bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicide among veterans with amyotrophic lateral sclerosis
Authors: Lund Emily M. , Hostetter Trisha A. , Forster Jeri E. , Hoffmire Claire A. , Stearns‐Yoder Kelly A. , Brenner Lisa A. , Tahmasbi Sohi Maryam
Published: January 2021

Background

The purpose of this study was to estimate the risk of death by suicide for those with amyotrophic lateral sclerosis (ALS) seeking care within the Veterans Health Administration (VHA).

Methods

This was a retrospective, cohort study. Extended Cox regression models were used to compare the hazard of suicide between the ALS and the unexposed groups.

Results

The hazard of suicide was 3.98 times higher for those with ALS than for those without (95% confidence interval [CI] , 2.64‐6.00; P < .0001). After adjusting for covariates, those with ALS remained at increased risk (hazard ratio, 3.48; 95% CI, 2.31‐5.24; P < .001).

Conclusions

Among those seeking care in the VHA, individuals with ALS are at increased risk for dying by suicide. Additional suicide prevention efforts, including strategies for reducing access to lethal means, are warranted.
Differential effect of vascularity between long‐ and short‐term survivors with IDH1/2 wild‐type glioblastoma
Authors: Álvarez‐Torres María del Mar , Fuster‐García Elies , Reynés Gaspar , Juan‐Albarracín Javier , Chelebian Eduard , Oleaga Laura , Pineda Jose , Auger Cristina , Rovira Alex , Emblem Kyrre E. , Filice Silvano , Mollà‐Olmos Enrique , García‐Gómez Juan Miguel
Published: January 2021

Introduction

IDH1/2 wt glioblastoma (GB) represents the most lethal tumour of the central nervous system. Tumour vascularity is associated with overall survival (OS), and the clinical relevance of vascular markers, such as rCBV, has already been validated. Nevertheless, molecular and clinical factors may have different influences on the beneficial effect of a favourable vascular signature.

Purpose

To evaluate the association between the rCBV and OS of IDH1/2 wt GB patients for long‐term survivors (LTSs) and short‐term survivors (STSs). Given that initial high rCBV may affect the patient's OS in follow‐up stages, we will assess whether a moderate vascularity is beneficial for OS in both groups of patients.

Materials and methods

Ninety‐nine IDH1/2 wt GB patients were divided into LTSs (OS ≥ 400 days) and STSs (OS < 400 days). Mann‐Whitney and Fisher, uni‐ and multiparametric Cox, Aalen’s additive regression and Kaplan‐Meier tests were carried out. Tumour vascularity was represented by the mean rCBV of the high angiogenic tumour (HAT) habitat computed through the haemodynamic tissue signature methodology (available on the ONCOhabitats platform).

Results

For LTSs, we found a significant association between a moderate value of rCBVmean and higher OS (uni‐ and multiparametric Cox and Aalen’s regression) (p = 0.0140, HR = 1.19; p = 0.0085, HR = 1.22) and significant stratification capability (p = 0.0343). For the STS group, no association between rCBVmean and survival was observed. Moreover, no significant differences (p > 0.05) in gender, age, resection status, chemoradiation, or MGMT methylation were observed between LTSs and STSs.

Conclusion

We have found different prognostic and stratification effects of the vascular marker for the LTS and STS groups. We propose the use of rCBVmean at HAT as a vascular marker clinically relevant for LTSs with IDH1/2 wt GB and maybe as a potential target for randomized clinical trials focused on this group of patients.
Mathematical modeling of bio‐magnetic fluid bounded within ciliated walls of wavy channel
Authors: Nazeer Mubbashar , Hussain Farooq , Iftikhar Sadia , Ijaz Khan Muhammad , Ramesh K. , Shehzad Nasir , Baig Afifa , Kadry Seifedine , Chu Yu‐Ming
Published: January 2021

Peristaltic transport of couple stress fluid with heat transfer is investigated through flexible walls of the channel furnished with hair‐like structures. Locomotion of biological fluid is the result of the simultaneous propagation of metachronal waves (MCWs) and peristaltic waves. MCW emerges due to multi‐movement of cilia, while the elastic‐walls of the channel are responsible for the peristaltic wave. The two‐dimensional rheological flow experiences the resistive behavior of applied magnetic fields, besides, the role of viscous dissipation and entropy generation. A closed‐form solution is achieved for the nonlinear coupled differential equation, which is vetted through graphs. Finally, the theoretical analysis introduces the manufacture of a ciliate bronchial tube that can efficiently; remove mucus out of the lungs and bloodstream.
Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer
Authors: Strickler John H. , Rushing Christel N. , Uronis Hope E. , Morse Michael A. , Niedzwiecki Donna , Blobe Gerard C. , Moyer Ashley N. , Bolch Emily , Webb Renee , Haley Sherri , Hatch Ace J. , Altomare Ivy P. , Sherrill Gary B. , Chang David Z. , Wells James L. , Hsu S. David , Jia Jingquan , Zafar S. Yousuf , Nixon Andrew B. , Hurwitz Herbert I.
Published: January 2021

Lessons Learned

Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted.

Background

The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance.

Methods

In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab.

Results

Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3–7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5–14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib.

