bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Computer-Aided Diagnosis Software for the Prevention of Retained Surgical Items
Authors: Yamaguchi Shun , Soyama Akihiko , Ono Shinichiro , Hamauzu Shin , Yamada Masahiko , Fukuda Toru , Hidaka Masaaki , Tsurumoto Toshiyuki , Uetani Masataka , Eguchi Susumu
Published: September 2021

Background

Retained surgical items are a serious human error. Surgical sponges account for 70% of retained surgical items. To prevent retained surgical sponges, it is important to establish a system that can identify errors and avoid the occurrence of adverse events. To date, no computer-aided diagnosis software specialized for detecting retained surgical sponges has been reported. We developed a software program that enables easy and effective computer-aided diagnosis of retained surgical sponges with high sensitivity and specificity using the technique of deep learning, a subfield of artificial intelligence.

Study Design

In this study, we developed the software by training it through deep learning using a dataset and then validating the software. The dataset consisted of a training set and validation set. We created composite x-rays consisting of normal postoperative x-rays and surgical sponge x-rays for a training set (n = 4,554) and a validation set (n = 470). Phantom x-rays (n = 12) were prepared for software validation. X-rays obtained with surgical sponges inserted into cadavers were used for validation purposes (formalin: Thiel’s method = 252:117). In addition, postoperative x-rays without retained surgical sponges were used for the validation of software performance to determine false-positive rates. Sensitivity, specificity, and false positives per image were calculated.

Results

In the phantom x-rays, both the sensitivity and specificity in software image interpretation were 100%. The software achieved 97.7% sensitivity and 83.8% specificity in the composite x-rays. In the normal postoperative x-rays, 86.6% specificity was achieved. In reading the cadaveric x-rays, the software attained both sensitivity and specificity of >90%.

Conclusions

Software with high sensitivity for diagnosis of retained surgical sponges was developed successfully.

Visual Abstract
Narcissistic Personality Traits and Sexual Dysfunction in Women: The Role of Body Image Self-Consciousness
Authors: Pavanello Decaro Sofia , Di Sarno Marco , Anzani Annalisa , Di Pierro Rossella , Prunas Antonio
Published: September 2021

Background

Individuals with narcissistic traits, specifically vulnerable ones, are more prone to experiencing concerns related to self-worth and physical appearance and to showing heightened sensitivity to appearance evaluation. Negative body image and body image self-consciousness may, in turn, undermine sexual functioning, especially when apprehension is related to body appearance in sexual contexts.

Methods

We aimed to evaluate the associations between self-reported pathological narcissistic traits, both grandiose and vulnerable, and sexual functioning in a large sample of nonclinical women (N = 656). Furthermore, we tested the mediating role of body image self-consciousness in these associations.

Outcomes

Sexual functioning was measured through the Female Sexual Function Index.

RESULTS

The results highlight that vulnerable narcissistic traits are associated with lower sexual functioning, this association being mediated by higher levels of body image self-consciousness. Conversely, grandiose narcissistic traits are linked to lower body image self-consciousness and, consequently, higher levels of sexual functioning.

Clinical Implications

Considering the link between body image self-consciousness and sexuality is of utmost importance in clinical practice with women, as well as in promoting positive body appreciation. Clinicians working with individuals presenting with pathological personality traits should consider including an assessment of their sexual functioning.
Greek Sculpture
Authors: Spivey Nigel
Published: September 2021

Ancient Greek sculpture seems to have a timeless quality – provoking reactions that may range from awe to alienation. Yet it was a particular product of its age: and to know how and why it was once created is to embark upon an understanding of its 'Classic' status. In this richly illustrated and carefully written survey, encompassing works from c.700 BC to the end of antiquity, Nigel Spivey expounds not only the social function of Greek sculpture but also its aesthetic and technical achievement. Fresh approaches are reconciled with traditional modes of study as the connoisseurship of this art is sympathetically unravelled, while source material and historical narratives are woven into detailed explanations, putting the art into its proper context. Greek Sculpture is the ideal textbook for students of classics, classical civilisation, art history and archaeology – and an accessible account for all interested readers.
Prejudice in Testimonial Justification: A Hinge Account
Authors: Boncompagni Anna
Published: September 2021

Although research on epistemic injustice has focused on the effects of prejudice in epistemic exchanges, the account of prejudice that emerges in Fricker's (2007) view is not completely clear. In particular, I claim that the epistemic role of prejudice in the structure of testimonial justification is still in need of a satisfactory explanation. What special epistemic power does prejudice exercise that prevents the speaker's words from constituting evidence for the hearer's belief? By clarifying this point, it will be possible to address two more general issues concerning the nature of prejudice: its resistance to counterevidence and the steps involved in overcoming prejudice. I propose a hinge account of prejudice, based on the recent perspective of hinge epistemology, to help clarify these aspects. According to the hinge account, prejudices share a fundamental feature with hinges: they work as norms of evidential significance, and as such, they determine what can and cannot count as evidence for belief.
INFORMATION IN PROPOSITIONAL PROOFS AND ALGORITHMIC PROOF SEARCH
Authors: KRAJÍČEK JAN
Published: September 2021

We study from the proof complexity perspective the (informal) proof search problem (cf. [17, Sections 1.5 and 21.5]):

•

Is there an optimal way to search for propositional proofs?

