bluuebunny/crossref_metadata_2025 huggingface dataset:
Persévérance aux études et processus général d’acculturation d’étudiants résidents permanents inscrits dans des universités québécoises : les défis d’intégration et d’adaptation
Authors: Kanouté Fasal , Darchinian Fahimeh , Guennouni Hassani Rajae , Bouchamma Yamina , Mainich Sarah , Norbert Gwendoline
Published: December 2020

La recherche dont il est question dans cet article s’intéresse à la persévérance aux études ainsi qu’au processus général d’acculturation d’étudiants résidents permanents inscrits dans six établissements d’enseignement supérieur au Québec. L’étude présentée a permis de documenter les défis d’intégration et d’adaptation à la société et à l’université auxquels sont confrontés ces étudiants. La problématisation aborde le manque de valorisation du capital humain de certains d’entre eux à leur arrivée au Québec, ce qui justifie en partie leur choix de s’inscrire à l’université pour se (re)qualifier. Une conceptualisation de l’expérience des étudiants résidents permanents, par le biais des concepts de persévérance aux études et d’acculturation, permet de comprendre la nature des défis rencontrés, le stress qu’ils génèrent et leur impact sur le cheminement universitaire des étudiants. À partir de données qualitatives issues de réponses à des questions ouvertes d’un questionnaire en ligne complété par près de 1000 étudiants résidents permanents, l’article met à jour des défis relatifs à l’insertion professionnelle, l’intégration sociale, la conciliation famille-études-travail, le décodage de la culture et des pratiques universitaires, ainsi que la perception de pratiques discriminatoires. Finalement, des pistes d’action sont présentées, interpelant la société en général, les établissements d’enseignement supérieur et la proactivité des étudiants eux-mêmes.
Dommage collatéral ou condition nécessaire à la colonisation ? Les épidémies et leur impact sur les Premières Nations dans les manuels d’histoire du Québec
Authors: Bories-Sawala Helga Elisabeth
Published: December 2020

La présente contribution propose de retracer la représentation du choc microbien dans les manuels scolaires des différents programmes d’histoire nationale au Québec du secondaire (Histoire du Québec et du Canada, 1982-2006 ; Histoire et éducation à la citoyenneté, 2006-2017 ; Histoire du Québec et du Canada, depuis 2017) ainsi que dans deux manuels autochtones. Tout compte fait, seul un manuel cri accède à une pleine compréhension de l’impact historique crucial du choc microbien.
Underwater ranging with intensity modulated 532 nm laser source
Authors: Li Kun , Yang Su-Hui , Liao Ying-Qi , Lin Xue-Tong , Wang Xin , Zhang Jin-Ying , Li Zhuo ,   School of Optics and Photonics, Beijing Institute of Technology, Beijing 100081, China,   Beijing Key Laboratory for Precision Optoelectronics Measurement Instrument and Technology, Beijing 100081, China,   Kunming Institute of Physics, Kunming 650223, China
Published: December 2020

Laser underwater detection has important applications in underwater target search, resource exploration, and other fields. The absorption and scattering of light by water are a big challenge to underwater detection. Absorption causes the laser signal to attenuate, thus limiting the detection distance. Scattering causes not only attenuation but also noise, the strong scattering noise can even submerge the target information. To reduce the absorption, the blue-green light band in the transmission window of water is chosen for lidar. Optically carried microwave radar (OCMR) has the advantages of resistance to turbulence and scattering. The intensity of the detection beam is modulated at radio frequency. The photons reflected by the target retain the intensity modulation information, while interference phase-out is generated between photons scattered by particles suspending in turbid water at different distances, resulting in the average of high-frequency modulation signals. The signal-to-noise ratio is improved when the received signal by the detector is correlated with the modulation signal.

High-power broadband intensity modulated light source is the key to achieving the long-distance, high-precision underwater ranging with the carrier modulation method. However, the carrier modulation technology for underwater detection is limited by the development of light source. The maximum power of intensity modulation green light used in underwater detection is on the order of hundreds of milliwatts, the receiver needs to adopt a photomultiplier tube (PMT).

