bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the cortical capillary renamed as the transcortical vessel in diaphyseal vascularity?
Authors: Asghar Adil , Kumar Ashutosh , Kant Narayan Ravi , Naaz Shagufta
Published: May 2020

A recent article published in Nature Metabolism, “A network of trans‐cortical capillaries as a mainstay for blood circulation in long bones,” explained the long bone vascularity. In the mouse model, the authors demonstrated hundreds of transcortical vessels (TCVs) commencing from the bone marrow and traversing the whole cortical thickness. They realized that TCVs were the same as bleeding vessels of periosteal bed observed in the human tibia and femoral epiphysis during surgery. TCVs expressed arterial or venous markers and were proposed to be the backbone of bone vascularity as 80% of arterial and 59% of venous blood distributed through them. This new evidence challenged the existence of the “cortical capillaries” stated in previous literature. We conducted a review of the existing literature to compare this model with those in earlier research. The bone vascularity model was explained by many researchers who did their work in animal models like pig, dog, rabbit, and mouse. The TCVs were identified in these animal model studies as cortical capillaries or vessels of cortical canals. Studies are scarce, showing the presence of TCVs in humans. The role of TCVs in human cortical vascularity remains ambiguous until the substantial evidence is collected in future studies.
Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation
Authors: Lorenzi Teresa , Graciotti Laura , Sagrati Andrea , Reguzzoni Marcella , Protasoni Marina , Minardi Daniele , Milanese Giulio , Cremona Ottavio , Fabri Mara , Morroni Manrico
Published: May 2020

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35–40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase‐3 and caspase‐9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo‐mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8–13%) and undifferentiated (4–13%) cells reminiscent of STCs suggests a non‐negligible cell turnover.
Investigate the layout and age of a large‐scale mausoleum in Hangzhou, China using combined geophysical technologies and archaeological documents
Authors: Shi Zhanjie , Yu Tianxiang , Shi Mengyi
Published: May 2020

Geophysical techniques are used to detect mounds and burial chambers, but detecting the shape and layout of large mausoleums containing main tombs and ancillary facilities is a developing field. The shape and layout of mausoleums are closely related to cultural practices. In this study, integrated geophysical technologies were used to survey a large‐scale mausoleum in Hangzhou, China. The layout of the main tomb was deduced from magnetic gradient measurements, and the depth and scale were inferred from electrical resistivity tomography (ERT). The location and burial depth of ancillary facilities, including the mausoleum path, were characterized using the depth (time) slice of ground‐penetrating radar (GPR) three‐dimensional (3D) attribute analysis. An integrated interpretation of geophysical results combined with archaeological documents provides the plan and section layouts of the mausoleum. Based on integrated analyses and archaeological documents, the age of the mausoleum was inferred (middle to late Southern Song Dynasty). Subsequent test excavations partly confirmed the results and showed that the combination of geophysical technologies and archaeological documents are effective and valuable for detecting large‐scale mausoleums.
Achieving Adaptive Aromaticity in Cyclo[10]carbon by Screening Cyclo[n]carbon (n=8−24)
Authors: Dai Chenshu , Chen Dandan , Zhu Jun
Published: May 2020

Discovery of species with adaptive aromaticity (being aromatic in both the lowest singlet and triplet states) is particularly challenging as cyclic species are generally aromatic either in the ground state or in the excited state only, according to Hückel's and Baird's rules. Inspired by the recent realization of cyclo[18]carbon, here we demonstrate that cyclo[10]carbon possesses adaptive aromaticity by screening cyclo[n]carbon (n=8−24), which is supported by nucleus‐independent chemical shift (NICS), anisotropy of the current‐induced density (ACID), π contribution of electron localization function (ELFπ) and electron density of delocalized bonds (EDDB) analyses. Further study reveals that the lowest triplet state of cyclo[10]carbon is formed by in‐plane ππ* excitation. Thus, the major contribution to the aromaticity from out‐of‐plane π molecular orbitals does not change significantly in the lowest singlet state. Our findings highlight a crucial role of out‐of‐plane π orbitals in maintaining aromaticity for both the lowest singlet and triplet states as well as the aromaticity dependence on the number of the carbon in cyclo[n]carbon.
N‐Confused Porphyrin – A Unique “Turn‐On” Chemosensor for CN− and F− ions and “Turn‐Off” Sensor for ClO4− ions
Authors: Grover Nitika , Sankar Muniappan
Published: May 2020