We note that, as a consequence of Levin’s universal search, for any fixed proof system there exists a time-optimal proof search algorithm. Using classical proof complexity results about reflection principles we prove that a time-optimal proof search algorithm exists without restricting proof systems iff a p-optimal proof system exists.

To characterize precisely the time proof search algorithms need for individual formulas we introduce a new proof complexity measure based on algorithmic information concepts. In particular, to a proof system P we attach information-efficiency function
$i_P(\tau )$
assigning to a tautology a natural number, and we show that:

•

$i_P(\tau )$
characterizes time any P-proof search algorithm has to use on
$\tau $
,

•

for a fixed P there is such an information-optimal algorithm (informally: it finds proofs of minimal information content),

•

a proof system is information-efficiency optimal (its information-efficiency function is minimal up to a multiplicative constant) iff it is p-optimal,

•

for non-automatizable systems P there are formulas
$\tau $
with short proofs but having large information measure
$i_P(\tau )$
.

We isolate and motivate the problem to establish unconditional super-logarithmic lower bounds for
$i_P(\tau )$
where no super-polynomial size lower bounds are known. We also point out connections of the new measure with some topics in proof complexity other than proof search.
DESCRIPTIVE COMPLEXITY IN CANTOR SERIES
Authors: AIREY DYLAN , JACKSON STEVE , MANCE BILL
Published: September 2021

A Cantor series expansion for a real number x with respect to a basic sequence
$Q=(q_1,q_2,\dots )$
, where
$q_i \geq 2$
, is a generalization of the base b expansion to an infinite sequence of bases. Ki and Linton in 1994 showed that for ordinary base b expansions the set of normal numbers is a
$\boldsymbol {\Pi }^0_3$
-complete set, establishing the exact complexity of this set. In the case of Cantor series there are three natural notions of normality: normality, ratio normality, and distribution normality. These notions are equivalent for base b expansions, but not for more general Cantor series expansions. We show that for any basic sequence the set of distribution normal numbers is
$\boldsymbol {\Pi }^0_3$
-complete, and if Q is
$1$
-divergent then the sets of normal and ratio normal numbers are
$\boldsymbol {\Pi }^0_3$
-complete. We further show that all five non-trivial differences of these sets are
$D_2(\boldsymbol {\Pi }^0_3)$
-complete if
$\lim _i q_i=\infty $
and Q is
$1$
-divergent. This shows that except for the trivial containment that every normal number is ratio normal, these three notions are as independent as possible.
Bookbinders in the Early Modern Venetian Book Trade
Authors: Gialdini Anna
Published: September 2021

Bookbinders are still among the least known of the professions of the early modern Italian book trade, partly because they rarely signed their work. However, they had an undeniably fundamental role in the production and circulation of books (both manuscript and printed) across Italy, and especially in Venice, where the book trade was a particularly lively industry. In recent years, there has been a strong interest in early modern material culture but little attention has been paid to bookbinders, who quite literally shaped the materiality of books. This article looks at the scarcity of documentary sources on Venetian bookbinders between 1450 and 1630 both as a methodological challenge and as evidence of their role in local production and consumption of books. It explores both the lack of sources documenting the professional lives of binders, and sources traditionally underused in book history, to highlight the social lives of binders. Evidence of binders’ family finances, marriages, and social and geographical mobilities is used to identify their lower social standing in the early modern Venetian book world in comparison to booksellers, the overlapping of their professional roles, and the locations of binders’ workshops in the topography of the city.
FAT-based robust adaptive control of cooperative multiple manipulators without velocity measurement
Authors: Deylami Ali , Izadbakhsh Alireza
Published: September 2021

This article addresses the problem of pose and force control in a cooperative system comprised of multiple n-degree-of-freedom (n-DOF) electrically driven robotic arms that move a payload. The proposed controller should be capable of maintaining the position and orientation of the payload in the desired path. In addition, the force exerted by robot end effectors on the object must remain limited. The system has unmodeled dynamics, and measuring the robot joint velocities is impossible. Therefore, a FAT-based observer–controller is designed to estimate the uncertainty and velocities based on universal approximation property of Fourier series expansion. The stability of the system is confirmed based on Lyapunov’s stability theorem. Finally, the proposed adaptive controller–observer is applied on two 3-DOF cooperative robotic arms carrying a payload, and the results are precisely analyzed. The results of the proposed approach are also compared with two state-of-art powerful approximation method.
Variable-time-interval trajectory optimization-based dynamic walking control of bipedal robot
Authors: Selim Erman , Alcı Musa , Altıntas Mert
Published: September 2021