In this paper, a laser underwater detection system is built with a 3-m-long water tank by using a home-made 532 nm light source. The maximum output power of the intensity-modulated 532 nm laser is 2.56 W. The modulation frequency is turned from 10 MHz to 2.1 GHz. Water with different attenuation coefficients is obtained by adding Mg(OH)2 into the water tank. When the maximum modulation frequency is 500 MHz by phase ranging, 4.3 attenuation lengths(a.l.) are measured. The ranging error is about 12 cm. In the future study, a PMT will be used as the detector to increase the range resolution. We will also increase the bandwidth of the signal processing unit in order to take full advantage of the broadband intensity to modulate light source.
Electrocardiogram Signal Denoising by Hilbert Transform and Synchronous Detection
Authors:   LASS Laboratory, Electronics Departement, Faculty of Technology, University of M’sila, Algeria, Assam Ouali Mohammed , Tinouna Asma , Ghanai Mouna , Chafaa Kheireddine
Published: December 2020

An efficient method for Electrocardiogram (ECG) signal denoising based on synchronous detection and Hilbert transform techniques is presented. The goal of the method is to decompose a noisy ECG signal into two components classified according to their energy: (1) component with high energy representing the dominant component which is the clean ECG signal, and (2) component with low energy representing the sub-dominant component which is the contaminant noise. The investigated approach is validated through out some experimentations on MIT-BIH ECG database. Experimental results show that random noises can be effectively suppressed from ECG signals.
A Smart Laparoscopic Instrument with Different Applications
Authors:   Institute of Robotics, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria, Ivanova Veronika , Batchvarov Ditchko ,   Institute of Information and Communication Technologies, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria, Boneva Ani ,   Institute of Information and Communication Technologies, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Published: December 2020

The main target of everyone engineering work associated with minimally-invasive surgery is to provide adequate tool-tissue force information to the surgeons so that they can regain the sense of touch that has been lost through laparoscopic surgery. In this context the main objective of the work design novel family laparoscopic tools with better technical characteristics, and incorporation of force and other sensors and elements in construction of tools for restore sense of touch in the process of laparoscopy. Thus it is improving some technical side of this laparoscopic instruments. In contrast to daVinchi robots by Intuitive Surgical Incorporation which instruments are designed for manipulation and imaging we offer family tools with additional functions such as diagnosis and therapeutics tasks. Therefore we decide two main problems: i) we designed and produced an original construction of an adequate experimental module for robots, where was incorporated two force sensors to provide tool-tissue information (some of which was described and discussed at previous works); and ii) we realized hardware and program resources for control and monitoring of this module which is the object of this work. The computer program includes information about various measurements of the tip tool – surface contact interactions and data obtained from the experimental module that is used to find the difference between date from previous measuring and received information in real time. Another signification advantage of the proposed program solution is the graphical visualization of the measuring and comparing the results. Therefore, the surgeon can give the adequate command to force interaction between the instrument and tissue. For verification of the functionality and working capacity of the experimental module with force feedback capabilities for robots were conducted different experiments with the designed control system.
N-Terminal Pro Brain Natriuretic Peptide in Assessment of Severity of Coronary Artery Disease in Patients with Non ST Elevation Acute Coronary Syndrome
Authors: Ashmawy Hesham Mohammed El , Sadaka Mohammed Ahmed , Youssef Gehan Magdy , Hassan Abdulkarem Saeed
Published: December 2020

Introduction: N-Terminal pro Brain Natriuretic Peptide (NT-pro BNP) is an important biomarker in the management of patients with heart failure. Several studies reported its importance as a predictor of morbidity and mortality in Acute Coronary Syndrome (ACS) patients. Aim: To compare serum NT-proBNP levels in Non ST Elevation Acute Coronary Syndrome (NSTE-ACS) patients and controls and to assess the relation between Nt-proBNP and the severity of Coronary Artery Disease (CAD) in patients with NSTE-ACS including unstable Angina (UA) and Non ST Elevation Myocardial Infarction (NSTEMI). Materials and Methods: Sixty NSTE-ACS patients and 20 matched control without significant obstructive CAD were included in the study. Cardiac enzymes, blood urea, serum creatinine, serum NT-proBNP were measured in all patients immediately before coronary angiography. Gensini score and Syntax score were calculated for all study patients. The NSTE-ACS patients were followed-up for six months for Major Adverse Cardiovascular Events (MACE) including mortality, myocardial infarction, heart failure, stroke, revascularisation by primary percutaneous coronary intervention or Coronary Artery Bypass Grafting (CABG). Results: The mean serum NT-proBNP in NSTE-ACS (UA and NSTEMI) patients was significantly higher (662.7±635.2) pg/mL than that in the control (102.3±96.4) pg/mL, p<0.001. The effective cut-off value for the diagnosis of CAD was 139 pg/mL, Area Under Curve (AUC)=0.950, 95% CI: 0.890-1.00). The serum NT-proBNP was correlated with the severity and complexity of CAD as measured by Gensini score (r=0.496, p<0.001) and Syntax score (r=0.443, p<0.001). The mean value of NT-proBNP in patients with six months MACE was insignificantly higher than in patients without six months MACE with Interquartile Range (IQR) of 418.5 (139-2037) vs. 366 (175-3237) pg/mL, p=0.970. Conclusion: NT-proBNP was correlated with the severity and complexity of CAD in NSTE-ACS with preserved left ventricular systolic function, but it has no impact on six months MACE.
Association of work-time control with sickness absence due to musculoskeletal and mental disorders: An occupational cohort study
Authors: Albrecht Sophie Charlotte , Leineweber Constanze , Ojajärvi Anneli , Oksanen Tuula , Kecklund Goran , Härmä Mikko
Published: December 2020

Objectives

Work-time control is associated with lower sickness absence rates, but it remains unclear whether this association differs by type of diagnosis and sub-dimension of work-time control (control over daily hours and control over time off) and whether certain vulnerable groups benefit more from higher levels of work-time control.

