bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine physiognomies of MSCs from varied sources confirm the regenerative commitment post‐coculture with activated neutrophils
Authors: Al‐Hakami Ahmed , Alqhatani Saad Qaddah , Shaik Sharaz , Jalfan Saaed Mohammed , Dhammam Mohammed Saad Abu , Asiri Wejdan , Alkahtani Abdullah Misfer , Devaraj Anantharam , Chandramoorthy Harish C.
Published: May 2020

The interaction of mesenchymal stromal cells (MSCs) with paracrine signals and immunological cells, and their responses and regenerative commitment thereafter, is understudied. In the current investigation, we compared MSCs from the umbilical cord blood (UCB), dental pulp (DP), and liposuction material (LS) on their ability to respond to activated neutrophils. Cytokine profiling (interleukin‐1α [IL‐1α], IL‐2, IL‐4, IL‐6, IL‐8, tumor necrosis factor‐α [TNF‐α], interferon‐γ [IFN‐γ], transforming growth factor‐β [TGF‐β]), cellular proliferation and osteogenic differentiation patterns were assessed. The results showed largely comparable cytokine profiles with higher TNF‐α and IFN‐γ levels in LSMSCs owing to their mature cellular phenotype. The viability and proliferation between LS/DP/UCB MSCs were comparable in the coculture group, while direct activation of MSCs with lipopolysaccharide (LPS) showed comparable proliferation with significant cell death in UCB MSCs and slightly higher cell death in the other two types of MSC. Furthermore, when MSCs post‐neutrophil exposure were induced for osteogenic differentiation, though all the MSCs devoid of the sources differentiated, we observed rapid and significant turnover of DPMSCs positive of osteogenic markers rather than LS and UCB MSCs. We further observed a significant turnover of IL‐1α and TGF‐β at mRNA and cytokine levels, indicating the commitment of MSCs to differentiate through interacting with immunological cells or bacterial products like neutrophils or LPS, respectively. Taken together, these results suggest that MSCs have more or less similar cytokine responses devoid of their anatomical niche. They readily switch over from the cytokine responsive cell phenotype at the immunological microenvironment to differentiate and regenerate tissue in response to cellular signals.
Bifidobacterium breve M‐16V alters the gut microbiota to alleviate OVA‐induced food allergy through IL‐33/ST2 signal pathway
Authors: Li Na , Yu Yi , Chen Xuehua , Gao Shenshen , Zhang Qingqing , Xu Chundi
Published: May 2020

There has been a marked increase in life‐threatening food allergy (FA). One hypothesis is that changes in bacterial communities may be key to FA. To better understand how gut microbiota regulates FA in humans, we established a mouse model with FA induced by ovalbumin. We found that the mice with FA had abnormal bacterial composition, accompanied by increased immunoglobulin G, immunoglobulin E, and interleukin‐4/interferon‐γ, and there existed a certain coherence between them. Interestingly, Bifidobacterium breve M‐16V may alter the gut microbiota to alleviate the allergy symptoms by IL‐33/ST2 signaling. Our results indicate that gut microbiota is essential for regulating FA to dietary antigens and demonstrate that intervention in bacterial community regulation may be therapeutically related to FA.
A global treatments for coronaviruses including COVID‐19
Authors: Yousefi Bahman , Valizadeh Saeid , Ghaffari Hadi , Vahedi Azadeh , Karbalaei Mohsen , Eslami Majid
Published: May 2020

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019‐nCoV). So far, there are no specific treatments for patients with coronavirus disease‐19 (COVID‐19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome‐related coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID‐19. Cathepsin L is required for entry of the 2019‐nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin‐converting‐enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID‐19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019‐nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS‐CoV disease and can be useful for patients of COVID‐19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS‐CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS‐CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID‐19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.
Soft tissue foreign bodies: A training manual for sonographic diagnosis and guided removal
Authors: Rooks Veronica J. , Shiels William E. , Murakami James W.
Published: May 2020

Sonography provides excellent detection, localization, and characterization of soft‐tissue foreign bodies. Ultrasound guided foreign body removal is a safe and highly successful minimally invasive procedure that facilitates effective treatment and avoidance of complications in patients with soft tissue foreign bodies. Focused laboratory training is critical to successful implementation of a sonographic foreign body management practice.
Refractory hemorrhagic esophageal ulcers by Candida esophagitis with advanced systemic sclerosis
Authors: Natsui Kazuki , Tsuchiya Atsunori , Terai Shuji
Published: May 2020