Bipedal robots by their nature show both hybrid and underactuated system features which are not stable and controllable at every point of joint space. They are only controllable on certain fixed equilibrium points and some trajectories that are periodically stable between these points. Therefore, it is crucial to determine the trajectory in the control of walking robots. However, trajectory optimization causes a heavy computational load. Conventional methods to reduce the computational load weaken the optimization accuracy. As a solution, a variable time interval trajectory optimization method is proposed. In this study, optimization accuracy can be increased without additional computational time. Moreover, a five-link planar biped walking robot is designed, produced, and the dynamic walking is controlled with the proposed method. Finally, cost of transport (CoT) values are calculated and compared with other methods in the literature to reveal the contribution of the study. According to comparisons, the proposed method increases the optimization accuracy and decreases the CoT value.
STATISTICAL INFERENCE WITH F-STATISTICS WHEN FITTING SIMPLE MODELS TO HIGH-DIMENSIONAL DATA
Authors: Leeb Hannes , Steinberger Lukas
Published: September 2021

We study linear subset regression in the context of the high-dimensional overall model
$y = \vartheta +\theta ' z + \epsilon $
with univariate response y and a d-vector of random regressors z, independent of
$\epsilon $
. Here, “high-dimensional” means that the number d of available explanatory variables is much larger than the number n of observations. We consider simple linear submodels where y is regressed on a set of p regressors given by
$x = M'z$
, for some
$d \times p$
matrix M of full rank
$p < n$
. The corresponding simple model, that is,
$y=\alpha +\beta ' x + e$
, is usually justified by imposing appropriate restrictions on the unknown parameter
$\theta $
in the overall model; otherwise, this simple model can be grossly misspecified in the sense that relevant variables may have been omitted. In this paper, we establish asymptotic validity of the standard F-test on the surrogate parameter
$\beta $
, in an appropriate sense, even when the simple model is misspecified, that is, without any restrictions on
$\theta $
whatsoever and without assuming Gaussian data.
Design and Verbal Fluency in Alzheimer’s Disease and Frontotemporal Dementia: Clinical and Metabolic Correlates
Authors: Delgado-Álvarez Alfonso , Cabrera-Martín María Nieves , Pytel Vanesa , Delgado-Alonso Cristina , Matías-Guiu Jorge , Matias-Guiu Jordi A.
Published: September 2021

Objective:

Cognitive processes underlying verbal and design fluency, and their neural correlates in patients with Alzheimer’s disease (AD) and behavioural variant Frontotemporal Dementia (bvFTD) remain unclear. We hypothesised that verbal and design fluency may be associated with distinct neuropsychological processes in AD and FTD, showing different patterns of impairment and neural basis.

Methods:

We enrolled 142 participants including patients with AD (n = 80, mean age = 74.71), bvFTD (n = 34, mean age = 68.18), and healthy controls (HCs) (n = 28, mean age = 71.14), that underwent cognitive assessment and 18F-fluorodeoxyglucose positron emission tomography imaging.

Results:

Semantic and phonemic fluency showed the largest effect sizes between groups, showing lower scores in bvFTD than AD and HCs, and lower scores in AD than HC. Both AD and bvFTD showed a lower number of unique designs in design fluency in comparison to HC. Semantic fluency was correlated with left frontotemporal lobe in AD, and with left frontal, caudate, and thalamus in bvFTD. Percentage of unique designs in design fluency was associated with the metabolism of the bilateral fronto-temporo-parietal cortex in AD, and the bilateral frontal cortex with right predominance in bvFTD. Repetitions in AD were correlated with bilateral frontal, temporal, and parietal lobes, and with left prefrontal cortex in bvFTD.

Conclusions:

Our findings demonstrate differential underlying cognitive processes in verbal and design fluency in AD and bvFTD. While memory and executive functioning associated with fronto-temporo-parietal regions were key in AD, attention and executive functions correlated with the frontal cortex and played a more significant role in bvFTD during fluency tasks.
Mental Health and Well-Being During the First vs. Second COVID-19 Pandemic Lockdown in Cyprus
Authors: Papageorgiou Danae , Kassianos Angelos P. , Constantinou Marios , Lamnisos Demetris , Nicolaou Christiana , Papacostas Savvas , Gloster Andrew T. , Karekla Maria
Published: September 2021

Abstract. Introduction: Following the onset of the COVID-19 pandemic, most countries imposed strict governmental lockdowns. Research investigating the psychological impact of pandemic-induced lockdowns is accumulating, though to date no study has examined the psychological health and associated parameters of well-being in countries that underwent additional lockdowns as the pandemic continued into resurgence “waves.” Aim: The present study provides an overview of the psychological impact of COVID-19 across the two lockdowns in the Cypriot population. Methods: In total, 957 participants completed an online survey during the first lockdown, 134 of whom completed a similar survey again during the second lockdown. The outcomes assessed included stress, positive and negative affect, and well-being. Results: The results indicated no population-wide severe reactions in the participants. Repeated measures analyses showed similar mental health levels during both the first and the second lockdowns. Further inspection of participants’ scores indicated that, for all mental health variables, approximately half of the participants improved, while the other half deteriorated. Discussion: Perceived social support and psychological flexibility predicted most psychological outcomes during both lockdowns. Further research is necessary to understand the continuing effects of the pandemic and associated lockdowns on mental health.
When Posting Is Believing
Authors: Winter Stephan , Remmelswaal Paola , Vos Anne
Published: September 2021

