bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐inflammatory and anti‐aggregating effects of rangpur in the first trimester of growth: ultra‐performance liquid chromatography–electrospray mass spectrometry profile and quantification of hesperidin
Authors: Lemos da Silva Layzon A , de Athayde Amanda E , Moreira Monalisa A , Tizziani Tiago , Gkionis Stephanie V , da Silva Lucas V , Biavatti Maique W , de Moraes Ana Carolina R , dos Santos Nascimento Marcus V P , Dalmarco Eduardo M , Sandjo Louis P
Published: January 2022

BACKGROUND

Citrus fruits are a rich source of valuable molecules, and their industrial processing produces bagasses, little explored to generate important by‐products. These Citrus residues, including seeds and peels, also contain numerous pharmacologically important substances. To reduce the impact of these Citrus by‐products, young, harvested fruits could be used as a functional supplemental food while another part is grown until maturity for industrial production. This study therefore aims to valorize rangpur (Citrus limonia) in the first 3 months of its growth by investigating and comparing its monthly chemical profiles using ultra‐performance liquid chromatography–electrospray mass spectrometry (UPLC–ESI–MS) and its anti‐inflammatory and antiplatelet activity.

RESULTS

Extracts obtained from the fruits harvested in November, December, and January, 2017 and 2018 (L221117, L161217, and L160118) showed different UPLC–ESI–MS profiles. Twenty‐five of the 26 detected metabolites were identified as cyclitol, pyrrolidine betaine, aryl propanoyl esters, chlorogenic acids, flavonoids, coumarins, and limonoids. Quantification studies indicated an increased concentration of hesperidin from the younger fruits to the older fruits of the series. L160118 reduced nitrogen oxide (NOx), tumor necrosis factor alpha (TNF‐α), and interleukin 6 (IL‐6) levels more than other extracts. Their activity followed the same trends as the hesperidin concentration in each fruit. In contrast, the most promising antiplatelet activity was observed with the extracts from the two youngest fruits. This suggests combined effects of the chemical components found in these fruits' extracts.

CONCLUSION

The extracts obtained from these young fruits showed considerable anti‐inflammatory and antiplatelet activity. Overall, young rangpur could be used as raw material to produce functional foods without producing any waste. © 2022 Society of Chemical Industry.
Proteomic analyses of mitochondrial damage in postmortem beef muscles
Authors: Liu Chunmei , Wei Qichao , Li Xia , Han Dong , Liu Jiqian , Huang Feng , Zhang Chunhui
Published: January 2022

BACKGROUND

The objective of the study was to examine the expression profiles of mitochondrial proteins in at‐death and 24 h postmortem (PM) using tandem mass tag (TMT) approach to characterize the mitochondria possible mechanisms that are affiliated with tenderization.

RESULTS

Results showed that the tender meat at 24 h PM emerged with more serious mitochondrial damage. Altogether 456 mitochondrial proteins were identified, including 442 down‐regulated and 14 up‐regulated proteins. These differentially‐expressed proteins were primarily involved in the progress of PM energy metabolism, apoptosis, and the morphological alterations of mitochondrial. Among them, 47 subunits (such as NDUFA2, COX4I1, and ATP5PB) were annotated into the oxidative phosphorylation pathway. VDAC1, VDAC2, and VDAC3 involving in the damage of MPTP, and IMMT, CHCHD3, APOL and APOO modulating the morphology of mitochondria, and DIABLO and AIFM1 released from mitochondria affect caspase's activation. HSPD1 and HSPE1 involved in apoptosis, mitochondrial physiological and morphological alterations.

CONCLUSION

The earlier‐mentioned proteins were validated as potential indicators of tenderness regulated by mitochondrial damage. These results highlighted that mitochondrial damage possibly participate in PM tenderization of beef muscles by energy metabolism and cell apoptosis status. © 2022 Society of Chemical Industry.
Chemical profiling of Qingfei Paidu Decoction by triplex off‐line two‐dimensional liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Shen Aijin , Zhou Weijia , Xiong Lele , Jin Hongli , Yu Long , Wu Huimin , Yu Wenyi , Yu Dongping , Guo Zhimou , Liu Yanfang , Liang Xinmiao
Published: January 2022

