bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro studies of Annona muricata L. extract‐loaded electrospun scaffolds for localized treatment of breast cancer
Authors: Akpan Udom M. , Pellegrini Michael , Salifu Ali A. , Obayemi John D. , Ezenwafor Theresa , Browe Daniel , Ani Chukwuemeka J. , Danyuo Yiporo , Dozie‐Nwachukwu Stella , Odusanya Olushola S. , Freeman Joseph , Soboyejo Winston O.
Published: May 2021

This paper presents in vitro studies of the sustained release of Annona muricata leaf extracts (AME) from hybrid electrospun fibers for breast cancer treatment. Electrospun hybrid scaffolds were fabricated from crude AME extracts, poly(lactic‐co‐glycolic acid)/gelatin (PLGA/Ge) and pluronic F127. The physicochemical properties of the AME extract and scaffolds were studied. The antiproliferative effects of the scaffolds were also assessed on breast cancer (MCF‐7 and MDA‐MB‐231) and non‐tumorigenic breast (MCF10A) cell lines. Scanning electron microscope micrographs revealed a random network of micro‐ and submicron fibers. In vitro drug release profiles, governed by quasi‐Fickian diffusion at pH 7.4 and non‐Fickian super case II at pH 6.7, showed initial burst AME release from the PLGA/Ge‐AME and PLGA/Ge‐F127/AME fibers at pH 7.4, and burst release from PLGA/Ge‐F127/AME (not observed from PLGA/Ge‐AME) at pH 6.7. Then, a slower, sustained release of the remaining AME from the fibers, attributed to the onset of degradation of the PLGA/Ge backbone, was observed for the next 72 hr. The cumulative release of AME was 89.33 ± 0.73% (PLGA/Ge‐AME) and 51.17 ± 7.96% (PLGA/Ge‐F127/AME) at pH 7.4, and 9.27 ± 2.3% and 73.5 ± 4.5%, respectively, at pH 6.7. Pluronic F127 addition increased the drug loading capacity and prolonged the sustained AME release from the fibers. The released AME significantly inhibited the in vitro growth of the breast cancer cells more than the non‐tumorigenic cells, due to the induction of apoptosis, providing evidence for using pluronic F127‐containing electrospun fibers for sustained and localized AME delivery to breast cancer cells.
The mechanism of cytotoxicity of 4‐nonylphenol in a human hepatic cell line involves ER‐stress, apoptosis, and mitochondrial dysfunction
Authors: Paolella Gaetana , Romanelli Antonio M. , Martucciello Stefania , Sposito Silvia , Lepretti Marilena , Esposito Carla , Capaldo Anna , Caputo Ivana
Published: May 2021

4‐Nonylphenol (4‐NP) is an emerging environmental pollutant widely diffused in waters and sediments. It mainly derives from the degradation of alkyl phenol ethoxylates, compounds commonly employed as industrial surfactants. 4‐NP strongly contaminates foods and waters for human use; thus, it displays a wide range of toxic effects not only for aquatic organisms but also for mammals and humans. After ingestion through the diet, it tends to accumulate in body fluids and tissues. One of the main organs where 4‐NP and its metabolites are concentrated is the liver, where it causes, even at low doses, oxidative stress and apoptosis. In the present study, we analyzed the effects of 4‐NP on a human hepatic cell line (HepG2) to deepen the knowledge of its cytotoxic mechanism. We found that 4‐NP, in a range of concentration from 50 to 100 μM, significantly reduced cell viability; it caused a partial block of proliferation and induced apoptosis with activation of caspase‐3 and overexpression of p53. Moreover, 4‐NP induced‐apoptosis seemed to involve both an ER‐stress response, with the appearance of high level of GRP78, CHOP and the spliced XBP1, and a dysregulation of mitochondrial physiology, characterized by an overexpression of main markers of mitochondrial dynamics. Our data support the idea that a daily consumption of 4‐NP‐contaminated foods may lead to local damages at the level of gastrointestinal system, including liver, with negative consequences for the organ physiology.
The comparison of structure, nature of bond, and electronic transitions in [M(η5‐Cp)(η5‐C60Me5)] (M = Fe2+, Ru2+, Os2+) hybrids and corresponding metallocenes; a theoretical study
Authors: Hokmi Samaneh , Salehzadeh Sadegh , Gholiee Yasin
Published: May 2021

In this paper, metallocene‐fullerene hybrid complexes, [M(η5‐Cp)(η5‐C60Me5)] (M = Fe2+, Ru2+, Os2+), as well as corresponding classical metallocenes have been studied theoretically at BP86/def2‐SVP and M06L/def2‐SVP levels of theory. With considering these metal complexes as an ABA′ system (B is the central metal ion and A and A′ are related η5‐ligands), the total interaction energies were calculated using common methods, as well as by calculating the interaction energies between the four defined pairs of fragments including A–B, B–A′, A–BA′, and AB–A′. The resulting data clearly showed that in all complexes there is a strong anticoopertivity between two metal‐(η5‐ligand) bonds. In order to understand the origin of difference in values of various calculated interactions in above two types of complexes, the nature of metal–ligand bonds was also studied using energy decomposition analysis‐natural orbital for chemical valence calculations. The results showed that in hybrid complexes, in contrast to metallocenes, the orbital interactions are considerably larger than electrostatic interactions.
High‐order harmonic generation by static coherent states method in single‐electron atomic and molecular systems
Authors: Eidi Mohammadreza , Vafaee Mohsen , Koochaki Kelardeh Hamed , Landsman Alexandra
Published: May 2021

