bluuebunny/crossref_metadata_2025 huggingface dataset:
Centre of mass location, flight modes, stability and dynamic modelling of gliders
Authors: Li Huilin , Goodwill Tristan , Jane Wang Z. , Ristroph Leif
Published: February 2022

Falling paper flutters and tumbles through air, whereas a paper airplane glides smoothly if its leading edge is appropriately weighted. We investigate this transformation from ‘plain paper’ to ‘paper plane’ through experiments, aerodynamic modelling and free flight simulations of thin plates with differing centre of mass (CoM) locations. Periodic modes such as fluttering, tumbling and bounding give way to steady gliding and then downward diving as the CoM is increasingly displaced towards one edge. To explain these observations, we formulate a quasi-steady aerodynamic model whose force and torque coefficients are informed by experimental measurements. The dependencies on angle of attack reflect the transition from attached to separated flow and a dynamic centre of pressure, effects that prove critical to reproducing the observed motions of paper planes in air and plates in water. Because the model successfully accounts for unsteady and steady flight modes, it may be usefully applied to further problems involving actuated motions, feedback control and interactions with ambient flows.
Structures of adnominal possession in Austria’s traditional dialects: Variation and change
Authors: Bülow Lars , Vergeiner Philip C. , Elspaß Stephan
Published: February 2022

By means of the first comprehensive apparent-time study of Austria’s traditional dialects, this paper explores the use of adnominal syntactic constructions of expressing the semantic relation of possession. The article focuses on both the geographical variation and the interplay of syntax, semantics, and pragmatics. The analyses are based on data from direct recordings of 162 speakers from forty villages and on written questionnaire data from 103 of these speakers from thirty-seven villages. The analyses reveal clear geographical patterns for those constructions in which the possessor phrase precedes the possessum phrase within the entire construction. We propose to focus on the discursive-pragmatic properties of the possessor phrase to explain the fact that each of the observed dialects allows the possessor to precede the possessum. We provide evidence that referential anchoring, combined with the concept of accessibility, is the key to explaining the syntactic order within the used constructions.
Characterisation of equalisation problems via random walks
Authors: Nakata Toshio
Published: February 2022

This is a follow-up to a recent Gazette Article by Abel [1]. We investigate probabilistic equalisation problems proposed in [1] using the Pólya urn, and characterise them through simple random walks.
How the “Jerusalem Scrolls” Became the Dead Sea Scrolls from Qumran Cave 1: Archaeology, the Antiquities Market, and the Spaces In Between
Authors: Nongbri Brent
Published: February 2022

Seven animal hide scrolls with Hebrew and Aramaic writing were sold in Jerusalem in 1947. Additional smaller fragments of similar scrolls were sold from 1948 to 1950. Within a few years of their appearance, these “Jerusalem Scrolls” as they were then known, became “the Dead Sea Scrolls from Qumran Cave 1.” While this change of names may seem trivial, it glosses over some difficult questions about the provenance of these materials. What we now call “Cave 1Q” or “Qumran Cave 1” was excavated in 1949, but scholarship reveals considerable confusion concerning which purchased scrolls can be materially connected to fragments that were excavated by archaeologists under controlled conditions in Cave 1. Furthermore, Cave 1 is often treated as if it was a sealed context rather than the highly contaminated site that it actually was at the time of its excavation by archaeologists. For these reasons, it is not completely clear whether all the scrolls usually assigned to Cave 1 actually originated at this site. This article is an attempt to sort through the evidence to determine exactly which scrolls and fragments attributed to Cave 1 were purchased, when and from whom such pieces were purchased, and what can actually be known with confidence about the connection of these “Jerusalem Scrolls” with the site we now call Qumran Cave 1.
From “God of the World” to “God of the Heavens”: From the Mishneh Torah to The Guide of the Perplexed
Authors: Hadad Eliezer
Published: February 2022

Maimonides opened almost all of his books with the verse “in the name of the Lord, the God of the world” (Gen 21:33). This verse describes the nature of Abraham’s calling, which Maimonides interprets, both in the Mishneh Torah and in the Guide of the Perplexed, as an effort to persuade others to abandon their idolatrous perceptions and affirm the uniqueness of God. There is, however, a difference between the way Maimonides describes Abraham and his calling in the Mishneh Torah and their portrayal in the Guide of the Perplexed. In the former, Abraham is presented as a philosopher; in the latter, as a biblical prophet. In the Mishneh Torah, Maimonides’s description of Abraham revolves around a verse that describes the “God of the world”; in the Guide of the Perplexed, Maimonides adds verses in which Abraham mentions “heaven.” In this article, I shall examine these differences and suggest that they represent developments and shifts in Maimonides’s own philosophical position.
A scoping review exploring reablement models of training and client assessment for older people in primary health care
Authors: Bramble Marguerite , Young Sarah , Prior Sarah , Maxwell Hazel , Campbell Steve , Marlow Annette , Doherty Douglass
Published: February 2022

Aim:

The aim of this scoping review is to explore the evidence by which community service providers have integrated reablement models of staff training and client assessment into practice.

