bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of a composite monolith with functional graphene oxide and its application in the online enrichment of ursolic acid in medicinal plant
Authors: Yu Huan , Liu Haiyan , Pang Xiaoya , Zhang Miaomiao , Yan Hongyuan , Bai Ligai
Published: February 2020

In this study, a composite poly(functional graphene oxide‐co‐N‐isopropylacrylamide‐co‐trimethylolpropane triacrylate‐co‐ethylene dimethacrylate) (poly(f‐GO‐co‐NIPAAm‐co‐TMPTA‐co‐EDMA)) monolith was prepared, in which f‐GO was added. The obtained monolith was characterized by nitrogen adsorption–desorption isotherm and scanning electron microscopy. The monolith exhibited a homogeneous and continuous structure, good permeability, and large surface area. The composite monolith was used as solid‐phase extraction absorbent in conjunction with high‐performance liquid chromatography for enrichment of ursolic acid. The calibration equation wasy= 73.3980x + 0.2555, and the linear regression coefficient was 0.9987; The calibration curve was ranged from 1 to 700 μg ml−1; The limit of detection and limit of quantification values were 0.3 and 1.0 μg ml−1, respectively; The intraday and interday precisions were less than 2.6 and 7.4%, respectively. The recovery was in the range of 84.44–111.76%. Moreover, the adsorption amount of ursolic acid on the composite monolith was compared with the monolith without f‐GO added and silica gel‐C18 adsorbent. The results showed that the composite monolithic column was feasible to be used as an online SPE absorbent, which exhibiting low back pressure, good permeability, and high adsorption capacity. In addition, this method provided the possibility to extract and analyze trace components from medicinal plants.
Clam‐like Cyclotricatechylene‐based Capsules: Identifying the Roles of Protonation State and Guests as well as the Drivers for Stability and (Anti‐)Cooperativity
Authors: Mehta Nisha , Abrahams Brendan F. , Goerigk Lars
Published: February 2020

Cyclotricatechylene (ctcH6) is a bowl‐shaped macrocyclic compound that can be used as a building block for self‐assembled capsules. ctcH6 and its derivatives in various protonation states – here collectively labeled as CTC – form dimers that resemble the shape of a clam. These clam‐shaped entities have been studied experimentally by Abrahams, Robson, and co‐workers [B. F. Abrahams, N. J. FitzGerald, T. A. Hudson, R. Robson and T. Waters, Angew. Chem. Int. Ed. 2009, 48, 3129–3132] where the capsules acted as an excellent host for large alkali‐metal cations. In this study, we present a detailed analysis based on accurate dispersion‐corrected Density Functional Theory approaches that reveals the factors that stabilise such CTC‐based capsules at different protonation states and their interaction with various encapsulated guests. Our results show that the capsules’ overall stability results as an interplay of hydrogen bonding, London dispersion, and electrostatic effects. The most stable capsules with group‐1 and group‐2 cations as guests contain only six phenolic hydrogens, as opposed to the maximum possible number of twelve. Inclusion of larger alkali‐metal cations is favoured due to larger London‐dispersion contributions. Cations are favoured as guests over isoelectronic neutral species, as the resulting host‐guest complexes experience additional stability due to cooperative effects. In fact, using the latter to drive the formation of specific capsules could be used in future strategies aimed at synthesising similar aggregates; our results provide an insightful understanding and useful guidance for such future endeavours.
Maneuver detection and tracking of a space target based on a joint filter model
Authors: Ye Liu , Hua Zhao , Chuankai Liu , Jianfeng Cao , Junkui Wang
Published: February 2020

Orbit maneuver of non‐cooperative space targets is difficult to detect, and thus greatly affects the accuracy of real‐time target tracking. To solve this problem, a joint filter‐based algorithm is proposed to detect and track targets with random pulse maneuvering. In the algorithm, the joint filter is constructed using two nonlinear filters. The first is an auxiliary filter that utilizes the kinematic model to predict the target motion and estimate the target movement according to the continuity of Keplerian elements. The other is a primary filter that uses an orbit dynamic model to predict the target motion and utilize the estimated results provided as feedback by the auxiliary filter as the constraints to re‐estimate the target orbit in real time. Moreover, simulations were conducted to detect and track non‐cooperative space targets with a series of random pulse maneuvers, and thus validate the efficiency of the new algorithm.
Effective resolution in high resolution global atmospheric models for climate studies
Authors: Klaver Remko , Haarsma Rein , Vidale Pier Luigi , Hazeleger Wilco
Published: February 2020

We estimate the extent of spatial scales that atmospheric models in a new generation of global climate models, used in the Coupled Model Intercomparison Project 6, are able to resolve on the basis of kinetic energy spectra, commonly referred to as the effective resolution. We examine the spectra derived from the rotational and divergent parts of the wind for six state‐of‐the‐art global climate models that have been run with at least two horizontal resolutions. For each of the high resolution configurations, the effective resolution enhancement is less than proportional to the increase of the nominal resolution. The highest effective resolution obtained by the models in this study is roughly 200 km. This shows that the newest generation of high resolution climate models starts to resolve synoptic scales relevant for the dynamics of weather events.
Maßnahmen zur Mitigation von Sicherheitsrisiken bei digital unterstützten Bauprojekten
Authors: Wittenborn Arne , Čadež Ivan , Schumann René
Published: February 2020