A 64‐year‐old woman diagnosed with rheumatoid arthritis (RA) and systemic sclerosis (SSc) was admitted to our hospital with chief complaints of uncontrolled bleeding from esophageal ulcers and an inability to consume meals. For RA and SSc, she was treated with prednisolone and abatacept and was taking vonoprazan as prophylaxis for steroid‐induced gastric ulcers. She was diagnosed with severe Candida esophagitis, with multiple large and small ulcers with bleeding, based on esophagogastroduodenoscopy and pathological findings. We performed comprehensive treatment; abatacept was discontinued, and total parenteral nutrition was initiated along with antifungal therapy. Improvement in the esophageal ulcers was observed. Although severe Candida esophagitis is a rare condition, we should keep in mind that severe Candida esophagitis can occur in patients with an immunosuppressive compromised host and esophageal movement disorders such as SSc. Regular follow up by endoscopy and prophylactic treatment to prevent severe esophagitis may be necessary.
Early child development in children who are HIV‐exposed uninfected compared to children who are HIV‐unexposed: observational sub‐study of a cluster‐randomized trial in rural Zimbabwe
Authors: Ntozini Robert , Chandna Jaya , Evans Ceri , Chasekwa Bernard , Majo Florence D , Kandawasvika Gwendoline , Tavengwa Naume V , Mutasa Batsirai , Mutasa Kuda , Moulton Lawrence H , Humphrey Jean H , Gladstone Melissa J , Prendergast Andrew J ,   the SHINE Trial Team
Published: May 2020

Introduction

Exposure to maternal HIV may affect early child development (ECD), although previous studies have reported heterogeneous findings. We evaluated ECD among children who were HIV‐exposed uninfected (CHEU) and children who were HIV‐unexposed (CHU) recruited to the SHINE trial in rural Zimbabwe.

Methods

SHINE was a community‐based cluster‐randomized trial of improved infant feeding and/or improved water, sanitation and hygiene. Pregnant women were enrolled between 2012 and 2015. We assessed ECD in a sub‐study at 24 months of age, between 2016 and 2017, using the Malawi Developmental Assessment Tool (MDAT; assessing motor, cognitive, language and social development); MacArthur‐Bates Communicative Development Inventory (CDI) (assessing vocabulary and grammar); A‐not‐B test (assessing object permanence); and a self‐control task. Mothers and infants were tested longitudinally for HIV. We used generalized estimating equations to compare ECD scores between CHEU and CHU, accounting for the cluster‐randomized design. Primary results were adjusted for trial‐related factors that could affect measurement reliability of ECD: study nurse, age of child, calendar month of birth, sex and randomized arm.

Results

A total of 205 CHEU and 1175 CHU were evaluated. Mean total MDAT score was 90.6 (SD 8.7) in CHEU compared to 92.4 (9.1) in CHU (adjusted mean difference −1.3, 95% CI: −2.3, −0.3), driven mostly by differences in gross motor (−0.5, 95% CI: −0.9, −0.2) and language scores (−0.6, 95% CI: −1.1, −0.1). There was evidence that fine motor scores were lower in CHEU (adjusted mean difference −0.4, 95% CI: −0.8, 0.0) but no evidence of a difference in social scores (0.1, 95% CI: −0.2, 0.4). Mean MacArthur‐Bates CDI vocabulary score was 57.9 (SD 19.2) in CHEU compared to 61.3 (18.8) in CHU (adjusted mean difference −2.9 words, 95% CI: −5.7, −0.1). Object permanence and self‐control scores were similar between groups.

Conclusions

CHEU in rural Zimbabwe had total child development and vocabulary scores that were approximately 0.15 standard deviations lower than CHU at two years of age. More detailed and specific studies are now needed to unravel the reasons for developmental delay in CHEU and the likelihood that these delays persist in the longer term.
Influenza A virus directly modulates mouse eosinophil responses
Authors: LeMessurier Kim S , Rooney Robert , Ghoneim Hazem E , Liu Baoming , Li Kui , Smallwood Heather S , Samarasinghe Amali E
Published: May 2020

Allergic asthma and influenza are common respiratory diseases with a high probability of co-occurrence. During the 2009 influenza pandemic, hospitalized patients with influenza experienced lower morbidity if asthma was an underlying condition. We have previously demonstrated that acute allergic asthma protects mice from severe influenza and have implicated eosinophils in the airways of mice with allergic asthma as participants in the antiviral response. However, very little is known about how eosinophils respond to direct exposure to influenza A virus (IAV) or the microenvironment in which the viral burden is high. We hypothesized that eosinophils would dynamically respond to the presence of IAV through phenotypic, transcriptomic, and physiologic changes. Using our mouse model of acute fungal asthma and influenza, we showed that eosinophils in lymphoid tissues were responsive to IAV infection in the lungs and altered surface expression of various markers necessary for cell activation in a niche-specific manner. Siglec-F expression was altered in a subset of eosinophils after virus exposure, and those expressing high Siglec-F were more active (IL-5RαhiCD62Llo). While eosinophils exposed to IAV decreased their overall transcriptional activity and mitochondrial oxygen consumption, transcription of genes encoding viral recognition proteins, Ddx58 (RIG-I), Tlr3, and Ifih1 (MDA5), were up-regulated. CD8+ T cells from IAV-infected mice expanded in response to IAV PB1 peptide-pulsed eosinophils, and CpG methylation in the Tbx21 promoter was reduced in these T cells. These data offer insight into how eosinophils respond to IAV and help elucidate alternative mechanisms by which they regulate antiviral immune responses during IAV infection.
Ultrastructural evidence for the origin of the subretinal pigment shield in the compound eye of Drosophila melanogaster
Authors: Mohr Tobias , Fischer Stefan
Published: May 2020