Abstract. Social network sites (SNS) facilitate the expression of users’ opinions to a large audience. This research aimed to investigate whether the characteristics of this new media context strengthen the adaptation of opinions to the majority and lead to an internalization of the expressed views. Based on literature on public self-presentation and identity shifts, it was assumed that the publicness of and the identifiability within SNS elicit stronger expression effects than online forums or non-public settings. A between-subjects experiment ( N = 302) varied the visible majority opinion on a news issue as well as the media context in which participants were asked to write down their opinion. Results showed significant adaptation effects to the majority (positive vs. negative comments) across media contexts. The internalization of attitudes was stronger in SNS groups with a more relevant audience but also occurred in other settings. Consequences for the formation of public opinion are discussed.
Is Alteration of Magnetite During Rock Weathering Climate‐Dependent?
Authors: Zhang Qi , Appel Erwin , Basavaiah Nathani , Hu Shouyun , Zhu Xiuhua , Neumann Udo
Published: September 2021

Magnetic records in sedimentary sequences are often used as paleoclimate proxies. Climate‐specific alteration of magnetite during rock weathering in the catchment might contribute to proxy variations in sediment sinks. In an actualistic study, we investigated the effects of magnetite alteration using weathered pebble material on basaltic parent rock. We collected samples from the Deccan basalts (India) across a large difference of mean annual precipitation (MAP; ∼800–3,200 mm), and also from the Emeishan basalts (SW‐China) to compare alteration effects at similar MAP (∼1,100 mm) but ∼12°C–15°C lower mean annual temperature (MAT). We used rocks with lamellar magnetite‐ilmenite texture to ensure the best possible uniform parent rock magnetic mineralogy. We separated the weathered material into five groups by grain size, assuming that alteration increases in finer pebbles. Only magnetic susceptibility (χ) shows a systematic change, with an increase that is weakly stronger for higher MAP. Consistent with a simplified model, the χ‐increase may represent progressive maghemitization. For the Emeishan basalts, we found a significantly stronger degree of alteration, including loss of magnetite. We explain this effect, which is surprising regarding the clearly lower MAT, by frost‐induced micro‐cracks due to physical weathering that opens pathways for oxygen and humidity into particle interiors. Based on these findings, we conclude that climate‐related alteration effects of magnetite during rock weathering are in most cases outweighed by parent rock heterogeneity, and magnetic proxy records in derived sediment archives are unlikely to record climate‐related magnetite alteration acquired during rock weathering, at least for catchment with basalts.
Surface Current Variations and Oceanic Fronts in the Southern East China Sea: Drifter Experiments, Coastal Radar Applications, and Satellite Observations
Authors: Hsu Po‐Chun , Centurioni Luca , Shao Huan‐Jie , Zheng Quanan , Lu Ching‐Yuan , Hsu Tai‐Wen , Tseng Ruo‐Shan
Published: September 2021

Ocean currents in the southern East China Sea (ECS) are complex and have long lacked systematic observational data. Observations from coastal radars in northern Taiwan, along with several drifters and satellite data, reveal a detailed ECS surface flow structure and thermal front. Drifter trajectories followed the seasonal flow field and were oscillatory and trapped due to strong tidal currents. Three drifters crossed the oceanic front off the northern coast of Taiwan following the tidal motion with a rapid change in the sea surface temperature by 2.5°C, which was recorded within a small distance of 500 m. A significant seasonal water mass exchange cycle occurred in the southern ECS. Starting in October, the Kuroshio Current intrudes onto the ECS shelf, causing the formation of a southwestward Northern Taiwan Coastal Current that mixes with the China Coastal Current to form a southward flow in the northern Taiwan Strait. Beginning in March, the ocean current off northwestern Taiwan shifts northward and then gradually flows eastward into the Kuroshio region. With satellite‐derived and model‐simulated surface currents contradicting each other over long periods of time, hourly coastal radar data have not only successfully explained the spatiotemporal variations in the sea surface temperature, salinity, and chlorophyll concentration observed by satellites but have also resolved the long‐standing disputes over the surface currents in the southern ECS.
Multi‐Source Data Based Investigation of Aerosol‐Cloud Interaction Over the North China Plain and North of the Yangtze Plain
Authors: Yang Yikun , Zhao Chuanfeng , Wang Yang , Zhao Xin , Sun Wenxiao , Yang Jie , Ma Zhanshan , Fan Hao
Published: September 2021

