bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Access to Dispirocyclic Scaffolds Enabled by Diastereoselective Intramolecular Double Functionalization of Benzene Rings
Authors: Yokoe Hiromasa , Mizumura Yuka , Sugiyama Kana , Yan Kejia , Hashizume Yuna , Endo Yuto , Yoshida Sae , Kiriyama Akiko , Tsubuki Masayoshi , Kanoh Naoki
Published: October 2020

Here we describe the diastereoselective synthesis of (5r,8r)‐1,9‐diazadispiro[4.2.48.25]tetradecatrienes via domino double spirocyclization of N‐arylamide derivatives. This reaction can serve as a fast way to synthesize diazadispirocycles, which are found in the core structures of bioactive natural products. Product diversification via Suzuki–Miyaura cross coupling and application to the synthesis of 1‐oxa‐9‐azadispiro[4.2.48.25]tetradecatrienes were also conducted.
Tyrosinase Inhibitory Effects of Derivatives of (E)‐2‐(Substituted Benzylidene)‐3,4‐Dihydronaphthalen‐1(2H)‐One
Authors: Ryu Il Young , Choi Inkyu , Ullah Sultan , Choi Heejeong , Chun Pusoon , Moon Hyung Ryong
Published: October 2020

Tyrosinase plays an essential role in melanin biosynthesis, and as such it has received great attention as a key target for the treatment of pigmentation disorders. In our earlier studies, we explored analogs with the β‐phenyl‐α,β‐unsaturated carbonyl template, and the results obtained indicated that this template confers potent tyrosinase inhibitory activity. Thus, in the present study, (E)‐2‐(substituted benzylidene)‐3,4‐dihydronaphthalen‐1(2H)‐one derivatives (compounds 1–6) with this template were synthesized and investigated with respect to their mushroom tyrosinase inhibitory effects. Derivative 4 with a 3‐hydroxy‐4‐methoxyl substituent on the β–phenyl ring of the template inhibited mushroom tyrosinase fourfold more than kojic acid (IC50 = 15.60 ± 0.32 μM vs. 57.06 ± 0.46 μM). In silico docking simulation supported this potent inhibitory activity of compound 4 by demonstrating a binding energy of −6.4 kcal/mol at the active site of mushroom tyrosinase. Kinetic results imply that 4 competitively inhibits mushroom tyrosinase.
Chalcogen‐Bonding Interactions in Telluroether Heterocycles [Te(CH2)m]n (n=1–4; m=3–7)
Authors: Rodewald| Marko , Rautiainen J. Mikko , Niksch Tobias , Görls Helmar , Oilunkaniemi Raija , Weigand Wolfgang , Laitinen Risto S.
Published: October 2020

Invited for the cover of this issue are the groups of Risto Laitinen at University of Oulu and Wolfgang Weigand at Friedrich Schiller University Jena. The image depicts a picturesque view of the Te⋅⋅⋅Te close contacts forming infinite tubular shafts in 1,9,17,25‐Te4(CH2)28. The cover artwork was designed and created by Marko Rodewald. Read the full text of the article at 10.1002/chem.202002510.
Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses
Authors: Wienen‐Schmidt Barbara , Oebbeke Matthias , Ngo Khang , Heine Andreas , Klebe Gerhard
Published: October 2020

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non‐covalent interaction inventories are essential to design follow‐up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment‐sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino‐acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.
2‐Isoxazolines: A Synthetic and Medicinal Overview
Authors: Kumar Gulshan , Shankar Ravi
Published: October 2020

Isoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1,3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies.
Multimodality treatment outcome in patients with primary malignant mediastinal germ cell tumor in adults
Authors: Biswas Bivas , Dabkara Deepak , Sengupta Moushumi , Ganguly Sandip , Ghosh Joydeep , Arunsingh S Moses , Sen Saugata
Published: October 2020

Background

Malignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource‐poor countries are scarce in the literature.

Aims

To evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center.

Methods and Results

Single institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non‐seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18‐36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre‐treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non‐seminoma histology with poor‐risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non‐seminoma histology underwent complete resection of residual disease post‐chemotherapy and five revealed residual viable tumors. After a median follow‐up of 10.8 months (range:2.9‐75), 3‐year progression‐free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3‐year PFS and OS estimate was 100% in patients with seminoma histology.

Conclusions

This is the largest data set of MGCT patients' outcomes reported from India with multi‐modality treatment. All patients were male and one‐fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non‐seminoma histology had a poor outcome even with chemotherapy and surgery.
Weaker Interactions in Zn2+ and Organic Ion‐pre‐intercalated Vanadium Oxide toward Highly Reversible Zinc‐ion Batteries
Authors: Zhang Feng , Sun Xiucai , Du Min , Zhang Xiaofei , Dong Wentao , Sang Yuanhua , Wang Jianjun , Li Yanlu , Liu Hong , Wang Shuhua
Published: October 2020

