bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in intestinal microbiota in postmenopausal oestrogen receptor-positive breast cancer patients treated with (neo)adjuvant chemotherapy
Authors: Aarnoutse Romy , Ziemons Janine , Hillege Lars E. , de Vos-Geelen Judith , de Boer Maaike , Bisschop Saskia M. P. , Vriens Birgit E. P. J. , Vincent Jeroen , van de Wouw Agnes J. , Le Giang N. , Venema Koen , Rensen Sander S. , Penders John , Smidt Marjolein L.
Published: July 2022

This clinical study explored the associations between the intestinal microbiota, chemotherapy toxicity, and treatment response in postmenopausal oestrogen receptor positive breast cancer patients.Oestrogen receptor positive postmenopausal breast cancer patients were prospectively enroled in a multicentre cohort study and treated with 4 cycles of (neo)adjuvant adriamycin, cyclophosphamide (AC) followed by 4 cycles of docetaxel (D). Patients collected a faecal sample and completed a questionnaire before treatment, during AC, during D, and after completing AC-D. Chemotherapy toxicity and tumour response were determined. Intestinal microbiota was analysed by amplicon sequencing of the 16 S rRNA V4 gene-region. In total, 44 patients, including 18 neoadjuvant patients, were included, and 153 faecal samples were collected before AC-D (n = 44), during AC (n = 43), during D (n = 29), and after AC-D treatment (n = 37), 28 participants provided all four samples. In the whole group, observed species richness reduced during treatment (p = 0.042). The abundance of Proteobacteria, unclassified Enterobacterales, Lactobacillus, Ruminococcaceae NK4A214 group, Marvinbryantia, Christensenellaceae R7 group, and Ruminococcaceae UCG-005 changed significantly over time. Patients with any grade diarrhoea during docetaxel treatment had a significantly lower observed species richness compared to patients without diarrhoea. In the small group neoadjuvant treated patients, pathologic response was unrelated to baseline intestinal microbiota richness, diversity and composition. While the baseline microbiota was not predictive for pathologic response in a rather small group of neoadjuvant treated patients in our study, subsequent shifts in microbial richness, as well as the abundance of specific bacterial taxa, were observed during AC-D treatment in the whole group and the neoadjuvant group.
Single-input single-output multi-touch soft sensor systems using band-pass filters
Authors: Kim Junhyung , Kim Suhan , Park Yong-Lae
Published: July 2022

In many soft sensor systems, external wires for connecting the sensors to control circuits have posed practical problems, in terms of compact form factors and physical robustness. This study proposes a design of soft sensor arrays that can operate with a drastically reduced number of wires without degrading the original performance. The proposed concept is an array of soft sensing modules, each of which consists of an inductor and a capacitor embedded next to the resistive sensing module, constructing a resistor-inductor-capacitor band-pass filter. By adjusting the values of the capacitance and the inductance, unique frequency band is assigned to each sensing module, enabling the distinctive detection using only two external wires regardless of the number of modules. The multi-touch sensing functionality of the system is analytically modeled and experimentally characterized. Taking advantage of the design, a fingertip tactile sensor and an insole foot pressure sensor are demonstrated as practical applications.
Evaluation of the PREDIGT score’s performance in identifying newly diagnosed Parkinson’s patients without motor examination
Authors: Li Juan , Mestre Tiago A. , Mollenhauer Brit , Frasier Mark , Tomlinson Julianna J. , Trenkwalder Claudia , Ramsay Tim , Manuel Douglas , Schlossmacher Michael G.
Published: July 2022

