bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity
Authors: Achdout Hagit , Vitner Einat. B. , Politi Boaz , Melamed Sharon , Yahalom-Ronen Yfat , Tamir Hadas , Erez Noam , Avraham Roy , Weiss Shay , Cherry Lilach , Bar-Haim Erez , Makdasi Efi , Gur David , Aftalion Moshe , Chitlaru Theodor , Vagima Yaron , Paran Nir , Israely Tomer
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The continued spread of SARS-CoV-2 increases the probability of influenza/SARS-CoV-2 coinfection, which may result in severe disease. In this study, we examine the disease outcome of influenza A virus (IAV) and SARS-CoV-2 coinfection in K18-hACE2 mice. Our data indicate enhance susceptibility of IAV-infected mice to developing severe disease upon coinfection with SARS-CoV-2 two days later. In contrast to nonfatal influenza and lower mortality rates due to SARS-CoV-2 alone, this coinfection results in severe morbidity and nearly complete mortality. Coinfection is associated with elevated influenza viral loads in respiratory organs. Remarkably, prior immunity to influenza, but not to SARS-CoV-2, prevents severe disease and mortality. This protection is antibody-dependent. These data experimentally support the necessity of seasonal influenza vaccination for reducing the risk of severe influenza/COVID-19 comorbidity during the COVID-19 pandemic.
An ethylene biosynthesis enzyme controls quantitative variation in maize ear length and kernel yield
Authors: Ning Qiang , Jian Yinan , Du Yanfang , Li Yunfu , Shen Xiaomeng , Jia Haitao , Zhao Ran , Zhan Jimin , Yang Fang , Jackson David , Liu Lei , Zhang Zuxin
Published: October 2021

Maize ear size and kernel number differ among lines, however, little is known about the molecular basis of ear length and its impact on kernel number. Here, we characterize a quantitative trait locus, qEL7, to identify a maize gene controlling ear length, flower number and fertility. qEL7 encodes 1-aminocyclopropane-1- carboxylate oxidase2 (ACO2), a gene that functions in the final step of ethylene biosynthesis and is expressed in specific domains in developing inflorescences. Confirmation of qEL7 by gene editing of ZmACO2 leads to a reduction in ethylene production in developing ears, and promotes meristem and flower development, resulting in a ~13.4% increase in grain yield per ear in hybrids lines. Our findings suggest that ethylene serves as a key signal in inflorescence development, affecting spikelet number, floral fertility, ear length and kernel number, and also provide a tool to improve grain productivity by optimizing ethylene levels in maize or in other cereals.
A study of real-world micrograph data quality and machine learning model robustness
Authors: Zhong Xiaoting , Gallagher Brian , Eves Keenan , Robertson Emily , Mundhenk T. Nathan , Han T. Yong-Jin
Published: October 2021

Machine-learning (ML) techniques hold the potential of enabling efficient quantitative micrograph analysis, but the robustness of ML models with respect to real-world micrograph quality variations has not been carefully evaluated. We collected thousands of scanning electron microscopy (SEM) micrographs for molecular solid materials, in which image pixel intensities vary due to both the microstructure content and microscope instrument conditions. We then built ML models to predict the ultimate compressive strength (UCS) of consolidated molecular solids, by encoding micrographs with different image feature descriptors and training a random forest regressor, and by training an end-to-end deep-learning (DL) model. Results show that instrument-induced pixel intensity signals can affect ML model predictions in a consistently negative way. As a remedy, we explored intensity normalization techniques. It is seen that intensity normalization helps to improve micrograph data quality and ML model robustness, but microscope-induced intensity variations can be difficult to eliminate.
Environmental screening and ligand-field effects to magnetism in CrI3 monolayer
Authors: Soriano D. , Rudenko A. N. , Katsnelson M. I. , Rösner M.
Published: October 2021

We study the microscopic origin of magnetism in suspended and dielectrically embedded CrI3 monolayer by down-folding minimal generalized Hubbard models from ab initio calculations using the constrained random phase approximation. These models are capable of describing the formation of localized magnetic moments in CrI3 and of reproducing electronic properties of direct ab initio calculations. Utilizing the magnet force theorem, we find a multi-orbital super-exchange mechanism as the origin of magnetism in CrI3 resulting from an interplay between ferro- and anti-ferromagnetic Cr-Cr d coupling channels, which is decisively affected by the ligand p orbitals. We show how environmental screening, such as resulting from encapsulation with hexagonal boron nitride, affects the Coulomb interaction in the film and how this controls its magnetic properties. Driven by a non-monotonic interplay between nearest and next-nearest neighbor exchange interactions we find the magnon dispersion and the Curie temperature to be non-trivially affected by the environmental screening.
Impact of convection on the damping of an oscillating droplet during viscosity measurement using the ISS-EML facility
Authors: Xiao Xiao , Brillo Jürgen , Lee Jonghyun , Hyers Robert W. , Matson Douglas M.
Published: October 2021