Conclusion

The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
Behavior of Pd‐supported catalysts in phenylacetylene hydrogenation: Effect of combined use of polyvinylpyrrolidone and NaOH for magnetic support modification
Authors: Zharmagambetova Alima , Talgatov Eldar , Auyezkhanova Assemgul , Tumabayev Nurmukhamet , Bukharbayeva Farida
Published: January 2021

Recently, magnetic nanoparticles have attracted the attention as catalyst supports due to the possibility of magnetic separation, allowing for easy, fast, and clean recovery of the catalysts. A synthesis strategy of such supports plays an important role in improving the properties of the magnetic catalysts. Here, we proposed a simple and effective method to increase the activity and lifetime of the Pd magnetic catalyst. Polyvinylpyrrolidone‐maghemite nanoparticles were synthesized via one‐pot coprecipitation method using an excess of the NaOH. This was followed by adsorption of Pd2+ on the magnetic nanoparticles. The resulting catalyst showed activity (WCC = 4.0 × 10−6 mol s−1, WCC = 12.7 × 10−6 mol s−1) and selectivity (94%) in phenylacetylene hydrogenation. The catalyst was then magnetically recovered and reused 58 times. The activity of the catalyst increased significantly during the first three runs, changing the rate ratio of WCC to WCC from 1:3.2 to 1:1.6, and then decreased in the following runs. To understand the reason for this behavior, the catalyst was characterized, as well as catalytic studies were performed using similar catalysts for comparison. The results show that the NaOH adsorbed on magnetic support affects the size, stability, and catalytic properties of the Pd particles, and the effect of alkali is enhanced in the presence of the polymer.
Characterization of human plasma lipoproteins using anion exchange fast protein liquid chromatography and targeted mass spectrometry assay
Authors: Seidl Claudia , Flaten Zachary , Li Danni
Published: January 2021

We described a targeted mass spectrometry assay based on selected reaction monitoring (SRM) for five apolipoproteins (apoA1, apoB, apoJ, apoD, and apoE) in plasma lipoproteins isolated by anion exchange fast protein liquid chromatography using only 100 μL of plasma. We performed analytical characterization of the SRM assay and evaluated reproducibility of the entire workflow. The limit of detections for apoA1, apoB, apoD, apoJ, and apoE were 0.6, 4.6, 0.8, 1.2, and 0.7 nM, respectively; the limit of quantifications was 8.3 nM for all peptides except apoD (4.2 nM). The SRM assay was linear from 0.4 to 1667 nM. The intra‐day and inter‐day and total repeatability (CV%) of the assay ranged from 2.2% to 21.7% for all five peptides. The intra‐day and inter‐day and total reproducibility of the entire workflow ranged from 12.2% to 43.9% for all five peptides in fractionated high‐density lipoprotein, low‐density lipoprotein, and IDL. In the future, we will apply this workflow to investigate the association of fractionated plasma lipoproteins with amyloid deposition and cognitive changes in the context of Alzheimer's disease.
Computational investigation of KICl2 iodination of thiophene and its electron‐poor derivatives
Authors: Sarkar Akash Mamon , Sereda Grigoriy A. , Miró Pere
Published: January 2021

Electrophilic iodination of thiophene and its electron‐poor derivatives has been studied with KICl2 in dichloromethane and methanol using density function theory. KICl2 easily dissociates forming KCl and ICl, the latter being the iodinating agent. ICl forms an adduct with thiophene (π‐complex) followed by a nucleophilic attack of the ICl component by the aromatic component that forms the C–I bond. The nucleophilic attack is always the rate determining step with higher barriers that are in agreement the experimental conditions required for this reaction. The abstraction of a proton by the chloride anion on the last step is barrierless leading to the mono‐ and di‐iodination of the thiophene derivatives. Side products derived from the nucleophilic addition of the chloride anion have been determined to be transient.
Chemokine Receptor 2 Targeted Gold Nanocluster Imaging Triple Negative Breast Cancer with Positron Emission Tomography
Authors: Zhao Yongfeng , You Meng , Detering Lisa , Sultan Deborah , Luehmann Hannah , Liu Yongjian
Published: January 2021

Due to the lack of effective biomarker and specific diagnosis, triple negative breast cancer (TNBC) patients frequently suffer early‐onset relapse and metastasis after conventional therapy, leading to overall poor survival. It is crucial to develop targeted approaches for accurate TNBC detection and drug delivery to improve patient survival. Herein, the potential of chemokine (C‐C motif) receptor 2 (CCR2) as a biomarker for TNBC is characterized. Through a 64Cu radiolabeled CCR2 targeting peptide radiotracer, the presence of CCR2 in TNBC is specifically imaged using positron emission tomography in a mouse 4T1 TNBC model, which is further confirmed by western blot, immunostaining, and reverse transcription polymerase chain reaction analysis. Through a well‐defined and straightforward radioactive synthesis, an ultrasmall gold nanocluster intrinsically radiolabeled with 64Cu is prepared for CCR2 targeted imaging in 4T1 tumor‐bearing mice. Time‐course study and quantitative uptake analysis reveal significantly improved tumor targeting efficiency and tumor‐to‐background contrast ratio compared to peptide tracer alone. Taken together, it is believed CCR2 is a useful biomarker for TNBC, and the targeted nanocluster can serve as a useful platform for sensitive and accurate diagnosis of TNBC.
Pharmacodynamic analysis of hypertension caused by lenvatinib using real‐world postmarketing surveillance data
Authors: Otani Yuki , Kasai Hidefumi , Tanigawara Yusuke
Published: January 2021

