bluuebunny/crossref_metadata_2025_split huggingface dataset:
A de novo peroxidase is also a promiscuous yet stereoselective carbene transferase
Authors: Stenner Richard , Steventon Jack W. , Seddon Annela , Anderson J. L. Ross 
Published: January 2020

Significance
While the bottom-up design of enzymes appears to be an intractably complex problem, a minimal approach that combines elementary, de novo-designed proteins with intrinsically reactive cofactors offers a simple means to rapidly access sophisticated catalytic mechanisms. Not only is this method proven in the reproduction of powerful oxidative chemistry of the natural peroxidase enzymes, but we show here that it extends to the efficient, abiological—and often asymmetric—formation of strained cyclopropane rings, nitrogen–carbon and carbon–carbon bonds, and the ring expansion of a simple cyclic molecule to form a precursor for NAD+, a fundamentally important biological cofactor. That the enzyme also functions in vivo paves the way for its incorporation into engineered biosynthetic pathways within living organisms.
Reconstruction of plasma density profiles by measuring spectra of radiation emitted from oscillating plasma dipoles
Authors: Kylychbekov S , Song H S , Kwon K B , Ra O , Yoon E S , Chung M , Yu K , Yoffe S R , Ersfeld B , Jaroszynski D A , Hur M S 
Published: January 2020

Abstract
We suggest a new method for characterising non-uniform density distributions of plasma by measuring the spectra of radiation emitted from a localised plasma dipole oscillator excited by colliding electromagnetic pulses. The density distribution can be determined by scanning the collision point in space. Two-dimensional particle-in-cell simulations demonstrate the reconstruction of linear and nonlinear density profiles corresponding to laser-produced plasma. The method can be applied to a wide range of plasma, including fusion and low temperature plasmas. It overcomes many of the disadvantages of existing methods that only yield average densities along the path of probe pulses, such as interferometry and spectroscopy.
Bidirectional tactile display driven by electrostatic dielectric elastomer actuator
Authors: Phung Hoa , Nguyen Canh Toan , Jung Hosang , Nguyen Tien Dat , Choi Hyouk Ryeol 
Published: January 2020

Abstract
This paper presents a novel bidirectional tactile display by integrating an antagonistic dielectric elastomer actuator (DEA) with a V-shaped electrostatic actuator (EA), called electrostatic dielectric elastomer actuator (EDEA). Within a simple structure, this device can provide large out-of-plane vibration of the silicone-based DEA membrane. It is noted that, compared to the DEA alone, combining the soft DEA and electrostatic actuator significantly enhances the device performance by about 19.1% in terms of displacement and by about 14%–26% in terms of blocking force. We also analyze the constitutive DEA and EA models to predict the displacement and blocking force behaviors. The simulation results are consistent with the experimental results. The device is successfully fabricated by using 3D printing technology which simplifies the fabrication process and improves the scalability of the system. The tactile display can provide up to 680 μm of displacement and up to 185 mN of blocking force more than the human hand stimulus threshold (displacement/force). By controlling the input voltage and frequency, the device can generate different haptic feelings to the user.
Collective effects of link failures in linear flow networks
Authors: Kaiser Franz , Strake Julius , Witthaut Dirk 
Published: January 2020

Abstract
The reliable operation of supply networks is crucial for the proper functioning of many systems, ranging from biological organisms such as the human blood transport system or plant leaves to man-made systems such as power grids or gas pipelines. Whereas the failure of single transportation links has been analysed thoroughly, the understanding of multiple failures is becoming increasingly important to prevent large scale damages. In this publication, we examine the collective nature of the simultaneous failure of several transportation links. In particular, we focus on the difference between single link failures and the collective failure of several links. We demonstrate that collective effects can amplify or attenuate the impacts of multiple link failures—and even lead to a reversal of flows on certain links. A simple classifier is introduced to predict the overall strength of collective effects that we demonstrate to be generally stronger if the failing links are close to each other. Finally, we establish an analogy between link failures in supply networks and dipole fields in discrete electrostatics by showing that multiple failures may be treated as superpositions of multiple electrical dipoles for lattice-like networks. Our results show that the simultaneous failure of multiple links may lead to unexpected effects that cannot be easily described using the theoretical framework for single link failures.
Resective epilepsy surgery in tuberous sclerosis complex: a nationwide multicentre retrospective study from China
Authors: Liu Shiyong , Yu Tao , Guan Yuguang , Zhang Kai , Ding Ping , Chen Lei , Shan Yongzhi , Guo Qiang , Liu Qingzhu , Yao Yi , Yang Meihua , Zhang Shaohui , Lin Yuanxiang , Zhao Rui , Mao Zhiqi , Zhang Juncheng , Zhang Chunqing , Zhang Rui , Yang Zhiquan , Qian Ruobing , Li Yunlin , Zhang Guangming , Yuan Liu , Yang Weidong , Tian Hong , Zhang Hua , Li Wenling , Zhang Xinwei , Yin Jian , Guo Yanwu , Zou Liping , Qin Jiong , Fang Fang , Wang Xu , Ge Ming , Liang Shuli 
Published: January 2020

