bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unrealized potential of drug repositioning in Europe during COVID-19 and beyond: a physician's perspective
Authors: Bayoumy A. B. , de Boer N. K. H. , Ansari A. R. , Crouwel F. , Mulder C. J. J. 
Published: July 2020

AbstractDrug repositioning is the scientific strategy of investigating existing drugs for additional clinical indications. The advantages of drug repositioning are that it benefits patients and that it adds new indications to existing drugs for lower costs compared to de novo drug development. Clinical research groups recognizing efficacy of these “old” drugs for a new indications often face an uphill struggle due to a lack of funding and support because of poor structural and regulatory support for clinical drug development. The current framework for drug repositioning allows “venture capital” companies to abuse loopholes in the legislation to gain long-term market authorization among with excessive high pricing. A new regulatory framework is needed to prevent abuse of the legislation and promote clinical investigator-driven drug repositioning. The COVID-19 pandemic has boosted funding and regulatory support for drug repositioning. The lessons learned from the COVID-19 pandemic should be implemented in a new clear blueprint for drug repositioning. This blueprint should guide clinicians through legislation for drug repositioning in the EU. This review summarizes the routes for registration and discusses the current state of drug repositioning in Europe.
Preoperative balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension led to successful anesthetic management for total hysterectomy under general anesthesia: a case report
Authors: Ota Tomoko , Kawai Kazumi , Niihata Tomoko , Fukuda Hideki 
Published: July 2020

Abstract
Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of obstructive pulmonary artery remodeling as a consequence of major vessel thromboembolism. Balloon pulmonary angioplasty (BPA) is an alternative treatment for patients with inoperable CTEPH. We report a case of CTEPH which improved following preoperative BPA intervention, allowing total hysterectomy to be performed.

Case presentation
A 48-year-old woman was transferred to our hospital to undergo total hysterectomy for endometrial cancer. She developed pulmonary embolism 7 months ago at another hospital, and a diagnosis of CTEPH was made based on multiple pulmonary emboli and pulmonary hypertension at our institute. Two BPA sessions for seven branches of the bilateral pulmonary arteries were conducted, resulting in a decrease of mean pulmonary artery pressure from 54 to 33 mmHg. Total hysterectomy was successfully performed under general anesthesia without any complications.

Conclusions
BPA could be effective for reducing PH in patients with CTEPH undergoing noncardiac surgery.
Flipped classroom in a therapeutic modality course: students’ perspective
Authors: Bates Dana , Ludwig Genevieve 
Published: July 2020

AbstractThe use of flipped classrooms has gained momentum and involves the instructor replacing the passive reception of material found in common lectures, so class time may be used for hands-on practical application, discussion, or assignments. The purpose of this paper is to explore students’ perceptions of a flipped therapeutic modality course. Focus group interviews were conducted with sixteen participants (14 female, 2 male) who completed a therapeutic modality course. Data were collected through 4 focus group interviews, which were digitally recorded and transcribed. Data were analyzed to uncover dominant themes—first by organizing the data, then summarizing data into codes, and finally interpreting. Credibility was secured through peer review, member checks, and investigator triangulation. The analysis resulted in three common themes: the flipped classroom (1) was perceived as valuable by students, (2) led to active participation in class, and (3) helped students feel better prepared for the class. Athletic training students, particularly in a flipped therapeutic modality course, valued this pedagogical approach.
Classifying the diagnosis of study participants in clinical trials: a structured and efficient approach
Authors: van Engelen Tjitske S. R. , Kanglie Maadrika M. N. P. , van den Berk Inge A. H. , Bouwman Merel L. J. , Suhooli Hind J. M. , Heckert Sascha L. , Stoker Jaap , Bossuyt Patrick M. M. , Prins Jan M. ,   For the OPTIMACT Study Group, Annema Jouke , Beenen Ludo F. M. , van den Berk Inge A. H. , Bipat Shandra , Bossuyt Patrick M. M. , Bresser Paul , Dijkgraaf Marcel , Donker Jos , van Engelen Tjitske S. R. , Frankemölle Betty , Groenink Maarten , Hochheimer Suzanne M. R. , Holleman Frits , Hulzebosch Dorine , Kanglie Maadrika M. N. P. , Keijzers Mitran , van der Lee Ivo , Leenhouts Peter , Luitse Jan , Meijboom Lilian J. , Middeldorp Saskia , Montauban van Swijndregt Alexander , de Monyé Wouter , Otker Jacqueline , Ridderikhof Milan , Romijn Johannes A. , Schoonderwoerd Antoinet J. N. , Sprengers Ralf W. , Stoker Jaap , Taal Elizabeth M. , Winter Michiel , Prins Jan M. 
Published: July 2020