Lenvatinib is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor used against nonoperative thyroid cancer; however, hypertension is a major dose‐limiting side effect. In this study, hypertension caused by lenvatinib was described through a novel population pharmacodynamic model using postmarketing surveillance data obtained in Japan. The model consists of two maximum effect model components based on the (1) concentration of lenvatinib in plasma and (2) cumulative area under the curve of lenvatinib. In addition, antihypertensive drug of either an angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker or calcium channel blocker accounted for by lowering effect on diastolic blood pressure. Based on virtual simulations, the combination of antihypertensive drug and dose adjustment of lenvatinib showed a reduction in the probability of grade greater than or equal to 3 hypertension. The present model provides useful guidance in managing hypertension during treatment with lenvatinib in the real‐world setting.
Thermal Dissipation Annealing for Crystallization of In‐Doped ZnO Films Deposited on Polyethylene Naphthalate Substrate without Substrate Deformation
Authors: Kim Dongwan , Jo Euije , Leem Jae-Young
Published: January 2021

High‐temperature annealing is essential to crystallize sol–gel spin‐coated ZnO films but is a critical disadvantage in manufacturing flexible and transparent electronics, owing to low thermal stability of polymer substrates. Thus, a novel annealing method, named thermal dissipation annealing (TDA), is developed. TDA method can anneal ZnO films without any deformation of polymer substrates. The effects of TDA method are confirmed by annealing ZnO films deposited on glass and polyethylene naphthalate substrates. Moreover, In‐doped ZnO (IZO) films are annealed by TDA method, and the properties of IZO films are investigated. ZnO films annealed by TDA method show graphene‐like nanosheets and exhibit much higher photosensitivity than ZnO films annealed by furnace or infrared (IR) lamp. For IZO films annealed by TDA method, entangled nanosheets begin to unravel with increasing doping concentration, and size of nanosheets significantly decreases at 0.04 at%. The photosensitivity of the IZO films decreases from 21.77 to 2.76 with increasing doping concentration. Therefore, flexible and transparent UV photodetectors based on sol–gel spin‐coated ZnO films can be fabricated through TDA method; however, when ZnO films annealed by TDA method are utilized to UV photodetectors, In dopant is not a suitable material to improve the performance of UV photodetectors.
Regression‐adjusted Poisson EWMA control chart
Authors: Wen Hongling , Liu Liu , Yan Xinlong
Published: January 2021

Exponentially weighted moving average (EWMA) control chart has a significant effect in improving product quality and is widely used in various fields. In addition to continuous data, there are many Count Data in life that need to be monitored. Poisson distribution is one of the models that study the probability distribution of discrete data, and has a wide range of applications. In previous monitoring, it was considered that the mean value of Poisson distribution in normal state was a constant value after it was determined. But in the actual situation, there are many unavoidable objective conditions that will affect the final results. We cannot monitor all situations according to the same criteria. If we ignore the conditions that affect the occurrence of the event and directly monitor the final result, on the one hand, it will increase the probability of false alarms from the control chart. On the other hand, the control chart will not be able to detect problems in time due to the untimely update of conditions. In response to this situation, this paper proposes a regression‐adjusted EWMA control chart to monitor the Poisson process. The control chart can continuously adjust and update the expected values according to the actual situation. It can make the monitoring process more reasonable and the monitoring results more valuable.
A side‐sensitive synthetic coefficient of variation chart
Authors: Yeong Wai Chung , Lee Ping Yin , Lim Sok Li , Khaw Khai Wah , Khoo Michael Boon Chong
Published: January 2021

Control charts for monitoring the coefficient of variation (γ) are useful for processes with an inconsistent mean (μ) and a standard deviation (σ) which changes with μ, by monitoring the consistency in the ratio σ over μ. The synthetic‐γ chart is one of the charts proposed to monitor γ, and its attractiveness lie in waiting until a second point to fall outside the control limits before a decision is made. However, existing synthetic‐γ charts do not differentiate between the points falling outside the upper control limit (UCL) and lower control limit (LCL). Hence, this paper proposes a side‐sensitive synthetic‐γ chart, where successive nonconforming samples must either fall above the UCL or below the LCL. Formulae to compute the average run length (ARL), the standard deviation of the run length (SDRL) and expected average run length (EARL) are derived using the Markov chain approach, and the algorithms to obtain the optimal charting parameters are proposed. Subsequently, the optimal charting parameters, ARL, SDRL and EARL values for various numerical examples are shown. Comparisons show that the side‐sensitive synthetic‐γ chart consistently outperforms the existing synthetic‐γ chart, especially for small shifts. The proposed chart also consistently outperforms the Shewhart‐γ chart, while showing comparable or better performance than the Exponentially Weighted Moving Average (EWMA) chart for most shift sizes, except for very small shifts. Finally, this paper shows the implementation of the proposed chart on an industrial example.
Enantio‐separation of pregabalin by ternary complexation using trapped ion mobility spectrometry
Authors: Gu Liancheng , Yang Shutong , Wu Fangling , Xu Fuxing , Yu Shaoning , Zhou Mingfei , Chu Yanqiu , Ding Chuan‐Fan
Published: January 2021

Rationale

The rapid identification of small‐molecule chiral drugs is challenging due to subtle structural differences. Different enantiomers of chiral drugs may produce inverse biological effects through their different pharmacokinetics. Therefore, it is highly desirable to distinguish the chirality of drug molecules.