Qingfei Paidu Decoction is a Chinese medicine formula that has been proved effective in the treatment of coronavirus disease 2019. However, the comprehensive separation and characterization of Qingfei Paidu Decoction are of a great challenge due to the diversity of chemical components in a wide range of polarity. In this study, a triplex off‐line two‐dimensional liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry is developed for the analysis of Qingfei Paidu Decoction. One reversed‐phase liquid chromatography×hydrophilic interaction liquid chromatography system and two reversed‐phase liquid chromatography×reversed phase liquid chromatography systems were constructed to separate polar components and weak‐polar components in Qingfei Paidu Decoction, respectively. Benefiting from the good orthogonality of two‐dimensional liquid chromatography and high sensitivity of quadrupole time‐of‐flight MS, chemical components with different polarities and content were discovered. A total of 749 peaks were detected in positive and negative ionization mode and presented as a four‐dimensional data plot. Meanwhile, 498 compounds belonging to 14 categories were tentatively identified. These results provide good supplementary to elucidate the material basis of Qingfei Paidu Decoction. The triplex off‐line two‐dimensional liquid chromatography‐quadrupole time‐of‐flight mass spectrometry strategy can be a powerful and efficient tool for the separation and characterization of chemical substances in traditional Chinese medicine formulas.
Salting‐out homogeneous liquid‐liquid microextraction for the determination of azole drugs in human urine: Validation using total error concept
Authors: Manousi Natalia , Vlachaki Adamantia , Kika Fotini S. , Markopoulou Catherine K. , Tzanavaras Paraskevas D. , Zacharis Constantinos K.
Published: January 2022

A salting‐out homogeneous liquid‐liquid microextraction was proposed for the quantification of four azole drugs in human urine prior to high‐performance liquid chromatography analysis. The procedure involved the mixing of the sample with acetonitrile in appropriate volumes followed by the addition of sodium sulfate solution in order to facilitate phase separation. The parameters influencing the extraction performance were studied and optimized using a two‐step experimental design. The analytical procedure was thoroughly validated using the accuracy profiles as a graphical decision‐making tool. The β‐expectation tolerance intervals did not exceed the acceptance criteria of ±15% meaning that 95% of future results will be included in the defined bias limits. The limits of detection of the procedure were satisfactory, ranging between 0.01 and 0.03 μg/mL. The mean analytical bias in the spiking levels was satisfactory and ranged between –10.3 and 4.2% while the relative standard deviation was lower than 5.6%. Monte‐Carlo simulations followed by capability analysis were employed to investigate the ruggedness of the sample preparation protocol. The developed method offers advantages compared to previously reported approaches for the same type of analysis including extraction efficiency and scaling down of the sample volume and extraction time.
Optimum design and thermal modeling for 2D and 3D natural convection problems incorporating level set‐based topology optimization with body‐fitted mesh
Authors: Li Hao , Kondoh Tsuguo , Jolivet Pierre , Furuta Kozo , Yamada Takayuki , Zhu Benliang , Zhang Heng , Izui Kazuhiro , Nishiwaki Shinji
Published: January 2022

Passive heat sinks cooled by natural convection are reliable, compact, and low‐noise. They are widely used in telecommunication devices, LEDs, and so forth. This work builds upon the recent advancements in fluid topology optimization (TO) to present a case study of two‐ and three‐dimensional optimum design and thermal modeling for the natural convection problems using a reaction–diffusion equation (RDE)‐based level‐set method. To this end, first, a high‐fidelity thermal‐fluid model is constructed where the full Navier–Stokes equations are strongly coupled with the energy equation through the Boussinesq approximation. We benchmark our simulation solver against the experimental analysis and other numerical analysis methods. Next, we carefully investigate the flow behavior under different Grashof numbers using a fully transient simulation solver. Then, we revisit the RDE‐based level‐set TO methodology and construct an open‐source parallel TO framework. The main findings reveal that using the body‐fitted mesh adaptation, the proposed methodology can capture the explicit fluid–solid boundary and we are free of the continuation approach to penalize the design variable to the binary structure. A moderately large‐scale TO problem with DOFs can be solved in parallel on a standard multi‐process platform. Our numerical implementation uses FreeFEM for finite element analysis, PETSc for distributed linear algebra, and Mmg for mesh adaptation. For comparison and for accessing our various techniques, a variety of 2D and 3D benchmarks are presented to support these remarkable features.
Systematic literature review of insulin dose adjustments when initiating hemodialysis or peritoneal dialysis
Authors: Blaine Emily , Tumlinson Robin , Colvin Marion , Haynes Tyler , Whitley Heather P.
Published: January 2022

