bluuebunny/crossref_metadata_2025 huggingface dataset:
Διερεύνηση των οικονομικών επιπτώσεων στις αστικές μετακινήσεις από την οικονομική κρίση
Authors: Νιμορακιωτάκη Δέσποινα
Published: November 2021

Οι μεταφορές συνδέονται άμεσα με τις εκάστοτε επικρατούσες οικονομικές συνθήκες, καθώς αυτές επιφέρουν μεταβολές στους τρόπους μετακίνησης των επιβατών και των αγαθών. Κατά το έτος 2009, η Ελλάδα εισήλθε σε μια περίοδο οικονομικής κρίσεως που είχε ως επακόλουθο διαταραχές στις αστικές μετακινήσεις. Στην παρούσα διδακτορική διατριβή διερευνούμε αν η οικονομική κρίση του 2009 επηρέασε την αλλαγή και την επιλογή του μέσου αστικής μεταφοράς. Πιο συγκεκριμένα, εξετάστηκε ο ρόλος των δημογραφικών, κοινωνικοοικονομικών και άλλων μεταφορικών παραγόντων σε ότι αφορά την αλλαγή και επιλογή του μέσου μεταφοράς που χρησιμοποιούν οι μετακινούμενοι στην αστική Αθήνα.Για την πραγμάτωση των παραπάνω, έγινε συλλογή δεδομένων από τη μητροπολιτική περιοχή της Αθήνας με την χρήση γραπτών ερωτηματολογίων το 2016, μέσα στην καρδιά της οικονομικής κρίσης. Για την διερεύνηση και ποσοτικοποίηση των επιπτώσεων της οικονομικής κρίσης στις αστικές μεταφορές χρησιμοποιήθηκαν μοντέλα διακριτής επιλογής. Τα αποτελέσματα δείχνουν πως λόγω της κρίσης, η κάλυψη από την δημόσια συγκοινωνία διαδραματίζει τον σημαντικότερο ρόλο στην αλλαγή του μέσου μεταφοράς, ενώ η επιλογή των αστικών συγκοινωνιών επηρεάζεται κυρίως από την ιδιοκτησία αυτοκινήτου, το φύλο, την ηλικία και το επίπεδο του εισοδήματος. Στη συγκεκριμένη έρευνα θα παρουσιαστούν παράλληλα τα ποιοτικά, ποσοτικά και κοινωνικά χαρακτηριστικά των μετακινουμένων, ώστε να συμβάλλουν, όποια μπορούν να συμβάλλουν στην εύρεση και στην πρόβλεψη των αλλαγών στην αστική κινητικότητα, αλλαγές οι οποίες θα μπορούσαν να αποτελέσουν πολύτιμα εργαλεία στα χέρια των υπεύθυνων χάραξης συγκοινωνιακής πολιτικής.
RNfuzzyApp: an R shiny RNA-seq data analysis app for visualisation, differential expression analysis, time-series clustering and enrichment analysis
Authors: Haering Margaux , Habermann Bianca H
Published: November 2021

RNA sequencing (RNA-seq) is a widely adopted affordable method for large scale gene expression profiling. However, user-friendly and versatile tools for wet-lab biologists to analyse RNA-seq data beyond standard analyses such as differential expression, are rare. Especially, the analysis of time-series data is difficult for wet-lab biologists lacking advanced computational training. Furthermore, most meta-analysis tools are tailored for model organisms and not easily adaptable to other species.

With RNfuzzyApp, we provide a user-friendly, web-based R shiny app for differential expression analysis, as well as time-series analysis of RNA-seq data. RNfuzzyApp offers several methods for normalization and differential expression analysis of RNA-seq data, providing easy-to-use toolboxes, interactive plots and downloadable results. For time-series analysis, RNfuzzyApp presents the first web-based, fully automated pipeline for soft clustering with the Mfuzz R package, including methods to aid in cluster number selection, cluster overlap analysis, Mfuzz loop computations, as well as cluster enrichments.

RNfuzzyApp is an intuitive, easy to use and interactive R shiny app for RNA-seq differential expression and time-series analysis, offering a rich selection of interactive plots, providing a quick overview of raw data and generating rapid analysis results. Furthermore, its assignment of orthologs, enrichment analysis, as well as ID conversion functions are accessible to non-model organisms.
COVID-19 impact: Customised economic stimulus package recommender system using machine learning techniques
Authors: Kannan Rathimala , Wang Ivan Zhi Wei , Ong Hway Boon , Ramakrishnan Kannan , Alamsyah Andry
Published: November 2021

Background: The Malaysian government reacted to the pandemic’s economic effect with the Prihatin Rakyat Economic Stimulus Package (ESP) to cushion the novel coronavirus 2019 (COVID-19) impact on households. The ESP consists of cash assistance, utility discount, moratorium, Employee Provident Fund (EPF) cash withdrawals, credit guarantee scheme and wage subsidies. A survey carried out by the Department of Statistics Malaysia (DOSM) shows that households prefer different types of financial assistance. These preferences forge the need to effectively customise ESPs to manage the economic burden among low-income households. In this study, a recommender system for such ESPs was designed by leveraging data analytics and machine learning techniques.

