bluuebunny/crossref_metadata_2025 huggingface dataset:
Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Authors: Richardson Paul G. , Kumar Shaji K. , Masszi Tamás , Grzasko Norbert , Bahlis Nizar J. , Hansson Markus , Pour Luděk , Sandhu Irwindeep , Ganly Peter , Baker Bartrum W. , Jackson Sharon R. , Stoppa Anne-Marie , Gimsing Peter , Garderet Laurent , Touzeau Cyrille , Buadi Francis K. , Laubach Jacob P. , Cavo Michele , Darif Mohamed , Labotka Richard , Berg Deborah , Moreau Philippe
Published: June 2021

PURPOSE

The double-blind, placebo-controlled, phase III TOURMALINE-MM1 study demonstrated a statistically significant improvement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed or refractory multiple myeloma. We report the final analyses for overall survival (OS).

PATIENTS AND METHODS

Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratified by number of prior therapies (1 v 2 or 3), previous proteasome inhibitor (PI) exposure (yes v no), and International Staging System disease stage (I or II v III). OS (intent-to-treat population) was a key secondary end point.

RESULTS

With a median follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 months (hazard ratio, 0.939; P = .495). Lower hazard ratios, indicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined subgroups: refractory to any (0.794) or last (0.742) treatment line; age > 65-75 years (0.757); International Staging System stage III (0.779); 2/3 prior therapies (0.845); high-risk cytogenetics (0.870); and high-risk cytogenetics and/or 1q21 amplification (0.862). Following ixazomib-Rd versus placebo-Rd, 71.7% versus 69.9% of patients received ≥ 1 anticancer therapy, of whom 24.7% versus 33.9% received daratumumab and 71.8% versus 76.9% received PIs (next-line therapy: 47.5% v 55.8%). Rates of new primary malignancies were similar with ixazomib-Rd (10.3%) and placebo-Rd (11.9%). There were no new or additional safety concerns.

CONCLUSION

Median OS values in both arms were the longest reported in phase III studies of Rd-based triplets in relapsed or refractory multiple myeloma at the time of this analysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a statistically significant OS benefit on intent-to-treat analysis. OS benefit was greater in subgroups with adverse prognostic factors. OS interpretation was confounded by imbalances in subsequent therapies received, especially PIs and daratumumab.
Reading Ambient Literature: Immersion, Distraction, and the Situated Reading Experience
Authors: Spencer Amy
Published: June 2021

This article considers the experience and process of reading works of ambient literature, a form of situated literary experience delivered by pervasive computing platforms, responding to the presence of a physically situated reader to deliver a story. This form of situated digital work does not need to be bound by a material form, such as a printed book. Without such a framing device, and its position embedded in the physical world, this narrative form has boundaries that are often in flux. It can shift and respond to the presence of the situated reader, and its beginning and ending can become blurred. This article addresses the specifics of this fluid literary form, open to distraction and unpredictability for the reader, and examines the potential of a reading experience informed by pervasive and ubiquitous computing practices. In doing so, it draws on Ulrich Schmidt's notions of distraction and immersion in relation to the position of the reader. In particular, it addresses the idea that attention can dissolve in two opposite directions, toward a lack of concentration or toward an absorbed trance, a time of focused concentration and immersion, and explores how in ambient literature these become literary devices that lead and shape the reader's experience.
Performing the Emperor: Sui Jingchen's “Han Gaozu Returns to His Home Village”
Authors: Myhre Karin
Published: June 2021

Reading Sui Jingchen's song suite “Gaozu Returns to His Home Village” against early sources, this article explores how Sui's work selects and inverts the elements that ground definitive historical accounts of rulership to refashion a familiar narrative in a theatrical mode. The sanqu's use of performance tropes expands the scope of criticism in this humorous piece past concerns about Yuan rulership, or even the imperial institution, to broader questions of representational instability and uncertainty. These shifts implicate readers in a social and political critique and engage issues often associated with early modern fiction and drama, including authenticity, imposture, and interpolations of author, character, player, reader, and audience.
A Dialectic between Genres and Extension of Poetic Functions: Zhang Kejiu's “Regulated Songs”
Authors: Lee Jaehyuk
Published: June 2021

Zhang Kejiu occupies an important position in the history of sanqu (colloquial song). Not only does the sheer volume of his sanqu songs account for one-fifth of the extant sanqu songs, but his significance also lies in the unique style of his songs. In particular, his sanqu songs hybridize traditional literary elements with the up-and-coming form of sanqu. This article examines how Zhang embodied the aesthetics of classical poetry in the format of sanqu through a detailed examination of meter, parallel lines, and rhyme. Also, to demonstrate that the synthetic style of Zhang's sanqu songs was not merely the result of combining literary and colloquial styles, this article aims to reconstruct Zhang's idea about poetic functions underlying his literary syncretism by exploring his literary activities in the cultural context at his time.
Effects of Acute Dance and Aerobic Exercise on Drug Craving and Food Reward in Women with Methamphetamine Dependence
Authors: ZHOU YU , FINLAYSON GRAHAM , LIU XUDONG , ZHOU QICHEN , LIU TIANZE , ZHOU CHENGLIN
Published: June 2021

Introduction

Drug dependence causes an overestimation of drug-related stimuli and an underestimation of non–drug-related stimuli, such as food. The purpose of this study was to investigate the effects of acute moderate-intensity dance and aerobic exercise on drug craving, appetite, prefrontal neural activation to food cues, and food reward in women with methamphetamine MA dependence.