Driven by safety issues, environmental concerns, and high costs, rechargeable aqueous zinc‐ion batteries (ZIBs) have received increasing attention in recent years owing to their unique advantages. However, the sluggish kinetics of divalent charge Zn2+ in the cathode materials caused by the strong electrostatic interaction and their unsatisfactory cycle life hinder the development of ZIBs. Herein, organic cations and Zn2+ ions co‐pre‐inserted vanadium oxide ([N(CH3)4]0.77,Zn0.23)V8O20·3.8H2O are reported as the cathode for ultra‐stable aqueous ZIBs, in which the weaker electrostatic interactions between Zn2+ and organic ion‐pinned vanadium oxide can induce the high reversibility of Zn2+ insertion and extraction, thereby improving the cycle life. It is demonstrated that ([N(CH3)4]0.77,Zn0.23)V8O20·3.8H2O cathodes deliver a discharge capacity of 181 mA h g−1 at 8 A g−1 and ultra‐long life span (99.5% capacity retention after 2000 cycles). A reversible Zn2+/H+ ions (de)intercalation storage process and pseudocapacitive charge storage are characterized. The weaker interactions between organic ion and Zn2+ open a novel avenue for the design of highly reversible cathode materials with long‐term cycling stability.
Prophylactic and therapeutic HBV vaccination by an HBs‐expressing cytomegalovirus vector lacking an interferon antagonist in mice
Authors: Huang Hongming , Rückborn Meike , Le‐Trilling Vu Thuy Khanh , Zhu Dan , Yang Shangqing , Zhou Wenqing , Yang Xuecheng , Feng Xuemei , Lu Yinping , Lu Mengji , Dittmer Ulf , Yang Dongliang , Trilling Mirko , Liu Jia
Published: October 2020

Cytomegalovirus (CMV)‐based vaccines show promising effects against chronic infections in nonhuman primates. Therefore, we examined the potential of hepatitis B virus (HBV) vaccines based on mouse CMV (MCMV) vectors expressing the small HBsAg. Immunological consequences of vaccine virus attenuation were addressed by either replacing the dispensable genem157(“MCMV‐HBsȍ) or the geneM27(“ΔM27‐HBs”), the latter encodes a potent IFN antagonist targeting the transcription factor STAT2.M27was chosen, since human CMV encodes an analogous gene product, which also induced proteasomal STAT2 degradation by exploiting Cullin RING ubiquitin ligases. Vaccinated mice were challenged with HBV through hydrodynamic injection. MCMV‐HBs and ΔM27‐HBs vaccination achieved accelerated HBV clearance in serum and liver as well as robust HBV‐specific CD8+T‐cell responses. When we explored the therapeutic potential of MCMV‐based vaccines, especially the combination of ΔM27‐HBs prime and DNA boost vaccination resulted in increased intrahepatic HBs‐specific CD8+T‐cell responses and HBV clearance in persistently infected mice. Our results demonstrated that vaccines based on a replication competent MCMV attenuated through the deletion of an IFN antagonist targeting STAT2 elicit robust anti‐HBV immune responses and mediate HBV clearance in mice in prophylactic and therapeutic immunization regimes.
Effect of storage time on biochemical characteristics and antioxidant activity of hawk tea (Litsea coreana) processed by boiling water fixation
Authors: Xu Qing , Zhou Yuanjing , Zhao Jingfang , Yao Songlin , Wang Jihong
Published: October 2020

This study investigated the effect of storage time on biochemical characteristics of hawk tea (Litsea coreana) and explored the correlation between the content of flavonoids and polyphenols and antioxidant activity. The antioxidant activity and the content of inclusions, amino acid, and mineral elements in hawk tea processed by boiling water fixation and packed in airtight polypropylene bags and stored in 0°C refrigerator under different storage time (one year, three years, and six years) were analyzed. Results indicated that the biochemical characteristics of hawk tea changed less within 12 months. The total content and types of amino acids in hawk tea reached the maximum in the third year, as well as the content of total trace elements. The water extracts, tea polyphenol, caffeine, lysine, valine, isoleucine, glycine, proline, Ca, and Zn decreased continuously in the storage period of 6 years, but the total flavonoids, Mg, and Ni changed just the opposite. Total polyphenol is the main antioxidant material in hawk tea. Results of the present study provided useful information for people to systematically understand the changes of tea in the storage process and to reasonably develop hawk tea product.
Clinical variables and magnetic resonance imaging‐based radiomics predict human papillomavirus status of oropharyngeal cancer
Authors: Bos Paula , van den Brekel Michiel W. M. , Gouw Zeno A. R. , Al‐Mamgani Abrahim , Waktola Selam , Aerts Hugo J. W. L. , Beets‐Tan Regina G. H. , Castelijns Jonas A. , Jasperse Bas
Published: October 2020

Background

Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) have better prognosis and treatment response compared to HPV‐negative OPSCC. This study aims to noninvasively predict HPV status of OPSCC using clinical and/or radiological variables.

Methods

Seventy‐seven magnetic resonance radiomic features were extracted from T1‐weighted postcontrast images of the primary tumor of 153 patients. Logistic regression models were created to predict HPV status, determined with immunohistochemistry, based on clinical variables, radiomic features, and its combination. Model performance was evaluated using area under the curve (AUC).