Background:

The concept of reablement, which has emerged during the last two decades globally, has recently been defined by health experts from 11 countries through a Delphi study. Reablement is seen as a way to support integrated frameworks that achieve person-centred, long-term care and assistance across community settings. International research indicates there is some evidence of developing models of reablement that include staff training and individual components of client assessment. However, evidence of integrating reablement into interdisciplinary practice continues to be sparse.

Methods:

The review adopted the preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) approach. Inclusion criteria for the review related to community care, primary care, long-term care, and residential care. Populations of interest included service providers, interdisciplinary staff, trainers, and assessors.

Results:

A total of 11 papers were reviewed. The studies varied in their approach to reablement training and client assessment frameworks. Three studies included assessment of staff well-being. All included evidence-based, person-centred components that can be integrated across health care settings. Single disciplinary approaches were used in all studies and some included training evaluation.

Conclusion:

This review has identified that currently reablement models are not yet embedded as frameworks for practice by community service providers in primary health care settings. Different programmes of training and assessment are being designed based on single disciplinary approaches and the context in which they are delivered. Further developmental work is required to integrate the components of discipline-specific training programmes within interdisciplinary frameworks. This will achieve not only an integrated framework for delivery across settings but also further the success of ‘ageing in place’ policy.
Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections
Authors: Villegas-Hernández Luis E. , Dubey Vishesh , Nystad Mona , Tinguely Jean-Claude , Coucheron David A. , Dullo Firehun T. , Priyadarshi Anish , Acuña Sebastian , Ahmad Azeem , Mateos José M. , Barmettler Gery , Ziegler Urs , Birgisdottir Åsa Birna , Hovd Aud-Malin Karlsson , Fenton Kristin Andreassen , Acharya Ganesh , Agarwal Krishna , Ahluwalia Balpreet Singh
Published: February 2022

Histology involves the observation of structural features in tissues using a microscope. While diffraction-limited optical microscopes are commonly used in histological investigations, their resolving capabilities are insufficient to visualize details at subcellular level. Although a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases, the system complexity, high operating cost, lack of multi-modality, and low-throughput imaging of these methods limit their wide adoption for histological analysis. In this study, we introduce the photonic chip as a feasible high-throughput microscopy platform for super-resolution imaging of histological samples. Using cryopreserved ultrathin tissue sections of human placenta, mouse kidney, pig heart, and zebrafish eye retina prepared by the Tokuyasu method, we demonstrate diverse imaging capabilities of the photonic chip including total internal reflection fluorescence microscopy, intensity fluctuation-based optical nanoscopy, single-molecule localization microscopy, and correlative light-electron microscopy. Our results validate the photonic chip as a feasible imaging platform for tissue sections and pave the way for the adoption of super-resolution high-throughput multimodal analysis of cryopreserved tissue samples both in research and clinical settings.
Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma
Authors: Cai Yongchao , Fu Yong , Liu Changcheng , Wang Xicheng , You Pu , Li Xiuhua , Song Yanxiang , Mu Xiaolan , Fang Ting , Yang Yang , Gu Yuying , Zhang Haibin , He Zhiying
Published: February 2022

Microvascular invasion (MVI) is presently evaluated as a high-risk factor to be directly relative to postoperative prognosis of hepatocellular carcinoma (HCC). Up to now, diagnosis of MVI mainly depends on the postoperative pathological analyses with H&E staining assay, based on numbers and distribution characteristics of MVI to classify the risk levels of MVI. However, such pathological analyses lack the specificity to discriminate MVI in HCC specimens, especially in complicated pathological tissues. In addition, the efficiency to precisely define stages of MVI is not satisfied. Thus, any biomarker for both conforming diagnosis of MVI and staging its levels will efficiently and effectively promote the prediction of early postoperative recurrence and metastasis for HCC. Through bioinformatics analysis and clinical sample verification, we discovered that Stathmin 1 (STMN1) gene was significantly up-regulated at the locations of MVI. Combining STMN1 immunostaining with classic H&E staining assays, we established a new protocol for MVI pathological diagnosis. Next, we found that the degrees of MVI risk could be graded according to expression levels of STMN1 for prognosis prediction on recurrence rates and overall survival in early HCC patients. STMN1 affected epithelial-mesenchymal transformation (EMT) of HCC cells by regulating the dynamic balance of microtubules through signaling of “STMN1-Microtubule-EMT” axis. Inhibition of STMN1 expression in HCC cells reduced their lung metastatic ability in recipients of mouse model, suggesting that STMN1 also could be a potential therapeutic target for inhibiting HCC metastasis. Therefore, we conclude that STMN1 has potentials for clinical applications as a biomarker for both pathological diagnosis and prognostic prediction, as well as a therapeutic target for HCC.
A fast Myosin super enhancer dictates muscle fiber phenotype through competitive interactions with Myosin genes
Authors: Dos Santos Matthieu , Backer Stéphanie , Auradé Frédéric , Wong Matthew Man-Kin , Wurmser Maud , Pierre Rémi , Langa Francina , Do Cruzeiro Marcio , Schmitt Alain , Concordet Jean-Paul , Sotiropoulos Athanassia , Jeffrey Dilworth F. , Noordermeer Daan , Relaix Frédéric , Sakakibara Iori , Maire Pascal
Published: February 2022