Chronically uncontrolled hyperglycemia is the leading cause of end stage kidney disease (ESKD) necessitating dialysis. During times of transition to hemodialysis (HD) or peritoneal dialysis (PD), considerations must be given to insulin dosing adjustments for persons with diabetes (PWD) in efforts to maintain glycemic control. However, the literature is sparse with few clear and direct practical clinical recommendations for therapeutic insulin dosing adjustments in PWD and ESKD. The objective of this systematic review was to identify and report the evidence and gaps in the literature for adjustments in therapeutic insulin recommendations when initiating HD or PD in patients with ESKD and diabetes mellitus. A literature search using PubMed, CENTRAL, MEDLINE, CINAHL, Google Scholar, and ClinicalTrials.gov revealed 242 results. After removing duplicates and articles not reaching pre‐specified criteria, 29 relevant articles remained for further analysis. Following the exclusion of 18 articles after full‐text review due to lack of relevance or inappropriate publication type, 11 articles remained and were included in the review. The most common recommendation regarding HD was to reduce the basal insulin dose up to 25% on HD days to prevent hypoglycemia, although a lack of consensus exists on the percent reduction. Little information was found relating to insulin management with continuous ambulatory PD or automated PD. During PD, insulin may be administered subcutaneously, IP, or with the dialysis fluid. Administration of insulin with dialysate may necessitate a dose increase of up to 30% due to a loss to tubing and dilution. Furthermore, the use of dextrose‐based dialysate may require additional insulin to mitigate systemic impact of dextrose absorption on BG. Overall, a gap exists in the primary literature regarding recommendations for prophylactically adjusting insulin therapy when initiating HD or PD, or when switching between the two. More research is needed to clarify ideal alterations in insulin dosing, administration techniques, and product selections for PWD and ESKD undergoing dialysis.
Self‐assembly of gemini amphiphiles with symmetric tails in selective solvent
Authors: Chen Hongrui , Chen Jianfa , Wan Daihong , Zhang Huikun , Mao Chengli , Wang Rong
Published: January 2022

Gemini amphiphile is a special type of block copolymers formed by connecting two traditional diblock molecules at hydrophilic head groups through spacers. The special structure makes gemini amphiphiles potentially promising for drug delivery and gene delivery. The self‐assembly behavior of gemini amphiphiles with tails of equal length in selective solvent was investigated using the dissipative particle dynamics method. The effects of the size of the hydrophilic head group, interaction parameters, concentration and hydrophobic tail chain length on the self‐assembled morphology of gemini amphiphiles were examined. By varying these parameters, worm‐like micelles, large compound micelles, vesicles, hierarchical rod‐like micelles, cylindrical bundles, pomegranate‐like micelles and bilayers were obtained. Compared with conventional diblock copolymers, the dominant feature of gemini amphiphiles is the presence of the spacer. By analyzing the distance between two head groups, we explored in depth the influence of spacer length on the self‐assembly of gemini amphiphile molecules. Through simulation probes, we hope to improve the understanding of ordered aggregates of gemini amphiphiles in selective solvent, to reveal theoretically the pattern variation of aggregation morphology and to provide guidance for their practical application. © 2022 Society of Industrial Chemistry.
A favorable path to domain separation in the orange carotenoid protein
Authors: Sharawy Mahmoud , Pigni Natalia B. , May Eric R. , Gascón José A.
Published: January 2022

The orange carotenoid protein (OCP) is responsible for nonphotochemical quenching (NPQ) in cyanobacteria, a defense mechanism against potentially damaging effects of excess light conditions. This soluble two‐domain protein undergoes profound conformational changes upon photoactivation, involving translocation of the ketocarotenoid inside the cavity followed by domain separation. Domain separation is a critical step in the photocycle of OCP because it exposes the N‐terminal domain (NTD) to perform quenching of the phycobilisomes. Many details regarding the mechanism and energetics of OCP domain separation remain unknown. In this work, we apply metadynamics to elucidate the protein rearrangements that lead to the active, domain‐separated, form of OCP. We find that translocation of the ketocarotenoid canthaxanthin has a profound effect on the energetic landscape and that domain separation only becomes favorable following translocation. We further explore, characterize, and validate the free energy surface (FES) using equilibrium simulations initiated from different states on the FES. Through pathway optimization methods, we characterize the most probable path to domain separation and reveal the barriers along that pathway. We find that the free energy barriers are relatively small (<5 kcal/mol), but the overall estimated kinetic rate is consistent with experimental measurements (>1 ms). Overall, our results provide detailed information on the requirement for canthaxanthin translocation to precede domain separation and an energetically feasible pathway to dissociation.
Remarks on the Effects of Quantum Corrections on Moduli Stabilization and de Sitter Vacua in Type IIB String Theory
Authors: Basiouris Vasileios , Leontaris George K.
Published: January 2022