Methods: This study used a dataset from DOSM titled “Effects of COVID-19 on the Economy and Individual - Round 2,” collected from April 10 to April 24, 2020. Cross-Industry Standard Process for Data Mining was followed to develop machine learning models to classify ESP receivers according to their preferred subsidies types. Four machine learning techniques—Decision Tree, Gradient Boosted Tree, Random Forest and Naïve Bayes—were used to build the predictive models for each moratorium, utility discount and EPF and Private Remuneration Scheme (PRS) cash withdrawals subsidies. The best predictive model was selected based on F-score metrics.

Results: Among the four machine learning techniques, Gradient Boosted Tree outperformed the rest. This technique predicted the following: moratorium preferences with 93.8% sensitivity, 82.1% precision and 87.6% F-score; utilities discount with 86% sensitivity, 82.1% precision and 84% F-score; and EPF and PRS with 83.6% sensitivity, 81.2% precision and 82.4% F-score. Households that prefer moratorium subsidies did not favour other financial aids except for cash assistance. 

Conclusion: Findings present machine learning models that can predict individual household preferences from ESP. These models can be used to design customised ESPs that can effectively manage the financial burden of low-income households.
Time-Inconsistent Preferences and Strategic Self-Control in Digital Content Consumption
Authors: Zhang Shuo , Chan Tat Y. , Luo Xueming , Wang Xiaoyi
Published: November 2021

This study examines consumers’ time-inconsistent preferences in digital content consumption and their strategic self-control behaviors.
Hedging the Drift: Learning to Optimize Under Nonstationarity
Authors: Cheung Wang Chi , Simchi-Levi David , Zhu Ruihao
Published: November 2021

We introduce data-driven decision-making algorithms that achieve state-of-the-art dynamic regret bounds for a collection of nonstationary stochastic bandit settings. These settings capture applications such as advertisement allocation, dynamic pricing, and traffic network routing in changing environments. We show how the difficulty posed by the (unknown a priori and possibly adversarial) nonstationarity can be overcome by an unconventional marriage between stochastic and adversarial bandit learning algorithms. Beginning with the linear bandit setting, we design and analyze a sliding window-upper confidence bound algorithm that achieves the optimal dynamic regret bound when the underlying variation budget is known. This budget quantifies the total amount of temporal variation of the latent environments. Boosted by the novel bandit-over-bandit framework that adapts to the latent changes, our algorithm can further enjoy nearly optimal dynamic regret bounds in a (surprisingly) parameter-free manner. We extend our results to other related bandit problems, namely the multiarmed bandit, generalized linear bandit, and combinatorial semibandit settings, which model a variety of operations research applications. In addition to the classical exploration-exploitation trade-off, our algorithms leverage the power of the “forgetting principle” in the learning processes, which is vital in changing environments. Extensive numerical experiments with synthetic datasets and a dataset of an online auto-loan company during the severe acute respiratory syndrome (SARS) epidemic period demonstrate that our proposed algorithms achieve superior performance compared with existing algorithms.

This paper was accepted by George J. Shanthikumar, Management Science Special Section on Data-Driven Prescriptive Analytics.
Incomplete Contracts in Multi-period Procurement
Authors: Gretschko Vitali , Pollrich Martin
Published: November 2021

We analyze the problem of a buyer who purchases a long-term project from one of several suppliers. A changing state of the world influences the costs of the suppliers. We distinguish between complete contracts conditioning on all future realizations of the state of the world and incomplete contracts renegotiated whenever the state of the world changes. We provide conditions such that incomplete contracting does not pose a problem. If the changing state of the world is publicly observable and the buyer cannot switch between suppliers during the lifetime of the project, the buyer achieves the same surplus irrespective of whether contracts are complete or incomplete. An English auction followed by renegotiation whenever the state of the world changes is optimal. To identify conditions when buyers should consider drafting complete contracts, we extend the analysis by considering private information about the changing state of the world and supplier switching. In both cases, incomplete contracting poses a problem. In a survey of procurement consultants, we confirm that publicly observable states of the world via price indexes play an important role in procurement. Moreover, the consultants confirm that supplier switching is infrequent in procurement practice. Thus, incomplete contracting is less of a problem in a considerable share of procurement projects. However, complete contracts are useful and could be used more often.