The contractile properties of adult myofibers are shaped by their Myosin heavy chain isoform content. Here, we identify by snATAC-seq a 42 kb super-enhancer at the locus regrouping the fast Myosin genes. By 4C-seq we show that active fast Myosin promoters interact with this super-enhancer by DNA looping, leading to the activation of a single promoter per nucleus. A rainbow mouse transgenic model of the locus including the super-enhancer recapitulates the endogenous spatio-temporal expression of adult fast Myosin genes. In situ deletion of the super-enhancer by CRISPR/Cas9 editing demonstrates its major role in the control of associated fast Myosin genes, and deletion of two fast Myosin genes at the locus reveals an active competition of the promoters for the shared super-enhancer. Last, by disrupting the organization of fast Myosin, we uncover positional heterogeneity within limb skeletal muscles that may underlie selective muscle susceptibility to damage in certain myopathies.
Circulating microbial content in myeloid malignancy patients is associated with disease subtypes and patient outcomes
Authors: Woerner Jakob , Huang Yidi , Hutter Stephan , Gurnari Carmelo , Sánchez Jesús María Hernández , Wang Janet , Huang Yimin , Schnabel Daniel , Aaby Michael , Xu Wanying , Thorat Vedant , Jiang Dongxu , Jha Babal K. , Koyuturk Mehmet , Maciejewski Jaroslaw P. , Haferlach Torsten , LaFramboise Thomas
Published: February 2022

Although recent work has described the microbiome in solid tumors, microbial content in hematological malignancies is not well-characterized. Here we analyze existing deep DNA sequence data from the blood and bone marrow of 1870 patients with myeloid malignancies, along with healthy controls, for bacterial, fungal, and viral content. After strict quality filtering, we find evidence for dysbiosis in disease cases, and distinct microbial signatures among disease subtypes. We also find that microbial content is associated with host gene mutations and with myeloblast cell percentages. In patients with low-risk myelodysplastic syndrome, we provide evidence that Epstein-Barr virus status refines risk stratification into more precise categories than the current standard. Motivated by these observations, we construct machine-learning classifiers that can discriminate among disease subtypes based solely on bacterial content. Our study highlights the association between the circulating microbiome and patient outcome, and its relationship with disease subtype.
Ultralarge anti-Stokes lasing through tandem upconversion
Authors: Sun Tianying , Chen Bing , Guo Yang , Zhu Qi , Zhao Jianxiong , Li Yuhua , Chen Xian , Wu Yunkai , Gao Yaobin , Jin Limin , Chu Sai Tak , Wang Feng
Published: February 2022

Coherent ultraviolet light is important for applications in environmental and life sciences. However, direct ultraviolet lasing is constrained by the fabrication challenge and operation cost. Herein, we present a strategy for the indirect generation of deep-ultraviolet lasing through a tandem upconversion process. A core–shell–shell nanoparticle is developed to achieve deep-ultraviolet emission at 290 nm by excitation in the telecommunication wavelength range at 1550 nm. The ultralarge anti-Stokes shift of 1260 nm (~3.5 eV) stems from a tandem combination of distinct upconversion processes that are integrated into separate layers of the core–shell–shell structure. By incorporating the core–shell–shell nanoparticles as gain media into a toroid microcavity, single-mode lasing at 289.2 nm is realized by pumping at 1550 nm. As various optical components are readily available in the mature telecommunication industry, our findings provide a viable solution for constructing miniaturized short-wavelength lasers that are suitable for device applications.
Parkinson’s disease severity clustering based on tapping activity on mobile device
Authors: Surangsrirat Decho , Sri-iesaranusorn Panyawut , Chaiyaroj Attawit , Vateekul Peerapon , Bhidayasiri Roongroj
Published: February 2022

In this study, we investigated the relationship between finger tapping tasks on the smartphone and the MDS-UPDRS I–II and PDQ-8 using the mPower dataset. mPower is a mobile application-based study for monitoring key indicators of PD progression and diagnosis. Currently, it is one of the largest, open access, mobile Parkinson’s Disease studies. Data from seven modules with a total of 8,320 participants who provided the data of at least one task were released to the public researcher. The modules comprise demographics, MDS-UPDRS I–II, PDQ-8, memory, tapping, voice, and walking. Finger-tapping is one of the tasks that easy to perform and has been analyzed for the quantitative measurement of PD. Therefore, participants who performed both the tapping activity and MDS-UPDRS I–II rating scale were selected for our analysis. Note that the MDS-UPDRS mPower Survey only contains parts of the original scale and has not been clinimetrically tested for validity and reliability. We obtained a total of 1851 samples that contained the tapping activity and MDS-UPDRS I–II for the analysis. Nine features were selected to represent tapping activity. K-mean was applied as an unsupervised clustering algorithm in our study. For determining the number of clusters, the elbow method, Sihouette score, and Davies–Bouldin index, were employed as supporting evaluation metrics. Based on these metrics and expert opinion, we decide that three clusters were appropriate for our study. The statistical analysis found that the tapping features could separate participants into three severity groups. Each group has different characteristics and could represent different PD severity based on the MDS-UPDRS I–II and PDQ-8 scores. Currently, the severity assessment of a movement disorder is based on clinical observation. Therefore, it is highly dependant on the skills and experiences of the trained movement disorder specialist who performs the procedure. We believe that any additional methods that could potentially assist with quantitative assessment of disease severity, without the need for a clinical visit would be beneficial to both the healthcare professionals and patients.
Orbital controls on eastern African hydroclimate in the Pleistocene
Authors: Lupien Rachel L. , Russell James M. , Pearson Emma J. , Castañeda Isla S. , Asrat Asfawossen , Foerster Verena , Lamb Henry F. , Roberts Helen M. , Schäbitz Frank , Trauth Martin H. , Beck Catherine C. , Feibel Craig S. , Cohen Andrew S.
Published: February 2022