Methods

Survey data from the Finnish 10-town study in 2004 were used to examine if baseline levels of work-time control were associated with register data on diagnose-specific sickness absence for 7 consecutive years (n = 22 599). Cox proportional hazard models were conducted, adjusted for age, sex, education, occupational status, shift work including nights, and physical/mental workload.

Results

During follow-up, 2,818 individuals were on sick leave (≥10 days) due to musculoskeletal disorders and 1724 due to mental disorders. Employees with high (HR = 0.80, 95% CI 0.74-0.87; HR = 0.76, 95% CI 0.70-0.82, respectively) and moderate (HR = 0.83, 95% CI 0.77-0.90; HR = 0.85, 95% CI 0.79-0.91, respectively) levels of control over daily hours/control over time off had a decreased risk of sickness absence due to musculoskeletal disorders. Sub-group analyses revealed that especially workers who were older benefitted the most from higher levels of work-time control. Neither sub-dimension of work-time control was related to sickness absence due to mental disorders.

Conclusions

Over a 7-year period of follow-up, high and moderate levels of work-time control were related to lower rates of sickness absence due to musculoskeletal disorders, but not due to mental disorders.
Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist
Authors: Kishimoto Takumi , Fujimoto Nobukazu , Mizuhashi Keiichi , Kozawa Satoko , Miura Motohiko
Published: December 2020

Objectives

In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process.

Method

Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE.

Results

Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3 months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE.

Conclusion

We consider that six items described above are suitable for diagnosing BAPE.
Single‐molecule studies of conformational states and dynamics in the ABC importer OpuA
Authors: Tassis Konstantinos , Vietrov Ruslan , de Koning Matthijs , de Boer Marijn , Gouridis Giorgos , Cordes Thorben
Published: December 2020

The current model of active transport via ABC importers is mostly based on structural, biochemical and genetic data. We here establish single‐molecule Förster resonance energy transfer (smFRET) assays to monitor the conformational states and heterogeneity of the osmoregulatory type I ABC importer OpuA from Lactococcus lactis. We present data probing both intradomain distances that elucidate conformational changes within the substrate‐binding domain (SBD) OpuAC, and interdomain distances between SBDs or transmembrane domains. Using this methodology, we studied ligand‐binding mechanisms, as well as ATP and glycine betaine dependences of conformational changes. Our work expands the scope of smFRET investigations towards a class of so far unstudied ABC importers, and paves the way for a full understanding of their transport cycle in the future.
Design and Synthesis of 5‐Aryl‐substituted Phenylpyrimidine‐2,4‐diamine Derivatives as Novel Mer and Tyro3 Kinase Inhibitors
Authors: Kim Yeonji , Lee Kyung Won , Yeom Hyesu , Kim Miok , Lee Yeon Kyung , Lee Joo‐Youn , Hwang Jong Yeon , Min Youngki , Ryu Do Hyun , Lee Chang Hoon , Cho Sung Yun
Published: December 2020

5‐Aryl‐substituted (piperdin‐4‐yl)pyrimidine‐2,4‐diamine derivatives were synthesized and their inhibitory activities were evaluated against TAM kinase (Tyro3, Axl, Mer), respectively. Detailed SAR studies on the fifth position of pyrimidine could lead to the discovery of potent and selective TAM kinase inhibitor. Compounds 6f, 7b, and 7f exhibited potent inhibitory activity and excellent selectivity toward Axl, Tyro3 and Mer kinases. Molecular docking studies corroborated that slight changes of substituents induced dramatic structural change of Met596, 623, 674 backbone carbonyl and amide in the hinge region of Axl, Tyro3, Mer, and resulted in different binding poses of 6f, 7b, and 7f, respectively. It was identified as a strong possibility to control selectivity by structural modification of phenyl substituents of pyrimidine as a new class of TAM kinase inhibitors.
Impact of screening and follow‐up colonoscopy adenoma sensitivity on colorectal cancer screening outcomes in the CRC‐AIM microsimulation model
Authors: Fisher Deborah A. , Saoud Leila , Hassmiller Lich Kristen , Fendrick A. Mark , Ozbay A. Burak , Borah Bijan J. , Matney Michael , Parton Marcus , Limburg Paul J.
Published: December 2020

Background

Real‐world data for patients with positive colorectal cancer (CRC) screening stool‐tests demonstrate that adenoma detection rates are lower when endoscopists are blinded to the stool‐test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow‐up to a known positive stool‐based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow‐up colonoscopies after positive stool‐tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC‐AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow‐up/surveillance colonoscopies.

