bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of metabolically healthy obesity and elevated risk of coronary artery calcification: a systematic review and meta-analysis
Authors: Hsueh Yu-wen , Yeh Tzu-Lin , Lin Chien-Yu , Tsai Szu-Ying , Liu Shu-Jung , Lin Chi-Min , Chen Hsin-Hao
Published: March 2020

Background

Metabolically healthy obesity (MHO) is defined as obesity with less than two parameters of metabolic abnormalities. Some studies report that MHO individuals show similar risk of cardiovascular disease (CVD) compared with metabolically healthy non-obese (MHNO) individuals, but the results are conflicting. Coronary artery calcium (CAC) reflects the extent of coronary atherosclerosis and is a useful tool to predict future risk of CVD. The objective of this meta-analysis was to investigate whether MHO is associated with elevated risk of CAC.

Method

We searched Cochrane, PubMed, and Embase up to April 19, 2019. Prospective cohort and cross-sectional studies examining the association between MHO subjects and CAC were included with MHNO as the reference. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effect models. Subgroup analysis and meta-regression were applied to define possible sources of heterogeneity. We conducted this research following a pre-established protocol registered on PROSPERO (CRD 42019135006).

Results

A total of nine studies were included in this review and six studies with 23,543 participants were eligible for the meta-analysis. Compared with MHNO subjects, MHO had a higher odds of CAC (OR 1.36, 95% CI [1.11 to 1.66]; I2 = 39%). In the subgroup analysis, the risk associated with MHO participants was significant in cohort studies (OR = 1.47, 95% CI [1.15,1.87], I2 = 0%), and borderline significant in cross-sectional studies. The risk of CAC was also significant in MHO participants defined by Adult Treatment Panel III (ATP III) (OR = 1.55, 95% CI [1.25,1.93], I2 = 0%). The univariate meta-regression model showed that age and smoking status were possible effect modifiers for MHO and CAC risk.

Conclusion

Our meta-analysis showed that MHO phenotypes were associated with elevated risk of CAC compared with MHNO, which reflects the extent of coronary atherosclerosis. People with obesity should strive to achieve normal weight even when only one metabolic abnormality is present.
Toluene 4‐Monooxygenase Reaction Intermediates
Authors: Acheson Justin F , Bailey Lucas J , Brunold Thomas C , Fox Brian G
Published: March 2020

Toluene 4‐monooxygenase (T4MO) is a four‐protein diiron enzyme complex that catalyzes the regiospecific oxidation of toluene to
p
‐cresol. Earlier high‐resolution crystal structures of the stoichiometric complex of hydroxylase and effector protein (T4moHD) revealed how protein–protein interactions and reduction of the diferric center produce an active site configuration poised for reaction with O
2
. In this article, additional crystal structures are described for the reductase (T4moF), a complex between the hydroxylase and the Rieske‐type ferredoxin (T4moHC), and the complex of hydroxylase and effector protein reacted with various combinations of H
2
O
2
, O
2
, and toluene;
p
‐cresol was added to the diferric enzyme or produced by catalytic turnover in the crystal. The structure of a catalytically competent arylperoxo Fe
2+
/Fe
3+
species with delocalized aryl radical character, along with those of two unreactive peroxo species, provides new insight into enzymatic aromatic ring hydroxylation, including the role of active site water molecules and how proton transfer mediated by a carboxylate shift may trigger catalysis.
αKG‐Dependent Enzyme
AndA
Involved in Anditomin Biosynthesis
Authors: Nakashima Yu , Mori Takahiro , Abe Ikuro
Published: March 2020

Oxidative modification reactions catalyzed by Fe(II)/α‐ketoglutarate (αKG)‐dependent dioxygenases are widely observed in the primary and secondary metabolic pathways. The members of this dioxygenase superfamily catalyze a variety of reactions, including hydroxylation, epimerization, desaturation, epoxidation, ring construction, and ring expansion. In particular, the dynamic skeletal rearrangement reactions by Fe(II)/αKG‐dependent dioxygenases are prevalent in fungal meroterpenoid biosynthesis. These reactions proceed
via
intramolecular radical transfer reactions, which are initiated by the abstraction of a hydrogen atom from the substrate with an activated Fe(IV)‐oxo species. In this article, we introduce the multifunctional enzyme AndA, in the biosynthetic pathway of the fungal meroterpenoid anditomin. AndA catalyzes unusual two‐step enzyme reactions to construct the bicyclo[2.2.2]octane system of anditomin. Crystallographic studies revealed that the multi‐step enzyme reaction occurs in the same active site, where the position of the initial hydrogen atom abstraction is enzymatically controlled by the binding mode of the substrates. The detailed catalytic mechanism of AndA is proposed, based on the crystal structures, mutagenesis analysis, and computational studies.
Recommendations of megavoltage computed tomography settings for the implementation of adaptive radiotherapy on helical tomotherapy units
Authors: Velten Christian , Boyd Robert , Jeong Kyoungkeun , Garg Madhur K. , Tomé Wolfgang A.
Published: March 2020