Understanding eastern African paleoclimate is critical for contextualizing early human evolution, adaptation, and dispersal, yet Pleistocene climate of this region and its governing mechanisms remain poorly understood due to the lack of long, orbitally-resolved, terrestrial paleoclimate records. Here we present leaf wax hydrogen isotope records of rainfall from paleolake sediment cores from key time windows that resolve long-term trends, variations, and high-latitude effects on tropical African precipitation. Eastern African rainfall was dominantly controlled by variations in low-latitude summer insolation during most of the early and middle Pleistocene, with little evidence that glacial–interglacial cycles impacted rainfall until the late Pleistocene. We observe the influence of high-latitude-driven climate processes emerging from the last interglacial (Marine Isotope Stage 5) to the present, an interval when glacial–interglacial cycles were strong and insolation forcing was weak. Our results demonstrate a variable response of eastern African rainfall to low-latitude insolation forcing and high-latitude-driven climate change, likely related to the relative strengths of these forcings through time and a threshold in monsoon sensitivity. We observe little difference in mean rainfall between the early, middle, and late Pleistocene, which suggests that orbitally-driven climate variations likely played a more significant role than gradual change in the relationship between early humans and their environment.
Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson’s disease
Authors: Matschke Lina A. , Komadowski Marlene A. , Stöhr Annette , Lee Bolam , Henrich Martin T. , Griesbach Markus , Rinné Susanne , Geibl Fanni F. , Chiu Wei-Hua , Koprich James B. , Brotchie Jonathan M. , Kiper Aytug K. , Dolga Amalia M. , Oertel Wolfgang H. , Decher Niels
Published: February 2022

Parkinson’s disease (PD) is clinically defined by the presence of the cardinal motor symptoms, which are associated with a loss of dopaminergic nigrostriatal neurons in the substantia nigra pars compacta (SNpc). While SNpc neurons serve as the prototypical cell-type to study cellular vulnerability in PD, there is an unmet need to extent our efforts to other neurons at risk. The noradrenergic locus coeruleus (LC) represents one of the first brain structures affected in Parkinson’s disease (PD) and plays not only a crucial role for the evolving non-motor symptomatology, but it is also believed to contribute to disease progression by efferent noradrenergic deficiency. Therefore, we sought to characterize the electrophysiological properties of LC neurons in two distinct PD models: (1) in an in vivo mouse model of focal α-synuclein overexpression; and (2) in an in vitro rotenone-induced PD model. Despite the fundamental differences of these two PD models, α-synuclein overexpression as well as rotenone exposure led to an accelerated autonomous pacemaker frequency of LC neurons, accompanied by severe alterations of the afterhyperpolarization amplitude. On the mechanistic side, we suggest that Ca2+-activated K+ (SK) channels are mediators of the increased LC neuronal excitability, as pharmacological activation of these channels is sufficient to prevent increased LC pacemaking and subsequent neuronal loss in the LC following in vitro rotenone exposure. These findings suggest a role of SK channels in PD by linking α-synuclein- and rotenone-induced changes in LC firing rate to SK channel dysfunction.
Machine learning detects altered spatial navigation features in outdoor behaviour of Alzheimer’s disease patients
Authors: Ghosh Abhirup , Puthusseryppady Vaisakh , Chan Dennis , Mascolo Cecilia , Hornberger Michael
Published: February 2022

Impairment of navigation is one of the earliest symptoms of Alzheimer’s disease (AD), but to date studies have involved proxy tests of navigation rather than studies of real life behaviour. Here we use GPS tracking to measure ecological outdoor behaviour in AD. The aim was to use data-driven machine learning approaches to explore spatial metrics within real life navigational traces that discriminate AD patients from controls. 15 AD patients and 18 controls underwent tracking of their outdoor navigation over two weeks. Three kinds of spatiotemporal features of segments were extracted, characterising the mobility domain (entropy, segment similarity, distance from home), spatial shape (total turning angle, segment complexity), and temporal characteristics (stop duration). Patients significantly differed from controls on entropy (p-value 0.008), segment similarity (p-value $${10}^{-7}$$