Although great progress has been made in the study of aerosol‐cloud interactions (ACIs), representation of ACI is still the largest uncertainty in current weather and climate models. In this study, the ACI over the North China Plain and north of the Yangtze Plain is investigated using multi‐source data including satellite, ground‐based, reanalysis, and fusion data. The effects of aerosol characteristics (PM2.5, PM10, and PM2.5/PM10 ratio), atmospheric conditions including liquid water path (LWP) and lower tropospheric stability (LTS), and drizzle on ACI are analyzed. Results suggest that both aerosol characteristics and atmospheric conditions can affect cloud effective radius (), but drizzle in clouds plays a decisive role on ACI. In the case of fixed LTS and LWP, the average cloud droplet increases first and then fluctuates for all clouds examined with the increase of PM2.5 concentration. The PM2.5 concentration corresponding to the turning point of increases with the increasing LWP due to the increased chance of collision and coalescence. In contrast, the average cloud droplet and PM2.5 concentration show a negative correlation for clouds without drizzle, which is mainly caused by competition of water vapor. The quantitative ACI results show that the values of the aerosol first indirect effect are negative for most cases when considering all clouds examined, but positive when only considering clouds without drizzle.
TCF4 enhances hepatic metastasis of colorectal cancer by regulating tumor-associated macrophage via CCL2/CCR2 signaling
Authors: Tu Wei , Gong Jin , Zhou Zhenzhen , Tian Dean , Wang Zhijun
Published: September 2021

Colorectal cancer (CRC) liver metastasis is a significant clinical problem for which better therapies are urgently needed. Tumor-associated macrophage, a major cell population in the tumor microenvironment, is a known contributor to primary cancer progression and cancer metastasis. Here, we found TAM recruitment and M2 polarization were increased in the hepatic metastatic lesion compared with the primary site of human CRC tissues. Moreover, Pearson correlation analysis showed that TAM recruitment and polarization were closely correlated with the elevated TCF4 expression in the metastatic site. To investigate the role of TCF4 in CRC liver metastasis, we generated a syngeneic mouse model using MC38 cells splenic injection. Results from in vivo experiments and mouse models revealed that TCF4 deficiency in MC38 cells does not affect their proliferation and invasion; however, it reduces TAM infiltration and M2 polarization in the metastasis site. Further studies indicated that these effects are mediated by the TCF4 regulated CCL2 and CCR2 expression. TCF4 or CCL2 silencing in the tumor cells prevent CRC liver metastasis in the mouse model. Altogether, these findings suggest that the TCF4-CCL2-CCR2 axis plays an essential role in CRC liver metastasis by enhancing TAMs recruitment and M2 polarization.
USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer
Authors: Huang Yu-Ting , Cheng An-Chieh , Tang Hui-Chi , Huang Guo-Cheng , Cai Ling , Lin Ta-Hsien , Wu Kou-Juey , Tseng Ping-Hui , Wang Greg G. , Chen Wei-Yi
Published: September 2021

USP7, one of the most abundant ubiquitin-specific proteases (USP), plays multifaceted roles in many cellular events, including oncogenic pathways. Accumulated studies have suggested that USP7, through modulating the MDM2/MDMX-p53 pathway, is a promising target for cancer treatment; however, little is known about the function of USP7 in p53-deficient tumors. Here we report that USP7 regulates the autoregulation of SMAD3, a key regulator of transforming growth factor β (TGFβ) signaling, that represses the cell progression of p53-deficient lung cancer. CRISPR/Cas9-mediated inactivation of USP7 in p53-deficient lung cancer H1299 line resulted in advanced cell proliferation in vitro and in xenograft tumor in vivo. Genome-wide analyses (ChIP-seq and RNA-seq) of USP7 KO H1299 cells reveal a dramatic reduction of SMAD3 autoregulation, including decreased gene expression and blunted function of associated super-enhancer (SE). Furthermore, biochemical assays show that SMAD3 is conjugated by mono-ubiquitin, which negatively regulates the DNA-binding function of SMAD3, in USP7 KO cells. In addition, cell-free and cell-based analyses further demonstrate that the deubiquitinase activity of USP7 mediates the removal of mono-ubiquitin from SMAD3 and facilitates the DNA-binding of SMAD3-SMAD4 dimer at SMAD3 locus, and thus enhance the autoregulation of SMAD3. Collectively, our study identified a novel mechanism by which USP7, through catalyzing the SMAD3 de-monoubiquitination, facilitates the positive autoregulation of SMAD3, and represses the cancer progression of p53-deficient lung cancer.
Water modulates the lamellar structure and interlayer correlation of poly(perfluorooctyl acrylate) films: a specular and off-specular neutron scattering study
Authors: Yamamoto Akihisa , Higaki Yuji , Thoma Judith , Kimmle Esther , Ishige Ryohei , Demé Bruno , Takahara Atsushi , Tanaka Motomu
Published: September 2021