Methods

Thirty-nine women who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition MA dependence criteria participated in the experiment and were randomly assigned to either a dance (n = 20) or exercise (n = 19) group. A moderate-intensity (65%–75% maximum heart rate) 35-min dance or treadmill intervention counterbalanced with a reading control session was conducted. After the intervention or control, subjective drug craving was measured before and after exposure to drug-related cues. Visual analog scales were used to measure subjective feelings of appetite. Participants then completed a visual food cue paradigm while using functional near-infrared spectroscopy to monitor prefrontal blood oxygen changes. Finally, the Leeds Food Preference Questionnaire was used to measure reward responses to different categories of food.

Results

The results showed that the dance and exercise interventions reduced subjective craving for drugs after being exposed to drug cues (P = 0.019). Implicit wanting (P < 0.001) and relative preferences (P = 0.001) for high-calorie savory foods were all increased after interventions relative to control. Compared with the control session, the left dorsolateral prefrontal cortex (P = 0.020) was activated when viewing high-calorie foods after moderate-intensity aerobic exercise.

Conclusions

The current results support the use of moderate-intensity exercise as a therapeutic intervention to restore the balance between drug and nondrug rewards by decreasing cue-induced MA craving and increasing food reward.
Quantitative diffusion and perfusion MRI in the evaluation of endometrial cancer: validation with histopathological parameters
Authors: Satta Serena , Dolciami Miriam , Celli Veronica , Di Stadio Francesca , Perniola Giorgia , Palaia Innocenza , Pernazza Angelina , Della Rocca Carlo , Rizzo Stefania , Catalano Carlo , Capuani Silvia , Manganaro Lucia
Published: June 2021

Objectives:

To investigate the role of quantitative Magnetic Resonance Imaging (MRI) in preoperative assessment of tumour aggressiveness in patients with endometrial cancer, correlating multiple parameters obtained from diffusion and dynamic contrast-enhanced (DCE) MR sequences with conventional histopathological prognostic factors and inflammatory tumour infiltrate.

Methods:

Forty-four patients with biopsy-proven endometrial cancer underwent preoperative MR imaging at 3T scanner, including DCE imaging, diffusion-weighted imaging (DWI) and intravoxel incoherent motion imaging (IVIM). Images were analysed on dedicated post-processing workstations and quantitative parameters were extracted: Ktrans, Kep, Ve and AUC from the DCE; ADC from DWI; diffusion D, pseudo diffusion D*, perfusion fraction f from IVIM and tumour volume from DWI. The following histopathological data were obtained after surgery: histological type, grading (G), lympho-vascular invasion (LVI), lymph node status, FIGO stage and inflammatory infiltrate.

Results:

ADC was significantly higher in endometrioid histology, G1-G2 (low grade), and stage IA. Significantly higher D* were found in endometrioid subptype, negative lymph nodes and stage IA. The absence of LVI is associated with higher f values. Ktrans and Ve values were significantly higher in low grade. Higher D*, f and AUC occur with the presence of chronic inflammatory cells, D * was also able to distinguish chronic from mixed type of inflammation. Larger volume was significantly correlated with the presence of mixed-type inflammation, LVI, positive lymph nodes and stage ≥IB.

Conclusions:

Quantitative biomarkers obtained from pre-operative DWI, IVIM and DCE-MR examination are an in vivo representation of the physiological and microstructural characteristics of endometrial carcinoma allowing to obtain the fundamental parameters for stratification into Risk Classes.

Advances in knowledge:

Quantitative imaging biomarkers obtained from DWI, DCE and IVIM may improve preoperative prognostic stratification in patients with endometrial cancer leading to a more informed therapeutic choice.
A comparison of the fusion model of deep learning neural networks with human observation for lung nodule detection and classification
Authors: Gürsoy Çoruh Ayşegül , Yenigün Bülent , Uzun Çağlar , Kahya Yusuf , Büyükceran Emre Utkan , Elhan Atilla , Orhan Kaan , Kayı Cangır Ayten
Published: June 2021

Objectives:

To compare the diagnostic performance of a newly developed artificial intelligence (AI) algorithm derived from the fusion of convolution neural networks (CNN) versus human observers in the estimation of malignancy risk in pulmonary nodules.

Methods:

The study population consists of 158 nodules from 158 patients. All nodules (81 benign and 77 malignant) were determined to be malignant or benign by a radiologist based on pathologic assessment and/or follow-up imaging. Two radiologists and an AI platform analyzed the nodules based on the Lung-RADS classification. The two observers also noted the size, location, and morphologic features of the nodules. An intraclass correlation coefficient was calculated for both observers and the AI; ROC curve analysis was performed to determine diagnostic performances.

Results:

Nodule size, presence of spiculation, and presence of fat were significantly different between the malignant and benign nodules (p < 0.001, for all three). Eighteen (11.3%) nodules were not detected and analyzed by the AI. Observer 1, observer 2, and the AI had an AUC of 0.917 ± 0.023, 0.870 ± 0.033, and 0.790 ± 0.037 in the ROC analysis of malignity probability, respectively. The observers were in almost perfect agreement for localization, nodule size, and lung-RADS classification [κ (95% CI)=0.984 (0.961–1.000), 0.978 (0.970–0.984), and 0.924 (0.878–0.970), respectively].