This paper was accepted by Yan Chen, behavioral economics and decision analysis.
On-farm culture and pathogen identification: risks and benefits
Authors: Manning Al
Published: November 2021

Selective treatment of clinical mastitis cases based on the results of on-farm culture (OFC) has been suggested by several international experts. It is based on the theory that mastitis cases caused by Gram-negative species has high resolution rates, and those that do not resolve respond poorly to therapy. Several peer-reviewed studies have evaluated the accuracy of different OFC test kits, which are between 60–85% accurate at identifying Gram-positive pathogens. Implementation studies consistently show a reduction in antimicrobial use, although further research across larger populations is needed to assess the impact on mastitis cure. Any OFC protocol should be regularly reviewed with the herd veterinarian. Herds with a high bulk cell count, a high prevalence of Gram-positive pathogens (e.g. Streptococcus uberis), or with a high prevalence of Klebsiella spp. should carefully consider the impact of deferred or withholding treatment on mastitis cure.
Occurrence of Halyomorpha halys (Stål, 1855) (Hemiptera: Pentatomidae) in Rhodes Island, Greece
Authors: CORSINI-FOKA MARIA , ZAVA BRUNO , INSACCO GIANNI
Published: November 2021

The first finding of Halyomorpha halys in the island of Rhodes, Greece, is reported and the fast range expansion of this invasive species over the Aegean region is briefly discussed.
Defining Length Stability in Paediatric Femoral Shaft Fractures Treated with Titanium Elastic Nails
Authors: Shieh Alvin K. , Saiz Augustine M. , Hideshima Kelsey S. , Haus Brian M. , Leshikar Holly B.
Published: November 2021

Introduction

Optimal paediatric femoral shaft fracture patterns or lengths amenable to titanium elastic nail stabilization have not been well defined. The purpose of this study is to identify radiographic parameters predictive of treatment failure with flexible intramedullary nails based upon fracture morphology.

Methods

A retrospective review was performed of all femoral shaft fractures treated with flexible intramedullary nails over a five-year period. All patients with at least six weeks of postoperative radiographic imaging were included. Fracture characteristics included location, pattern, length, obliquity, angulation, translation and shortening. Postoperative radiographs were reviewed to determine shortening and angulation.

Results

There were 58 patients with 60 femoral shaft fractures stabilized with titanium nails, with 46 healing within acceptable parameters and 14 considered malunions. Six of the 14 malunions developed complications requiring early unplanned intervention. No patients in the treatment success group had a complication. Between the treatment success and failure groups, fracture pattern, location, length, obliquity, angulation, translation or shortening were not statistically different. Mean nail canal fill was significantly lower in the failure group (0.72 versus 0.81; p = 0.0146), with a receiver operating characteristic curve identifying canal fill 76% as the optimal threshold.

Conclusion

This is the first study to measure the length and obliquity of paediatric femoral shaft fractures and to determine their relationship to radiographic alignment after healing. None of the preoperative fracture characteristics were predictive of malalignment or shortening. We recommend the use of larger nail sizes in the treatment of paediatric femoral shaft fractures, especially if there is concern for residual instability.

Level of evidence

IV
Intensity-interrogated magnetic sensor based on S-tapered and multimode fiber integrated with ferrofluids
Authors: Duan Shaoxiang , Liu Bo , Zhang Hao , Liu Haifeng , Lin Wei , Wu Jixuan , Song Binbin
Published: November 2021

In this study, a high-sensitivity intensity-interrogated fiber sensor integrated with ferrofluids is proposed for the measurement of a weak magnetic field (MF) with resolved temperature cross-sensitivity. The MF sensor is fabricated simply by an offset tapering single-mode fiber concatenated with a multimode fiber (MMF), which is then encapsulated into a capillary tube filled with ferrofluids. In the presence of MMF, stronger mode coupling could be achieved over the S-tapered fiber region. Its spectral response to variations in the applied MF intensity and ambient temperature have been investigated in detail. The proposed sensor shows a high MF sensitivity up to

−

0.1130

d
B

/

O
e

for the measurement range of 40 to 120 Oe, which, to our best knowledge, is higher than other previously reported MF sensors. And moreover, the measurement errors caused by temperature cross-sensitivity have been corrected by using a sensing matrix for the temperature range of 25°C to 35°C. Our proposed MF sensor possesses the advantages of high sensitivity, low cost, and applicability for applications in weak MF measurements.
Extraction of phase-based optoretinograms (ORG) from serial B-scans acquired over tens of seconds by mouse retinal raster scanning OCT system
Authors: Pijewska Ewelina , Zhang Pengfei , Meina Michał , Meleppat Ratheesh K. , Szkulmowski Maciej , Zawadzki Robert J.
Published: November 2021

