bluuebunny/crossref_metadata_2025 huggingface dataset:
Covariance Between Parent and Child Symptoms Before and During the COVID-19 Pandemic
Authors: Black Sarah R , Evans Miranda L , Aaron Lauren , Brabham David R , Kaplan Rachel M
Published: July 2021

Objective

COVID-19 has had unprecedented effects on American families, including increases in depression, anxiety, and irritability for both parents and children. While parents and children influence each other’s psychological functioning during non-disaster times, this effect may be amplified during times of disaster. The current study investigated how COVID-19 influenced covariance of depressive symptoms and irritability in children and their parents.

Methods

Three hundred and ninety-one parents and their 8- to 17-year-old children (Mage = 10.68 years old, 70% male, 86% White) from a large sample of children and parents, primarily from Southeastern Louisiana, completed self-report measures of depression and irritability approximately 6 weeks into the COVID-19 pandemic, as well as providing retrospective reports of their symptoms prior to the pandemic. Actor–partner interdependence models were used to measure the reciprocal effects of parent symptoms on children and vice versa, both before and during the pandemic.

Results

Actor effects in both the depressive symptoms and irritability models suggested that pre-COVID-19 depressive symptoms and irritability were robust predictors of early-COVID-19 depressive symptoms and irritability for both parents and children. Partner effects were also detected in the irritability model, in that parental irritability prior to COVID-19 was associated with decreased child irritability during the pandemic. Both before and during the pandemic, associations between parent and child depressive symptoms and irritability scores were weaker in families evidencing greater dysfunction.

Conclusions

Results suggest that COVID-19-related stress is associated with increases in both parent and child symptomatology, and that family relationships likely influence associations between these symptoms.
Abrogation of STAT3 activation cascade by Ginkgolide C mitigates tumourigenesis in lung cancer preclinical model
Authors: Yang Min Hee , Ha In Jin , Lee Seok-Geun , Um Jae-Young , Ahn Kwang Seok
Published: July 2021

Objectives

Ginkgolide C (GGC) isolated from Ginkgo biloba (Ginkgoaceae) leaf can demonstrate pleiotropic pharmacological actions. However, its anti-oncogenic impact in non-small cell lung cancer (NSCLC) model has not been reconnoitered. As signal transducer and activator of transcription 3 (STAT3) cascade can promote tumour growth and survival, we contemplated that GGC may interrupt this signalling cascade to expend its anti-cancer actions in NSCLC.

Methods

The effect of GGC on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation and apoptosis was examined. The in-vivo effect of GGC on the growth of human NSCLC xenograft tumours in athymic nu/nu female mice was also investigated.

Key findings

GGC attenuated the phosphorylation of STAT3 and STAT3 upstream kinases effectively. Exposure to pervanadate modulated GGC-induced down-regulation of STAT3 activation and promoted an elevation in the level of PTPε protein. Indeed, silencing of the PTPε gene reversed the GGC-promoted abrogation of STAT3 activation and apoptosis. Moreover, GGC exposure significantly reduced NSCLC tumour growth without demonstrating significant adverse effects via decreasing levels of p-STAT3 in mice tissues.

Conclusions

Overall, the findings support that GGC may exhibit anti-neoplastic actions by mitigation of STAT3 signalling cascade in NSCLC.
Plant epigenomics for extenuation of abiotic stresses: challenges and future perspectives
Authors: Singh Dharmendra , Chaudhary Priya , Taunk Jyoti , Kumar Singh Chandan , Sharma Shristi , Singh Vikram Jeet , Singh Deepti , Chinnusamy Viswanathan , Yadav Rajbir , Pal Madan
Published: July 2021

Climate change has escalated abiotic stresses, leading to adverse effects on plant growth and development, eventually having deleterious consequences on crop productivity. Environmental stresses induce epigenetic changes, namely cytosine DNA methylation and histone post-translational modifications, thus altering chromatin structure and gene expression. Stable epigenetic changes are inheritable across generations and this enables plants to adapt to environmental changes (epipriming). Hence, epigenomes serve as a good source of additional tier of variability for development of climate-smart crops. Epigenetic resources such as epialleles, epigenetic recombinant inbred lines (epiRILs), epigenetic quantitative trait loci (epiQTLs), and epigenetic hybrids (epihybrids) can be utilized in epibreeding for improving stress tolerance of crops. Epigenome engineering is also gaining momentum for developing sustainable epimarks associated with important agronomic traits. Different epigenome editing tools are available for creating, erasing, and reading such epigenetic codes in plant genomes. However, epigenome editing is still understudied in plants due to its complex nature. Epigenetic interventions such as epi-fingerprinting can be exploited in the near future for health and quality assessment of crops under stress conditions. Keeping in view the challenges and opportunities associated with this important technology, the present review intends to enhance understanding of stress-induced epigenetic changes in plants and its prospects for development of climate-ready crops.
A tomato receptor-like cytoplasmic kinase, SlZRK1, acts as a negative regulator in wound-induced jasmonic acid accumulation and insect resistance
Authors: Sun Zongyan , Zang Yudi , Zhou Leilei , Song Yanping , Chen Di , Zhang Qiaoli , Liu Chengxia , Yi Yuetong , Zhu Benzhong , Fu Daqi , Zhu Hongliang , Qu Guiqin
Published: July 2021