Several recent publications described algorithms to identify subjects with Parkinson’s disease (PD). In creating the “PREDIGT Score”, we previously developed a hypothesis-driven, simple-to-use formula to potentially calculate the incidence of PD. Here, we tested its performance in the ‘De Novo Parkinson Study’ (DeNoPa) and ‘Parkinson’s Progression Marker Initiative’ (PPMI); the latter included participants from the ‘FOllow Up persons with Neurologic Disease’ (FOUND) cohort. Baseline data from 563 newly diagnosed PD patients and 306 healthy control subjects were evaluated. Based on 13 variables, the original PREDIGT Score identified recently diagnosed PD patients in the DeNoPa, PPMI + FOUND and the pooled cohorts with area-under-the-curve (AUC) values of 0.88 (95% CI 0.83–0.92), 0.79 (95% CI 0.72–0.85), and 0.84 (95% CI 0.8–0.88), respectively. A simplified version (8 variables) generated AUC values of 0.92 (95% CI 0.89–0.95), 0.84 (95% CI 0.81–0.87), and 0.87 (0.84–0.89) in the DeNoPa, PPMI, and the pooled cohorts, respectively. In a two-step, screening-type approach, self-reported answers to a questionnaire (step 1) distinguished PD patients from controls with an AUC of 0.81 (95% CI 0.75–0.86). Adding a single, objective test (Step 2) further improved classification. Among seven biological markers explored, hyposmia was the most informative. The composite AUC value measured 0.9 (95% CI 0.88–0.91) in DeNoPa and 0.89 (95% CI 0.84–0.94) in PPMI. These results reveal a robust performance of the original PREDIGT Score to distinguish newly diagnosed PD patients from controls in two established cohorts. We also demonstrate the formula’s potential applicability to enriching for PD subjects in a population screening-type approach.
Stochastic gradient line Bayesian optimization for efficient noise-robust optimization of parameterized quantum circuits
Authors: Tamiya Shiro , Yamasaki Hayata
Published: July 2022

Optimizing parameterized quantum circuits is a key routine in using near-term quantum devices. However, the existing algorithms for such optimization require an excessive number of quantum-measurement shots for estimating expectation values of observables and repeating many iterations, whose cost has been a critical obstacle for practical use. We develop an efficient alternative optimization algorithm, stochastic gradient line Bayesian optimization (SGLBO), to address this problem. SGLBO reduces the measurement-shot cost by estimating an appropriate direction of updating circuit parameters based on stochastic gradient descent (SGD) and further utilizing Bayesian optimization (BO) to estimate the optimal step size for each iteration in SGD. In addition, we formulate an adaptive measurement-shot strategy and introduce a technique of suffix averaging to reduce the effect of statistical and hardware noise. Our numerical simulation demonstrates that the SGLBO augmented with these techniques can drastically reduce the measurement-shot cost, improve the accuracy, and make the optimization noise-robust.
Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead
Authors: Trottmann Felix , Ishida Keishi , Ishida-Ito Mie , Kries Hajo , Groll Michael , Hertweck Christian
Published: July 2022

Bacteria of the Burkholderia pseudomallei (BP) group pose a global health threat, causing the infectious diseases melioidosis, a common cause of pneumonia and sepsis, and glanders, a contagious zoonosis. A trait of BP bacteria is a conserved gene cluster coding for the biosynthesis of polyketides (malleicyprols) with a reactive cyclopropanol unit that is critical for virulence. Enzymes building this warhead represent ideal targets for antivirulence strategies but the biochemical basis of cyclopropanol formation is unknown. Here we describe the formation of the malleicyprol warhead. We show that BurG, an unusual NAD+-dependent member of the ketol-acid reductoisomerase family, constructs the strained cyclopropanol ring. Biochemical assays and a suite of eight crystal structures of native and mutated BurG with bound analogues and inhibitors provide snapshots of each step of the complex reaction mechanism, involving a concealed oxidoreduction and a C–S bond cleavage. Our findings illustrate a remarkable case of neofunctionalisation, where a biocatalyst from central metabolism has been evolutionarily repurposed for warhead production in pathogens.
Balsam fir (Abies balsamea) needles and their essential oil kill overwintering ticks (Ixodes scapularis) at cold temperatures
Authors: Adamo Shelley A. , El Nabbout Amal , Ferguson Laura V. , Zbarsky Jeffrey S. , Faraone Nicoletta
Published: July 2022