Oscillating droplet experiments are conducted using the Electromagnetic Levitation (EML) facility under microgravity conditions. The droplet of molten metal is internally stirred concurrently with the pulse excitation initiating shape oscillations, allowing viscosity measurement of the liquid melts based on the damping rate of the oscillating droplet. We experimentally investigate the impact of convection on the droplet’s damping behavior. The effective viscosity arises and increases as the internal convective flow becomes transitional or turbulent, up to 2–8 times higher than the intrinsic molecular viscosity. The enhanced effective viscosity decays when the stirring has stopped, and an overshoot decay pattern is identified at higher Reynolds numbers, which presents a faster decay rate as the constraint of flow domain size becomes influential. By discriminating the impact of convection on the viscosity results, the intrinsic viscosity can be evaluated with improved measurement accuracy.
Multipartite entanglement of billions of motional atoms heralded by single photon
Authors: Li Hang , Dou Jian-Peng , Pang Xiao-Ling , Zhang Chao-Ni , Yan Zeng-Quan , Yang Tian-Huai , Gao Jun , Li Jia-Ming , Jin Xian-Min
Published: October 2021

Quantum theory does not prevent entanglement from being created and observed in macroscopic physical systems, in reality however, the accessible scale of entanglement is still very limited due to decoherence effects. Recently, entanglement has been observed among atoms from thousands to millions levels in extremely low-temperature and well isolated systems. Here, we create multipartite entanglement of billions of motional atoms in a quantum memory at room temperature and certify the genuine entanglement via M-separability witness associated with photon statistics. The information contained in a single photon is found strongly correlated with the excitation shared by the motional atoms, which intrinsically address the large system and therefore stimulate the multipartite entanglement. Remarkably, our heralded and quantum memory built-in entanglement generation allows us to directly observe the dynamic evolution of entanglement depth and further to reveal the effects of decoherence. Our results verify the existence of genuine multipartite entanglement among billions of motional atoms at ambient conditions, significantly extending the boundary of the accessible scale of entanglement.
Preparation and characterization of graphitic carbon nitride-supported l-arginine as a highly efficient and recyclable catalyst for the one-pot synthesis of condensation reactions
Authors: Ghafuri Hossein , Tajik Zeinab , Ghanbari Nastaran , Hanifehnejad Peyman
Published: October 2021

In this work, graphitic carbon nitride-supported l-arginine (g-C3N4@l-arginine) nanocatalyst was synthesized and evaluated using FT-IR, EDX, XRD, TGA, and FESEM analyses. The performance of the prepared nanocatalyst was examined in the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. The novel g-C3N4@l-arginine nanocatalyst showed high thermal stability, easy separation from reaction media, the capability to be used in various multicomponent reactions, and acceptable reusability.
A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening
Authors: Dornbierer Dario A. , Yerlikaya Firat , Wespi Rafael , Boxler Martina I. , Voegel Clarissa D. , Schnider Laura , Arslan Aslihan , Baur Diego M. , Baumgartner Markus R. , Binz Tina Maria , Kraemer Thomas , Landolt Hans-Peter
Published: October 2021

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.

Trials registration: NCT04975360.
Free versus bound entanglement, a NP-hard problem tackled by machine learning
Authors: Hiesmayr Beatrix C.
Published: October 2021

Entanglement detection in high dimensional systems is a NP-hard problem since it is lacking an efficient way. Given a bipartite quantum state of interest free entanglement can be detected efficiently by the PPT-criterion (Peres-Horodecki criterion), in contrast to detecting bound entanglement, i.e. a curious form of entanglement that can also not be distilled into maximally (free) entangled states. Only a few bound entangled states have been found, typically by constructing dedicated entanglement witnesses, so naturally the question arises how large is the volume of those states. We define a large family of magically symmetric states of bipartite qutrits for which we find $$82\%$$

82
%

to be free entangled, $$2\%$$

2
%

to be certainly separable and as much as $$10\%$$

10
%

to be bound entangled, which shows that this kind of entanglement is not rare. Via various machine learning algorithms we can confirm that the remaining $$6\%$$

6
%

of states are more likely to belonging to the set of separable states than bound entangled states. Most important we find via dimension reduction algorithms that there is a strong two-dimensional (linear) sub-structure in the set of bound entangled states. This revealed structure opens a novel path to find and characterize bound entanglement towards solving the long-standing problem of what the existence of bound entanglement is implying.
Label-free photothermal disruption of cytotoxic aggregates rescues pathology in a C. elegans model of Huntington’s disease
Authors: Nedosekin Dmitry A. , Chen TsungYen , Ayyadevara Srinivas , Zharov Vladimir P. , Shmookler Reis Robert J.
Published: October 2021