Abstract
Background
A challenge in imaging research is a diagnostic classification of study participants. We hypothesised that a structured approach would be efficient and that classification by medical students, residents, and an expert panel whenever necessary would be as valid as classification of all patients by experts.

Methods
OPTIMACT is a randomised trial designed to evaluate the effectiveness of replacing chest x-ray for ultra-low-dose chest computed tomography (CT) at the emergency department. We developed a handbook with diagnostic guidelines and randomly selected 240 cases from 2,418 participants enrolled in OPTIMACT. Each case was independently classified by two medical students and, if they disagreed, by the students and a resident in a consensus meeting. Cases without consensus and cases classified as complex were assessed by a panel of medical specialists. To evaluate the validity, 60 randomly selected cases not referred to the panel by the students and the residents were reassessed by the specialists.

Results
Overall, the students and, if necessary, residents were able to assign a diagnosis in 183 of the 240 cases (76% concordance; 95% confidence interval [CI] 71–82%). We observed agreement between students and residents versus medical specialists in 50/60 cases (83% concordance; 95% CI 74–93%).

Conclusions
A structured approach in which study participants are assigned diagnostic labels by assessors with increasing levels of medical experience was an efficient and valid classification method, limiting the workload for medical specialists. We presented a viable option for classifying study participants in large-scale imaging trials (Netherlands National Trial Register number NTR6163).
Adoption of Immune Checkpoint Inhibitors and Patterns of Care at the End of Life
Authors: Riaz Fauzia , Gan Geliang , Li Fangyong , Davidoff Amy J. , Adelson Kerin B. , Presley Carolyn J. , Adamson Blythe J. , Shaw Pooja , Parikh Ravi B. , Mamtani Ronac , Gross Cary P. 
Published: July 2020

PURPOSE: As immune checkpoint inhibitors (ICIs) have transformed the care of patients with cancer, it is unclear whether treatment at the end of life (EOL) has changed. Because aggressive therapy at the EOL is associated with increased costs and patient distress, we explored the association between the Food and Drug Administration (FDA) approvals of ICIs and treatment patterns at the EOL. METHODS: We conducted a retrospective, observational study using patient-level data from a nationwide electronic health record–derived database. Patients had advanced melanoma, non–small-cell lung cancer (NSCLC; cancer types with an ICI indication), or microsatellite stable (MSS) colon cancer (a cancer type without an ICI indication) and died between 2013 and 2017. We calculated annual proportions of decedents who received systemic cancer therapy in the final 30 days of life, using logistic regression to model the association between the post-ICI FDA approval time and use of systemic therapy at the EOL, adjusting for patient characteristics. We assessed the use of chemotherapy or targeted/biologic therapies at the EOL, before and after FDA approval of ICIs using Pearson chi-square test. RESULTS: There was an increase in use of EOL systemic cancer therapy in the post-ICI approval period for both melanoma (33.9% to 43.2%; P < .001) and NSCLC (37.4% to 40.3%; P < .001), with no significant change in use of systemic therapy in MSS colon cancer. After FDA approval of ICIs, patients with NSCLC and melanoma had a decrease in the use of chemotherapy, with a concomitant increase in use of ICIs at the EOL. CONCLUSION: The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at the EOL in melanoma and a smaller yet significant increase in NSCLC.
Considerations and Caveats when Applying Global Sensitivity Analysis Methods to Physiologically Based Pharmacokinetic Models
Authors: Liu Dan , Li Linzhong , Rostami-Hodjegan Amin , Bois Frederic Y. , Jamei Masoud 
Published: July 2020

