bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells
Authors: Lloyd Rebecca L. , Wijnhoven Paul W. G. , Ramos-Montoya Antonio , Wilson Zena , Illuzzi Giuditta , Falenta Katarzyna , Jones Gemma N. , James Neil , Chabbert Christophe D. , Stott Jonathan , Dean Emma , Lau Alan , Young Lucy A.
Published: May 2020

The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is FDA approved for the treatment of BRCA-mutated breast, ovarian and pancreatic cancers. Olaparib inhibits PARP1/2 enzymatic activity and traps PARP1 on DNA at single-strand breaks, leading to replication-induced DNA damage that requires BRCA1/2-dependent homologous recombination repair. Moreover, DNA damage response pathways mediated by the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia mutated and Rad3-related (ATR) kinases are hypothesised to be important survival pathways in response to PARP-inhibitor treatment. Here, we show that olaparib combines synergistically with the ATR-inhibitor AZD6738 (ceralasertib), in vitro, leading to selective cell death in ATM-deficient cells. We observe that 24 h olaparib treatment causes cells to accumulate in G2-M of the cell cycle, however, co-administration with AZD6738 releases the olaparib-treated cells from G2 arrest. Selectively in ATM-knockout cells, we show that combined olaparib/AZD6738 treatment induces more chromosomal aberrations and achieves this at lower concentrations and earlier treatment time-points than either monotherapy. Furthermore, single-agent olaparib efficacy in vitro requires PARP inhibition throughout multiple rounds of replication. Here, we demonstrate in several ATM-deficient cell lines that the olaparib and AZD6738 combination induces cell death within 1–2 cell divisions, suggesting that combined treatment could circumvent the need for prolonged drug exposure. Finally, we demonstrate in vivo combination activity of olaparib and AZD6738 in xenograft and PDX mouse models with complete ATM loss. Collectively, these data provide a mechanistic understanding of combined PARP and ATR inhibition in ATM-deficient models, and support the clinical development of AZD6738 in combination with olaparib.
Sustainable sanitation and gaps in global climate policy and financing
Authors: Dickin Sarah , Bayoumi Moustafa , Giné Ricard , Andersson Kim , Jiménez Alejandro
Published: May 2020

Although sanitation systems are fundamental for human health and sustainable development, limited focus has been placed on their contributions to climate mitigation and adaptation. Climate change threatens existing systems, as well as efforts to increase services for 2.3 billion people who lack even a basic sanitation service. At the same time, the sanitation and wastewater sector directly produces emissions associated with breakdown of organic matter, and treatment processes require large energy inputs. In light of these challenges, we describe gaps in how sanitation is being addressed in mitigation and adaptation, discuss how this results in little inclusion of sanitation in climate policy and financing at the global level, and implications of these gaps for different sanitation systems and geographic regions. Finally, we describe the need for planning frameworks to facilitate integration of climate change into sanitation policy and programming. This will be critical to increasing understanding of sanitation and climate change linkages among stakeholders, and more effectively including sanitation in climate action.
SATB1 as oncogenic driver and potential therapeutic target in head & neck squamous cell carcinoma (HNSCC)
Authors: Panchal Omkar , Wichmann Gunnar , Grenman Reidar , Eckhardt Lisa , Kunz-Schughart Leoni A. , Franke Heike , Dietz Andreas , Aigner Achim
Published: May 2020

The Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer protein that controls gene expression of numerous genes by regulating chromatin architecture and targeting chromatin-remodeling/-modifying enzymes onto specific chromatin regions. SATB1 is overexpressed in various tumors. In head and neck squamous cell carcinoma (HNSCC), SATB1 upregulation is correlated with TNM classification, metastasis, poor prognosis and reduced overall survival. In this paper, we comprehensively analyze cellular and molecular effects of SATB1 in a large set of primary cell lines from primary HNSCC or metastases, using RNAi-mediated knockdownin vitroand, therapeutically, in tumor xenograft mouse modelsin vivo. In a series of 15 cell lines, major differences in SATB1 levels are observed. In various 2-D and 3-D assays, growth inhibition upon efficient siRNA-mediated SATB1 knockdown depends on the cell line rather than initial SATB1 levels. Inhibitory effects are found to be based on cell cycle deceleration, apoptosis induction, decreased HER3 and Heregulin A&B expression, and effects on EMT genes.In vivo, systemic treatment of tumor xenograft-bearing mice with siRNAs formulated in polymeric nanoparticles inhibits tumor growth of two HNSCC xenograft models, resulting from therapeutic SATB1 reduction and concomitant decrease of proliferation and induction of apoptosis. In conclusion, SATB1 represents a promising target in HNSCC, affecting crucial cellular processes and molecular pathways.
Reduced gravity promotes bacterially mediated anoxic hotspots in unsaturated porous media
Authors: Borer Benedict , Jimenez-Martinez Joaquin , Stocker Roman , Or Dani
Published: May 2020