N‐Confused meso‐tetrakis(4‐carbomethoxyphenyl)porphyrin (1) and its Ni(II) complex (1 a) have been synthesized and utilized for anion sensing studies, and the results are compared with N‐confused meso‐tetraphenylporphyrin (NCTPP). Anion susceptibilities of 1 and 1 a were investigated using spectroscopic, electrochemical, and DFT studies. Porphyrins 1 and 1 a were able to detect CN−, F−, and ClO4− ions selectively over the tested set of anions even at ppm level. Interestingly, the addition of ClO4− ions resulted in fluorescence quenching (turn off) whereas the addition of F− or CN− resulted in fluorescence enhancement (turn on). Notably, the TFA addition resulted in fluorescence quenching, whereas the fluorescence enhancement was observed while adding TBAOH. The higher association constant (Ka) values with anions, lower detection limit, and shifts in redox potentials are due to the electron‐withdrawing effect of the −COOCH3 group at the para‐position of the meso‐phenyl ring. This electron‐withdrawing nature is crucial for the higher affinity towards anions. The anion sensing description in this article may not only unveil the built‐in nature of N‐confused porphyrins, but may also provide a general proposal for the development of novel anion sensors based on porphyrinoids. The electron‐deficient porphyrin framework, large polarisable π‐system, and anion binding through the outer NH or a combination of the above factors serve as a foundation for N‐confused porphyrin to act as an anion sensor.
Twenty first century changes in Antarctic and Southern Ocean surface climate in CMIP6
Authors: Bracegirdle Thomas J. , Krinner Gerhard , Tonelli Marcos , Haumann F. Alexander , Naughten Kaitlin A. , Rackow Thomas , Roach Lettie A. , Wainer Ilana
Published: May 2020

Two decades into the 21st century there is growing evidence for global impacts of Antarctic and Southern Ocean climate change. Reliable estimates of how the Antarctic climate system would behave under a range of scenarios of future external climate forcing are thus a high priority. Output from new model simulations coordinated as part of the Coupled Model Intercomparison Project Phase 6 (CMIP6) provides an opportunity for a comprehensive analysis of the latest generation of state‐of‐the‐art climate models following a wider range of experiment types and scenarios than previous CMIP phases. Here the main broad‐scale 21st century Antarctic projections provided by the CMIP6 models are shown across four forcing scenarios: SSP1‐2.6, SSP2‐4.5, SSP3‐7.0 and SSP5‐8.5. End‐of‐century Antarctic surface‐air temperature change across these scenarios (relative to 1995–2014) is 1.3, 2.5, 3.7 and 4.8°C. The corresponding proportional precipitation rate changes are 8, 16, 24 and 31%. In addition to these end‐of‐century changes, an assessment of scenario dependence of pathways of absolute and global‐relative 21st century projections is conducted. Potential differences in regional response are of particular relevance to coastal Antarctica, where, for example, ecosystems and ice shelves are highly sensitive to the timing of crossing of key thresholds in both atmospheric and oceanic conditions. Overall, it is found that the projected changes over coastal Antarctica do not scale linearly with global forcing. We identify two factors that appear to contribute: (a) a stronger global‐relative Southern Ocean warming in stabilisation (SSP2‐4.5) and aggressive mitigation (SSP1‐2.6) scenarios as the Southern Ocean continues to warm and (b) projected recovery of Southern Hemisphere stratospheric ozone and its effect on the mid‐latitude westerlies. The major implication is that over coastal Antarctica, the surface warming by 2100 is stronger relative to the global mean surface warming for the low forcing compared to high forcing future scenarios.
The Binding Ability of a Bicyclic Somatostatin Analogue Towards Cu(II) Ions
Authors: Marciniak Aleksandra , Witak Weronika , Pieniężna Aleksandra , Brasuń Justyna
Published: May 2020

Somatostatin (SST) analogues have aroused the interest of scientists for years. This group of compounds is used in the diagnosis and treatment of neuroendocrine tumors. However, new molecules useful as radiopharmaceuticals in targeted therapy are still searched for. Bicyclic peptides seem to be very interesting in this context. These molecules are associated with beneficial properties. In this work, we present studies on the binding ability of the bicyclic analogue of somatostatin toward Cu(II) ions which could potentially be a chelator for copper radionuclides. The research is focused on the analysis of Cu(II) interactions with the metal binding cycle of the ligand and the influence of the receptor binding site on the coordination process. This is a novelty in comparison to the SST analogues used in medicine, where a metal ion is coordinated by a chelator and connected with a bioactive molecule by the linker. In this work, we present the first coordination study for a bicyclic ligand. The obtained results showed that the complexes with only imidazole donors are characterized by significantly higher stability in comparison to the other peptides.
Differential mechanisms of autophagy in cancer stem cells: Emphasizing gastrointestinal cancers
Authors: El‐Gowily Afnan H. , Abosheasha Mohammed A.
Published: May 2020

Gastrointestinal (GI) cancers are one of the most common forms of malignancies and still are the most important cause of cancer‐related mortality worldwide. Autophagy is a conserved catabolic pathway involving lysosomal degradation and recycling of whole cellular components, which is essential for cellular homeostasis. For instance, it acts as a pivotal intracellular quality control and repair mechanism but also implicated in cell reformation during cell differentiation and development. Indeed, GI cancer stem cells (CSCs) are thought to be responsible for tumour initiation, traditional therapies resistance, metastasis and tumour recurrence. Molecular mechanisms of autophagy in normal vs CSCs gain great interest worldwide. Here, we shed light on the role of autophagy in normal stem cells differentiation for embryonic progression and its role in maintaining the activity and self‐renewal capacity of CSCs which offer novel viewpoints on promising cancer therapeutic strategies based on the differential roles of autophagy in CSCs.
Emphysematous cystitis: A case report and literature review
Authors: Mukendi Alain Mwamba
Published: May 2020