The blacklegged tick, Ixodes scapularis, vectors Borrelia burgdorferi, a bacterium that causes Lyme Disease. Although synthetic pesticides can reduce tick numbers, there are concerns about their potential effects on beneficial insects, such as pollinators. Plant-based pest control agents such as essential oils could provide an alternative because they have low environmental persistency; however, these products struggle to provide effective control. We found a new natural acaricide, balsam fir (Abies balsamea) needles, that kill overwintering I. scapularis ticks. We extracted the essential oil from the needles, analyzed its chemical composition, and tested it for acaricidal activity. We placed ticks in tubes with substrate and positioned the tubes either in the field or in incubators simulating winter temperatures. We added balsam fir essential oil, or one of the main components of balsam fir essential oil (i.e., ß-pinene), to each tube. We found that both the oil and ß-pinene kill overwintering ticks. Whole balsam fir needles require several weeks to kill overwintering ticks, while the essential oil is lethal within days at low temperatures (≤ 4 °C). Further, low temperatures increased the efficacy of this volatile essential oil. Higher temperatures (i.e., 20 °C) reduce the acaricidal effectiveness of the essential oil by 50% at 0.1% v/v. Low temperatures may promote the effectiveness of other natural control products. Winter is an overlooked season for tick control and should be explored as a possible time for the application of low toxicity products for successful tick management.
Photo-responsive hydrogel-based re-programmable metamaterials
Authors: Patel Herit , Chen Jiehao , Hu Yuhang , Erturk Alper
Published: July 2022

This paper explores a novel programmable metamaterial using stimuli-responsive hydrogels with a demonstration of bandgap formation and tuning. Specifically, a photo-responsive hydrogel beam that can achieve re-programmable periodicity in geometric and material properties through patterned light irradiation is designed. Hydrogels consist of polymeric networks and water molecules. Many unique properties of hydrogels, including bio-compatibility, stimuli-responsiveness, and low dissipation make them ideal for enabling re-programmable metamaterials for manipulating structural dynamic response and wave propagation characteristics. Bandgap generation and tunability in photo-responsive hydrogel-based metamaterial (in the form of a diatomic phononic chain) as well as the effects of system parameters such as light exposure pattern and photo-sensitive group concentration on the bandgap width and center frequency are systematically studied. In agreement with finite-element model simulations, it is observed that an increase in light exposure region size reduces both the bandgap width and center frequency, while an increase in the concentration of photo-sensitive group increases bandgap width, attenuation and reduces its center frequency. This work unveils the potential of stimuli-response hydrogels as a new class of low-loss soft metamaterials, unlike most other soft materials that are too lossy to sustain and exploit wave phenomena.
Research on smoke control for an underground mall fire, based on smoke barrier and mechanical smoke exhaust system
Authors: Jia Jinzhang , Tian Xiuyuan , Wang Fengxiao
Published: July 2022

This study examines smoke spread in an underground mall fire under the composite smoke control mode of a smoke barrier and a mechanical smoke exhaust system. The objective is to optimize the selection of smoke containment and exhaust methods in an underground mall in Fuxin City, China. A Fire Dynamics Simulator was used for numerical simulation to investigate the effects of the sagging height and spacing of smoke barriers on smoke containment, as well as the effects of size, number, and arrangement of smoke vents in the mechanical smoke exhaust system on the effectiveness of smoke exhaust. The results indicated that a smoke barrier with a sagging height of 1 m and a spacing of 5 m was effective in preventing the spread of high-temperature smoke. When the sagging height of the smoke barrier increased to 1.2 m, the smoke barrier effect was comparable to that of a 1 m height barrier. Regarding the mechanical smoke exhaust system, the size of the opening area of the smoke vent had no significant effect on the smoke exhaust effect. The best smoke exhaust effect was achieved when the number of smoke vents was 12. Additionally, the double-row setting of smoke vents was more efficient than the single-row setting. Combining a smoke barrier and a mechanical smoke exhaust system can provide a more effective smoke control compared to either system alone. Comprehensively, considering the effectiveness and economy of smoke containment and exhaust, the optimal combination of smoke containment and exhaust was determined to be a smoke barrier with a sagging height of 1 m and spacing of 5 m, and a mechanical smoke exhaust system with 12 smoke vents in a double-row arrangement.
ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children
Authors: Suurbaar Jennifer , Moussiliou Azizath , Tahar Rachida , Olsen Rebecca W. , Adams Yvonne , Dalgaard Nanna , Baafour Eric K. , Adukpo Selorme , Hviid Lars , Kusi Kwadwo A. , Alao Jules , Ofori Michael F. , Ndam Nicaise T. , Jensen Anja R.
Published: July 2022