Die im ersten Beitrag identifizierten Sicherheitsrisiken haben Auswirkungen auf mehrere Bereiche der digital unterstützten Projektabwicklung. Die dafür erforderlichen personellen und technologischen Ressourcen sind im Sinne eines übergeordneten Prozesses zu koordinieren. Die Implementierung eines ganzheitlichen Informationssicherheitskonzepts bei BIM‐gestützten Bauprojekten wird dadurch erschwert, dass das Bewusstsein hinsichtlich der Risikopotenziale für digitalisierte Projektinformationen bei vielen Projektbeteiligten gegenwärtig noch nicht ausgeprägt ist. In diesem Beitrag werden daher beispielhafte Möglichkeiten aufgezeigt, wie den identifizierten Sicherheitsrisiken entgegengewirkt werden kann.

Gemäß der Kategorisierung in prozessuale, personelle und technologische Risikobereiche werden daher zunächst Handlungsempfehlungen für jedes der 16 identifizierten Sicherheitsrisiken vorgestellt. Eine davon abgeleitete Risikoklassifizierung in fünf Klassen (A, B1, B2, B3, C) zeigt auf, welche Bedeutung bzw. Priorität diese bei der Erarbeitung eines Informationssicherheitskonzepts haben können. Darauf aufbauend werden die Ansätze der ISO 19650‐5 zu dessen Implementierung auf Projektebene vorgestellt und bewertet. Abschließend wird der aktuelle Entwicklungsstand zusammengefasst und der weitere Handlungsbedarf benannt.
Take a risk or proceed with caution: Prevention motivation moderates responses to near‐loss events
Authors: Paine Jill W. , Federspiel Florian , Seifert Matthias , Zou Xi
Published: February 2020

A persistently pressing issue identified in the decision‐making literature is that people not only fail to recognize the risks entailed in a near‐loss event but also subsequently engage in further risk‐taking. We contend in this paper that prevention motivation critically regulates decision‐makers' responses to a near‐loss. Across three studies, we found that high prevention‐focused individuals perceive greater risks in a near‐loss event and are subsequently less likely to take risks, compared with low prevention‐focused individuals. This finding highlights the significance of applying a motivational perspective to studying decision‐making and risk.
Presidential Address: The academic discipline of education. Reciprocal relationships between practical knowledge and academic knowledge
Authors: Wyse Dominic
Published: February 2020

This article explores the nature of education as a vital part of human knowledge. The argument that is presented addresses the critique of education as having epistemological weaknesses as an academic discipline. The argument is framed by scholarship that has categorised the discipline of education as derived from three main traditions of knowledge. In order to explore the coherence of education as a discipline, contrasts are made with other disciplines such as mathematics and sciences. The article also reviews scholarship in relation to the concept of education research that is close‐to‐practice, and the relevance of this to understanding education as an academic discipline. The article concludes by suggesting a new model that shows the relationships between practical knowledge and academic knowledge that are an intrinsic part of education. A more confident portrayal of education as an academic discipline is also advocated.
IV estimation without distributional assumptions
Authors: Lange Theis , Jensen Aksel K. G.
Published: February 2020

It is widely known that Instrumental Variable (IV) estimation allows the researcher to estimate causal effects between an exposure and an outcome even in face of serious uncontrolled confounding. The key requirement for IV estimation is the existence of a variable, the instrument, which only affects the outcome through its effects on the exposure and that the instrument–outcome relationship is unconfounded. Countless papers have employed such techniques and carefully addressed the validity of the IV assumption just mentioned. However, less appreciated is that fact that the IV estimation also depends on a number of distributional assumptions in particular linearities. In this paper, we propose a novel bounding procedure which can bound the true causal effect relying only on the key IV assumption and not on any distributional assumptions. For a purely binary case (instrument, exposure, and outcome all binary), such boundaries have been proposed by Balke and Pearl in 1997. We extend such boundaries to non‐binary settings. In addition, our procedure offers a tuning parameter such that one can go from the traditional IV analysis, which provides a point estimate, to a completely unrestricted bound and anything in between. Subject matter knowledge can be used when setting the tuning parameter. To the best of our knowledge, no such methods exist elsewhere. The method is illustrated using a pivotal study which introduced IV estimation to epidemiologists. Here, we demonstrate that the conclusion of this paper indeed hinges on these additional distributional assumptions. R‐code is provided in the Supporting Information.
Comparison of Modeling Methods for DoE‐Based Holistic Upstream Process Characterization
Authors: Bayer Benjamin , von Stosch Moritz , Striedner Gerald , Duerkop Mark
Published: February 2020