Emphysematous cystitis is a rare potentially life‐threatening condition and a distinct type of complicated lower urinary tract infection generally associated with diabetes mellitus and diagnosed radiologically. This case report presents a case of emphysematous cystitis as post hiatal hernia repair infectious complication incidentally found on CT abdomen/pelvis.
Boronate Covalent and Hybrid Organic Frameworks Featuring PIII and P=O Lewis Base Sites
Authors: Pacholak Piotr , Gontarczyk Krzysztof , Kamiński Radosław , Durka Krzysztof , Luliński Sergiusz
Published: May 2020

Two covalent organic frameworks comprising Lewis basic PIII centers and Lewis acidic boron atoms were prepared by poly‐condensation reactions of newly obtained tris(4‐diisopropoxyborylphenyl)phosphine with 2,3,6,7,10,11‐hexahydroxytriphenylene and 2,3,6,7‐tetrahydroxy‐9,10‐dimethylanthracene. Obtained materials exhibit significant sorption of dihydrogen (100 cm3 g−1 at 1 bar at 77 K), methane (20 cm3 g−1 at 1 bar at 273 K) and carbon dioxide (50 cm3 g−1 at 1 bar at 273 K). They were exploited as solid‐state ligands for coordination of Pd0 centers. Alternatively, in a bottom‐up approach, boronated phosphine was treated with Pd2dba3 and poly‐condensated, yielding hybrid materials where the polymer networks are formed by means of covalent boronate linkages and coordination P−Pd bonds. In addition, the analogous materials based on phosphine oxide were synthesized. The DFT calculations on framework–guest interactions revealed that the behavior of adjacent boron and phosphorus/phosphine oxide centers is reminiscent of that found in Frustrated Lewis Pairs and may improve sorption of selected molecules.
A Facile Strategy to Fabricate Polysaccharide‐Based Magnetic Hydrogel Based on Enamine Bond†
Authors: Liu Hongchen , Yang Jingru , Yin Yunlei , Qi Haisong
Published: May 2020

Summary of main observation and conclusion

Magnetic hydrogels have found extensive applications in fields such as soft robotics, drug delivery and shape morphing. Here a facile method was fabricated to prepare polysaccharide‐based magnetic hydrogels. The chitosan‐Fe3O4 ferrofluid was obtained by dispersing carboxyl groups modified Fe3O4 nanoparticles uniformly in chitosan matrix. Subsequently, the magnetic polysaccharide hydrogel was obtained by simply mixing cellulose acetoacetate solution with chitosan‐Fe3O4 ferrofluid. The structures and properties of the magnetic hydrogel were analyzed using Fourier‐transform infrared spectroscopy, rheological recovery, responsiveness, and stability measurements. The results indicated that magnetic polysaccharide hydrogel showed pH responsiveness and excellent self‐healing properties, and the hydrogel manifested outstanding stability under physiological conditions (37 °C) for 72 h. In addition, the injectable polysaccharide‐based hydrogel exhibited sensitive magnetic responsive and shape‐shifting ability under an external magnetic field. Therefore, the strategy for the facile preparation of the magnetic polysaccharide‐based hydrogel in this work could provide a benign and versatile method for achieving self‐healing, responsive, injectable properties for the application in biomedical fields.
Genome‐defined African ancestry is associated with distinct mutations and worse survival in patients with diffuse large B‐cell lymphoma
Authors: Lee Michelle J. , Koff Jean L. , Switchenko Jeffrey M. , Jhaney C. Ileen , Harkins R. Andrew , Patel Sharvil P. , Dave Sandeep S. , Flowers Christopher R.
Published: May 2020

Background

Significant racial differences have been observed in the incidence and clinical outcomes of diffuse large B‐cell lymphoma (DLBCL) in the United States, but to the authors' knowledge it remains unclear whether genomic differences contribute to these disparities.

METHODS

To understand the influences of genetic ancestry on tumor genomic alterations, the authors estimated the genetic ancestry of 1001 previously described patients with DLBCL using unsupervised model‐based Admixture global ancestry analysis applied to exome sequencing data and examined the mutational profile of 150 DLBCL driver genes in tumors obtained from this cohort.

Results

Global ancestry prediction identified 619 patients with >90% European ancestry, 81 patients with >90% African ancestry, and 50 patients with >90% Asian ancestry. Compared with patients with DLBCL with European ancestry, patients with African ancestry were aged >10 years younger at the time of diagnosis and were more likely to present with B symptoms, elevated serum lactate dehydrogenase, extranodal disease, and advanced stage disease. Patients with African ancestry demonstrated worse overall survival compared with patients with European ancestry (median, 4.9 years vs 8.8 years; P = .04). Recurrent mutations of MLL2 (KMT2D), HIST1H1E, MYD88, BCL2, and PIM1 were found across all ancestry groups, suggesting shared mechanisms underlying tumor biology. The authors also identified 6 DLBCL driver genes that were more commonly mutated in patients with African ancestry compared with patients with European ancestry: ATM (21.0% vs 7.75%; P < .001), MGA (19.7% vs 5.33%; P < .001), SETD2 (17.3% vs 5.17%; P < .001), TET2 (12.3% vs 5.82%; P = .029), MLL3 (KMT2C) (11.1% vs 4.36%; P = .013), and DNMT3A (11.1% vs 4.52%; P = .016).