10

-
7

), and distance from home (p-value $${10}^{-14}$$

10

-
14

). Graph-based analyses yielded preliminary data indicating that topological features assessing the connectivity of visited locations may also differentiate patients from controls. In conclusion, our results show that specific outdoor navigation features discriminate AD patients from controls, which has significant implication for future AD diagnostics, outcome measures and interventions. Furthermore, this work illustrates how wearables-based sensing of everyday behaviour may be used to deliver ecologically-valid digital biomarkers of AD pathophysiology.
A two-stage approach for the spatio-temporal analysis of high-throughput phenotyping data
Authors: Pérez-Valencia Diana M. , Rodríguez-Álvarez María Xosé , Boer Martin P. , Kronenberg Lukas , Hund Andreas , Cabrera-Bosquet Llorenç , Millet Emilie J. , Eeuwijk Fred A. van
Published: February 2022

High throughput phenotyping (HTP) platforms and devices are increasingly used for the characterization of growth and developmental processes for large sets of plant genotypes. Such HTP data require challenging statistical analyses in which longitudinal genetic signals need to be estimated against a background of spatio-temporal noise processes. We propose a two-stage approach for the analysis of such longitudinal HTP data. In a first stage, we correct for design features and spatial trends per time point. In a second stage, we focus on the longitudinal modelling of the spatially corrected data, thereby taking advantage of shared longitudinal features between genotypes and plants within genotypes. We propose a flexible hierarchical three-level P-spline growth curve model, with plants/plots nested in genotypes, and genotypes nested in populations. For selection of genotypes in a plant breeding context, we show how to extract new phenotypes, like growth rates, from the estimated genotypic growth curves and their first-order derivatives. We illustrate our approach on HTP data from the PhenoArch greenhouse platform at INRAE Montpellier and the outdoor Field Phenotyping platform at ETH Zürich.
Strength deterioration mechanism of bentonite modified loess after wetting–drying cycles
Authors: Niu Ze-Lin , Xu Jian , Li Yan-Feng , Wang Ze-Feng , Wang Bao
Published: February 2022

The employment of bentonite modified loess (BML) is a common method of constructing the anti-seepage lining of landfills in the loess region of China, and its long-term secure performance is threatened by wetting–drying (W–D) cycles. Taking the remolded loess (RL) and BML with 15% in mass of bentonite as research objects, the W–D cycles test, scanning electron microscope test and direct shear test were carried out to analyze the effects of W–D cycles on the microstructure and shear strength of samples. The regression equations between strength and micro-pore structure parameters were established by the multivariate linear stepwise regression method. The damage mechanism of BML after W–D cycles was studied by establishing damage degree models based on pore area ratio and cohesion. Results indicate that the water absorption and expansion of bentonite effectively block the intergranular pores, resulting in more medium and small pores and more pronounced surface contact of particles. After W–D cycles, the particle arrangement of samples before and after bentonite modification tends to be loose. Both the pore area ratio and fractal dimension increase and tend to stabilize after five cycles. The BML exhibits lower pore area ratio and greater fractal dimension while its cohesion and internal friction angle show more significant decrease after W–D cycles than those of RL. The damage variables based on pore area ratio and cohesion well describe the W–D induced damage of loess before and after modification from macro- and micro-scale perspectives. The damage degree of samples increases with W–D cycles, but the increment decreases.
Bridging the macro to micro resolution gap with angiographic optical coherence tomography and dynamic contrast enhanced MRI
Authors: Zabel W. Jeffrey , Allam Nader , Foltz Warren D. , Flueraru Costel , Taylor Edward , Vitkin I. Alex
Published: February 2022

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is emerging as a valuable tool for non-invasive volumetric monitoring of the tumor vascular status and its therapeutic response. However, clinical utility of DCE-MRI is challenged by uncertainty in its ability to quantify the tumor microvasculature ($$\mu \mathrm{m}$$

μ
m

scale) given its relatively poor spatial resolution (mm scale at best). To address this challenge, we directly compared DCE-MRI parameter maps with co-registered micron-scale-resolution speckle variance optical coherence tomography (svOCT) microvascular images in a window chamber tumor mouse model. Both semi and fully quantitative (Toft’s model) DCE-MRI metrics were tested for correlation with microvascular svOCT biomarkers. svOCT’s derived vascular volume fraction (VVF) and the mean distance to nearest vessel ($$\overline{\mathrm{DNV} }$$

DNV
¯

) metrics were correlated with DCE-MRI vascular biomarkers such as time to peak contrast enhancement ($$r=-0.81$$

r
=
-
0.81

and $$0.83$$

0.83

respectively, $$P<0.0001$$

P
<
0.0001

for both), the area under the gadolinium-time concentration curve ($$r=0.50$$

r
=
0.50

and $$-0.48$$

-
0.48

respectively, $$P<0.0001$$

P
<
0.0001

for both) and $${k}_{trans}$$

k

trans

($$r=0.64$$

r
=
0.64

and $$-0.61$$

-
0.61

respectively, $$P<0.0001$$

P
<
0.0001

for both). Several other correlated micro–macro vascular metric pairs were also noted. The microvascular insights afforded by svOCT may help improve the clinical utility of DCE-MRI for tissue functional status assessment and therapeutic response monitoring applications.
Prognostic indicators of arthroscopic discopexy for management of temporomandibular joint closed lock
Authors: Sah Manoj Kumar , Abdelrehem Ahmed , Chen Shihui , Shen Pei , Jiao ZiXian , Hu Ying Kai , Nie Xin , Yang Chi
Published: February 2022