We solve the time‐dependent Schrodinger equation using the coherent states as basis sets for computing high harmonic generation (HHG) in a full‐dimensional single‐electron “realistic” system. We apply the static coherent states (SCS) method to investigate HHG in the hydrogen molecular ion induced by a linearly polarized laser field. We show that SCS gives reasonable agreement compared to the three dimensional unitary split‐operator approach. Next, we study isolated attosecond pulse generation in . To do so, we employ the well‐known polarization gating technique, which combines two delayed counter‐rotating circular laser pulses, and opens up a gate at the central portion of the superposed pulse. Our results suggest that the SCS method can be used for full‐dimensional quantum simulation of higher dimensional systems such as the hydrogen molecule in the presence of an external laser field.
Screening of tumor grade‐related mRNAs and lncRNAs for Esophagus Squamous Cell Carcinoma
Authors: Gao Xin , Liu Qian , Chen Xue , Chen Shaoping , Yang Jianmei , Liu Qiang , Cheng Yufeng
Published: May 2021

Background

The goal of our study was to screen tumor grade‐related lncRNAs and mRNAs to reveal the underlying molecular mechanism of esophagus squamous cell carcinoma (ESCC).

Methods

The lncRNA and mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA). Tumor grade correlation analysis of lncRNAs and mRNAs was executed, followed by the functional enrichment analysis of all tumor grade‐related mRNAs. The differentially expression mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were obtained. PPI network and DEmRNA‐DElncRNA interaction analysis were constructed. The functional annotation of the DEmRNAs co‐expressed with DElncRNAs was performed. The expression levels of the candidate genes were validated using qRT‐PCR.

Results

A total of 1864 tumor grade‐related mRNAs (846 positively related and 1018 negatively related) and 552 tumor grade‐related lncRNAs (331 positively related and 221 negatively related) were obtained. The top 10 significantly grade‐related mRNAs and lncRNAs included CA12, FABP4, DECR1, BAIAP2, IL1RAPL2, PPARD, LAD1, TSPAN10, LDOC1, ZNF853, RP11‐25G10.2, RP11‐557H15.3, RP11‐521D12.5, CHKB‐AS1, RP11‐219B4.3, CH17‐335B8.4, RP11‐99 J16‐A.2, CTB‐111H14.1, ADNP‐AS1, and JHDM1D‐AS1. SFN, IL1RAPL2, and RP11‐25G10.2 were overlapped from grade 1, grade 2, and grade 3. PPI network showed that top 10 proteins with higher degrees, including GNAI1, RAP2B, GNAZ, SHH, ADCY1, PRKAR2B, SH3GL1, GNA15, and ARRB1. A DElncRNAs‐nearby DEmRNAs network was constructed to obtain hub lncRNAs including ADAMTS9‐AS2, RP11‐210 M15.2, RP11‐13 K12.1, ZBED3‐AS1, and RP11‐25G10.2. Except for RP11‐25G10.2, ADAMTS9‐AS1, ZBED3‐AS1, SFN, ATP1A2, and GNA15 were consistent with our TCGA analysis.

Conclusions

Alterations of DEmRNAs and DElncRNAs may provide key insights into the molecular mechanisms of ESCC.
Nonradioactive direct telomerase activity detection using biotin‐labeled primers
Authors: Wang Ruiguan , Li Jiangbo , Jin Rui , Ye Qinong , Cheng Long , Liu Rong
Published: May 2021

Background

Telomerase is a ribonucleoprotein enzyme responsible for maintenance of telomere length which expressed in more than 85% of cancer cells but undetectable in most normal tissue cells. Therefore, telomerase serves as a diagnostic marker of cancers. Two commonly used telomerase activity detection methods, the telomerase repeated amplification protocol (TRAP) and the direct telomerase assay (DTA), have disadvantages that mainly arise from reliance on PCR amplification or the use of an isotope. A safe, low‐cost and reliable telomerase activity detection method is still lacking.

Method

We modified DTA method using biotin‐labeled primers (Biotin‐DTA) and optimized the method by adjusting cell culture temperature and KCl concentration. The sensitivity of the method was confirmed to detect endogenous telomerase activity. The reliability was verified by detection of telomerase activity of published telomerase regulators. The stability was confirmed by comparing the method with TRAP method.

Results

Cells cultured in 32°C and KCl concentration at 200 mM or 250 mM resulted in robust Biotin‐DTA signal. Endogenous telomerase activity can be detected, which suggested an similar sensitivity as DTA using radioactive isotope markers. Knockdown of telomerase assembly regulator PES1 and DKC1 efficiently reduced telomerase activity. Compared with TRAP method, Biotin‐DTA assay offers greater signal stability over a range of analyte protein amounts.

Conclusion

Biotin‐labeled, PCR‐free, and nonradioactive direct telomerase assay is a promising new method for the easy, low‐cost, and quantitative detection of telomerase activity.
Alcohol consumption and serum uric acid are synergistically associated with renal dysfunction among community‐dwelling persons
Authors: Kawamoto Ryuichi , Kikuchi Asuka , Akase Taichi , Ninomiya Daisuke , Tokumoto Yoshio , Kumagi Teru
Published: May 2021

Background

Serum uric acid (SUA) is a key risk factor contributing to renal failure, a serious public health problem. However, few studies have examined whether the interactive relationship between alcohol consumption and SUA is independently associated with the estimated glomerular filtration rate (eGFR).