Comb-like polymers with pendant-like perfluorocarbon side chains self-assemble into smectic lamellae and have been extensively used as water-repellent, hydrophobic coating materials characterized by large water contact angles (θ > 120°). As poly(perfluorooctyl acrylate) films are “apparently hydrophobic” (θ > 120°), the interaction of such materials and water molecules has been largely overlooked. To unravel the molecular-level interactions between water and apparently hydrophobic polymers, specular and off-specular neutron scattering experiments were conducted at defined osmotic pressure ΠH2O. The poly{2-[(perfluorooctylethyl)carbamate]ethyl} acrylate (PFAUr-C8), which had a carbamate linker, transitioned to another lamellar phase at 89 °C. At T = 25 °C; the lamellar periodicity of PFAUr-C8 slightly increased with decreasing osmotic pressure, while the vertical correlation length increased. However, the poly[(perfluorooctyl)ethyl] acrylate (PFA-C8) that did not contain a carbamate linker directly transitioned to a disordered phase at 84 °C. The lamellar periodicity of PFA-C8 was largely independent of the osmotic pressure, suggesting that PFA-C8 was poorly hydrated. Remarkably, the vertical correlation length decreased with decreasing osmotic pressure. Because hydration facilitated by the linker modulated the smectic lamellae of the poly(perfluoroalkyl acrylate), water molecules could be used to optimize the self-assembly of apparently hydrophobic liquid crystalline polymers.
Virus detection via programmable Type III-A CRISPR-Cas systems
Authors: Sridhara Sagar , Goswami Hemant N. , Whyms Charlisa , Dennis Jonathan H. , Li Hong
Published: September 2021

Among the currently available virus detection assays, those based on the programmable CRISPR-Cas enzymes have the advantage of rapid reporting and high sensitivity without the requirement of thermocyclers. Type III-A CRISPR-Cas system is a multi-component and multipronged immune effector, activated by viral RNA that previously has not been repurposed for disease detection owing in part to the complex enzyme reconstitution process and functionality. Here, we describe the construction and application of a virus detection method, based on an in vivo-reconstituted Type III-A CRISPR-Cas system. This system harnesses both RNA- and transcription-activated dual nucleic acid cleavage activities as well as internal signal amplification that allow virus detection with high sensitivity and at multiple settings. We demonstrate the use of the Type III-A system-based method in detection of SARS-CoV-2 that reached 2000 copies/μl sensitivity in amplification-free and 60 copies/μl sensitivity via isothermal amplification within 30 min and diagnosed SARS-CoV-2-infected patients in both settings. The high sensitivity, flexible reaction conditions, and the small molecular-driven amplification make the Type III-A system a potentially unique nucleic acid detection method with broad applications.
Comprehensive deletion landscape of CRISPR-Cas9 identifies minimal RNA-guided DNA-binding modules
Authors: Shams Arik , Higgins Sean A. , Fellmann Christof , Laughlin Thomas G. , Oakes Benjamin L. , Lew Rachel , Kim Shin , Lukarska Maria , Arnold Madeline , Staahl Brett T. , Doudna Jennifer A. , Savage David F.
Published: September 2021

Proteins evolve through the modular rearrangement of elements known as domains. Extant, multidomain proteins are hypothesized to be the result of domain accretion, but there has been limited experimental validation of this idea. Here, we introduce a technique for genetic minimization by iterative size-exclusion and recombination (MISER) for comprehensively making all possible deletions of a protein. Using MISER, we generate a deletion landscape for the CRISPR protein Cas9. We find that the catalytically-dead Streptococcus pyogenes Cas9 can tolerate large single deletions in the REC2, REC3, HNH, and RuvC domains, while still functioning in vitro and in vivo, and that these deletions can be stacked together to engineer minimal, DNA-binding effector proteins. In total, our results demonstrate that extant proteins retain significant modularity from the accretion process and, as genetic size is a major limitation for viral delivery systems, establish a general technique to improve genome editing and gene therapy-based therapeutics.
Near-infrared manipulation of multiple neuronal populations via trichromatic upconversion
Authors: Liu Xuan , Chen Heming , Wang Yiting , Si Yueguang , Zhang Hongxin , Li Xiaomin , Zhang Zhengcheng , Yan Biao , Jiang Su , Wang Fei , Weng Shijun , Xu Wendong , Zhao Dongyuan , Zhang Jiayi , Zhang Fan
Published: September 2021

Using multi-color visible lights for independent optogenetic manipulation of multiple neuronal populations offers the ability for sophisticated brain functions and behavior dissection. To mitigate invasive fiber insertion, infrared light excitable upconversion nanoparticles (UCNPs) with deep tissue penetration have been implemented in optogenetics. However, due to the chromatic crosstalk induced by the multiple emission peaks, conventional UCNPs or their mixture cannot independently activate multiple targeted neuronal populations. Here, we report NIR multi-color optogenetics by the well-designed trichromatic UCNPs with excitation-specific luminescence. The blue, green and red color emissions can be separately tuned by switching excitation wavelength to match respective spectral profiles of optogenetic proteins ChR2, C1V1 and ChrimsonR, which enables selective activation of three distinct neuronal populations. Such stimulation with tunable intensity can not only activate distinct neuronal populations selectively, but also achieve transcranial selective modulation of the motion behavior of awake-mice, which opens up a possibility of multi-color upconversion optogenetics.
Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia
Authors: Feleke Sindew M. , Reichert Emily N. , Mohammed Hussein , Brhane Bokretsion G. , Mekete Kalkidan , Mamo Hassen , Petros Beyene , Solomon Hiwot , Abate Ebba , Hennelly Chris , Denton Madeline , Keeler Corinna , Hathaway Nicholas J. , Juliano Jonathan J. , Bailey Jeffrey A. , Rogier Eric , Cunningham Jane , Aydemir Ozkan , Parr Jonathan B.
Published: September 2021