Members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on the surface of infected erythrocytes (IEs) are important virulence factors, which mediate vascular adhesion of IEs via endothelial host receptors and are targets of naturally acquired immunity. The PfEMP1 family can be divided into clinically relevant subgroups, of which some bind intercellular adhesion molecule 1 (ICAM-1). While the acquisition of IgG specific for ICAM-1-binding DBLβ domains is known to differ between PfEMP1 groups, its ability to induce antibody-dependent cellular phagocytosis (ADCP) is unclear. We therefore measured plasma levels of DBLβ-specific IgG, the ability of such IgG to inhibit PfEMP1-binding to ICAM-1, and its ability to opsonize IEs for ADCP, using plasma from Beninese children with severe (SM) or uncomplicated malaria (UM). IgG specific for DBLβ from group A and B ICAM-1-binding PfEMP1 were dominated by IgG1 and IgG3, and were similar in SM and UM. However, levels of plasma IgG inhibiting ICAM-1-binding of group A DBLβ of PFD1235w was significantly higher in children with UM than SM, and acute UM plasma induced a higher ADCP response than acute SM plasma.
Therapeutic exercise to improve motor function among children with Down Syndrome aged 0 to 3 years: a systematic literature review and meta‑analysis
Authors: Rodríguez-Grande Eliana-Isabel , Buitrago-López Adriana , Torres-Narváez Martha-Rocio , Serrano-Villar Yannely , Verdugo-Paiva Francisca , Ávila Camila
Published: July 2022

The effects and the prescription parameters of therapeutic exercise are not clear. For this reason, is needed to determine the effect of therapeutic exercises on the motor function of children with Down Syndrome (DS) aged 0 to 3 years. The present study is systematic review and meta-analysis of effectiveness outcomes in this population: gait, balance, motor development, fine motor skills, and executive functions. The databases of PubMed, PEDro, EMBASE, SCIELO, Lilacs, Cochrane library were searched from January to December 2019. We recruited Randomized Controlled Trials (RCTs) which met the inclusion criteria in our study. Six studies and 151 participants were included. Two types of therapeutic exercises, aerobic and neuromuscular, were identified. Both types of exercise were effective in improving outcomes. There were no differences between the modes of application of the exercise. No differences were identified between the treadmill and the physiotherapy plan for the reduction of the time to reach independent walking, Mean Difference (MD) 46.79, 95% Confidence Interval (IC) (− 32.60, 126.19), nor for the increase in walking speed MD 0.10 IC (− 0.02, 0.21) m/s. This study suggests that aerobic exercise therapy has a potentially effective role to promote the gait and motor development of children with DS aged 0 to 3 years when it is applied using a treadmill with a frequency of 5 days, a duration of 6–8 min, and an intensity of between 0.2 and 0.5 m/s. Studies with less heterogeneity and larger sample sizes are required.
Contamination analysis of Arctic ice samples as planetary field analogs and implications for future life-detection missions to Europa and Enceladus
Authors: Coelho Lígia F. , Blais Marie-Amélie , Matveev Alex , Keller-Costa Tina , Vincent Warwick F. , Costa Rodrigo , Martins Zita , Canário João
Published: July 2022

Missions to detect extraterrestrial life are being designed to visit Europa and Enceladus in the next decades. The contact between the mission payload and the habitable subsurface of these satellites involves significant risk of forward contamination. The standardization of protocols to decontaminate ice cores from planetary field analogs of icy moons, and monitor the contamination in downstream analysis, has a direct application for developing clean approaches crucial to life detection missions in these satellites. Here we developed a comprehensive protocol that can be used to monitor and minimize the contamination of Arctic ice cores in processing and downstream analysis. We physically removed the exterior layers of ice cores to minimize bioburden from sampling. To monitor contamination, we constructed artificial controls and applied culture-dependent and culture-independent techniques such as 16S rRNA amplicon sequencing. We identified 13 bacterial contaminants, including a radioresistant species. This protocol decreases the contamination risk, provides quantitative and qualitative information about contamination agents, and allows validation of the results obtained. This study highlights the importance of decreasing and evaluating prokaryotic contamination in the processing of polar ice cores, including in their use as analogs of Europa and Enceladus.
Estimation of biological heart age using cardiovascular magnetic resonance radiomics
Authors: Raisi-Estabragh Zahra , Salih Ahmed , Gkontra Polyxeni , Atehortúa Angélica , Radeva Petia , Boscolo Galazzo Ilaria , Menegaz Gloria , Harvey Nicholas C. , Lekadir Karim , Petersen Steffen E.
Published: July 2022