AbstractThree global sensitivity analysis (GSA) methods (Morris, Sobol and extended Sobol) are applied to a minimal physiologically based PK (mPBPK) model using three model drugs given orally, namely quinidine, alprazolam, and midazolam. We investigated how correlations among input parameters affect the determination of the key parameters influencing pharmacokinetic (PK) properties of general interest, i.e., the maximal plasma concentration (Cmax) time at which Cmax is reached (Tmax), and area under plasma concentration (AUC). The influential parameters determined by the Morris and Sobol methods (suitable for independent model parameters) were compared to those determined by the extended Sobol method (which considers model parameter correlations). For the three drugs investigated, the Morris method was as informative as the Sobol method. The extended Sobol method identified different sets of influential parameters to Morris and Sobol. These methods overestimated the influence of volume of distribution at steady state (Vss) on AUC24h for quinidine and alprazolam. They also underestimated the effect of volume of liver (Vliver) for all three drugs, the impact of enzyme intrinsic clearance of CYP2C9 and CYP2E1 for quinidine, and that of UGT1A4 abundance for midazolam. Our investigation showed that the interpretation of GSA results is not straightforward. Dismissing existing model parameter correlations, GSA methods such as Morris and Sobol can lead to biased determination of the key parameters for the selected outputs of interest. Decisions regarding parameters’ influence (or otherwise) should be made in light of available knowledge including the model assumptions, GSA method limitations, and inter-correlations between model parameters, particularly in complex models.
TCR-Seq Identifies Distinct Repertoires of Distant-Metastatic and Nondistant-Metastatic Thyroid Tumors
Authors: Lan Xiabin , Cao Jun , Ye Ke , Zhang Chao , Zhang Qihong , Ge Xinyang , Wang Changxi , Zhang Chunliu , Tai Zaixian , Wei Wei , Huang Yi , Yi Xin , Tan Zhuo , Zheng Chuanming , Chen Chao , Zhu Xin , Wang Jiafeng , Xu Jiajie , Zhu Xuhang , Ge Minghua 
Published: July 2020

AbstractContextMalignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance.ObjectiveThyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis.DesignA retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration.SettingThis study took place at Zhejiang Cancer Hospital.PatientsSixty-eight patients with papillary thyroid cancer (PTC) (distinct metastatic status) and 21 patients with benign nodules were enrolled. All patients had not received any treatment before surgery.Main Outcome MeasureThe characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing.ResultsThe TCRβ diversity of malignant tumors is significantly higher than benign nodules both in blood and tumor samples (Shannon index, blood, P &lt; .01; tumor, P &lt; .001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than nonmetastasis (Shannon index, P &lt; .01) or noninvasive (Shannon index, P &lt; .01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated significant TCRβ repertoire similarity between tumor and blood in distant-metastatic patients (comparison with nonmetastasis, P &lt; .05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant-metastatic individuals. A promising area under the curve value of 83.8% was obtained with the number of overlapping CDR3 clonotypes.ConclusionThe availability and reliability of TCR-seq render it prospective to translate these intrinsic attributes into clinical practice for monitoring distant metastasis in PTC patients.
Terrorism Prosecutions, Material Support, and Islamophobia
Authors: Said Wadie E. 
Published: July 2020

Abstract
With Islamophobia rife and the government list of foreign terrorist organizations (FTOs) telling us who is a threat, marginalized populations are being targeted and can expect a hostile and negative prosecutorial outcome. The large majority of terrorism prosecutions center on material support charges, which by their very structure concentrate on FTOs that are largely Islamist in ideology. Attaching a terrorist taint to a population based on its religious affiliation generates a kind of self-perpetuating law enforcement bias and prosecutorial outcome. Such police state tactics and assumptions only assure the adverse results of insisting that an exceptional status applies to those accused of terrorist activity or support for it. That, in the government's eyes, those individuals stem from one of the major monotheistic faiths in large part, seems to be a foregone conclusion that continues to affect the law's development in largely negative ways.
Lex Mercatoria, Legal Pluralism, and the Modern State through the Lens of the East India Company, 1600–1757
Authors: Bose Neilesh , Ramraj Victor V. 
Published: July 2020