Methods

The chirality of pregabalin was distinguished by studying the ion mobility spectra of the ternary non‐covalent complexes formed with cyclodextrins (CDs), pregabalin, and alkali‐earth cations using trapped ion mobility spectrometry (TIMS). The ternary non‐covalent complex ions were determined by electrospray ionization of mixed solutions. The analyzed sample was simply mixed, without derivatization or sample pretreatment. The relative contents of pregabalin enantiomers were derived using a calibration curve method.

Results

The ion mobility spectra of several ternary non‐covalent complexes formed with α‐, β‐, and γ‐CD, pregabalin, and alkali‐earth cations were obtained. We compared their ability to distinguish the chirality of pregabalin. The best peak‐to‐peak resolution (Rp‐p) was estimated to be 2.20 for [2β‐CD + pregabalin + Sr]2+, which can be ascribed as baseline separation. The derived relative contents for S‐pregabalin were in agreement with the actual contents.

Conclusions

A novel and convenient method for discriminating the chirality of the pregabalin molecule by TIMS was developed and optimized. The chirality of pregabalin was recognized by studying the ion mobility spectra of the ternary non‐covalent complexes, such as [2β‐CD + pregabalin + Sr]2+. This TIMS method could also be used to quantify the relative contents of pregabalin enantiomers.
Research on spatial motion safety constraints and cooperative control of robot‐assisted craniotomy: Beagle model experiment verification
Authors: Xu Cheng , Lin Li , Mar Aung Zin , Chai Gang , Xie Le
Published: January 2021

Background

Traditional craniotomy depends primarily on the experience of the surgeon. However, the accuracy of manual operation is limited and carries certain surgical risks. The interaction method of current robot‐assisted craniotomy is unnatural and inadaptive to the operating style of the surgeon. In this research, we built a hands‐on synergistic robotics craniotomy system with human–machine collaboration. Safe isometric surfaces and virtual restraint methods are combined to achieve highly accurate, efficient, minimally invasive and safe craniotomy.

Materials and methods

Fifteen three‐dimensional (3D)‐printed beagle skull models were used to evaluate the system accuracy and the related image guidance process. It mainly includes the design of the surgical plan, the adopted strategy based on motion constraint and safe isometric surface, and the impedance control method based on the position inner loop via the human–machine collaboration method. The trajectory tracking experiment was performed by applying human–machine collaboration, and completed an experiment on the 3D‐printed beagle skull models involving drilling and milling of the skull performed by the robot, and evaluation of accuracy via computed tomographic (CT) scanning verification after the operation.

Results

The 3D‐printed beagle skull model experiment shows that the average errors for the top surface and the bottom surface, and the angle error were 0.81 ± 0.15 mm, 0.89 ± 0.12 mm, and 1.74° ± 0.16°, respectively. The average milling position errors for the top and bottom surfaces were 0.87 ± 0.19 and 0.93 ± 0.22 mm, respectively.

Conclusion

The performance of the robot system was evaluated and verified using a 3D‐printed beagle model experiment. The proposed collaborative surgical robot system is feasible and can complete a craniotomy, with improved accuracy and surgical safety.
Leaders pay it forward by becoming mentors
Authors: Hodges Dawn Z.
Published: January 2021

Paying it forward is not a new concept. It's probably as old as time. But in the past few years, the phrase has gained popularity. The meaning is simple. Paying it forward is to return a kindness to someone else rather than the original benefactor, and thus expand its reach.
Gimme a Break offers intentional programming for student well‐being in the absence of spring break
Authors: Hilton Warren , Storch Christine Nardone
Published: January 2021

The COVID‐19 pandemic continues to present challenges and opportunities for student affairs professionals. A particular challenge for the spring 2021 semester centers around how to help our students with their well‐being in the absence of spring break.
Boost student connections, support during pandemic
Authors: McCarthy Claudine
Published: January 2021

Like many student affairs professionals, Pauline M. Dobrowski, Ed.D., has found it particularly challenging to help students — especially first‐year students — to engage and connect in meaningful ways with college life in the midst of the pandemic. “This has been challenging due to our inability to gather and interact with one another as we have in the past, which has inhibited the cultivation of those relationships that are so key to developing a sense of belonging within a community,” said Dobrowski, Vice President for Student Affairs at Stonehill College in Massachusetts. “As a result, some students have shared with us some of their struggles with feelings of isolation, increased anxiety, and inability to make new friends,” she added.
Multiple imputation strategies for a bounded outcome variable in a competing risks analysis
Authors: Curnow Elinor , Hughes Rachael A. , Birnie Kate , Crowther Michael J. , May Margaret T. , Tilling Kate
Published: January 2021