Several specialized retinal optical coherence tomography (OCT) acquisition and processing methods have been recently developed to allow in vivo probing of light-evoked photoreceptors function, focusing on measurements in individual photoreceptors (rods and cones). Recent OCT investigations in humans and experimental animals have shown that the outer segments in dark-adapted rods and cones elongate in response to the visible optical stimuli that bleach fractions of their visual photopigment. We have previously successfully contributed to these developments by implementing OCT intensity-based “optoretinograms” (ORG), the paradigm of using near-infrared OCT (NIR OCT) to measure bleaching-induced back-scattering and/or elongation changes of photoreceptors in the eye in vivo. In parallel, several groups have successfully implemented phase-based ORGs, mainly in human studies, exploiting changes in the phases of back-scattered light. This allowed more sensitive observations of tiny alterations of photoreceptors structures. Applications of the phase-based ORG have been implemented primarily in high speed and cellular resolution AO-OCT systems that can visualize photoreceptor mosaic, allowing phase measurements of path length changes in outer segments of individual photoreceptors. The phase-based ORG in standard resolution OCT systems is much more demanding to implement and has not been explored extensively. This manuscript describes our efforts to implement a phase analysis framework to retinal images acquired with a standard resolution and raster scanning OCT system, which offers much lower phase stability than line-field or full-field OCT detection schemes due to the relatively slower acquisition speed. Our initial results showcase the successful extraction of phase-based ORG signal from the B-scans acquired at ∼100 Hz rate and its favorable comparison with intensity-based ORG signal extracted from the same data sets. We implemented the calculation of phase-based ORG signals using Knox-Thompson paths and modified signal recovery by adding decorrelation weights. The phase-sensitive ORG signal analysis developed here for mouse retinal raster scanning OCT systems could be in principle extended to clinical retinal raster scanning OCT systems, potentially opening doors for clinically friendly ORG probing.
Arrayed dual-mode integrated liquid crystal microlens driven jointly by both independent signal voltages
Authors: Wang Zhe , Chen Mingce , Hu Chai , Liu Kewei , Li Zhexun , Ye Mao , Chen Zhaomin , Yuan Xiangdong , Wang Haiwei , Xie Changsheng , Zhang Xinyu
Published: November 2021

A new type of liquid crystal microlens array (LCMLA) constructed by a single-layered LC material is proposed. The basic dual-mode integrated LC microlens includes a concentric microhole electrode and a central plate electrode. Compared with traditional LC microlenses driven electrically, the dual-mode integrated LC microlens presents a better light control effect, such as being flexibly adjusted between the beam convergence and divergence modes, enlarging both the tunable range of the signal voltage and the focal length and also reducing the focal spot assisted by a convex electric-field generated by the central plate electrode, acquiring a sharper beam diverging microring formed by the concave LC microlens assisted by a concave electric-field generated by the microhole electrode. At the same time, we have also verified that the electric-field filling factor of the dual-mode integrated LCMLA can be obviously increased through jointly tuning the signal voltages applied independently over both the microhole electrode and the central plate electrode. This research has laid a solid foundation for continuously developing LCMLA technology.
Cylindrical wave-based off-axis digital holography with long field of view
Authors: Chen Gui-Xiang , Huang Hong-Yi , Zhao Qian , Yue Qing-Yang , Guo Cheng-Shan
Published: November 2021

We present a new, to the best of our knowledge, type of off-axis digital holographic imaging method with a long field of view (FOV). In the method, the pre-magnification recording geometry is realized by a cylindrical lens (CL) or cylindrical beam instead of a conventional objective or spherical beam in traditional off-axis digital holography (DH). At the same time, the reference beam is replaced by a divergent cylindrical beam. Theoretical analysis and experiments have justified that, in off-axis DHs, the adoption of the cylindrical beams can realize a one-dimensional pre-magnification of the object beam only in the off-axis direction to satisfy the bandwidth constraint, and at the same time the FOV of the reconstructed image in the orthogonal direction can remain unaffected. In comparison with existing off-axis DHs, this cylindrical wave-based DH (CWDH) method has a distinct advantage in expanding the FOV of the reconstructed image. The FOV feature of the CWDH makes it especially suitable for applications that require a long FOV such as imaging samples in microfluidic channels.
Enhanced sensitivity of optical fiber vibration sensor based on radio-frequency Michelson interferometer
Authors: Deng Ming , Zhang Tianheng , Nan Xinhao , Tang Yangxu , Feng Danqi , Guo Nan , Deng Shudan , Zhu Tao
Published: November 2021

We propose and demonstrate a new scheme for enhancing the sensitivity
of an optical fiber vibration sensor based on microwave
interferometry, which is realized by an incoherent optical Michelson
interferometer (MI). The sensing arm of the MI is sensitive to
environmental vibration; this will cause changes in the phase of the
reflection spectra in the microwave domain. The phase sensitivity can
be improved by adjusting the power ratio of the two beams in the
interferometer and the driving frequency of the modulator. The system
can overcome the problem of interference fading so that it is immune
to environmental disturbance. The proposed scheme has merits of
simplicity and compact configuration, and may provide a new type of
high-precision fiber sensor for measuring vibration, temperature,
strain, and so on.
Incoherent two-color pulse compounds: publisher’s note
Authors: Melchert O. , Demircan A.
Published: November 2021

This publisher’s note contains corrections to Opt. Lett.
46, 5603 (2021)OPLEDP0146-959210.1364/OL.440567.
Hyperuniform disordered metal-insulator-metal gap plasmon metasurface near perfect light absorber
Authors: Kim Wonkyu , Simpkins Blake S. , Guo Hong , Hendrickson Joshua R. , Guo Junpeng
Published: November 2021