Results

Model performance showed AUCs of 0.794, 0.764, and 0.871 for the clinical, radiomic, and combined models, respectively. Smoking, higher T‐classification (T3 and T4), larger, less round, and heterogeneous tumors were associated with HPV‐negative tumors.

Conclusion

Models based on clinical variables and/or radiomic tumor features can predict HPV status in OPSCC patients with good performance and can be considered when HPV testing is not available.
How actors, processes, context and evidence influenced the development of Malawi's Health Sector Strategic Plan II
Authors: Walsh Caitlin M. , Mwase Takondwa , De Allegri Manuela
Published: October 2020

Health sector strategic plans are health policies outlining health service delivery in low‐ and middle‐ income countries, guiding health sectors to meet health needs while maximizing resources. However, little research has explored the formulation of these plans. This study utilized qualitative methods to explore the formulation of Malawi's Health Sector Strategic Plan II, including processes utilized, actors involved, important contextual factors and the use of evidence‐based decision‐making. Thirteen semi‐structured key informant interviews with health policy actors were conducted to explore perceptions and experiences of formulating the policy. Data analysis used an inductive‐deductive approach and interpretation of the data was guided by an adapted version of the Walt and Gilson Health Policy Triangle. Our results indicate that HSSP II formulation was complex and inclusive but that the Ministry of Health may have given up ownership of the formulation process to development partners to ensure their continued involvement. Disagreements between actors centered around inclusion of critical services in the Essential Health Package and selection of performance‐based financing as purchasing strategy. Resource constraints and the Cashgate Scandal are critical contextual elements influencing the formulation and content of the policy. Evidence‐based decision‐making contributed to the plan's development despite respondents' divergent opinions regarding evidence availability, quality and the weight that evidence carried. The study raises questions regarding the roles of policy actors during health policy formulation, the inclusivity of health policy processes and their potential influence on government ownership of health policy, as well as the use of evidence in developing health sector strategic plans.
Security Issue Detection and Mitigation Patterns for Product Line Resource Variation
Authors: Dove Rick
Published: October 2020

Product Line Engineering (PLE) builds upon an Agile Architectural Pattern—with reusable resources, evolving resource variations, and a standardized interconnect and sustainment infrastructure. Commercial PLE systems attract alternative resource suppliers, such as automotive parts. Defense PLE systems typically result from acquirers encouraging Open System Architectures to enable alternative resource suppliers. Alternative resource suppliers are a major resource variation source in product line engineered systems. Product line engineered systems are systems of systems with potential for complex interactions and unintended emergent behaviors. This article focuses on PLE cyber‐physical‐social system products, the security issues resource variation can introduce, and security patterns for detecting and mitigating these security issues. Resource variations may cause security issues unintentionally, but intentional introduction is also possible by malicious alternative resource suppliers, supply chain interdiction, and insiders. This article assumes malicious intent in resource variation as its security issue base line, as patterns for effective detection and mitigation of malicious variation intent encompass unintentional occurrences.
Hydroxyurea Pharmacokinetics in Pediatric Patients After Total Pancreatectomy With Islet Autotransplantation
Authors: Boucher Alexander A. , Dong Min , Vinks Alexander A. , Marahatta Anu , Howard Thad A. , Ware Russell E. , Nathan Jaimie D. , Abu‐El‐Haija Maisam , Luchtman‐Jones Lori
Published: October 2020

Total pancreatectomy with islet autotransplantation is a complex surgical approach for acute recurrent or chronic pancreatitis that frequently triggers extreme thrombocytosis (platelets ≥ 1000 × 109/L). Thrombocytosis can be prothrombotic, so cytoreductive hydroxyurea is often initiated after this surgery; however, optimal dosing strategy and efficacy are unknown. This prospective pilot study characterized the pharmacokinetics of hydroxyurea after this procedure in children. It also compared them with previously published pediatric parameters in sickle cell anemia (SCA), the disease in which pediatric hydroxyurea pharmacokinetics have primarily been studied. Plasma hydroxyurea levels were quantified in 14 participants aged 4‐19 years using high‐performance liquid chromatography. Blood collections were scheduled 20 minutes, 1 hour, and 4 hours after the first dose, on pharmacokinetic day 1 (PK1), and again 2‐3 months later if still on hydroxyurea (PK2). Six participants had PK1 and PK2 data at all 3 postdose timed collections, 5 only had PK1 samples, and 3 only had PK2 samples. Total pancreatectomy with islet autotransplantation participants had reduced and delayed absorption compared with sickle cell anemia participant data from the Hydroxyurea Study of Long‐Term Effects, regardless of timing or dosing methodology. Total pancreatectomy with islet autotransplantation participants had different pharmacokinetic profiles at PK1 versus PK2, with lower dose‐normalized exposures than previously reported in sickle cell anemia. These results suggest variability exists in hydroxyurea absorption and bioavailability in total pancreatectomy with islet autotransplantation patients, suspected to be primarily because of Roux‐en‐Y reconstruction, and suggest that more pharmacokinetic data are needed for scenarios when hydroxyurea is prescribed to children without sickle cell anemia.
Effect of Supplemental Enteral Fish Oil on the Development of Psychological Complications in Critically Ill Multiple‐Trauma Patients: 6 Months’ Follow‐Up
Authors: Kagan Ilya , Mesilati‐Stahy Ronit , Green Pnina , Singer Pierre
Published: October 2020

Background

Posttraumatic stress disorder (PTSD) is common in intensive care unit (ICU) patients. Defic it intake of ω‐3 polyuns aturated fatty ac ids (PUFAs) may be as sociated with developm ent of PTSD.