Methods

Our sample comprised 742 men aged 69 ± 11 years (mean ± standard deviation) and 977 women aged 69 ± 10 years from a rural area. We cross‐sectionally examined the relationships between the confounding factors of alcohol consumption and SUA with renal function denoted by eGFR estimated using CKD‐EPI (Chronic Kidney Disease Epidemiology Collaboration) equations modified by a Japanese coefficient.

Results

In both genders, eGFR increased with a rise in alcohol consumption. This tendency was more pronounced in participants with hyperuricemia, where SUA was greater than 7.0 mg/dL in men and greater than 6.0 mg/dl in women (men: F = 41.98, p < 0.001; women: F = 41.98, p < 0.001). A multiple linear regression analysis showed that alcohol consumption (men: β = 0.112, p < 0.001; women: β = 0.060, p = 0.011) and SUA (men: β = −0.282, p < 0.001; women: β = 0.317, p < 0.001) were significantly and independently related to eGFR. Further, the interactive relationship between alcohol consumption and SUA (men: F = 6.388, p < 0.001; women: F = 5.368, p < 0.001) was a significant and independent indicator of eGFR.

Conclusions

These results suggested that alcohol consumption and SUA were synergistically associated with renal dysfunction among community‐dwelling persons.
Meaningful military engagement among male and female post‐9/11 veterans: An examination of correlates and implications for resilience
Authors: Finkelstein‐Fox Lucy , Sinnott Sinead M. , Lee Sharon Y. , Carney Lauren M. , Park Crystal L. , Mazure Carolyn M. , Hoff Rani
Published: May 2021

Objective

Post‐9/11 military deployment is commonly reported as stressful and is often followed by psychological distress after returning home. Yet veterans also frequently report experiencing meaningful military engagement (MME) that may buffer detrimental effects of military stressors. Focusing on the under‐investigated topic of association of MME with post‐deployment psychological adjustment, this study tests gender differences in MME and post‐deployment outcomes.

Method

This cross‐sectional study examined the relationship of MME with deployment stressors, subsequent psychological distress (posttraumatic stress symptoms (PTSS) and depression), and gender among 850 recent‐era U.S. veterans (41.4% female).

Results

On average, both male and female veterans reported high MME. Greater MME was associated with less PTSS and depression following combat and general harassment, and more depression after sexual harassment. For men only, MME associated with less PTSS after sexual harassment.

Conclusions

MME is high among post‐9/11 veterans, but its stress‐buffering effects depend on gender and specific stressor exposure.
AMPK/mTOR downregulated autophagy enhances aberrant endometrial decidualization in folate‐deficient pregnant mice
Authors: Zhang Yan , Gao Rufei , Zhang Lei , Geng Yanqing , Chen Qiutong , Chen Xuemei , Liu Xueqing , Mu Xinyi , Ding Yubin , Wang Yingxiong , He Junlin
Published: May 2021

Existing evidence suggests that adverse pregnancy outcomes are closely related to dietary factors. Folate plays an important role in neural tube formation and fetal growth, folate deficiency is a major risk factor of birth defects. Our early studies showed that folate deficiency could impair enddecidualization, however, the mechanism is still unclear. Dysfunctional autophagy is associated with many diseases. Here, we aimed to evaluate the adverse effect of folate deficiency on endometrial decidualization, with a particular focus on endometrial cell autophagy. Mice were fed with no folate diet in vivo and the mouse endometrial stromal cell was cultured in a folate‐free medium in vitro. The decrease of the number of endometrial autophagosomes and the protein expressions of autophagy in the folate‐deficient group indicated that autophagosome formation, autophagosome‐lysosome fusion, and lysosomal degradation were inhibited. Autophagic flux examination using mCherry‐GFP‐LC3 transfection showed that the fusion of autophagosomes with lysosomes was inhibited by folate deficiency. Autophagy inducer rapamycin could reverse the impairment of folate deficiency on endometrial decidualization. Moreover, folate deficiency could reduce autophagy by disrupting AMPK/mTOR signaling, resulting in aberrant endometrial decidualization and adverse pregnancy outcomes. Further co‐immunoprecipitation examination showed that decidual marker protein Hoxa10 could interact with autophagic marker protein Cathepsin L, and the interaction was notably reduced by folate deficiency. In conclusion, AMPK/mTOR downregulated autophagy was essential for aberrant endometrial decidualization in early pregnant mice, which could result in adverse pregnancy outcomes. This provided some new clues for understanding the causal mechanisms of birth defects induced by folate deficiency.
Increased myocellular lipid and IGFBP‐3 expression in a pre‐clinical model of pancreatic cancer‐related skeletal muscle wasting
Authors: Cole Calvin L. , Bachman John F. , Ye Jian , Murphy Joseph , Gerber Scott A. , Beck Christopher A. , Boyce Brendan F. , Muthukrishnan Gowrishankar , Chakkalakal Joe V. , Schwarz Edward M. , Linehan David
Published: May 2021

Background

Skeletal muscle wasting (SMW) in cancer patients is associated with increased morbidity, mortality, treatment intolerance and discontinuation, and poor quality of life. This is particularly true for patients with pancreatic ductal adenocarcinoma (PDAC), as over 85% experience SMW, which is responsible for ~30% of patient deaths. While the established paradigm to explain SMW posits that muscle catabolism from systemic inflammation and nutritional deficiencies, the cause of death, and the cellular and molecular mechanisms responsible remain to be elucidated. To address this, we investigated the relationship between tumour burden and survival in the KCKO murine PDAC model.