Aggregation of proteins is a prominent hallmark of virtually all neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Little progress has been made in their treatment to slow or prevent the formation of aggregates by post-translational modification and regulation of cellular responses to misfolded proteins. Here, we introduce a label-free, laser-based photothermal treatment of polyglutamine (polyQ) aggregates in a C. elegans nematode model of huntingtin-like polyQ aggregation. As a proof of principle, we demonstrated that nanosecond laser pulse-induced local photothermal heating can directly disrupt the aggregates so as to delay their accumulation, maintain motility, and extend the lifespan of treated nematodes. These beneficial effects were validated by confocal photothermal, fluorescence, and video imaging. The results obtained demonstrate that our theranostics platform, integrating photothermal therapy without drugs or other chemicals, combined with advanced imaging to monitor photothermal ablation of aggregates, initiates systemic recovery and thus validates the concept of aggregate-disruption treatments for neurodegenerative diseases in humans.
Cas9-mediated genome editing reveals a significant contribution of calcium signaling pathways to anhydrobiosis in Pv11 cells
Authors: Miyata Yugo , Fuse Hiroto , Tokumoto Shoko , Hiki Yusuke , Deviatiiarov Ruslan , Yoshida Yuki , Yamada Takahiro G. , Cornette Richard , Gusev Oleg , Shagimardanova Elena , Funahashi Akira , Kikawada Takahiro
Published: October 2021

Pv11 is an insect cell line established from the midge Polypedilum vanderplanki, whose larval form exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 itself is also capable of anhydrobiosis, which is induced by trehalose treatment. Here we report the successful construction of a genome editing system for Pv11 cells and its application to the identification of signaling pathways involved in anhydrobiosis. Using the Cas9-mediated gene knock-in system, we established Pv11 cells that stably expressed GCaMP3 to monitor intracellular Ca2+ mobilization. Intriguingly, trehalose treatment evoked a transient increase in cytosolic Ca2+ concentration, and further experiments revealed that the calmodulin–calcineurin–NFAT pathway contributes to tolerance of trehalose treatment as well as desiccation tolerance, while the calmodulin–calmodulin kinase–CREB pathway conferred only desiccation tolerance on Pv11 cells. Thus, our results show a critical contribution of the trehalose-induced Ca2+ surge to anhydrobiosis and demonstrate temporally different roles for each signaling pathway.
Unexpected involvement of a second rodent species makes impacts of introduced rats more difficult to detect
Authors: Lambert M. , Carlisle S. , Cain I. , Douse A. , Watt L.
Published: October 2021

Rodent predators are implicated in declines of seabird populations, and removing introduced rats, often, but not always, results in the expected conservation gains. Here we investigated the relationship between small mammal (Norway rat, wood mouse and pygmy shrew) abundance and Manx shearwater breeding success on the island of Rum, Scotland, and tested whether localised rodenticide treatments (to control introduced Norway rats) increased Manx shearwater breeding success. We found that Manx shearwater breeding success was negatively correlated with late summer indices of abundance for rats and mice, but not shrews. On its own, rat activity was a poor predictor of Manx shearwater breeding success. Rat activity increased during the shearwater breeding season in untreated areas but was supressed in areas treated with rodenticides. Levels of mouse (and shrew) activity increased in areas treated with rodenticides (likely in response to lower levels of rat activity) and Manx shearwater breeding success was unchanged in treated areas (p < 0.1). The results suggest that, unexpectedly, negative effects from wood mice can substitute those of Norway rats and that both species contributed to negative impacts on Manx shearwaters. Impacts were intermittent however, and further research is needed to characterise rodent population trends and assess the long-term risks to this seabird colony. The results have implications for conservation practitioners planning rat control programmes on islands where multiple rodent species are present.
Asymptomatic individuals can increase the final epidemic size under adaptive human behavior
Authors: Espinoza Baltazar , Marathe Madhav , Swarup Samarth , Thakur Mugdha
Published: October 2021

Infections produced by non-symptomatic (pre-symptomatic and asymptomatic) individuals have been identified as major drivers of COVID-19 transmission. Non-symptomatic individuals, unaware of the infection risk they pose to others, may perceive themselves—and be perceived by others—as not presenting a risk of infection. Yet, many epidemiological models currently in use do not include a behavioral component, and do not address the potential consequences of risk misperception. To study the impact of behavioral adaptations to the perceived infection risk, we use a mathematical model that incorporates the behavioral decisions of individuals, based on a projection of the system’s future state over a finite planning horizon. We found that individuals’ risk misperception in the presence of non-symptomatic individuals may increase or reduce the final epidemic size. Moreover, under behavioral response the impact of non-symptomatic infections is modulated by symptomatic individuals’ behavior. Finally, we found that there is an optimal planning horizon that minimizes the final epidemic size.
The relationship between ultrasound findings and thyroid function in children and adolescent autoimmune diffuse thyroid diseases
Authors: Park Ji Eun , Hwang Sook Min , Hwang Ji-Young , Moon Jin Hee , Yang Ik , Woo Ji Young , Lee Hye Jin
Published: October 2021