In this work, we first introduce hyperuniform disordered patterns to a metal-insulator-metal gap plasmon metasurface and demonstrate enhanced wideband light absorption in the visible and near-infrared spectral region. Measurement of optical reflectance from fabricated periodic, hyperuniform disordered, and random pattern gap plasmon metasurface devices has revealed the origins of the two resonance modes of the gap plasmon metasurface structure: a localized gap plasmon resonance mode and a non-local guided optical resonance mode. The technique of using hyperuniform disordered patterns for investigating complex resonance modes of structured materials can be used for design of a variety of new metamaterials.
A shared transcriptional code orchestrates temporal patterning of the central nervous system
Authors: Sagner Andreas , Zhang Isabel , Watson Thomas , Lazaro Jorge , Melchionda Manuela , Briscoe James
Published: November 2021

The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell−derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.
Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability
Authors: Lombardi Aniello , Luhmann Heiko J. , Kilb Werner
Published: November 2021

GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as shunting inhibition and GABAergic effects on spatiotemporal filtering of excitatory inputs must be considered. To evaluate at which reversal potential a net excitatory effect was imposed by GABA (EGABAThr), we performed a detailed in-silico study using simple neuronal topologies and distinct spatiotemporal relations between GABAergic and glutamatergic inputs.

These simulations revealed for GABAergic synapses located at the soma an EGABAThrclose to action potential threshold (EAPThr), while with increasing dendritic distance EGABAThrshifted to positive values. The impact of GABA on AMPA-mediated inputs revealed a complex temporal and spatial dependency. EGABAThrdepends on the temporal relation between GABA and AMPA inputs, with a striking negative shift in EGABAThrfor AMPA inputs appearing after the GABA input. The spatial dependency between GABA and AMPA inputs revealed a complex profile, with EGABAThrbeing shifted to values negative to EAPThrfor AMPA synapses located proximally to the GABA input, while for distally located AMPA synapses the dendritic distance had only a minor effect on EGABAThr. For tonic GABAergic conductances EGABAThrwas negative to EAPThrover a wide range of gGABAtonicvalues. In summary, these results demonstrate that for several physiologically relevant situations EGABAThris negative to EAPThr, suggesting that depolarizing GABAergic responses can mediate excitatory effects even if EGABAdid not reach EAPThr.
Binding free energy decomposition and multiple unbinding paths of buried ligands in a PreQ1 riboswitch
Authors: Hu Guodong , Zhou Huan-Xiang
Published: November 2021

Riboswitches are naturally occurring RNA elements that control bacterial gene expression by binding to specific small molecules. They serve as important models for RNA-small molecule recognition and have also become a novel class of targets for developing antibiotics. Here, we carried out conventional and enhanced-sampling molecular dynamics (MD) simulations, totaling 153.5 μs, to characterize the determinants of binding free energies and unbinding paths for the cognate and synthetic ligands of a PreQ1 riboswitch. Binding free energy analysis showed that two triplets of nucleotides, U6-C15-A29 and G5-G11-C16, contribute the most to the binding of the cognate ligands, by hydrogen bonding and by base stacking, respectively. Mg2+ ions are essential in stabilizing the binding pocket. For the synthetic ligands, the hydrogen-bonding contributions of the U6-C15-A29 triplet are significantly compromised, and the bound state resembles the apo state in several respects, including the disengagement of the C15-A14-A13 and A32-G33 base stacks. The bulkier synthetic ligands lead to significantly loosening of the binding pocket, including extrusion of the C15 nucleobase and a widening of the C15-C30 groove. Enhanced-sampling simulations further revealed that the cognate and synthetic ligands unbind in almost opposite directions. Our work offers new insight for designing riboswitch ligands.
Immunoprofiling of fresh HAM/TSP blood samples shows altered innate cell responsiveness
Authors: Rocamonde Brenda , Futsch Nicolas , Orii Noemia , Allatif Omran , Penalva de Oliveira Augusto Cesar , Mahieux Renaud , Casseb Jorge , Dutartre Hélène
Published: November 2021

The Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. Immune cells from the adaptive compartment are involved in disease manifestation but whether innate cell functions participate in disease occurrence has not been evaluated. In this study, we analyzed innate cell responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower response of IFNα+ DCs and monocytes in HAM/TSP compared to asymptomatic carriers, as a potential consequence of corticosteroid treatments. In contrast, a higher frequency of monocytes producing MIP-1α and pDC producing IL-12 was detected in HAM/TSP blood samples, together with higher IFNγ responsiveness of NK cells, suggesting an increased sensitivity to inflammatory response in HAM/TSP patients compared to asymptomatic carriers. This sustained inflammatory responsiveness could be linked or be at the origin of the neuroinflammatory status in HAM/TSP patients. Therefore, the mechanism underlying this dysregulations could shed light onto the origins of HAM/TSP disease.
Effects of Importin α1/KPNA1 deletion and adolescent social isolation stress on psychiatric disorder-associated behaviors in mice
Authors: Sakurai Koki , Itou Taichi , Morita Makiko , Kasahara Emiko , Moriyama Tetsuji , Macpherson Tom , Ozawa Takaaki , Miyamoto Yoichi , Yoneda Yoshihiro , Sekiyama Atsuo , Oka Masahiro , Hikida Takatoshi
Published: November 2021