We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a “heart age delta”, which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.
Long-term changes in serum silver concentrations after extremity reconstruction with silver-coated megaprostheses
Authors: Smolle Maria Anna , Bergovec Marko , Scheipl Susanne , Gössler Walter , Amerstorfer Florian , Glehr Mathias , Leithner Andreas , Friesenbichler Jörg
Published: July 2022

Silver-coated megaprostheses are considered to reduce infection rate following reconstruction of bone defects in tumour surgery or revision arthroplasty. However, little is known about systemic silver exposure and possible side effects. The aim of this study was to analyse serum silver concentrations in patients with silver-coated megaprostheses over a prolonged time period. Between 2004 and 2016, 46 patients (52.2% female, mean age at surgery 47.1 ± 24.2 years) received silver-coated megaprostheses for septic (n = 26) or oncological (n = 17; main implant since 2013) indications, or aseptic loosening (n = 3). Blood was drawn from all patients within the first few days following surgery (without silver ion levels) and thereafter every 6 months at the outpatient department (with silver ion levels). Inductively coupled plasma mass spectrometry was used to determine silver ion levels. Median follow-up was 47.3 months (IQR: 16.1–78.9). Overall, 29 revision surgeries became necessary in 20 patients, equivalent to a cumulative complication rate of 63.0%. Revisions were most commonly for periprosthetic joint infections (PJIs, n = 12) and instability/soft tissue problems (n = 10). Revision-free implant survival was 81.4%, 42.3% and 35.2% at one, 5 and 10 years. Incidence of local argyria was 8.7% (n = 4). Silver ion levels at two or more consecutive time points during follow-up were available for 26 patients. An increment of silver levels within the first months (“run-in”) was observed, followed by an unspecific undulating course. Median initial and latest follow-up (median, 49.5 months) serum silver ion levels were 16.0 ppb (IQR: 9.1–29.1) and 7.4 ppb (IQR: 2.7–14.1), respectively. According to the multivariate mixed linear random-effects model, development of PJI was associated with significantly higher silver ion levels over time (p = 0.002), irrespective of time from surgery (p = 0.274). In the current series, a cumulative complication rate of 63.0% was observed for patients receiving silver-coated megaprostheses for septic of oncological indications. An overall unspecific course of silver ion concentration was present. Development of PJI was significantly associated with increased silver ion levels over time. Yet, no systemic complication associated to high silver levels occurred. It can be concluded that silver-coated implants constitute a safe solution for megaprosthetic reconstruction, but monitoring of silver concentrations is recommended.
Thermoresponsive C22 phage stiffness modulates the phage infectivity
Authors: Sae-Ueng Udom , Bhunchoth Anjana , Phironrit Namthip , Treetong Alongkot , Sapcharoenkun Chaweewan , Chatchawankanphanich Orawan , Leartsakulpanich Ubolsree , Chitnumsub Penchit
Published: July 2022

Bacteriophages offer a sustainable alternative for controlling crop disease. However, the lack of knowledge on phage infection mechanisms makes phage-based biological control varying and ineffective. In this work, we interrogated the temperature dependence of the infection and thermo-responsive behavior of the C22 phage. This soilborne podovirus is capable of lysing Ralstonia solanacearum, causing bacterial wilt disease. We revealed that the C22 phage could better infect the pathogenic host cell when incubated at low temperatures (25, 30 °C) than at high temperatures (35, 40 °C). Measurement of the C22 phage stiffness revealed that the phage stiffness at low temperatures was 2–3 times larger than at high temperatures. In addition, the imaging results showed that more C22 phage particles were attached to the cell surface at low temperatures than at high temperatures, associating the phage stiffness and the phage attachment. The result suggests that the structure and stiffness modulation in response to temperature change improve infection, providing mechanistic insight into the C22 phage lytic cycle. Our study signifies the need to understand phage responses to the fluctuating environment for effective phage-based biocontrol implementation.
Optical barcoding using polarisation sensitive plasmonic biosensors for the detection of self-assembled monolayers
Authors: Balaur Eugeniu , Sadatnajafi Catherine , Abbey Brian
Published: July 2022