In order to optimize patient selection for temporomandibular joint (TMJ) arthroscopic discopexy to achieve favorable outcomes, prognostic indicators impacting the results are important to analyze. This longitudinal retrospective study aimed to analyze various prognostic factors impacting surgical outcomes following arthroscopic discopexy for management of TMJ closed lock using success criteria based on pain, maximal interincisal opening, diet, and quality of life. Furthermore, a quantitative MRI assessment was performed pre- and post-operatively. Multivariate analysis was used to evaluate various prognostic variables including gender, age, side, duration of illness, Wilkes staging, parafunctional habits, splint therapy and orthodontic treatment. A total of 147 patients (201 joints) were included. The outcome was categorized as excellent (n = 154/76.61%), good (n = 34/16.91%), or poor (n = 13/6.46%) with a success rate of 93.54%. Patients aged > 30 years old (p = 0.048), longer duration of illness (12–24 months: p = 0.034) and (> 24 months: p = 0.022), and patients with Wilkes stage IV (p = 0.002) were all significantly more likely to be in the poor outcome group. Finally, orthodontic treatment showed a significant association with excellent outcomes (p = 0.015). Age, duration of illness, Wilkes staging, and orthodontic treatment are considered significant prognostic factors that can predict the outcomes following the arthroscopic discopexy for management of TMJ closed lock.
Identification of natural and anthropogenic signals in controlled source seismic experiments
Authors: Díaz J. , DeFelipe I. , Ruiz M. , Andrés J. , Ayarza P. , Carbonell R.
Published: February 2022

The analysis of the background noise in seismic networks has proved to be a powerful tool not only to acquire new insights on the crustal structure, but also to monitor different natural and anthropogenic processes. We show that data acquired during controlled source experiments can also be a valuable tool to monitor such processes, in particular when using high-density deployments. Data from a wide-angle reflection and refraction seismic profile in the central-northwest part of Iberia is used to identify signals related to aircrafts, road traffic, quarry blasts, wind blow, rainfall or thunders. The most prominent observations are those generated by a helicopter and an airplane flying following trajectories subparallel to the profile, which are tracked along 200 km with a spatial resolution of 350 m, hence providing an exceptional dataset. Other highlights are the observation of the Doppler effect on signals generated by moving cars and the high-density recording of acoustic waves generated by thunders. In addition to the intrinsic interest of identifying such signals, this contribution proves that it is worth inspecting the data acquired during seismic experiments beyond the time interval including the arrival of the seismic waves generated by the controlled source.
A role for cortical dopamine in the paradoxical calming effects of psychostimulants
Authors: Harris Sharonda S. , Green Sara M. , Kumar Mayank , Urs Nikhil M.
Published: February 2022

Psychostimulants have a paradoxical calming effect in the treatment of attention deficit hyperactivity disorder (ADHD), but their mechanism of action is unclear. Studies using dopamine (DA) transporter (DAT) knockout (KO) mice have suggested that the paradoxical calming effect of psychostimulants might occur through actions on serotonin (5-HT) neurotransmission. However, newer non-stimulant drugs, such as atomoxetine and guanfacine, suggest that targeting the norepinephrine (NE) system in the prefrontal cortex (PFC) might explain this paradoxical calming effect. Thus, we sought to clarify the mechanism of this paradoxical action of psychostimulants. Our ex vivo efflux experiments reveal that the NE transporter (NET) blocker desipramine elevates both norepinephrine (NE) and dopamine (DA), but not 5-HT levels, in PFC tissue slices from wild-type (WT) and DAT-KO, but not NET-KO mice. However, the 5-HT transporter (SERT) inhibitor fluoxetine elevates only 5-HT in all three genotypes. Systemic administration of desipramine or fluoxetine inhibits hyperactivity in DAT-KO mice, whereas local PFC infusion of desipramine alone produced this same effect. In contrast, pharmacological NE depletion and DA elevation using nepicastat also inhibits hyperactivity in DAT-KO mice. Together, these data suggest elevation of PFC DA and not NE or 5-HT, as a convergent mechanism for the paradoxical effects of psychostimulants observed in ADHD therapy.
Comprehensive assessment of NR ligand polypharmacology by a multiplex reporter NR assay
Authors: Medvedev Alexander , Moeser Matt , Medvedeva Liubov , Martsen Elena , Granick Alexander , Raines Lydia , Gorman Kristen , Lin Benjamin , Zeng Ming , Houck Keith A. , Makarov Sergei S.
Published: February 2022