Methods

This study randomized mechanically ventilated patients suffering from multiple trauma (n = 150) into 2 groups: a study and a control group that received enteral feeding with or without fish oil. Fifty‐one patients were interviewed 6 months after discharge from the ICU. Psychometric parameters of PTSD were assessed by questionnaires. The fatty acid composition of erythrocyte membranes was performed by homogenization of the cells in hexane‐isopropanol.

Results

No differences were found in baseline characteristics between the groups. Erythrocyte membrane composition showed significantly higher concentrations of ω‐3 fatty acids in the study group. Anxiety and depression symptoms were correlated with an increase in eicosapentaenoic acid (EPA) on days 4 and 8 for depression and EPA on day 4 and docosahexaenoic acid (DHA) on day 8 for anxiety. Total ω‐3 content was positively correlated with anxiety and depression as well. An inverse correlation was found between DHA and EPA in the treatment group and with the total ω‐3 and DHA in the control group for the Brief Illness Perceptions Questionnaire.

Conclusion

Administration of an ω‐3 PUFA–enriched diet during the ICU stay did not prevent development of PTSD in trauma patients 6 months after discharge from ICU.
High‐reliability gate driver circuit to prevent ripple voltage
Authors: Lee Jungwoo , Oh Jongsu , Jung Eun Kyo , Park KeeChan , Jeon Jae‐Hong , Lee Soo‐Yeon , Kim Yong‐Sang
Published: October 2020

In this paper, a high‐reliability gate driver circuit is proposed to prevent multiple outputs. The proposed circuit ensures reliability of the pull‐up thin‐film transistor (TFT) by periodically discharging the Q node voltage to the low‐level voltage (VGL) in the off stage. In addition, the output node is composed of two pull‐down TFTs that are driven alternately to ensure stability against bias stress. Thus, because the reliabilities of the pull‐up and pull‐down TFTs can be guaranteed simultaneously, the stability of the entire circuit is improved. Based on the simulation results, the rising and falling times of the output pulse are stable within 1.77 and 1.28 μs, respectively, even when the threshold voltage of the entire TFT is shifted by +10.0 V. In addition, the ripple voltage of the proposed circuit is almost eliminated and is within 0.79% of the total swing voltage. Moreover, through current is prevented in the proposed circuit because the turn‐on durations of the pull‐up and pull‐down units are completely nonoverlapping, which suggests that unnecessary power consumption can be eliminated. Therefore, based on 2,160 stages, the total power consumption of the proposed circuit is reduced by 34.7 mW from 276.3 to 241.6 mW.
Does nasal surgery improve multilevel surgical outcome in obstructive sleep apnea: A multicenter study on 735 patients
Authors: Pang Kenny P. , Montevecchi Filippo , Vicini Claudio , Carrasco‐Llatas Marina , Baptista Peter M. , Olszewska Ewa , Braverman Itzhak , Kishore Srivinas , Chandra Sudipta , Yang Hyung Chae , Chan Yiong Huak , Pang Scott B. , Pang Kathleen A. , Pang Edward B. , Rotenberg Brian
Published: October 2020

Objective

Does nasal surgery affect multilevel surgical success outcome.

Methods

Prospective eight country nonrandomized trial of 735 obstructive sleep apnea (OSA) patients, who had multilevel palate and/or tongue surgery, divided into two groups, with or without nose surgery.

Results

There were 575 patients in nose group, 160 patients in no nose group. The mean age for nose group 44.6 ± 11.4, no nose group 44.2 ± 11.8. Mean preoperative BMI for nose group 27.5 ± 3.6, no nose group 27.5 ± 4.1, mean postoperative BMI nose group 26.3 ± 3.7, no nose group 27.1 ± 3.8 (P = .006). Mean preoperative AHI nose group 32.7 ± 19.4, no nose group 34.3 ± 25.0 (P = .377); and mean postoperative AHI nose group 13.5 ± 10.2, no nose group 17.1 ± 16.0 (P = .001). Mean preoperative ESS nose group was 11.3 ± 4.7, no nose group was 10.4 ± 5.4 (P = .051); and mean postoperative ESS nose group was 5.3 ± 3.2, no nose group was 6.7 ± 2.8 (P = .001). The nose group had higher percentage change (adjusted for age, gender, BMI) in AHI (33.7%, 95% CI 14% to 53.5%) compared to the no nose group (P = .001); the nose group also had more percentage change in ESS (37%, 95% CI 23.6% to 50.3%) compared to the no nose group (P < .001). Change in BMI did not affect AHI nor ESS change (Cohen effect 0.03 and 0.14, respectively). AHI change in both groups were also statistically significant in the mild OSA (P = .008) and the severe OSA (P = .01). Success rate of surgery for the nose group 68.2%, while the no nose group 55.0% (P = .002).