Conclusion:

The performance of the fusion AI algorithm in estimating the risk of malignancy was slightly lower than the performance of the observers. Fusion AI algorithms might be applied in an assisting role, especially for inexperienced radiologists.

Advances in knowledge:

In this study, we proposed a fusion model using four state-of-art object detectors for lung nodule detection and discrimination. The use of fusion of deep learning neural networks might be used in a supportive role for radiologists when interpreting lung nodule discrimination.
Perturbation of ribosomal subunit dynamics by inhibitors of tRNA translocation
Authors: Belardinelli Riccardo , Sharma Heena , Peske Frank , Rodnina Marina V.
Published: June 2021

Many antibiotics that bind to the ribosome inhibit translation by blocking the movement of tRNAs and mRNA or interfering with ribosome dynamics, which impairs the formation of essential translocation intermediates. Here we show how translocation inhibitors viomycin (Vio), neomycin (Neo), paromomycin (Par), kanamycin (Kan), spectinomycin (Spc), hygromycin B (HygB), and streptomycin (Str, an antibiotic that does not inhibit tRNA movement), affect principal motions of the small ribosomal subunits (SSU) during EF-G-promoted translocation. Using ensemble kinetics, we studied the SSU body domain rotation and SSU head domain swiveling in real time. We show that although antibiotics binding to the ribosome can favor a particular ribosome conformation in the absence of EF-G, their kinetic effect on the EF-G-induced transition to the rotated/swiveled state of the SSU is moderate. The antibiotics mostly inhibit backward movements of the SSU body and/or the head domains. Vio, Spc, and high concentrations of Neo completely inhibit the backward movements of the SSU body and head domain. Kan, Par, HygB, and low concentrations of Neo slow down both movements, but their sequence and coordination are retained. Finally, Str has very little effect on the backward rotation of the SSU body domain, but retards the SSU head movement. The data underscore the importance of ribosome dynamics for tRNA-mRNA translocation and provide new insights into the mechanism of antibiotic action.
Μεταφραστικές παρεμβάσεις και τροποποιήσεις σε διηγήματα του Αλέξανδρου Παπαδιαμάντη κατά τη μεταφορά τους στην Νεοελληνική για παιδιά και νέους
Authors: Κόρκα Νικολέττα
Published: June 2021

Οι διασκευές θεωρούνταν κατ’ εξακολούθηση φτωχές αντανακλάσεις των πρωτοτύπων τους. Μολαταύτα, έχουν επιτρέψει τη μετάδοση γνώσεων και συμπυκνωμένης σοφίας, καθώς και τη διατήρηση διαχρονικών πολιτισμικών αξιών, ιδίως, όταν πρόκειται για έργα κλασικής λογοτεχνίας. Στην Ελλάδα συναντάμε πολυάριθμες εκδόσεις με διασκευές έργων Ελλήνων λογοτεχνών του 19ου αιώνα για ανήλικους αναγνώστες, όπως είναι αυτά του Αλέξανδρου Παπαδιαμάντη. Ο Παπαδιαμάντης είναι ψυχογράφος και ηθογράφος του λαϊκού ανθρώπου της εποχής του και το έργο του φέρει έντονες θρησκευτικές αναφορές και ιδιαίτερη γλώσσα εμπλουτισμένη με σκιαθίτικο ιδίωμα και καθαρευουσιάνικους τύπους. Λόγω αυτών των χαρακτηριστικών υποθέτουμε ότι οι μεταφραστές θα έρθουν αντιμέτωποι με μεταφραστικές δυσκολίες και διλήμματα, που πρέπει να ξεπεράσουν για να μεταφέρουν τα διηγήματα στο νέο αναγνωστικό κοινό-στόχος. Στόχος της έρευνας είναι ο εντοπισμός των διασκευασμένων διηγημάτων του Παπαδιαμάντη για ανηλίκους και των μεταφραστικών ελιγμών, στους οποίους έχουν καταφύγει οι μεταφραστές για την απόδοσή τους. Σημείο εξέτασης και κριτικής προσέγγισης αποτελούν και οι τυχόν εικονογραφικές αναπαραστάσεις και τα περικειμενικά δεδομένα των βιβλίων, καθώς λειτουργούν διαμορφωτικά για το τελικό νόημα της εξιστόρησης, αποκαλύπτουν σημαντικές για την εξέταση πληροφορίες ως προς τις στρατηγικές μετάφρασης και τους λόγους για τους οποίους έγιναν κατά περίσταση συγκεκριμένες γλωσσικά μεταφραστικές επιλογές. Οι όποιες προσαρμογές, παραλείψεις ή προσθήκες αναδεικνύουν και τις συμβάσεις που ακολουθεί η σύγχρονη παιδική λογοτεχνία στη χώρα μας, καθώς και τις αντιλήψεις που έχουμε σχετικά με τις δεξιότητες, προσδοκίες και ανάγκες των αναγνωστών-παιδιών. Παράλληλα, η μελέτη των αναμεταφράσεων σε συγχρονία και διαχρονία επιτρέπει να συναχθούν συμπεράσματα σχετικά με τα μεταφραστικά ήθη της κάθε εποχής. Επιμέρους στόχος της εξέτασης είναι η συμβολή στον διάλογο περί θεμιτού ή όχι της ενδογλωσσικής μετάφρασης των διηγημάτων του Παπαδιαμάντη. Με την έρευνα αυτή αποσκοπούμε, ακόμη, στη συμβολή στη δημιουργία ενός εξατομικευμένου μοντέλου μελέτης ενδογλωσσικής μετάφρασης για παιδιά. Η εξέταση αντλεί μεθοδολογικά εργαλεία από το πεδίο της διαγλωσσικής μετάφρασης και των «Περιγραφικών Μεταφραστικών Σπουδών».
Fracture resistance and 3D finite element analysis of machined ceramic crowns bonded to endodontically treated molars with two planes versus flat occlusal preparation designs: an in vitro study
Authors: Nabil Omnia , Halim Carl Hany , Mokhtar Ashraf Hassan
Published: June 2021