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders.
Treatment selection using prototyping in latent-space with application to depression treatment
Authors: Kleinerman Akiva , Rosenfeld Ariel , Benrimoh David , Fratila Robert , Armstrong Caitrin , Mehltretter Joseph , Shneider Eliyahu , Yaniv-Rosenfeld Amit , Karp Jordan , Reynolds Charles F. , Turecki Gustavo , Kapelner Adam
Published: November 2021

Machine-assisted treatment selection commonly follows one of two paradigms: a fully personalized paradigm which ignores any possible clustering of patients; or a sub-grouping paradigm which ignores personal differences within the identified groups. While both paradigms have shown promising results, each of them suffers from important limitations. In this article, we propose a novel deep learning-based treatment selection approach that is shown to strike a balance between the two paradigms using latent-space prototyping. Our approach is specifically tailored for domains in which effective prototypes and sub-groups of patients are assumed to exist, but groupings relevant to the training objective are not observable in the non-latent space. In an extensive evaluation, using both synthetic and Major Depressive Disorder (MDD) real-world clinical data describing 4754 MDD patients from clinical trials for depression treatment, we show that our approach favorably compares with state-of-the-art approaches. Specifically, the model produced an 8% absolute and 23% relative improvement over random treatment allocation. This is potentially clinically significant, given the large number of patients with MDD. Therefore, the model can bring about a much desired leap forward in the way depression is treated today.
Stroke risk associated with NSAIDs uses in women with dysmenorrhea: A population-based cohort study
Authors: Lin Ya-Wen , Wang Jong-Yi , Lin Ming-Hung
Published: November 2021

Objective

Dysmenorrhea is among the most common type of gynecological problem, affecting young women across the globe. This study assessed the comparative risk of stroke associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and non-NSAIDs in women with dysmenorrhea while taking into account the following factors such as age, history of pregnancy, NSAIDs uses and its duration of use, and selected comorbidities.

Methodology

We used a quantitative research approach based on a comparative case-control study design. The study data was selected from the Longitudinal Health Insurance Database (LHID) 2000, of the Taiwan National Health Research Institutes. Among the estimated 23.4 million insured Taiwanese, who were covered by the Taiwan health insurance system, in the 2000 registry of beneficiaries, one million individuals were randomly selected from the database. A total of 24,955 females suffering from dysmenorrhea were selected for the study. Out of those 3238 (13%) participated in the study group and 21,717 (87%) were randomly distributed into the controls group. Women in the age range, 15–49 years, who did not have any history of stroke, hysterectomy, and/or ovariectomy, were included in the study. A comparative proportional distribution analysis was used for data analysis.

Results

Age and use of NSAIDs and its duration of usage were factors associated with an increased incidence of stroke. The stroke incidence rate was 12.77 per 10,000 person-years, and 1.83-fold higher in NSAIDs use cohort than in comparisons with adjusted hazard ratio (aHR) of 1.47 (95% CI = 0.93–2.32). Among women with dysmenorrhea use of NSAIDs, the stroke incidence increased to 2.29-fold (aHR 95% CI = 1.36–3.84) in those use for ≧24 days per month and to 0.51-fold (aHR 95% CI = 0.13–2.10) in those use for 6–12 days per month.

Conclusions

Women with dysmenorrhea who use NSAIDs have a higher risk of stroke. Especially young women, the risk of stroke is further increased, and the longer the medication, the higher the risk of stroke. Every woman with symptoms of dysmenorrhea deserves specialized outpatient treatment and care.
A novel serum biomarker quintet reveals added prognostic value when combined with standard clinical parameters in prostate cancer patients by predicting biochemical recurrence and adverse pathology
Authors: Athanasiou Alcibiade , Tennstedt Pierre , Wittig Anja , Huber Ramy , Straub Oliver , Schiess Ralph , Steuber Thomas
Published: November 2021