In patient follow‐up studies, events of interest may take place between periodic clinical assessments and so the exact time of onset is not observed. Such events are known as “bounded” or “interval‐censored.” Methods for handling such events can be categorized as either (i) applying multiple imputation (MI) strategies or (ii) taking a full likelihood‐based (LB) approach. We focused on MI strategies, rather than LB methods, because of their flexibility. We evaluated MI strategies for bounded event times in a competing risks analysis, examining the extent to which interval boundaries, features of the data distribution and substantive analysis model are accounted for in the imputation model. Candidate imputation models were predictive mean matching (PMM); log‐normal regression with postimputation back‐transformation; normal regression with and without restrictions on the imputed values and Delord and Genin's method based on sampling from the cumulative incidence function. We used a simulation study to compare MI methods and one LB method when data were missing at random and missing not at random, also varying the proportion of missing data, and then applied the methods to a hematopoietic stem cell transplantation dataset. We found that cumulative incidence and median event time estimation were sensitive to model misspecification. In a competing risks analysis, we found that it is more important to account for features of the data distribution than to restrict imputed values based on interval boundaries or to ensure compatibility with the substantive analysis by sampling from the cumulative incidence function. We recommend MI by type 1 PMM.
Engineering the Near‐Surface of PtRu3 Nanoparticles to Improve Hydrogen Oxidation Activity in Alkaline Electrolyte
Authors: Zhang Junming , Qu Ximing , Shen Linfan , Li Guang , Zhang Tianen , Zheng Jinhong , Ji Lifei , Yan Wei , Han Yu , Cheng Xiaoyang , Jiang Yanxia , Sun Shigang
Published: January 2021

Tailoring the near‐surface composition of Pt‐based alloy can optimize the surface chemical properties of a nanocatalyst and further improve the sluggish H2 electrooxidation performance in an alkaline electrolyte. However, the construction of alloy nanomaterials with a precise near‐surface composition and smaller particle size still needs to overcome huge obstacles. Herein, ultra‐small PtRu3 binary nanoparticles (<2 nm) evenly distributed on porous carbon (PtRu3/PC), with different near‐surface atomic compositions (Pt‐increased and Ru‐increased), are successfully synthesized. XPS characterizations and electrochemical test confirm the transformation of a near‐surface atomic composition after annealing PtRu3/PC‐300 alloy; when annealing in CO atmosphere, forming the Pt‐increased near‐surface structure (500 °C), while the Ru‐increased near‐surface structure appears in an Ar heat treatment process (700 °C). Furthermore, three PtRu3/PC nanocatalysts all weaken the hydrogen binding strength relative to the Pt/PC. Remarkably, the Ru‐increased nanocatalyst exhibits up to 38.8‐fold and 9.2‐fold HOR improvement in mass activity and exchange current density, compared with the Pt/PC counterpart, respectively. CO‐stripping voltammetry tests demonstrate the anti‐CO poisoning ability of nanocatalysts, in the sequence of Ru‐increased ≥ PtRu3/PC‐300 > Pt‐increased > Pt/PC. From the perspective of engineering a near‐surface structure, this study may open up a new route for the development of high‐efficiency electrocatalysts with a strong electronic effect and oxophilic effect.
Electrospun TiO2‐Based Photocatalysts
Authors: Xu Feiyan , Tan Haiyan , Fan Jiajie , Cheng Bei , Yu Jiaguo , Xu Jingsan
Published: January 2021

Solar‐driven semiconductor photocatalysis shows great potential to solve growing energy and environmental crises. Electrospun TiO2nanofibers (NFs) attract attention due to their chemical stability, nontoxicity, cheapness, large specific surface area, and porous structures. The unique unwoven nanofibrous network facilitates mass transportation compared with bulk materials. Electrospun TiO2NFs are an ideal substrate for growing secondary nanostructures and constructing heterojunction photocatalysts. The hybrid heterojunctions show enhanced electron–hole separation, improved light absorption, effective activation of reactants, and therefore increased photocatalytic performance. Herein, the electrospinning principle and preparing tactics of electrospun TiO2fibrous nanostructures including solid, hollow, and core/shell NFs are first described. The construction strategies of electrospun TiO2‐based heterojunctions by loading electron or hole cocatalysts and hybridizing secondary semiconductors to engineer catalytic active sites and steer charge carrier separation are outlined. Dopant‐induced increased light absorption and enhanced charge transfer of TiO2NFs are discussed. Further, the applications of electrospun TiO2‐based photocatalysts for solar‐to‐chemical conversion and environmental remediation are elucidated. Finally, the challenges and perspectives for the development of electrospun TiO2‐based photocatalysts are underlined, which deepen a systematic understanding of the design and fabrication of more efficient electrospun NFs in the future.
Size‐Dependent Light Harvesting from Nonthermalized Excited States of Gold Clusters
Authors: Pyo Kyunglim , Han Sang Myeong , Xu Hongmei , Saha Sukanya , Ramakrishna Guda , Lee Dongil
Published: January 2021