Conclusions

Distinct prevalence and patterns of mutation highlight an important difference in the mutational landscapes of DLBCL arising in different ancestry groups. To the authors' knowledge, the results of the current study provide the first‐ever characterization of genetic alterations among patients with African descent who are diagnosed with DLBCL.
EndoVIPER‐seq for Improved Detection of A‐to‐I Editing Sites in Cellular RNA
Authors: Knutson Steve D. , Heemstra Jennifer M.
Published: May 2020

Adenosine to‐inosine (A‐to‐I) RNA editing is a conserved post‐transcriptional modification that is critical for a variety of cellular processes. A‐to‐I editing is widespread in nearly all types of RNA, directly imparting significant global changes in cellular function and behavior. Dysfunctional RNA editing is also implicated in a number of diseases, and A‐to‐I editing activity is rapidly becoming an important biomarker for early detection of cancer, immune disorders, and neurodegeneration. While millions of sites have been identified, the biological function of the majority of these sites is unknown, and the regulatory mechanisms for controlling editing activity at individual sites is not well understood. Robust detection and mapping of A‐to‐I editing activity throughout the transcriptome is vital for understanding these properties and how editing affects cellular behavior. However, accurately identifying A‐to‐I editing sites is challenging because of inherent sampling errors present in RNA‐seq. We recently developed Endonuclease V immunoprecipitation enrichment sequencing (EndoVIPER‐seq) to directly address this challenge by enrichment of A‐to‐I edited RNAs prior to sequencing. This protocol outlines how to process cellular RNA, enrich for A‐to‐I edited transcripts with EndoVIPER pulldown, and prepare libraries suitable for generating RNA‐seq data. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: mRNA fragmentation and glyoxalation

Basic Protocol 2: EndoVIPER pulldown

Basic Protocol 3: RNA‐seq library preparation and data analysis
Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease
Authors: Cimini Flavia Agata , Barchetta Ilaria , Ciccarelli Gea , Leonetti Frida , Silecchia Gianfranco , Chiappetta Caterina , Di Cristofano Claudio , Capoccia Danila , Bertoccini Laura , Ceccarelli Valentina , Carletti Raffaella , Fraioli Antonio , Baroni Marco Giorgio , Morini Sergio , Cavallo Maria Gisella
Published: May 2020

Aims

Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non‐alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity.

Methods

We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies.

Results

Within our study population, NAFLD was significantly associated with greater VAT CD68+macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1‐α, IL‐8, MIP2, WISP‐1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco‐metabolic profile.

Conclusions

In obese patients, NAFLD is associated in a dose‐dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications.
Water balance of municipal wastewater irrigation in a coastal forested watershed
Authors: Gibson Nancy E. , Sun Ge , Nichols Elizabeth Guthrie
Published: May 2020

In the southeastern United States, coastal communities face challenges for water resources and wastewater treatment capacity. In North Carolina, 51 municipalities irrigate forests with municipal wastewater to absorb nutrients, reduce direct effluent discharge to surface waters, and recharge groundwater. Most facilities have land‐applied wastewater for decades, but there are no quantitative studies on the hydrologic impacts of this practice. This study developed a simulated water balance for the largest forest land‐application system in North Carolina which treats wastewater daily by irrigating 30 km2 of a mixed hardwood‐loblolly pine forest. A distributed hydrological model (MIKE SHE) was adapted to simulate 20 years of watershed evapotranspiration (ET) and water table depth (WTD) under irrigated and nonirrigated conditions. We found that irrigation impact to annual and monthly WTD was negligible in years with average and above average rainfall. For wet years, drainage increased with irrigation while ET and WTD remained similar to nonirrigated conditions. In dry years, ET was 31 to 39 mm higher in irrigated forest than nonirrigated forest though the change in groundwater storage remained close to zero annually. Our simulation study suggested that the drivers of on‐site drainage were predominantly rainfall and irrigation, and the annual watershed drainage increased in volumes equal to 93%–100% of the added annual irrigation input. This study offers insights to water balance dynamics in irrigated forests and coastal forest resiliency to variable wastewater hydraulic loading.
Plasma testosterone and arrhythmic events in male patients with arrhythmogenic right ventricular cardiomyopathy
Authors: Ren Jie , Chen Liang , Zhang Ningning , Chen Xiao , Zhao Qian , Chen Kai , Li Xiangjie , Ruschitzka Frank , Duru Firat , Song Jiangping
Published: May 2020

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with life‐threatening ventricular arrhythmia and progressive ventricular dysfunction. Previous studies suggested that sex hormones play an important role in the onset and prognosis of ARVC. This study aimed to investigate the role of testosterone in predicting major adverse cardiac events in the Chinese ARVC cohort.