Human endeavours into deep space exploration and the prospects of establishing colonies on nearby planets would invariably involve components of bioregenerative life support for food production, cabin atmosphere renewal, and waste recycling. Growing plants and their microbiomes in porous media under different gravitational fields may present new challenges due to effects of liquid distribution on gaseous exchange with roots and microorganisms. We provide the first direct evidence that capillary driven liquid reconfiguration in porous media under reduced gravity conditions reduces oxygen diffusion pathways and enhances anoxic conditions within bacterial hotspots. Parabolic flight experiments using model porous media inoculated with aerobic and facultative anaerobic bacteria reveal the systematic enhancement of anoxic conditions during the reduced gravity periods in the presence but not in the absence of bacterial activity. The promotion of anoxic conditions under reduced gravity may lead to higher nitrous oxide and methane emissions relative to Earth conditions, on the other hand, anoxic conditions could be beneficial for perchlorate bioremediation of Martian soil. The results highlight changes in soil bacterial microhabitats under reduced gravity and the challenges of managing bioregenerative life support systems in space.
Preservation of global synaptic excitatory to inhibitory ratio during long postmortem intervals
Authors: Scaduto Pietro , Sequeira Adolfo , Vawter Marquis P. , Bunney William , Limon Agenor
Published: May 2020

The study of postsynaptic excitation to inhibition (E/I ratio) imbalances in human brain diseases, is a highly relevant functional measurement poorly investigated due to postmortem degradation of synaptic receptors. We show that near-simultaneous recording of microtransplanted synaptic receptors after simulated morgue conditions allows the determination of the postsynaptic E/I ratio for at least 120 h after death, expanding the availability and use of human diseased tissue stored in brain banks.
Development of type I/II oligodendrocytes regulated by teneurin-4 in the murine spinal cord
Authors: Hayashi Chikako , Suzuki Nobuharu , Takahashi Riko , Akazawa Chihiro
Published: May 2020

In the spinal cord, the axonal tracts with various caliber sizes are myelinated by oligodendrocytes and function as high-velocity ways for motor and sensory nerve signals. In some neurological disorders, such as multiple sclerosis, demyelination of small caliber axons is observed in the spinal cord. While type I/II oligodendrocytes among the four types are known to myelinate small diameter axons, their characteristics including identification of regulating molecules have not been understood yet. Here, we first found that in the wild-type mouse spinal cord, type I/II oligodendrocytes, positive for carbonic anhydrase II (CAII), were located in the corticospinal tract, fasciculus gracilis, and the inside part of ventral funiculus, in which small diameter axons existed. The type I/II oligodendrocytes started to appear between postnatal day (P) 7 and 11. We further analyzed the type I/II oligodendrocytes in the mutant mice, whose small diameter axons were hypomyelinated due to the deficiency of teneurin-4. In the teneurin-4 deficient mice, type I/II oligodendrocytes were significantly reduced, and the onset of the defect was at P11. Our results suggest that CAII-positive type I/II oligodendrocytes myelinate small caliber axons in the spinal cord and teneurin-4 is the responsible molecule for the generation of type I/II oligodendrocytes.
Biomagnetic monitoring combined with support vector machine: a new opportunity for predicting particle-bound-heavy metals
Authors: Dai Qian’ying , Zhou Mengfan , Li Huiming , Qian Xin , Yang Meng , Li Fengying
Published: May 2020

Biomagnetic monitoring includes fast and simple methods to estimate airborne heavy metals. Leaves of Osmanthus fragrans Lour and Ligustrum lucidum Ait were collected simultaneously with PM10 from a mega-city of China during one year. Magnetic properties of leaves and metal concentrations in PM10 were analyzed. Metal concentrations were estimated using leaf magnetic properties and meteorological factors as input variables in support vector machine (SVM) models. The mean concentrations of many metals were highest in winter and lowest in summer. Hazard index for potentially toxic metals was 5.77, a level considered unsafe. The combined carcinogenic risk was higher than precautionary value (10−4). Ferrimagnetic minerals were dominant magnetic minerals in leaves. Principal component analysis indicated iron & steel industry and soil dust were the common sources for many metals and magnetic minerals on leaves. However, the poor simulation results obtained with multiple linear regression confirmed strong nonlinear relationships between metal concentrations and leaf magnetic properties. SVM models including leaf magnetic variables as inputs yielded better simulation results for all elements. Simulations were promising for Ti, Cd and Zn, whereas relatively poor for Ni. Our study demonstrates the feasibility of prediction of airborne heavy metals based on biomagnetic monitoring of tree leaves.
Melanocytic lesion in children and adolescents: an Italian observational study
Authors: Lanna Caterina , Tartaglia Chiara , Caposiena Caro Raffaele Dante , Mazzilli Sara , Ventura Alessandra , Bianchi Luca , Campione Elena , Diluvio Laura
Published: May 2020

Malignant melanoma is a rare neoplasm in the pediatric age group. One of the main risks factors is represented by the presence of a high number of melanocytic nevi. Sun exposure in pediatric age represents a predictor of melanocytic nevi number in the adult age and there is a direct correlation between the presence of melanocytic moles in early childhood and the development of many nevi in adults, suggesting that a high number of nevi in childhood should be considered as a predictor of melanoma development during adult life. The predominance of dermoscopic types of melanocytic nevi varies according to the individual’s age and depends on endogenous or exogenous signaling, suggesting different pathways of nevogenesis. We evaluated the total amount of melanocytic nevi of pediatric patients and their prevalent dermoscopic pattern. We investigated the reasons for dermatological examination, pointing out the role of older parents’ populations in the decision to refer to a dermatological consultant. We performed a prospective observational study on 295 pediatric outpatients consecutively enrolled from July 2018 to July 2019. Descriptive and inferential statistical analyses were performed using logistic and linear regression. 49% of children were characterized by less than 10 nevi, 45% of children by a number of nevi between 10 and 30, whilst 17 patients (5%) had a number of nevi between 30 and 50. The most prevalent dermoscopic pattern was the globular one. An older parenting age was correlated with an autonomous reason for referral and a later first visit. Our data agreed with previous suggestions demonstrating a strong influence of latitude, sun exposure and ethnic background in the development of the number of nevi. To our knowledge, this is the first study, which evaluated the reasons for dermatological examination and the role of older parents’ populations in the decision to refer to a dermatological consultant
Porphyrin functionalized bismuth ferrite for enhanced solar light photocatalysis
Authors: Tudisco C. , Pulvirenti L. , Cool P. , Condorelli G. G.
Published: May 2020