Methods

Female C57BL/6J mice 6–8 weeks of age underwent orthotopic injection with KCKO‐luc tumour cells. Solid tumour was verified on Day 5, post‐tumour inoculation. In vivo, longitudinal lean mass and tumour burden were assessed via dual‐energy X‐ray absorptiometry and IVIS imaging, respectively, and total body weight was assessed, weekly. Animals were sacrificed at a designated end point of ‘failure to thrive’. After sacrifice, lower limb hind muscles were harvested for histology and RNA extraction.

Results

We found a strong correlation between primary tumour size and survival (r2 = 0.83, P < 0.0001). A significant decrease in lower limb lean mass was first detected at Day 38 post‐implantation vs. no tumour controls (NTCs) (P < 0.0001). SMW was confirmed by histology, which demonstrated a 38%, 32.7%, and 39.9% decrease in fibre size of extensor digitorum longus, soleus, and tibialis anterior muscles, respectively, in PDAC mice vs. NTC (P < 0.002). Histology also revealed a 67.6% increase in haematopoietic cells within the muscle of PDAC mice when compared with NTC. Bulk RNAseq on muscles from PDAC mice vs. NTC revealed significant increases in c/ebpβ/Δ, il‐1, il‐6, and tnf gene expression. Pathway analyses to identify potential upstream factors revealed increased adipogenic gene expression, including a four‐fold increase in igfbp‐3. Histomorphometry of Oil Red‐O staining for fat content in tibialis anterior muscles demonstrated a 95.5% increase in positively stained fibres from PDAC mice vs. NTC.

Conclusions

Together, these findings support a novel model of PDAC‐associated SMW and mortality in which systemic inflammation leads to inflammatory cell infiltration into skeletal muscle with up‐regulated myocellular lipids.
Light microscopy proved to be useful technique for morpho‐anatomical examination of four wild plant species growing sideways wastewater tunnels
Authors: Nadeem‐Ullah  , Ashraf Waqas , Shafiq‐ur‐Rehman  , Jaffer Mehwish , Qurat‐ul‐ain
Published: May 2021

The present study was conducted to determine the influence of wastewater used for irrigation purposes on anatomical characters of four wild plants with the help of light microscopy (LM). The plant selected were Trianthema portulacastrum L., Amaranthes viridis L., Portulaca oleracea L., and Persicaria barbata L. This wastewater comprises of municipal, industrial, and dairy waste containing organic matter, Ca++, Mg++, nitrogen, phosphorus, and potassium. It was found that T. portulacastrum L. and P. oleracea L. were directly affected and the size of vascular tissues and cortex reduced many times as compared to control, while on the other hand A. viridis L. and Persicaria berbata L. showed high growth than control these characters were clear using LM technique.
Land use and landscape position influence soil organic phosphorus speciation in a mixed land use watershed
Authors: Perillo Vanesa L. , Cade‐Menun Barbara J. , Ivancic Monika , Ross Donald S. , Wemple Beverley C.
Published: May 2021

Land use can significantly alter soil P forms, which will influence P loss in runoff. Organic P (Po) compounds are an important component of soil P, but their forms and cycling in soils with different land uses are still poorly understood. In addition, streambanks are potential sources of P loss; P forms and concentrations in streambank soils may vary with land use, affecting potential P loss to water. This study used solution 31P nuclear magnetic resonance spectroscopy to characterize and quantify P in interior and streambank soils (0–10 cm) under duplicate sites from four different land uses along streams in the Missisquoi River basin (VT, USA): silage corn, hay meadow, emergent wetlands, and forest. Orthophosphate monoesters were the dominant P compound class regardless of land use or landscape position. Forest soils had the lowest Po concentrations, less labile P forms than other soils, and significantly lower concentrations of total inositol hexakisphosphates and total orthophosphate monoesters compared with corn soils. Riparian buffer zones for agricultural soils lowered P concentrations in streambank soils for many soil P pools relative to interior soils. The wetland soils of this study had P concentrations and P forms that were similar to those for interior agricultural soils and generally showed no reduction in P concentrations in streambank soils relative to interior soils. This is consistent with the role of wetlands as P sinks in the landscape but also suggests these wetlands should be carefully monitored to minimize P accumulation, especially in streambank soils.
Abnormal VLCADD newborn screening resembling MADD in four neonates with decreased riboflavin levels and VLCAD activity
Authors: Hagemeijer Marne C. , Oussoren Esmee , Ruijter George J. G. , Onkenhout Willem , Huidekoper Hidde H. , Ebberink Merel S. , Waterham Hans R. , Ferdinandusse Sacha , de Vries Maaike C. , Huigen Marleen C. D. G. , Kluijtmans Leo A. J. , Coene Karlien L. M. , Blom Henk J
Published: May 2021

Early detection of congenital disorders by newborn screening (NBS) programs is essential to prevent or limit disease manifestation in affected neonates. These programs balance between the detection of the highest number of true cases and the lowest number of false‐positives. In this case report, we describe four unrelated cases with a false‐positive NBS result for very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD). Three neonates presented with decreased but not deficient VLCAD enzyme activity and two of them carried a single heterozygous ACADVL c.1844G>A mutation. Initial biochemical investigations after positive NBS referral in these infants revealed acylcarnitine and organic acid profiles resembling those seen in multiple acyl‐CoA dehydrogenase deficiency (MADD). Genetic analysis did not reveal any pathogenic mutations in the genes encoding the electron transfer flavoprotein (ETF alpha and beta subunits) nor in ETF dehydrogenase. Subsequent further diagnostics revealed decreased levels of riboflavin in the newborns and oral riboflavin administration normalized the MADD‐like biochemical profiles. During pregnancy, the mothers followed a vegan, vegetarian or lactose‐free diet which probably caused alimentary riboflavin deficiency in the neonates. This report demonstrates that a secondary (alimentary) maternal riboflavin deficiency in combination with reduced VLCAD activity in the newborns can result in an abnormal VLCADD/MADD acylcarnitine profile and can cause false‐positive NBS. We hypothesize that maternal riboflavin deficiency contributed to the false‐positive VLCADD neonatal screening results.
T2 Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing–Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance
Authors: Papadaki Efrosini , Mastorodemos Vasileios , Panou Theodora , Pouli Styliani , Spyridaki Eirini , Kavroulakis Eleftherios , Kalaitzakis Georgios , Maris Thomas G. , Simos Panagiotis
Published: May 2021