Megavoltage computed tomography (MVCT) image quality metrics were evaluated on an Accuray Radixact unit to recommend scan settings for the implementation of a consistent adaptive radiotherapy program. Megavoltage computed tomography image quality was evaluated and compared to a kilovoltage CT (kVCT) simulator using a commercial cone beam computed tomography image quality phantom. Megavoltage computed tomographies were acquired on the Accuray Radixact using fine, normal, and coarse pitches, with all available reconstruction slice thicknesses, each of which were reconstructed using standard and iterative reconstruction (IR). Image quality metrics (IQM) were evaluated using DoseLab: automatically and manually calculated spatial resolution, subject contrast, and contrast‐to‐noise ratio (CNR). Scanning time was 15.6 s/cm for fine, 8.1 s/cm for normal, and 5.6 s/cm for coarse pitch. Automatically evaluated spatial resolutions ranged from 0.39, 0.41, to 0.42 lp/mm for standard reconstruction and from 0.24, 0.21, to 0.18 lp/mm for soft‐tissue IR, respectively, with general IR yielding values in between these. Spatial resolution for kVCT was measured to be at least 0.42 lp/mm. Contrast was consistent across MVCT settings with 8.1 ± 0.2%, while kVCT contrast was 10.27 ± 0.05%. CNR was calculated to be 3.3 ± 0.4 for standard reconstruction, 7.4 ± 0.4 for general IR, and 12.0 ± 1.9 for soft‐tissue IR. It was found that increasing reconstruction slice thickness for a given pitch does not improve IQMs. Based on the consistency of contrast metrics across pitch values and the only slightly reduced spatial resolution using normal compared to fine pitch, we recommend the use of normal pitch with 2 mm slice thickness to maximize image quality for ART while limiting scanning time. Only for sites for which improved CNR is required and reduced spatial resolution is acceptable, soft‐tissue IR is recommended.
Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52
Authors: D’Amore Angelica , Tessa Alessandra , Naef Valentina , Bassi Maria Teresa , Citterio Andrea , Romaniello Romina , Fichi Gianluca , Galatolo Daniele , Mero Serena , Battini Roberta , Bertocci Giulia , Baldacci Jacopo , Sicca Federico , Gemignani Federica , Ricca Ivana , Rubegni Anna , Hirst Jennifer , Marchese Maria , Sahin Mustafa , Ebrahimi‐Fakhari Darius , Santorelli Filippo M.
Published: March 2020

Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP‐4). Using next‐generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP‐4 complex formation in patient‐derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP‐4 deficiency using morpholino‐mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability.
Most Appropriate Conventional Disease‐Modifying Antirheumatic Drug to Combine With Different Advanced Therapies in Rheumatoid Arthritis: A Systematic Literature Review With Meta‐Analysis
Authors: Decarriere Guillaume , Barnetche Thomas , Combe Bernard , Gaujoux-Viala Cécile , Lukas Cédric , Morel Jacques , Daien Claire
Published: March 2020

Objective

In rheumatoid arthritis, the association between advanced therapies (including biologic disease‐modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non‐MTX csDMARDs in combination with advanced therapies.

Methods

We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non‐MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta‐analysis was performed with RevMan, using an inverse variance approach with fixed or random‐effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated.

Results

The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta‐analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non‐MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0],P= 0.04; n = 3,843; I2= 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68],P= 0.001; n = 2,078; I2= 0%), with similar adverse event rates. Meta‐analysis for tocilizumab or JAK inhibitors could not be performed.

Conclusion

The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.
World's First Thermoelectric Generator Made of Tailored Carbon Allotropes
Authors: Borchardt Rudolf , Fromm Timo , Haase Armin , Fecher Jonas , Rosiwal Stefan M.
Published: March 2020

Carbon and carbon‐based compounds are today's mostly used sources of energy. By burning them, their chemically stored energy can be transformed to mechanical energy and further on to electrical energy. These transformation steps entail huge thermal losses. Thermoelectric generators (TEGs) are devices that allow the direct conversion of thermal gradients into electrical energy through a smart combination of n‐ and p‐conducting materials and are therefore an appealing approach to tackle thermal losses. However, the materials in today's TEGs, e.g., Bi2Te3, show limited thermal stability and often are toxic or not abundantly available which only allow for niche applications like military and aerospace equipment. Herein, the fabrication of the first, fully functional all‐carbon TEG is shown. The used carbon materials, made by chemical vapor deposition (CVD) processes, are both, nontoxic and abundant, and potentially paves the way for the large‐scale use of TEGs. Not only the thermal losses of conventional combustion processes but also thermal gradients established by solar thermal systems are potential fields of application. The assay is anticipated to spark further interest in carbon‐based thermoelectric materials. Such materials can be produced on a large scale and combined to a fully functional thermoelectric device.
Synthesis of a Counteranion‐Stabilized Bis(silylium) Ion
Authors: Wu Qian , Roy Avijit , Wang Guoqiang , Irran Elisabeth , Klare Hendrik F. T. , Oestreich Martin
Published: March 2020