Jasmonates accumulate rapidly and act as key regulators in response to mechanical wounding, but few studies have linked receptor-like cytoplasmic kinases (RLCKs) to wound-induced jasmonic acid (JA) signaling cascades. Here, we identified a novel wounding-induced RLCK-XII-2 subfamily member (SlZRK1) in tomato (Solanum lycopersicum) that was closely related to Arabidopsis HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases 1 based on phylogenetic analysis. SlZRK1 was targeted to the plasma membrane of tobacco mesophyll protoplasts as determined by transient co-expression with the plasma membrane marker mCherry–H+-ATPase. Catalytic residue sequence analysis and an in vitro kinase assay indicated that SlZRK1 may act as a pseudokinase. To further analyse the function of SlZRK1, we developed two stable knock-out mutants by CRISPR/Cas9. Loss of SlZRK1 significantly altered the expression of genes involved in JA biosynthesis, salicylic acid biosynthesis, and ethylene response. Furthermore, after mechanical wounding treatment, slzrk1 mutants increased transcription of early wound-inducible genes involved in JA biosynthesis and signaling. In addition, JA accumulation after wounding and plant resistance to herbivorous insects also were enhanced. Our findings expand plant regulatory networks in the wound-induced JA production by adding RLCKs as a new component in the wound signal transduction pathway.
COVID-19 Crisis: The Pandemic Highlights the Unique Training and Skills of Military Physicians Afforded by Military-Specific Graduate Medical Education
Authors: Shahbodaghi David , Farnell Edwin
Published: July 2021

Military physicians trained in military Graduate Medical Education programs are uniquely prepared to lead in austere and chaotic environments based on formal and informal curricula taught in military treatment facilities. The coronavirus disease-2019 pandemic highlighted this reality when military-trained physician leaders were challenged to lead change directly from the front.
Cancers of Unknown Primary: A Descriptive Study in the U.S. Military Health System
Authors: Bytnar Julie A , Lin Jie , Moncur Joel T , Shriver Craig D , Zhu Kangmin
Published: July 2021

Introduction

Cancers of unknown primary (CUP) are defined as histologically confirmed metastatic cancers that do not have an identified primary site of origin despite an appropriate diagnostic workup. Although accessibility to and quality of medical care influence diagnosis of cancer including CUP, previous studies describing CUP have generally been conducted in patients with various accessibilities to care. This study aimed to describe the demographic, histologic, and temporal trend characteristics of CUP patients in the DoD Cancer Registry of the Military Health System (MHS), which provides universal health care access, reducing the potential effects of accessibility to care on research results.

Materials and Methods

The data were obtained from the DoD’s Automated Central Tumor Registry (ACTUR), which collects cancer data from beneficiaries who were diagnosed or received treatment in the MHS. We described the demographic and histologic distributions in CUP patients aged 18 years or older diagnosed from 1987 to 2013. We calculated the proportion of CUP patients among all metastatic cancers and the most common histologic categories of those tumors. We then evaluated whether the proportion of histologic types changed over time.

Results

CUP comprised 13.3% of all metastatic cancers in ACTUR during the study period. The majority of CUP within ACTUR was moderately and well-differentiated adenocarcinoma (51.3%) and poorly differentiated carcinomas (23.2%) followed by squamous cell carcinomas (12.5%). The percentages of CUP among metastasized cancers of the same histologic category ranged 12%-15% for moderately and well-differentiated adenocarcinomas, squamous cell, and poorly differentiated carcinomas, and 41%-46% for malignant neuroendocrine carcinomas and undifferentiated neoplasms. However, the percentages varied by sex, race, and age for certain pathologies. The proportion of CUP patients among all metastatic cancer patients has steadily declined from 22.4% to 8.3% from 1987 to 2013.

Conclusion

The proportion and trends of CUP in the ACTUR were generally consistent with other descriptive CUP studies. This study provides a description of CUP in a health care system with universal access in the USA and provides a foundation for future studies on CUP.
The evolution of merger fraction of galaxies at z < 0.6 depending on the star formation mode in the AKARI NEP-Wide Field
Authors: Kim Eunbin , Hwang Ho Seong , Jeong Woong-Seob , Kim Seong Jin , Burgarella Denis , Goto Tomotsugu , Hashimoto Tetsuya , Jo Young-Soo , Lee Jong Chul , Malkan Matthew , Pearson Chris , Shim Hyunjin , Toba Yoshiki , Ho Simon C-C , Santos Daryl Joe , Ikeda Hiroyuki , Kim Helen K , Miyaji Takamitsu , Matsuhara Hideo , Oi Nagisa , Takagi Toshinobu , Wang Ting-Wen
Published: July 2021

We study the galaxy merger fraction and its dependence on star formation mode in the 5.4 deg2 of the North Ecliptic Pole-Wide Field. We select 6352 galaxies with AKARI 9 $\mu$m detections, and identify mergers among them using the Gini coefficient and M20 derived from the Subaru/Hyper Suprime-Cam (HSC) optical images. We obtain the total infrared luminosity and star formation rate of galaxies using the spectral energy distribution templates based on one band, AKARI$9\, \mu$m. We classify galaxies into three different star formation modes (i.e. starbursts, main-sequence, and quiescent galaxies) and calculate the merger fractions for each. We find that the merger fractions of galaxies increase with redshift at z < 0.6. The merger fractions of starbursts are higher than those of main-sequence and quiescent galaxies in all redshift bins. We also examine the merger fractions of far-infrared-detected galaxies that have at least one detection from Herschel/Spectral and Photometric Imaging Receiver (SPIRE). We find that Herschel-detected galaxies have higher merger fraction compared to non-Herschel-detected galaxies, and both Herschel-detected and non-Herschel-detected galaxies show clearly different merger fractions depending on the star formation modes.
Radio afterglow of magnetars’ giant flares
Authors: Mehta Riddhi , Barkov Maxim , Lyutikov Maxim
Published: July 2021