Upstream bioprocess characterization and optimization are time and resource‐intensive tasks. Regularly in the biopharmaceutical industry, statistical design of experiments (DoE) in combination with response surface models (RSMs) are used, neglecting the process trajectories and dynamics. Generating process understanding with time‐resolved, dynamic process models allows to understand the impact of temporal deviations, production dynamics, and provides a better understanding of the process variations that stem from the biological subsystem. The authors propose to use DoE studies in combination with hybrid modeling for process characterization. This approach is showcased on Escherichia coli fed‐batch cultivations at the 20L scale, evaluating the impact of three critical process parameters. The performance of a hybrid model is compared to a pure data‐driven model and the widely adopted RSM of the process endpoints. Further, the performance of the time‐resolved models to simultaneously predict biomass and titer is evaluated. The superior behavior of the hybrid model compared to the pure black‐box approaches for process characterization is presented. The evaluation considers important criteria, such as the prediction accuracy of the biomass and titer endpoints as well as the time‐resolved trajectories. This showcases the high potential of hybrid models for soft‐sensing and model predictive control.
Comprehensive understanding of Saccharomyces cerevisiae phenotypes with whole‐cell model WM_S288C
Authors: Ye Chao , Xu Nan , Gao Cong , Liu Gaoqiang , Xu Jianzhong , Zhang Weiguo , Chen Xiulai , Nielsen Jens , Liu Liming
Published: February 2020

Biological network construction for Saccharomyces cerevisiae is a widely used approach for simulating phenotypes and designing cell factories. However, due to a complicated regulatory mechanism governing the translation of genotype to phenotype, precise prediction of phenotypes remains challenging. Here, we present WM_S288C, a computational whole‐cell model that includes 15 cellular states and 26 cellular processes and which enables integrated analyses of physiological functions of Saccharomyces cerevisiae. Using WM_S288C to predict phenotypes of S. cerevisiae, the functions of 1140 essential genes were characterized and linked to phenotypes at five levels. During the cell cycle, the dynamic allocation of intracellular molecules could be tracked in real‐time to simulate cell activities. Additionally, one‐third of non‐essential genes were identified to affect cell growth via regulating nucleotide concentrations. These results demonstrated the value of WM_S288C as a tool for understanding and investigating the phenotypes of S. cerevisiae.
Repeat cytoreductive surgery with or without intraperitoneal chemotherapy for recurrent epithelial appendiceal neoplasms
Authors: Karpes J B , Lansom J D , Alshahrani M , Parikh R , Shamavonian R , Alzahrani N A , Liauw W , Morris D L
Published: February 2020

Background

With recurrence rates after primary cytoreductive surgery (CRS) in excess of 50 per cent, repeat CRS is being performed increasingly, but survival outcomes have not been reported widely. This study examined the outcomes following repeat CRS for appendiceal cancer with peritoneal surface malignancy (PSM), and evaluated its feasibility and safety.

Methods

A retrospective cohort of patients who had surgery between 1996 and 2018 were analysed. Patients who underwent a single CRS procedure with or without heated intraperitoneal chemotherapy (HIPEC) were compared with those who had multiple procedures with or without HIPEC. Perioperative morbidity and survival outcomes were analysed.

Results

Some 462 patients were reviewed, 102 of whom had repeat procedures. For high-grade tumours, patients who had a single CRS procedure had significantly reduced overall survival (OS) compared with those who had repeat CRS (55·6 versus 90·7 months respectively; P = 0·016). For low-grade tumours, there was no difference in OS (P = 0·153). When patients who had a single procedure were compared with those who had multiple procedures, there was no significant difference in major morbidity (P = 0·441) or in-hospital mortality (P = 0·080). For multiple procedures, no differences were found in major morbidity (P = 0·262) or in-hospital mortality (P = 0·502) when the first procedure was compared with the second. For low-grade cancers, the peritoneal carcinomatosis index was a significant prognostic factor for OS (hazard ratio (HR) 1·11, 95 per cent c.i. 1·05 to 1·17; P < 0·001), whereas for high-grade cancers repeat CRS (HR 0·57, 0·33 to 0·95; P = 0·033), complete cytoreduction score (HR 1·55, 1·01 to 2·40; P = 0·046) and presence of signet ring cells (HR 2·77, 1·78 to 4·30; P < 0·001) were all significant indicators of long-term survival.

Conclusion

In selected patients presenting with PSM from epithelial appendiceal neoplasms, repeat CRS performed in high-volume centres could provide survival benefits.
Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Li Zi‐ting , Zhang Feng‐xiang , Chen Wei‐wu , Chen Ming‐hao , Tang Xi‐yang , Ye Meng‐nan , Yao Zhi‐hong , Yao Xin‐sheng , Dai Yi
Published: February 2020

Periplocae Cortex, named Xiang‐Jia‐Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the in vivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats’ biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S‐4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the in vivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research.
Relation of infarction location and volume to vertigo in vertebrobasilar stroke
Authors: Elhfnawy Ahmed Mohamed , Abd El‐Raouf Mervat , Volkmann Jens , Fluri Felix , Elsalamawy Doaa
Published: February 2020

Objective

Vertigo is a common presentation of vertebrobasilar stroke. Anecdotal reports have shown that vertigo occurs more often in multiple than in single brainstem or cerebellar infarctions. We examined the relation between the location and volume of infarction and vertigo in patients with vertebrobasilar stroke.

Methods

Consecutive patients with vertebrobasilar stroke were prospectively recruited. The infarction location and volume were assessed in the diffusion‐weighted magnetic resonance imaging.