Little morphological information is available about subretinal pigment shields in insect compound eyes, especially ultrastructural information. The latter is however needed in order to detect possible smallest projections that emanate from pigment‐granule‐bearing cells and pass through the basal matrix (BM), but that are not visible in light micrographs. Previous work on the subretinal pigment shield in Drosophila melanogaster suggests that the pigment cell population located below the BM is closely associated with secondary and tertiary pigment cells. Whether these cells stay in connection throughout life with the subretinal regions via thin projections that pass through the fenestrae of the BM, or whether the subretinal parts later become separated during eye development remained so far unknown. Our investigation of the periphery of the BM by three‐dimensional reconstruction based on serial‐sectioning transmission electron microscopy has revealed that the secondary and tertiary pigment cells possess thin projections that pass through the fenestrae of the BM and thus connect the cellular regions above and below the BM in the adult compound eye. The subretinal pigment shield of D. melanogaster is therefore of retinal origin and is not composed of additional subretinal pigment cells. The maintained bond allows the active displacement of pigment granules below the BM during the process of dark and light adaptation of the compound eye.
Dexamethasone prevents the Epstein‐Barr virus induced epithelial‐mesenchymal transition in A549 cells
Authors: Zhang Fengqin , Chen Lei , Zhou Ying , Ding Dan , Hu Qiongjie , Liu Yiwen , Li Kaiyan , Wu Sisi , He Li , Lei Mei , Du Ronghui
Published: May 2020

Clinical data have shown that pulmonary interstitial fibrosis is likely to occur in the later stages of viral pneumonia. While viral infections are thought to cause chronic pulmonary interstitial inflammation and pulmonary fibrosis, it remains unclear if they promote pulmonary fibrosis by epithelial‐mesenchymal transition (EMT). In this study, human epithelial cell line A549 has been used to model the infection of the Epstein‐Barr virus (EBV) and the respiratory syncytial virus (RSV). Their differences were compared and the possible infection mechanisms analyzed by randomly assigning cells to one of five treatments. Exposure of the LMP1 is thought to be the key gene during EBV‐induced EMT in the A549 cells. Enzyme‐linked immunosorbent assay analysis revealed that the EBV infection was associated with the induction of a number of cytokines (interleukin‐8 [IL‐8], IL‐13, tumor necrosis factor‐α, and transforming growth factor‐β) and dexamethasone (DXM) could significantly prevent the phenotypic changes, and partly the mechanisms related with the IL‐13 pathway. Surprisingly, different results were seen with the RSV infection as the A549 cells still displayed an epithelial morphology but the levels of E‐cadherin, α‐SMA, vimentin, and fibronectin did not change. This is the first study demonstrating the different reactions induced by different viruses, and the protective effects of DXM on the EBV‐induced EMT in the A549 cells by partially inhibiting the IL‐13 pathway. These findings suggest a novel mechanism, by which DXM or anti‐IL‐13 may delay the progression of pulmonary fibrosis by preventing the progress of EBV‐induced EMT.
Tracking mesoscale convective systems in central equatorial Africa
Authors: Hartman Adam T.
Published: May 2020

The Congo basin in central equatorial Africa is home to some of the most intense convection in the global tropics. Mesoscale convective systems (MCSs) provide much of the annual rainfall over this region during the March–April–May (MAM) and September–October–November (SON) rainy seasons. Features of these systems are essential to rainfall variability in this region and greatly impact human health, agriculture, livestock, and drought monitoring. Knowledge of variability is hindered by the lack of in‐situ observations and meteorological stations. The present study identifies and tracks MCSs for the 33‐year period 1983–2015 for MAM and SON. MCS and environmental parameters are calculated for the rainy seasons using satellite and reanalysis data. Spatial distributions of MCS parameters and diurnal cycles for select MCS parameters are compared to prior research. Statistical significance testing is performed to determine if there are meaningful differences between the seasons. Seasonal differences are briefly discussed. 650 hPa relative vorticity patterns suggest localized terrain effects may play a role near a local maximum in MCS initiation frequency in the lee of the Great Rift Valley. Spatial distributions of 33‐year MCS counts, trajectories, speeds, sizes, maximum intensities, and durations, based on initiation locations, agree well with prior research. Differences between seasons are statistically significant and variable and latitude dependent. There is high interannual variability among all MCS and environmental parameters.
Regional variability in lightning activity over South Asia
Authors: Kamra Adarsh Kumar , Ramesh Kumar Penki
Published: May 2020