The preparation of a molecule with two alkyl‐tethered silylium‐ion sites from the corresponding bis(hydrosilanes) by two‐fold hydride abstraction is reported. The length of the conformationally flexible alkyl bridge is crucial as otherwise the hydride abstraction stops at the stage of a cyclic bissilylated hydronium ion. With an ethylene tether, the open form of the hydronium‐ion intermediate is energetically accessible and engages in another hydride abstraction. The resulting bis(silylium) ion has been NMR spectroscopically and structurally characterized. Related systems based on rigid naphthalen‐n,m‐diyl platforms can only be converted into the dications when the positively charged silylium‐ion units are remote from each other (1,8 versus 1,5 and 2,6).
Devising Efficient Red‐Shifting Strategies for Bioimaging: A Generalizable Donor‐Acceptor Fluorophore Prototype
Authors: Chen Cheng , Fang Chong
Published: March 2020

Long emission wavelengths, high fluorescence quantum yields (FQYs), and large Stokes shifts are highly desirable features for fluorescent probes in biological imaging. However, the current development of many fluorescent probes remains largely trial‐and‐error and lacks efficiency. Moreover, to achieve far‐red/near‐infrared emission, a significant extension in the
‐conjugation is usually adopted but accompanied by other drawbacks such as fluorescence loss. In this review, we discuss an effective red‐shifting strategy built upon the green fluorescent protein chromophore, which enables a synergistic tuning of both the electronic ground and excited states. This approach could shorten the path toward redder emission in comparison to the conventional intramolecular charge transfer (ICT) strategy. We envision that this spectroscopy and computation‐aided strategy may advance the noncanonical fluorescent protein design and be generalized to various fluorophore scaffolds for redder emission while preserving other superior properties such as high FQYs.
S‐Nitroso‐N‐acetylpenicillamine impregnated endotracheal tubes for prevention of ventilator‐associated pneumonia
Authors: Homeyer Katie H. , Singha Priyadarshini , Goudie Marcus J. , Handa Hitesh
Published: March 2020

The chances of ventilator‐associated pneumonia (VAP) increases 6–20 folds when an endotracheal tube (ETT) is placed in a patient. VAP is one of the most common hospital‐acquired infections and comprises 86% of the nosocomial pneumonia cases. This study introduces the idea of nitric oxide‐releasing ETTs (NORel‐ETTs) fabricated by the incorporation of the nitric oxide (NO) donor S‐nitroso‐N‐acetylpenicillamine (SNAP) into commercially available ETTs via solvent swelling. The impregnation of SNAP provides NO release over a 7‐day period without altering the mechanical properties of the ETT. The NORel‐ETTs successfully reduced the bacterial infection from a commonly found pathogen in VAP, Pseudomonas aeruginosa, by 92.72 ± 0.97% when compared with the control ETTs. Overall, this study presents the incorporation of the active release of a bactericidal agent in ETTs as an efficient strategy to prevent the risk of VAP.
Validation of EORTC, CUETO, and EAU risk stratification in prediction of recurrence, progression, and death of patients with initially non–muscle‐invasive bladder cancer (NMIBC): A cohort analysis
Authors: Jobczyk Mateusz , Stawiski Konrad , Fendler Wojciech , Różański Waldemar
Published: March 2020

Brief Description: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non–muscle‐invasive bladder who were treated with, or without, Bacillus Calmette‐Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction.

This retrospective cohort analysis of 322 patients with newly diagnosed non–muscle‐invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU‐recommended tools (EAU risk groups, EORTC, and CUETO). One‐year and five‐year c‐indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1‐year recurrence risk based on CUETO groups, to 0.82 for 1‐year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39‐2.61) and tumor extent (HR: 1.21; 95% CI: 1.01‐1.46 for recurrence; HR: 3.1; 95% CI: 1.40‐6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c‐index c = 0.64; 95% CI: 0.61‐0.68) was superior to the EAU (P = .035; .62; 95% CI: 0.59‐0.66) and CUETO (P < .001; c = 0.53; 95% CI: 0.50‐0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77‐0.86) also performed better than CUETO (P = .008; c = 0.73; 95% CI: 0.66‐0.81) but there was no sufficient evidence that it performed better than EAU (P = .572; c = 0.81; 95% CI: 0.77‐0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG‐treated EAU high‐risk patients (P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy.
Eco‐Friendly Sugar‐Based Natural Deep Eutectic Solvents as Effective Electrolyte Solutions for Dye‐Sensitized Solar Cells
Authors: Boldrini Chiara Liliana , Manfredi Norberto , Perna Filippo Maria , Capriati Vito , Abbotto Alessandro
Published: March 2020