Methods

Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt‐sDNA), or annual fecal immunochemical test (FIT) from 50 to 75 years. Outcomes were reported per 1000 individuals without diagnosed CRC at age 40. Base‐case adenoma sensitivity values were identical for screening and follow‐up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios.

Results

As the differences in adenoma sensitivity for screening versus follow‐up/surveillance colonoscopies became greater, life‐years gained (LYG) and reductions in CRC‐related incidence and mortality versus no screening increased for mt‐sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached >90% with FIT in the base‐case scenario and with mt‐sDNA in a “medium impact” scenario.

Conclusions

Assuming identical adenoma sensitivities for screening and follow‐up/surveillance colonoscopies underestimate the potential benefits of stool‐based screening strategies.
Analyzing non‐cancer causes of death of colorectal carcinoma patients in the US population for the years 2000–2016
Authors: Lu Lili , Ma Li , Zhang Xianbin , Susanne Mullins Christina , Linnebacher Michael
Published: December 2020

Background

Colorectal cancer (CRC) treatment and patient survival improved greatly. Consequently an increased incidence of non‐cancer‐related deaths is observed. This study analyzed the causes of non‐cancer death for people suffering from CRC based on the year of diagnosis, follow‐up time, and patient's age.

Methods

The data from patients diagnosed with CRC in the years 2000–2016 were taken from the Surveillance, Epidemiology, and End Results 18 database. Patients were categorized according to: death from CRC, non‐CRC cancer, and non‐cancer. Constituent ratios and standardized mortality ratios (SMRs) were calculated to describe the death causes distribution and relative death risks.

Results

Between 2000 and 2016, a stable and rapid drop for the original diagnosis as death cause for CRC patients was observed (70.19% to 49.35%). This was coupled to an increase in non‐cancer‐associated death reasons (23.38% to 40.00%). The most common non‐cancer death cause was heart disease, especially for elderly patients. However, deaths from accidents and adverse effects were frequent in younger CRC patients. Patients died from septicemia more often within the first follow‐up year; however, a 6‐fold increase in death from Alzheimer's disease was found for after at least 180 months follow‐up time.

The SMRs of all 25 non‐cancer death causes initially decreased in all CRC subgroups, followed by an increase with follow‐up times. Gradually decreasing SMR values were observed with increasing age of CRC patients.

Conclusions

These findings could help modify and sharpen preventive measures and clinical management and raise physician's awareness to potential non‐CRC death risk factors for CRC patients.
A huge right ventricular hydatid cyst related to tricuspid valve causing severe pulmonary hypertension
Authors: Bakr Lubna , Alnajar Somar
Published: December 2020

Preserving tricuspid valve's function is the cornerstone in surgical excision of cardiac hydatid cysts present in the right side of the heart. The perfect surgical technique may not exist. However, further studies are needed to ensure the clear path.
Axo‐axonic synapses: Diversity in neural circuit function
Authors: Cover Kara K. , Mathur Brian N.
Published: December 2020

The chemical synapse is the principal form of contact between neurons of the central nervous system. These synapses are typically configured as presynaptic axon terminations onto postsynaptic dendrites or somata, giving rise to axo‐dendritic and axo‐somatic synapses, respectively. Beyond these common synapse configurations are less‐studied, non‐canonical synapse types that are prevalent throughout the brain and significantly contribute to neural circuit function. Among these are the axo‐axonic synapses, which consist of an axon terminating on another axon or axon terminal. Here, we review evidence for axo‐axonic synapse contributions to neural signaling in the mammalian nervous system and survey functional neural circuit motifs enabled by these synapses. We also detail how recent advances in microscopy, transgenics, and biological sensors may be used to identify and functionally assay axo‐axonic synapses.
Experts, expertise and health and physical education teaching: A scoping review of conceptualisations
Authors: Williams Benjamin , Lee Jessica
Published: December 2020

