogendoorn Pancras C W
Published: April 2021

Lymphoma of bone is a rare neoplasm composed of malignant lymphoid cells, producing a tumefactive lesion within bone. We report a 13-year-old male who presented with progressively increasing swellings at the right shoulder and right mid-thigh for one month. Radiological images revealed lytic destructive lesions associated with soft tissue masses in both sites and a pathological fracture on the right humerus. The patient had no significant medical history. Histological, immunohistochemical and fluorescent in-situ hybridization assessment of biopsies from the lesions confirmed the diagnosis of primary non-Hodgkin lymphoma of bone. Unfortunately, due to coronavirus disease 2019 outbreak, the patient was unable to follow-up treatment and died shortly after establishment of the diagnosis. Delay in diagnosis and treatment is of serious concern when it comes to improve the prognosis of patients with this disease.
Stress memory gene FaHSP17.8-CII controls thermotolerance via remodeling PSII and ROS signaling in tall fescue
Authors: Bi Aoyue , Wang Tao , Wang Guangyang , Zhang Liang , Wassie Misganaw , Amee Maurice , Xu Huawei , Hu Zhengrong , Liu Ao , Fu Jinmin , Chen Liang , Hu Tao
Published: April 2021

High temperature is the most limiting factor in the growth of cool-season turfgrass. To cope with high-temperature stress, grass often adopt a memory response by remembering one past recurring stress and preparing a quicker and more robust reaction to the next stress exposure. However, little is known about how stress memory genes regulate the thermomemory response in cool-season turfgrass. Here, we characterized a transcriptional memory gene, Fa-heat shock protein 17.8 Class II (FaHSP17.8-CII) in a cool-season turfgrass species, tall fescue (Festuca arundinacea Schreb.). The thermomemory of FaHSP17.8-CII continued for more than 4 d and was associated with a high H3K4me3 level in tall fescue under heat stress (HS). Furthermore, heat acclimation or priming (ACC)-induced reactive oxygen species (ROS) accumulation and photosystem II (PSII) electron transport were memorable, and this memory response was controlled by FaHSP17.8-CII. In the fahsp17.8-CII mutant generated using CRISPR/Cas9, ACC+HS did not substantially block the ROS accumulation, the degeneration of chloroplast ultra-structure, and the inhibition of PSII activity compared with HS alone. However, overexpression of FaHSP17.8-CII in tall fescue reduced ROS accumulation and chloroplast ultra-structure damage, and improved chlorophyll content and PSII activity under ACC+HS compared with that HS alone. These findings unveil a FaHSP17.8-CII–PSII-ROS module regulating transcriptional memory to enhance thermotolerance in cool-season turfgrass.
A Systematic Review of Practiced-Based Research of Complementary and Integrative Health Therapies as Provided for Pain Management in Clinical Settings: Recommendations for the Future and a Call to Action
Authors: Dyer Natalie L , Surdam Jessica , Dusek Jeffery A
Published: April 2021

Objective

The goal of this systematic review was to evaluate practice-based, real-world research of individualized complementary and integrative health (CIH) therapies for pain as provided in CIH outpatient clinics.

Methods

A systematic review was conducted on articles in PubMed, Ovid, Cochrane, Web of Science, Scopus, and Embase published through December 2020. The study was listed in the PROSPERO database (CRD42020159193). Major categories of variables extracted included study details and demographics, interventions, and outcomes.

Results

The literature search yielded 3,316 records, with 264 assessed for full-text review. Of those, 23 studies (including ∼8,464 patients) were specific to pain conditions as a main outcome. Studies included chiropractic, acupuncture, multimodal individualized intervention/programs, physiotherapy, and anthroposophic medicine therapy. Retention rates ranged from 53% to 91%, with studies offering monetary incentives showing the highest retention. The 0–10 numerical rating scale was the most common pain questionnaire (n = 10; 43% of studies), with an average percent improvement across all studies and time points of 32% (range: 18–60%).