To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.
Differentiating coronavirus disease 2019 (COVID-19) from influenza and dengue
Authors: Thein Tun-Linn , Ang Li Wei , Young Barnaby Edward , Chen Mark I-Cheng , Leo Yee-Sin , Lye David Chien Boon
Published: October 2021

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.
Lung microbiome of stable and exacerbated COPD patients in Tshwane, South Africa
Authors: Goolam Mahomed T. , Peters R. P. H. , Allam M. , Ismail A. , Mtshali S. , Goolam Mahomed A. , Ueckermann V. , Kock M. M. , Ehlers M. M.
Published: October 2021

Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of exacerbations triggered by infections. The aim of this study was to determine the composition of the lung microbiome and lung virome in patients with COPD in an African setting and to compare their composition between the stable and exacerbated states. Twenty-four adult COPD patients were recruited from three hospitals. Sputum was collected and bacterial DNA was extracted. Targeted metagenomics was performed to determine the microbiome composition. Viral DNA and RNA were extracted from selected samples followed by cDNA conversion. Shotgun metagenomics sequencing was performed on pooled DNA and RNA. The most abundant phyla across all samples were Firmicutes and Proteobacteria. The following genera were most prevalent: Haemophilus and Streptococcus. There were no considerable differences for alpha and beta diversity measures between the disease states. However, a difference in the abundances between disease states was observed for: (i) Serratia (3% lower abundance in exacerbated state), (ii) Granulicatella (2.2% higher abundance in exacerbated state), (iii) Haemophilus (5.7% higher abundance in exacerbated state) and (iv) Veillonella (2.5% higher abundance in exacerbated state). Virome analysis showed a high abundance of the BeAn 58058 virus, a member of the Poxviridae family, in all six samples (90% to 94%). This study is among the first to report lung microbiome composition in COPD patients from Africa. In this small sample set, no differences in alpha or beta diversity between stable and exacerbated disease state was observed, but an unexpectedly high frequency of BeAn 58058 virus was observed. These observations highlight the need for further research of the lung microbiome of COPD patients in African settings.
Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
Authors: Lekva Tove , Roland Marie Cecilie Paasche , Estensen Mette E. , Norwitz Errol R. , Tilburgs Tamara , Henriksen Tore , Bollerslev Jens , Normann Kjersti R. , Magnus Per , Olstad Ole Kristoffer , Aukrust Pål , Ueland Thor
Published: October 2021

Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (PBMC) and circulating telomere associated senescence markers would be dysregulated in women with PE. We measured long non-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5′–3′ Exoribonuclease 1 (XRN1) in extracellular vesicles at 22–24 weeks, 36–38 weeks and, 5-year follow-up in controls and PE. We also measured telomere length at 22–24 weeks and 5-year follow-up. The circulating senescence markers cathelicidin antimicrobial peptide (CAMP), β-galactosidase, stathmin 1 (STMN1) and chitotriosidase/CHIT1 were measured at 14–16, 22–24, 36–38 weeks and at 5-year follow-up in the STORK study and before delivery and 6 months post-partum in the ACUTE PE study. We found decreased expression of TERC in PBMC early in pregnant women who subsequently developed PE. XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up. Further, we found that the senescence markers CAMP and β-galactosidase were increased in PE pregnancies, and CAMP remained higher at 5-year follow-up. β-galactosidase was associated with atherogenic lipid ratios during pregnancy and at 5-year follow-up, in PE particularly. This study suggests a potential involvement of dysfunctional telomerase biology in the pathophysiology of PE, which is not restricted to the placenta.
Perioperative Doppler measurements of renal perfusion are associated with acute kidney injury in patients undergoing cardiac surgery
Authors: Hermansen Johan Lyngklip , Pettey Gabriela , Sørensen Heidi Tofte , Nel Samantha , Tsabedze Nqoba , Hørlyck Arne , Chakane Palesa Motshabi , Gammelager Henrik , Juhl-Olsen Peter
Published: October 2021