The regional variability of lightning activity over 10 different regions, selected with at least one major meteorological/topographical feature, of South Asia (8°N–36°N, 90°E–100°E) have been examined on all time scales from the data obtained from July 1995 to December 2013 from the Tropical Rainfall Measuring Mission satellite. A comparative study of the correlation coefficients calculated between lightning flash rate and convective parameters, aerosol optical depth (AOD) and topography for different regions is carried out. Impact of the progress of the Asian Monsoon on the spatio‐temporal variability of flash rate is also examined. Monthly‐averaged variations are annual at the regions >2,700 m in altitude and are semi‐annual at the regions <2,700 m in altitude. The annually averaged flash rates increase during the study period in most of the regions. However, such long‐term changes are nonlinearly related to the change in convective parameters and AOD and such inter‐relationships differ from one meteorological region to another. Small changes in AOD in high altitude regions are associated with very large changes in the surface temperature and flash rate. The flash rate is strongly correlated with surface temperature in the dry region of the north‐west but with CAPE in moist region of the north‐east. Progress of the Asian monsoon strongly impacts the flash rate in different regions. Ratio of the amplitudes of primary to secondary maxima at land stations increases with latitude in case of the monthly‐averaged variations in flash rate. The primary maxima in these variations are highly correlated with the atmospheric surface temperature. However, the secondary maxima are associated with the low‐level convergence during the withdrawal phase of the monsoon. Incursion of moisture by the Bay of Bengal branch of monsoon current determines the sequence of occurrence of lightning activity in different regions along the Himalayan foothills and north‐west.

Key Points

Lightning flash rate in the South Asian regions is sensitive to the surface temperature and to the altitude in the Himalayas

Progress of the Asian monsoon strongly impacts the regional distribution of the flash rate in the South Asia

Long‐term changes in flash rate during 1995–2013 in the South Asian regions increased with the surface temperature and aerosols
Evaluation of the Global Leadership Initiative on Malnutrition Criteria Using Different Muscle Mass Indices for Diagnosing Malnutrition and Predicting Survival in Lung Cancer Patients
Authors: Yin Liangyu , Lin Xin , Li Na , Zhang Mengyuan , He Xiumei , Liu Jie , Kang Jun , Chen Xiao , Wang Chang , Wang Xu , Liang Tingting , Liu Xiangliang , Deng Li , Li Wei , Song Chunhua , Cui Jiuwei , Shi Hanping , Xu Hongxia
Published: May 2020

Background

Malnutrition is prevalent in lung cancer (LC) patients, yet there are no globally accepted criteria for diagnosing malnutrition. Recently, the Global Leadership Initiative on Malnutrition (GLIM) criteria were proposed. However, the role of these criteria in prospective LC cohorts remains unclear.

Methods

We performed a multicenter, observational cohort study including 1219 LC patients. Different anthropometric measures were compared for assessment of reduced muscle mass (RMM) in the GLIM criteria. Least absolute shrinkage and selection operator and multivariate Cox regressions were performed to analyze the association between the GLIM criteria and survival. Independent prognostic predictors were incorporated to develop a nomogram for individualized survival prediction, and decision curve was applied to assess the clinical significance of the nomogram.

Results

Patients in the stage II (severe) malnutrition group, diagnosed using combined calf circumference (CC) plus body weight–standardized handgrip strength (HGS/W) criteria, had the highest hazard ratio (HR, 2.07; 95%CI, 1.50–2.86) compared with other methods used to evaluate RMM. The GLIM criteria diagnosed malnutrition in 24% of cases (292 patients, using the CC and HGS/W criteria) and were effective for determining the nutrition status of LC patients. GLIM‐diagnosed malnutrition was an independent risk factor for survival, and malnutrition severity was monotonically associated with death hazards (P = .002). The GLIM nomogram showed good performance in predicting the survival of LC patients, and the decision‐curve analysis demonstrated that the nomogram was clinically useful.

Conclusion

These findings support the effectiveness of GLIM in diagnosing malnutrition and predicting survival among LC patients.
Solid‐phase extraction using chloropropyl functionalized sol–gel hybrid sorbent for simultaneous determination of organophosphorus pesticides in selected fruit samples
Authors: Veloo Krishna Veni , Ibrahim Nur Amirah Syahirah
Published: May 2020

A new sol–gel hybrid methyltrimethoxysilane‐chloropropyltriethoxysilane was prepared as sorbent for solid‐phase extraction. The extraction efficiency of the prepared sol–gel hybrid methyltrimethoxysilane‐chloropropyltriethoxysilane was assessed by using three selected organophosphorus pesticides, namely, chlorpyrifos, profenofos, and malathion. Gas chromatography–mass spectrometry was used for detection of organophosphorus pesticides. Several vital parameters were optimized to identify the best extraction conditions. Under the optimum extraction conditions, solid‐phase extraction‐methyltrimethoxysilane‐chloropropyltriethoxysilane method showed good linearity range (0.05‐1 μg/mL) with coefficient of determination more than 0.995. The limits of detection obtained were in the range of 0.01–0.07 μg/mL and limits of quantification ranging from 0.03 to 0.21 μg/mL. The limits of detection obtained for the developed method were 2.3–6.5× lower than the limits of detection of commercial octadecyl silica sorbent. Real samples analysis was carried out by applying the developed method on red apple and purple grape samples. The developed method exhibited good recoveries (88.33–120.7%) with low relative standard deviations ranging from 1.6 to 3.3% compared to commercial octadecyl silica sorbent, which showed acceptable recoveries (70.3–100.2%) and relative standard deviations (6.3–8.8%). The solid‐phase extraction‐methyltrimethoxysilane‐chloropropyltriethoxysilane method is presented as an alternative extraction method for determination of organophosphorus pesticides.
Optimization of l‐arginine purification from Corynebacterium crenatum fermentation broth
Authors: Xu Meijuan , Qiao Zhina , Huang Genshu , Long Mengfei , Yang Taowei , Zhang Xian , Shao Minglong , Xu Zhenghong , Rao Zhiming
Published: May 2020