Background

Although diffusely abnormal white matter (DAWM) is commonly seen in multiple sclerosis (MS), it is rarely considered in clinical/imaging studies.

Purpose

To evaluate quantitative markers of microstructural changes in DAWM of patients with clinically isolated syndrome (CIS) and relapsing–remitting MS (RR‐MS) in relation to MS lesions and degree of neurocognitive impairment, by using a multi‐echo spin echo (MESE) Proton Density PD‐to‐T2 sequence.

Study Type

Prospective, cross‐sectional.

Population

Thirty‐seven RR‐MS patients, 33 CIS patients, and 52 healthy controls.

Field Strength/Sequence

1.5 T/T1‐, T2‐weighted, fluid‐attenuated inversion recovery, and MESE sequences.

Assessment

Long T2, short T2, and myelin water fraction (MWF) values were estimated as indices of intra/extracellular water content and myelin content, respectively, in DAWM, posterior periventricular normal appearing white matter (NAWM), and focal MS lesions, classified according to their signal intensity on T1 sequences. Patients were, also, administered a battery of neuropsychological tests.

Statistical Tests

Comparisons of T2 and MWF values in DAWM, NAWM, and MS lesions were examined, using two‐way mixed analyses of variance. Associations of Grooved Pegboard performance with T2 and MWF values in DAWM and NAWM were assessed using Pearson correlation coefficients.

Results

T2 and MWF values of DAWM were intermediate between the respective values of NAWM and T1 hypointense focal lesions, while there was no difference between the respective values of DAWM and T1‐isointense lesions. T2 values in DAWM were strongly associated with visuomotor performance in CIS patients.

Data Conclusion

Intra/extracellular water and myelin water content of DAWM are similar to those of T1‐isointense lesions and predict visuomotor performance in CIS patients.

Level of Evidence

2

Technical Efficacy

Stage 2
Cross‐Scanner Harmonization of Neuromelanin‐Sensitive MRI for Multisite Studies
Authors: Wengler Kenneth , Cassidy Clifford , van der Pluijm Marieke , Weinstein Jodi J. , Abi‐Dargham Anissa , van de Giessen Elsmarieke , Horga Guillermo
Published: May 2021

Background

Neuromelanin‐sensitive magnetic resonance imaging (NM‐MRI) is a validated measure of neuromelanin concentration in the substantia nigra–ventral tegmental area (SN–VTA) complex and is a proxy measure of dopaminergic function with potential as a noninvasive biomarker. The development of generalizable biomarkers requires large‐scale samples necessitating harmonization approaches to combine data collected across sites.

Purpose

To develop a method to harmonize NM‐MRI across scanners and sites.

Study Type

Prospective.

Population

A total of 128 healthy subjects (18–73 years old; 45% female) from three sites and five MRI scanners.

Field Strength/Sequence

3.0 T; NM‐MRI two‐dimensional gradient‐recalled echo with magnetization‐transfer pulse and three‐dimensional T1‐weighted images.

Assessment

NM‐MRI contrast (contrast‐to‐noise ratio [CNR]) maps were calculated and CNR values within the SN–VTA (defined previously by manual tracing on a standardized NM‐MRI template) were determined before harmonization (raw CNR) and after ComBat harmonization (harmonized CNR). Scanner differences were assessed by calculating the classification accuracy of a support vector machine (SVM). To assess the effect of harmonization on biological variability, support vector regression (SVR) was used to predict age and the difference in goodness‐of‐fit (Δr) was calculated as the correlation (between actual and predicted ages) for the harmonized CNR minus the correlation for the raw CNR.

Statistical Tests

Permutation tests were used to determine if SVM classification accuracy was above chance level and if SVR Δr was significant. A P‐value <0.05 was considered significant.

Results

In the raw CNR, SVM MRI scanner classification was above chance level (accuracy = 86.5%). In the harmonized CNR, the accuracy of the SVM was at chance level (accuracy = 29.5%; P = 0.8542). There was no significant difference in age prediction using the raw or harmonized CNR (Δr = −0.06; P = 0.7304).

Data Conclusion

ComBat harmonization removes differences in SN–VTA CNR across scanners while preserving biologically meaningful variability associated with age.