We develop a model for the radio afterglow of the giant flare of SGR 1806-20 arising due to the interaction of magnetically dominated cloud, an analogue of Solar Coronal Mass Ejections (CMEs), with the interstellar medium (ISM). The CME is modelled as a spheromak-like configuration. The CME is first advected with the magnetar’s wind and later interacts with the ISM, creating a strong forward shock and complicated backwards exhaust flow. Using 3D magnetohydrodynamic simulations, we study various relative configurations of the magnetic field of the CME with respect to the ISM’s magnetic field. We show that the dynamics of the forward shock mostly follows the Sedov–Taylor blastwave, while the internal structure of the shocked medium is considerably modified by the back flow, creating a multiple shock configuration. We calculate synthetic synchrotron emissivity maps and light curves using two assumptions: (i) magnetic field compression; (ii) amplification of the magnetic field at the shock. We find that models with magnetic field amplification account better for the observed radio emission.
Methylglyoxal induces chromosomal instability and mitotic dysfunction in lymphocytes
Authors: Donnellan Leigh , Simpson Bradley , Dhillon Varinderpal S , Costabile Maurizio , Fenech Michael , Deo Permal
Published: July 2021

Type 2 diabetes is associated with elevated levels of DNA damage, in particular micronuclei (MNi) which are formed by acentric chromosome fragments caused by double-stranded DNA breaks (DSBs), or whole chromosomes which fail to segregate during mitosis. We investigated if methylglyoxal (MGO), a reactive dicarbonyl known to be elevated in type 2 diabetes is capable of increasing chromosomal instability and DNA damage as measured by the cytokinesis block micronucleus cytome (CBMNcyt) assay in B-lymphoblastoid WIL2-NS cells and primary peripheral blood lymphocytes (PBL). We also investigated the level of various dicarbonyl stress biomarkers, including extracellular and intracellular MGO, protein and MGO modifications of DNA. WIL2-NS cells exposed to either MGO or a glyoxalase 1 inhibitor showed increases in MNi and nuclear buds, which were associated with an increase in intracellular MGO. DNA damage in the form of MNi and nucleoplasmic bridges were observed in primary PBL exposed to 10 µM MGO, suggesting low concentrations of MGO may be genotoxic. Furthermore, we showed, using fluorescent in situ hybridisation, that the majority of MNi caused by MGO in WIL2-NS cells were caused by whole chromosome loss events, rather than DSBs. Our data suggest that MGO, a reactive metabolite elevated in type 2 diabetes and other pathologies, can affect genomic integrity by impairing chromosome segregation during mitosis.
Protein cofactors and substrate influence Mg2+-dependent structural changes in the catalytic RNA of archaeal RNase P
Authors: Marathe Ila A , Lai Stella M , Zahurancik Walter J , Poirier Michael G , Wysocki Vicki H , Gopalan Venkat
Published: July 2021

The ribonucleoprotein (RNP) form of archaeal RNase P comprises one catalytic RNA and five protein cofactors. To catalyze Mg2+-dependent cleavage of the 5′ leader from pre-tRNAs, the catalytic (C) and specificity (S) domains of the RNase P RNA (RPR) cooperate to recognize different parts of the pre-tRNA. While ∼250–500 mM Mg2+ renders the archaeal RPR active without RNase P proteins (RPPs), addition of all RPPs lowers the Mg2+ requirement to ∼10–20 mM and improves the rate and fidelity of cleavage. To understand the Mg2+- and RPP-dependent structural changes that increase activity, we used pre-tRNA cleavage and ensemble FRET assays to characterize inter-domain interactions in Pyrococcus furiosus (Pfu) RPR, either alone or with RPPs ± pre-tRNA. Following splint ligation to doubly label the RPR (Cy3-RPRC domain and Cy5-RPRS domain), we used native mass spectrometry to verify the final product. We found that FRET correlates closely with activity, the Pfu RPR and RNase P holoenzyme (RPR + 5 RPPs) traverse different Mg2+-dependent paths to converge on similar functional states, and binding of the pre-tRNA by the holoenzyme influences Mg2+ cooperativity. Our findings highlight how Mg2+ and proteins in multi-subunit RNPs together favor RNA conformations in a dynamic ensemble for functional gains.
Wnt target enhancer regulation by a CDX/TCF transcription factor collective and a novel DNA motif
Authors: Ramakrishnan Aravinda-Bharathi , Chen Lisheng , Burby Peter E , Cadigan Ken M
Published: July 2021

Transcriptional regulation by Wnt signalling is primarily thought to be accomplished by a complex of β-catenin and TCF family transcription factors (TFs). Although numerous studies have suggested that additional TFs play roles in regulating Wnt target genes, their mechanisms of action have not been investigated in detail. We characterised a Wnt-responsive element (WRE) downstream of the Wnt target gene Axin2 and found that TCFs and Caudal type homeobox (CDX) proteins were required for its activation. Using a new separation-of-function TCF mutant, we found that WRE activity requires the formation of a TCF/CDX complex. Our systematic mutagenesis of this enhancer identified other sequences essential for activation by Wnt signalling, including several copies of a novel CAG DNA motif. Computational and experimental evidence indicates that the TCF/CDX/CAG mode of regulation is prevalent in multiple WREs. Put together, our results demonstrate the complex nature of cis- and trans- interactions required for signal-dependent enhancer activity.
Transcriptional silencing of fetal hemoglobin expression by NonO
Authors: Li Xinyu , Chen Mengxia , Liu Biru , Lu Peifen , Lv Xiang , Zhao Xiang , Cui Shuaiying , Xu Peipei , Nakamura Yukio , Kurita Ryo , Chen Bing , Huang David C S , Liu De-Pei , Liu Ming , Zhao Quan
Published: July 2021