Background: The flat occlusal preparation design (FOD) of posterior teeth offers promising results of fracture resistance and stress distribution, but its application in vital teeth is limited as there may be a danger of pulp injury. Although this danger is omitted in endodontically treated teeth, there is no research work assessing the impact of FOD on the fracture resistance and distribution of stresses among these teeth. The aim of this study was to assess the impact of FOD of endodontically treated molars on the fracture resistance and distribution of stresses among a ceramic crown-molar structure when compared to the two planes occlusal preparation design (TOD).

Methods: 20 human mandibular molars were endodontically treated and distributed equally to two groups: Group I (TOD) and Group II (FOD). Ceramic CAD/CAM milled lithium disilicate (IPS e.max CAD) crowns were produced for all preparations and adhered using self-adhesive resin cement. Using a universal testing machine, the fracture resistance test was performed. The fractured samples were examined using a stereomicroscope and scanning electron microscope to determine modes of failure. Stress distribution was evaluated by 3D finite element analysis, which was performed on digital models of endodontically treated mandibular molars (one model for each design).

Results: Group II recorded statistically non-significant higher fracture resistance mean values (3107.2± 604.9 N) than Group I mean values (2962.6 ±524.27 N) as indicated by Student’s t-test (t=0.55, p= 0.57). Also, Group II resulted in more favorable failure mode as compared to Group I. Both preparation designs yielded low von-Mises stresses within the factor of safety. However, the stress distribution among different layers of the model differed.

Conclusions: FOD having comparable fracture strength to TOD and a more favorable fracture behavior can be used for the preparation of endodontically treated molars.
Challenges of Online Education in a Lockdown Environment
Authors: Kalugina Tat'yana
Published: June 2021

Lockdowns in Europe, the United States and Russia have forced universities to abandon the traditional format of education and move to online. The article analyzes the statistics of a sharp decline in foreign students studying at universities in the United States, Great Britain and Russia, and examines the attempts of world universities to reduce financial losses. Comparison of the difficulties faced by the teachers of Russian and Western universities revealed similar problems, the main ones of which are devaluation of co-presence, the growth of academic cheating and the lack of control over the student's independent work. The only possible way to objectively assess the student's knowledge during an online session is to change the format of the exam, namely the introduction of the Open Book Exam. Exam questions within this format are formed in the form of a solution to a specific "case", which makes it possible to assess not the student's ability to memorize theoretical material, but his ability for critical and analytical thinking, the skills of applying the knowledge gained in practice.
Cross-Functional Interaction and Some Principles of Team Cohesion
Authors: Mirzoeva A.
Published: June 2021

The article aims to analyze cross-functional interaction and suggests several principles of the cohesion of a team of staff. The issues of cross-functional principles of interaction are currently quite a new phenomenon in company management and business environment, which involves co-working, mutually-connected activity of the staff from various departments, which has a potential to ensure fast and integral cooperation to achieve common goals. The author highlights different sides and multidimensional nature of cross-functional interaction. By relying on the academic work by national and international researchers the author arrives at the conclusion that the given interaction can be achieved by means of employees’ awareness of the significance of co-working and employers’ efficient application of management tools. The article provides examples of the managers applying principles conducive to ensuring cross-functional cooperation and team-building. The author comes to the conclusion that to create cross-functional interaction a special role is given to effective communication between departments, employees’ recognition of the reality that cooperation in a company is multifaceted and multi-track work.
Risks in Polycode Internet Communication: Communicative-Pragmatic and Legal Aspects
Authors: Nesterova T.
Published: June 2021

The article analyzes polycode texts and polycode Internet communication in terms of their riskiness. Theoretical approaches to the study of the phenomenon of risk and risky communications are presented, the concepts of “risk”, “communicative risk”, “legal risk”, “zones of communicative and legal risks”, “criminogenic speech aggression” are considered. The study of polycode texts associated with the concept of "risk" is carried out in two aspects: communicative-pragmatic and legal.
Influence of the dissolution medium type on the release of diclofenac sodium and papaverine hydrochloride from granules and tablets
Authors: Kasperek Regina , Naleśniak Magdalena , Iwaniak Karol , Poleszak Ewa
Published: June 2021