A new organic-inorganic material which combines the BFO photocatalytic properties with peculiar porphyrin absorption was synthesized.
Synthesis of 3D magnetic porous carbon derived from a metal–organic framework for the extraction of clenbuterol and ractopamine from mutton samples
Authors: Zhang Xinyang , Wen Jianan , Lian Lili , Ma Xianhong , Wang Xiyue , Lou Dawei
Published: May 2020

Synthesis of MIL-100(Fe)-derived MPC and its application for the MSPE of CLB and RAC.
Development of AIEgen–montmorillonite nanocomposite powders for computer-assisted visualization of latent fingermarks
Authors: Li Jiawei , Jiao Zhe , Zhang Pengfei , Wan Xuejuan , Song Chao , Guo Zongning , Huang Xuelin , Tang Ben Zhong
Published: May 2020

AIE–active montmorillonite nanocomposite powders (AIE–MMT) were developed for computer-assistant latent fingerprint (LFP) imaging.
A simple and effective strategy to enhance the stability and solid–liquid interfacial interaction of an emulsion by the interfacial dilational rheological properties
Authors: Lei Jinmei , Gao Yuxia , Hou Xu , Sheng Zhizhi , Zhang Chenhui , Du Fengpei
Published: May 2020

Schematic showing the influence of dilational rheological properties on the emulsion stability and solid–liquid interfacial interaction.
3D-conductive pathway written on leather for highly sensitive and durable electronic whisker
Authors: Xie Ruijie , Zhu Jingyu , Wu Haibo , Zhang Kang , Zou Binghua , Zhang Xueyan , Liang Jiayuan , Zheng Bing , Li Sheng , Zhang Weina , Huang Wei , Wu Jiansheng , Huo Fengwei
Published: May 2020

A leather-based e-whisker with 3D conductive pathway was assembled by writing conductive ink on leather. The sensor possessed good durability, and was sensitive enough to detect a height difference of 50 μm, making it capable of surface texture detection, spatial distribution mapping, wind mapping, etc.
Experimental validation of coronagraphic focal-plane wavefront sensing for future segmented space telescopes
Authors: Leboulleux Lucie , Sauvage Jean-François , Soummer Rémi , Fusco Thierry , Pueyo Laurent , Mugnier Laurent M. , Moriarty Christopher , Petrone Peter , Brooks Keira
Published: May 2020

Context. Direct imaging of Earth-like planets from space requires dedicated observatories, combining large segmented apertures with instruments and techniques such as coronagraphs, wavefront sensors, and wavefront control in order to reach the high contrast of 1010 that is required. The complexity of these systems would be increased by the segmentation of the primary mirror, which allows for the larger diameters necessary to image Earth-like planets but also introduces specific patterns in the image due to the pupil shape and segmentation and making high-contrast imaging more challenging. Among these defects, the phasing errors of the primary mirror are a strong limitation to the performance.

Aims. In this paper, we focus on the wavefront sensing of segment phasing errors for a high-contrast system, using the COronagraphic Focal plane wave-Front Estimation for Exoplanet detection (COFFEE) technique.

Methods. We implemented and tested COFFEE on the High-contrast imaging for Complex Aperture Telescopes (HiCAT) testbed, in a configuration without any coronagraph and with a classical Lyot coronagraph, to reconstruct errors applied on a 37 segment mirror. We analysed the quality and limitations of the reconstructions.

Results. We demonstrate that COFFEE is able to estimate correctly the phasing errors of a segmented telescope for piston, tip, and tilt aberrations of typically 100 nm RMS. We also identified the limitations of COFFEE for the reconstruction of low-order wavefront modes, which are highly filtered by the coronagraph. This is illustrated using two focal plane mask sizes on HiCAT. We discuss possible solutions, both in the hardware system and in the COFFEE optimizer, to mitigate these issues.
Further complexities on the pre-reversal vertical drift modeling over the Brazilian region: A comparison between long-term observations and model results
Authors: Sousasantos Jonas , Abdu Mangalathayil Ali , Santos Angela , Batista Inez , Silva André , Loures Luis Eduardo
Published: May 2020