AbstractAt least 50% of patients with tuberous sclerosis complex present with intractable epilepsy; for these patients, resective surgery is a treatment option. Here, we report a nationwide multicentre retrospective study and analyse the long-term seizure and neuropsychological outcomes of epilepsy surgery in patients with tuberous sclerosis complex. There were 364 patients who underwent epilepsy surgery in the study. Patients’ clinical data, postoperative seizure outcomes at 1-, 4-, and 10-year follow-ups, preoperative and postoperative intelligence quotients, and quality of life at 1-year follow-up were collected. The patients’ ages at surgery were 10.35 ± 7.70 years (range: 0.5–47). The percentage of postoperative seizure freedom was 71% (258/364) at 1-year, 60% (118/196) at 4-year, and 51% (36/71) at 10-year follow-up. Influence factors of postoperative seizure freedom were the total removal of epileptogenic tubers and the presence of outstanding tuber on MRI at 1- and 4-year follow-ups. Furthermore, monthly seizure (versus daily seizure) was also a positive influence factor for postoperative seizure freedom at 1-year follow-up. The presence of an outstanding tuber on MRI was the only factor influencing seizure freedom at 10-year follow-up. Postoperative quality of life and intelligence quotient improvements were found in 43% (112/262) and 28% (67/242) of patients, respectively. Influence factors of postoperative quality of life and intelligence quotient improvement were postoperative seizure freedom and preoperative low intelligence quotient. The percentage of seizure freedom in the tuberectomy group was significantly lower compared to the tuberectomy plus and lobectomy groups at 1- and 4-year follow-ups. In conclusion, this study, the largest nationwide multi-centre study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient.
High Rates of Influenza-Associated Invasive Pulmonary Aspergillosis May Not Be Universal: A Retrospective Cohort Study from Alberta, Canada
Authors: Schwartz Ilan S , Friedman Daniel Z P , Zapernick Lori , Dingle Tanis C , Lee Nelson , Sligl Wendy , Zelyas Nathan , Smith Stephanie W 
Published: January 2020

Abstract
From 2014–2019, invasive pulmonary aspergillosis complicated 7.2% (0–23.1% in different influenza seasons) of cases of influenza-associated respiratory failure in Edmonton, Alberta. Disease outcomes ranged from survival without therapy to death despite antifungals. Clinician vigilance, longitudinal local surveillance, and refined criteria to identify patients requiring therapy are needed.
The African Green Monkey Model of Pneumonic Plague and US Food and Drug Administration Approval of Antimicrobials Under the Animal Rule
Authors: Hewitt Judith A , Lanning Lynda L , Campbell Joseph L 
Published: January 2020

Abstract

Background
Additional treatment options for pneumonic plague, the most severe form of infection by Yersinia pestis, are needed, as past US Food and Drug Administration (FDA) approvals were not based on clinical trials that meet today’s standards, and multiple drugs are sought to counter resistance or use in special populations. Due to the sporadic nature of outbreaks and the low number of pneumonic cases of disease, we sought FDA approval of antimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-characterized animal models that sufficiently represent human disease.

Methods
A model was developed in African green monkeys (AGMs) after challenge with a lethal dose of Y. pestis delivered as an aerosol, in 4 independent studies in 3 laboratories. The primary data points were bacteremia (daily), body temperature and heart rate (continuously monitored by telemetry), and survival. In antimicrobial efficacy studies, human-equivalent doses of gentamicin, ciprofloxacin, levofloxacin, and doxycycline were administered upon fever onset for 10 days.