Conclusion

Combining nose surgery in multilevel surgery improves surgical success.

Level of evidence

IIC.
Whole‐exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy
Authors: Zhang Xinyue , You Yanqin , Xie Xiaoxiao , Xu Hong , Zhou Honghui , Lei Yuanmei , Sun Pei , Meng Yuanguang , Wang Longxia , Lu Yanping
Published: October 2020

Background

Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short‐rib polydactyly syndrome (SRPS)‐like phenotype.

Method

Karyotyping and NGS‐based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole‐exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family.

Results

No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS‐like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short‐rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family.

Conclusion

Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling.
Producing a Beam Model of the Varian ProBeam Proton Therapy System using TOPAS Monte Carlo Toolkit
Authors: Rahman Mahbubur , Bruza Petr , Lin Yuting , Gladstone David J. , Pogue Brian W. , Zhang Rongxiao
Published: October 2020

Purpose

A Geant4‐based TOPAS Monte Carlo toolkit was utilized to model a Varian ProBeam proton therapy system, with the aim of providing an independent computational platform for validating advanced dosimetric methods.

Materials and Methods

The model was tested for accuracy of dose and linear energy transfer (LET) prediction relative to the commissioning data, which included integral depth dose (IDD) in water and spot profiles in air measured at varying depths (for energies of 70 to 240 MeV in increments of 10 MeV, and 242 MeV), and absolute dose calibration. Emittance was defined based on depth‐dependent spot profiles and Courant–Snyder’s particle transport theory, which provided spot size and angular divergence along the inline and crossline plane. Energy spectra were defined as Gaussian distributions that best matched the range and maximum dose of the IDD. The validity of the model was assessed based on measurements of range, dose to peak difference, mean point to point difference, spot sizes at different depths, and spread‐out Bragg peak (SOBP) IDD and was compared to the current treatment planning software (TPS).

Results

Simulated and commissioned spot sizes agreed within 2.5%. The single spot IDD range, maximum dose, and mean point to point difference of each commissioned energy agreed with the simulated profiles generally within 0.07 mm, 0.4%, and 0.6%, respectively. A simulated SOBP plan agreed with the measured dose within 2% for the plateau region. The protons/MU and absolute dose agreed with the current TPS to within 1.6% and exhibited the greatest discrepancy at higher energies.

Conclusions

The TOPAS model agreed well with the commissioning data and included inline and crossline asymmetry of the beam profiles. The discrepancy between the measured and TOPAS‐simulated SOBP plan may be due to beam modeling simplifications of the current TPS and the nuclear halo effect. The model can compute LET, and motivates future studies in understanding equivalent dose prediction in treatment planning, and investigating scintillation quenching.
Liver perfusion MRI in a rodent model of cirrhosis: Agreement with bulk‐flow phase‐contrast MRI and noninvasive evaluation of inflammation in chronic liver disease using flow‐sensitive alternating inversion recovery arterial spin labelling and tissue T1
Authors: Chouhan Manil Dinesh , Ramasawmy Rajiv , Bainbridge Alan , Campbell‐Washburn Adrienne , Halligan Steve , Davies Nathan , Walker‐Samuel Simon , Lythgoe Mark F. , Mookerjee Rajeshwar Prosad , Taylor Stuart Andrew
Published: October 2020

Noninvasive measurements of liver perfusion and fibrosis in cirrhotic small animals can help develop treatments for haemodynamic complications of liver disease. Here, we measure liver perfusion in cirrhotic rodents using flow‐sensitive alternating inversion recovery arterial spin labelling (FAIR ASL), evaluating agreement with previously validated caval subtraction phase‐contrast magnetic resonance imaging (PCMRI) total liver blood flow (TLBF). Baseline differences in cirrhotic rodents and the haemodynamic effects of acute inflammation were investigated using FAIR ASL and tissue T1. Sprague–Dawley rats (nine bile duct ligated [BDL] and ten sham surgery controls) underwent baseline hepatic FAIR ASL with T1 measurement and caval subtraction PCMRI (with two‐dimensional infra‐/supra‐hepatic inferior vena caval studies), induction of inflammation with intravenous lipopolysaccharide (LPS) and repeat liver FAIR ASL with T1 measurement after ~90 minutes. The mean difference between FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF was −51 ± 30 ml/min/100 g (Bland–Altman 95% limits‐of‐agreement ±258 ml/min/100 g). The FAIR ASL coefficient of variation was smaller than for caval subtraction PCMRI (29.3% vs 50.1%; P = .03). At baseline, FAIR ASL liver perfusion was lower in BDL rats (199 ± 32 ml/min/100 g vs sham 316 ± 24 ml/min/100 g; P = .01) but liver T1 was higher (BDL 1533 ± 50 vs sham 1256 ± 18 ms; P = .0004). Post‐LPS FAIR ASL liver perfusion response differences were observed between sham/BDL rats (P = .02), approaching significance in sham (+78 ± 33 ml/min/100 g; P = .06) but not BDL rats (−49 ± 40 ml/min/100 g; P = .47). Post‐LPS differences in liver tissue T1 were nonsignificant (P = .35). FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF agreement was modest, with significant baseline FAIR ASL liver perfusion and tissue T1 differences in rodents with advanced cirrhosis compared with controls. Following inflammatory stress, differences in hepatic perfusion response were detected between cirrhotic/control animals, but liver T1 was unaffected. Findings underline the potential of FAIR ASL in the assessment of vasoactive treatments for patients with chronic liver disease and inflammation.
In search of network resilience: An optimization‐based view
Authors: Sharkey Thomas C. , Nurre Pinkley Sarah G. , Eisenberg Daniel A. , Alderson David L.
Published: October 2020