The vertical component of the plasma drift, especially the evening-time pre-reversal drift, constitutes an important aspect of the nighttime electrodynamics of the equatorial ionosphere. Over the years, several studies using measurements and models have been performed to understand the characteristics of this process and its implications for the development of the instabilities leading to the plasma bubble formation and ionospheric scintillation. However, the Brazilian region presents some unique features that bring some difficulties for the vertical drift prognosis, which is required for the scintillation forecasting. These features are mainly related to the geomagnetic field lines topology that presents strong differences when compared to those of other equatorial longitudes. In this work, some of the difficulties for the pre-reversal vertical drift modeling and estimation are discussed; also, a dataset containing long-term observation (2001–2009) is compared with a widely used empirical model. The results show an intrinsic trend of underestimation by the model, which seems to be independent of latitude and seasonality thus suggesting an additional contribution arising from sources other than solely the geomagnetic topology. Also, the results indicate that the deviation can vary in the range of 0–40 m/s and the percentage error enhances with increasing values of pre-reversal vertical drift peak and reduces with increasing F10.7 values, thereby, indicating a clear possibility of meridional winds contribution which is not included in the empirical model used and may account for these differences.
Impact of propofol sedation versus opioid/benzodiazepine sedation on colonoscopy outcomes: a systematic review with meta-analysis
Authors: Aziz Muhammad , Weissman Simcha , Fatima Rawish , Khan Zubair , Mohan Babu P. , Mehta Tej I. , Lee-Smith Wade , Hassan Ammar , Sciarra Michael , Nawras Ali , Adler Douglas G.
Published: May 2020

Background and study aims Choice of sedation (propofol vs opioid/benzodiazepine) has been studied in the literature and has shown variable outcomes. The majority of recent studies have evaluated propofol sedation (PS) versus opioids, benzodiazepines, or a combination of both. We performed a systematic review and meta-analysis of studies comparing PS to other sedation methods to assess the impact on colonoscopy outcomes.

Methods Multiple databases were searched and studies of interest were extracted. Primary outcome of the study was adenoma detection rate (ADR) and secondary outcomes included polyp detection rate (PDR), advanced adenoma detection rate (AADR), and cecal intubation rate (CIR).

Results A total of 11 studies met the inclusion criteria with a total of 177,016 patients (148,753 and 28,263 in the opioids/benzodiazepine group and PS group, respectively). Overall, ADR (RR: 1.07, 95 % CI 0.99–1.15), PDR (RR: 1.01, 95 % CI 0.93–1.10), and AADR (RR: 1.17, 95 % CI 0.92–1.48) did not improve with the use of PS. The CIR was slightly higher for propofol sedation group (RR 1.02, 95 % CI 1.00–1.03).

Conclusion Based on our analysis, PS and opioid/benzodiazepine sedation seem to have comparable ADR. Our results do not favor use of a particular sedation method and the choice of sedation should be individualized based on patient preference, risk factors and resource availability.
Usefulness of endoscopic nasobiliary drainage-guided ERCP in patients with surgically altered anatomy (with video)
Authors: Takano Yuichi , Azami Tetsushi , Niiya Fumitaka , Kobayashi Takahiro , Maruoka Naotaka , Nagahama Masatsugu
Published: May 2020

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is one of the most challenging endoscopic procedures. Although single- or double-balloon endoscopes have been widely used, reaching the papilla of Vater (hepaticojejunostomy/pancreaticojejunostomy site) is often difficult. For patients in whom treatment cannot be completed in a single session, we placed endoscopic nasobiliary drainage (ENBD) at the end of the procedure; in the second session, the scope was inserted following ENBD placement.

Patients and methods Three patients with surgically altered anatomy and who underwent ENBD-guided ERCP were retrospectively examined using the medical records.

Results There were two men and one woman, with an average age of 75 years. The surgical procedure were distal gastrectomy and Roux-en-Y reconstruction in all patients. The diagnosis were choledocholithiasis in two and bile duct stricture in one. Average time to reach the papilla was 50 minutes (range, 21–102) for the first ERCP and was shortened to 11 minutes (range, 5–17) for the second session under an indwelling ENBD. Treatment was successful in all patients without complications.

Conclusion ENBD-guided ERCP in patients with surgically altered anatomy was a useful method that facilitated scope insertion and shortened the procedure time.
Onlinebasierte, qualifizierte Zweitmeinung für Patienten mit kolorektalem Karzinom – eine Pilotstudie der Felix Burda Stiftung in Zusammenarbeit mit dem Netzwerk gegen Darmkrebs
Authors: Berger Ursula , Beckenbauer Udo E. , Rimkus Caroline , Bader Franz G. , Seufferlein Thomas Theodor Werner , Maar Christa
Published: May 2020

Hintergrund Moderne, individualisierte Therapien können das Überleben von Patienten mit kolorektalem Karzinom verbessern. Jedoch werden nicht alle Patienten zur Behandlung in ein zertifiziertes Darmkrebszentrum überwiesen, wo ihre Therapie, unterstützt durch ein Tumorboard, leitliniengerecht durchgeführt wird. Daher wird derzeit die Zweitmeinung bei Krebserkrankungen diskutiert. Diese Studie beschreibt Ergebnisse einer Pilotstudie hinsichtlich der Machbarkeit und des Bedarfs einer strukturierten, onlinebasierten, qualifizierten Zweitmeinung für Patienten mit kolorektalem Karzinom.

Methoden Im Rahmen einer 15-monatigen Pilotphase zwischen 2009 und 2011 konnten Patienten mit kolorektalem Karzinom mittels einer onlinebasierten Elektronischen Patientenakte, unterstützt durch einen Case Manager, kostenfrei eine qualifizierte Zweitmeinung eines Tumorboards einholen. Ihre Zufriedenheit und ihre Lebensqualität (EORCT QLQ-C30) wurden über ein Jahr nachbeobachtet.