Human fetal globin (γ-globin) genes are developmentally silenced after birth, and reactivation of γ-globin expression in adulthood ameliorates symptoms of hemoglobin disorders, such as sickle cell disease (SCD) and β-thalassemia. However, the mechanisms by which γ-globin expression is precisely regulated are still incompletely understood. Here, we found that NonO (non-POU domain-containing octamer-binding protein) interacted directly with SOX6, and repressed the expression of γ-globin gene in human erythroid cells. We showed that NonO bound to the octamer binding motif, ATGCAAAT, of the γ-globin proximal promoter, resulting in inhibition of γ-globin transcription. Depletion of NonO resulted in significant activation of γ-globin expression in K562, HUDEP-2, and primary human erythroid progenitor cells. To confirm the role of NonO in vivo, we further generated a conditional knockout of NonO by using IFN-inducible Mx1-Cre transgenic mice. We found that induced NonO deletion reactivated murine embryonic globin and human γ-globin gene expression in adult β-YAC mice, suggesting a conserved role for NonO during mammalian evolution. Thus, our data indicate that NonO acts as a novel transcriptional repressor of γ-globin gene expression through direct promoter binding, and is essential for γ-globin gene silencing.
Steady axisymmetric vortices in radial stagnation flows
Authors: Rajamanickam Prabakaran , Weiss Adam D
Published: July 2021

A class of axisymmetric vortex solutions superposed upon radial stagnation flows is described. The new vortex solutions generalize the classical Burgers’ vortex and Sullivan’s vortex solutions in the presence of a volumetric line source at the symmetry axis, the former approaching the Burgers’ vortex sheet when the source strength becomes very large. The stability of the generalized Burgers’ vortex is studied. In a different manner from the classical solution, the generalized Burgers’ vortices are found to be unstable for two-dimensional disturbances when the vortex Reynolds number is increased above a critical value, for a fixed strength of the volumetric source.
Fluorodeoxyglucose positron emission tomography–computed tomography findings in a first series of 10 patients with polyarteritis nodosa
Authors: Fagart Alexandre , Machet Thomas , Collet Guillaume , Quéméneur Thomas , Ben Ticha Rim , Verstraete Marion , Le Gouellec Noémie , Demailly Franck , Rousselin Clémentine
Published: July 2021

Objective

18F-fluorodeoxyglucose PET/CT (FDG-PET/CT) is widely used in patients with large vessel vasculitis. The benefits of FDG-PET/CT in PAN has only ever been assessed in three case reports. Our aim was to describe FDG-PET/CT findings in 10 patients with newly diagnosed PAN.

Methods

This was a retrospective study of patients with PAN who underwent FDG-PET/CT at diagnosis between 2017 and 2020. The FDG-PET/CT data were analysed retrospectively.

Results

Ten patients were included: nine men and one woman with a median age of 67 years (range 43–78). PAN was diagnosed according to ACR criteria in nine patients and histologically in one. All patients had high CRP levels (median 223 mg/l). The main FDG-PET/CT abnormality was increased tracer uptake in the muscles, particularly in the connective tissue (perimysium, epimysium) (n = 7), and in linear (n = 5) or focal (n = 2) patterns. Increased FDG uptake in large-diameter vessels was observed in four patients, in the humeral (n = 4), femoral (n = 1) and common interosseous arteries (n = 1). Nine patients had bone marrow FDG uptake and six had splenic FDG uptake. Three had synovitis and three had lymph node uptake. One patient had subcutaneous FDG uptake with a ‘leopard skin’ appearance.

Conclusions

FDG-PET/CT seems to be a useful non-invasive imaging technique for diagnosing PAN, particularly in patients with non-specific systemic features. Tracer uptake in muscular connective tissue seems to be a recurrent sign in patients with PAN and may be pathognomonic.
The burden of psoriasis in patients with early psoriatic arthritis
Authors: Kasiem Fazira R , Kok Marc R , Luime Jolanda J , Tchetverikov Ilja , Wervers Kim , Korswagen Lindy-Anne , Denissen Nastasja H A M , Goekoop-Ruiterman Yvonne P M , van Oosterhout Maikel , Fodili Faouzia , Hazes Johanna M W , Vis Marijn ,   CICERO
Published: July 2021

Objectives

Psoriasis impacts health-related quality of life (HRQoL) in PsA patients. However, this is not adequately measured with a general HRQoL questionnaire. The aim of this study was to quantify the degree of psoriasis evolution in PsA patients over the first year of follow-up and to evaluate whether the impact of psoriasis on HRQoL can be adequately measured with a dermatology-specific HRQoL questionnaire.

Methods

Data were used from PsA patients in the Dutch south west Early Psoriatic Arthritis cohort. Psoriasis severity was measured with the Psoriasis Area and Severity Index (PASI). Dermatology-specific HRQoL was assessed with the Skindex-17 questionnaire. We used a Sankey diagram to illustrate the evolution of psoriasis severity during the first year of follow-up. To assess the association between psoriasis severity and the symptoms and psychosocial subscale of the Skindex-17, a linear regression analysis with hierarchical variable selection and zero-inflated negative binominal regression analysis were performed, respectively.