Conclusions

Findings from this systematic review of practice-based, real-word research indicate that CIH therapies exert positive effects on various pain outcomes. Although all studies reported beneficial impacts on one or more pain outcomes, the heterogeneous nature of the studies limits our overall understanding of CIH as provided in clinical settings. Accordingly, we present numerous recommendations to improve publication reporting and guide future research. Our call to action is that future practice-based CIH research is needed, but it should be more expansive and conducted in association with a CIH scientific society with academic and health care members.
The synergistic efficacy of hydroxychloroquine with methotrexate is accompanied by increased erythrocyte mean corpuscular volume
Authors: Shipa Muhammad Ruhul Amin , Yeoh Su-Ann , Embleton-Thirsk Andrew , Mukerjee Dev , Ehrenstein Michael R
Published: April 2021

Objectives

To determine whether concomitant HCQ modulates the increase in erythrocyte mean corpuscular volume (MCV) caused by MTX therapy, and whether this is associated with improved clinical response in RA.

Methods

A retrospective observational analysis was conducted on two independent hospital datasets of biologic-naïve, early-RA patients who started oral MTX. Baseline characteristics, DAS28-ESR and monthly MCV after starting MTX were obtained. Conventional and machine-learning statistical approaches were applied to the discovery cohort (Cohort 1, 655 patients) and results validated using Cohort 2 (225 patients).

Results

HCQ therapy with MTX was associated with a 2-fold increase in the likelihood of response defined in this study as clinical remission or low disease activity at 6 months (P <0.001). The improved clinical outcome of combination HCQ and MTX therapy was associated with an accelerated rise in MCV from 2 months after commencing therapy. The increase in MCV at 3 months was equivalent to the contemporaneous reduction in the DAS (DAS28-ESR) in predicting clinical response at 6 months. Using latent class mixed modelling, five trajectories of MCV change over 6 months from baseline were identified. The odds ratio of response to treatment was 16.2 (95% CI 5.7, 46.4, P <0.001) in those receiving combination therapy classified within the MCV elevation >5 fl class, which contained the most patients, compared with MTX alone.

Conclusion

Our data provide mechanistic insight into the synergistic clinical benefit of concomitant HCQ with MTX, boosting the rise in MCV, which could serve as a companion biomarker of treatment response.
A systematic review and meta-analysis of the incidence rate of Takayasu arteritis
Authors: Rutter Megan , Bowley Jonathan , Lanyon Peter C , Grainge Matthew J , Pearce Fiona A
Published: April 2021

Objectives

Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK.

Methods

Three databases (MEDLINE, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle–Ottawa scale. Further subgroup analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg’s funnel plot.

Results

The incidence rate for TAK was 1.11 per million person-years (95% CI 0.70–1.76). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39–2.90).

Conclusions

TAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.
The intergenerational transmission of gender norms—why and how adolescent males with working mothers matter for female labour market outcomes
Authors: Schmitz Sophia , Spiess C Katharina
Published: April 2021

Social norms are put forward as a prominent explanation for the changing labour supply decisions of women. This paper studies the intergenerational transmission of these norms, examining how they affect subsequent female labour supply decisions, taking into account not only the early socialization of women but also that of their partner. Using large representative panel data sets from West Germany, results suggest that women with partners who grew up with a working mother are more likely to participate in the labour force, work longer hours and earn higher labour income. The main contribution of our study is that we assess a variety of potential mechanisms for this intergenerational link. We find no evidence that this finding reflects assortative mating; rather, analysis suggests that the partner’s preferences are based on their experiences with the employment of their mothers and play a decisive role for the labour supply decision of partnered women. Moreover, we identify various effect heterogeneities, finding stronger associations for women with potentially less bargaining power. Our results suggest that policy measures supporting the labour force participation of today’s mothers will increase the female labour force participation of the next generation.
Discrimination and sleep among Asians and Pacific Islanders adults
Authors: Ogbenna Bethany Townsend , Ryu Soomin , Lee Sunmin , Slopen Natalie
Published: April 2021

Study Objectives

To examine the association between discrimination and sleep duration and difficulty among Asians and Pacific Islanders (APIs) in the United States, and to test nativity and ethnic identity (EI) as effect modifiers.

Methods

This cross-sectional study of 1,765 adults from the National Epidemiology Study of Alcohol and Related Conditions III, assessed discrimination using the Experiences of Discrimination scale. Discrimimation was classified as low, moderate, and high. Regression models were used to examine self-reported sleep duration and difficulty.