The role of string loop corrections on the existence of de Sitter vacua and the moduli stabilization problem is examined in type IIB effective theories. The fundamental building blocks are a minimum of three intersecting D7 brane stacks, three Kähler moduli, and a novel Einstein‐Hilbert term associated with higher derivative terms of the 10‐dimensional effective action. It was shown in previous works that loop corrections appear which induce novel logarithmic volume‐dependent terms in the effective potential. When D‐term contributions are considered, all Kähler moduli are stabilized and de Sitter vacua are achieved. In the present work, a comprehensive study of multiple non‐perturbative terms in the superpotential is undertaken. The combined effects of the logarithmic loop corrections and two non‐perturbative superpotential Kaehler moduli dependent terms have been investigated. It is shown that a variety of fluxes exist for large as well as moderate volume compactifications which define a de Sitter space and stabilize the moduli fields. For large volumes, a generic simple form of the potential is achieved. The so obtained effective potential appears to be promising for cosmological applications.
Maternal echocardiographic changes in twin pregnancies with and without pre‐eclampsia
Authors: Giorgione V. , Melchiorre K. , O'Driscoll J. , Khalil A. , Sharma R. , Thilaganathan B.
Published: January 2022

Objective

Twin pregnancies are at increased risk of developing hypertensive disorders of pregnancy (HDP) compared with singleton pregnancies, resulting in a substantially higher rate of maternal and perinatal complications. The strain caused by twin pregnancy on the maternal cardiovascular system has not been studied extensively. The objective of this study was to evaluate the changes in maternal cardiac morphology and diastolic function in a cohort of women with normotensive and those with hypertensive twin pregnancies.

Methods

This was a cross‐sectional study conducted at a tertiary referral university center. Women with singleton or twin pregnancy were enrolled prospectively to undergo maternal transthoracic echocardiography throughout pregnancy. Multiples of the median (MoM) were calculated for each index using a reference group of uncomplicated singleton pregnancies (n = 411) in order to adjust for changes associated with gestational age. Cardiac findings were indexed for body surface area and compared among normotensive twin pregnancies, singleton pregnancies complicated by HDP and twin pregnancies complicated by HDP.

Results

The total cohort included 119 HDP singleton pregnancies, 52 normotensive twin pregnancies and 24 HDP twin pregnancies. Left ventricular mass index (LVMi) MoM (median (interquartile range)) did not differ between singleton pregnancies complicated by HDP and normotensive twin pregnancies, but was significantly higher in HDP twin compared with HDP singleton pregnancies (1.31 (1.08–1.53) vs 1.17 (0.98–1.35), P = 0.032). Two diastolic indices, left atrial volume index MoM (1.12 (0.66–1.38) vs 0.65 (0.55–0.84), P = 0.003) and E/e′ MoM (1.29 (1.09–1.54) vs 0.99 (0.99–1.02), P = 0.036), were significantly higher in HDP twin compared with normotensive twin pregnancies. In normotensive twin compared with HDP singleton pregnancies, stroke volume index (SVi) MoM was higher (1.20 (1.03–1.36) vs 1.00 (0.81–1.15), P = 0.004) and total vascular resistance index (TVRi) was lower (0.73 (0.70–0.86) vs 1.29 (1.04–1.56), P < 0.0001). In contrast, SVi MoM was lower (1.10 (1.02–1.35) vs 1.20 (1.03–1.36), P = 0.018) and TVRi was higher (1.00 (0.88–1.31) vs 0.73 (0.70–0.86), P = 0.029) in HDP twin compared with normotensive twin pregnancies.

Conclusion

The maternal cardiovascular system is altered severely in twin pregnancy with or without HDP. Despite the low total vascular resistance, cardiac changes in normotensive twin pregnancies are comparable to those seen in singleton pregnancies complicated by HDP, reflecting the high cardiovascular demand imposed by twin pregnancy. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells
Authors: Cacho-Navas Cristina , Reglero-Real Natalia , Colás-Algora Natalia , Barroso Susana , de Rivas Gema , Stamatakis Kostantinos , Feito Jorge , Andrés Germán , Fresno Manuel , Kremer Leonor , Correas Isabel , Alonso Miguel A. , Millán Jaime
Published: January 2022

Apical localization of Intercellular Adhesion Receptor (ICAM)-1 regulates the adhesion and guidance of leukocytes across polarized epithelial barriers. Here, we investigate the molecular mechanisms that determine ICAM-1 localization into apical membrane domains of polarized hepatic epithelial cells, and their effect on lymphocyte-hepatic epithelial cell interaction. We had previously shown that segregation of ICAM-1 into apical membrane domains, which form bile canaliculi and bile ducts in hepatic epithelial cells, requires basolateral-to-apical transcytosis. Searching for protein machinery potentially involved in ICAM-1 polarization we found that the SNARE-associated protein plasmolipin (PLLP) is expressed in the subapical compartment of hepatic epithelial cells in vitro and in vivo. BioID analysis of ICAM-1 revealed proximal interaction between this adhesion receptor and PLLP. ICAM-1 colocalized and interacted with PLLP during the transcytosis of the receptor.PLLPgene editing and silencing increased the basolateral localization and reduced the apical confinement of ICAM-1 without affecting apicobasal polarity of hepatic epithelial cells, indicating that ICAM-1 transcytosis is specifically impaired in the absence of PLLP. Importantly, PLLP depletion was sufficient to increase T-cell adhesion to hepatic epithelial cells. Such an increase depended on the epithelial cell polarity and ICAM-1 expression, showing that the epithelial transcytotic machinery regulates the adhesion of lymphocytes to polarized epithelial cells. Our findings strongly suggest that the polarized intracellular transport of adhesion receptors constitutes a new regulatory layer of the epithelial inflammatory response.
Jumping into the artistic deep end: building the catalogue raisonné
Authors: Dobbs Todd , Benedict Aileen , Ras Zbigniew
Published: January 2022