Dye‐sensitized solar cells containing sugar‐based natural deep eutectic solvents (NADESs) as active electrolyte solvents have been studied in terms of their photovoltaic (PV) properties, including main PV characteristics, incident photon‐to‐current efficiency, and impedance properties. Five monosaccharides were selected as NADES H‐bond donors and investigated with a phenothiazine‐based sensitizer carrying a glucose functionality and a glucose‐based co‐adsorbent (glucuronic acid) to explore directional intermolecular interactions and to improve the PV performance. The highest power conversion efficiencies were recorded for cells containing the glucose‐based sensitizer in the presence of glucuronic acid in the sugar‐based NADES. When one of these components was omitted, performances were lower, suggesting that the best response came from an interplay between the sugar‐based units. Not only has the unprecedented use of a NADES as a fully natural and bio‐renewable dye‐sensitized solar cell medium been presented, but for the first time an active role of the electrolyte solvent has been reported and exploited to increase the performance of the solar device.
Interface Engineering of MoS2‐Modified Graphitic Carbon Nitride Nano‐photocatalysts for an Efficient Hydrogen Evolution Reaction
Authors: Koutsouroubi Eirini D. , Vamvasakis Ioannis , Papadas Ioannis T. , Drivas Charalampos , Choulis Stelios A. , Kennou Stella , Armatas Gerasimos S.
Published: March 2020

Understanding of photochemical charge transfer processes at nanoscale heterojunctions is essential in developing effective catalysts. Here, we utilize a controllable synthesis method and a combination of optical absorption, photoluminescence, and electrochemical impedance spectroscopic studies to investigate the effect of MoS2 nanosheet lateral dimension and edge length size on the photochemical behavior of MoS2‐modified graphitic carbon nitride (g‐C3N4) heterojunctions. These nano‐heterostructures, which comprise interlayer junctions with variable area (i. e., MoS2 lateral size ranges from 18 nm to 52 nm), provide a size‐tunable interfacial charge transfer through the MoS2/g‐C3N4 contacts, while exposing a large fraction of surface MoS2 edge sites available for the hydrogen evolution reaction. Importantly, modification of g‐C3N4 with MoS2 layers of 39±5 nm lateral size (20 wt % loading) creates interfacial contacts with relatively large number of MoS2 edge sites and efficient electronic transport phenomena, yielding a high photocatalytic H2‐production activity of 1497 μmol h−1 gcat−1 and an apparent QY of 3.3 % at 410 nm light irradiation. This study thus offers a design strategy to improve light energy conversion efficiency of catalysts by engineering interfaces at the nanoscale in 2D‐layered heterojunction materials.
Improved Chemical Stability of Organometal Halide Perovskite Solar Cells Against Moisture and Heat by Ag Doping
Authors: Park Chaneui , Yang Seok Joo , Choi Jinhyeok , Song Sungwon , Choi Wookjin , Cho Kilwon
Published: March 2020

Organometal halide perovskite (OHP) solar cells have been intensively studied because of their promising optoelectronic features, which has resulted in high power conversion efficiencies >23 %. Although OHP solar cells exhibit high power conversion efficiencies, their relatively poor stability is a significant obstacle to their practical use. We report that the chemical stability of OHP solar cells with respect to both moisture and heat can be improved by adding a small amount of Ag to the precursor. Ag doping increases the size of the OHP grains and reduces the size of the amorphous intergranular regions at the grain boundaries, and thereby hinders the infiltration of moisture into the OHP films and their thermal degradation. Quantum mechanical simulation reveals that Ag doping increases the energies of both the hydration reaction and heat‐induced vacancy formation in OHP crystals. This procedure also improves the power conversion efficiencies of the resulting solar cells.
Template assisted synthesis of Sn@C microspheres and SnO2@C micro bowls as anode for Li‐Ion batteries
Authors: Gurunathan Padalingam , Karthick Babu Morekonda Ganesh , Ramesha Kannadka
Published: March 2020

There are ongoing efforts to improve the energy density of current day Li‐ion batteries by using alloy‐based anodes such as Si, Sn, or SnO2 in place of graphite. Here we report template‐assisted synthesis of Sn@C microspheres and SnO2@C microbowls prepared by phloroglucinol (P) − formaldehyde (F) gel method. The structural and morphological characterizations are carried out using XRD, FESEM, and HR‐TEM. The electrochemical performance of SnO2@C as anode for Li‐ion battery is investigated through cyclic voltammetry (CV) and galvanostatic charge‐discharge cycling. At 1C rate, SnO2@C delivers a discharge capacity of 651 mA h g−1 over 150 cycles. Even at 5C rate, a reversible capacity of 494 mA h g−1 is observed with 72% of capacity retention over 200 cycles. Electrochemical impedance measurements also infer faster Li‐ion transport kinetics in the electrode material. The postmortem FESEM images on electrochemically cycled material show that porous hollow structure is retained even after prolonged cycling. For comparison, the Li storage property of Sn@C microspheres (MS) tested as anode for Li‐ion battery applications. This Sn@C composite delivered an excellent cycling capacity of 636 mA h g−1 at 1C rate over 400 cycles. When cycled at higher rate 5C, Sn@C composite exhibits high reversible capacity of 257 mA h g−1 with 68% of capacity retention over 250 cycles. These results highlight that combination of hollow architecture and porous carbon matrix of Sn@C and SnO2@C electrode provides better mechanical support to alleviate volume expansion issue of Sn electrode.
Privacy‐preserving data aggregation scheme for edge computing supported vehicular ad hoc networks
Authors: Zhao Ouyang , Liu Xuchong , Li Xiong , Singh Pitam , Wu Fan
Published: March 2020