The release studies of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) from composed granules and tablets into the dissolution media at different pH using the flow-through cell apparatus were carried out. The solubilities of these active substances vary and depend on the pH of a dissolution medium which confirmed the outcomes of the release studies on granules and tablets containing only one substance DIC or PAP. The most effective dissolution medium for the carried out release study of DIC and PAP from composed solid dosage form as granules or tablets was citrate buffer at pH 6.5.
The analysis of flavonoids in the flowering herbs of Carduus acanthoides L.
Authors: Kozyra Małgorzata , Głowniak Kazimierz , Boguszewska Małgorzata
Published: June 2021

The present paper discusses the analysis of flavonoids in the methanol extract from the flowering herbs of Carduus acanthoides (L.), where flavonois were indentified by TLC and SPE HPLC. The quantitative analysis was performed using spectrophotometric Christ-Müller’s method. The samples containing flavonoids and those released after acid hydrolysis were investigated by 1D TLC on silica gel and polyamide. After purification by SPE, the samples were also analyzed by RP-HPLC. Apigenin-7-glucoside, luteolin-7-glucoside, kaempferol-3-rhamnoglucoside, kaempferol-3-glucoside, apigenin, luteolin and chlorogenic acid and p-coumaric acid were detected in the fractions of methanol extracts obtained from the plant. This method is very simple for the analysis and suitable for rapid screening of flavonoids in plants.
Rewards and challenges
Authors: Francis Emily
Published: June 2021

The early years team at Lessness Heath have been enjoying seeing the rapid development in their children. But there is still a lot to do, Emily Francis discusses the team's preparation for transitions and the new statutory guidance.
Catch up needs a playful antidote
Authors: Edwards Helen
Published: June 2021

There has been a lot of discourse around lost learning, but Dr Helen Edwards believes that we need a calm approach to address this. Early educators know best, and playful learning opportunities is the way forward.
Water as liquid, solid and gas
Authors: Clarke Jenni
Published: June 2021

Exploration with water can bring so much more on top of the all-important sensory opportunities. Jenni Clarke suggests many ways in which the three different states of water can be explored through maths.
Towards in vivo photoacoustic imaging of vulnerable plaques in the carotid artery
Authors: Muller Jan-Willem , van Hees Roy , van Sambeek Marc , Boutouyrie Pierre , Rutten Marcel , Brands Peter , Wu Min , Lopata Richard
Published: June 2021

The main indicator for endarterectomy is the grade of stenosis, which results in severe overtreatment. Photoacoustic imaging (PAI) can provide patient-specific assessment of plaque morphology, and thereby vulnerability. A pilot study of PAI on carotid plaques in patients (n=16) was performed intraoperatively with a hand-held PAI system. By compensating for motion, the photoacoustic (PA) signal-to-noise ratio (SNR) could be increased by 5 dB in vivo. PA signals from hemorrhagic plaques had different characteristics compared to the signals from the carotid blood pool. This study is a key step towards a non-invasive application of PAI to detect vulnerable plaques.
Plasmonics–mine the gap: opinion
Authors: Gordon Reuven , Dobinson Michael
Published: June 2021

Gap plasmon structures could enable future ultrafast communication by allowing simultaneous nanoscale integration of electromagnetic waves, nonlinear and optical-electrical conversion, and providing a critical element often overlooked in this context: electrical contacts. Here, the fundamental limit of these structures is discussed, and it is argued that the conventional concept of “smaller is better" for higher confinement is not true when the loss is considered, but few nanometer gaps will be required to give the best performance. Overall, to achieve widescale adoption, plasmonics will likely have to combine forces with emerging CMOS-like nanophotonics.
Disrupting hierarchical control of nitrogen fixation enables carbon-dependent regulation of ammonia excretion in soil diazotrophs
Authors: Bueno Batista Marcelo , Brett Paul , Appia-Ayme Corinne , Wang Yi-Ping , Dixon Ray
Published: June 2021

The energetic requirements for biological nitrogen fixation necessitate stringent regulation of this process in response to diverse environmental constraints. To ensure that the nitrogen fixation machinery is expressed only under appropriate physiological conditions, the dedicated NifL-NifA regulatory system, prevalent in Proteobacteria, plays a crucial role in integrating signals of the oxygen, carbon and nitrogen status to control transcription of nitrogen fixation (nif) genes. Greater understanding of the intricate molecular mechanisms driving transcriptional control of nif genes may provide a blueprint for engineering diazotrophs that associate with cereals. In this study, we investigated the properties of a single amino acid substitution in NifA, (NifA-E356K) which disrupts the hierarchy of nif regulation in response to carbon and nitrogen status in Azotobacter vinelandii. The NifA-E356K substitution enabled overexpression of nitrogenase in the presence of excess fixed nitrogen and release of ammonia outside the cell. However, both of these properties were conditional upon the nature of the carbon source. Our studies reveal that the uncoupling of nitrogen fixation from its assimilation is likely to result from feedback regulation of glutamine synthetase, allowing surplus fixed nitrogen to be excreted. Reciprocal substitutions in NifA from other Proteobacteria yielded similar properties to the A. vinelandii counterpart, suggesting that this variant protein may facilitate engineering of carbon source-dependent ammonia excretion amongst diverse members of this family.
Cost of illness for severe and non-severe diarrhea borne by households in a low-income urban community of Bangladesh: A cross-sectional study
Authors: Sultana Rebeca , Luby Stephen P. , Gurley Emily S. , Rimi Nadia Ali , Swarna Sayeda Tasnuva , Khan Jahangir A. M. , Nahar Nazmun , Ghosh Probir Kumar , Howlader Sushil Ranjan , Kabir Humayun , Khan Shifat , Jensen Peter Kjær Mackie
Published: June 2021