In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia’s borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5–11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.
A best–worst scaling experiment to prioritize concern about ethical issues in citizen science reveals heterogeneity on people-level v. data-level issues
Authors: Guerrini Christi J. , Crossnohere Norah L. , Rasmussen Lisa , Bridges John F. P.
Published: September 2021

“Citizen science” refers to the participation of lay individuals in scientific studies and other activities having scientific objectives. Citizen science gives rise to unique ethical issues that stem from the potentially multifaceted contributions of citizen scientists to the research process. We sought to explore the ethical issues that are most concerning to citizen scientist practitioners, participants, and scholars to support ethical practices in citizen science. We developed a best–worst scaling experiment using a balanced incomplete block design and fielded it with respondents recruited through the U.S.-based Citizen Science Association. Respondents were shown repeated subsets of 11 ethical issues and identified the most and least concerning issues in each subset. Latent class analysis revealed two respondent classes. The “Power to the People” class was most concerned about power imbalance between project leaders and participants, exploitation of participants, and lack of diverse participation. The “Show Me the Data” class was most concerned about the quality of data generated by citizen science projects and failure of projects to share data and other research outputs.
Immersive virtual reality interferes with default head–trunk coordination strategies in young children
Authors: Miehlbradt Jenifer , Cuturi Luigi F. , Zanchi Silvia , Gori Monica , Micera Silvestro
Published: September 2021

The acquisition of postural control is an elaborate process, which relies on the balanced integration of multisensory inputs. Current models suggest that young children rely on an ‘en-block’ control of their upper body before sequentially acquiring a segmental control around the age of 7, and that they resort to the former strategy under challenging conditions. While recent works suggest that a virtual sensory environment alters visuomotor integration in healthy adults, little is known about the effects on younger individuals. Here we show that this default coordination pattern is disrupted by an immersive virtual reality framework where a steering role is assigned to the trunk, which causes 6- to 8-year-olds to employ an ill-adapted segmental strategy. These results provide an alternate trajectory of motor development and emphasize the immaturity of postural control at these ages.
Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy
Authors: Merino-Caviedes Susana , Gutierrez Lilian K. , Alfonso-Almazán José Manuel , Sanz-Estébanez Santiago , Cordero-Grande Lucilio , Quintanilla Jorge G. , Sánchez-González Javier , Marina-Breysse Manuel , Galán-Arriola Carlos , Enríquez-Vázquez Daniel , Torres Carlos , Pizarro Gonzalo , Ibáñez Borja , Peinado Rafael , Merino Jose Luis , Pérez-Villacastín Julián , Jalife José , López-Yunta Mariña , Vázquez Mariano , Aguado-Sierra Jazmín , González-Ferrer Juan José , Pérez-Castellano Nicasio , Martín-Fernández Marcos , Alberola-López Carlos , Filgueiras-Rama David
Published: September 2021

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection.
Age-period-cohort analysis of stroke mortality attributable to high systolic blood pressure in China and Japan
Authors: Cao Jinhong , Eshak Ehab S. , Liu Keyang , Arafa Ahmed , Sheerah Haytham A. , Yu Chuanhua
Published: September 2021

Stroke is a principal cause of mortality in China and Japan. High systolic blood pressure (SBP) was considered a chief risk factor for stroke mortality. Herein, we evaluated temporal trends of high SBP-attributable stroke mortality in China and Japan between 1990 and 2017. Data on stroke mortality were retrieved from the Global Burden of Disease Study 2017 (GBD 2017). Using the age-period-cohort method, we computed overall net drifts, local drifts, longitudinal age curves, and cohort/period rate ratios (RRs) for high SBP-attributable stroke mortality. The age-standardized mortality rates (ASMRs) displayed decreasing trends for high SBP-attributable stroke mortality. The annual net drift values were − 1.4% and − 3.5% in Chinese men and women versus − 3.1% and − 4.9% in Japanese men and women. The local drift values in both countries were < 0 among all age groups but were lower in women than in men. The longitudinal age curves showed a greater high SBP-attributable stroke mortality in men than in women across all age groups. Similar decreasing patterns were shown in the period and cohort RRs in both sexes with women having a quicker decline than men. In China and Japan, the ASMRs, as well as the period and cohort RRs of high SBP-attributable stroke mortality, decreased between 1990 and 2017 in both sexes and across all age groups. Yet, the prevalence of high SBP remained worrisome in both countries. Thus, SBP control should be encouraged to prevent stroke mortality.
Violet bioluminescent Polycirrus sp. (Annelida: Terebelliformia) discovered in the shallow coastal waters of the Noto Peninsula in Japan
Authors: Kanie Shusei , Miura Daisuke , Jimi Naoto , Hayashi Taro , Nakamura Koji , Sakata Masahiko , Ogoh Katsunori , Ohmiya Yoshihiro , Mitani Yasuo
Published: September 2021