Vehicular ad hoc networks (VANETs) allow vehicles getting road situation by connecting with roadside unit (RSU) through the on‐board unit, and this information can be processed to improve transportation services in a timely manner. Meanwhile, the three‐tier edge computing system can support the VANETs well. However, the limited bandwidth of the VANETs and the privacy of uploaded data are still issues to be resolved. Data aggregation is an effective way to address the issue of limited bandwidth and data privacy protection for individual devices. In this article, based on the bilinear pairing and Paillier homomorphic encryption, we design a privacy‐preserving data aggregation scheme for edge computing supported VANETs, which not only preserves the privacy of uploaded data but also realizes batch operations. Also, the proposed scheme guarantees the features of data integrity and source authentication. Moreover, the comparison of performance evaluation between ours and other recent schemes shows that the proposed scheme significantly reduces the communication overhead and is more suitable for resource‐constrained terminal device.
Multi‐scale network regression for brain‐phenotype associations
Authors: Xia Cedric Huchuan , Ma Zongming , Cui Zaixu , Bzdok Danilo , Thirion Bertrand , Bassett Danielle S. , Satterthwaite Theodore D. , Shinohara Russell T. , Witten Daniela M.
Published: March 2020

Brain networks are increasingly characterized at different scales, including summary statistics, community connectivity, and individual edges. While research relating brain networks to behavioral measurements has yielded many insights into brain‐phenotype relationships, common analytical approaches only consider network information at a single scale. Here, we designed, implemented, and deployed Multi‐Scale Network Regression (MSNR), a penalized multivariate approach for modeling brain networks that explicitly respects both edge‐ and community‐level information by assuming a low rank and sparse structure, both encouraging less complex and more interpretable modeling. Capitalizing on a large neuroimaging cohort (n = 1, 051), we demonstrate that MSNR recapitulates interpretable and statistically significant connectivity patterns associated with brain development, sex differences, and motion‐related artifacts. Compared to single‐scale methods, MSNR achieves a balance between prediction performance and model complexity, with improved interpretability. Together, by jointly exploiting both edge‐ and community‐level information, MSNR has the potential to yield novel insights into brain‐behavior relationships.
Interoceptive accuracy and its impact on neuronal responses to olfactory stimulation in the insular cortex
Authors: Koeppel Carina J. , Ruser Paul , Kitzler Hagen , Hummel Thomas , Croy Ilona
Published: March 2020

The insular cortex plays a key role in the integration of multimodal information and in interoceptive and exteroceptive processing. For instance, neurons in the central dorsal insula that are active during interoceptive tasks, also show an adaptation to gustatory stimulation. We tested the link between interoception and exteroception for the olfactory system (i.e., the second domain of chemosensation). In a sample of 31 participants, olfactory function was assessed in a two dimensional approach while the Heartbeat Perception Task served as a measurement for cardiac interoceptive accuracy. Subsequent fMRI sessions were performed on a 3‐Tesla MR scanner containing 12–15 olfactory stimulation trials with a mildly pleasant food‐related odor (coffee). Persons scoring high in the cardiac interoceptive accuracy task presented stronger smelling abilities as well as enhanced BOLD responses following olfactory stimulation. The olfactory stimulation triggered enhanced insular activation patterns in the central dorsal insular cortex. Consistent with prior findings on the coherence of gustatory and interoceptive processing in the central dorsal insula, these results base the insula as a common region for the integration of interoception and exteroception. We propose an explanatory model of how exteroception triggers the integration of intero‐ and exteroceptive sensations in the central dorsal insular cortex.
Evaluation of a pharmacist‐driven renal dosing protocol at an academic medical center
Authors: Cheung Dora , Go Amy , Cooper Margaret , Schwarz Kerry
Published: March 2020

Introduction

Kidney disease is a major worldwide public health problem. An increased risk for adverse drug events is associated with drug dosing errors in hospitalized patients with renal impairment. A pharmacist‐driven renal protocol may improve dosing compliance by allowing pharmacists to monitor renal function and adjust drug doses as needed.

Objectives

To evaluate the utilization and financial impact of a pharmacist‐driven renal dosing protocol.

Methods

This was a retrospective cohort study of patients admitted to an academic medical center from 1 April 2017 to 30 May 2017 who had drug(s) from the protocol dose adjusted by a pharmacist. Outcomes of interest included protocol use frequency, patient characteristics, type of dose adjustments, and when adjustments were made. Two subgroup analyses were performed to: (1) determine cost savings of the seven most adjusted drugs and (2) determine if any missed opportunities for dose adjustments for cefepime.

Results

A total of 422 dosage adjustments, performed on 317 patients, were included. The mean age of the patients was 63 years with 51.2% female. The majority (62.8%) had no history of renal dysfunction, 22.4% had chronic kidney disease, 14.8% had end‐stage renal disease, and 25.3% had acute kidney injury on admission. Most dose adjustments (73.5%) were dose decreases, while 24.4% were dose increases. The seven most commonly adjusted drugs contributed to a cost savings of approximately $3919.87 per duration of therapy which extrapolates to an annual cost savings of $23 519.22. Of all the cefepime orders reviewed over a 7‐day period, 84% were dosed correctly, 9% needed dose adjustments that could have been made sooner, and 7% had incorrect dose based on renal function.