The illness cost borne by households, known as out-of-pocket expenditure, was 74% of the total health expenditure in Bangladesh in 2017. Calculating economic burden of diarrhea of low-income urban community is important to identify potential cost savings strategies and prioritize policy decision to improve the quality of life of this population. This study aimed to estimate cost of illness and monthly percent expenditure borne by households due diarrhea in a low-income urban settlement of Dhaka, Bangladesh. We conducted this study in East Arichpur area of Tongi township in Dhaka, Bangladesh from September 17, 2015 to July 26, 2016. We used the World Health Organization (WHO) definition of three or more loose stool in 24 hours to enroll patients and enrolled 106 severe patients and 158 non-severe patients from Tongi General Hospital, local pharmacy and study community. The team enrolled patients between the first to third day of the illness (≤ 72 hours) and continued daily follow-up by phone until recovery. We considered direct and indirect costs to calculate cost-per-episode. We applied the published incidence rate to estimate the annual cost of diarrhea. The estimated average cost of illness for patient with severe diarrhea was US$ 27.39 [95% CI: 24.55, 30.23] (2,147 BDT), 17% of the average monthly income of the households. The average cost of illness for patient with non-severe diarrhea was US$ 6.36 [95% CI: 5.19, 7.55] (499 BDT), 4% of the average monthly income of households. A single diarrheal episode substantially affects financial condition of low-income urban community residents: a severe episode can cost almost equivalent to 4.35 days (17%) and a non-severe episode can cost almost equivalent to 1 day (4%) of household’s income. Preventing diarrhea preserves health and supports financial livelihoods.
Temperature, traveling, slums, and housing drive dengue transmission in a non-endemic metropolis
Authors: Gurevitz Juan Manuel , Antman Julián Gustavo , Laneri Karina , Morales Juan Manuel
Published: June 2021

Dengue is steadily increasing worldwide and expanding into higher latitudes. Current non-endemic areas are prone to become endemic soon. To improve understanding of dengue transmission in these settings, we assessed the spatiotemporal dynamics of the hitherto largest outbreak in the non-endemic metropolis of Buenos Aires, Argentina, based on detailed information on the 5,104 georeferenced cases registered during summer-autumn of 2016. The highly seasonal dengue transmission in Buenos Aires was modulated by temperature and triggered by imported cases coming from regions with ongoing outbreaks. However, local transmission was made possible and consolidated heterogeneously in the city due to housing and socioeconomic characteristics of the population, with 32.8% of autochthonous cases occurring in slums, which held only 6.4% of the city population. A hierarchical spatiotemporal model accounting for imperfect detection of cases showed that, outside slums, less-affluent neighborhoods of houses (vs. apartments) favored transmission. Global and local spatiotemporal point-pattern analyses demonstrated that most transmission occurred at or close to home. Additionally, based on these results, a point-pattern analysis was assessed for early identification of transmission foci during the outbreak while accounting for population spatial distribution. Altogether, our results reveal how social, physical, and biological processes shape dengue transmission in Buenos Aires and, likely, other non-endemic cities, and suggest multiple opportunities for control interventions.
Relative transmissibility of shigellosis among different age groups: A modeling study in Hubei Province, China
Authors: Zhao Zeyu , Chen Qi , Wang Yao , Chu Meijie , Hu Qingqing , Hannah Mikah Ngwanguong , Rui Jia , Liu Xingchun , Yu Yunhan , Zhao Fuwei , Ren Zhengyun , Yu Shanshan , An Ran , Pan Lili , Chiang Yi-Chen , Zhao Benhua , Su Yanhua , Zhao Bin , Chen Tianmu
Published: June 2021

Shigellosis is a heavy disease burden in China especially in children aged under 5 years. However, the age-related factors involved in transmission of shigellosis are unclear. An age-specific Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to shigellosis surveillance data maintained by Hubei Province Centers for Disease Control and Prevention from 2005 to 2017. The individuals were divided into four age groups (≤ 5 years, 6–24 years, 25–59 years, and ≥ 60 years). The effective reproduction number (Reff), including infectivity (RI) and susceptibility (RS) was calculated to assess the transmissibility of different age groups. From 2005 to 2017, 130,768 shigellosis cases were reported in Hubei Province. The SEIAR model fitted well with the reported data (P< 0.001). The highest transmissibility (Reff) was from ≤ 5 years to the 25–59 years (mean: 0.76, 95% confidence interval [CI]: 0.34–1.17), followed by from the 6–24 years to the 25–59 years (mean: 0.69, 95% CI: 0.35–1.02), from the ≥ 60 years to the 25–59 years (mean: 0.58, 95% CI: 0.29–0.86), and from the 25–59 years to 25–59 years (mean: 0.50, 95% CI: 0.21–0.78). The highest infectivity was in ≤ 5 years (RI= 1.71), and was most commonly transmitted to the 25–59 years (45.11%). The highest susceptibility was in the 25–59 years (RS= 2.51), and their most common source was the ≤ 5 years (30.15%). Furthermore, “knock out” simulation predicted the greatest reduction in the number of cases occurred by when cutting off transmission routes among ≤ 5 years and from 25–59 years to ≤ 5 years. Transmission in ≤ 5 years occurred mainly within the group, but infections were most commonly introduced by individuals in the 25–59 years. Infectivity was highest in the ≤ 5 years and susceptibility was highest in the 25–59 years. Interventions to stop transmission should be directed at these age groups.
Ayurveda botanicals in COVID-19 management: An in silico multi-target approach
Authors: Borse Swapnil , Joshi Manali , Saggam Akash , Bhat Vedika , Walia Safal , Marathe Aniket , Sagar Sneha , Chavan-Gautam Preeti , Girme Aboli , Hingorani Lal , Tillu Girish
Published: June 2021