Results
Disease in AGMs was similar to case reports of human disease. Fever was determined to be a reliable sign of disease and selected as a treatment trigger. Gentamicin was 60%–80% effective depending on the dose given to animals. Ciprofloxacin and levofloxacin were found to be &gt;90% efficacious. These data were submitted to FDA and plague indications were approved. Doxycycline was less effective.

Conclusions
The AGM model of pneumonic plague is reproducible, well-characterized, and mimics human disease. It has been used to support plague indications for fluoroquinolones and to test the efficacy of additional antimicrobials.
Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism
Authors: Guo Zeng , Poglitsch Marko , McWhinney Brett C , Ungerer Jacobus P J , Ahmed Ashraf H , Gordon Richard D , Wolley Martin , Stowasser Michael 
Published: January 2020

Abstract

Background
Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system.

Methods
Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured.

Results
EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P &lt; 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays’ functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P &lt; 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P &lt; 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880).

Conclusions
Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.
Debiasing International Economic Law
Authors: Puig Sergio 
Published: January 2020

Abstract
A flourishing number of bodies evaluate the conduct of government officials against broad standards, decide complex questions of scientific probity and calculate the present value of past decisions. The effects of implicit biases (systematic patterns of deviation from rationality in judgment) impact the assessment of these issues, which are central to international economic law. Such effects are well understood by psychologists and increasingly confirmed by experiments involving legal actors, including judges. In this article, I provide three concrete examples of implicit biases affecting international tax, trade and investment adjudication, and I call for the incorporation of mechanisms to overcome such biases as well as their strategic exploitation by litigants. At a conceptual level, I propose a typology to think of ‘debiasing tools’ for international adjudication – mechanisms that can act as a centrepiece of coordination of information rather than mere inoculants of the habits of mind on adjudicators. At a normative level, I pose that biases may impact confidence in dispute settlement systems and that both concerns for sovereignty and a predilection for negotiated solutions make international economic law ripe for testing these interventions.
Role of ethylene response factors (ERFs) in fruit ripening
Authors: Gao Jin , Zhang Yaoxin , Li Zhengguo , Liu Mingchun 
Published: January 2020

Abstract
The ethylene response factors (ERFs) belong to the APETALA2/ethylene response factor (AP2/ERF) superfamily and act downstream of the ethylene signalling pathway to regulate the expression of ethylene responsive genes. In different species, ERFs have been reported to be involved in plant development, flower abscission, fruit ripening, and defense responses. In this review, based on the new progress made by recent studies, we summarize the specific role and mode of action of ERFs in regulating different aspects of ripening in both climacteric and non-climacteric fruits, and provide new insights into the role of ethylene in non-climacteric fruit ripening.
Feigin–Frenkel Image of Witten–Kontsevich Points
Authors: Luu Martin T 
Published: January 2020

AbstractThe Witten–Kontsevich KdV tau function of topological gravity has a generalization to an arbitrary Drinfeld–Sokolov hierarchy associated to a simple complex Lie algebra. Using the Feigin–Frenkel isomorphism we describe the affine opers describing such generalized Witten–Kontsevich functions in terms of Segal–Sugawara operators associated to the Langlands dual Lie algebra. In the case where the Lie algebra is simply laced there is a second role these Segal–Sugawara operators play: their action, in the basic representation of the affine algebra associated to the Lie algebra, singles out the Witten–Kontsevich tau function within the phase space. We show that these two Langlands dual roles of Segal–Sugawara operators correspond to a duality between the first and last operator for a complete set of Segal–Sugawara operators.
Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption
Authors: De Scheerder Marie-Angélique , Van Hecke Clarissa , Zetterberg Henrik , Fuchs Dietmar , De Langhe Nele , Rutsaert Sofie , Vrancken Bram , Trypsteen Wim , Noppe Ytse , Van Der Gucht Bea , Pelgrom Jolanda , Van Wanzeele Filip , Palmer Sarah , Lemey Philippe , Gisslén Magnus , Vandekerckhove Linos 
Published: January 2020

Abstract

Background
Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health.

Objectives
ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated.

Methods
PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation.

Results
Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption.