Nuclear receptors (NR) are ligand-modulated transcription factors that regulate multiple cell functions and thus represent excellent drug targets. However, due to a considerable NR structural homology, NR ligands often interact with multiple receptors. Here, we describe a multiplex reporter assay (the FACTORIAL NR) that enables parallel assessment of NR ligand activity across all 48 human NRs. The assay comprises one-hybrid GAL4-NR reporter modules transiently transfected into test cells. To evaluate the reporter activity, we assessed their RNA transcripts. We used a homogeneous RNA detection approach that afforded equal detection efficacy and permitted the multiplex detection in a single-well format. For validation, we examined a panel of selective NR ligands and polypharmacological agonists and antagonists of the progestin, estrogen, PPAR, ERR, and ROR receptors. The assay produced highly reproducible NR activity profiles (r > 0.96) permitting quantitative assessment of individual NR responses. The inferred EC50 values agreed with the published data. The assay showed excellent quality (  = 0.73) and low variability ( = 7.2%). Furthermore, the assay permitted distinguishing direct and non-direct NR responses to ligands. Therefore, the FACTORIAL NR enables comprehensive evaluation of NR ligand polypharmacology.
Surface ruptures and off-fault deformation of the October 2016 central Italy earthquakes from DInSAR data
Authors: Carboni Filippo , Porreca Massimiliano , Valerio Emanuela , Mariarosaria Manzo , De Luca Claudio , Azzaro Salvatore , Ercoli Maurizio , Barchi Massimiliano R.
Published: February 2022

Large magnitude earthquakes produce complex surface deformations, which are typically mapped by field geologists within the months following the mainshock. We present detailed maps of the surface deformation pattern produced by the M. Vettore Fault System during the October 2016 earthquakes in central Italy, derived from ALOS-2 SAR data, via DInSAR technique. On these maps, we trace a set of cross-sections to analyse the coseismic vertical displacement, essential to identify both surface fault ruptures and off-fault deformations. At a local scale, we identify a large number of surface ruptures, in agreement with those observed in the field. At a larger scale, the inferred coseismic deformation shows a typical long-wavelength convex curvature of the subsiding block, not directly recognizable in the field. The detection of deformation patterns from DInSAR technique can furnish important constraints on the activated fault segments, their spatial distribution and interaction soon after the seismic events. Thanks to the large availability of satellite SAR acquisitions, the proposed methodological approach can be potentially applied to worldwide earthquakes (according to the environmental characteristics of the sensed scene) to provide a wider and faster picture of surface ruptures. Thus, the derived information can be crucial for emergency management by civil protection and helpful to drive and support the geological field surveys during an ongoing seismic crisis.
Variations in intraocular pressure and visual parameters before and after using mobile virtual reality glasses and their effects on the eyes
Authors: Lin Ching-Huang , Lin Hsien-Chang , Chen Chien-Yu , Lih Chong-Chung
Published: February 2022

We examined the effects of using mobile devices with immersive virtual reality for a short period on the physiological parameters of both eyes. The average age of the 50 participants (23 men and 27 women) was 17.72 ± 1.48 years, and refractive error ranged from 0 D to − 5.00 D. All the participants wore + 3.00 D glasses and underwent a 5-min relaxation adjustment through the atomization method. The participants wore immersive virtual reality (VR) glasses to watch a movie on a roller coaster for 10 min. Their relevant physiological parameters of the eyes were measured both before and after using VR glasses. Compared with before VR use, no significant difference (P > 0.05) was observed in the near-horizontal vergence and refractive error but a significant difference (P < 0.05) was observed in the amplitude of accommodation, intraocular pressure, divergence/convergence, and stereopsis after VR use. The corneal elastic coefficient was > 0.2 MPa, and we used Friedenwald’s eye rigidity relationship to obtain the K value (0.065–0.09). Approximately 10% of the participants experienced cybersickness symptoms such as nausea and dizziness. The use of VR to watch three-dimensional movies reduced intraocular pressure, which may help prevent or treat glaucoma. Moreover, the binocular convergence was higher when viewing near-field objects in VR than in the real world. Therefore, individuals with convergence excess may experience symptoms. Binocular parallax is the most likely cause of cybersickness symptoms. Thus, mobile VR devices with higher quality and comfort are necessary.
Robust tests for combining p-values under arbitrary dependency structures
Authors: Chen Zhongxue
Published: February 2022

Recently Liu and Xie proposed a p-value combination test based on the Cauchy distribution (CCT). They showed that when the significance levels are small, CCT can control type I error rate and the resulting p-value can be simply approximated using a Cauchy distribution. One very special and attractive property of CCT is that it is applicable to situations where the p-values to be combined are dependent. However, in this paper, we show that under some conditions the commonly used MinP test is much more powerful than CCT. In addition, under some other situations, CCT is powerless at all. Therefore, we should use CCT with caution. We also proposed new robust p-value combination tests using a second MinP/CCT to combine the dependent p-values obtained from CCT and MinP applied to the original p-values. We call the new tests MinP-CCT-MinP (MCM) and CCT-MinP-CCT (CMC). We study the performance of the new tests by comparing them with CCT and MinP using comprehensive simulation study. Our study shows that the proposed tests, MCM and CMC, are robust and powerful under many conditions, and can be considered as alternatives of CCT or MinP.
Early neurological deterioration after intravenous thrombolysis of anterior vs posterior circulation stroke: a secondary analysis of INTRECIS
Authors: Cui Yu , Meng Wei-Hong , Chen Hui-Sheng
Published: February 2022