Periodic subwavelength apertures have the ability to passively detect variations in the dielectric properties of the local sample environment through modification of the plasmon resonances associated with these structures. The resulting resonance peak can effectively provide a ‘fingerprint’ indicative of the dielectric properties of the medium within the near-surface region. Here we report on the use of bimodal silver-based plasmonic colour filters for molecular sensing. Firstly, by exploring the optical output of these devices as a function of the incident polarisation for a range of different analytes of known refractive index, we were able to both maximise and quantify their sensitivity. We then apply this concept to the real-time monitoring of the formation of self-assembled monolayers based on detection of the optical output using a spectrometer. This highlights the potential for bimodal plasmonic devices to be able to dynamically monitor variations in the local environment down to the level of single molecules without the need for specific functionalisation or labelling. Advantages of using this technique include the ability for these devices to be miniaturised and to dynamically tailor their optical output permitting the analysis of very small sample volumes and maximise their dynamic range for a specific analyte.
Miscibility of rock and ice in the interiors of water worlds
Authors: Kovačević Tanja , González-Cataldo Felipe , Stewart Sarah T. , Militzer Burkhard
Published: July 2022

Super-Earths and sub-Neptunes are the most common planet types in our galaxy. A subset of these planets is predicted to be water worlds, bodies that are rich in water and poor in hydrogen gas. The interior structures of water worlds have been assumed to consist of water surrounding a rocky mantle and iron core. In small planets, water and rock form distinct layers with limited incorporation of water into silicate phases, but these materials may interact differently during the growth and evolution of water worlds due to greater interior pressures and temperatures. Here, we use density functional molecular dynamics (DFT-MD) simulations to study the miscibility and interactions of enstatite (MgSiO3), a major end-member silicate phase, and water (H2O) at extreme conditions in water world interiors. We explore pressures ranging from 30 to 120 GPa and temperatures from 500 to 8000 K. Our results demonstrate that enstatite and water are miscible in all proportions if the temperature exceeds the melting point of MgSiO3. Furthermore, we performed smoothed particle hydrodynamics simulations to demonstrate that the conditions necessary for rock-water miscibility are reached during giant impacts between water-rich bodies of 0.7–4.7 Earth masses. Our simulations lead to water worlds that include a mixed layer of rock and water.
Direct and remote induced actuation in artificial muscles based on electrospun fiber networks
Authors: Bunea Mihaela-Cristina , Beregoi Mihaela , Evanghelidis Alexandru , Galatanu Andrei , Enculescu Ionut
Published: July 2022

The present work reports a new configuration of soft artificial muscle based on a web of metal covered nylon 6/6 micrometric fibers attached to a thin polydimethylsiloxane (PDMS) film. The preparation process is simple and implies the attachment of metalized fiber networks to a PDMS sheet substrate while heating and applying compression. The resulting composite is versatile and can be cut in different shapes as a function of the application sought. When an electric current passes through the metallic web, heat is produced, leading to local dilatation and to subsequent controlled deformation. Because of this, the artificial muscle displays a fast and ample movement (maximum displacement of 0.8 cm) when applying a relatively low voltage (2.2 V), a consequence of the contrast between the thermal expanse coefficients of the PDMS substrate and of the web-like electrode. It was shown that the electrical current producing this effect can originate from both direct electric contacts, and untethered configurations i.e. radio frequency induced. Usually, for thermal activated actuators the heating is produced by using metallic films or conductive carbon-based materials, while here a fast heating/cooling process is obtained by using microfiber-based heaters. This new approach for untethered devices is an interesting path to follow, opening a wide range of applications were autonomous actuation and remote transfer of energy are needed.
Tailoring magnetism in silicon-doped zigzag graphene edges
Authors: Ugartemendia Andoni , Garcia−Lekue Aran , Jimenez−Izal Elisa
Published: July 2022