Results

We included 644 patients; 109 (17%) patients had no psoriasis (PASI = 0), 456 (71%) had mild psoriasis (PASI < 7), 56 (9%) had moderate psoriasis (PASI 7–12) and 23 (4%) had severe psoriasis (PASI > 12). Psoriasis severity did not fluctuate much during the first year. PASI was significantly associated with both subscales of the Skindex-17 at baseline and 12 months.

Conclusion

Psoriasis severity in PsA patients is mostly mild but impacts HRQoL when measured using a dermatology-specific HRQoL questionnaire. For optimal management of PsA patients, we recommend rheumatologists acquire information on skin burden by using a dermatology-specific HRQoL questionnaire.
Theta-gamma coupling during REM sleep depends on breathing rate
Authors: Hammer Maximilian , Schwale Chrysovalandis , Brankačk Jurij , Draguhn Andreas , Tort Adriano B L
Published: July 2021

Temporal coupling between theta and gamma oscillations is a hallmark activity pattern of several cortical networks and becomes especially prominent during REM sleep. In a parallel approach, nasal breathing has been recently shown to generate phase-entrained network oscillations which also modulate gamma. Both slow rhythms (theta and respiration-entrained oscillations) have been suggested to aid large-scale integration but they differ in frequency, display low coherence, and modulate different gamma sub-bands. Respiration and theta are therefore believed to be largely independent. In the present work, however, we report an unexpected but robust relation between theta-gamma coupling and respiration in mice. Interestingly, this relation takes place not through the phase of individual respiration cycles, but through respiration rate: the strength of theta-gamma coupling exhibits an inverted V-shaped dependence on breathing rate, leading to maximal coupling at breathing frequencies of 4–6 Hz. Noteworthy, when subdividing sleep epochs into phasic and tonic REM patterns, we find that breathing differentially relates to theta-gamma coupling in each state, providing new evidence for their physiological distinctiveness. Altogether, our results reveal that breathing correlates with brain activity not only through phase-entrainment but also through rate-dependent relations with theta-gamma coupling. Thus, the link between respiration and other patterns of cortical network activity is more complex than previously assumed.
Inhibition of testosterone synthesis induced by oral TiO2 NPs is associated with ROS-MAPK(ERK1/2)-StAR signaling pathway in SD rat
Authors: Liu Shanji , Tang Yizhou , Chen Bolu , Zhao Yu , Aguilar Zoraida P , Tao Xueying , Xu Hengyi
Published: July 2021

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in food, medical, and other fields; their reproductive toxicity has been reported in numerous studies. However, the relevant toxicity mechanism still requires further exploration. In this paper, the effect of oral exposure to 500 mg/kg TiO2 NPs (anatase and rutile) in adult male SD rats was studied over 3 and 7 days. Results showed that the total sperm count and testosterone level of 7 days of exposure in serum decreased in the experimental group. Testicular tissue lesions, such as disappearance of Leydig cells, disorder of arrangement of spermatogenic cells in the lumen of convoluted seminiferous tubules, and disorder of arrangement of germ cells, were observed. Meanwhile, the expression of steroidogenic acute regulatory (StAR; the key factors of testosterone synthesis), MAPK (ERK1/2), and phosphorylated ERK1/2 in testes of SD rats after exposure to TiO2 NPs for 7 days decreased, while the malondialdehyde content increased and superoxide dismutase activity decreased in serum. The present study showed that TiO2 NPs could cause reproductive toxicity. Notably, anatase is more toxic than rutile. In addition, exposure to 500 mg/kg TiO2 NPs for 7 days inhibited testosterone synthesis in male rat, which may be related to the reactive oxygen species (ROS)-MAPK (ERK1/2)-StAR signal pathway. Warning that the use of TiO2 NPs should be regulated.
Genome Resource: Draft Genome of Fusarium avenaceum, Strain F156N33, Isolated from the Atmosphere Above Virginia and Annotated Based on RNA Sequencing Data
Authors: Yang Shu , Coleman Jeffrey J. , Vinatzer Boris A.
Published: July 2021

Fusarium avenaceum is a filamentous fungus commonly associated with plants and soil. It is a causal agent of Fusarium head blight (FHB) on maize and small-grain cereals and blights on other plant species, and is one of the very few fungal species known to have ice nucleation activity (i.e., it catalyzes ice formation). Here, we report the draft genome of the ice-nucleation-active F. avenaceum strain F156N33 isolated from the atmosphere above Virginia. The genome assembly is 41,175,306 bp long, consists of 214 contigs, and is predicted to encode 11,233 proteins, which were annotated using RNA-sequencing data obtained from the same strain.
Stringent Response in Bacteria and Plants with Infection
Authors: Petrova Olga , Parfirova Olga , Gogolev Yuri , Gorshkov Vladimir
Published: July 2021