Ergebnisse In 95 % der Fälle konnten eine vollständige Elektronische Patientenakte und eine Zweitmeinung erstellt werden. Weniger als die Hälfte der Teilnehmer erhielt die erste Therapieempfehlung aus einer Klinik mit Tumorboard. Die Erstmeinung konnte in 40 % der Fälle durch die Zweitmeinung bestätigt werden, in 33 % zeigte sich ein teilweises, in 27 % ein deutliches Abweichen. Bei Umsetzung der abweichenden Zweitmeinung verbesserte sich die Lebensqualität der Patienten.

Schlussfolgerung Die Erstellung einer onlinebasierten, qualifizierten Zweitmeinung durch ein interdisziplinäres Tumorboard ist technisch und logistisch gut durchführbar. Die onlinebasierte Zweitmeinung könnte zukünftig die Qualität der Behandlung von Patienten mit kolorektalem Karzinom deutlich verbessern und damit ihre Lebensqualität erhöhen.
Neue Klassifikationskriterien des SLE: was helfen sie für die
klinische Diagnose des SLE?
Authors: Aringer Martin , Wiefel Kristin , Leuchten Nicolai
Published: May 2020

Im September 2019 sind die gemeinsamen Klassifikationskriterien der European
League Against Rheumatism (EULAR) und des American College of Rheumatology (ACR)
für den systemischen Lupus erythematodes (SLE) erschienen. Die
EULAR/ACR 2019 Klassifikationskriterien verwenden (jemals) positive
antinukleäre Antikörper (ANA) als obligates Eingangskriterium
und gewichtete Kriterien mit Werten von 2 bis 10 und einem Cut-off von 10. Die
Kriterien sind in 10 Domänen geordnet, innerhalb derer Assoziationen
zwischen verschiedenen Manifestationen bestehen, und nur der höchste
Wert in einer Domäne wird verwendet. Kriterien werden nur gewertet, wenn
es für sie keine andere Erklärung gibt, die wahrscheinlicher ist
als der SLE. Die neuen Kriterien sind statistisch den älteren
Kriteriensets überlegen. Sie gelten aber nur für die
Klassifikation. Für die meisten Rheumatologinnen und Rheumatologen ist
das Stellen der Diagnose eines SLE wesentlich relevanter als der Einschluss in
SLE-Studien, für den die Klassifikationskriterien gedacht sind. Daher
stellt sich die Frage, wie weit die Klassifikationskriterien für die
Diagnose helfen können. Direkt dafür verwendet werden
dürfen sie wirklich nicht. Erfahrene Ärztinnen und Ärzte
sind besser und v. a. sensitiver als die besten Kriterien. Manche
Detailinformationen helfen aber dennoch dabei, die individuelle Diagnose
für konkret Patientinnen und Patienten zu stellen. Die vorliegende
Arbeit erörtert die Neuigkeiten in den EULAR/ACR 2019-Kriterien,
stellt den Unterschied zwischen Klassifikation und Diagnose dar und diskutiert,
welche Informationen auch im klinischen Alltag Anwendung finden
können.
Übung des Monats – Balance Front Hop
Authors: Hacker Volker , Keller Matthias , Kurz Eduard
Published: May 2020

Sprünge sind Grundlage und Voraussetzung für viele sportliche Aktivitäten. Der Körper muss systematisch auf diese Belastungen vorbereitet werden. Entscheidend ist dabei ein hohes Maß an Bewegungsqualität, die sich mit dem Balance Front Hop trainieren lässt.
Molecular Diagnostics in Non-Small Cell Lung Carcinoma
Authors: Sholl Lynette M.
Published: May 2020

Current clinical practice guidelines recognize EGFR, BRAF, ALK, and ROS1 as essential molecular biomarkers, and a host of other genetic alterations as emerging biomarkers for non-small cell lung carcinoma patients. The available approaches to detecting relevant alterations in these genes are diverse and often complementary. Laboratories have increasingly migrated away from a “single-gene test” approach, embracing assays that incorporate panels of genes capable of detecting a diverse set of alterations. The adoption of next generation sequencing (NGS) techniques has driven this shift; however, the approach to incorporation of NGS varies greatly between practices. Choice of molecular diagnostics assay, be it single-gene or NGS-based panel, will be driven by cost, urgency, clinical and laboratory focus, and professional considerations. Preanalytic factors including operator expertise, sample type and choice of fixative, and postanalytic factors including informatics pipeline and approaches to variant reporting have a significant impact on the quality of molecular diagnostics results. There is no real “one-size-fits-all” test for genomic profiling for lung cancer; clinicians and laboratorians must be prepared to offer a diverse set of assays in order to address turnaround time requirements and optimize detection of critical but difficult-to-detect tumor alterations such as gene fusions.
Antepartum Hemorrhage and Outcome of Very Low Birth Weight, Very Preterm Infants: A Population-Based Study
Authors: Klinger Gil , Bromiker Reuben , Zaslavsky-Paltiel Inna , Sokolover Nir , Lerner-Geva Liat , Yogev Yariv , Reichman Brian ,   in collaboration with the Israel Neonatal Network
Published: May 2020

Objective We aimed to determine the independent effect of maternal antepartum hemorrhage (APH) on mortality and major neonatal morbidities among very low birth weight (VLBW), very preterm infants.