Recently, the edges of single-layer graphene have been experimentally doped with silicon atoms by means of scanning transmission electron microscopy. In this work, density functional theory is applied to model and characterize a wide range of experimentally inspired silicon doped zigzag-type graphene edges. The thermodynamic stability is assessed and the electronic and magnetic properties of the most relevant edge configurations are unveiled. Importantly, we show that silicon doping of graphene edges can induce a reversion of the spin orientation on the adjacent carbon atoms, leading to novel magnetic properties with possible applications in the field of spintronics.
Long-term clinical outcomes and predictive factors in patients with chronic ocular graft-versus-host disease
Authors: Yoon Hyeon-Jeong , Song Ga-Young , Yoon Kyung Chul
Published: July 2022

We investigate long-term clinical outcomes and predictive factors associated with poor vision outcomes in patients with ocular graft-versus-host disease (oGVHD). This retrospective cohort study involved 94 patients with chronic oGVHD, classified into severe (n = 25) and non-severe (n = 69) groups. Factors associated with oGVHD severity and poor vision outcomes were examined using multivariate logistic regression. In the severe oGVHD group, the disease activity pattern tended to be persistent, whereas flare-up episodes were more frequent and occurred over shorter intervals in this group. Myelodysplastic syndrome (MDS) and lung GVHD were more common and systemic calcineurin inhibitors were used more frequently in the severe group than in the non-severe group. Finally, 5-year survival rates were poorer in the severe group. Multivariate analysis revealed that MDS, lung GVHD involvement, and no history of systemic calcineurin inhibitor use were risk factors for severe oGVHD. Risk factors for poor vision outcomes were conjunctival scarring and persistent epithelial defects. In conclusion, MDS, lung GVHD, and no history of systemic calcineurin inhibitors are associated with severe oGVHD. Conjunctival scarring and persistent epithelial defects are risk factors for poor vision outcomes.
New insights into sperm rheotaxis, agglutination and bundle formation in Sharkasi chickens based on an in vitro study
Authors: El-Sherry Taymour M. , Abd-Elhafeez Hanan H. , Sayed M. A. M.
Published: July 2022

Fertility in birds is dependent on their ability to store adequate populations of viable sperm for extended durations in sperm storage tubules (SSTs). The exact mechanisms by which sperm enter, reside, and egress from the SSTs are still controversial. Sharkasi chicken sperm showed a high tendency to agglutinate, forming motile thread-like bundles comprising many cells. Since it is difficult to observe sperm motility and behavior inside the opaque oviduct, we employed a microfluidic device with a microchannel cross-section resembling close to that of sperm glands allowing for the study of sperm agglutination and motility behavior. This study discusses how sperm bundles are formed, how they move, and what role they may have in extending sperm residency inside the SSTs. We investigated sperm velocity and rheotaxis behavior when a fluid flow was generated inside a microfluidic channel by hydrostatic pressure (flow velocity = 33 µm/s). Spermatozoa tended to swim against the flow (positive rheotaxis) and sperm bundles had significantly lower velocity compared to lonesome sperm. Sperm bundles were observed to swim in a spiral-like motion and to grow in length and thickness as more lonesome sperm are recruited. Sperm bundles were observed approaching and adhering to the sidewalls of the microfluidic channels to avoid being swept with fluid flow velocity > 33 µm/s. Scanning and transmission electron microscopy revealed that sperm bundles were supported by a copious dense substance. The findings show the distinct motility of Sharkasi chicken sperm, as well as sperm's capacity to agglutinate and form motile bundles, which provides a better understanding of long-term sperm storage in the SSTs.
Macrophage-compatible magnetic achiral nanorobots fabricated by electron beam lithography
Authors: Jiang Teng , Song Xiaoxia , Mu Xueliang , Cheang U. Kei
Published: July 2022