Acute kidney injury (AKI) is a frequent and severe complication in cardiac surgery. Normal renal function is dependent on adequate renal perfusion, which may be altered in the perioperative period. Renal perfusion can be assessed with Doppler measurement. We aimed to determine the association between Doppler measurements of renal perfusion and the development of AKI. This was a prospective, observational study of 100 patients with ≥ one risk factor for postoperative AKI undergoing open-heart surgery. Doppler ultrasound examinations were performed before surgery and on the first and fourth postoperative day. AKI was defined according to the KDIGO criteria and subdivided into mild (KDIGO stage 1) and severe AKI (KDIGO stage 2 + 3). Thirty-three patients developed AKI, 25 developed mild and eight developed severe AKI. Abnormal renal venous flow pattern on the first postoperative day was significantly associated with the development of severe AKI (OR 8.54 (95% CI 1.01; 72.2), P = 0.046), as were portal pulsatility fraction (OR 1.07 (95% CI 1.02; 1.13), P = 0.005). Point-of-care Doppler ultrasound measurements of renal perfusion are associated with the development of AKI after cardiac surgery. Renal and portal Doppler ultrasonography can be used to identify patients at high risk or very low risk of AKI after cardiac surgery.
A novel approach to understanding Parkinsonian cognitive decline using minimum spanning trees, edge cutting, and magnetoencephalography
Authors: Simon Olivier B. , Buard Isabelle , Rojas Donald C. , Holden Samantha K. , Kluger Benzi M. , Ghosh Debashis
Published: October 2021

Graph theory-based approaches are efficient tools for detecting clustering and group-wise differences in high-dimensional data across a wide range of fields, such as gene expression analysis and neural connectivity. Here, we examine data from a cross-sectional, resting-state magnetoencephalography study of 89 Parkinson’s disease patients, and use minimum-spanning tree (MST) methods to relate severity of Parkinsonian cognitive impairment to neural connectivity changes. In particular, we implement the two-sample multivariate-runs test of Friedman and Rafsky (Ann Stat 7(4):697–717, 1979) and find it to be a powerful paradigm for distinguishing highly significant deviations from the null distribution in high-dimensional data. We also generalize this test for use with greater than two classes, and show its ability to localize significance to particular sub-classes. We observe multiple indications of altered connectivity in Parkinsonian dementia that may be of future use in diagnosis and prediction.
Dimension-reduction simplifies the analysis of signal crosstalk in a bacterial quorum sensing pathway
Authors: Miller Taylor , Patel Keval , Rodriguez Coralis , Stabb Eric V. , Hagen Stephen J.
Published: October 2021

Many pheromone sensing bacteria produce and detect more than one chemically distinct signal, or autoinducer. The pathways that detect these signals are typically noisy and interlocked through crosstalk and feedback. As a result, the sensing response of individual cells is described by statistical distributions that change under different combinations of signal inputs. Here we examine how signal crosstalk reshapes this response. We measure how combinations of two homoserine lactone (HSL) input signals alter the statistical distributions of individual cell responses in the AinS/R- and LuxI/R-controlled branches of the Vibrio fischeri bioluminescence pathway. We find that, while the distributions of pathway activation in individual cells vary in complex fashion with environmental conditions, these changes have a low-dimensional representation. For both the AinS/R and LuxI/R branches, the distribution of individual cell responses to mixtures of the two HSLs is effectively one-dimensional, so that a single tuning parameter can capture the full range of variability in the distributions. Combinations of crosstalking HSL signals extend the range of responses for each branch of the circuit, so that signals in combination allow population-wide distributions that are not available under a single HSL input. Dimension reduction also simplifies the problem of identifying the HSL conditions to which the pathways and their outputs are most sensitive. A comparison of the maximum sensitivity HSL conditions to actual HSL levels measured during culture growth indicates that the AinS/R and LuxI/R branches lack sensitivity to population density except during the very earliest and latest stages of growth respectively.
Land use mix and leukocyte telomere length in Mexican Americans
Authors: Zhao Hua , Shen Jie , Chang David , Ye Yuanqing , Wu Xifeng , Chow Wong-Ho , Zhang Kai
Published: October 2021

It has been well-known that built environment features influence the risk of chronic diseases. However, the existing data of its relationship with telomere length, a biomarker of biological aging, is still limited, with no study available for Mexican Americans. This study investigates the relationship between several factors of the built environment with leukocyte telomere length among 5508 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the quartile levels of telomere length, the study population was categorized into four groups, from the lowest (1st quartile) to the highest telomere length group (4th quartile). For individual built environment factors, their levels did not differ significantly across four groups. However, in the multinominal logistic regression analysis, increased Rundle’s land use mixture (LUM) and Frank’s LUM were found statistically significantly associated with increased odds of having high levels of telomere length (Rundle’s LUM: 2nd quartile: Odds ratio (OR) 1.26, 95% Confidence interval (CI) 1.07, 1.48; 3rd quartile: OR 1.25, 95% CI 1.06, 1.46; 4th quartile: OR 1.19, 95% CI 1.01, 1.41; Frank’s LUM: 2nd quartile: OR 1.34, 95% CI 1.02, 2.63; 3rd quartile: OR 1.55, 95% CI 1.04, 2.91; 4th quartile: OR 1.36, 95% CI 1.05, 2.72, respectively). The associations for Rundle’s LUM remained significant after further adjusting other non-redundant built environment factors. Finally, in stratified analysis, we found the association between Rundle’s LUM and telomere length was more evident among younger individuals (< 38 years old), women, and those with obesity, born in Mexico, having low levels of physical activity, and having low levels of acculturation than their relative counterparts. In summary, our results indicate that land use mixture may impact telomere length in leukocytes in Mexican Americans.
Versatilely tuned vertical silicon nanowire arrays by cryogenic reactive ion etching as a lithium-ion battery anode
Authors: Refino Andam Deatama , Yulianto Nursidik , Syamsu Iqbal , Nugroho Andika Pandu , Hawari Naufal Hanif , Syring Alina , Kartini Evvy , Iskandar Ferry , Voss Tobias , Sumboja Afriyanti , Peiner Erwin , Wasisto Hutomo Suryo
Published: October 2021