Stringent response (SR), a primary stress reaction in bacteria and plant chloroplasts, is a molecular switch that provides operational stress-induced reprogramming of transcription under conditions of abiotic and biotic stress. Because the infection is a stressful situation for both partners (the host plant and the pathogen), we analyzed the expression of bacterial and plastid SR-related genes during plant–microbial interaction. In the phytopathogenic bacterium Pectobacterium atrosepticum, SpoT-dependent SR was induced after contact with potato or tobacco plants. In plants, two different scenarios of molecular events developed under bacterial infection. Plastid SR was not induced in the host plant potato Solanum tuberosum, which co-evolved with the pathogen for a long time. In this case, the salicylic acid defense pathway was activated and plants were more resistant to bacterial infection. SR was activated in the tobacco Nicotiana tabacum (experimental host) along with activation of jasmonic acid-related genes, resulting in plant death. These results are important to more fully understand the evolutionary interactions between plants and symbionts/pathogens.
High-Energy Transsyndesmotic Ankle Fracture Dislocation—Injury Characteristics, Radiographic Outcomes, and Factors Affecting the Rate of Posttraumatic Arthritis in Logsplitter Injuries
Authors: Sidhu Sahil Prabhnoor , Atwan Yousif , Cavanagh Joseph , Sidhu Veer Sohail , Del Balso Christopher , Schemitsch Emil H. , Sanders David W. , Lawendy Abdel R.
Published: July 2021

Objectives:

To investigate patient demographics, injury characteristics, radiographic outcomes, and identify risk factors for developing posttraumatic arthritis in high-energy transsyndesmotic ankle fracture dislocations or “logsplitter” injuries.

Design:

Retrospective cohort study.

Setting:

Academic level one trauma center.

Patients/Participants:

Twenty-seven adult patients with logsplitter injuries.

Intervention:

All patients were treated with open reduction internal fixation, with possible addition of syndesmosis screw(s) and deltoid repair.

Main Outcome Measurements:

The rate of posttraumatic arthritis at one year along with rate and reasons for reoperation.

Results:

Twenty-seven patients were included with a mean follow-up of 14.5 ± 12.5 months. At one-year postoperative, 14 of the 20 patients (70%) demonstrated posttraumatic arthritis. Two patients (7.4%) went onto fusion. The reoperation rate was 51.9%. There was no significant difference in the arthritis rate with the number of syndesmosis screws used, quality of reduction, or addition of deltoid repair.

Conclusions:

The logsplitter injury is one with devastating outcomes and high rates of arthritis; it should be considered separately from conventional ankle fractures. The role of deltoid repair remains unclear. Further study of this injury pattern is required.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Corneal Endothelial Cell Changes After Femtosecond Laser–Assisted Cataract Surgery in Diabetic and Nondiabetic Patients
Authors: Kang Kyoung Hae , Song Mi Yeon , Kim Kook Young , Hwang Kyu Yeon , Kwon Young A , Koh Kyungmin
Published: July 2021

Objective:

To compare corneal endothelial cell changes after femtosecond laser–assisted cataract surgery (FLACS) in diabetic and nondiabetic patients.

Methods:

This retrospective study included patients with cataract who underwent FLACS performed by a single surgeon between August 2018 and November 2020. Changes in corneal endothelial cell density (ECD), hexagonality, coefficient of variation in cell size (CV), and central corneal thickness (CCT) at baseline and at the 1-month and 3-month postoperative follow-ups were investigated by dividing the patients into diabetic and nondiabetic groups.

Results:

We included 75 patients (60% men, mean age: 57.7±11.4 years, range: 27–80 years) in the analysis: 31 diabetic patients (64% men, mean age: 58.7±11.9 years, range: 27–79 years) and 44 nondiabetic patients (56% men, mean age: 57.1±11.3 years, range: 34–80 years). No differences were observed between the two groups as regards preoperative and intraoperative parameters, the mean postoperative ECD, hexagonality, and CV. At 1 month postoperatively, the CCT was significantly greater in the diabetic group (P=0.034); however, at 3 months, there was no significant difference between the two groups (P=0.927).

Conclusions:

Changes in postoperative corneal endothelial cells were comparable between patients with and without diabetes after FLACS. Femtosecond laser–assisted cataract surgery seems to cause less damage to the corneal endothelium in diabetic patients because it uses less phacoemulsification energy.
Implantation of an Artificial Endothelial Layer for Treatment of Chronic Corneal Edema
Authors: Auffarth Gerd U. , Son Hyeck-Soo , Koch Matthias , Weindler Jan , Merz Patrick , Daphna Ofer , Marcovich Arie L. , Augustin Victor A.
Published: July 2021

Purpose:

The purpose of this study was to describe a novel device that may serve as an alternative to Descemet membrane endothelial keratoplasty (DMEK) for the treatment of chronic corneal edema.

Methods:

The EndoArt (EyeYon Medical, Israel) is a flexible, 50-μm thin artificial endothelial layer that matches the cornea's posterior curvature and functions as a fluid barrier at the posterior stroma, replacing the diseased endothelium. Similar to a DMEK approach, it is implanted into the anterior chamber, carefully positioned on the posterior stroma, and secured using an air–gas mixture. Two patients with chronic corneal edema resulting from endothelial decompensation underwent implantation of the new artificial lamella.

Results:

In patient 1, the central corneal thickness (CCT) decreased from 730 μm preoperatively to 593 μm at 1 day postoperatively. In patient 2, the CCT decreased from 761 μm preoperatively to 487 μm at 1 day postoperatively. Both patients reported high satisfaction and an overall brighter visual quality. Although dislocation of the lamella occurred in both cases, the CCT was promptly restored after a repositioning procedure and remained stable at the 17-month follow-up (CCT of 526 and 457 μm for patients 1 and 2, respectively). In contrast to DMEK donor tissue, the artificial lamella is sufficiently robust to allow easy intraocular manipulation without the risk of damaging the implant. It is easily removable and does not require any immunosuppressive treatment because of its nonbiological nature.