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. AyurvedicRasayanatherapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others,Withania somnifera(Ashwagandha),Tinospora cordifolia(Guduchi) andAsparagus racemosus(Shatavari) play an important role inRasayanatherapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents anin-siliconetwork pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of theseRasayanabotanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.
Epidermal growth factor as a potential prognostic and predictive biomarker of response to platinum-based chemotherapy
Authors: Geens Margot , Stappers Sofie , Konings Heleen , De Winter Benedicte Y. , Specenier Pol , Van Meerbeeck Jan P. , Verpooten Gert A. , Abrams Steven , Janssens Annelies , Peeters Marc , Van de Heyning Paul , Vanderveken Olivier M. , Ledeganck Kristien J.
Published: June 2021

In this study, we investigated serum epidermal growth factor (EGF) in an oncological population of head- and neck and pulmonary neoplasms and whether serum EGF could serve as a prognostic marker of survival and as a predictive marker for treatment response to platinum-based chemotherapy. A total of 59 oncological patients and a control group of age- and sex-matched healthy volunteers were included in this study. Pre-treatment serum EGF from both groups was determined. Patient’s and tumour characteristics and mortality were recorded during a 5-year follow up period. Baseline serum EGF significantly differed between the oncological patients and the healthy volunteers (p<0.001). Serum EGF was associated with lymph node metastasis (p = 0.004) but not with sex (p = 0.753), age (p = 1.00), TNM stage (p = 0.191) or tumour size (p = 0.077). Neither serum EGF (p = 0.81) nor age (p = 0.55) showed an effect on the patient’s survival. Tumour location was significantly associated with overall 5-year survival (p = 0.003). The predictive capacity of serum EGF of response to chemotherapy was limited (AUC = 0.606), a sensitivity of 80% and a specificity of 56% was observed resulting in a likelihood ratio of a positive and negative test equal to 1.81 and 0.36, respectively. In conclusion, serum EGF levels are 5.5 times higher in an oncological population compared to a control group. Within the oncological population, low serum EGF values are associated with the presence of lymph node metastasis. Further investigation is necessary to determine if the serum EGF levels could serve as a diagnostic biomarker.
Evaluation of Air Transport Benefits for the Czech Republic
Authors: Vittek Peter , Van den Bergh Sarah , Zozulak Radoslav
Published: June 2021

The article's main purpose is to describe the proposed Methodology, which aims to present an approach to expressing the value of the air transport industry in the Czech Republic. This approach methodically divides the primary and secondary effects and finds metrics based on which the value of the air transport can be quantified. The proposed approach is based on equivalent methodological materials by ICAO, FAA, and other organizations describing and analyzing the value of air transports. The calculations are based on open data sources as well as data that are available by request. The methodology also proposes collecting new data to complete the picture of the value of air transport.
CHALLENGES IN DEVELOPING AND SUPPORTING ENTREPRENEURSHIP EDUCATION: A CASE STUDY OF THE UNIVERSITY OF ZULULAND
Authors:   University of Zululand, Radebe Thobile , Vezi-Magigaba Makhosazana
Published: June 2021

Entrepreneurship education is broadly considered an important factor in promoting an entrepreneurial culture among higher education students. Considering the importance of entrepreneurship with regard to economic growth, job creation and poverty alleviation, there is a need to train entrepreneurs and to equip them with an entrepreneurial culture that promotes entrepreneurship. However, the South African education system is lacking when it comes to entrepreneurship education. The education system seems to promote the white-collar jobs rather than self-employment, and the methodology that is used to teach entrepreneurship studies, focuses more on the theory of entrepreneurship than on its practice. Against this background, this study sought to identify the challenges to develop and support entrepreneurship education by focusing on the University of Zululand as a case study. The researcher used primary data for this study. The study adopted a qualitative approach, where data was collected using interview schedules from 11 heads of departments of the university’s faculties. The results from the study show that the development of curriculum, inexperienced educators, and the methodology used to teach entrepreneurship education, are some of the challenges that are hindering the promotion of entrepreneurship education. A policy implication that arose from these findings, is that there is a need for the development of entrepreneurship-based curriculum to promote entrepreneurship. The policymakers were also encouraged to employ educators who are qualified and experienced in teaching entrepreneurship. The development of incubation centres for grooming entrepreneurs at higher learning institutions was also recommended.
La fleur inverse, la flors enversa, la fleur en vers
Authors: Manzari Francesca
Published: June 2021