Results

Fifty‐nine patients were included, 32 (54.2%) with vertigo and 27 (45.8%) without vertigo. The infarction volume did not correlate with National Institute of Health Stroke Scale (NIHSS) score on admission (Spearman ρ = .077, p = .56) but correlated with modified Rankin Scale (ρ = .37, p = .004) on discharge. In the vertigo group, the proportion of men was lower (53.1% vs. 77.8%, p = .049), fewer patients had focal neurological deficits (65.6% vs. 96.3%, p = .004), patients tended to present later (median [IQR] was 7.5 [4–46] vs. 4 [2–12] hours, p = .052), numerically fewer patients received intravenous thrombolysis (15.6% vs. 37%, p = .06), and the total infarction volume was larger (5.6 vs. 0.42 cm3, p = .008) than in nonvertigo group. In multivariate logistic regression, infarction location either in the cerebellum or in the dorsal brainstem (odds ratio [OR] 16.97, 95% CI 3.1–92.95, p = .001) and a total infarction volume of >0.48 cm3 (OR 4.4, 95% CI 1.05–18.58, p = .043) were related to vertigo. In another multivariate logistic regression, after adjusting for age, sex, intravenous thrombolysis, serum level of white blood cells, and atrial fibrillation, vertigo independently predicted a total infarction volume of >0.48 cm3 (OR 5.75, 95% CI 1.43–23.08, p = .01).

Conclusion

Infarction location in the cerebellum and/or dorsal brainstem is an independent predictor of vertigo. Furthermore, larger infarction volume in these structures is associated with vertigo. A considerable proportion of patients with vascular vertigo present without focal neurological deficits posing a diagnostic challenge. National Institute of Health Stroke Scale is not sensitive for vertebrobasilar stroke.
The admissibility of other specified paraphilic disorder (non‐consent) in sexually violent predator proceedings
Authors: Holoyda Brian
Published: February 2020

Following the advent of sexually violent predator (SVP) legislation in the early 1990s, forensic evaluators began to apply diagnostic labels related to a paraphilic interest in rape as a mental condition predisposing individuals convicted of sexual offenses to recidivate. The most recent iteration of the concept, other specified paraphilic disorder (non‐consent) (OSPD (non‐consent)), is a commonly utilized diagnostic entity in SVP proceedings. Research on paraphilic interest in coercive sex has failed to define a valid methodology or set of criteria to make a diagnosis of OSPD (non‐consent) and has repeatedly demonstrated that the diagnostic construct has poor interrater reliability. The state of the science pertaining to OSPD (non‐consent) thus raises serious concerns regarding its admissibility in SVP proceedings. Indeed, there are recent cases in which courts have deemed it inadmissible. The forensic expert involved in SVP proceedings should understand admissibility concerns related to OSPD (non‐consent) and how to address them in court.
Arterial anatomy of the anterior abdominal wall: Ultrasound evaluation as a real‐time guide to percutaneous instrumentation
Authors: Le Saint‐Grant Alexander , Taylor Alasdair , Varsou Ourania , Grant Calum , Cezayirli Enis , Bowness James
Published: February 2020

Introduction

Instrumenting the anterior abdominal wall carries a potential for vascular trauma. We previously assessed the presence, position, and size of the anterior abdominal wall superior and inferior (deep) epigastric arteries with computed tomography (CT). We now present a study using ultrasound (US) assessment of these arteries, to evaluate its use for real time guidance of percutaneous procedures involving the rectus sheath.

Materials and Methods

Twenty‐four participants (mean age 67.9 ± 9 years, 15 M:9 F [62:38%]) were assessed with US at three axial planes on the anterior abdominal wall: transpyloric plane (TPP), umbilicus, and anterior superior iliac spine (ASIS).

Results

An artery was visible least frequently at the TPP (62.5 – 45.8%), compared with the umbilicus (95.8–100%) and ASIS (100%), on the left, χ2(2) = 20.571; p < .001, and right, χ2(2) = 27.842; p < .001, with a moderate strength association (Cramer's V = 0.535 [left] and 0.622 [right]). Arteries were most commonly observed within the rectus abdominis muscle at the level of the TPP and umbilicus, but posterior to the muscle at the level of the ASIS (95.8–100%). As with the CT study, the inferior epigastric artery was observed to be larger in diameter, start more laterally, and move medially as it coursed superiorly.

Conclusions

These data corroborate our previous results and suggest that the safest level to instrument the rectus sheath (with respect to vascular anatomy) is at the TPP. Such information may be particularly relevant to anesthetists performing rectus sheath block and surgeons during laparoscopic port insertion.
First‐line pembrolizumab for non–small cell lung cancer patients with PD‐L1 ≥50% in a multicenter real‐life cohort: The PEMBREIZH study
Authors: Amrane Karim , Geier Margaux , Corre Romain , Léna Hervé , Léveiller Guillaume , Gadby Florence , Lamy Régine , Bizec Jean‐Louis , Goarant Eric , Robinet Gilles , Gouva Sylvie , Quere Gilles , Abgral Ronan , Schick Ulrike , Bernier Cyril , Chouaid Christos , Descourt Renaud
Published: February 2020

Background

The KEYNOTE‐024 trial demonstrated that pembrolizumab, a PD‐1 inhibitor, significantly improves progression‐free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non–small cell lung cancer (NSCLC) with a PD‐L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real‐life conditions.

Method

This was a French retrospective multicenter longitudinal study of 108 consecutive patients with advanced NSCLC, a PD‐L1 TPS ≥50% and without EGFR/ALK aberrations who were treated by pembrolizumab, in first line. Patient data were obtained from medical files.