Production of high-aspect-ratio silicon (Si) nanowire-based anode for lithium ion batteries is challenging particularly in terms of controlling wire property and geometry to improve the battery performance. This report demonstrates tunable optimization of inductively coupled plasma reactive ion etching (ICP-RIE) at cryogenic temperature to fabricate vertically-aligned silicon nanowire array anodes with high verticality, controllable morphology, and good homogeneity. Three different materials [i.e., photoresist, chromium (Cr), and silicon dioxide (SiO2)] were employed as masks during the subsequent photolithography and cryogenic ICP-RIE processes to investigate their effects on the resulting nanowire structures. Silicon nanowire arrays with a high aspect ratio of up to 22 can be achieved by tuning several etching parameters [i.e., temperature, oxygen/sulfur hexafluoride (O2/SF6) gas mixture ratio, chamber pressure, plasma density, and ion energy]. Higher compressive stress was revealed for longer Si wires by means of Raman spectroscopy. Moreover, an anisotropy of lattice stress was found at the top and sidewall of Si nanowire, indicating compressive and tensile stresses, respectively. From electrochemical characterization, half-cell battery integrating ICP-RIE-based silicon nanowire anode exhibits a capacity of 0.25 mAh cm−2 with 16.67% capacity fading until 20 cycles, which has to be improved for application in future energy storage devices.
Theaflavins as a novel cross-linker quickly stabilize demineralized dentin collagen against degradation
Authors: Liu Hang , Guo Jing , Wang Rong , Wang Yong
Published: October 2021

To investigate the ability of theaflavins (TF) from black tea to protect dentin collagen against enzymatic degradation via cross-linking effect under clinically relevant conditions. 10-µm-thick dentin films were microtomed from dentin slabs of human molars. Following demineralization, films or slabs were treated with TF at two concentrations (0.4% and 2%) for 30 s. A well-known collagen cross-linker grape seed proanthocyanidins (PA) was used as control. Collagen cross-linking interactions and stabilization against enzymatic degradation were investigated by Fourier transform infrared spectroscopy, weight loss, hydroxyproline release, and scanning/transmission electron microscopy. Data were analyzed by ANOVA, Tukey’s and Student’s T test (α = 0.05%). The results showed collagen cross-linking and stabilization efficacy was dependent on TF/PA concentrations. At 2.0%, TF and PA offered nearly full protection to collagen; at 0.4%, TF exhibited a significantly better collagen stabilization effect than PA (P < 0.05), while untreated collagen was completely digested. It’s concluded that TF cross-links dentin collagen within a clinically relevant time (30 s) and offers excellent collagen protection against enzymatic degradation, with efficacy comparable to or better than PA. The study supports the potential use of TF as a novel, promising collagen cross-linker for degradation resistant, long-lasting dentin bonding in composite restorations.
Temporalis muscle thickness as an indicator of sarcopenia predicts progression-free survival in head and neck squamous cell carcinoma
Authors: Lee Boeun , Bae Yun Jung , Jeong Woo-Jin , Kim Hyojin , Choi Byung Se , Kim Jae Hyoung
Published: October 2021

Temporalis muscle thickness (TMT) on brain magnetic resonance imaging (MRI) is correlated with sarcopenia and can be a predictive marker for survival in patients with brain tumors, but the association of TMT on head and neck computed tomography (CT) with survival in head and neck squamous cell carcinoma (HNSCC) remains unclear. We investigated whether TMT on CT could predict progression-free survival (PFS) in patients with HNSCC. A total of 106 patients with newly diagnosed HNSCC were included in this retrospective study. The patients underwent baseline head and neck CT and/or MRI between July, 2008 and August, 2018. The correlation between TMT on CT and MRI was tested using intraclass correlation coefficient (ICC). The cut-off value of TMT on CT for determining tumor progression was identified using receiver-operating characteristic curve analysis. Uni- and consecutive multi-variable Cox regression models were used to verify the association between TMT and PFS. TMT on CT and MRI showed excellent correlation (ICC, 0.894). After a mean follow-up of 37 months, 49 out of 106 patients showed locoregional recurrence and/or distant metastasis. The cut-off TMT of 6.47 mm showed good performance in predicting tumor progression (area under the curve, 0.779). The Cox regression model showed that TMT ≤ 6.24 mm (median value in study population) was a significant contributing factor for predicting shorter PFS (hazard ratio 0.399; 95% confidence interval 0.209–0.763; P = .005). TMT may be used as a surrogate parameter for pre-treatment sarcopenia and could help predict PFS in patients with HNSCC.
Looking into the flora of Dutch Brazil: botanical identifications of seventeenth century plant illustrations in the Libri Picturati
Authors: Alcàntara-Rodríguez Mireia , Françozo Mariana , Van Andel Tinde
Published: October 2021