l‐Arginine has many special physiological and biochemical functions, with wide applications in the food and pharmaceutical industry. Few studies on the purification of l‐arginine from fermentation broth have been conducted; however, none of them were systematic enough for industrial scale‐up. Therefore, it is necessary to develop a highly efficient and systematic process for the purification of l‐arginine from fermentation broth. In this study, we screened out a cation exchange resin, D155, having high exchange capacity, high selectivity, and easy elution capacity, and analyzed its adsorption isotherm, thermodynamics, and kinetics using different models. Further, the process parameters of fixed‐bed ion exchange adsorption and elution were optimized, and the penetration curve during the operation was modeled. Based on the fixed‐bed ion‐exchange parameters, a 30‐column continuous ion‐exchange system was designed, and the flow velocity in each zone was optimized. Finally, to obtain a high purity of l‐arginine, the purification tests were conducted using anion exchange resin 711, and an l‐arginine yield of 99.1% and purity of 98.5% was obtained. This effective and economical method also provides a promising strategy for separation of other amino acids from the fermentation broth, which is of great significance to the l‐arginine fermentation industry.
Progress in the Application of Ultrasound Elastography for Brain Diseases
Authors: Liao Jianyi , Yang Huihui , Yu Jinsui , Liang Xiaowen , Chen Zhiyi
Published: May 2020

Ultrasound (US) can be used to evaluate the brain structure and nervous system damage. Patients with neurologic symptoms need rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging is currently the most sensitive and specific imaging method for evaluating neuropathologic conditions. This approach does present some challenges, such as the need to transport patients who may be seriously ill to the magnetic resonance imaging suite and the need for patients to remain for a considerable time. Cranial US provides a very valuable imaging method for clinicians, which can make a rapid diagnosis and evaluation without ionizing radiation. The main disadvantage of cranial US is its low sensitivity and specificity for subtle/early lesions. In recent years, with the rapid development of anatomic and functional US technology, the practicability of US diagnosis and intervention has been greatly improved. Ultrasound elastography may have the potential to improve the sensitivity and specificity of various cranial nerve conditions. Ultrasound elastography has received considerable critical attention, and an increasing number of studies have recognized its critical role in evaluating brain diseases. At present, US elastography has been applied to the evaluation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and hypoxic ischemic encephalopathy. The latest animal experiments and human clinical trial developments in the applications of US elastography for brain diseases are summarized in this review.
Ultrasound Differential Diagnosis in Deep Infiltrating Endometriosis of the Urinary Tract
Authors: Scioscia Marco , Zanetti Isabella , Raspanti Xenia , Spoto Elide , Portuese Antonella , Noventa Marco , Pontrelli Giovanni , Greco Pantaleo , Virgilio Bruna Anna
Published: May 2020

Endometriosis of the urinary tract is a rare condition that may lead to severe complications. At present, the major challenge appears to be the ultrasound differential diagnosis with diseases that can afflict the ureter and the bladder. Preoperative scan findings were compared with surgical and histologic records. Twenty‐three cases were selected as being of interest, as they were referred for suspected endometriosis, whereas second‐level ultrasound revealed a different disease in some cases. This case series aims to help in becoming familiar with the possible differential diagnosis of lesions of the urinary tract that resemble endometriosis.
Contrast‐Enhanced Ultrasound in Patients With COVID‐19
Authors: Soldati Gino , Giannasi Gianfranco , Smargiassi Andrea , Inchingolo Riccardo , Demi Libertario
Published: May 2020

Coronavirus disease 2019 (COVID‐19) represents a very heterogeneous disease. Some aspects of COVID‐19 pneumonia question the real nature of ground glass opacities and its consolidative lesions. It has been hypothesized that COVID‐19 lung involvement could represent not only a viral effect but also an immune response induced by the infection, causing epithelial/endothelial lesions and coagulation disorders. We report 3 cases of COVID‐19 pneumonia in which contrast‐enhanced ultrasound was suggestive of consolidations with perfusion defects, at least in part caused by ischemic or necrotic changes and not only by inflammatory or atelectasis events.
Twenty‐species and 15‐species chemical kinetic mechanisms for cyclohexane using the local self‐similarity tabulation method
Authors: Kourdis Panayotis D. , Bellan Josette
Published: May 2020

The 1081 species cyclohexane‐oxidation elementary reaction mechanism of Silke et al. (DOI:10.1021/jp067592d) is reduced in the number of species by a factor using the local self‐similarity tabulation (LS2T) method. Reduced‐species mechanisms of both 20 (R20) and 15 (R15) species are created in the high‐pressure combustion regime typical of diesel engines. To evaluate the performance of R20 and R15 against the elementary kinetics, simulations are performed for cyclohexane/air mixtures at initial temperatures of 1150, 900, 750, and 680 K and constant pressures of 20 and 40 bar for a variety of equivalence ratios (, 1.0, and 2 for 1150 and 900 K; for 750 K; for 680 K). Very good agreement between R20 and R15 with the elementary kinetics mechanism is demonstrated at 1150 and 900 K for which the self‐similarity is very well obeyed; however, only fair agreement is obtained at 750 and 680 K, a fact which is traced to the less faithful adherence to the self‐similarity due to the one order of magnitude increase in ignition time over the range 750‐680 K. These results are found to be quasi‐independent of the tabulation grid. Future work is proposed to improve the reduction in the cold‐ignition, high‐pressure regime.
Removing Subcutaneous Microvessels Using Photo‐Mediated Ultrasound Therapy
Authors: Wang Mingyang , Qin Yu , Wang Tao , Orringer Jeffrey S. , Paulus Yannis M. , Yang Xinmai , Wang Xueding
Published: May 2020