Methods and results

Ninety‐nine ARVC patients (median age, 40 years; 70.7% male) and 96 healthy controls (median age, 41 years; 62.5% male) were enrolled. The circulating levels of testosterone were measured by enzyme‐linked immunosorbent assays (ELISA). The median follow‐up time of all ARVC male patients was 17 months (interquartile range/IQR 9–29). Cox proportional hazards regression was used to analyse the effect of plasma testosterone and other well‐described risk factors on malignant arrhythmic events in male ARVC patients. The male ARVC patients had significantly elevated levels of total testosterone [TT, 6.390 (4.438–8.768) ng/mL vs. 3.617 (2.073–4.479) ng/mL, P < 0.0001, data shown as the median with IQR], bioavailable testosterone [BT, 4.11 (1.990–6.545) ng/mL vs. 1.32 (0.7965–2.0350) ng/mL, P < 0.0001, median with IQR], and free testosterone [FT, 0.2055 (0.1000–0.4073) ng/mL vs. 0.0768 (0.0405–0.1105) ng/mL, P < 0.0001, median with IQR] than healthy male volunteer, whereas no differences were observed among female counterparts. There was no significant correlation between the baseline clinical characteristics and testosterone levels in male ARVC patients (Spearman's correlation test, P > 0.05). During the follow‐up, the levels of testosterone were higher in male patients who experienced malignant arrhythmic events (N = 22) than in those who did not (N = 25) [TT, 9.034 (7.222–15.370) ng/mL vs. 4.633 (3.363–6.375) ng/mL, P < 0.001; BT, 7.485 (2.070–9.163) ng/mL vs. 3.300 (1.685–4.690) ng/mL, P < 0.05; FT, 0.453 (0.221–0.758) ng/mL vs. 0.161 (0.075–0.337) ng/mL P < 0.05, data expressed as median (IQR) and adjusted by Dunn's multiple comparisons test], whereas such distinction was not observed among patients with significant structural progression events (N = 16). Through multivariable adjustments, the Cox regression analysis showed the level of plasma total testosterone (HR = 1.325, 95% confidence interval = 1.171–1.498, P < 0.001) was an independent predictor for malignant arrhythmic events.

Conclusions

The levels of plasma testosterone in ARVC male patients are higher than those in healthy males. Testosterone level, without relation to the baseline cardiac function and future significant structural progression events, is a strong predictor of future adverse arrhythmic events in male patients with ARVC. Therefore, our results suggest that testosterone may be a useful biomarker in arrhythmic risk prediction in the ARVC.
Diuretic and renal effects of spironolactone and heart failure hospitalizations: a TOPCAT Americas analysis
Authors: Kalogeropoulos Andreas P. , Thankachen Jincy , Butler Javed , Fang James C.
Published: May 2020

Aims

It is unclear whether spironolactone reduced heart failure (HF) hospitalizations in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial through potential diuretic or other effects. We examined the effects of spironolactone on weight, diuretic use, and renal function, and their subsequent impact on outcomes.

Methods and results

We analysed data from TOPCAT Americas (1767 patients with HF and preserved ejection fraction; 886 in spironolactone, 881 in placebo arm). We used mixed‐effects models for serial data and shared frailty models to identify determinants of recurrent HF hospitalizations among baseline and serial parameters. There were 800 HF hospitalizations after a median of 3.0 years. Despite more weight loss with spironolactone initially, weight trajectories overlapped after 12 months. Daily furosemide dose (time‐averaged Δ: −4.8% vs. +11.6%, P < 0.001) and thiazide use (−4.3% vs. +1.7%; P = 0.003) decreased with spironolactone; however, angiotensin‐converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use decreased also (−13.1% vs. −7.3%; P = 0.004). Serum creatinine increased more with spironolactone (+12.5% vs. +3.5%; P < 0.001). In time‐updated models, loop diuretic dose [hazard ratio (HR) per doubling 1.21; 95% confidence interval (CI) 1.10–1.32; P < 0.001], creatinine (HR per doubling 1.28; 95% CI 1.04–1.40; P = 0.019), and ACEI/ARB use (HR 0.82; 95% CI 0.67–1.00; P = 0.048) were associated with HF hospitalizations. However, the effect of spironolactone on HF hospitalizations persisted (HR 0.77; 95% CI 0.62–0.96; P = 0.021) in these models. Results were similar for cardiovascular mortality and time to first HF hospitalization.