Results

The main characteristics of the cohort were: median age [range] 66.7 [37‐87] years, 64.8% male, 23.1% with a performance status (PS) of 2, and 88.9% current or former smokers. Eighty‐seven percent had stage IV NSCLC at diagnosis, 9.2% untreated brain metastases at inclusion,. With a median follow‐up of 8.2 months, the median PFS was 10.1 months (95% CI, 8.8‐11.4). The objective response rate was 57.3% (complete response 2.7%, partial response 54.6%). Disease control rate was 71.1%. At 6 months, the OS rate estimated was 86.2%. Treatment‐related adverse events (AE) of grade 3 occurred in 8% of patients. There were no grade 4 or 5 AEs.

Conclusion

In a real‐life cohort of advanced NSCLC patients (including PS 2 and untreated brain metastases), with PD‐L1 TPS ≥50%, pembrolizumab demonstrates similar PFS to the pivotal clinical trial.
A pediatric regimen for adolescents and young adults with Philadelphia chromosome‐negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial
Authors: Ribera Josep‐Maria , Morgades Mireia , Montesinos Pau , Tormo Mar , Martínez‐Carballeira Daniel , González‐Campos José , Gil Cristina , Barba Pere , García‐Boyero Raimundo , Coll Rosa , Pedreño María , Ribera Jordi , Mercadal Santiago , Vives Susana , Novo Andrés , Genescà Eulàlia , Hernández‐Rivas Jesús‐María , Bergua Juan , Amigo María‐Luz , Vall‐Llovera Ferran , Martínez‐Sánchez Pilar , Calbacho María , García‐Cadenas Irene , Garcia‐Guiñon Antoni , Sánchez‐Sánchez María‐José , Cervera Marta , Feliu Evarist , Orfao Alberto ,   the PETHEMA Group, Spanish Society of Hematology
Published: February 2020

Background

Pediatric‐based or ‐inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome‐negative (Ph‐neg) acute lymphoblastic leukemia (ALL).

Methods

This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15‐30 years with standard‐risk (SR) ALL.

Results

From 2008 to 2018, 89 patients (38 adolescents [15‐18 years] and 51 young adults [YA, 19‐30 years], median age: 20 [15‐29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty‐two patients were transferred to a high‐risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high‐level of end‐induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%‐47%), with significant differences between adolescents and YA: 13% (4%‐28%) vs 52% (34%‐67%), P = .012. No treatment‐related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5‐year overall survival (OS) was 74% (95%CI: 63%‐85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%‐100%) vs 63% (46%‐80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%‐47%] vs 37% [14%‐61%]; OS: 78% [66%‐90%] vs 61% [31%;91%]).

Conclusion

A full pediatric trial is feasible and effective for AYA with Ph‐neg, SR‐ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior.
Expression of p16 and HPV E4 on biopsy samples and methylation of FAM19A4 and miR124‐2 on cervical cytology samples in the classification of cervical squamous intraepithelial lesions
Authors: Leeman Annemiek , Jenkins David , del Pino Marta , Ordi Jaume , Torné Aureli , Doorbar John , Meijer Chris J. L. M. , van Kemenade Folkert J. , Quint Wim G. V.
Published: February 2020

The decision to treat a cervical squamous intraepithelial lesion (SIL) by loop electrosurgical excision procedure (LEEP) relies heavily on a colposcopy‐directed biopsy showing high‐grade (H)SIL. Diagnosis is often supported by p16, an immunohistochemical (IHC) biomarker of high‐risk (hr)HPV E7 gene activity. Additional potential markers include methylation of tumor suppressor genes FAM19A4/miR124‐2 in cervical cytology for advanced transforming HSIL and the IHC marker HPV E4 for productive, potentially regressing lesions. In 318 women referred for colposcopy, we investigated the relationship between staining patterns of p16 and E4 IHC in the worst biopsy, and the relation of these to FAM19A4/miR124‐2 methylation status in cytology. E4‐positive staining decreased with increasing SIL/CIN grade from 41% in LSIL to 3% in HSIL/CIN3. E4 positivity increased with grade of p16 when p16 expression was limited to the lower two third of the epithelium (r = 0.378), but fell with expression over. Loss of E4 expression in the worst lesion was associated with the methylation of FAM19A4/miR124‐2. We also examined whether these biomarkers can predict the histological outcome of the LEEP biopsy in a subgroup of 119 who underwent LEEP treatment. About 85% of women with ≥lower two third p16 staining/E4‐negative HSIL biopsies and 65% with limited p16 staining/E4‐positive HSIL biopsies had ≥HSIL in the LEEP specimen (P = .025). p16 expression in a biopsy is related both to viral production and transformation, while decreased E4 expression relates to methylation, indicating advanced HSIL. p16 expression in ≥2/3 of the epithelium and absent E4 indicate likely HSIL on a subsequent LEEP specimen.
Microsatellite instability and its associations with the clinicopathologic characteristics of diffuse large B‐cell lymphoma
Authors: Tian Tian , Li Jiwei , Xue Tian , Yu Baohua , Li Xiaoqiu , Zhou Xiaoyan
Published: February 2020