Background and Objectives

We have developed a novel anti‐vascular technique, termed photo‐mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove the microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing subcutaneous microvessels.

Study Design/Materials and Methods

The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at 1 hour, 3 days, 2 weeks, and 4 weeks post‐treatment. Perfusion rates of 38 individual vessels from four rabbit ears were tracked during this time period for longitudinal assessment.

Results

The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate, showed a statistically significant decrease for all time points post‐treatment (P < 0.001). The mean decrease in perfusion is 50.79% immediately after treatment and is 32.14% at 4 weeks post‐treatment. Immediately after treatment, the perfusion rate decreased rapidly. Following this, there was a partial recovery in perfusion rate up to 3 days post‐treatment, followed by a plateau in the perfusion from 3 days to 4 weeks.

Conclusions

This study demonstrated that a single PUT treatment could significantly reduce blood perfusion by 32.14% in the skin for up to 4 weeks. With unique advantages such as low laser fluence as compared with photothermolysis and agent‐free treatment as compared with photodynamic therapy, PUT holds the potential to be developed into a new tool for the treatment of cutaneous vascular lesions. Lasers Surg. Med. © 2020 Wiley Periodicals, LLC
T‐cell receptor affinity in the age of cancer immunotherapy
Authors: Hoffmann Michele M. , Slansky Jill E.
Published: May 2020

The strength of the interaction between T‐cell receptors (TCRs) and their ligands, peptide/major histocompatibility complex complexes (pMHCs), is one of the most frequently discussed and investigated features of T cells in immuno‐oncology today. Although there are many molecules on the surface of T cells that interact with ligands on other cells, the TCR/pMHC is the only receptor‐ligand pair that offers antigen specificity and dictates the functional response of the T cell. The strength of the TCR/pMHC interaction, along with the environment in which this interaction takes place, is key to how the T cell will respond. The TCR repertoire of T cells that interact with tumor‐associated antigens is vast, although typically of low affinity. Here, we focus on the low‐affinity interactions between TCRs from CD8+ T cells and different models used in immuno‐oncology.
Age‐Related Parkinsonian Signs in Microdeletion 22q11.2
Authors: Boot Erik , Mentzel Thierry Q. , Palmer Lisa D. , van Harten Peter N. , Marras Connie , Lang Anthony E. , Bassett Anne S.
Published: May 2020

Background

The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early‐onset PD. However, little is known about early motor signs in this condition.

Objectives

We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD.

Methods

We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS‐UPDRS part III, and three‐dimensional motion‐tracker technology to quantify components of bradykinesia.

Results

Median MDS‐UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17–65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = –0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS‐UPDRS–defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%.

Conclusions

Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Mass Spectrometry–Based Analysis of Urinary Biomarkers for Dietary Tomato Intake
Authors: Hövelmann Yannick , Lewin Lea , Steinert Katharina , Hübner Florian , Humpf Hans‐Ulrich
Published: May 2020

Scope

In this study, the applicability of several β‐carboline, imidazole, and steroidal alkaloids as biomarkers for tomato juice intake is evaluated.

Methods and results

Over the course of a 2‐week crossover dietary intervention study, 14 volunteers were given low and high doses of tomato juice after 3 days of avoiding tomato‐based products. On the day of consumption and the following days, volunteers provided urine samples that were quantitatively analyzed by high‐performance liquid chromatography‐tandem mass spectrometry. Herein, glucose‐derived β‐carboline alkaloids are determined as supporting, yet non‐specific dietary biomarkers for tomato juice intake. Several imidazole alkaloids represent further biomarkers, which are shown to specifically indicate consumption of tomato juice for 24 h and partly >24 h. Additionally, steroidal alkaloids derived from esculeogenin B are determined to be specific biomarkers for tomato juice detectable for at least 48 h after consumption. The intake of low and high amounts of tomato juice is significantly distinguishable based on the urinary excretion of all determined biomarkers as well.

Conclusions

The dietary intake of tomato juice is conclusively traceable based on urinary excretion of multiple β‐carboline, imidazole, and steroidal alkaloids, and can be determined for up to 48 h after consumption. Furthermore, different intake doses can clearly be distinguished based on their urinary excretion.
A transmit–receive array for brain imaging with a high‐performance gradient insert
Authors: Rösler Manuela B. , Leussler Christoph , Brunner David O. , Schmid Thomas , Hennel Franciszek , Luechinger Roger , Weiger Markus , Pruessmann Klaas P.
Published: May 2020

Purpose

The aim of this work was to provide parallel imaging capability for the human head in a gradient insert of 33‐cm inner diameter within the related constraints of space, encoding ambiguity, and eddy current immunity.