Conclusions
ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.
Pharmacokinetic analysis of an extended-pulsed fidaxomicin regimen for the treatment of Clostridioides (Clostridium) difficile infection in patients aged 60 years and older in the EXTEND randomized controlled trial
Authors: Guery Benoit , Georgopali Areti , Karas Andreas , Kazeem Gbenga , Michon Ingrid , Wilcox Mark H , Cornely Oliver A 
Published: January 2020

Abstract

Background
Fidaxomicin is a recommended treatment for Clostridioides difficile infection (CDI) and reduces CDI recurrence incidence versus vancomycin. An extended-pulsed fidaxomicin (EPFX) regimen further reduces recurrence frequency. However, the pharmacokinetic profile of fidaxomicin in an EPFX regimen is unknown.

Objectives
To evaluate plasma and stool concentrations of fidaxomicin and its metabolite, OP-1118, after EPFX administration for CDI.

Methods
In the Phase 3b/4 EXTEND trial, patients aged ≥60 years with toxin-confirmed CDI were randomized to receive EPFX (oral fidaxomicin twice daily, Days 1–5; once daily on alternate days, Days 7–25). Fidaxomicin and OP-1118 concentrations were determined using post-dose plasma samples obtained on Days 5 ± 1, 12 ± 1 and 25/26, and post-dose stool samples obtained on Days 5 ± 1, 12 ± 1 and 26 ± 1.

Results
Plasma samples from 14 patients were included in the pharmacokinetic analysis; 12 of these patients provided stool samples. Median (range) plasma concentrations of fidaxomicin on Day 5 ± 1 and Day 25/26 were 0.0252 (0.0038–0.1220) mg/L and 0.0069 (0–0.0887) mg/L, respectively, and those of OP-1118 were 0.0648 (0.0142–0.3250) mg/L and 0.0206 (0–0.3720) mg/L, respectively. Median (range) stool concentrations of fidaxomicin and OP-1118 on Day 26 ± 1 were 272.5 (0–524) mg/kg and 280.5 (0–1120) mg/kg, respectively.

Conclusions
EPFX treatment maintained fidaxomicin stool concentrations above the C. difficile MIC90 until Day 26 ± 1. Systemic exposure to fidaxomicin and OP-1118 was low throughout and there was no evidence of accumulation in plasma or stool during treatment.
The potential for developing new antimicrobial resistance from the use of medical devices containing chlorhexidine, minocycline, rifampicin and their combinations: a systematic review
Authors: Reitzel Ruth A , Rosenblatt Joel , Gerges Bahgat Z , Jarjour Andrew , Fernández-Cruz Ana , Raad Issam I 
Published: January 2020

Abstract

Background
Catheter infections remain one of the most persistent adverse events causing significant morbidity, economic impact and mortality. Several strategies have been proposed to reduce these infections including the use of catheters embedded with antibiotics and/or antiseptics. One reoccurring challenge is the fear that antimicrobial medical devices will induce resistance. The aim of this systematic review is to evaluate the evidence for induced antimicrobial resistance caused by exposure to antimicrobial medical devices.

Methods
Four electronic databases [MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus] were screened for studies published between 1983 and 2019 regarding assessment of microbial resistance with use of medical devices containing chlorhexidine, minocycline, rifampicin or combinations thereof. Development of new resistance, selection for tolerant organisms and ‘no change in resistance’ were assessed.

Results
Forty-four publications, grouped by study type and stratified by drug assessed, were included for analyses. The majority of studies found no change in resistance after exposure to antimicrobial medical devices (13 in vitro, 2 in vivo, 20 clinical). Development of new resistance was commonly reported with the use of rifampicin as a single agent and only reported in one study assessing the minocycline/rifampicin combination (M/R); however, the increase in MIC was well below clinical relevance.

Conclusions
Emergence of new resistance to combinations of M/R, minocycline/rifampicin/chlorhexidine (M/R/CH) and chlorhexidine/silver sulfadiazine (CHXSS) was rare. No clinical trials confirmed its occurrence and some refuted it. The risk of development of new resistance to these antimicrobial combinations appears more fear-based than substantiated by clinical and experimental evidence but warrants continued surveillance.
Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer
Authors: Ogita Mami , Yamashita Hideomi , Sawayanagi Subaru , Takahashi Wataru , Nakagawa Keiichi 
Published: January 2020

Abstract

Objectives
We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion.

Methods
The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%.

Results
Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P &lt; 0.01) and high (P &lt; 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate.

Conclusions
A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.