Microsatellite instability (MSI) has been investigated as a prognostic and predictive factor for chemotherapy in colorectal cancer and has recently been demonstrated to be predictive of the PD‐1/PD‐L1 checkpoint blockade response in various solid tumors. However, MSI status in diffuse large B‐cell lymphomas (DLBCLs) has not been thoroughly explored. This study investigated MSI status in DLBCLs and analyzed the associations between MSI and clinicopathologic characteristics and clinical outcomes. Ninety‐two cases of primary DLBCLs treated with R‐CHOP/CHOP chemotherapy between 2009 and 2017 were collected. MSI detection was performed by the Promega MSI Analysis System. The protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry. The associations of MSI‐H and MSI‐L with progression‐free survival (PFS) and overall survival (OS) were assessed by COX models and Kaplan–Meier curves. The correlations of complete response (CR) after R‐CHOP/CHOP chemotherapy with MSI‐H and MSI‐L were examined by univariate and multivariate logistic regression analyses, respectively. 3 of 92 cases (3.2%) were high MSI (MSI‐H), and 9 cases (9/92, 9.8%) exhibited low MSI (MSI‐L). One case with MSI‐H showed negative expression of MSH2 and MSH6. Univariate analysis indicated that MSI‐L was correlated with poor response to R‐CHOP/CHOP chemotherapy in DLBCLs (OR, 0.178; 95% CI, 0.041‐0.776; P = .022). Multivariate analysis showed that MSI‐L was an independent predictive factor for non‐CR to R‐CHOP/CHOP chemotherapy (OR, 0.144; 95% CI, 0.027‐0.761; P = .023). Kaplan‐Meier curves showed that there was a trend that MSI‐H patients had favorable PFS (P = .36) and OS (P = .48), which did not have statistical significance and MSI‐L was not significantly correlated with PFS (P = .24) and OS (P = .52).Our study indicated that there existed MSI‐H and MSI‐L in DLBCLs. MSI‐L could be an independent predictive factor for the chemotherapy response in DLBCLs.
Management and risk factors of recurrent gestational trophoblastic neoplasia: An update from 2004 to 2017
Authors: Kong Yujia , Zong Liju , Cheng Hongyan , Jiang Fang , Wan Xirun , Feng Fengzhi , Ren Tong , Zhao Jun , Yang Junjun , Xiang Yang
Published: February 2020

Objective

We investigated the clinical characteristics, treatments, and survival of patients with gestational trophoblastic neoplasia (GTN) who experienced recurrence. Factors predictive of recurrence were also investigated.

Methods

Patients with GTN who recurred after completing chemotherapy at Peking Union Medical College Hospital Trophoblastic Disease Center were identified between January 2004 and December 2017. Logistic regression analysis was used to identify factors predictive of GTN recurrence.

Results

A total of 1827 patients with GTN achieved complete remission (CR) at our center, of whom 118 (6.5%) experienced recurrence during follow‐up. The recurrence rates for patients initially treated at our center and those referred to us were 2.7% and 14.6%, respectively. The majority of recurrent patients received floxuridine‐based multiagent chemotherapy (n = 64). Patients who underwent surgery achieved a significantly higher CR rate than those who did not (88.6% vs 61.1%, P = .001). Although 94.1% of recurrent patients reachieved CR, 33.3% of them recurred for a second time. The 5‐year survival rate of the entire cohort was 80.4%. An interval between antecedent pregnancy and chemotherapy >12 months (OR: 6.600, 95% CI [3.217‐13.540], P < .001), and an interval from first chemotherapy to achieving β‐human chorionic gonadotropin (β‐hCG) normalization >14 weeks (OR: 2.226, 95% CI [1.080‐4.588], P = .030) were predictors of recurrence.

Conclusions

Patients with recurrent GTN are prone to recurring for a second time. Surgery plays a beneficial role in the management of recurrent GTN. An interval between antecedent pregnancy and chemotherapy >12 months, and an interval from first chemotherapy to achieving β‐hCG normalization >14 weeks were predictors of recurrence.
Reciprocal language style matching in psychotherapy research
Authors: Aafjes‐van Doorn Katie , Müller‐Frommeyer Lena
Published: February 2020

Successful coordination of language, that is language style matching (LSM; Gonzales, Hancock, & Pennebaker, 2010) indicated by interdependent use of function words, might be of particular relevance to the psychotherapy process. Empirically, two previous psychotherapy studies indicate that LSM may provide a deeper understanding of the quality of the therapeutic alliance. Theoretically, this process of implicit linguistic coordination may be conceptualised as interpersonal synergy (Riley, Richardson, Shockley, & Ramenzoni, 2011). To illustrate the potential of LSM in psychotherapy research, patterns of LSM per 5 min segments and reciprocal LSM per speaking turn were assessed in a seven‐session treatment demonstration of a narcissistic client. First, LSM predicted observed frequency of ruptures but did not predict observer‐rated working alliance in the corresponding 5 min segments. Second, LSM in these 5 min segments showed a quadratic trajectory of change within session and a stable pattern between sessions. Reciprocal LSM per speaking turn showed that within the majority of this treatment, the client followed the therapist's language style; however, this influence appeared to be bidirectional during the time of a physical altercation in session five. LSM may thus provide a novel way to study some of the more elusive aspects of the therapeutic interaction.
Microtubule stabilizer epothilone B as a motor neuron differentiation agent for human endometrial stem cells
Authors: Mahmoodi Narges , Ai Jafar , Ebrahimi‐Barough Somayeh , Hassannejad Zahra , Hasanzadeh Elham , Basiri Arefeh , Vaccaro Alexander R. , Rahimi‐Movaghar Vafa
Published: February 2020