Methods

Eddy current behavior of the 8‐channel transmit–receive array coil was investigated via heating and field deviation measurements. RF performance was evaluated using S‐parameters, noise statistics, B1 maps, and g‐factor maps. In vivo images of a human head and knee were acquired with Cartesian readout and TE below 0.45 ms.

Results

Under intense gradient use, the shield was heated up to 55°C and other coil structures to 40°C. After standard preemphasis calibration, eddy current‐related field distortions caused by the developed RF coil were smaller than for a commercial receive‐only coil. In the ambiguous regions of the gradient, is 20 dB lower than in the center of the FOV. Coupling between elements is below −15 dB, and noise correlation is less than 0.31 when the coil is loaded with a head. Power efficiency was 0.52 ± 0.02 μT/√W, and the SD of the flip angle was below 10% in central slices of the brain. 2D, up to fourfold acceleration causes less than 30% noise amplification. The RF coil can be used during full gradient performance.

Conclusion

Based on the described features, the presented coil enables parallel imaging in the high‐performance gradient insert.
Quantitative measurement of redox state in human brain by 31P MRS at 7T with spectral simplification and inclusion of multiple nucleotide sugar components in data analysis
Authors: Ren Jimin , Malloy Craig R. , Sherry A. Dean
Published: May 2020

Purpose

To develop a simplified method for quantitative measurement of NAD+/NADH (nicotinamide adenine dinucleotides) levels in human brain by 31P MRS without interference from the α‐ATP signal and with inclusion of multiple UDP‐sugar components.

Methods

Simple pulse‐acquire 31P MR spectra were collected at 7T with and without a frequency‐selective inversion pulse to remove the dominant α‐ATP signal from the underlying NAD(H) signal. Careful inspection of the 31P signal at −9.8 ppm previously assigned to UDP‐glucose revealed multiple UDP‐sugar components that must also be considered when deconvoluting the NAD(H) signal to quantify NAD+ and NADH. Finally, the overlapping NAD(H) and UDP(G) resonances were deconvoluted into individual components using Voigt lineshape analysis and UDP(G) modeling.

Results

The inversion‐based spectral editing method enabled clean separation of the NAD(H) signal from the otherwise dominant α‐ATP signal. In addition, the upfield signal near −9.8 ppm appears more “quartet‐like” than a simple doublet consistent with contributions from other nucleotide sugars such as UDP‐galactose, UDP‐N‐acetyl‐galactosamine, and UDP‐N‐acetyl‐glucosamine in addition to UDP‐glucose. Deconvolution of the combined NAD(H) and UDP(G) signals showed that the measured NAD+/NAD ratio was heavily influenced by UDP(G) modeling (7.5 ± 1.8 when the UDP(G) signal was fitted as multiple doublets versus 5.3 ± 0.6 when a simplified pseudo doublet model was used). In a test/re‐test experiments separated by 2 weeks, consistent NAD+/NADH ratios were measured in the brain of seven human subjects.

Conclusions

The NAD+/NADH ratio in human brain can be measured using 31P MR spectra simplified by spectral editing and with inclusion of multiple UDP‐sugar components in the data analysis.
Mucosal barrier injury–associated bloodstream infections in pediatric oncology patients
Authors: Hakim Hana , Billett Amy L. , Xu Jiahui , Tang Li , Richardson Troy , Winkle Cynthia , Werner Eric J. , Hord Jeffrey D. , Bundy David G. , Gaur Aditya H. ,   Children's Hospital Association Childhood Cancer and Blood Disorders Network
Published: May 2020

Background

Single‐center reports of central line–associated bloodstream infection (CLABSI) and the subcategory of mucosal barrier injury laboratory–confirmed bloodstream infection (MBI‐LCBI) in pediatric hematology oncology transplant (PHO) patients have focused on the inpatient setting. Characterization of MBI‐LCBI across PHO centers and management settings (inpatient and ambulatory) is urgently needed to inform surveillance and prevention strategies.

Methods

Prospectively collected data from August 1, 2013, to December 31, 2015, on CLABSI (including MBI‐LCBI) from a US PHO multicenter quality improvement network database was analyzed. CDC National Healthcare Safety Network definitions were applied for inpatient events and adapted for ambulatory events.

Results

Thirty‐five PHO centers reported 401 ambulatory and 416 inpatient MBI‐LCBI events. Ambulatory and inpatient MBI‐LCBI rates were 0.085 and 1.01 per 1000 line days, respectively. Fifty‐three percent of inpatient CLABSIs were MBI‐LCBIs versus 32% in the ambulatory setting (P  <  0.01). Neutropenia was the most common criterion defining MBI‐LCBI in both settings, being present in ≥90% of events. The most common organisms isolated in MBI‐LCBI events were Escherichia coli (in 28% of events), Klebsiella spp. (23%), and viridans streptococci (12%) in the ambulatory setting and viridans streptococci (in 29% of events), E. coli (14%), and Klebsiella spp. (14%) in the inpatient setting.