Light harvesting is central to many photonic materials. The light harvesting efficiency in these materials is, however, generally reduced because upper excited‐state energy is lost by energy‐dissipating internal conversion (IC) and vibrational relaxation processes. Herein, size‐dependent energy harvesting from nonthermalized, upper excited states of glutathione‐protected gold clusters of various sizes, including Au18, Au22, Au25, Au67, Au102, and Au≈940, is reported. Femtosecond transient absorption measurements reveal that the IC processes of Au18, Au22, and Au25 are relatively slow wherein the upper excited‐state energy of gold clusters efficiently is harvested by an energy acceptor, aminofluorescein (AF), covalently attached to the gold cluster on the time scales of 150 fs (Au18), 220 fs (Au22), and 380 fs (Au25). Steady‐state photoluminescence measurements of AF‐conjugated Au18, Au22, and Au25 clusters show notable AF emission upon high‐energy excitation of gold clusters. Herein, a new avenue for energy harvesting from nonthermalized upper excited states of gold clusters, which would otherwise be lost as heat, is opened up.
Dealing with complexity by using multilevel system boundary models
Authors: Pinzon‐Salcedo Luis Arturo , Bernal‐Alvarado Juanita
Published: January 2021

Increasingly, researchers and practitioners operate in complex systems difficult to comprehend. In them, the multiplicity of perspectives, elements and relationships operating on multiple levels makes the practice of systems thinking and boundary critique considerably difficult. Drawing upon boundary critique and hierarchy theory, this paper presents ways of thinking in terms of multilevel boundary judgements models useful for addressing the aforementioned problem in all fields of study. A real example of the use of these models is presented. This paper also discusses how thinking in terms of multiple levels of boundary judgements is important to better deal with values and moral frameworks and to promote critical reflexivity in systemic interventions, while escaping the dangers of reductionism. Furthermore, a systemic way of exploring the role of moral frameworks in systems practice is discussed, contributing with new concepts useful to develop a deeper understanding of ethical issues in systems practice.
Haploinsufficiency of cohesin protease, Separase, promotes regeneration of hematopoietic stem cells in mice
Authors: Kumar Praveen , Cheng Haizi , Paudyal Samridhdi , Nakamura Lanelle V. , Zhang Nenggang , Li Jessica T. , Sasidharan Rajkumar , Jeong Mira , Pati Debananda
Published: January 2021

Cohesin recently emerged as a new regulator of hematopoiesis and leukemia. In addition to cohesin, whether proteins that regulate cohesin’s function have any direct role in hematopoiesis and hematologic diseases has not been fully examined. Separase, encoded by the ESPL1 gene, is an important regulator of cohesin’s function. Canonically, protease activity of Separase resolves sister chromatid cohesion by cleaving cohesin subunit-Rad21 at the onset of anaphase. Using a Separase haploinsufficient mouse model, we have uncovered a novel role of Separase in hematopoiesis. We report that partial disruption of Separase distinctly alters the functional characteristics of hematopoietic stem/progenitor cells (HSPCs). Although analyses of peripheral blood and bone marrow of Espl1+/Hyp mice broadly displayed unperturbed hematopoietic parameters during normal hematopoiesis, further probing of the composition of early hematopoietic cells in Espl1+/Hyp bone marrow revealed a mild reduction in the frequencies of the Lin−Sca1+Kit− (LSK) or LSK CD48+CD150− multipotent hematopoietic progenitors population without a significant change in either long-term or short-term hematopoietic stem cells (HSCs) subsets at steady state. Surprisingly, however, we found that Separase haploinsufficiency promotes regeneration activity of HSCs in serial in vivo repopulation assays. In vitro colony formation assays also revealed an enhanced serial replating capacity of hematopoietic progenitors isolated from Espl1+/Hyp mice. Microarray analysis of differentially expressed genes showed that Separase haploinsufficiency in HSCs (SP-KSL) leads to enrichment of gene signatures that are upregulated in HSCs compared to committed progenitors and mature cells. Taken together, our findings demonstrate a key role of Separase in promoting hematopoietic regeneration of HSCs.
Signaling pathways essential for triple-negative breast cancer stem-like cells
Authors: Ehmsen Sidse , Ditzel Henrik J.
Published: January 2021

Since the discovery of breast cancer stem cells (CSCs), a significant effort has been made to identify and characterize these cells. It is a generally believe that CSCs play an important role in cancer initiation, therapy resistance, and progression of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor prognosis. Thus, therapies targeting these cells would be a valuable addition to standard treatments that primarily target more differentiated, rapidly dividing TNBC cells. Although several cell surface and intracellular proteins have been described as biomarkers for CSCs, none of these are specific to this population of cells. Recent research is moving toward cellular signaling pathways as targets and biomarkers for CSCs. The WNT pathway, the nuclear factor-kappa B (NF-κB) pathway, and the cholesterol biosynthesis pathway have recently been identified to play a key role in proliferation, survival, and differentiation of CSCs, including those of breast cancer. In this review, we assess recent findings related to these three pathways in breast CSC, with particular focus on TNBC CSCs, and discuss how targeting these pathways, in combination with current standard of care, might prove effective and improve the prognosis of TNBC patients.
Old Is the New New: The Rhetoric of Anchoring Innovation
Authors: Sluiter Ineke
Published: January 2021