Level of Evidence

2

Technical Efficacy

1
Cyber forensic framework for big data analytics using Sunflower Jaya optimization‐based Deep stacked autoencoder
Authors: Venugopal Sabaresan , Sathianesan Godfrey Winster , Rengaswamy Ramesh
Published: May 2021

The skills of forensic analysts are at risk to process the increasing data in the Internet of Things‐based environment platforms. However, the technical issues like anti‐forensics, variety of traffic formats, steganography or encrypted data, and real‐time live investigation degrades the performance of the cyber forensic framework. Therefore, an effective method named Sunflower Jaya Optimization‐based Deep stacked autoencoder (SFJO‐based Deep stacked autoencoder) is proposed to perform the cyber forensic framework. The finite element model of Sunflower optimization is integrated with the control parameters of Jaya optimization to solve the issues in the cyber forensic framework. The proposed SFJO‐based Deep stacked autoencoder uses the pollination and the peculiar behaviors to enable the cyber forensic framework based on the error value in the big data analytics model. Accordingly, the solution with the minimal value of error is accepted as the best optimal solution by computing the orientation vector. However, the proposed model is illustrated based on the unconstrained benchmark function, which in turn results in the fitness function to reveal the best candidate solution. The proposed SFJO‐based Deep stacked autoencoder attained better performance using metrics like precision, sensitivity, and specificity with the values of 0.9053, 0.8865, and 0.8839 using dataset‐1.
Comparison of the effects of two therapeutic strategies based on olfactory ensheathing cell transplantation and repetitive magnetic stimulation after spinal cord injury in female mice
Authors: Delarue Quentin , Robac Amandine , Massardier Romane , Marie Jean‐Paul , Guérout Nicolas
Published: May 2021

Spinal cord injury (SCI) is a debilitating condition, which leads to a permanent loss of functions below the injury site. The events which take place after SCI are characterized by cellular death, release of inhibitory factors, and inflammation. Many therapies have been studied to cure SCI, among them magnetic stimulation aims to reduce the secondary damages in particular by decreasing apoptosis, while, cellular transplantation promotes neuroregeneration by enhancing axonal regrowth. In the present study, we compared individually primary olfactory ensheathing cell (OEC) transplantation and repetitive trans‐spinal magnetic stimulation (rTSMS) and then, we combined these two therapeutic approaches on tissue repair and functional recovery after SCI. To do so, SCIs were performed at Th10 level on female C57BL/6 mice, which were randomized into four groups: SCI, SCI + primary bOECs, SCI + STM, SCI + primary bulbar olfactory ensheathing cells (bOECs) + stimulation (STM). On these animals bioluminescence, immunohistological, and behavioral experiments were performed after SCI. Our results show that rTSMS has beneficial effect on the modulation of spinal scar by reducing fibrosis, demyelination, and microglial cell activation and by increasing the astroglial component of the scar, while, primary bOEC transplantation decreases microglial reactivity. At the opposite, locotronic experiments show that both treatments induce functional recovery. We did not observed any additional effect by combining the two therapeutic approaches. Taken together, the present study indicates that primary bOEC transplantation and rTSMS treatment act through different mechanisms after SCI to induce functional recovery. In our experimental paradigm, the combination of the two therapies does not induce any additional benefit.
Endogenous µ‐opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain
Authors: Cooper Andrew H. , Hedden Naomi S. , Corder Gregory , Lamerand Sydney R. , Donahue Renee R. , Morales‐Medina Julio C. , Selan Lindsay , Prasoon Pranav , Taylor Bradley K.
Published: May 2021

Tissue injury induces a long‐lasting latent sensitization (LS) of spinal nociceptive signaling that is kept in remission by an opposing µ‐opioid receptor (MOR) constitutive activity. To test the hypothesis that supraspinal sites become engaged, we induced hindpaw inflammation, waited 3 weeks for mechanical hypersensitivity to resolve, and then injected the opioid receptor inhibitors naltrexone, CTOP or β‐funaltrexamine subcutaneously, and/or into the cerebral ventricles. Intracerebroventricular injection of each inhibitor reinstated hypersensitivity and produced somatic signs of withdrawal, indicative of LS and endogenous opioid dependence, respectively. In naïve or sham controls, systemic naloxone (3 mg/kg) produced conditioned place aversion, and systemic naltrexone (3 mg/kg) increased Fos expression in the central nucleus of the amygdala (CeA). In LS animals tested 3 weeks after plantar incision, systemic naltrexone reinstated mechanical hypersensitivity and produced an even greater increase in Fos than in sham controls, particularly in the capsular subdivision of the right CeA. One third of Fos+ profiles co‐expressed protein kinase C delta (PKCδ), and 35% of PKCδ neurons co‐expressed tdTomato+ in Oprm1Cre::tdTomato transgenic mice. CeA microinjection of naltrexone (1 µg) reinstated mechanical hypersensitivity only in male mice and did not produce signs of somatic withdrawal. Intra‐CeA injection of the MOR‐selective inhibitor CTAP (300 ng) reinstated hypersensitivity in both male and female mice. We conclude that MORs in the capsular subdivision of the right CeA prevent the transition from acute to chronic postoperative pain.
Characterizing clinical outcomes and factors associated with conduction gaps in VISITAG SURPOINT‐guided catheter ablation for atrial fibrillation
Authors: Inoue Koichi , Tanaka Nobuaki , Ikada Yusuke , Mizutani Akihiro , Yamamoto Kazuhiko , Matsuhira Hana , Harada Shinichi , Okada Masato , Iwakura Katsuomi , Fujii Kenshi
Published: May 2021

Purpose

Although usefulness of VISITAG SURPOINT (VS) on pulmonary vein isolation (PVI) in catheter ablation of atrial fibrillation has been reported, optimal VS thresholds can depend on the inter‐tag distance (ITD) and vice versa. We validated the efficacy of PVI with lower target ITDs and VS values than in previous studies.

Methods

Retrospective review of consecutive patients (N = 100) with paroxysmal (n = 32) or persistent AF (n = 68) undergoing VS‐guided ablation between 09/2018 and 08/2019 was conducted. All procedures were performed by two operators. Target VS values were 425 (anterior), 375 (posterior), and 325 (near the esophagus). Target ITD was 4 mm.