Concerns about the supply of, and demand for, experts and expertise are prominent in research on outsourcing in health and physical education (HPE), and the state of the subject more broadly. Yet, precisely what is meant by ‘expert’ and ‘expertise’ in this scholarship is not always clear or uncontested. In this research, we used a scoping review framework to examine how scholarly research has conceptualised experts and expertise in the context of HPE teaching. We enhanced this framework by analysing the ways these conceptualisations have, and have not, attended to the relationality, materiality and performativity of either concept. Following searching and screening processes, 72 articles were included in the review. Eighteen articles provided definitions or detailed descriptions of what an expert or expertise was taken to be in the context of HPE teaching, four of which were commonly cited across the sample. Three ontologies of experts and/or expertise were evident within these definitions/descriptions: psychological, social and network. These ontologies and the conceptualisations based upon them exhibited varying sensitivity to relationality, materiality and performativity. To better register the complexities of HPE teaching in contemporary contexts, we encourage researchers to become more attuned to these dimensions of experts and expertise, and advocate a material‐semiotic approach to doing so.
Effects of energy supplements on the differentiation of skeletal muscle satellite cells
Authors: Su Rina , Wang Bohui , Zhang Min , Luo Yulong , Wang Debao , Zhao Lihua , Su Lin , Duan Yan , Faucitano Luigi , Jin Ye
Published: December 2020

To investigate the effects of the activator of AMPK and high glucose on the differentiation of mouse SMSCs, primary SMSCs were isolated from mouse extensor digitorum longus muscle and grown to near confluence (80%). Postconfluent cells were cultured in a growth medium with different inductors: AICAR, glucose, and AICAR mixed with glucose. The specific protein expressions of SMSCs, myoblasts, adipocytes, and brown adipocytes were analyzed on days 0, 3, 5, 7, and 10. The results showed treatment with AICAR in SMSCs markedly activated AMPK phosphorylation (p < .05) and increased protein expression of Pax7 and MyoD (p < .05), high concentrations of intracellular glucose upregulated UCP‐1 protein expression and enhanced lipid accumulation (p < .05), the cowork of AICAR and glucose affected a decrease on MyoD, PPARg, and UCP‐1 expression (p < .05) and an increase on Pax7. The present study indicated that the certain energy supplements influence the direction of SMSC differentiation which may contribution on the structure of muscle and meat quality, sequentially.
Differential Binding of Sarilumab and Tocilizumab to IL‐6Rα and Effects of Receptor Occupancy on Clinical Parameters
Authors: Xu Christine , Rafique Ashique , Potocky Terra , Paccaly Anne , Nolain Patrick , Lu Qiang , Iglesias‐Rodriguez Melitza , St John Gregory , Nivens Michael C. , Kanamaluru Vanaja , Fairhurst Jeanette , Ishii Tomonori , Maldonado Rafael , Choy Ernest , Emery Paul
Published: December 2020

We evaluated interleukin‐6 (IL‐6) receptor‐α subunit (IL‐6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL‐6Rα receptor occupancy (RO) and C‐reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL‐6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL‐6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28‐joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL‐6Rα in vitro with 15‐ to 22‐fold higher affinity than tocilizumab, and inhibits IL‐6–mediated classical and trans signaling via membrane‐bound and soluble IL‐6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady‐state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28‐joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL‐6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.
The antibacterial and antiproliferative ability of kānuka, Kunzea ericoides, leaf extracts obtained by subcritical water extraction
Authors: Essien Sinemobong O , Young Brent , Baroutian Saeid
Published: December 2020

BACKGROUND

Subcritical water kānuka leaf extracts contain high levels of polyphenols. However, whether these extracts can serve as natural antimicrobial and chemopreventive agents is still a question. This study aimed to evaluate the antibacterial and antiproliferative efficacy of SWE kanuka leaf extracts. Subcritical water extraction (SWE) was used to obtain natural extracts from kānuka leaves potentially rich in biologically active compounds. The antibacterial and antiproliferative capacities were assessed by broth microdilution assay and MTT‐assay, respectively. The assessed properties were compared to extraction from ethanol extraction (EE).

Results

The screening results for antibacterial properties demonstrated that subcritical water kānuka leaf extracts were active against Escherichia coli (minimum conc. 0.8 mg/mL) and Staphylococcus aureus (minimum conc. 3.8 mg/mL). These extracts also exerted dose‐dependent antiproliferative effects on the viability of cancerous human cervical cell lines (Hep‐2 and RD cells) and mouse cell lines (L cells). The extraction temperature had significantly affected the extract's activities by enhancing neoformed compounds with beneficial effects.