Terebellidae worms have large numbers of tentacles responsible for various biological functions. Some Terebellidae worms whose tentacles emit light are found around the world, including exceptional violet-light-emitting Polycirrus spp. found in Europe and North America. However, there is no video-recorded observation of the luminous behavior of such unique species in nature, and the genetic information related to their ecology are lacking. Here, for the first time, we video-recorded the violet-light-emitting behavior of an undescribed Japanese worm in its natural habitat. The worm was designated as Polycirrus sp. ISK based on morphological observations, and the luminescence spectrum showed a peak at 444 nm, which is an exceptionally short wavelength for bioluminescence in a shallow coastal water environment. An analysis of differentially expressing genes based on separate RNA-Seq analysis for the tentacles and the rest of body revealed the specific expression of genes that are probably involved in innate immunity in the tentacles exposed to predators. We also found a Renilla luciferase homologous gene, but coelenterazine was not detected in the worm extract by analyses using a liquid chromatography and a recombinant Renilla luciferase. These results will promote an understanding of the ecology and luminescence mechanisms of luminous Polycirrus spp.
Curcumin inhibited hepatitis B viral entry through NTCP binding
Authors: Thongsri Piyanoot , Pewkliang Yongyut , Borwornpinyo Suparerk , Wongkajornsilp Adisak , Hongeng Suradej , Sa-ngiamsuntorn Khanit
Published: September 2021

Hepatitis B virus (HBV) has been implicated in hepatitis and hepatocellular carcinoma. Current agents (nucleos(t)ide analogs and interferons) could only attenuate HBV infection. A combination of agents targeting different stages of viral life cycle (e.g., entry, replication, and cccDNA stability) was expected to eradicate the infection. Curcumin (CCM) was investigated for inhibitory action toward HBV attachment and internalization. Immortalized hepatocyte-like cells (imHCs), HepaRG and non-hepatic cells served as host cells for binding study with CCM. CCM decreased viral load, HBeAg, HBcAg (infectivity), intracellular HBV DNA, and cccDNA levels. The CCM-induced suppression of HBV entry was directly correlated with the density of sodium-taurocholate co-transporting polypeptide (NTCP), a known host receptor for HBV entry. The site of action of CCM was confirmed using TCA uptake assay. The affinity between CCM and NTCP was measured using isothermal titration calorimetry (ITC). These results demonstrated that CCM interrupted HBV entry and would therefore suppress HBV re-infection.
Development of a highly efficient ion-ozone cavitation technology for accelerated bread production
Authors: Tursunbayeva Sholpan , Iztayev Auyelbek , Mynbayeva Aizhan , Alimardanova Mariam , Iztayev Baurzhan , Yakiyayeva Madina
Published: September 2021

The bakery market is one of the most capacious in Kazakhstan. Manufacturers of bread products are in dire need of the introduction of intensive technologies for improving product quality and safety. This article presents the results of research to develop technology for accelerated production of bread with ion-ozone cavitation treatment. The influence of various modes of exposure to ion-ozone cavitation has been investigated. After baking, bread samples were examined for organoleptic, physicochemical, rheological and microbiological indicators. The optimal method is treatment with ion-ozone at a concentration of 0.0025 units/mg, at a pressure of 1.0 atm for 1 min. As a result, it was proved that this mode accelerates the process of obtaining dough and shortens the fermentation time, and baking bread increases the qualitative and quantitative indicators according to the control method. The results showed that the ion-ozone technology reduces the length of the process of making dough and bread by three times compared to traditional technologies. The developed products with existing analogues in the Kazakhstan market will differ due to their high taste and consumer properties, product safety, long shelf life and low cost.
Quantum-circuit black hole lasers
Authors: Katayama Haruna
Published: September 2021

A black hole laser in analogues of gravity amplifies Hawking radiation, which is unlikely to be measured in real black holes, and makes it observable. There have been proposals to realize such black hole lasers in various systems. However, no progress has been made in electric circuits for a long time, despite their many advantages such as high-precision electromagnetic wave detection. Here we propose a black hole laser in Josephson transmission lines incorporating metamaterial elements capable of producing Hawking-pair propagation modes and a Kerr nonlinearity due to the Josephson nonlinear inductance. A single dark soliton obeying the nonlinear Schrödinger equation produces a black hole-white hole horizon pair that acts as a laser cavity through a change in the refractive index due to the Kerr effect. We show that the resulting laser is a squeezed-state laser characterized by squeezing parameters. We also evaluate the degree of quantum correlation between Hawking and its partner radiations using entanglement entropy which does not require simultaneous measurements between them. As a result, the obtained entanglement entropy depending on the soliton velocity provides strong evidence that the resulting laser is derived from Hawking radiation with quantum correlation generated by pair production from the vacuum.