Microtubule‐stabilizing agents (MSAs), until now, have primarily been considered for their anti‐proliferative effects in the setting of cancer. However, recent studies have revealed that one particular MSA, epothilone B (EpoB), can promote axonal regeneration after traumatic spinal cord injuries (SCI) even in the presence of inhibitor molecules such as neurite outgrowth inhibitor‐A (Nogo‐A). On the basis of the importance of having an efficient motor neuron (MN) differentiation protocol for stem cell therapy and the attention of MSAs for SCI treatment, our study investigated the effect of EpoB on human endometrial stem cells (hEnSCs) differentiation into MN‐like cells. hEnSCs were isolated and characterized by flow cytometry. The hEnSC cell viability was evaluated by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. To mimic the in vivo inhibitory environment, hEnSCs were also differentiated in the presence of Nogo‐A. After 15 days of differentiation, the expressions of MN‐markers were evaluated by real‐time reverse‐transcriptase polymerase chain reaction and immunofluorescence. According to the MTT assay results, three doses (1, 5, and 10 nM) of EpoB were selected to evaluate their effect on MN‐differentiation. All selected doses can increase the efficacy of hEnSCs differentiation into MN‐like cells. In particular, the 10 nM EpoB dosage was shown to increase the axon elongation, cell alignment, and upregulation of these MN‐markers compared with other doses. EpoB can improve MN differentiation from hEnSC and potentially provide a unique route for neuronal replacement in the setting of SCI.
Catheter cryoablation of ventricular ectopy originating from his region
Authors: Rossi Andrea , Frontera Antonio , Panchetti Luca , Startari Umberto , Mirizzi Gianluca , Formichi Bruno Antonio , Piacenti Marcello
Published: February 2020

Careful mapping, early detection of AV conduction damage and cryothermal energy availability are essential in dealing with ablation procedures at the parahisian region.
Accidental poisoning with Aconitum: Case report and review of the literature
Authors: Bonanno Giuseppe , Ippolito Mariachiara , Moscarelli Alessandra , Misseri Giovanni , Caradonna Rosaria , Accurso Giuseppe , Cortegiani Andrea , Giarratano Antonino
Published: February 2020

Aconitine intoxication by ingestion of Aconitum roots can lead to ventricular tachycardia and cardiac arrest and provides an example of the potential effect of self‐medication. Educational campaigns should be implemented to contain acute intoxications caused by herbal‐derived products.
Myiasis
Authors: Qaradaghy Seerwan Hama Shareef , Hadad Sirwan
Published: February 2020

Late presentation of breast cancer is more likely to be complicated and fatal. Local invasion, tissue destruction, skin lose, and superadded infection/infestation make surgical intervention very challenging.
Calcium pyrophosphate deposition disease: A case report with bilateral involvement of the temporomandibular joints and concurrence of psoriatic arthritis
Authors: Loro Lado Lako , Bjørnland Tore
Published: February 2020

Calcium pyrophosphate dehydrate deposition (CPDD) disease very rarely affects the temporomandibular joint (TMJ). It may resemble synovial chondromatosis, chondrosarcoma, chondroblastoma, or a parotid tumor. Clinical examination, CT, and MRI are important in making the correct diagnosis. Surgical removal of CPDD is necessary with or without excision of the TMJ.
Hierarchical Transition Metal Oxide Arrays Grown on Graphene‐Based Fibers with Enhanced Interface by Thin Layer of Carbon toward Solid‐State Asymmetric Supercapacitors
Authors: Xu Ting , Yang Dongzhi , Liu Yaxin , Zhang Shiyi , Zhang Ming , Zhao Tianyu , Li Xiaofeng , Yu Zhong‐Zhen
Published: February 2020

Carbon‐based asymmetric supercapacitors with high performance hold broad application prospects in wearable devices. Forming a smooth interface between the active transition metal oxides and carbon substrate for providing electron‐transfer channels and accommodating the volume contraction for hybrid electrodes is a key issue to be tackled. Herein, both fibrous cathode and anode are designed on the basis of conductive graphene/carbon nanotube hybrid fibers by introducing pseudocapacitive NiCo2O4 nano‐grass arrays or forming interconnected pores, respectively. For hierarchical positive fibers, a nitrogen‐doped carbon (NC) middle layer is employed to effectively regulate the electronic structural states between NiCo2O4 and fiber substrate. The cycling and rate performance of cathode are significantly improved due to the strong interfacial bonding and abundant electrochemical active sites. Moreover, an interconnected porous structure is also developed to provide both unlimited axial and radial channels to promote electrolyte ion diffusion sufficiently in the porous negative electrode. The assembled solid‐state flexible asymmetric supercapacitor delivers a high energy density of 11.2 μWh cm−2 with a power density of 472.1 μW cm−2, as well as an excellent long cycling performance with 93 % capacitance retention after 10000 cycles.
Synergistic Effect of Molybdenum and Tungsten in Highly Mixed Carbide Nanoparticles as Effective Catalysts in the Hydrogen Evolution Reaction under Alkaline and Acidic Conditions
Authors: Fu Qi , Peng Baoxiang , Masa Justus , Chen Yen‐Ting , Xia Wei , Schuhmann Wolfgang , Muhler Martin
Published: February 2020