Anterior circulation stroke (ACS) differs from posterior circulation stroke (PCS) in many ways, but it remains unclear whether there is any difference in early neurological deterioration (END) in two stroke territories. We compared post-thrombolytic END between ACS and PCS based on the data from INTRECIS. We screened patients receiving intravenous 0.9 mg/kg alteplase within 4.5 h in the INTRECIS cohort. According to stroke territory, patients were divided into ACS and PCS groups. The primary outcome was incidence of END, which was defined as an increase in NIHSS score ≥ 4 or death within 24 h from baseline. The secondary outcomes were associated factors of END and 90-day modified Rankin Scale (mRS) distribution. Overall, 1194 patients were enrolled in this study: 942 in ACS group and 252 in PCS group. There was no significant difference in the incidence of END between two groups (3.8% vs 5.2%, adjusted p = 0.406). Atrial fibrillation (adjusted p = 0.012) and TOAST classification (adjusted p = 0.009) were associated with END in ACS, while hypertension history (adjusted p = 0.046) and baseline NIHSS score (adjusted p = 0.011) with END in PCS. END was associated with worse outcome on 90-day mRS in ACS and PCS (adjusted p < 0.001). Based on a prospective nationwide cohort, we provided first report for similar incidence, but different risk factors of post-thrombolytic END in ACS vs PCS patients.

Trial Registration-URL: https://www.clinicaltrials.gov; Unique identifier: NCT02854592.
Deconvolution of ferromagnetic resonance spectrum of magnetic nanoparticle assembly using genetic algorithm
Authors: Usov N. A. , Serebryakova O. N.
Published: February 2022

The ferromagnetic resonance (FMR) spectra of dilute random assemblies of magnetite nanoparticles with cubic magnetic anisotropy and various aspect ratios are calculated using the stochastic Landau–Lifshitz equation at a finite temperature, T = 300 K, taking into account the thermal fluctuations of the particle magnetic moments. Particles of non-spherical shape in the first approximation are described as elongated spheroids with a given semiaxes ratio a/b, where a and b are the long and transverse semiaxes of a spheroid, respectively. A representative database of FMR spectra is created for assemblies of randomly oriented spheroidal magnetite nanoparticles with various transverse diameters D = 5–25 nm, moderate aspect ratios a/b = 1.0–1.8, and magnetic damping constants κ = 0.1, 0.2. The basic FMR spectra of assemblies with D = 25 nm at different aspect ratios can be considered as representatives of assemblies of single-domain magnetite nanoparticles with transverse diameters D > 25 nm. The database is calculated at exciting frequency f = 4.9 GHz (S-band) to clarify the details of the FMR spectrum that depend on the particle magnetic anisotropy nature. The data obtained make it possible to analyze arbitrary combined FMR spectra constructed as weighted linear combinations of FMR spectra of the base assemblies. In addition, using a genetic algorithm, the corresponding inverse problem is solved. The latter consists in determining the volume fractions of the base assemblies in some arbitrary nanoparticle assembly, which is represented by its FMR spectrum.
Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal
Authors: Corripio-Miyar Yolanda , Hayward Adam , Lemon Hannah , Sweeny Amy R. , Bal Xavier , Kenyon Fiona , Pilkington Jill G. , Pemberton Josephine M. , Nussey Daniel H. , McNeilly Tom N.
Published: February 2022

The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines. We tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan and helminth parasite burdens, respectively. All measures of Th-associated cytokine production increased with age, while Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. Independent of age, sex, and each other, IL-4 and Gata3 negatively predicted gastro-intestinal nematode faecal egg count, while IFN-γ negatively predicted coccidian faecal oocyst count. Our results provide important support from outside the laboratory that Th1 and Th2 responses predict resistance to different kinds of parasites, and illustrate how harnessing specific reagents and tools from laboratory immunology will illuminate our understanding of host-parasite interactions in the wild.
Characterization of exhaled e-cigarette aerosols in a vape shop using a field-portable holographic on-chip microscope
Authors: Çetintaş Ege , Luo Yi , Nguyen Charlene , Guo Yuening , Li Liqiao , Zhu Yifang , Ozcan Aydogan
Published: February 2022

The past decade marked a drastic increase in the usage of electronic cigarettes. The adverse health impact of secondhand exposure due to exhaled e-cig particles has raised significant concerns, demanding further research on the characteristics of these particles. In this work, we report direct volatility measurements on exhaled e-cig aerosols using a field-portable device (termed c-Air) enabled by deep learning and lens-free holographic microscopy; for this analysis, we performed a series of field experiments in a vape shop where customers used/vaped their e-cig products. During four days of experiments, we periodically sampled the indoor air with intervals of ~ 16 min and collected the exhaled particles with c-Air. Time-lapse inline holograms of the collected particles were recorded by c-Air and reconstructed using a convolutional neural network yielding phase-recovered microscopic images of the particles. Volumetric decay of individual particles due to evaporation was used as an indicator of the volatility of each aerosol. Volatility dynamics quantified through c-Air experiments showed that indoor vaping increased the percentage of volatile and semi-volatile particles in air. The reported methodology and findings can guide further studies on volatility characterization of indoor e-cig emissions.