The catalogue raisonné compiled by art scholars holds information about an artist’s work such as a painting’s image, medium, provenance, and title. The catalogue raisonné as a tangible asset suffers from the challenges of art authentication and impermanence. As the catalogue raisonné is born digital, the impermanence challenge abates, but the authentication challenge persists. With the popularity of artificial intelligence and its deep learning architectures of computer vision, we propose to address the authentication challenge by creating a new artefact for the digital catalogue raisonné: a digital classification model. This digital classification model will help art scholars with new artwork claims via a tool that authenticates a proposed artwork with an artist. We create this tool by training a machine learning model with 90 artists having at least 150 artworks and achieve an accuracy of 87.31%. We use the ResNet Convolutional Neural Network to improve accuracy and number of artist classes over state-of-the-art artist classification experiments using the WikiArt database. We address inconsistencies in the way scholars approach artist classification by providing a consistent method to recreate our dataset and providing a consistent method to calculate performance metrics based on imbalanced data.
Eulerian time-stepping schemes for the non-stationary Stokes equations on time-dependent domains
Authors: Burman Erik , Frei Stefan , Massing Andre
Published: January 2022

This article is concerned with the discretisation of the Stokes equations on time-dependent domains in an Eulerian coordinate framework. Our work can be seen as an extension of a recent paper by Lehrenfeld and Olshanskii (ESAIM: M2AN 53(2):585–614, 2019), where BDF-type time-stepping schemes are studied for a parabolic equation on moving domains. For space discretisation, a geometrically unfitted finite element discretisation is applied in combination with Nitsche’s method to impose boundary conditions. Physically undefined values of the solution at previous time-steps are extended implicitly by means of so-called ghost penalty stabilisations. We derive a complete a priori error analysis of the discretisation error in space and time, including optimal $$L^2(L^2)$$

L
2

(

L
2

)

-norm error bounds for the velocities. Finally, the theoretical results are substantiated with numerical examples.
Hypoxia-inducible factor-1 alpha expression is induced by IL-2 via the PI3K/mTOR pathway in hypoxic NK cells and supports effector functions in NKL cells and ex vivo expanded NK cells
Authors: Cluff Emily , Magdaleno Carina C. , Fernandez Emyly , House Trenton , Swaminathan Srividya , Varadaraj Archana , Rajasekaran Narendiran
Published: January 2022

Natural killer (NK) cells are cytotoxic innate lymphocytes that are specialized to kill tumor cells. NK cells are responsive to the primary cytokine IL-2 in the tumor microenvironment (TME), to activate its effector functions against tumors. Despite their inherent ability to kill tumor cells, dysfunctional NK cells observed within advanced solid tumors are associated with poor patient survival. Hypoxia in the TME is a major contributor to immune evasion in solid tumors that could contribute to impaired NK cell function. HIF-1α is a nodal regulator of hypoxia in driving the adaptive cellular responses to changes in oxygen concentrations. Whether HIF-1α is expressed in hypoxic NK cells in the context of IL-2 and whether its expression regulates NK cell effector function are unclear. Here, we report that freshly isolated NK cells from human peripheral blood in hypoxia could not stabilize HIF-1α protein coincident with impaired anti-tumor cytotoxicity. However, ex vivo expansion of these cells restored HIF-1α levels in hypoxia to promote antitumor cytotoxic functions. Similarly, the human NK cell line NKL expressed HIF-1α upon IL-2 stimulation in hypoxia and exhibited improved anti-tumor cytotoxicity and IFN-γ secretion. We found that ex vivo expanded human NK cells and NKL cells required the concerted activation of PI3K/mTOR pathway initiated by IL-2 signaling in combination with hypoxia for HIF-1α stabilization. These findings highlight that HIF-1α stabilization in hypoxia maximizes NK cell effector function and raises the prospect of NK cells as ideal therapeutic candidates for solid tumors.
Survival Prediction Capabilities of Preoperative Inflammatory and Nutritional Status in Esophageal Squamous Cell Carcinoma Patients
Authors: Sugawara Kotaro , Yagi Koichi , Okumura Yasuhiro , Aikou Susumu , Yamashita Hiroharu , Seto Yasuyuki
Published: January 2022

Background

Studies have revealed the impacts of various inflammatory and nutritional markers in patients with esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic values of multiple inflammation‐ or nutrition‐based markers, either alone or in combination with pStage, in ESCC patients.