Conclusions

In TOPCAT Americas, the benefit of spironolactone on outcomes could not be solely attributed to potential diuretic effects, suggesting the presence of non‐diuretic mechanisms.
Enhanced oral bioavailability and bioefficacy of phloretin using mixed polymeric modified self‐nanoemulsions
Authors: Wang Yiling , Li Dongli , Lin Huiqiong , Jiang Sen , Han Lei , Hou Shuli , Lin Shuying , Cheng Zhefeng , Bian Wangqing , Zhang Xinxin , He Yan , Zhang Kun
Published: May 2020

Phloretin (Ph) is a natural active ingredient with wide biological properties. However, its poor water‐solubility and low oral bioavailability limit the application significantly in functional food and drug. This study was to explore the mixed polymer Pluronic® F127 and P123 modified the different triglycerides (LCT, MCT, SCT) in self‐nanoemulsions (SNEs) for enhancing the oral bioavailability and bioefficacy of Ph. The SNEs were characterized in terms of physical property study, lipolysis study, pharmacokinetic study, and anti‐inflammatory effect. The water‐solubility of LCT‐Ph‐SNE increased 3000‐fold compared with Ph solution. Pharmacokinetic study of SNEs and other carriers (HP‐β‐CD, PVP) results indicated that LCT‐Ph‐SNE was 7.9‐fold more bioavailable compared with unformulated Ph. The anti‐inflammatory activity of LCT‐Ph‐SNE in vivo represented a 6.8‐fold enhancement compared with unformulated Ph. This novel SNE formulation may also be used for other poorly soluble ingredients with high loading capacity, which made a significant impact on functional food and drug.
Effect of salt mixture on flavor of reduced‐sodium restructured bacon with ultrasound treatment
Authors: Zhou Yu , Wang Yu , Pan Qiong , Wang Xi‐xi , Li Pei‐jun , Cai Ke‐zhou , Chen Cong‐gui
Published: May 2020

Flavor loss from sodium reduction is a large challenge faced in the meat industry. The effects of salt mixture (KCl: CaCl2 = 1:1, w/w) content (0%–1.0%) on flavor of reduced‐sodium (1.5% NaCl) restructured bacon with ultrasound treatment (UT, 600 w for 30 min) were investigated. The results showed that 0.5% salt mixture (0.25% KCl and 0.25% CaCl2) could significantly (p < .05) enhance the lipid oxidation, the protein oxidation, and the formation of free amino acids of reduced‐sodium UT‐restructured bacon and could also markedly (p < .05) improve its flavor and the overall quality of sensory evaluation via promoting the release of five kinds of volatile phenolic compounds (o‐cresol, m‐cresol, 2‐methoxy‐phenol, 2‐methoxy‐4‐methylphenol, and 2‐methoxy‐5‐methylphenol) and the formation of five kinds of volatile aldehyde compounds (hexanal, nonanal, decanal, furfural, and 5‐methyl furfural). It is interesting to understand the mechanism for the effect of salt mixture on flavor and to efficiently develop a technique for improving the flavor of reduced‐sodium products in the meat industry.
Vaccine Rationing and the Urgency of Social Justice in the Covid‐19 Response
Authors: Schmidt Harald
Published: May 2020

The Covid‐19 pandemic needs to be considered from two perspectives simultaneously. First, there are questions about which policies are most effective and fair in the here and now, as the pandemic unfolds. These polices concern, for example, who should receive priority in being tested, how to implement contact tracing, or how to decide who should get ventilators or vaccines when not all can. Second, it is imperative to anticipate the medium‐ and longer‐term consequences that these policies have. The case of vaccine rationing is particularly instructive. Ethical, epidemiological, and economic reasons demand that rationing approaches give priority to groups who have been structurally and historically disadvantaged, even if this means that overall life years gained may be lower.
Innovative Technologies to Promote Sustainable Recirculating Aquaculture in Eastern Africa—A Case Study of a Nile Tilapia (Oreochromis niloticus) Hatchery in Kisumu, Kenya
Authors: Clough Samuel , Mamo Julian , Hoevenaars Kyra , Bardocz Tamas , Petersen Paw , Rosendorf Poul , Atiye Tahla , Gukelberger Ephraim , Guya Edwin , Hoinkis Jan
Published: May 2020

Lake Victoria, regionally important both as a source of food and income, is under pressure due to overfishing and severe pollution. Currently, the vast majority of east African aquaculture is open-pond based. The adoption of modern and sustainable aquaculture technologies and practices—in this case study recirculating aquaculture systems (RAS)—will help the region increase food security and decrease its current reliance on imported fish and stressed wild stock. To this end, VicInAqua, a project under the EU Horizon 2020 program, has developed a pilot Nile Tilapia (Oreochromis niloticus) hatchery in Kisumu, Kenya using RAS adapted to local conditions. The hatchery is designed as a flexible, scalable, and modular system. An online monitoring system enables farmers to access farm data from both fish tanks and the supporting renewable energy systems, allowing around-the-clock monitoring and control. The hatchery is linked to a 14.3 kWp Photovoltaic (PV) system, including a 30 kWh Li-battery storage, to supply sustainable electricity. The water for the RAS, treated by a membrane bioreactor (MBR) and certified for use in aquaculture and agriculture, comes chiefly from Kisumu's municipal sewage, which reduces the farms' reliance on an expensive and occasionally intermittent potable water supply. Combining these technologies represents an industry first and offers a working example for larger-scale future developments. The purpose of the project is to demonstrate the possible technologies and practices in situ as well as provide a template for future development and investment. The hatchery is used by the Department of Livestock, Agriculture and Fisheries, Kisumu County, Kenya, as a training and demonstration facility to promote the aquaculture sector and increase the awareness, knowledge, and skills of fish farmers, as well as provide high quality fingerlings to cage farmers within the lake. Integr Environ Assess Manag 2020;16:934–941. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Distinct immune evasion in APOBEC‐enriched, HPV‐negative HNSCC
Authors: Messerschmidt Clemens , Obermayer Benedikt , Klinghammer Konrad , Ochsenreither Sebastian , Treue Denise , Stenzinger Albrecht , Glimm Hanno , Fröhling Stefan , Kindler Thomas , Brandts Christian H. , Schulze‐Osthoff Klaus , Weichert Wilko , Tinhofer Ingeborg , Klauschen Frederick , Keilholz Ulrich , Beule Dieter , Rieke Damian T.
Published: May 2020

Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA‐sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10). Public single‐cell gene expression data from 17 HPV‐negative HNSCC were separately reanalyzed. APOBEC3‐associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV‐negative HNSCC samples. An APOBEC‐enriched, HPV‐negative subgroup was identified, that showed higher T‐cell inflammation and immune checkpoint expression, as well as expression of APOBEC3 genes. Mutations in immune‐evasion pathways were also enriched in these tumors. Analysis of single‐cell sequencing data identified expression of APOBEC3B and 3C genes in malignant cells. We identified an APOBEC‐enriched subgroup of HPV‐negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
Attention and memory biases for aggressive information in college students with fragile high self‐esteem
Authors: Dai Jiaxing , Gao Heming , Zhang Lihua , Chen Hong
Published: May 2020

In this study, we examined attention and memory biases for aggressive information in two groups of college students. Individuals with fragile high self‐esteem (n = 30) and individuals with secure high self‐esteem (n = 30) first performed a dot‐probe task investigating attention bias, followed by a memory task. Incidental free recall of words presented in the memory task was then completed to assess memory bias. Results revealed that individuals with fragile high self‐esteem exhibited significant attention and memory biases for aggressive words compared with secure high self‐esteem individuals. Attention bias for aggressive words was positively correlated with memory bias in individuals with fragile high self‐esteem, but no correlation was found for individuals with secure high self‐esteem. These findings suggest that individuals with fragile high self‐esteem selectively attend to and remember aggression‐related information. They may process information in ways that are congruent with an aggression‐related schema. This study reveals the aggressive cognitive processes of individuals with fragile high self‐esteem, which may be related to aggression.
Cell and nucleus refractive‐index mapping by interferometric phase microscopy and rapid confocal fluorescence microscopy
Authors: Cohen‐Maslaton Shir , Barnea Itay , Taieb Almog , Shaked Natan T.
Published: May 2020

We present a multimodal technique for measuring the integral refractive index and the thickness of biological cells and their organelles by integrating interferometric phase microscopy (IPM) and rapid confocal fluorescence microscopy. First, the actual thickness maps of the cellular compartments are reconstructed using the confocal fluorescent sections, and then the optical path difference (OPD) map of the same cell is reconstructed using IPM. Based on the co‐registered data, the integral refractive index maps of the cell and its organelles are calculated. This technique enables rapidly measuring refractive index of live, dynamic cells, where IPM provides quantitative imaging capabilities and confocal fluorescence microscopy provides molecular specificity of the cell organelles. We acquire human colorectal adenocarcinoma cells and show that the integral refractive index values are similar for the whole cell, the cytoplasm and the nucleus on the population level, but significantly different on the single cell level.
On the maximum double independence number of Steiner triple systems
Authors: Lusi Dylan , Colbourn Charles J.
Published: May 2020

The maximum independence number of Steiner triple systems of order is well‐known. Motivated by questions of access balancing in storage systems, we determine the maximum total cardinality of a pair of disjoint independent sets of Steiner triple systems of order for all admissible orders.
Human cytomegalovirus infection is correlated with atherosclerotic plaque vulnerability in carotid artery
Authors: Li Dan , Li Bo , Yang Ling , Wang Jiawei
Published: May 2020

Background

Several studies have suggested that human cytomegalovirus (CMV) infection is closely related to the pathogenesis of atherosclerosis. The present study aimed to investigate the association between human CMV infection and carotid atherosclerotic plaque vulnerability in a Chinese population.

Methods

In total, 42 patients with carotid atherosclerosis (observation group) and 30 healthy volunteers (control group) were recruited in our study from October 2016 to January 2018. Statistical analysis was carried out to calculate the infection rate of CMV in subjects. Spearman's rank analysis was performed to evaluate the correlation between CMV infection and atherosclerotic plaque vulnerability.

Results

The positive rate of CMV was significantly higher in the observation group compared to the control group, and matrix metalloproteinase 9 (MMP‐9), tumor necrosis factor‐α (TNF‐α) and lectin‐like oxidized low density lipoprotein receptor‐1 (LOX‐1) expression levels were also elevated in the observation group compared to those in the control group. In carotid atherosclerotic patients, the detection rate of unstable plaques and the Crouse scores in vulnerable plaque were significantly higher in the CMV‐positive group compared to those in the CMV‐negative group. As revealed by correlation analysis, CMV infection was significantly positively correlated with plaque vulnerability and expression levels of MMP‐9, TNF‐α and LOX‐1 in carotid atherosclerotic patients.