Conclusion

This analysis demonstrates that implementation of a pharmacist‐driven renal dose adjustment protocol was consistently utilized at our institution and resulted in cost savings.
Radiomic Features of Primary Rectal Cancers on Baseline T2‐Weighted MRI Are Associated With Pathologic Complete Response to Neoadjuvant Chemoradiation: A Multisite Study
Authors: Antunes Jacob T. , Ofshteyn Asya , Bera Kaustav , Wang Erik Y. , Brady Justin T. , Willis Joseph E. , Friedman Kenneth A. , Marderstein Eric L. , Kalady Matthew F. , Stein Sharon L. , Purysko Andrei S. , Paspulati Rajmohan , Gollamudi Jayakrishna , Madabhushi Anant , Viswanath Satish E.
Published: March 2020

Background

Twenty‐five percent of rectal adenocarcinoma patients achieve pathologic complete response (pCR) to neoadjuvant chemoradiation and could avoid proctectomy. However, pretreatment clinical or imaging markers are lacking in predicting response to chemoradiation. Radiomic texture features from MRI have recently been associated with therapeutic response in other cancers.

Purpose

To construct a radiomics texture model based on pretreatment MRI for identifying patients who will achieve pCR to neoadjuvant chemoradiation in rectal cancer, including validation across multiple scanners and sites.

Study Type

Retrospective.

Subjects

In all, 104 rectal cancer patients staged with MRI prior to long‐course chemoradiation followed by proctectomy; curated from three institutions.

Field Strength/Sequence

1.5T–3.0T, axial higher resolution T2‐weighted turbo spin echo sequence.

Assessment

Pathologic response was graded on postsurgical specimens. In total, 764 radiomic features were extracted from single‐slice sections of rectal tumors on processed pretreatment T2‐weighted MRI.

Statistical Tests

Three feature selection schemes were compared for identifying radiomic texture descriptors associated with pCR via a discovery cohort (one site,N =60, cross‐validation). The top‐selected radiomic texture features were used to train and validate a random forest classifier model for pretreatment identification of pCR (two external sites,N =44). Model performance was evaluated via area under the curve (AUC), accuracy, sensitivity, and specificity.

Results

Laws kernel responses and gradient organization features were most associated with pCR (P ≤ 0.01); as well as being commonly identified across all feature selection schemes. The radiomics model yielded a discovery AUC of 0.699 ± 0.076 and a hold‐out validation AUC of 0.712 with 70.5% accuracy (70.0% sensitivity, 70.6% specificity) in identifying pCR. Radiomic texture features were resilient to variations in magnetic field strength as well as being consistent between two different expert annotations. Univariate analysis revealed no significant associations of baseline clinicopathologic or MRI findings with pCR (P= 0.07–0.96).

Data Conclusion

Radiomic texture features from pretreatment MRIs may enable early identification of potential pCR to neoadjuvant chemoradiation, as well as generalize across sites.

Level of Evidence

3

Technical Efficacy Stage

2
New insights into paper—Chemical paper analysis using Raman microscopy
Authors: Pigorsch Enrico
Published: March 2020

Raman microscopic measurements were used to analyse the detailed chemical composition and structure of three old papers dating from the 15th and 19th centuries. Raman mapping measurements were performed on the surface and along the cross‐section of the papers with a lateral resolution of 1 μm. The resulting Raman images visualise the detailed chemical structure of the papers including all components such as the different types of cellulose fibre, filler pigments, sizing agents, colour pigments and also inadvertently added trace particles, such as minerals or products of biological activity. The results of the paper analysis are discussed in connection with their use for the detailed characterisation and dating of paper.

This study demonstrates the great potential and the possibilities offered by Raman microscopy or Raman imaging for chemical paper analysis. Raman microscopy allows new insights into the chemical composition and structure of old papers and could considerably enhance the understanding of former papermaking practices and also combat forgery and the fraud of documents and artworks on paper.
Hepatic artery infusion pumps
Authors: Thiels Cornelius A. , D'Angelica Michael I.
Published: March 2020

The preferential blood supply from the hepatic artery to liver tumors allows for the regional delivery of chemotherapy, commonly referred to as hepatic artery infusion chemotherapy via a subcutaneous pump. Hepatic artery infusion chemotherapy has been demonstrated to improve overall survival in select patients with colorectal liver metastasis and is a promising treatment for unresectable intrahepatic cholangiocarcinoma. This review focuses on the technical aspects of hepatic artery infusion pump placement.
A novel C2 symmetric chiral stationary phase with N‐[(4‐Methylphenyl)sulfonyl]‐l‐leucine as chiral side chains
Authors: Zhu Junchen , Zhu Lunan , Wu Yaling , Cheng Lingping , Wang Huiying , Sun Xiaotong , Shen Jiawei , Zhou Yang , Ke Yanxiong
Published: March 2020