Methods

In total, 360 patients undergoing upfront surgery for ESCC were retrospectively reviewed. The prognostic capabilities of 7 inflammatory and 3 nutritional parameters were investigated. Furthermore, we devised new staging systems by adding these markers to pStage and examined the prognostic abilities of our new approach. Time‐dependent receiver operating characteristic curves and the areas under the curve (AUCs) were estimated to compare prognostic capabilities among the parameters.

Results

The AUCs for predicting overall survival (OS) of the prognostic nutritional index (PNI), CRP to albumin ration (CAR), lymphocyte to CRP ratio (LCR) and the Naples prognostic score (NPS) were similar to that of pStage. Notably, CAR and LCR showed high predictive capabilities for OS (AUCs; 0.627 and 0.634 for 3‐year OS, respectively). New staging systems combining inflammatory or nutritional markers with pStage provided higher AUCs for predicting OS than pStage alone. In particular, NPpStage (NPS and pStage) (P = 0.03), PNpStage (PNI and pStage) (P = 0.03) and LCpStage (LCR and pStage) (P = 0.05) showed significantly higher accuracy for predicting OS than pStage alone.

Conclusions

Various inflammatory or nutritional markers, especially those derived from CRP, are useful for predicting survival outcomes of ESCC patients. The predictive capabilities of these indices were augmented when used in combination with pStage.
Effects of changing from a diet with saturated fat to a diet with n-6 polyunsaturated fat on the serum metabolome in relation to cardiovascular disease risk factors
Authors: Pigsborg Kristina , Gürdeniz Gözde , Rangel-Huerta Oscar Daniel , Holven Kirsten B. , Dragsted Lars Ove , Ulven Stine M.
Published: January 2022

Purpose

Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers.

Methods

In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25–70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups.

Results

PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia.

Conclusion

The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT 01679496 on September 6th 2012.
Variable seed bed microsite conditions and light influence germination in Australian winter annuals
Authors: Towers Isaac R. , Merritt David J. , Erickson Todd E. , Mayfield Margaret M. , Dwyer John M.
Published: January 2022

Environmentally cued germination may play an important role in promoting coexistence in Mediterranean annual plant systems if it causes niche differentiation across heterogeneous microsite conditions. In this study, we tested how microsite conditions experienced by seeds in the field and light conditions in the laboratory influenced germination in 12 common annual plant species occurring in the understorey of the York gum-jam woodlands in southwest Western Australia. Specifically, we hypothesized that if germination promotes spatial niche differentiation, then we should observe species-specific germination responses to light. In addition, we hypothesized that species’ laboratory germination response may depend on the microsite conditions experienced by seeds while buried. We tested the laboratory germination response of seeds under diurnally fluctuating light and complete darkness, which were collected from microsites spanning local-scale environmental gradients known to influence community structure in this system. We found that seeds of 6 out of the 12 focal species exhibited significant positive germination responses to light, but that the magnitude of these responses varied greatly with the relative light requirement for germination ranging from 0.51 to 0.86 for these species. In addition, germination increased significantly across a gradient of canopy cover for two species, but we found little evidence to suggest that species’ relative light requirement for germination varied depending on seed bank microsite conditions. Our results suggest that variability in light availability may promote coexistence in this system and that the microsite conditions seeds experience in the intra-growing season period can further nuance species germination behaviour.
The lexicon for periprosthetic bone loss versus osteolysis after cervical disc arthroplasty: a systematic review
Authors: Wahbeh Jenna M. , Park Sang-Hyun , Campbell Patricia , Ebramzadeh Edward , Sangiorgio Sophia N.
Published: January 2022

Background

Periprosthetic bone loss is a common observation following arthroplasty. Recognizing and understanding the nature of bone loss is vital as it determines the subsequent performance of the device and the overall outcome. Despite its significance, the term “bone loss” is often misused to describe inflammatory osteolysis, a complication with vastly different clinical outcomes and treatment plans. Therefore, the goal of this review was to report major findings related to vertebral radiographic bone changes around cervical disc replacements, mitigate discrepancies in clinical reports by introducing uniform terminology to the field, and establish a precedence that can be used to identify the important nuances between these distinct complications.

Methods

A systematic review of the literature was conducted following PRISMA guidelines, using the keywords “cervical,” “disc replacement,” “osteolysis,” “bone loss,” “radiograph,” and “complications.” A total of 23 articles met the inclusion criteria with the majority being retrospective or case reports.