Conclusions:

Implantation of the EndoArt led to rapid corneal deturgescence and CCT restoration, presenting a possible option for patients with chronic corneal edema.
First or Second Biologic in Inflammatory Bowel Disease
Authors: Aoun Roni , Jabak Suha , Mourad Fadi H. , Francis Fadi F. , Regueiro Miguel , Hashash Jana G.
Published: July 2021

The therapeutic armamentarium for patients with inflammatory bowel disease has been expanding. Current guidelines make recommendations about whether patients who are biologic naive should be receiving biologic monotherapy or combination therapy, depending on the class of biologics. However, due to the limited available data, guidance to inform clinical practice for patients receiving their second or more biologic are lacking. We hereby review the available data about the use of biologic monotherapy or combination therapy with concomitant immunomodulator therapies in patients receiving their first as well as those receiving their second biologic.
“Doing What Only I Can Do”
Authors: Mikkelsen Marta Kramer , Michelsen Hanne , Nielsen Dorte Lisbet , Vinther Anders , Lund Cecilia Margareta , Jarden Mary
Published: July 2021

Background

Sparse evidence exists regarding the feasibility and patients’ experiences of exercise programs among older cancer populations.

Objective

The aim of this study was to explore the experiences of older patients with advanced cancer who participated in a 12-week supervised and multimodal exercise program in a hospital setting.

Methods

Individual interviews were conducted with 18 participants (≥65 years) with advanced cancer who completed the intervention program regardless of compliance rate. In addition, written evaluation questionnaires were collected. Data were analyzed using thematic analysis.

Results

Three main themes were identified: (1) Motivated to strengthen body and mind, with the subthemes “Doing what only I can do” and “Reaching goals with support from healthcare professionals and peers”; (2) Exercise as an integrated part of the treatment course; and (3) Overcoming undeniable physical limitations.

Conclusions

The participants experienced several benefits from participation, including physical improvements, increased energy, reduction of symptoms, and improved social engagement. Goal setting, being positively pushed and cheered on, and integration of fun games increased motivation. In contrast, being pushed beyond physical limitations and experiencing severe symptoms were experienced as barriers toward exercising. Adherence to the exercise program was facilitated by coordinating a tailored program with medical appointments and receiving comprehensive support and guidance.

Implications for Practice

Multimodal exercise programs seem to be beneficial for older patients with advanced cancer and should be coordinated with oncological treatment in combination with targeted support and advice on symptom management.
Severe Postnatal Cytomegalovirus Enterocolitis in Immunocompetent Term Infants Requiring Total Parenteral Nutrition
Authors: Howard-Jones Annaleise R. , Cristerna-Tarrasa Giancarlo H. , Khan Rabia , Stormon Michael , Arbuckle Susan , Britton Philip N.
Published: July 2021

Postnatal cytomegalovirus enterocolitis is uncommon in immunocompetent infants. We report a 10-week-old term boy with severe and prolonged secretory diarrhea, leading to dependence on total parenteral nutrition and a 10-week hospitalization. Cytomegalovirus enterocolitis was diagnosed based on duodenal biopsy in the context of marked viremia, and the child recovered promptly on initiation of ganciclovir. Collated case reports reveal delayed diagnoses as the norm but rapid improvement with antiviral treatment. Cytomegalovirus enterocolitis should be considered early as a differential diagnosis in infants with refractory diarrhea.
Reactive Arthritis After Intravesical Bacillus Calmette-Guérin Therapy
Authors: Taniguchi Yoshinori , Nishikawa Hirofumi , Kimata Takahito , Yoshinaga Yasuhiko , Kobayashi Shigeto , Terada Yoshio
Published: July 2021

Reactive arthritis (ReA) is a sterile arthritis that occurs in genetically predisposed individuals secondary to an extra-articular infection, usually of the gastrointestinal or genitourinary tract. Sterile arthritis associated with instillation of intravesical bacillus Calmette-Guérin (iBCG) therapy used for bladder cancer can also be included under ReA based on the pathogenic mechanism. Similar to spondyloarthritis, HLA-B27 positivity is a known contributor to the genetic susceptibility underlying iBCG-associated ReA. Other genetic factors, such as HLA-B39 and HLA-B51, especially in Japanese patients, can also be involved in the pathophysiology of iBCG-associated ReA. The frequencies of ReA- and ReA-related symptoms are slightly different between Japanese and Western studies. Proper understanding of possible complications, their epidemiology and pathogenesis, and their management is important for the rheumatologist when noting symptomatic patients using iBCG. Herein, we will review the most current information on ReA after iBCG therapy.
Staphylococcus caledonicus sp. nov. and Staphylococcus canis sp. nov. isolated from healthy domestic dogs
Authors: Newstead Logan L. , Harris J. , Goodbrand S. , Varjonen K. , Nuttall T. , Paterson Gavin K.
Published: July 2021