Fifty years of research in Networks coincides with 50 years of advances in resilience theory and applications. The purpose of this review is to identify how these two technical communities influenced each other in the past and can bolster each other in the future. Advances in resilience theory show that there are at least four ways networks demonstrate resilience: robustness, rebound, extensibility, and adaptability. Research published in Networks and by the broader network optimization community has focused primarily on technical methods for robustness and rebound. We review this literature to organize seminal problems and papers on the ability of networks to manage increasing stressors and return to normal activities after a stressful event. In contrast, the Networks community has made less progress addressing issues for network extensibility and adaptability. Extensibility refers to the ability to stretch current operations to surprising situations and adaptability refers to the ability to sustain operations into the future. We discuss ways to harness existing network optimization methods to study these forms of resilience and outline their limitations. We conclude by providing a research agenda that ensures the Networks community remains central to future advances in resilience while being pragmatic about the limitations of network optimization for achieving this task.
A method for computing the Perron root for primitive matrices
Authors: Dembélé Doulaye
Published: October 2020

Following the Perron theorem, the spectral radius of a primitive matrix is a simple eigenvalue. It is shown that for a primitive matrix A, there is a positive rank one matrix X such that B = A ∘ X, where ∘ denotes the Hadamard product of matrices, and such that the row (column) sums of matrix B are the same and equal to the Perron root. An iterative algorithm is presented to obtain matrix B without an explicit knowledge of X. The convergence rate of this algorithm is similar to that of the power method but it uses less computational load. A byproduct of the proposed algorithm is a new method for calculating the first eigenvector.
Predicting psychological factors affecting regular physical activity in hypertensive patients: Application of health action process approach model
Authors: Mohammadi Zeidi Isa , Morshedi Hadi , Shokohi Abdollah
Published: October 2020

Aim

The aim of this study was to determine the factors affecting the behaviour of regular physical activity in patients with hypertension using the health action process approach (HAPA) model.

Design

This cross‐sectional study was conducted on 176 hypertension patients, in Astaneh‐e‐Ashrafiyeh, Guilan, Iran, 2018–2019.

Methods

Data collection tools included demographic characteristics, medical history, the short form of International Physical Activity Questionnaire (IPAQ) and scales related to the HAPA model. The data were analysed using chi‐square, independent t test, one‐way ANOVA, Pearson's correlation coefficient and path analysis on AMOS, version 23.0.

Results

Action self‐efficacy (β = 0.59), outcome expectancy (β = 0.20) and risk perception (β = 0.18) had a statistically significant effect on intention. Moreover, the path coefficient between intention (β = 0.35) and coping self‐efficacy (β = 0.29) with physical activity was statistically significant. The results revealed that HAPA constructs were able to describe 45% of the variance in intention and 31% of the variance in physical activity behaviour.

Conclusion

The HAPA model is a useful framework for describing the factors affecting physical activity in hypertension patients.
Procedures for Measuring Excreted and Ingested Calories to Assess Nutrient Absorption Using Bomb Calorimetry
Authors: Basolo Alessio , Parrington Shannon , Ando Takafumi , Hollstein Tim , Piaggi Paolo , Krakoff Jonathan
Published: October 2020

Objective

With the upsurge in interest in the gut microbiome, complete and accurate measurement of ingested calories and calories lost through excreted stool is crucial for assessing the effect of the microbiota on nutrient absorption.

Methods

Measurement of ingested and excreted calories was conducted over 3 days. Meals were made in duplicate: one was given to the participant, and one was used for the measurement of calories. Stool was marked by nonabsorbable dye ingested prior to and at the end of each 3‐day diet period and was collected for caloric assessment from the appearance of the first dye marker until the appearance of the second dye marker.

Results

Stool calories per gram for pellets were 4.91 ± 0.06 kcal/g. The mean stool calorie loss as a percentage of ingested calories was 7.3% ± 1.6% (range, 6.6%‐8.5%). The stool measurement of kilocalories per gram was not associated with the total measured stool calories or with stool weight (P = 0.2 and P = 0.2, respectively) over the 3‐day period. However, the weight of stool samples during each dietary intervention was positively associated with the calorie loss in stool (r = 0.58, P < 0.0001).