In this study, a series of chiral stationary phases based on N‐[(4‐methylphenyl)sulfonyl]‐l‐leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N‐[(4‐methylphenyl)sulfonyl]‐l‐leucine showed much better enantioselectivities than that based on N‐(4‐methylbenzoyl)‐l‐leucine amide. The construction of C2 symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C2 symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C2 symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π–π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans‐N,N′‐(1,2‐diphenyl‐1,2‐ethanediyl)bis‐acetamide, which had an excellent separation factor on the C2 symmetric chiral stationary phase, was investigated by 1H‐NMR spectroscopy and 2D 1H‐1H nuclear overhauser enhancement spectroscopy.
Women's Sexual Desire, Trauma Exposure, and Posttraumatic Stress Disorder
Authors: O'Loughlin Julia I. , Brotto Lori A.
Published: March 2020

Research suggests that posttraumatic stress disorder (PTSD) is associated with sexual dysfunction; however, there is a paucity of research examining the relations among trauma exposure, PTSD, and low sexual desire, specifically. Thus, the goal of the present study was to investigate whether women with hypoactive sexual desire disorder (HSDD; n = 132) were more likely to meet criteria for a diagnosis of current or lifetime PTSD relative to women with no sexual desire concerns (n = 137). We also sought to compare the type, frequency, and intensity of PTSD symptoms between the two groups. Finally, we examined whether women in the two groups were exposed to more, or different types of, potentially traumatic events. Compared to women with no sexual health concerns, women with HSDD were more likely to meet criteria for current PTSD, odds ratio (OR) = 5.50, 95% CI [1.18, 25.61]; and lifetime PTSD, OR = 2.78, 95% CI [1.56, 4.94]. Women in the HSDD group also had higher odds of meeting criteria for avoidance (5.10 times) and hyperarousal symptoms (4.48 times) and scored higher on measures of past‐month PTSD symptom frequency, d = 0.62, and intensity, d = 0.57. No group differences were observed regarding reexperiencing symptoms, the associated features of PTSD, or type or frequency of exposure to potentially traumatic events. The findings indicate PTSD symptomatology may be a predisposing or perpetuating contributor to low sexual desire, and low sexual desire and PTSD may be related through an alteration in stress adaptability.
Immunogenic cell death in colon cancer prevention and therapy
Authors: Ruan Hang , Leibowitz Brian J. , Zhang Lin , Yu Jian
Published: March 2020

Colorectal cancer (CRC) is a leading cause of cancer‐related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well‐known to increase cancer risk. During tumor development, neoplastic cells continuously interact with and shape the tumor microenvironment (TME), which becomes progressively immunosuppressive. The clinical success of immune checkpoint blockade therapies is limited to a small set of CRCs with high tumor mutational load and tumor‐infiltrating T cells. Induction of immunogenic cell death (ICD), a type of cell death eliciting an immune response, can therefore help break the immunosuppressive TME, engage the innate components, and prime T cell‐mediated adaptive immunity for long‐term tumor control. In this review, we discuss the current understanding of ICD induced by antineoplastic agents, the influence of driver mutations, and recent developments to harness ICD in colon cancer. Mechanism‐guided combinations of ICD‐inducing agents with immunotherapy and actionable biomarkers will likely offer more tailored and durable benefits to patients with colon cancer.
Simultaneous trajectory generation and volumetric modulated arc therapy optimization
Authors: Mullins Joel , Renaud Marc‐André , Serban Monica , Seuntjens Jan
Published: March 2020

Purpose

Trajectory‐based treatment planning involves the combination of a gantry‐couch trajectory with volumetric modulated arc therapy (VMAT) treatment plan optimization. This work presents the implementation of an optimization methodology that generates a trajectory simultaneous with treatment plan optimization (simTr‐VMAT).

Methods

The optimization algorithm is based on the column generation approach, in which a treatment plan is iteratively constructed through the solution of a subproblem called the “pricing problem.” The property of the pricing problem to rank candidate apertures based on their associated price is leveraged to select an optimal aperture while simultaneously determining the trajectory path. A progressively increasing gantry‐couch grid resolution is used to provide an initial coarse sampling of the angular solution space while maintaining fine control point spacing with the final treatment plan. The trajectory optimization was applied and compared to coplanar VMAT treatment plans for a lung patient, a glioblastoma patient, and a prostate patient. Algorithm validation was performed through the generation of 5000 random trajectories and optimization using column generation VMAT for each patient case, representing the solution space for the trajectory optimization problem. The simTr‐VMAT trajectories were compared against these random trajectories based on a quality metric that prefers trajectories with few control points and low objective function value over long, inefficient trajectories.

Results

For the lung patient, the simTr‐VMAT plan resulted in a decrease of the mean dose of 1.5 and 1.0 Gy to the heart and ipsilateral lung, respectively. For the glioblastoma patient, the simTr‐VMAT plan resulted in improved planning target volume coverage with a decrease in mean dose to the eyes, lens, nose, and contralateral temporal lobe between 2 and 7 Gy. The prostate patient showed no clinically relevant dosimetric improvement. The simTr‐VMAT treatment plans ranked at the 99.6, 96.3, and 99.4 percentiles compared to the distribution of randomly generated trajectories for the lung, glioblastoma, and prostate patients, respectively.