CONCLUSIONS

Subcritical water extracts of kānuka demonstrated a better efficacy against bacterial growth and malignant cells viability in comparison to extracts obtained using conventional ethanol extraction. This SWE kānuka leaf product could be used in a range of applications where antimicrobial and antiproliferative properties are required. Further studies are needed to examine the mechanism and markers of these properties. © 2020 Society of Chemical Industry
BPDCN: When polychemotherapy does not compromise allogeneic CD123 CAR‐T cell cytotoxicity
Authors: Poussard Margaux , Philippe Laure , Fredon Maxime , Bôle‐Richard Elodie , Biichle Sabeha , Renosi Florian , Perrin Sophie , Kroemer Marie , Limat Samuel , Bonnefoy Francis , Daguindau Etienne , Deconinck Eric , Gruson Bérengère , Saas Philippe , Adotévi Olivier , Garnache‐Ottou Francine , Angelot‐Delettre Fanny
Published: December 2020

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poor prognosis and no treatment consensus. Combining chemotherapy and immunotherapy is a promising strategy to enhance therapeutic effect. Before combining these therapies, the influence of one on the other has to be explored. We set up a model to test the combination of polychemotherapy ‐ named methotrexate, idarubicine, dexamethasone, and L‐asparaginase (MIDA) ‐ and CD123 CAR‐T cell therapy. We showed that CD123 CAR‐T cells exert the same effect on BPDCN models alone, or after MIDA regimen. These data support a preclinical rationale to use immunotherapy after a treatment with polychemotherapy for BPDCN patients.
Enzymatic diagnosis of neuronal lipofuscinoses in dried blood spots using substrates for concomitant tandem mass spectrometry and fluorimetry
Authors: Maeser Stefan , Petre Brindusa‐Alina , Ion Laura , Rawer Stephan , Kohlschütter Alfried , Santorelli Filippo M. , Simonati Alessandro , Schulz Angela , Przybylski Michael
Published: December 2020

Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative diseases predominantly in childhood that are characterized by psychomotor deterioration, epilepsy, and early death of patients. The NCLs analyzed in the present study are caused by defects of the specific enzymes, CLN1 (palmitoyl protein thioesterase 1; PPT1), CLN2 (tripeptidyl peptidase 1; TPP1), and CLN10 (cathepsin D). Specific and sensitive diagnostic assays of NCLs were the main goal of this study. They are of increasing importance, particularly since enzyme replacement therapy (ERT) for NCL2 has recently become available for clinical treatment, and ERTs for further NCLs are under development. Here, we report specific and sensitive determinations for CLN1, CLN2, and CLN10 on dried blood spots by tandem mass spectrometry using multiple reaction monitoring mass spectrometry (MRM‐MS). Identical substrates suitable for (i) fluorimetric determination of single enzymes and (ii) for MRM‐MS determination of multiple enzymes were synthesized by chemical coupling of alkyl‐umbelliferone building blocks with the corresponding peptidyl‐substrate groups recognized by the target enzyme. Enzymatic determinations were performed both by fluorimetry and MRM‐MS in patients with NCL1, NCL2, and NCL10 and showed good agreement in single assays. Moreover, duplex and triplex determinations were successfully performed for NCL1, NCL2, and NCL10. Specific peptidyl‐(4‐alkyl‐umbelliferone) substrates were also synthesized for mass spectrometric determinations of different cathepsins (cathepsins‐D, ‐F, and ‐B), to provide a differentiation of proteolytic specificities.
Engaging endogenous opioid circuits in pain affective processes
Authors: Kimmey Blake A. , McCall Nora M. , Wooldridge Lisa M. , Satterthwaite Theodore D. , Corder Gregory
Published: December 2020

The pervasive use of opioid compounds for pain relief is rooted in their utility as one of the most effective therapeutic strategies for providing analgesia. While the detrimental side effects of these compounds have significantly contributed to the current opioid epidemic, opioids still provide millions of patients with reprieve from the relentless and agonizing experience of pain. The human experience of pain has long recognized the perceived unpleasantness entangled with a unique sensation that is immediate and identifiable from the first‐person subjective vantage point as “painful.” From this phenomenological perspective, how is it that opioids interfere with pain perception? Evidence from human lesion, neuroimaging, and preclinical functional neuroanatomy approaches is sculpting the view that opioids predominately alleviate the affective or inferential appraisal of nociceptive neural information. Thus, opioids weaken pain‐associated unpleasantness rather than modulate perceived sensory qualities. Here, we discuss the historical theories of pain to demonstrate how modern neuroscience is revisiting these ideas to deconstruct the brain mechanisms driving the emergence of aversive pain perceptions. We further detail how targeting opioidergic signaling within affective or emotional brain circuits remains a strong avenue for developing targeted pharmacological and gene‐therapy analgesic treatments that might reduce the dependence on current clinical opioid options.
Small shards and long distances — three cryptotephra layers from the Nahe palaeolake including the first discovery of Laacher See Tephra in Schleswig‐Holstein (Germany)
Authors: Krüger Sascha , van den Bogaard Christel
Published: December 2020