The objective was to determine the prognostic utility of a new biomarker combination in prostate cancer (PCa) patients undergoing Radical Prostatectomy (RP). Serum samples and clinical data of 557 men who underwent RP for PCa with pathological stage (pT) <3 at Martini Clinic (Hamburg, Germany) were used for analysis. Clinical Grade Group and clinical stage was determined using biopsy samples while tumor marker concentrations were measured in serum using immunoassays. The prognostic utility of the proposed marker combination was assessed using Cox proportional hazard regression and Kaplan-Meier analysis. The performance was compared to the Cancer of the Prostate Risk Assessment (CAPRA) score in the overall cohort and in a low-risk patient subset. A multivariable model comprising fibronectin 1, galectin-3-binding protein, lumican, matrix metalloprotease 9, thrombospondin-1 and PSA together with clinical Grade Group (GG) and clinical stage (cT) was created. The proposed model was a significant predictor of biochemical recurrence (BCR) (HR 1.29 per 5 units score, 95%CI 1.20–1.38, p<0.001). The Kaplan-Meier analysis showed that the proposed model had a better prediction for low-risk disease after RP compared to CAPRA (respectively 5.0% vs. 9.1% chance of BCR). In a pre-defined low risk population subset, the risk of BCR using the proposed model was below 5.2% and thus lower when compared to CAPRA = 0–2 (9%), GG<2 (7%) and NCCN = low-risk (6%) subsets. Additionally, the proposed model could significantly (p<0.001) discriminate patients with adverse pathology (AP) events at RP from those without. In conclusion, the proposed model is superior to CAPRA for the prediction of BCR after RP in the overall cohort as well as a in a pre-defined low risk patient population subset. It is also significantly associated with AP at RP.
Cost-effectiveness analysis of apixaban versus vitamin K antagonists for antithrombotic therapy in patients with atrial fibrillation after acute coronary syndrome or percutaneous coronary intervention in Spain
Authors: Rivolo Simone , Di Fusco Manuela , Polanco Carlos , Kang Amiee , Dhanda Devender , Savone Mirko , Skandamis Aristeidis , Kongnakorn Thitima , Soto Javier
Published: November 2021

Background/Objective

AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI.

Methods

A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%.

Results

Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, –13.9 and –1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA.

Conclusions

Apixaban was a dominant treatment strategy than VKA from both the Spanish payer’s and societal perspectives, regardless of treatment strategy considered.
Blood bank storage of red blood cells increases RBC cytoplasmic membrane order and bending rigidity
Authors: Himbert Sebastian , Qadri Syed M. , Sheffield William P. , Schubert Peter , D’Alessandro Angelo , Rheinstädter Maikel C.
Published: November 2021

Blood banks around the world store blood components for several weeks ensuring its availability for transfusion medicine. Red blood cells (RBCs) are known to undergo compositional changes during storage, which may impact the cells’ function and eventually the recipients’ health. We extracted the RBC’s cytoplasmic membrane (RBCcm) to study the effect of storage on the membranes’ molecular structure and bending rigidity by a combination of X-ray diffraction (XRD), X-ray diffuse scattering (XDS) and coarse grained Molecular Dynamics (MD) simulations. Blood was stored in commercial blood bags for 2 and 5 weeks, respectively and compared to freshly drawn blood. Using mass spectrometry, we measured an increase of fatty acids together with a slight shift towards shorter tail lengths. We observe an increased fraction (6%) of liquid ordered (lo) domains in the RBCcms with storage time, and an increased lipid packing in these domains, leading to an increased membrane thickness and membrane order. The size of both,loand liquid disordered (ld) lipid domains was found to decrease with increased storage time by up to 25%. XDS experiments reveal a storage dependent increase in the RBCcm’s bending modulusκby a factor of 2.8, from 1.9 kBT to 5.3 kBT. MD simulations were conducted in the absence of proteins. The results show that the membrane composition has a small contribution to the increased bending rigidity and suggests additional protein-driven mechanisms.
Blood transfusion and the risk for infections in kidney transplant patients
Authors: Massicotte-Azarniouch David , Sood Manish M. , Fergusson Dean A. , Chassé Michaël , Tinmouth Alan , Knoll Greg A.
Published: November 2021

Background

Receipt of a red blood cell transfusion (RBCT) post-kidney transplantation may alter immunity which could predispose to subsequent infection.

Methods

We carried out a single-center, retrospective cohort study of 1,258 adult kidney transplant recipients from 2002 to 2018 (mean age 52, 64% male). The receipt of RBCT post-transplant (468 participants transfused, total 2,373 RBCT) was analyzed as a time-varying, cumulative exposure. Adjusted cox proportional hazards models were used to calculate hazard ratios (HR) for outcomes of bacterial or viral (BK or CMV) infection.

Results

Over a median follow-up of 3.8 years, bacterial infection occurred in 34% of participants at a median of 409 days post-transplant and viral infection occurred in 25% at a median of 154 days post-transplant. Transfusion was associated with a step-wise higher risk of bacterial infection (HR 1.35, 95%CI 0.95–1.91; HR 1.29, 95%CI 0.92–1.82; HR 2.63, 95%CI 1.94–3.56; HR 3.38, 95%CI 2.30–4.95, for 1, 2, 3–5 and >5 RBCT respectively), but not viral infection. These findings were consistent in multiple additional analyses, including accounting for reverse causality.