Two strains, H8/1Tand H16/1AT, of Gram-stain-positive, coagulase-negative staphylococci were isolated from separate healthy domestic dogs in Scotland. Both strains were genome sequenced and their inferred DNA–DNA hybridisation indicates that H8/1Tand H16/1ATrepresent two novel species of the genusStaphylococcus. On the basis of the results of genome sequence analysis (genomeblastdistance phylogeny and single nucleotide polymorphism analysis) H8/1Tis most closely related toStaphylococcus devrieseiand H16/1ATmost closely related toStaphylococcus felis. Also, average nucleotide identity distinguished H8/1Tand H16/1ATfromS. devrieseiandS. felisas did minor phenotypic differences. On the basis of these results, it is proposed that H8/1Tand H16/1ATrepresent novel species with the respective namesStaphylococcus caledonicusandStaphylococcus canis. The type strain ofS. caledonicusis H8/1T(=NCTC 14452T=CCUG 74789T). The type strain ofS. canisis H16/1AT(=NCTC 14451T=CCUG 74790T)
Adaptation of gltA and ssrA assays for diversity profiling by Illumina sequencing to identify Bartonella henselae, B. clarridgeiae and B. koehlerae
Authors: Power Rosemonde Isabella , Calvani Nichola Elisa Davies , Nachum-Biala Yaarit , Salant Harold , Harrus Shimon , Šlapeta Jan
Published: July 2021

Introduction. Bartonellosis is an emerging zoonotic disease caused by bacteria of the genus

Bartonella

. Mixed

Bartonella

infections are a well-documented phenomenon in mammals and their ectoparasites. The accurate identification of

Bartonella

species in single and mixed infections is valuable, as different

Bartonella

species have varying impacts on infected hosts.

Gap Statement. Current diagnostic methods are inadequate at identifying the

Bartonella

species present in mixed infections.

Aim. The aim of this study was to adopt a Next Generation Sequencing (NGS) approach using Illumina sequencing technology to identify

Bartonella

species and demonstrate that this approach can resolve mixed

Bartonella

infections.

Methodology. We used Illumina PCR amplicon NGS to target the ssrA and gltA genes of

Bartonella

in fleas collected from cats, dogs and a hedgehog in Israel. We included artificially mixed

Bartonella

samples to demonstrate the ability for NGS to resolve mixed infections and we compared NGS to traditional Sanger sequencing.

Results. In total, we identified 74 Ctenocephalides felis, two Ctenocephalides canis, two Pulex irritans and three Archaeopsylla e. erinacei fleas. Real-time PCR of a subset of 48 fleas revealed that twelve were positive for

Bartonella

, all of which were cat fleas. Sanger sequencing of the ssrA and gltA genes confirmed the presence of

Bartonella henselae

,

Bartonella clarridgeiae

and

Bartonella koehlerae

. Illumina NGS of ssrA and gltA amplicons further confirmed the

Bartonella

species identity in all 12 flea samples and unambiguously resolved the artificially mixed

Bartonella

samples.

Conclusion. The adaptation and multiplexing of existing PCR assays for diversity profiling via NGS is a feasible approach that is superior to traditional Sanger sequencing for

Bartonella

speciation and resolving mixed

Bartonella

infections. The adaptation of other PCR primers for Illumina NGS will be useful in future studies where mixed bacterial infections may be present.
Estimation of COVID-19 recovery and decease periods in Canada using machine learning algorithms
Authors: Paul Subhendu , Lorin Emmanuel
Published: July 2021

We derive a novel model escorted by large scale compartments, based on a set of coupled delay differential equations with extensive delays, in order to estimate the incubation, recovery and decease periods of COVID-19, and more generally any infectious disease. This is possible thanks to machine learning algorithms applied to publicly available database of confirmed corona cases, recovered cases and death toll. In this purpose, we separate i) the total cases into 14 groups corresponding to 14 incubation periods, ii) the recovered cases into 406 groups corresponding to a combination of incubation and recovery periods, and iii) the death toll into 406 groups corresponding to a combination of incubation and decease periods. In this paper, we focus on recovery and decease periods and their correlation with the incubation period. The estimated mean recovery period we obtain is 22.14 days (95% Confidence Interval(CI): 22.00 to 22.27), and the 90th percentile is 28.91 days (95% CI: 28.71 to 29.13), which is in agreement with statistical supported studies. The bimodal gamma distribution reveals that there are two groups of recovered individuals with a short recovery period, mean 21.02 days (95% CI: 20.92 to 21.12), and a long recovery period, mean 38.88 days (95% CI 38.61 to 39.15). Our study shows that the characteristic of the decease period and the recovery period are alike. From the bivariate analysis, we observe a high probability domain for recovered individuals with respect to incubation and recovery periods. A similar domain is obtained for deaths analyzing bivariate distribution of incubation and decease periods.
1H-NMR metabolomics-based surrogates to impute common clinical risk factors and endpoints
Authors: Bizzarri D. , Reinders M.J.T. , Beekman M. , Slagboom P.E. ,   BBMRI-NL, van den Akker E.B.
Published: July 2021

Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. ‘metabolomics’, is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage metabolomics to impute missing data in clinical variables routinely assessed in large epidemiological and clinical studies. To this end, we have employed ∼25,000 1H-NMR metabolomics samples from 28 Dutch cohorts collected within the BBMRI-NL consortium, to create 19 metabolomics-based predictors for clinical variables, including diabetes status (AUC5-Fold CV = 0.94) and lipid medication usage (AUC5-Fold CV = 0.90). Subsequent application in independent cohorts confirmed that our metabolomics-based predictors can indeed be used to impute a wide array of missing clinical variables from a single metabolomics data resource. In addition, application highlighted the potential use of our predictors to explore the effects of totally unobserved confounders in omics association studies. Finally, we show that our predictors can be used to explore risk factor profiles contributing to mortality in older participants. To conclude, we provide 1H-NMR metabolomics-based models to impute clinical variables routinely assessed in epidemiological studies and illustrate their merit in scenarios when phenotypic variables are partially incomplete or totally unobserved.