In life, language, and argument, we need to feel at home. “Anchoring” connects whatever seems “new” to what is considered familiar. This paper studies the argumentative use of “anchoring” in the wider context of its role in language use. “Anchoring” provides a unifying perspective in analyzing linguistic and rhetorical elements identified by different schools of thought (Sect. 2). Several features of language, elsewhere studied in the context of “discourse linguistics”, direct the addressee on how to anchor new information to the common ground. Categorizing, labeling and naming (topics from philosophy and psychology) can be considered anchoring functions. And formal linguistic iconicity anchors linguistic representations in evolutionarily older senso-motor systems. Section 3 discusses the anchoring effects of some specific discourse types: genealogy, mythology, aetiology, and etymology. All of these frequently take the form of narrative and are used in affective, “engaged” argumentation. Finally, the rhetorical and argumentative implications of the terminology of “new” and “old” itself are discussed, and one specific “anchoring trope” is analyzed, which sets up an anchor as a reference point for something new: the phrase “X is the new Y” (Sect. 4).
Introduction
Authors: Linder Wolf , Mueller Sean
Published: January 2021

The introductory chapter presents the main puzzle of Swiss democracy as combining an extraordinary degree of political stability with openness and broad forms of participation. It also explains the structure of the book and summarises the main contribution of each chapter.
Strong CP violation in spin-1/2 singly charmed baryons
Authors: Ünal Y. , Meißner Ulf-G.
Published: January 2021

Abstract

We report on the calculation of the CP-violating form factor F3 and the corresponding electric dipole moment for charmed baryons in the spin-1/2 sector generated by the QCD θ-term. We work in the framework of covariant baryon chiral perturbation theory within the extended-on-mass-shell renormalization scheme up to next-to-leading order in the chiral expansion.
A novel deletion in FLOWERING LOCUS T modulates flowering time in winter oilseed rape
Authors: Vollrath Paul , Chawla Harmeet S. , Schiessl Sarah V. , Gabur Iulian , Lee HueyTyng , Snowdon Rod J. , Obermeier Christian
Published: January 2021

Key message

A novel structural variant was discovered in the FLOWERING LOCUS T orthologue BnaFT.A02 by long-read sequencing. Nested association mapping in an elite winter oilseed rape population revealed that this 288 bp deletion associates with early flowering, putatively by modification of binding-sites for important flowering regulation genes.

Perfect timing of flowering is crucial for optimal pollination and high seed yield. Extensive previous studies of flowering behavior in Brassica napus (canola, rapeseed) identified mutations in key flowering regulators which differentiate winter, semi-winter and spring ecotypes. However, because these are generally fixed in locally adapted genotypes, they have only limited relevance for fine adjustment of flowering time in elite cultivar gene pools. In crosses between ecotypes, the ecotype-specific major-effect mutations mask minor-effect loci of interest for breeding. Here, we investigated flowering time in a multiparental mapping population derived from seven elite winter oilseed rape cultivars which are fixed for major-effect mutations separating winter-type rapeseed from other ecotypes. Association mapping revealed eight genomic regions on chromosomes A02, C02 and C03 associating with fine modulation of flowering time. Long-read genomic resequencing of the seven parental lines identified seven structural variants coinciding with candidate genes for flowering time within chromosome regions associated with flowering time. Segregation patterns for these variants in the elite multiparental population and a diversity set of winter types using locus-specific assays revealed significant associations with flowering time for three deletions on chromosome A02. One of these was a previously undescribed 288 bp deletion within the second intron of FLOWERING LOCUS T on chromosome A02, emphasizing the advantage of long-read sequencing for detection of structural variants in this size range. Detailed analysis revealed the impact of this specific deletion on flowering-time modulation under extreme environments and varying day lengths in elite, winter-type oilseed rape.
Autonomous Reboot: Kant, the categorical imperative, and contemporary challenges for machine ethicists
Authors: White Jeffrey
Published: January 2021

Ryan Tonkens (2009) has issued a seemingly impossible challenge, to articulate a comprehensive ethical framework within which artificial moral agents (AMAs) satisfy a Kantian inspired recipe—"rational" and "free"—while also satisfying perceived prerogatives of machine ethicists to facilitate the creation of AMAs that are perfectly and not merely reliably ethical. This series of papers meets this challenge by landscaping traditional moral theory in resolution of a comprehensive account of moral agency. The first paper established the challenge and set out autonomy in Aristotelian terms. The present paper interprets Kantian moral theory on the basis of the preceding introduction, argues contra Tonkens that an engineer does not violate the categorical imperative in creating Kantian AMAs, and proposes that a Kantian AMA is not only a possible goal for Machine ethics research, but a necessary one.
Accuracy of Electrode Placement in IRE Treatment with Navigated Guidance
Authors: Stillström David , Sandu Raluca-Maria , Freedman Jacob
Published: January 2021

Purpose

Evaluate the accuracy of multiple electrode placements in IRE treatment of liver tumours using a stereotactic CT-based navigation system.