Study Design A population-based cohort study of VLBW singleton infants born at 24 to 31 weeks of gestation between 1995 and 2016 was performed. Infants born with the following pregnancy associated complications were excluded: maternal hypertensive disorders, prolonged rupture of membranes, amnionitis, maternal diabetes, and small for gestational age. APH included hemorrhage due to either placenta previa or placental abruption. Univariate and multivariable logistic regression analyses were performed to assess the effect of maternal APH on mortality and major neonatal morbidities.

Results The initial cohort included 33,627 VLBW infants. Following exclusions, the final study population comprised 6,235 infants of whom 2,006 (32.2%) were born following APH and 4,229 (67.8%) without APH. In the APH versus no APH group, there were higher rates of extreme prematurity (24–27 weeks of gestation; 51.6% vs. 45.3%, p < 0.0001), mortality (20.2 vs. 18.5%, p = 0.011), bronchopulmonary dysplasia (BPD, 16.1 vs. 13.0%, p = 0.004) and death or adverse neurologic outcome (37.4 vs. 34.5%, p = 0.03). In the multivariable analyses, APH was associated with significantly increased odds ratio (OR) for BPD in the extremely preterm infants (OR: 1.31, 95% confidence interval: 1.05–1.65). The OR's for mortality, adverse neurological outcomes, and death or adverse neurological outcome were not significantly increased in the APH group.

Conclusion Among singleton, very preterm VLBW infants, maternal APH was associated with increased odds for BPD only in extremely premature infants, but was not associated with excess mortality or adverse neonatal neurological outcomes.

Key Points
Enhanced Recovery after Thoracic Surgery
Authors: Martin Linda W.
Published: May 2020

Enhanced recovery programs (ERPs) aim to reduce psychological and physiological stress related to surgery, and minimize opioid use. This article describes the tenets of enhanced recovery, the guidelines for ERP in lung surgery, and the University of Virginia experience with developing and implementing a program. The impact of these strategies on short-term patient outcomes and potential long-term benefits including influence on lung cancer-specific outcomes are reviewed. The opioid crisis is of utmost importance; this article will explore how ERPs may be a mitigating factor.
Platelets and Immature Neutrophils in Preterm Infants with Feeding Intolerance
Authors: Alhamad Moath M.A. , Kumar Ambuj , Chaaban Hala , Wickline Karen M. , Ho Thao T.B.
Published: May 2020

Objective Feeding intolerance (FI) is a common presentation of necrotizing enterocolitis (NEC) and sepsis. NEC and sepsis are associated with hematological changes, but these changes alone are not reliable biomarkers for early diagnosis. This study examined whether the combination of hematological indices and FI can be used as an early diagnostic tool for NEC or sepsis.

Study Design This retrospective cohort study included infants born at <1,500 g or <30 weeks who had symptoms of FI. The exclusion criteria were congenital or chromosomal disorders, thrombocytopenia or platelet transfusion before the onset of FI, and history of bowel resection. We compared the hematological indices from infants with pathologic FI (due to NEC or sepsis) to infants with benign FI.

Results During the study period, 211 infants developed FI; 185 met the inclusion criteria. Infants with pathologic FI (n = 90, 37 cases with NEC and 53 with sepsis) had lower birth gestational age and weight compared with 95 infants with benign FI (n = 95). Pathologic FI was associated with lower platelet count (median 152 × 103/μL vs. 285 × 103/μL, p < 0.001) and higher immature-to-total neutrophil (I/T) ratio (median 0.23 vs. 0.04, p < 0.001) at the onset of FI. Pathologic FI was also associated with a decrease in baseline platelets compared with an increase in benign FI. For diagnosis of pathologic FI, a decrease ≥10% in platelets from baseline had a sensitivity and specificity of 0.64 and 0.73, respectively, I/T ratio ≥0.1 had a sensitivity and specificity of 0.71 and 0.78, respectively, and the combination of both parameters had a sensitivity and specificity of 0.50 and 0.97, respectively.

Conclusion FI caused by NEC or sepsis was associated with a decrease in platelets from baseline, and a lower platelet level and higher I/T ratio at the onset of FI. These findings can help clinicians in the management of preterm infants with FI.

Key Points
Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up
Authors: Zayek Michael , Parker Kaitlyn , Rydzewska Monika , Rifai Aref , Bhat Ramachandra , Eyal Fabien
Published: May 2020

Objective This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only).

Study Design This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age.

Results Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420–583) versus 547 (473–640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33–2.20).

Conclusion Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants.

Key Points
Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions
Authors: Bajwa Raazi , Madoff David C. , Kishore Sirish A.
Published: May 2020

Primary and secondary liver cancers are a major cause of mortality worldwide. Transarterial liver-directed therapy, or embolotherapy, represents an important locoregional treatment strategy for primary and secondary liver tumors. Embolotherapeutic modalities include bland embolization (transarterial embolization), chemoembolization (transarterial chemoembolization), and radioembolization or selective internal radiotherapy. A brief technical overview of embolotherapeutic modalities as well as supportive evidence for the treatment of most common primary and secondary liver tumors will be discussed in this review. Several potential future applications, including synergy with systemic therapy, interventional theranostics, and artificial intelligence will also be reviewed briefly.
Giant Cell Tumor of Bone: 6 Years Institutional Retrospective Review
Authors: Ali Nadeem , Nabi Dar Ghulam , Shah Azad Ahmad , Kawoosa Altaf Ahmad , Mumtaz Mohammad Umar
Published: May 2020

Introduction Surgery is the cornerstone for the management of giant cell tumors (GCTs). There are no definite guidelines for the management. The purpose of this series was to study the patient demography and results of the surgical intervention for skeletal GCTs in our population.