Results

Fourteen studies reported periprosthetic osteolysis in a total of 46 patients with onset ranging from 15–96 months after the index procedure. Reported causes included: metal hypersensitivity, infection, mechanical failure, and wear debris. Osteolysis was generally progressive and led to reoperation. Nine articles reported non-inflammatory bone loss in 527 patients (52.5%), typically within 3–6 months following implantation. The reported causes included: micromotion, stress shielding, and interrupted blood supply. With one exception, bone loss was reported to be non-progressive and had no effect on clinical outcome measures.

Conclusions

Non-progressive, early onset bone loss is a common finding after CDA and typically does not affect the reported short-term pain scores or lead to early revision. By contrast, osteolysis was less common, presenting more than a year post-operative and often accompanied by additional complications, leading to revision surgery. A greater understanding of the clinical significance is limited by the lack of long-term studies, inconsistent terminology, and infrequent use of histology and explant analyses. Uniform reporting and adoption of consistent terminology can mitigate some of these limitations. Executing these actionable items is critical to assess device performance and the risk of revision.

Level of Evidence IV

Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study
Authors: Pant Sanjay , Sizarov Aleksander , Knepper Angela , Gossard Gaëtan , Noferi Alberto , Boudjemline Younes , Vignon-Clementel Irene
Published: January 2022

Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. PS, however, can result in poorly understood mortality. Here, a patient-specific geometrical multiscale model of PAH physiology and PS is developed for a paediatric PAH patient with stent-based PS. In the model, 7.6mm-diameter PS produces near-equalisation of the aortic and PA pressures and $$Q_p/Q_s$$

Q
p

/

Q
s

(oxygenated vs deoxygenated blood flow) ratio of 0.72 associated with a 16% decrease of left ventricular (LV) output and 18% increase of RV output. The flow from LV to aortic arch branches increases by 16%, while LV contribution to the lower body flow decreases by 29%. Total flow in the descending aorta (DAo) increases by 18% due to RV contribution through the PS with flow into the distal PA branches decreasing. PS induces 18% increase of RV work due to its larger stroke volume pumped against lower afterload. Nonetheless, larger RV work does not lead to increased RV end-diastolic volume. Three-dimensional flow assessment demonstrates the PS jet impinging with a high velocity and wall shear stress on the opposite DAo wall with the most of the shunt flow being diverted to the DAo. Increasing the PS diameter from 5mm up to 10mm results in a nearly linear increase in post-operative shunt flow and a nearly linear decrease in shunt pressure-drop. In conclusion, this model reasonably represents patient-specific haemodynamics pre- and post-creation of the PS, providing insights into physiology of this complex condition, and presents a predictive tool that could be useful for clinical decision-making regarding suitability for PS in PAH patients with drug-resistant suprasystemic PAH.
Flight plan for the future: floatplane pilots and researchers team up to predict invasive species dispersal in Alaska
Authors: Schwoerer Tobias , Dial Roman J. , Little Joseph M. , Martin Aaron E. , Morton John M. , Schmidt Jennifer I. , Ward Eric J.
Published: January 2022

Aircraft can transport aquatic invasive species (AIS) from urban sources to remote waterbodies, yet little is known about this long-distance pathway. In North America and especially Alaska, aircraft with landing gear for water called floatplanes are used for recreation access to remote, often road-less wilderness destinations. Human-mediated dispersal of AIS is particularly concerning for the conservation of pristine wildlands, yet resource managers are often challenged by limited monitoring and response capacity given the vast areas they manage. We collected pathway data through a survey with floatplane pilots and used a Bayesian hierarchical model to inform early detection in a data-limited situation. The study was motivated by Alaska’s first known AIS, Elodea spp. (Elodea) and its floatplane-related dispersal. For 682 identified floatplane destinations, a Bayesian hierarchical model predicts the chance of flights originating from AIS source locations in freshwater and estimates the expected number of flights from these sources. Model predictions show the potential for broad spread across remote regions currently not known to have Elodea and informed monitoring and early detection efforts. Our result underlines the small window of opportunity for Arctic conservation strategies targeting an AIS free Arctic. We recommend management that focuses on long-distance connectivity, keeping urban sources free of AIS. We discuss applicability of the approach for other data-limited situations supporting data-informed AIS management responses.
“You Have to be Resilient”: A Qualitative Study Exploring Advice Newcomer Youth Have for Other Newcomer Youth
Authors: Smith Alexandra C. G. , Crooks Claire V. , Baker Linda
Published: January 2022