Method

Analysing data from all IRE treatments of liver tumours at one institution until 31 December 2018. Comparing planned with validated electrode placement. Analysing lateral and angular errors and parallelism between electrode pairs

Results

Eighty-four tumours were treated in 60 patients. Forty-six per cent were hepatocellular carcinoma, and 36% were colorectal liver metastases. The tumours were located in all segments of the liver. Data were complete from 51 treatments. Two hundred and six electrodes and 336 electrode pairs were analysed. The median lateral and angular error, comparing planned and validated electrode placement, was 3.6 mm (range 0.2–13.6 mm) and 3.1° (range 0°–16.1°). All electrodes with a lateral error >10 mm were either re-positioned or excluded before treatment. The median angle between the electrode pairs was 3.8° (range 0.3°–17.2°). There were no electrode placement-related complications.

Conclusion

The use of a stereotactic CT-based system for navigation of electrode placement in IRE treatment of liver tumours is safe, accurate and user friendly.
Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis
Authors: Little M. W. , Gibson M. , Briggs J. , Speirs A. , Yoong P. , Ariyanayagam T. , Davies N. , Tayton E. , Tavares S. , MacGill S. , McLaren C. , Harrison R.
Published: January 2021

Purpose

Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres.

Methods

Thirty-eight patients, median age = 60 (45–83), attended for GAE using 100–300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0–100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively.

Results

Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53–66) at baseline to 36 (SD = 24, 95% CI 28–44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30–60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis.

Conclusion

GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.
Dreimuskelchirurgie bei großwinkliger Esotropie
Authors: Gräf Michael , Röhm Julia , Wassill Heiko
Published: January 2021

Hintergrund

Zur Korrektur großwinkliger Esotropie sind die kombinierte Konvergenzoperation und die beidseitige Medialisrücklagerung ohne und mit Myopexie verbreitet. Nur wenige Berichte liegen zu Dreimuskeleingriffen (3 ME) vor. Wir analysierten die Ergebnisse von 3 ME.

Patienten und Methoden

Von Juni 2016 bis Mai 2020 erhielten 61 Patienten einen 3 ME wegen Esotropie ≥ 27°. Schrägschielen wurde mitbehandelt. Die Schielwinkel wurden in 5 m und 0,3 m im simultanen (SPCT) und alternierenden Prismenabdecktest (APCT) gemessen. Die Dosierung betrug 0,51 mm/° (APCT, 5 m). Die Ergebnisse von 57 Patienten waren auswertbar.

Ergebnisse

Die Mediane und Streubreiten (min-max) betrugen: Alter: 6 Jahre (3–56). APCT präoperativ: fern 34° (27–45), nah 36° (27–50). Operationsdosis: 17 mm (15–21), 21 Fälle mit Obliquuschirurgie. APCT 5 Monate (3–24) postoperativ: fern 2° (−10–18), nah 2° (−8–18). Einen Restwinkel im Betrag ≤ 6° (≈ 10 PD) wiesen (APCT) fern 39 (68 %), nah 38 (67 %) und (SPCT) fern 45 (79 %), nah 42 Patienten (74 %) auf. Eine konsekutive Exotropie > 6° im APCT hatten fern 4 (7 %), nah 3 (5 %), eine Esotropie > 6° hatten 14 (25 %) bzw. 16 Patienten (28 %).

Schlussfolgerung

Die 3 ME ist als Ersteingriff bei großwinkliger Esotropie gut geeignet.
Volume electron microscopy: analyzing the lung
Authors: Schneider Jan Philipp , Hegermann Jan , Wrede Christoph
Published: January 2021

Since its entry into biomedical research in the first half of the twentieth century, electron microscopy has been a valuable tool for lung researchers to explore the lung’s delicate ultrastructure. Among others, it proved the existence of a continuous alveolar epithelium and demonstrated the surfactant lining layer. With the establishment of serial sectioning transmission electron microscopy, as the first “volume electron microscopic” technique, electron microscopy entered the third dimension and investigations of the lung’s three-dimensional ultrastructure became possible. Over the years, further techniques, ranging from electron tomography over serial block-face and focused ion beam scanning electron microscopy to array tomography became available. All techniques cover different volumes and resolutions, and, thus, different scientific questions. This review gives an overview of these techniques and their application in lung research, focusing on their fields of application and practical implementation. Furthermore, an introduction is given how the output raw data are processed and the final three-dimensional models can be generated.
Studying molecular interactions in the intact organism: fluorescence correlation spectroscopy in the living zebrafish embryo
Authors: Dawes Michael L. , Soeller Christian , Scholpp Steffen
Published: January 2021

Cell behaviour and function is determined through the interactions of a multitude of molecules working in concert. To observe these molecular dynamics, biophysical studies have been developed that track single interactions. Fluorescence correlation spectroscopy (FCS) is an optical biophysical technique that non-invasively resolves single molecules through recording the signal intensity at the femtolitre scale. However, recording the behaviour of these biomolecules using in vitro-based assays often fails to recapitulate the full range of variables in vivo that directly confer dynamics. Therefore, there has been an increasing interest in observing the state of these biomolecules within living organisms such as the zebrafish Danio rerio. In this review, we explore the advancements of FCS within the zebrafish and compare and contrast these findings to those found in vitro.