Conclusions

Our methods provide a direct measure of ingested calories and stool calories needed to accurately assess relative stool calorie loss as a measure of nutrient absorption. The weight of stool samples across the marked diet period is crucial to determining total stool calories.
Results of the Survey Conducted Among Caribbean Physicians on a Zoom Meeting Discussing the Article “A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group”
Authors: Shanbhag Nandan Maruti , Duncan Albert , Santos Elizabet Gomes Dos , Yazigi Hanybal , Grant-Tate Merisa , Girgis Nevein Farouk Francis , MoyaSantos Niurka B. , Vinh-Hung Vincent , Duran Yanelis Leon
Published: October 2020

Coronavirus disease 2019 (COVID-19) has resulted in a worldwide public health emergency, disrupting health care services and especially affecting at-risk populations. In this letter to the editor, oncologists from the Caribbean region report the results of an online meeting that was organized to seek guidance on patient care during the COVID-19 pandemic.
Toward an efficient stress transfer with a fully connected hybrid network from epoxy, oxidized UHMWPE fibers, and silane surface modified silicon carbide nanoparticles
Authors: Belgacemi Raouf , Derradji Mehdi , Trache Djalal , Zegaoui Abdeldjalil , Mehelli Oussama
Published: October 2020

In this work, a new high‐performance hybrid material was designed targeting excellent static and dynamic mechanical properties. To achieve this goal, the hybrid constituents, namely the ultra‐high molecular weight polyethylene fibers and silicon carbide nanoparticles, were respectively, surface modified to graft the proper chemical species in order to maximize the interactions between the reinforcing phases and the epoxy matrix. The adopted grafting procedures were characterized by vibrational and morphological analyses. The generation a fully connected network resulted in consequent ameliorations in the mechanical and thermomechanical properties. Meanwhile, the effect of various amounts of the treated silicon carbide nanoparticles was also investigated. The finding indicated a gradual improvement in the overall mechanical properties up to 5 wt% for which the tensile strength reached its maximum value of about 477 MPa. The same hybrid materials displayed the remarkable storage modulus of 7.7 GPa at 25°C and a glass transition temperature of about 66°C. The synergistic stress transfer between the constituents was further evidenced by a proper investigation of the sample's fractured surfaces. Overall, the study revealed the great advantage of a fully connected network in developing lightweight and high‐performance materials for exigent applications.
Polymethyl methacrylate reinforced with nickel coated multi‐walled carbon nanotubes: Flame, electrical and mechanical properties
Authors: Ameen Khan M , Madhu G. M. , Sailaja R. R. N.
Published: October 2020

Composites of polymethyl methacrylate (PMMA) as matrix and nickel‐coated multi‐walled carbon nanotubes (Ni‐MWCNT) as nanofillers were prepared using a melt mixing process. In order to improve the dispersion of the nanofillers in the PMMA matrix and thus enhance matrix‐filler interactions, Ni‐MWCNT was treated with amino propyl triethoxy‐silane (APTS). The shielding effectiveness (SE) of the composites improved with increasing Ni‐MWCNT content. In addition, the effects of various combinations of fillers like silver, copper, and nickel nanoparticles on SE have been studied. Among these nanoparticles, copper nanoparticles in combination with MWCNT and Ni‐MWCNT showed optimal shielding effectiveness of 55 dB. The volume and surface resistivity of the composites decreased with increase in nanofiller content. The tensile strength values were increased by 51% at 0.8 wt% loading of Ni‐MWCNT as compared to that of composite without filler. The improvement in tensile strength was further analyzed using micromechanical models. Cone calorimeter studies showed 25.3% reduction in the peak heat release rate for the composite loaded with 1.5 wt% of Ni‐MWCNT as compared to that of neat PMMA. The nanocomposites also showed enhanced thermal stability with the formation of char as the filler content increased.
Cognitive Flexibility Inventory: Factor structure, invariance, reliability, convergent, and discriminant validity among Italian university students
Authors: Portoghese Igor , Lasio Mirko , Conti Rachele , Mascia Maria L. , Hitchcott Paul , Agus Mirian , Gemignani Angelo , Penna Maria P.
Published: October 2020

Cognitive flexibility (CF) is a fundamental human ability to adjust cognitive processing strategies to deal with new and unpredicted situations. In this sense, using valid and theoretically grounded measures of cognitive flexibility is critical. A new measure of CF, the Cognitive Flexibility Inventory, has recently been validated. This measure comprises two subscales: (1) Alternatives, which assesses ability in identifying alternative solutions and generating several explanations; and (2) Control, which assesses ability in perceiving difficult conditions as controllable. The main purpose of our study was to investigate the factorial structure, reliability, and measurement invariance of the Cognitive Flexibility Inventory in an Italian sample of university students. A self‐report questionnaire was administered to 543 Italian university students. Results showed acceptable construct validity for the Italian version of the Cognitive Flexibility Inventory. Specifically, both exploratory and confirmatory factor analysis supported a two‐factor model, Alternatives and Control, with19 items. Moreover, multigroup analyses showed structural invariance across sex. In sum, our results suggested that the Italian version of the Cognitive Flexibility Inventory is a valid instrument for assessing cognitive flexibility.
Model error covariance estimation in particle and ensemble Kalman filters using an online expectation–maximization algorithm
Authors: Cocucci Tadeo J. , Pulido Manuel , Lucini Magdalena , Tandeo Pierre
Published: October 2020