Materials and Methods All the histologically diagnosed cases of GCT of bone from year 2012 to 2018 were retrospectively analyzed for patient demographics, site, and grade of the lesion, type of biopsy taken (if any), nature of surgical intervention, and final outcome with respect to complications.

Results Seventeen cases of skeletal GCT were diagnosed on histopathology. The mean age at presentation was 31.5 ± 10.9 years with females affected 1.4 times more. Proximal tibia was the most common site (29.4%) followed by distal radius and distal femur in that order. About 58.8% of the lesions were of Campanacci grade 2 and remaining were grade 3 lesions. Ten patients had extended curettage, five had en bloc resection, and one had amputation as the primary treatment. Twenty percent patients (n = 3) had local recurrence of the pathology and one patient developed distant recurrence (lung metastasis).

Conclusion Proximal tibia followed by distal radius was the most common site of GCT in our population. The tumor behavior and recurrence cannot be predicted with any grading system. The goal should be salvage of the joint by intralesional curettage, with resection reserved for distal radius GCTs, cases with extensive soft tissue extension or those with destruction of the articular cartilage and joint involvement.
Sealed culture system for supporting mouse preimplantation embryo development in vitro
Authors: Liu Jie , Wang Zhao , Gao Zhen , Zhang Hui , Gu Jianfeng , Zhao Xiaoe , Wei Qiang , Ma Baohua
Published: May 2020

This study investigated the possibility of a sealed culture system in polymerase chain reaction (PCR) tubes to maintain embryo development. The embryo density that could support the development of 2-cell stage mouse embryos to the hatching stage was determined. At an embryo density of 1:2 (100 embryos cultured in 200μL CZB medium that had been pretreated with a reference gas containing 5% O2), the developmental rate was higher and fewer embryos exhibited reactive oxygen species- or hypoxia-induced injury compared with other sealed culture groups. Expression of growth factors (insulin-like growth factor (IGF) 1, IGF2, epidermal growth factor and transforming growth factor-α) and their receptors was evaluated, with similar expression patterns seen for embryos in sealed culture (5% O2, embryo density of 1:2) compared with the control group (embryos cultured in microdrops and placed in a 37°C, 5% CO2 water-jacketed incubator; P>0.05). After transfer of blastocysts generated by the sealed culture into recipients, there were no obvious differences in the rate of normal live pups births between the sealed culture and control groups (P>0.05). Thus, the sealed embryo culture system in PCR tubes is feasible for use in situations which cannot use a traditional incubator, such as in space and during the transport of embryos.
Language ideological debates about linguistic landscapes
Authors: Vessey Rachelle , Sheyholislami Jaffer
Published: May 2020

In 2013, Richmond city council was presented with a petition calling for the regulation of all language signs, drawing national attention to the amount of Chinese-only signage. The signage debate has become well-known in Canada as a result of the media, which has provided a platform for debate through online reader commentary. By applying concepts from linguistic landscapes, language ideologies and nationalism in addition to analytical tools from SFL, we employ critical discourse studies to examine how representations of and responses to language signage in online news commentary contribute to the construction of in-groups and out-groups in the Canadian context. Findings show that stereotypical representations of ethnicity and culture are represented as a threat to the Canadian status quo. Also, contradictory ideologies of Canadian official bilingualism are employed to justify discrimination against Chinese language speakers. Findings suggest that language ideologies remain deeply tied to understandings of Canadian nationhood and belonging.
Degenerate antiferromagnetic states in spinel oxide LiV2O4*
Authors: Gong Ben-Chao , Yang Huan-Cheng , Jin Kui , Liu Kai , Lu Zhong-Yi
Published: May 2020

The magnetic and electronic properties of spinel oxide LiV2O4 have been systematically studied by using the spin-polarized first-principles electronic structure calculations. We find that a series of magnetic states, in which the ferromagnetic (FM) V4 tetrahedra are linked together through the corner-sharing antiferromagnetic (AFM) V4 tetrahedra, possess degenerate energies lower than those of other spin configurations. The large number of these energetically degenerated states being the magnetic ground state give rise to strong magnetic frustration as well as large magnetic entropy in LiV2O4. The corresponding band structure and density of states of such a typical magnetic state in this series, i.e., the ditetrahedron (DT) AFM state, demonstrate that LiV2O4 is in the vicinity of a metal–insulator transition. Further analysis suggests that the t2g and eg orbitals of the V atoms play different roles in the magnetic exchange interactions. Our calculations are consistent with previous experimental measurements and shed light on understanding the exotic magnetism and the heavy-fermion behavior of LiV2O4.
Role of potential on high-order harmonic generation from atoms irradiated by bichromatic counter-rotating circularly polarized laser fields*
Authors: Shen Xu-Xu , Wang Jun , Guo Fu-Ming , Chen Ji-Gen , Yang Yun-Jun
Published: May 2020