Results

In bivariate analyses, individuals with high discrimination had the shortest sleep and reported sleep difficulty most often. Using linear models adjusted for sociodemographic and health characteristics, moderate and high discrimination were associated with 9 min (standard error [SE]: 4.8, p < .10) and 14.4 min (SE: 6.0, p < .05) less sleep, respectively, relative to low discrimination. Individuals with moderate and high discrimination had higher prevalence of sleep difficulty compared to those with low discrimination (prevalence ratio [PR]: 1.51, 95% confidence interval [CI]: 1.14–1.99 and PR: 1.73, 95% CI: 1.33–2.24, respectively). Interaction effect was observed in sleep difficulty by nativity and EI, but not duration. The association between discrimination and sleep difficulty was stronger among U.S.-born relative to foreign-born participants. Among participants with low EI, moderate and high discrimination were associated with sleep difficulty, whereas among those with high EI, only high discrimination displayed this association.

Conclusions

Discrimination is associated with sleep duration and difficulty, and varies by nativity and EI. Research is needed to improve sleep among APIs that experience discrimination.
Stability and Change in German Parents’ Childcare Patterns Across Two Decades
Authors: Steinbach Anja , Schulz Florian
Published: April 2021

Although German mothers’ labor force participation has increased in recent decades, German men’s participation in domestic labor has not increased proportionally. Thus, mothers still face a “double burden.” We analyzed the total time parents spent on childcare and on various particular activities, such as learning with children, playing with children, basic childcare, talking with children, managing children’s activities, and reading with children. We identified a very slow gender convergence in childcare patterns in Germany over the last two decades. However, as in other Western countries, German parents’ division of childcare remains unequal; mothers do much more routine care and spend more time overall on care than fathers.
Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy
Authors: Gao Jiapan , Che Delu , Du Xueshan , Zheng Yi , Jing Huiling , Wang Nan
Published: April 2021

Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.
Clinical Outcomes of Children Diagnosed Dengue-Associated Acute Liver Failure with or without N-Acetylcysteine Treatment: A Retrospective Cohort Study
Authors: Sriphongphankul Hansa , Liabsuetrakul Tippawan , Osatakul Seksit
Published: April 2021

Objectives

N-acetylcysteine (NAC) has been shown to prevent hepatic damage and improve microcirculatory blood flow and oxygen delivery to the tissue. Previous studies have proposed the benefit of NAC in dengue-associated acute liver failure (ALF). However, most studies are descriptive and lack comparison between groups. We aimed to compare the ALF resolution rate and mortality rate of those who received and did not receive NAC treatment.

Methods

A retrospective cohort study was conducted among children aged <15 years who were diagnosed with dengue-associated ALF at a tertiary hospital in Thailand, between January 2002 and July 2019. Demographic and clinical information were collected. Main outcomes were ALF resolution and mortality rate.

Results

Thirty-three patients were included of which 16 received NAC treatment (48.5%). Mean ages were 8.5 years (SD 3.7) and mean onset of ALF was 6.3 days (SD 1.6) after onset of fever. The grading of hepatic encephalopathy (HE) and organ failure was not significantly different between the two groups. In the NAC group, 13/16 children were prescribed 100 mg/kg/day of NAC until INR <2 without HE or <1.5 with HE. NAC was initiated 1.1 days (SD 0.3) after the ALF diagnosis. The NAC group showed a higher rate of ALF resolution (75% vs. 53% in the non-NAC group, p = 0.34) with a lower mortality rate (31% vs. 53%, p = 0.36). Side effects of NAC were not found.

Conclusion

NAC may be beneficial in dengue-associated pediatric ALF. Further well-designed randomized control trials should be carried out.
Early Pension Claiming and Expected Longevity: A Register-Based Study on the Take-up of the Partial Old-Age Pension in Finland
Authors: Nivalainen Satu
Published: April 2021