Investigations of Lateglacial to Early Holocene lake sediments from the Nahe palaeolake (northern Germany) provided a high‐resolution palynological record. To increase the temporal resolution of the record a targeted search for cryptotephra was carried out on the basis of pollen stratigraphy. Three cryptotephra horizons were detected and geochemically identified as G10ka series tephra (a Saksunarvatn Ash), Vedde Ash and Laacher See Tephra. Here we present the first geochemically confirmed finding of the ash from the Laacher See Eruption in Schleswig‐Holstein—extending the so far detected fallout fan of the eruption further to the north‐west. These finds enable direct stratigraphical correlations and underline the potential of the site for further investigations.
Effects of mandibular setback surgery on the sleep architecture and respiratory function (Clinical observations)
Authors: Ogata Kinuko , Tanoue Ryuichiro , Mori Hiroyuki , Kotorii Nozomu , Kusukawa Jingo
Published: December 2020

Cephalometric analyses and full channel laboratory‐based polysomnography (PSG) were performed to clarify the relationship between mandibular setback surgery and the respiratory function at sleep and the sleep architecture. Thirty‐nine Japanese adults (male, n = 13; female, n = 26) with skeletal Class Ⅲ malocclusion who were treated with mandibular setback surgery were examined. All patients underwent lateral cephalography and full PSG before and at more than 6 months after advanced surgery. All radiographs were traced and the measurements were statistically analyzed. The anteroposterior airway width tended to decrease at all sites after mandibular setback, but no significant difference was observed. Among the full PSG data, the 5% oxygen desaturation index (ODI), wake time, and lighter stages of sleep (Stage N1, N2) were statistically significant parameter (P < .05).

It was suggested that mandibular setback surgery tended to result in a worse respiratory function at sleep and worse sleep architecture, even if the patient did not develop obstructive sleep apnea syndrome (OSAS).
“I know my body better than you:” patient focus groups to inform a decision aid on oral corticosteroid use during pregnancy
Authors: Palmsten Kristin , Bredesen Dani , JaKa Meghan M. , Kumar Pritika C. , Ziegenfuss Jeanette Y. , Kharbanda Elyse O.
Published: December 2020

Purpose

There is unmet need for decision support regarding medication use during pregnancy. We aimed to inform the development of a decision aid on oral corticosteroid (OCS) use during pregnancy through focus groups.

Methods

We invited patients from one health system who had a recent live birth and a condition for which OCSs may be prescribed (ie, asthma or other autoimmune disease) to participate in focus groups. We conducted conventional qualitative content analysis of verbatim transcripts of the focus groups using inductive coding.

Results

There were 30 participants across five focus groups from May to June 2019. Women endorsed the need for patient‐provider discussions about OCS use during pregnancy in which the provider shares risks and benefits and the patient makes her decision. Furthermore, women generally expressed support for patient‐centered handouts about OCS use during pregnancy that the provider discusses with the patient. When considering whether to take OCSs in pregnancy, women had concerns about: the medication's impact on their baby (eg, miscarriage, birth defects, long‐term effects), themselves (eg, effects on mood, sleep, weight gain), pregnancy complications (eg, preterm birth, increased blood pressure), and lactation. Women wanted information on OCSs (eg, indications, length of treatment, and cost), alternative treatments, and risks of not taking OCSs.

Conclusions

We established patient need for a decision aid on OCS use during pregnancy that providers can discuss with patients. To address patient concerns, the aid should at a minimum describe the medication's impact on baby, including long‐term effects, maternal health, pregnancy complications, and lactation.
Correlates of school bullying victimization among Black/White biracial adolescents: Are they similar to their monoracial Black and White peers?
Authors: Hong Jun Sung , Yan Yueqi , Gonzalez‐Prendes A. Antonio , Espelage Dorothy L. , Allen‐Meares Paula
Published: December 2020

Guided by the social‐ecological perspective, we examined familial, peer, and school‐related predictors of bullying victimization among a large sample of U.S. White, Black, and biracial adolescents. Data were drawn from the Health Behavior in School‐aged Children study, drawn from adolescents who self‐identified as White, Black, or biracial. Of the total sample, 3211 were White, 1188 were Black, and 175 were biracial. Adolescents completed measures of bullying victimization, perceptions of family relations, peer relationships, and school connectedness. Biracial students reported more bullying victimization than White and Black students. For biracial adolescents, family affluence off, and negative perceptions of other students were both found to be positively associated with victimization. For Whites, age, difficulty in talking with parents, parents sometimes like me to make my own decision, parents almost never like me to make my own decisions were negatively associated with victimization. On the other hand, talking with friends and negative perceptions of other students were positively associated with victimization. Among Blacks, age, and parents who almost never like me to make my own decisions were negatively associated with victimization. However, a parent who is almost never loving was positively associated with victimization. Implications for future research and school‐based practice are provided.
Rectification of AC Electric Current at the Edge of 2D Electron Gas
Authors: Durnev Mikhail V. , Tarasenko Sergey A.
Published: December 2020