The article is a reading/interpretation of Raimbaut d’Aurenga’s La flors enversa. The co-presence of winter and spring in the canso’s coblas is the point of departure of an investigation of the meaning of the adjective enversa. It is also an analysis of the devices by which the troubadour links the distance between winter and poetry, and the one between the trobar and its inverse.
« Ici rien n’est vert. Ici rien n’est végétal. Ici rien n’est vivant » : l’hiver dans les témoignages des camps de concentration
Authors: Teklik Joanna
Published: June 2021

For the prisoners of the concentration camps winter with its seasonal attributes as the icy cold or snow is more than a meteorogical phenomenon. The arrival of winter not only announces the annihilation of the prisonners, but also and perhaps above all their dashing and the unspeakable suffering to come out. In this paper we wish to study in the light of such authors as Robert Antelme, Charlotte Delbo, Primo Levi, David Rousset and Jorge Semprún how the hard weather conditions are able to redraw the space and the prisoners’Horizon of despair.
The effect of aerosolized indomethacin on lung inflammation and injury in a rat model of blunt chest trauma
Authors: Kao Raymond L. , Huang Weixiong , Martin Claudio M. , Rui Tao
Published: June 2021

Background: Acute lung contusion from blunt chest trauma (BCT) is characterized by an intense inflammatory response in the pulmonary parenchyma, which is associated with acute lung injury (ALI), acute respiratory distress syndrome and ventilator-associated pneumonia. We hypothesized that aerosolized indomethacin may reduce pulmonary inflammation and ALI in a rat model of BCT. Methods: Sprague-Dawley rats were anesthetized and received a tracheotomy for administration of aerosolized medication through a catheter. The BCT procedure involved free-dropping a hollow metal weight (200 g) from a height of 25.5, 38.3 or 51.2 cm onto the right thorax. We administered 1 mg/kg of indomethacin or 1 mL/kg of saline intratracheally 15 minutes after BCT. The sham group had a similar procedure without the exposure to BCT and treatment. Three hours postimpact, we obtained arterial blood gas and analyzed bronchoalveolar lavage for protein concentration, polymorphonuclear leukocytes (PMN) and cytokine levels, and lung tissue samples were taken for histopathological analysis. Results: The rats’ mean arterial pressure and heart rate dropped immediately postimpact but recovered close to that of the sham group after 30 minutes in both control and treatment groups. Compared to BCT alone, indomethacin significantly reduced the total protein level in the lungs (1.06 ± 0.39 mg/mL v. 3.75 ± 1.95 mg/mL, p = 0.006) and alveolar FD-70 leak (0.23 ± 0.19 μg/mL v. 0.53 ± 0.19 μg/mL, p = 0.02). Indomethacin also significantly attenuated the acute inflammatory response in percent PMN (13.33 ±7.5% v. 28.0 ± 12.96%, p = 0.04). Tumour necrosis factor-α and interleukin-6 decreased in the indomethacin group, but the decreases were not significant compared with other groups. Conclusion: Aerosolized indomethacin has a protective effect against alveloar tissue permeability and inflammatory response induced by BCT.
The Relief of Harput
Authors: Abay Eşref , Demir Bülent , Sevin Veli
Published: June 2021

In the spring of 2016 a unique stone slab carved in relief was accidentally discovered on Kurey Tepesi near Harput/Elazığ in eastern Turkey. The relief depicts the capture of a heavily fortified city in horizontally arranged registers. At first sight it comes to recognition that the Harput Relief stands in the tradition of Mesopotamian victory steles, starting with the Eannatum Stele (Stele of Vultures) in Early Dynastic Sumer (c. 2900–2350 BC) and continuing with the kings of Akkad (c. 2350–2150 BC). From a stylistic and iconographic point of view, the relief seems closer to the victory stele of Daduša of Ešnunna and the Mardin Stele of the early Old Babylonian period (c. 2000–1600 BC). The subsequently excavated archaeological context, a heavily burned architectural layer, contained Middle Bronze Age I pottery typical of the Elazığ-Malatya region, corroborating a date in the early second millennium BC.
Active Participles in Hittite
Authors: Lyutikova Ekaterina A. , Sideltsev Andrei V.
Published: June 2021

The paper reassesses the evidence for active transitive participles in Hittite and suggests that they are in reality formed from the unergative class of intransitive verbs.
Developing interpersonal and intercultural skills in a university language course
Authors: Bavieri Luisa , Beaven Ana
Published: June 2021

Intercultural language learning and teaching is generally endorsed in contemporary foreign and second language classroom contexts. This article reports the use of an intercultural education activity taught in an Italian L2 elementary course at the Language Centre of the University of Bologna attended by exchange and degree-seeking students. The intercultural tasks proposed invite students to reflect on their experiences of studying and living in a different country, and encourage them to reflect on their intercultural learning objectives and on their goals for study abroad in relation to their intercultural encounters. Our aim was to explore students’ willingness to engage with the intercultural tasks, their commitment and the possible influence on their behaviours, attitudes and beliefs, considering their relatively limited level of target language proficiency. The data, collected through audio-recorded interviews, show individual differences among the students. Our report concludes with our reflections as practitioners working in a university language centre, on the importance of intercultural language teaching and learning.