As of February 2017, Finns have been able to claim a partial old-age pension early at age 61 independent of their working hours or earnings. Focusing on the take-up of the partial old-age pension in Finland, this article investigates whether early pension claiming is associated with expected longevity. We assume parental longevity to signal expected longevity. We use total register data on those eligible to claim a partial pension at age 61 in 2018 or 2019 and link this data to the information on their parents’ birth and death dates. To our knowledge, there exists no previous register-based study that uses parental longevity to explain pension claiming behavior. Since the longevity of the same-sex parent in particular influences subjective life expectancy, the variables of interest were the same-sex parent being alive and the age (at death) of the same-sex parent. The baseline results show a negative connection between the same-sex parent being alive and claiming. The connection disappears after controlling for gender, but the negative connection between the age (at death) of the same-sex parent and the claiming remains significant in a fully adjusted model. Known risk factors for shorter longevity, such as being male, having a lower income and wealth, also increase the likelihood of claiming. The results indicate that people take their expected longevity into account when making pension claiming decisions. This may hold critical implications for actuarial neutrality, the key assumption of the pension system design, and can lead to an unexpected increase in public pension expenditure.
Pushing the Needle of Entrepreneurship and Innovation: Where Do Plastic and Reconstructive Surgeons Stand?
Authors: Khetpal Sumun , Reátegui Alvaro , Lopez Joseph , Sacks Justin M. , Prsic Adnan
Published: April 2021

Background:

Plastic and reconstructive surgery has a well-recognized history of disruption and innovation. It remains unclear, however, how the specialty’s priority on innovation materializes into commercialization or bench to bedside led by plastic surgeons.

Methods:

Our analysis utilized Pitchbook (Seattle, Wash.), a market database of companies and investors, for ventures that have designed innovations related to plastic and reconstructive surgery. Companies were categorized into 5 focus areas: provider (outpatient surgical or hospital entity), aesthetics (cosmetics/injectables), devices (instrumentation, lasers, implants), regenerative medicine (tissue engineering/wound healing), and software (digital solutions). Company websites, LinkedIn (Sunnyvale, Calif.) profiles, and Crunchbase (San Francisco, Calif.) were reviewed to determine the leadership roles of plastic surgeons.

Results:

Plastic surgeons primarily serve as advisors, as opposed to founders or chief executive officers (CEOs). Our analysis additionally found that provider and software solutions had a greater degree of plastic surgeon-led leadership, whereas regenerative medicine and device innovation remains less frequented. There was a relatively balanced representation of academic and private plastic surgeons in entrepreneurial pursuits.

Conclusions:

Plastic surgeons typically serve as board advisors, as opposed to founders and CEOs. Reasons for disengagement from leadership roles may include satisfaction with clinical work, time constraint, lack of business knowledge, financial constraint, and opportunity cost associated with starting a venture. To promote participation in innovation, future studies should explore tangible ways to engage in such opportunities. In doing so, plastic surgeons can own the “organ” of innovation, and continue to contribute to the legacy and the advancement of the specialty.
The Impact of the COVID-19 Pandemic on Cleft Care
Authors: Bruce Madeleine K. , Pfaff Miles J. , Anstadt Erin E. , Losee Joseph E. , Goldstein Jesse A.
Published: April 2021

Background:

The COVID-19 pandemic had multiple effects on the provision of health care, including the suspension of elective and nonessential surgeries. The objective of this study was to determine the early effect of the COVID-19 pandemic on the surgical care of patients with cleft lip and/or palate at a high-volume cleft center.

Methods:

A retrospective comparative cohort study of patients with cleft lip and/or palate undergoing lip adhesion, cleft lip and nose repair, and palatoplasty before and during the pandemic was conducted. There were 50 patients in the prepandemic cohort and 53 in the pandemic cohort.

Results:

Mean age at lip adhesion was 3.1 ± 1.1 months prepandemic (n = 8) and 3.5 ± 2.5 months in the pandemic cohort (n = 8) (P= 0.75). One lip adhesion was delayed by 1.6 months. Mean age at cleft lip and nose repair was 6.6 ± 1.9 months prepandemic (n = 23) and 8.0 ± 2.1 months in the pandemic cohort (n = 23) (P= 0.03). Six pandemic cleft lip and nose repairs were delayed; the mean delay was 2.6 ± 1.8 months. The mean age at palatoplasty was 13.9 ± 2.2 months prepandemic (n = 26) and 14.1 ± 2.9 months in the pandemic cohort (n = 26) (P= 0.79). Seven pandemic palatoplasties were delayed; the mean delay was 3.3 ± 1.4 months.

Conclusions:

The COVID-19 pandemic caused delays at each stage of repair for cleft lip and/or palate-related procedures; however, only cleft lip and nose repair were significantly affected. This study emphasizes the importance of remaining vigilant regarding the care of this vulnerable population during this challenging time.