Conclusion

In this largest study of PHO MBI‐LCBI inpatient events and the first such study in the ambulatory setting, the burden of MBI‐LCBI across the continuum of care of PHO patients was substantial. These data should raise awareness of MBI‐LCBI among healthcare providers for PHO patients, help benchmarking across centers, and help inform prevention and treatment strategies.
Genetic tests aid in counseling of fetuses with cerebellar vermis defects
Authors: Li Lushan , Fu Fang , Li Ru , Xiao Weiqiang , Yu Qiuxia , Wang Dan , Jing Xiangyi , Zhang Yongning , Yang Xin , Pan Min , Liu Zequn , Liao Can
Published: May 2020

Objective

To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD).

Methods

From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy‐Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs).

Results

Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants.

Conclusion

The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.
Access to psychotherapy for patients with personality disorders
Authors: Paris Joel
Published: May 2020

The best evidence for effective treatment of personality disorder supports the use of specialized forms of psychotherapy. However, these forms of treatment are generally unavailable in health care systems. This may be partly due to the expense of routinely offering long‐term therapies. There is evidence that psychotherapy for personality disorder is cost‐effective. One way to address this problem is to treat most patients more briefly. © 2020 John Wiley & Sons, Ltd.
Comparison of Proteomic Assessment Methods in Multiple Cohort Studies
Authors: Raffield Laura M. , Dang Hong , Pratte Katherine A. , Jacobson Sean , Gillenwater Lucas A. , Ampleford Elizabeth , Barjaktarevic Igor , Basta Patricia , Clish Clary B. , Comellas Alejandro P. , Cornell Elaine , Curtis Jeffrey L. , Doerschuk Claire , Durda Peter , Emson Claire , Freeman Christine M. , Guo Xiuqing , Hastie Annette T. , Hawkins Gregory A. , Herrera Julio , Johnson W. Craig , Labaki Wassim W. , Liu Yongmei , Masters Brett , Miller Michael , Ortega Victor E. , Papanicolaou George , Peters Stephen , Taylor Kent D. , Rich Stephen S. , Rotter Jerome I. , Auer Paul , Reiner Alex P. , Tracy Russell P. , Ngo Debby , Gerszten Robert E. , O'Neal Wanda K. , Bowler Russell P. ,   NHLBI Trans‐Omics for Precision Medicine (TOPMed) Consortium
Published: May 2020

Novel proteomics platforms, such as the aptamer‐based SOMAscan platform, can quantify large numbers of proteins efficiently and cost‐effectively and are rapidly growing in popularity. However, comparisons to conventional immunoassays remain underexplored, leaving investigators unsure when cross‐assay comparisons are appropriate. The correlation of results from immunoassays with relative protein quantification is explored by SOMAscan. For 63 proteins assessed in two chronic obstructive pulmonary disease (COPD) cohorts, subpopulations and intermediate outcome measures in COPD Study (SPIROMICS), and COPDGene, using myriad rules based medicine multiplex immunoassays and SOMAscan, Spearman correlation coefficients range from −0.13 to 0.97, with a median correlation coefficient of ≈0.5 and consistent results across cohorts. A similar range is observed for immunoassays in the population‐based Multi‐Ethnic Study of Atherosclerosis and for other assays in COPDGene and SPIROMICS. Comparisons of relative quantification from the antibody‐based Olink platform and SOMAscan in a small cohort of myocardial infarction patients also show a wide correlation range. Finally, cis pQTL data, mass spectrometry aptamer confirmation, and other publicly available data are integrated to assess relationships with observed correlations. Correlation between proteomics assays shows a wide range and should be carefully considered when comparing and meta‐analyzing proteomics data across assays and studies.
Characterization of the Myofibrillar Proteome as a Way to Better Understand Differences in Bovine Meats Having Different Ultimate pH Values
Authors: Fuente‐Garcia Claudia , Sentandreu Enrique , Aldai Noelia , Oliván Mamen , Sentandreu Miguel Ángel
Published: May 2020

Influence of ultimate pH (pHu) on the occurrence of defective meats known as dark, firm, and dry (DFD) meats has been studied through a proteomic approach at early post‐mortem times. The myofibrillar sub‐proteome of longissimus thoracis et lumborum muscle from twelve loin samples from Asturiana de los Valles x Friesian yearling bulls, previously classified into two groups of six samples according to their pH values (normal, pHu < 6.0 and high, pHu ≥ 6.0), is analyzed at 24 h post‐mortem. Fractionation/enrichment of muscle samples is carried out by combining OFFGEL fractionation in the pH range 4–7 followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) of the retrieved liquid fractions. Four protein bands satisfactorily discriminate between meat samples with normal and high pHu. These bands are quantified by image analysis, and further identified by liquid chromatography‐mass spectrometry as desmin, pyruvate kinase, myosin light chain, and myosin heavy chain‐1 and ‐2. Coupling OFFGEL and SDS‐PAGE separation with MS provides detailed and reproducible myofibrillar protein profiles enabling comparison among the sample groups assayed. This makes feasible to identify biomarkers capable to better understand pre‐slaughter stress condition susceptible to give DFD meats with high pHu values.