The Libri Picturati includes a collection of plant illustrations from seventeenth century Dutch Brazil that is kept in the Jagiellonian library in Krakow since World War II. While many studies focused on the artistic details and history of these images, we identified the flora depicted. We used contemporary textual sources (e.g., Historia Naturalis Brasiliae), monographs and taxonomist’ assessments. We checked origin, life form, domestication and conservation status and the plant parts that are represented. We identified 198 taxa, consisting mostly of wild, native rainforest trees and 35 introduced species. Fertile branches are the most represented, although some loose dry fruits and sterile material were also painted, which sheds light into the collection methods by naturalists in Dutch Brazil. Several species are no longer abundant or have become invasive due to anthropogenic influences since colonialism. Through this botanical iconography, we traced the first records of the sunflower and the Ethiopian pepper in Brazil, as well as the dispersion and assimilation of the flora encountered in the colony by Indigenous, African and European peoples. We emphasized the relevance of combining visual and textual sources when studying natural history collections and we highlighted how digitalization makes these artistic and scientific collections more accessible.
Particular matter influences the incidence of acute otitis media in children
Authors: Park Mina , Han Jiyeon , Park Jiwon , Jang Myoung-jin , Park Moo Kyun
Published: October 2021

Particulate matter (PM) is the main component of air pollution. Children are vulnerable to PM and acute otitis media (AOM), which is one of the most common diseases in children. However, studies on the relationship between AOM in children and PM are rare and their results are inconsistent. The aim of this study is to investigate the effect of PM on AOM in children on the basis of the Korea National Health Insurance service (NHIS) claims data. NHIS claim data from 2008 to 2015 was used to identify outpatient visits, antibiotic use to treat AOM, and demographic data. This data was combined with the data on PM2.5 (≤ 2.5 μm) and PM10 (≤ 10 μm according to its aerodynamic diameter) level extracted from air pollution data from Korean National Institute of Environmental Research for 16 administrative regions. The children with AOM were divided into three age groups (< 2, 2–4, 5–10 years). Generalized linear Poisson regression model was used to estimate the association between AOM and PM using daily counts of AOM and daily mean PM concentrations. It was adjusted to temperature, wind, humidity, season, year, age, and region. With an increase in PM2.5 of 10 μg/m3, the relative risk of OM increased by 4.5% in children under 2 years of age. The effect of PM2.5 was strongest influence on the day of exposure. The exposure to PM10 was related to the incidence of AOM on the day of exposure and the following seven days in all three age groups. The PM concentrations did not strongly affect either AOM duration or the use of antibiotics to cure AOM. The RR in the each lag day after exposure to PM10 was diverse according to the age groups. Regardless of PM size and children’s age, the PM levels are positively related to the incidence of AOM. Both PM2.5 and PM10 have the most adverse effects on children under 2 years of age and on the day of exposure.
First direct determination of the 93Mo half-life
Authors: Kajan I. , Heinitz S. , Kossert K. , Sprung P. , Dressler R. , Schumann D.
Published: October 2021

This work presents the first direct measurement of the 93Mo half-life. The measurement is a combination of high-resolution mass spectrometry for the determination of the 93Mo concentration and liquid scintillation counting for determining the specific activity. A 93Mo sample of high purity was obtained from proton irradiated niobium by chemical separation of molybdenum with a decontamination factor larger than 1.6 × 1014 with respect to Nb. The half-life of 93Mo was deduced to be 4839(63) years, which is more than 20% longer than the currently adopted value, whereas the relative uncertainty could be reduced by a factor of 15. The probability that the 93Mo decays to the metastable state 93mNb was determined to be 95.7(16)%. This value is a factor of 8 more precise than previous estimations. Due to the man-made production of 93Mo in nuclear facilities, the result leads to significantly increased precision for modelling the low-level nuclear waste composition. The presented work demonstrates the importance of chemical separations in combination with state-of-the-art analysis techniques, which are inevitable for precise and accurate determinations of nuclear decay data.
Genomic epidemiology of rifampicin ADP-ribosyltransferase (Arr) in the Bacteria domain
Authors: Morgado Sergio , Fonseca Érica , Vicente Ana Carolina
Published: October 2021