Conclusion

Blood transfusion after kidney transplant is associated with a higher risk for bacterial infection, emphasizing the need to use transfusions judiciously in this population already at risk for infections.
Acceptability, effectiveness and cost-effectiveness of blended cognitive-behavioural therapy (bCBT) versus face-to-face CBT (ftfCBT) for anxiety disorders in specialised mental health care: A 15-week randomised controlled trial with 1-year follow-up
Authors: Romijn Geke , Batelaan Neeltje , Koning Jeroen , van Balkom Anton , de Leeuw Aart , Benning Friederike , Hakkaart van Roijen Leona , Riper Heleen
Published: November 2021

Background

Anxiety disorders are highly prevalent and cause substantial economic burden. Blended cognitive-behavioural therapy (bCBT), which integrates Internet-based CBT and face-to-face CBT (ftfCBT), is an attractive and potentially cost-saving treatment alternative to conventional CBT for patients with anxiety disorders in specialised mental health care. However, little is known about the effectiveness of bCBT in routine care. We examined the acceptability, effectiveness and cost-effectiveness of bCBT versus ftfCBT in outpatient specialised care to patients with panic disorder, social anxiety disorder and generalised anxiety disorder.

Methods and findings

Patients with anxiety disorders were randomised to bCBT (n = 52) or ftfCBT (n = 62). Acceptability of bCBT and ftfCBT were evaluated by assessing treatment preference, adherence, satisfaction and therapeutic alliance. Costs and effects were assessed at post-treatment and one-year follow-up. Primary outcome measure was the Beck Anxiety Inventory (BAI). Secondary outcomes were depressive symptoms, general psychopathology, work and social adjustment, quality of life and mastery. Incremental cost-effectiveness ratios (ICERs) were computed from societal and healthcare perspectives by calculating the incremental costs per incremental quality-adjusted life year (QALY). No significant differences between bCBT and ftfCBT were found on acceptability or effectiveness measures at post-treatment (Cohen’s d between-group effect size on BAI = 0.15, 95% CI −0.30 to 0.60) or at one-year follow-up (d = −0.38, 95% CI −0.84 to 0.09). The modelled point estimates of societal costs (bCBT €10945, ftfCBT €10937) were higher and modelled point estimates of direct medical costs (bCBT €3748, ftfCBT €3841) were lower in bCBT. The acceptability curves showed that bCBT was expected to be a cost-effective intervention. Results should be carefully interpreted due to the small sample size.

Conclusions

bCBT appears an acceptable, clinically effective and potentially cost-saving alternative option for treating patients with anxiety disorders. Trials with larger samples are needed to further investigate cost-effectiveness.

Trial registration

Netherlands Trial Register: NTR4912.
Antimicrobial prescription practices for outpatients with acute respiratory tract infections: A retrospective, multicenter, medical record-based study
Authors: Ishida Tomoharu , Hagiya Hideharu , Honda Hiroyuki , Nakano Yasuhiro , Ogawa Hiroko , Obika Mikako , Ueda Keigo , Kataoka Hitomi , Hanayama Yoshihisa , Otsuka Fumio
Published: November 2021

Antimicrobial stewardship for outpatients with acute respiratory tract infections (ARTIs) should be urgently promoted in this era of antimicrobial resistance. Previous large-sample studies were based on administrative data and had limited reliability. We aimed to identify current antimicrobial prescription practices for ARTIs by directly basing on medical records. This multicenter retrospective study was performed from January to December in 2018, at five medical institutes in Japan. We targeted outpatients aged ≥18 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting ARTIs. We divided the eligible cases into three age groups (18–64 years, 65–74 years, and ≥75 years). We defined broad-spectrum antimicrobials as third-generation cephalosporins, macrolides, fluoroquinolones, and faropenem. Primary and secondary outcomes were defined as the proportion of antimicrobial prescriptions for the common cold and other respiratory tract infections, respectively. Totally, data of 3,940 patients were collected. Of 2,914 patients with the common cold, 369 (12.7%) were prescribed antimicrobials. Overall, compared to patients aged ≥75 years (8.5%), those aged 18–64 years (16.6%) and those aged 65–74 years (12.1%) were frequently prescribed antimicrobials for the common cold (odds ratio [95% confidential interval]; 2.15 [1.64–2.82] and 1.49 [1.06–2.09], respectively). However, when limited to cases with a valid diagnosis of the common cold by incorporating clinical data, no statistical difference was observed among the age groups. Broad-spectrum antimicrobials accounted for 90.2% of the antimicrobials used for the common cold. Of 1,026 patients with other respiratory infections, 1,018 (99.2%) were bronchitis, of which antimicrobials were prescribed in 49.9% of the cases. Broad-spectrum antimicrobials were the main agents prescribed, accounting for nearly 90% of prescriptions in all age groups. Our data suggested a favorable practice of antimicrobial prescription for outpatients with ARTIs in terms of prescribing proportions, or quantitative aspect. However, the prescriptions were biased towards broad-spectrum antimicrobials, highlighting the need for further antimicrobial stewardship in the outpatient setting from a qualitative perspective.