Conclusion

The simTr‐VMAT optimization methodology resulted in treatment plans with equivalent or improved dosimetric outcomes compared to coplanar VMAT treatment plans, with the trajectories resulting from the optimization ranking among the optimal trajectories for each patient case.
Evaluation of Stocking Density and Dietary Fish Meal Inclusion for Intensive Tank Production of Pacific White Shrimp Litopenaeus vannamei Cultured in Low-Salinity Waters of Western Alabama
Authors: Roy Luke A , Teichert-Coddington David , Beck Benjamin H , Dahl Sunni , James Jesse , Guo Jingping , Davis D Allen
Published: March 2020

Shrimp farmers in Alabama are seeking to increase efficiency and intensify production. Semi-intensive earthen ponds are the traditional production system used by Alabama shrimp farmers; however, there is interest in evaluating intensive pond-based production systems, such as split ponds. These alternative systems are more intensive and require higher stocking densities to offset capital investment costs required for initial construction and maintenance. Two trials were carried out with Pacific white shrimp Litopenaeus vannamei using on-levee flow-through systems (twelve 800-L tanks per system) at an Alabama shrimp farm to evaluate stocking densities of 29, 88, 176, and 264 shrimp/m2 (trial 1) and higher levels of fish meal (5, 10, and 20%) at a high density of 264 shrimp/m2 (trial 2). Results from trial 1 revealed that as stocking density was increased Pacific white shrimp final weight decreased, while shrimp biomass and feed conversion ratio increased. Survival of Pacific white shrimp at the two highest densities (176 and 264 shrimp/m2) was lower than at the two lowest densities (29 and 88 shrimp/m2). There were no significant differences in performance for Pacific white shrimp offered diets with varying levels of fish meal in trial 2; however, overall survival in trial 2, which was carried out at a high density (264 shrimp/m2), ranged between 47.9% and 65.5%.
A theory of loosening earth pressure above a shallow tunnel in unsaturated ground
Authors: Fang Xu , Kikumoto Mamoru , Cui Ying
Published: March 2020

A theory is proposed to evaluate the loosening earth pressure (vertical earth pressure after excavation) acting on a shallow tunnel in unsaturated ground with an arbitrary groundwater level. The theory is developed based on the limit equilibrium theory, combining soil–water characteristic curves, Mohr–Coulomb failure criteria, and effective stress for unsaturated soils. The proposed theory is applied to predict the vertical distribution of loosening earth pressure in unsaturated ground, which shows a significant difference from that in saturated ground. In unsaturated ground, suction contributes to the increase in effective loosening earth pressure and shear resistance. The remarkable effects of groundwater depth, soil type, and scale of overburden height and trapdoor width on loosening earth pressure are also revealed. Based on the soil–water characteristic curve, the degree of saturation decreases, which causes wet density to decrease and the total and effective loosening earth pressures to have contrary tendencies. Moreover, effective loosening earth pressures vary with soil type as the degree of saturation varies. The total loosening earth pressures are, however, very similar regardless of soil type, because wet density and shear resistance have similar tendencies. The proposed theory provides a valid model for loosening earth pressure in unsaturated ground that will be useful for shallow tunnel excavations.
Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: an fMRI study
Authors: Stefancin Patricia , Cahaney Christine , Parker Robert I. , Preston Thomas , Coulehan Kelly , Hogan Laura , Duong Timothy Q.
Published: March 2020

The goal of this study is to investigate the neural correlates of working memory function associated with chemotherapy in pediatric cancer survivors using event‐related functional MRI (fMRI) analysis. Fifteen pediatric cancer survivors treated with chemotherapy and 15 healthy controls were studied. Blood oxygenation level dependent (BOLD) fMRI was acquired. A visual n‐back task was used to test working memory function during the fMRI scan. Responses were recorded via an MRI compatible button box for analysis. fMRI scans were analyzed using statistical parametric mapping software. All statistics were corrected for multiple comparisons by false discovery rate, with p < 0.05 as significance. Patients however gave more incorrect responses (p < 0.05), more no responses (p < 0.05), and longer response times (p < 0.05) compared with healthy controls. Correct responses generated significantly lower BOLD responses in the posterior cingulate for pediatric cancer survivors compared with controls (p < 0.05). Incorrect responses generated significantly greater BOLD responses in the angular gyrus in survivors (p < 0.05), and no response trials generated greater BOLD responses within the superior parietal lobule (p < 0.05) compared with controls. Working memory impairment appears to be due to an inability to manipulate information and to retrieve information from memory. The ability to delineate the affected neural circuits associated with chemotherapy‐induced cognitive impairment could inform treatment strategies, identify patients at high risk of developing cognitive deficits, and pre‐emptively tailor behavioral enrichment to overcome specific cognitive deficits.