Results

Acute PVI was achieved in all cases, however, 13 residual gaps in 12 patients were observed after initial encirclement (first pass isolation: 88%). Ten gaps due to spontaneous PV reconnections (PVR) were found in nine patients (9%). These 23 gaps had similar median VS (gap‐related vs non‐gap: 429 vs 410, P = .4545) and power (36 vs 36W, P = .4843), higher contact force (13.8 vs 11.0g, P = .0061), and larger ITD (5.3 vs 3.7mm, P < .001) when compared to the remaining tags. Only ITDs were independently associated with gap formation in multivariate analysis. One‐year Kaplan‐Meier freedom from any atrial arrhythmia was 87.2%. Eight patients received repeat ablation (8.1%) and of these, 6 (75%) were free from PVR.

Conclusion

Favorable rates of first pass isolation, acute PVR, and long‐term procedure success were achieved using lower VS values than in previous reports. With a target VS value of 375‐425, ITDs of 4 mm was sufficient for durable PVI.
Heat waves in spring from Senegal to Sahel: Evolution under climate change
Authors: Sambou Marie‐Jeanne Gnacoussa , Pohl Benjamin , Janicot Serge , Landry Famien Adjoua Moïse , Roucou Pascal , Badiane Daouda , Gaye Amadou Thierno
Published: May 2021

This study analyses the long‐term (1950–2100) observed and projected changes in springtime (March–May) heat waves (HWs) in West Africa under climate change. To that end, 28 climate models participating to the fifth Coupled Model Intercomparison Project (CMIP5) are considered, after a statistical post‐correction of their biases. A multi‐scale approach is proposed, covering the Sahel, Senegal, and three thermally‐coherent zones within Senegal. HWs are defined as a sequence of at least three consecutive days above a moving 95th percentile of current temperature distributions. Climate change over Senegal translates into a general shift of the whole statistical distribution towards higher temperature values, with a general stability in the shape of the distribution. Ongoing mean warming could reach +5°C in 2100 under RCP8.5 scenario, implying that coastal Senegal could experience then a mean climate comparable to the hinterland parts today. HWs have increased in intensity, frequency and duration across Sahel and Senegal over the past years, such intensification being higher on recent decades. Future HWs over all regions present intrinsic properties that radically differ from those observed so far. The severity and length of HWs displayed stationary conditions until the late 1990s, but started increasing since then. Projected changes show marked and rapid increase in these variables, the amplitude of which is primarily RCP‐dependent, and secondarily region‐dependent. For both metrics, the largest changes occur over hinterland Senegal and Sahel. There, under RCP8.5 and after the 2070s, the whole spring season could be considered as a permanent HW lasting 3 months. Along the coast, by contrast, average temperatures are both weaker and more variable, causing more frequent threshold crossings and limiting the duration of HWs. The multi‐scale approach used here highlights contrast within Senegal, which constitutes important information for public policy decision‐makers and its inhabitants in terms of adaptation to climate change.
Maximum extent and readvance dynamics of the Irish Sea Ice Stream and Irish Sea Glacier since the Last Glacial Maximum
Authors: Scourse J. D. , Chiverrell R. C. , Smedley R. K. , Small D. , Burke M. J. , Saher M. , Van Landeghem K. J. J. , Duller G. A. T. , Cofaigh C. Ó , Bateman M. D. , Benetti S. , Bradley S. , Callard L. , Evans D. J. A. , Fabel D. , Jenkins G. T. H. , McCarron S. , Medialdea A. , Moreton S. , Ou X. , Praeg D. , Roberts D. H. , Roberts H. M. , Clark C. D.
Published: May 2021

The BRITICE‐CHRONO Project has generated a suite of recently published radiocarbon ages from deglacial sequences offshore in the Celtic and Irish seas and terrestrial cosmogenic nuclide and optically stimulated luminescence ages from adjacent onshore sites. All published data are integrated here with new geochronological data from Wales in a revised Bayesian analysis that enables reconstruction of ice retreat dynamics across the basin. Patterns and changes in the pace of deglaciation are conditioned more by topographic constraints and internal ice dynamics than by external controls. The data indicate a major but rapid and very short‐lived extensive thin ice advance of the Irish Sea Ice Stream (ISIS) more than 300 km south of St George's Channel to a marine calving margin at the shelf break at 25.5 ka; this may have been preceded by extensive ice accumulation plugging the constriction of St George's Channel. The release event between 25 and 26 ka is interpreted to have stimulated fast ice streaming and diverted ice to the west in the northern Irish Sea into the main axis of the marine ISIS away from terrestrial ice terminating in the English Midlands, a process initiating ice stagnation and the formation of an extensive dead ice landscape in the Midlands.
Transarterial Embolization for Bleeding in Patients with Head and Neck Cancer: Who Benefits?
Authors: Chatani Shohei , Sato Yozo , Murata Shinichi , Hasegawa Takaaki , Tsukii Ryota , Nagasawa Kyohei , Machida Masanori , Yoshihara Terutaka , Yamaura Hidekazu , Hanai Nobuhiro , Matsuo Keitaro , Inaba Yoshitaka
Published: May 2021

Objectives/Hypothesis

The present study aimed to investigate the efficacy of transarterial embolization (TAE) for bleeding in patients with head and neck cancer (HNC) and to evaluate the prognostic factors after TAE.

Study design

Outcome study.