Monometallic Mo and W carbides as well as highly mixed (Mo,W) carbides with various Mo/W ratios were synthesized directly on oxygen‐functionalized carbon nanotubes (OCNTs), and used as noble‐metal‐free electrocatalysts in the hydrogen evolution reaction (HER) under both acidic and alkaline conditions. A purely orthorhombic structure was found in both monometallic and mixed carbide samples by X‐ray diffraction. Transmission electron microscopy images showed that the carbide particles were highly dispersed on the OCNTs with well‐controlled particle size. The homogeneous distribution of Mo and W in the carbides was confirmed by elemental mapping. (Mo,W)2C/OCNT with a Mo/W ratio of 3 : 1 showed the lowest overpotential to reach a current density of 10 mA/cm2 (87 mV in 0.1 M KOH and 92 mV in 0.5 M H2SO4), and the smallest Tafel slope of 34 mV/dec. Long‐term stability under both alkaline and acidic conditions was demonstrated for 24 h. Our results revealed that an optimal amount of W in the mixed carbide can significantly improve its performance in the HER following the Tafel reaction pathway, most likely due to the weakened Mo−Hads bond.
Persistent Radical Pairs between N‐Substituted Naphthalimide and Carbanion Exhibit pKa‐Dependent UV/Vis Absorption
Authors: Nie Xiancheng , Su Hao , Chen Xiaoyu , Huang Wenhuan , Huang Linkun , Chen Biao , Miao Hui , Jiang Jun , Wang Tao , Zhang Guoqing
Published: February 2020

A new strategy was devised for estimating and screening pKa values among different carbon acids under ambient conditions by using the UV/Vis absorption spectrum of persistent radical pairs (PRPs), which are generated from an N‐substituted naphthalimide (NNI) derivative in the presence of various carbanions in organic solutions. The electron paramagnetic resonance (EPR) spectroscopy was used to examine the presence of radicals. Unexpectedly, it was discovered that the UV/Vis spectrum of PRPs reveals a distinct linear relationship between the PRP absorption and the pKa value of a corresponding carbon acid, which is likely due to the energy difference among different RPRs. The finding may offer organic chemists an alternative reference to conduct carbanion‐mediated reactions in various organic solutions.
Asymmetric Construction of Alkaloids by Employing a Key ω‐Transaminase Cascade
Authors: Taday Freya , Ryan James , Argent Stephen P. , Caprio Vittorio , Maciá Beatriz , O'Reilly Elaine
Published: February 2020

An ω‐transaminase‐triggered intramolecular aza‐Michael reaction has been employed for the preparation of cyclic β‐enaminones in good yield and excellent enantio‐ and diastereoselectivity, starting from easily accessible prochiral ketoynones and commercially available enzymes. The powerful thermodynamic driving force associated with the spontaneous aza‐Michael reaction effectively displaces the transaminase reaction equilibrium towards product formation, using only two equivalents of isopropylamine. To demonstrate the potential of this methodology, this biocatalytic aza‐Michael step was combined with annulation chemistry, affording unique stereo‐defined fused alkaloid architectures.
Graphen‐Nanoschicht schützt vor Moskitostichen
Authors: Müller Dominik
Published: February 2020

Blutsaugende Insekten wie Moskitos können durch einen Stich gefährliche Krankheiten auf den Menschen übertragen. Dazu zählen Malaria, Gelbfieber oder Denguefieber. Die bisherigen Schutzkonzepte beruhen auf zwei Ansätzen: keine angreifbare Oberfläche anzubieten oder durch chemische Substanzen die Mücken abzuschrecken. Nun prüften Forscher einen anderen Weg, der auf der zweidimensionalen Kohlenstoffmodifikation Graphen basiert.
Cr (VI) adsorption from aqueous solutions on grafted chitosan
Authors: Sanchez Ramirez Diego O. , Periolatto Monica , Carletto Riccardo A. , Varesano Alessio , Vineis Claudia , Tonetti Cinzia , Bongiovanni Roberta
Published: February 2020

Chitosan was grafted on the surface of a cotton gauze (20, 50, and 100 mg chitosan g−1 cotton) to improve its stability in aqueous solutions. The adsorption of hexavalent chromium ions from water on the grafted chitosan was evaluated to determine, by means of linear and nonlinear models, the kinetic and isotherm adsorption of the process. The kinetics of pseudo second‐order, pseudo first‐order, and adsorption isotherms type II were obtained, that is, a monolayer adsorption on nonporous adsorbents with physical adsorption was present. The most probable energy of adsorption corresponded to a physisorption with hydrogen bond interactions between chromium ions and ammonium groups. Moreover, three different cross‐sectional areas of hexavalent chromium ions were calculated and used to estimate the specific surface area employed by active sites to adsorb metal ions in terms of chitosan or cotton mass. Finally, the percentage of the area occupied by chromium ions on the surface was estimated by dividing the resulting specific surface area in terms of cotton mass by the specific surface area of cotton reported in literature. As a result, it was determined that the occupied area is between 6% (for 20 mg chitosan g−1 cotton)‐24% (for 100 mg chitosan g−1 cotton) from the total area of cotton.