Research infrequently includes the perspectives of vulnerable and marginalized youth. As the population of newcomer youth in Canada continues to grow, it is imperative that attention is devoted not only to challenges they experience, but also to resilience factors they perceive to support their adjustment and well-being. To address this gap, this qualitative research explored newcomer youths’ experiences and advice for other newcomer youth who have recently arrived in Canada. Thirty-seven newcomer youth from two medium-sized cities in Ontario participated in focus groups. Participants ranged from 14 to 22 in age and identified mostly as female refugees from the Middle East. Through thematic analysis, five overarching themes were found across groups: (1) moving to a new country is hard, (2) maintain a healthy mindset, (3) take an active role in the adjustment process, (4) stay true to who you are, (5) and you are not alone. Youth described hardships that make moving to a new country difficult including lack of belonging due to racism and bullying, insufficient orientation to new systems, language barriers, and high levels of stress. Findings demonstrated youths’ resilience, coping skills, and strategies to lead meaningful lives. Youth discussed resilience strategies such as maintaining a connection with home culture and religion, reframing thinking to be positive, receiving emotional support, accessing community support at newcomer agencies, and building language proficiency. Findings provide implications for professionals working with newcomer youth and reflect the importance of addressing structural barriers and racism. The opportunity for newcomer youth to share experiences as experts in research may also help to promote resilience.
Synthesis and characterization of TEMPO-oxidized peptide-cellulose conjugate biosensors for detecting human neutrophil elastase
Authors: Mackin Robert T. , Fontenot Krystal R. , Edwards J. Vincent , Prevost Nicolette T. , Grimm Casey , Condon Brian D. , Liebner Falk , Jordan Jacobs H. , Easson Michael W. , French Alfred D.
Published: January 2022

Here we describe the synthesis and characterization of a peptide-cellulose conjugate biosensor based on TEMPO-oxidized nanofibrillated cellulose (tNFC) for detecting elevated levels of human neutrophil elastase (HNE) in chronic wounds. The fluorescent peptide HNE substrate constructed from n-succinyl-Ala-Pro-Ala-7-amino-4-methyl-coumarin was attached to the TEMPO-oxidized cellulose surface via polyethylene glycol linker. The characterization of the biosensor conjugate shows a high degree of peptide incorporation onto the surface with the degree of substitution of 0.057. The relatively small crystallite size of 26.0 Å compared to other cellulose- and nanocellulose-based materials leads to a large specific surface area which can promote access of HNE to the enzyme substrates due to decreased steric interactions. Likewise, the porosity for tNFC was found to be higher than all other samples, including the nanocellulosic aerogel, lending to its hydrogel-like nature. The properties of tNFC were compared to other cellulose-based materials. The volume of each crystallite and volume ratio to the largest sample was calculated. tNFC was found to occupy the smallest space resulting in high amounts of sensors per crystallite unit volume. With a small crystallite volume and large number of sensors, the tNFC peptide-cellulose conjugate biosensor could provide a more sensitive system and is a good candidate for point of care diagnostic devices for detecting elevated protease levels in humans.
The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma
Authors: Kawahara Kenji , Takano Shigetsugu , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Ohtsuka Masayuki
Published: January 2022

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.
The Denotation of Copredicative Nouns
Authors: Ortega-Andrés Marina
Published: January 2022

Copredication is the phenomenon whereby two or more predicates seem to require that their argument denotes different things. The denotation of words that copredicate has been broadly discussed. In this paper, I investigate the metaphysics behind this question. Thus, mereological theories of dot objects claim that these nouns denote complex entities; Asher (Lexical
meaning in context, Cambridge University Press, 2011, https://doi.org/10.1017/CBO9780511793936) thinks that they denote bare particulars; and the Activation Package Theory contends that they stand for multiple denotations. According to the Activation Package Theory, copredicative nouns stand for complex knowledge structures that offer a range of multiple potential denotations. In this paper, I claim that the Activation Package Theory contributes to solve some of the metaphysical questions that arise from copredication.
Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model
Authors: Chen Xun , Lu Wei , Tsai Min-Yeh , Jin Shikai , Wolynes Peter G.
Published: January 2022

Heme is an active center in many proteins. Here we explore computationally the role of heme in protein folding and protein structure. We model heme proteins using a hybrid model employing the AWSEM Hamiltonian, a coarse-grained forcefield for the protein chain along with AMBER, an all-atom forcefield for the heme. We carefully designed transferable force fields that model the interactions between the protein and the heme. The types of protein–ligand interactions in the hybrid model include thioester covalent bonds, coordinated covalent bonds, hydrogen bonds, and electrostatics. We explore the influence of different types of hemes (heme b and heme c) on folding and structure prediction. Including both types of heme improves the quality of protein structure predictions. The free energy landscape shows that both types of heme can act as nucleation sites for protein folding and stabilize the protein folded state. In binding the heme, coordinated covalent bonds and thioester covalent bonds for heme c drive the heme toward the native pocket. The electrostatics also facilitates the search for the binding site.