Driving a 2D electron gas by AC electric field leads to a DC electric current flowing along the edge of the system. The effect is caused by the local breaking of space inversion symmetry at the edge. The current is generated in a narrow stripe determined by the screening length of the AC electric field and the mean free path of carriers. The developed microscopic theory of the effect shows that the excitation spectrum of the edge current and even the current direction depend on the mechanism of electron scattering. In an external magnetic field, the excitation spectrum of the current features the cyclotron resonance.
Model diagnostics for censored regression via randomized survival probabilities
Authors: Li Longhai , Wu Tingxuan , Feng Cindy
Published: December 2020

Residuals in normal regression are used to assess a model's goodness‐of‐fit (GOF) and discover directions for improving the model. However, there is a lack of residuals with a characterized reference distribution for censored regression. In this article, we propose to diagnose censored regression with normalized randomized survival probabilities (RSP). The key idea of RSP is to replace the survival probability (SP) of a censored failure time with a uniform random number between 0 and the SP of the censored time. We prove that RSPs always have the uniform distribution on(0, 1)under the true model with the true generating parameters. Therefore, we can transform RSPs into normally distributed residuals with the normal quantile function. We call such residuals by normalized RSP (NRSP residuals). We conduct simulation studies to investigate the sizes and powers of statistical tests based on NRSP residuals in detecting the incorrect choice of distribution family and nonlinear effect in covariates. Our simulation studies show that, although the GOF tests with NRSP residuals are not as powerful as a traditional GOF test method, a nonlinear test based on NRSP residuals has significantly higher power in detecting nonlinearity. We also compared these model diagnostics methods with a breast‐cancer recurrent‐free time dataset. The results show that the NRSP residual diagnostics successfully captures a subtle nonlinear relationship in the dataset, which is not detected by the graphical diagnostics with CS residuals and existing GOF tests.
Effects of in vitro‐induced drug resistance on the virulence of Streptococcus
Authors: Ding Yue‐Xia , Wu Qun , Guo Yan , Li Man , Li Pei‐Feng , Ma Yi , Liu Wen‐Chao
Published: December 2020

This study aimed to evaluate the effects of in vitro‐induced drug resistance on the virulence of Streptococcus. Micro‐dilution method was used to determine the minimal inhibitory concentration (MIC). In vitro‐induced drug resistance was conducted for S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) by gradually increasing the antimicrobial concentration (strains were from IVDC, China). PCR was used to detect the resistance and virulence genes of the strains before and after resistance induction. Colony morphology was observed to compare the physiological and biochemical properties of the strains. A total of 88 clean‐grade Kunming mice (obtained from Inner Mongolia University, Hohhot, China) were used in half of the lethal dose (LD50) test for detecting the changes in virulence of strains. The results showed that S. agalactiae (CVCC1886) and S. dysgalactiae (CVCC3701) developed resistance against seven kinds of antibiotics, respectively. Resistance and virulence genes of CVCC3701 were changed when treated by the Penicillin‐inducing. The growth of the CVCC3701‐PEN was decreased compared to the CVCC3701. Virulence test in mice indicated that the LD50 of CVCC3701 before induction and CVCC3701‐PEN after induction were 5.45 × 106 and 5.82 × 108 CFU/ml, respectively. Compared with the untreated bacteria, the bacterial virulence was reduced 1.1 × 102 times after resistance induction. In conclusion, S. dysgalactiae (CVCC3701) is a susceptible strain of drug resistance to antibiotics, in vitro‐induced drug resistance reduced the virulence of CVCC3701, but the virulence is still existing and also could result in the death of mice. For public health safety, it must be alert to the emergence of drug resistance of Streptococcus in animal production.
Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors
Authors: Dageforde Leigh Anne , Vachharajani Neeta , Tabrizian Parissa , Agopian Vatche , Halazun Karim , Maynard Erin , Croome Kristopher , Nagorney David , Hong Johnny C. , Lee David , Ferrone Cristina , Baker Erin , Jarnagin William , Hemming Alan , Schnickel Gabriel , Kimura Shoko , Busuttil Ronald , Lindemann Jessica , Florman Sander , Holzner Matthew L. , Srouji Rami , Najjar Marc , Yohanathan Lavanya , Cheng Jane , Amin Hiral , Rickert Charles A. , Yang Ju Dong , Kim Joohyun , Pasko Jennifer , Chapman William C. , Majella Doyle Maria B.
Published: December 2020

BACKGROUND:

Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA.

STUDY DESIGN:

Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis.

RESULTS:

Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001).

CONCLUSIONS:

Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.