Arr is an ADP-ribosyltransferase enzyme primarily reported in association with rifamycin resistance, which has been used to treat tuberculosis in addition to Gram-positive infections and, recently, pan-resistant Gram-negative bacteria. The arr gene was initially identified on the Mycolicibacterium smegmatis chromosome and later on Proteobacteria plasmids. This scenario raised concerns on the distribution and spread of arr, considering the Bacteria domain. Based on 198,082 bacterial genomes/metagenomes, we performed in silico analysis, including phylogenetic reconstruction of Arr in different genomic contexts. Besides, new arr alleles were evaluated by in vitro analysis to assess their association with rifampin resistance phenotype. The arr gene was prevalent in thousands of chromosomes and in hundreds of plasmids from environmental and clinical bacteria, mainly from the phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. Furthermore, this gene was identified in other and new genomic contexts. Interestingly, Arr sequences associated with rifampin resistance were distributed across all phylogeny, indicating that, despite the diversity, their association with rifampin resistance phenotype were maintained. In fact, we found that the key residues were highly conserved. In addition, other analyzes have raised evidence of another Arr function, which is related to guanidine metabolism. Finally, this scenario as a whole also suggested the Actinobacteria phylum as a potential ancestral source of arr within the Bacteria domain.
Biosafety assessment of Acinetobacter strains isolated from the Three Gorges Reservoir region in nematode Caenorhabditis elegans
Authors: Deng Yunjia , Du Huihui , Tang Mingfeng , Wang Qilong , Huang Qian , He Ying , Cheng Fei , Zhao Feng , Wang Dayong , Xiao Guosheng
Published: October 2021

Acinetobacter has been frequently detected in backwater areas of the Three Gorges Reservoir (TGR) region. We here employed Caenorhabditis elegans to perform biosafety assessment of Acinetobacter strains isolated from backwater area in the TGR region. Among 21 isolates and 5 reference strains of Acinetobacter, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii ATCC 19606T, A. junii NH88-14, and A. lwoffii DSM 2403T resulted in significant decrease in locomotion behavior and reduction in lifespan of Caenorhabditis elegans. In nematodes, exposure to Acinetobacter strains of AC1, AC15, AC18, AC21, A. baumannii, A. junii and A. lwoffii also resulted in significant reactive oxygen species (ROS) production. Moreover, exposure to Acinetobacter isolates of AC1, AC15, AC18, and AC21 led to significant increase in expressions of both SOD-3::GFP and some antimicrobial genes (lys-1, spp-12, lys-7, dod-6, spp-1, dod-22, lys-8, and/or F55G11.4) in nematodes. The Acinetobacter isolates of AC1, AC15, AC18, and AC21 had different morphological, biochemical, phylogenetical, and virulence gene properties. Our results suggested that exposure risk of some Acinetobacter strains isolated from the TGR region exists for environmental organisms and human health. In addition, C. elegans is useful to assess biosafety of Acinetobacter isolates from the environment.
Soluble PD-L1 is a predictive and prognostic biomarker in advanced cancer patients who receive immune checkpoint blockade treatment
Authors: Oh So Yeon , Kim Soyeon , Keam Bhumsuk , Kim Tae Min , Kim Dong-Wan , Heo Dae Seog
Published: October 2021

Circulating soluble programmed death-1 ligand (sPD-L1) is measurable in the serum of cancer patients. This study aimed to investigate the significance of sPD-L1 in cancer patients receiving immune checkpoint inhibitor therapy. Blood samples were obtained before and after immune checkpoint inhibitor therapy (January 2015 to January 2019). The study cohort consisted of 128 patients who were diagnosed with non-small cell lung cancer (n = 50), melanoma (n = 31), small cell lung cancer (n = 14), urothelial carcinoma (n = 13), and other cancers (n = 20). Patients with a high level (> 11.0 pg/μL) of sPD-L1 were more likely to exhibit progressive disease compared with those with a low level (41.8% versus 20.7%, p = 0.013). High sPD-L1 was also associated with worse prognosis; the median PFS was 2.9 (95% confidence interval [CI] 2.1–3.7) months versus 6.3 (95% CI 3.0–9.6) months (p = 0.023), and the median OS was 7.4 (95% CI 6.3–8.5) months versus 13.3 (95% CI 9.2–17.4) months (p = 0.005). In the multivariate analyses, high sPD-L1 was an independent prognostic factor for both decreased PFS (HR 1.928, p = 0.038) and OS (HR 1.788, p = 0.004). sPD-L1 levels did not correlate with tissue PD-L1 expression. However, sPD-L1 levels were positively correlated with neutrophil to lymphocyte ratios and negatively correlated with both the proportion and the total number of lymphocytes. We found that high pretreatment sPD-L1 levels were associated with progressive disease and were an independent prognostic factor predicting lower PFS and OS in these patients.