Conclusions

Human CMV infection might be a potential risk factor for increased plaque vulnerability in patients with carotid atherosclerosis.
Longitudinal Structural MRI in Neurologically Healthy Adults
Authors: Gregory Sarah , Lohse Keith R. , Johnson Eileanoir B. , Leavitt Blair R. , Durr Alexandra , Roos Raymund A.C. , Rees Geraint , Tabrizi Sarah J. , Scahill Rachael I. , Orth Michael
Published: May 2020

Background

Structural brain MRI measures are frequently examined in both healthy and clinical groups, so an understanding of how these measures vary over time is desirable.

Purpose

To test the stability of structural brain MRI measures over time.

Population

In all, 112 healthy volunteers across four sites.

Study Type

Retrospective analysis of prospectively acquired data.

Field Strength/Sequence

3 T, magnetization prepared – rapid gradient echo, and single‐shell diffusion sequence.

Assessment

Diffusion, cortical thickness, and volume data from the sensorimotor network were assessed for stability over time across 3 years. Two sites used a Siemens MRI scanner, two sites a Philips scanner.

Statistical Tests

The stability of structural measures across timepoints was assessed using intraclass correlation coefficients (ICC) for absolute agreement, cutoff ≥0.80, indicating high reliability. Mixed‐factorial analysis of variance (ANOVA) was used to examine between‐site and between‐scanner type differences in individuals over time.

Results

All cortical thickness and gray matter volume measures in the sensorimotor network, plus all diffusivity measures (fractional anisotropy plus mean, axial and radial diffusivities) for primary and premotor cortices, primary somatosensory thalamic connections, and the cortico‐spinal tract met ICC. The majority of measures differed significantly between scanners, with a trend for sites using Siemens scanners to produce larger values for connectivity, cortical thickness, and volume measures than sites using Philips scanners.

Data Conclusion

Levels of reliability over time for all tested structural MRI measures were generally high, indicating that any differences between measurements over time likely reflect underlying biological differences rather than inherent methodological variability.

Level of Evidence

4.

Technical Efficacy Stage

1.
Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID‐19
Authors: Ni Ming , Tian Fang‐Bing , Xiang Dan‐Dan , Yu Bing
Published: May 2020

To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID‐19). A total of 27 patients with severe COVID‐19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin‐1β (IL‐1β), IL‐2 receptor (IL‐2R), IL‐6, IL‐8, IL‐10, tumor necrosis factor‐α (TNF)‐α, C‐reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL‐1β, IL‐2R, IL‐6, IL‐8, IL‐10, CRP, and serum ferritin) between male and female patients. Levels of IL‐2R, IL‐6, TNF‐α, and CRP decreased significantly after treatment, followed by IL‐8, IL‐10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL‐1β was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID‐19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro‐inflammatory response and decreased level of T lymphocytes were associated with severe COVID‐19.
Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID‐19 in Chongqing
Authors: Duan Jun , Wang Xiaohui , Chi Jing , Chen Hong , Bai Linfu , Hu Qianfang , Han Xiaoli , Hu Wenhui , Zhu Linxiao , Wang Xue , Li You , Zhou Chenmei , Mou Huaming , Yan Xiaofeng , Guo Shuliang
Published: May 2020

Mortality is high among severe patients with 2019 novel coronavirus‐infected disease (COVID‐19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID‐19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO2/FiO2 ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3‐6.0). Pulmonary inflammation index, platelet counts, sodium, C‐reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7‐0.8). And potassium, creatinine, temperature, and D‐dimer showed mild distinguishing power (each AUC between 0.6‐0.7). In addition, higher C‐reactive protein was associated with shorter time to progress to severe cases (r = −0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID‐19.
Association of gene polymorphisms of CD55 with susceptibility to and severity of hand, foot, and mouth disease caused by enterovirus 71 in the Han Chinese population
Authors: Li Mei , Li Ya‐Ping , Deng Hui‐Ling , Wang Mu‐Qi , Wang Wen‐Jun , Wang Jun , Wu Feng‐Ping , Dang Shuang‐Suo
Published: May 2020

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) can lead to high morbidity and mortality, and genetic background plays an important role during the disease process. We investigated the association between the single‐nucleotide polymorphism (SNP) rs2564978 of the CD55 gene and susceptibility to and severity of HFMD using the SNPs can multiple SNP typing methods. Soluble CD55 (sCD55) expression was significantly lower in the EV71 HFMD group than in the control group and lower in severe cases than in mild cases (P < .001). Moreover, CD55 rs2564978 (C vs T OR = 1.300, 95% CI, 1.120‐1.509) was associated with the risk of EV71 infection, and genotype TC was related to the severity of the infection (TC vs TT OR = 4.523, 95% CI, 2.033‐10.066). Our results suggest that sCD55 expression and the CD55 polymorphism rs2564978 may influence the susceptibility to and severity of EV71 infection.