AbstractAs the debate over historical antecedents to contemporary forms of lex mercatoria suggests, the nature of legal authority appears to be changing into a less familiar, more pluralistic form, even as states struggle to reassert their power. In seeking to understand this transformation in—and decentering of—the modern state's authority, we consider the multiple sources of legal authority claimed by the East India Company (1600–1757) and the way in which it positioned its legal and political legitimacy in relation to multiple and often competing centers of power in India. This article proposes the notion that the hegemony of a centralized modern state belongs only to a narrow sliver of history, hiding a much deeper pluralism within global history. In so doing, this article sets the stage for a sustained consideration of the plural nature of authority in the waxing and waning phases of the modern state.
Entanglements of Translation
Authors: Khan Razak 
Published: July 2020

AbstractThis article examines literary and cultural translations in the domain of thoughts on education by following the trajectories of intellectual networks among South Asian and German scholars. The main protagonists of this entangled intellectual history are Syed Abid Husain (1896–1978) and his teacher Eduard Spranger (1882–1963) and other actors who thought beyond British imperial educational ideology and practices. Husain engaged with the original writings of German educationists and translated Spranger's canonical text Psychologie des Jugendalters into Urdu as Nafsiyat-i unfuvan-i shabab. This text showcases a deep concern with the subject of youth that simultaneously exhibits immense potential but also shows glimpses of qualities inimical to national development. By drawing attention to how concepts, which are considered to be culturally and historically specific to German history, were translated into Urdu and Muslim cultural contexts in South Asia, this study seeks to arrive at a finer understanding of the entangled nature of Indo-German intellectual history that extends beyond nationalist frames.
Networks of Knowledge Production
Authors: Liebau Heike 
Published: July 2020

Abstract
This essay explores networks of knowledge exchange and practices of knowledge production between South Asian Muslims and academic circles in Germany between 1915 and 1930. It centers on the brothers Abdul Jabbar Kheiri and Abdul Sattar Kheiri and foregrounds their interaction and encounters with German scholars during the First World War and in Weimar Germany until the brothers' return to India. Taking into consideration the asymmetries at play, the article looks at the motivations for the interest in knowledge exchange on the German and on the Indian sides, which changed in accordance with the different political situations and the positionalities and dependencies of the actors. The knowledge exchange went far beyond the newly emerging discipline of Islamic studies and classical Indology to include disciplines like sociology, economy, philosophy, and art.
Novel Anxieties
Authors: Lorenz Beyza 
Published: July 2020

AbstractBuilding on recent scholarship on postcolonial theory and the history of the modern Middle East, this article analyzes the viewpoints of late nineteenth-century Ottoman novelists on the modernization projects of the Tanzimat and post-Tanzimat periods. It argues that the Ottoman novelists Ahmet Midhat, Fatma Aliye, and Recaizade Mahmut Ekrem developed a counter-discourse against rapid modernization projects in Istanbul. Through a depiction of everyday life experiences related to the latest inventions of modern technology, Ottoman novelists thematize individual anxieties on a range of topics, which included a criticism of productivity, changing gender roles for men and women, and the new order of time and space. Keeping in mind that drastic changes in technology introduced distinctive modes of experiencing time and space in the nineteenth century, this article suggests that criticism by Ottoman intellectuals can be better understood within the context of the reaction to shifting time-space schemes and the proliferation of new technologies across the globe.
Identification of 6-(piperazin-1-yl)-1,3,5-triazine as a chemical scaffold with broad anti-schistosomal activities
Authors: Padalino Gilda , Chalmers Iain W. , Brancale Andrea , Hoffmann Karl F. 
Published: July 2020