We investigate high-order harmonic generation from atoms irradiated by bichromatic counter-rotating circularly polarized laser pulses by numerically solving the time-dependent Schrödinger equation. It is found that the minimum energy position of the harmonic spectrum and the non-integer order optical radiation are greatly discrepant for different atomic potentials. By analyzing the quantum trajectory of the harmonic emission, discrepancies among the harmonic spectra from different potentials can be attributed to the action of the potential on the ionized electrons. In addition, based on the influence of the driving light intensity on the overall intensity and ellipticity of higher order harmonics, the physical conditions for generating a high-intensity circularly polarized harmonic can be obtained.
Learning the properties of Buton asphalt as an oil shale in Buton island to expand the knowledge of students about physics
Authors: Zainuddin E S , Hendrajaya L
Published: May 2020

Asphalt in Buton Island, Southeast Sulawesi, Indonesia, has a large reserve amount of around 650 million tons. In Buton, asphalt is only used for road construction, but this asphalt has characteristics that can be utilized as a substance to produce crude oil. The purposes of this research are to increase or expand the knowledge of educated participants about the characteristics and advantages of Buton asphalt and oil shale as community natural resources and to compare the density of each asphalt mining area namely Kabungka (winto mine), Lawele, and Sampolawa. It aims is to make Buton asphalt as a source of learning. The research method used is the literature study and experiment. The results of the study are that the characteristics of asphalt Buton approach the characteristics of oil shale in Green River, US. The density of Buton asphalt in each region is different. Conclusion of the research that asphalt/tar sand on Buton Island is categorized as a solid/semi-solid type hydrocarbon oil shale. The implementation of this study can be used for senior high school of class X student by visiting the asphalt mine to conduct simple experiments such as measuring the height of the asphalt cliff and determining the direction of the wind eye. Asphalt is used to measure its density. The experiment procedure is made in a module that will later be used by students.
Construction and testing of decision-problem solving skills test instruments related basic physics content
Authors: Yusal Y , Suhandi A , Setiawan W , Kaniawati I
Published: May 2020

The aim of this study is to produce test instrument items decision-problem solving skills related to the content of Heat Transfer. The construction of the test instrument has been done using scaffolding which includes stages: description of indicator of decision-problem solving skills, operationalization of indicators, construction of items scenarios, writing of test items, validation of test items, and test of reliability. Validation of test items has been done by five experts namely three education evaluation experts and two physics experts. Test of reliability was carried out by involving 35 students of physics education program at one of the universities in South Sulawesi province. The construction process of the test instrument produced two items of test decision problem solving skills related to the concept of conduction and heat radiation. The results of expert validation of the decision-problem solving test items stated that the constructed items had high validity, and the results of the test reliability showed that the constructed test instruments had a high degree of consistency permanence. These results indicate that the product of decision-problem solving test instrument is worthy of being used for measuring decision-problem solving skills for students of Physics education programs who contract Basic Physics courses.
Improving the mental model of high school students related to the concept of global warming through the implementation of the context based learning (CBL) model combined with the CM2RA strategy
Authors: Ulum A S , Basori H , Suhandi A , Samsudin A
Published: May 2020

The aim of this study was to improve the mental model of high school students related to the concept of global warming through the application of the CBL model using the CM2RA strategy (context, microscopic models, macroscopic phenomena, and analogy representation). The mental model categories reviewed include scientific, synthetic and initial mental models. This mental model category is determined based on the test results data level of conceptual understanding. A pre-experiment method with one group pretest-posttest design was used in this research. The number of research subjects was 40 students consisting of 24 female students and 16 male students, in one of the high schools in the Tasikmalaya district of West Java province. The instrument used to collect data is a test of understanding the concept of global warming in the form of essays covering three parts of the question. The results showed that before the application of CBL, the number of students in each mental model category was: scientific mental model (5%), synthetic (40%), and initial (55%), whereas after the application of CBL, the number of students in each category of mental models becomes: scientific mental model (78%), synthetic (15%), and initial (7%). These results indicate that the implementation of CBL with CM2RA strategies has high effectiveness in facilitating the achievement of the scientific mental model.
PhET simulation software-based learning to improve science process skills
Authors: Haryadi R , Pujiastuti H
Published: May 2020

The purpose of this study is to find out the results of the application of media PhET Simulation in physics learning in matter of temperature and heat. The research design used was a randomized design control group pre-test post-test. The study population was all 11th grade students of SMA Y Serang which numbered five classes. The research sample consisted of one experimental class and one control class. The results showed that the application of physics learning using media PhET simulation on temperature and heat material produced a 37% higher N-gain value than the control class using direct learning. It can be concluded that PhET simulation software-based learning is interactive learning in physics learning and can improve students’ science process skills.
The exploration of character education contents in the physics textbooks about newton’s law
Authors: Dewi T S , Suresman E , Ramalis T R
Published: May 2020

Character education is recommended to be integrated into all school subjects as an effort to solve the problem of moral degradation among the Indonesian students. Therefore, this study aims to explore the character education contents in the physics textbooks used by the teachers in the learning process. The findings demonstrated that there were 14 character values contained in the textbooks, which have had recommendations from the Ministry of National Education of Indonesia as the feasible learning sources.