The performance of ensemble‐based data assimilation techniques that estimate the state of a dynamical system from partial observations depends crucially on the prescribed uncertainty of the model dynamics and of the observations. These are not usually known and have to be inferred. Many approaches have been proposed to tackle this problem, including fully Bayesian, likelihood maximization and innovation‐based techniques. This work focuses on maximization of the likelihood function via the expectation–maximization (EM) algorithm to infer the model error covariance combined with ensemble Kalman filters and particle filters to estimate the state. The classical application of the EM algorithm in a data assimilation context involves filtering and smoothing a fixed batch of observations in order to complete a single iteration. This is an inconvenience when using sequential filtering in high‐dimensional applications. Motivated by this, an adaptation of the algorithm that can process observations and update the parameters on the fly, with some underlying simplifications, is presented. The proposed technique was evaluated and achieved good performance in experiments with the Lorenz‐63 and Lorenz‐96 dynamical systems designed to represent some common scenarios in data assimilation such as nonlinearity, chaoticity and model mis‐specification.
Swimming through the urban heat island: Can thermal mitigation practices reduce the stress?
Authors: Timm Anne , Ouellet Valerie , Daniels Melinda
Published: October 2020

Green infrastructure (GI) and other stormwater management practices are commonly designed to reduce stormflow volume and pollutant loads by using infiltration, retention, and evapotranspiration to capture stormwater. Although these methods are be designed to reduce impacts of stormwater volumes and pollutant loads, they may not be designed to mitigate thermal load from stormwater runoff in urban areas. This review of literature identifies key drivers of stream temperature in urban streams, including heat transference from stormflow and effects of pipe networks and evapotranspiration on baseflow. Recent simulation studies indicate the need for more than bioretention, increased infiltration, and tree canopy mitigation practices to reduce heat stress in urban streams. These studies show greatest reductions in thermal load by applying cool surfaces as a single thermal mitigation practice (TMP) and comprehensive applications of TMPs to all available areas at the watershed scale. This review of available literature suggests that incorporating TMPs into current and future GI designs will help maintain water resources, water quality, aquatic ecosystems, and coldwater stream species across the landscape. Further research is needed on the most effective ways to implement TMPs as part of our current and future GI designs for stormwater and how to best incorporate these measures into urban design concepts at larger spatial scales.
Rational Design of DNA Framework‐Based Hybrid Nanomaterials for Anticancer Drug Delivery
Authors: Wang Congshan , Yu Yingjie , Irfan Muhammad , Xu Bolong , Li Junjie , Zhang Linghao , Qin Zhaohui , Yu Changyuan , Liu Huiyu , Su Xin
Published: October 2020

Engineered DNA frameworks have been extensively exploited as affinity scaffolds for drug delivery. However, few studies focus on the rational design to comprehensively improve their stability, internalization kinetics, and drug loading efficiency. Herein, DNA framework‐based hybrid nanomaterials are rationally engineered by using a molecular docking tool, where the framework acts as a template to support conjugated polymers. The hybrid materials exhibit high stability in biofluids owning to the multiple interactions between DNA and cationic conjugated polymer. Through molecular docking, it is found that a specific structure of the conjugated polymer at major grooves of DNA gives rise to a unique pocket for small‐molecular drug doxorubicin (DOX) yielding lower binding energy than conventional DOX binding sites. This increases the binding affinity of DOX, allowing for high drug loading content and efficiency, and preventing drug leakage under physiological condition. As a proof of concept, the hybrid nanomaterials equipped with aptamer are used to carry DOX and antisense oligonucleotide G3139, which effectively inhibits solid tumor growth and shows negligible side effects on mice. It is anticipated that this approach would find broad applications in hybrid materials design and precise medicine.
Electrically Driven Rotation and Nonreciprocal Motion of Microparticles in Nematic Liquid Crystals
Authors: Solodkov Nikita V. , Saxena Antariksh , Jones J. Cliff
Published: October 2020

Dispersion of microparticles in nematic liquid crystals offers a novel means for controlling both their orientation and position through the combination of topology and external stimuli. Here, cuboidal and triangular prism shaped microparticles in parallel plate capacitor cells filled with a nematic liquid crystal are studied. Experimental observations are compared with numerical simulations to show that the optimal orientation of the particles is determined by their aspect rations, the relative separation gap of their containers and the applied voltage. It is observed that in systems that allow unrestricted particle rotation, the long axes of the particles are able to fully align themselves with the external electric field. However, when particle rotation is geometrically restricted, it is found that increasing the voltage past a critical value causes the short axis of the particle to realign with the electric field due to anchoring breaking. It is shown that symmetry of the particles then plays a key role in their dynamics following the removal of the electric field, allowing the triangular prisms to travel perpendicular to the applied electric field, whereas only rotation is possible for the cuboidal particles.