Background: Schistosomiasis, caused by infection with blood fluke schistosomes, is a neglected tropical disease of considerable importance in resource-poor communities throughout the developing world. In the absence of an immunoprophylactic vaccine and due to over-reliance on a single chemotherapy (praziquantel), schistosomiasis control is at risk should drug insensitive schistosomes develop. In this context, application of in silico virtual screening on validated schistosome targets has proven successful in the identification of novel small molecules with anti-schistosomal activity. Methods: Focusing on the Schistosoma mansoni histone methylation machinery, we herein have used RNA interference (RNAi), ELISA-mediated detection of H3K4 methylation, homology modelling and in silico virtual screening to identify a small collection of small molecules for anti-schistosomal testing. A combination of low to high-throughput whole organism assays were subsequently used to assess these compounds’ activities on miracidia to sporocyst transformation, schistosomula phenotype/motility metrics and adult worm motility/oviposition readouts. Results: RNAi-mediated knockdown of smp_138030/smmll-1 (encoding a histone methyltransferase, HMT) in adult worms (~60%) reduced parasite motility and egg production. Moreover, in silico docking of compounds into Smp_138030/SmMLL-1’s homology model highlighted competitive substrate pocket inhibitors, some of which demonstrated significant activity on miracidia, schistosomula and adult worm lifecycle stages together with variable effects on HepG2 cells. Particularly, the effect of compounds containing a 6-(piperazin-1-yl)-1,3,5-triazine core on adult schistosomes recapitulated the results of the smp_138030/smmll-1 RNAi screens. Conclusions: The biological data and the structure-activity relationship presented in this study define the 6-(piperazin-1-yl)-1,3,5-triazine core as a promising starting point in ongoing efforts to develop new urgently needed schistosomicides.
Mniejszość węgierska w polityce rządu Republiki Słowackiej w latach 1993‑1998
Authors: Żarna Krzysztof 
Published: July 2020

The Hungarian Minority in the Policy of the Government of the Slovak Republic in 1993‑1998
The article deals with the analysis of the policy of the Slovak Republic government towards the Hungarian minority in 1993‑1998. This is the period of the first five years of the country’s existence on the political map of Europe. During this period, Vladimír Mečiar (twice) and Jozef Moravčík served as prime ministers. The study is based on the assumption that in the analyzed period the policy of the Slovak authorities towards the Hungarian minority affected the tense relations between the Slovak Republic and the Republic of Hungary. In addition, it had a decisive impact on slowing down the process of Slovakia’s accession to the North Atlantic Alliance and the European Union. The method of decision analysis found its application in the study, which allowed the presentation of situations and processes that are the culmination of decisions taken by representatives of the Slovak authorities. The institutional and legal method allowed to analyze multilateral and bilateral agreements to which the Slovak Republic was a party, and legal acts.
“Hiding” a low-intensity 50  Gbit/s QPSK free-space OAM beam using an orthogonal coaxial high-intensity 50  Gbit/s QPSK beam
Authors: Song Haoqian , Almaiman Ahmed , Song Hao , Zhao Zhe , Zhang Runzhou , Pang Kai , Liu Cong , Li Long , Manukyan Karapet , Zach Shlomo , Cohen Nadav , Tur Moshe , Willner Alan E. 
Published: July 2020

In this paper, we experimentally demonstrate an approach that “hides” a low-intensity 50 Gbit/s quadrature-phase-keying (QPSK) free-space optical beam when it coaxially propagates on the same wavelength with an orthogonal high-intensity 50 Gbit/s QPSK optical beam. Our approach is to coaxially transmit the strong and weak beams carrying different orthogonal spatial modes within a modal basis set, e.g., orbital angular momentum (OAM) modes. Although the weak beam has much lower power than that of the strong beam, and the beams are in the same frequency band and on the same polarization, the two beams can still be effectively demultiplexed with little inherent crosstalk at the intended receiver due to their spatial orthogonality. However, an eavesdropper may not readily identify the weak beam when simply analyzing the spatial intensity profile. The correlation coefficient between the intensity profiles of the strong beam and the combined strong and weak beams is measured to characterize the potential for “hiding” a weak beam when measuring intensity profiles. Such a correlation coefficient is demonstrated to be higher than 0.997 when the power difference between the strong fundamental Gaussian beam and the weak OAM beam is

∼

8

,
∼

10

, and

∼

10

d
B

for the weak OAM

−

1

,
−

2

, and

−

3

beams, respectively. Moreover, a 50 Gbit/s QPSK data link having its

Q

factor above the 7% forward error correction limit is realized when the power of the weak OAM

−

3

beam is 30 dB lower than that of the strong fundamental Gaussian beam.