Methods

This retrospective study included 31 consecutive patients (27 men and 4 women; median age, 61 years) who presented uncontrollable hemorrhage associated with HNC and underwent emergency TAE at our institution during a 10‐year period (January 2011–December 2020). This corresponded to 40 TAE procedures, including 27 cases with an unstable status (circulatory and/or respiratory insufficiency) and 10 cases with carotid blowout syndrome. The technical success rate and adverse events were analyzed on a per‐procedure basis. The rebleeding and overall survival (OS) rates were analyzed on a per‐patient basis, and the factors related to OS were evaluated.

Results

The technical success rate was 100%. As an adverse event, cerebral infarction was found in three cases with carotid blowout syndrome. The rebleeding rate at 30 days after TAE and in the follow‐up period (range, 9–3,004 days) was 17.2% and 35.5%, respectively. The median survival time was 263 days (95% confidence interval: 124.0–402.0 days). In the log‐rank test, complete remission (CR) of the primary cancer at the time of the first TAE was identified as a significant influencing factor of survival.

Conclusion

TAE is effective for the treatment of hemorrhage associated with HNC even in patients with an unstable status. Patients with CR can gain a long life span.

Level of Evidence

4 Laryngoscope, 131:E2777–E2783, 2021
Pea and lentil flour quality as affected by roller milling configuration
Authors: Motte Jean‐Charles , Tyler Robert , Milani Aidin , Courcelles Janelle , Der Tanya
Published: May 2021

This study examined the effects of roller mill configuration on pulse flour quality. Dehulled yellow pea and green lentil were ground to flour using a laboratory roller mill characterized by its flexibility to control particle size reduction while maintaining a constant feed rate. The milling diagram length (long, six passes vs. short, four passes) and sieve sizes (large, 300 μm vs. tight, 180/150 μm) were adjusted for a total of four milling configurations. Each flour stream was characterized with respect to its physical properties and chemical composition. No notable differences were identified between pea and lentil based on how the milling configuration influenced flour characteristics. Overall, combining streams to produce a whole flour did not affect the chemical composition but resulted in variability for physical characteristics as indicated by a tendency toward increased levels of damaged starch with the shorter milling diagram. Damaged starch content was found to be indirectly associated (p < 0.05) with the particle size distribution, where the highest concentrations were noted in flours with median distributions below 30 μm. When individual streams were compared across milling configurations, the stream itself was rarely found to significantly influence flour physicochemical properties. However, the variation exhibited in particle‐size distribution, protein, starch, ash, and damaged starch content could have practical relevance given the many significant (p < 0.05) correlations with functional properties that could subsequently affect the end‐use applicability of flours. This would imply that specialized flours could be made with the intention of being used for defined food applications.
Evaluating the effect of light exposure and seed coat on lentil cotyledon color by computer vision
Authors: Jackson Nsuhoridem , Noble Scott D. , Vandenberg Albert
Published: May 2021

A computer vision system and color analysis algorithms were employed to study the influence of UVA (ultraviolet‐A) and visible light on the color of lentils with red, green, and yellow cotyledons. Twenty samples of cotyledons from each of the three‐color classes were subjected to six light treatments (ultraviolet, full‐spectrum visible, red, green, blue, and dark control) for 7 days at room temperature. The International Commission on Illumination L*a*b* (CIE L*a*b*) color values of the individual seeds were obtained before and after each treatment using the computer vision and image analysis system. Results of the analysis showed that light exposure had a statistically significant effect on all three cotyledon color classes. The effect size was largest for green lentils, smaller in yellow, and least in red lentils. By having established that light exposure affects the color of lentil cotyledons, it was hypothesized that seed coats may protect cotyledons against the effects of light exposure and that the degree of protection would vary with seed coat color classification. This hypothesis was tested using green‐cotyledon lentil varieties with different seed coat classes. Results confirmed that light‐induced color loss in the cotyledons was significantly influenced by seed‐coat color class. The order of protective effect of lentil seed coat from least to highest was found to be as follows: gray‐zero tannin, green, normal gray, and black. Thus, breeding for seed coat protection may improve the overall quality of green lentils. The results from this study will be informative to breeding programs that focus on enhancing the cotyledon color of lentils, and in making decisions regarding the dehulling of lentils and the design of dehulled lentil materials handling.
The new “cubism” graft technique in tympanoplasty: A randomized controlled trial
Authors: Kaya İsa , Şahin Fetih Furkan , Tanrıverdi O Hasan , Kirazlı Tayfun
Published: May 2021

Objectives

The aim of this prospective, randomized‐controlled study is to analyze the outcomes of a new graft technique in tympanoplasty and compare its outcomes with cartilage island graft plus extra perichondrium.

Methods

A total of 44 patients with noncomplicated chronic otitis media were included in this prospective randomized‐controlled clinical trial. Patients were randomly divided into 2 double‐layer graft groups: The cartilage island graft + cubism graft (study group) and the cartilage island graft + extra perichondrium (control group). The main outcome measures of the study were the air‐bone gap (ABG), ABG gain, and graft status.

Results

Graft success rate was 100% and 95.5% in the study group and the control group, respectively. There were statistically significant differences in the postoperative first month ABG and ABG gain between study and control groups (P < .05). ABG and ABG gain showed no significant differences in the postoperative sixth month between groups (P > .05).

Conclusion

This study revealed that both graft techniques have satisfactory functional and morphological results compared to preoperative findings. The use of cubism graft with cartilage island graft has significantly better auditory outcomes in short‐term and similar results in long‐term compared to double‐layered cartilage island graft with extra perichondrium. Cubism graft is a highly promising graft technique with its many advantages.

Level of Evidence

1b.