With the development and progress of nanotechnology, the prospect of using nanorobots to achieve targeted drug delivery is becoming possible. Although nanorobots can potentially improve nano-drug delivery systems, there remains a significant challenge to fabricating magnetically controllable nanorobots with a size suitable for drug delivery in complex in vivo environments. Most of the current research focused on the preparation and functionalization of microscale and milliscale robots due to the relative difficulties in fabricating nanoscale robots. To address this problem and move towards in vivo applications, this study uses electron beam lithography to fabricate achiral planar L-shaped nanorobots that are biocompatible with immune cells. Their minimal planar geometry enabled nanolithography to fabricate nanorobots with a minimum feature size down to 400 nm. Using an integrated imaging and control system, the locomotive behavior of the L-shaped nanorobots in a fluidic environment was studied by examining their velocity profiles and trajectories. Furthermore, the nanorobots exhibit excellent cell compatibility with various types of cells, including macrophage cells. Finally, the long-term cell culture medium immersion test demonstrated that the L-shaped nanorobots have robust stability. This work will demonstrate the potential to use these nanorobots to operate in vivo without triggering immune cell responses.
Exploring the parameters of central redox hub for screening salinity tolerant rice landraces of coastal Bangladesh
Authors: Roy Uthpal Krishna , Bhattacharjee Soumen
Published: July 2022

Regulation of oxidative stress towards origin of favorable internal redox cue plays a decisive role in salinity stress acclimation and least studied in rice and hence is the subject of present investigation. Redox landscaping of seedlings of ten experimental land races of rice of coastal Bangladesh grown under post imbibitional salinity stress (PISS) has been done through characterization of ROS-antioxidant interaction dynamics at metabolic interface, transcriptional reprogramming of redox-regulatory genes along with the assessment of biomarkers of oxidative threat for standardizing redox strategies and quality parameters for screening. The results exhibited a strong correlation between salinity induced redox status (pro-oxidant/antioxidant ratio, efficacy of H2O2 turnover through integrated RboH-Ascorbate–Glutathione/Catalase pathway and estimation of sensitive redox biomarkers of oxidative deterioration) and germination phenotypes of all landraces of rice. Transcript abundance of the marker genes of the enzymes associated with central antioxidant hub for H2O2 processing (CatA, OsAPx2, SodCc2, GRase and RboH) of all experimental landraces of the rice advocate the central role of H2O2 turnover dynamics in regulating redox status and salinity tolerance. Landraces suffering greater loss of abilities of decisive regulation of H2O2 turnover dynamics exhibited threat on the oxidative windows of the germinating seeds under salinity.
Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus
Authors: Valderas-García Elora , Escala Nerea , Álvarez-Bardón María , Castilla-Gómez de Agüero Verónica , Cambra-Pellejà Maria , González del Palacio Laura , Vallejo García Raquel , de la Vega Jennifer , San Feliciano Arturo , del Olmo Esther , Martínez-Valladares María , Balaña-Fouce Rafael
Published: July 2022

The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants.
Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use
Authors: Farokhnia Mehdi , Fede Samantha J. , Grodin Erica N. , Browning Brittney D. , Crozier Madeline E. , Schwandt Melanie L. , Hodgkinson Colin A. , Momenan Reza , Leggio Lorenzo
Published: July 2022

Growing evidence suggests that the glucagon-like peptide-1 (GLP-1) system is involved in mechanisms underlying alcohol seeking and consumption. Accordingly, the GLP-1 receptor (GLP-1R) has begun to be studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The aim of this study was to investigate the association between genetic variation at the GLP-1R and brain functional connectivity, according to the severity of alcohol use. Participants were 181 individuals categorized as high-risk (n = 96) and low-risk (n = 85) alcohol use, according to their AUD identification test (AUDIT) score. Two uncommon single nucleotide polymorphisms (SNPs), rs6923761 and rs1042044, were selected a priori for this study because they encode amino-acid substitutions with putative functional consequences on GLP-1R activity. Genotype groups were based on the presence of the variant allele for each of the two GLP-1R SNPs of interest [rs6923761: AA + AG (n = 65), GG (n = 116); rs1042044: AA + AC (n = 114), CC (n = 67)]. Resting-state functional MRI data were acquired for 10 min and independent component (IC) analysis was conducted. Multivariate analyses of covariance (MANCOVA) examined the interaction between GLP-1R genotype group and AUDIT group on within- and between-network connectivity. For rs6923761, three ICs showed significant genotype × AUDIT interaction effects on within-network connectivity: two were mapped onto the anterior salience network and one was mapped onto the visuospatial network. For rs1042044, four ICs showed significant interaction effects on within-network connectivity: three were mapped onto the dorsal default mode network and one was mapped onto the basal ganglia network. For both SNPs, post-hoc analyses showed that in the group carrying the variant allele, high versus low AUDIT was associated with stronger within-network connectivity. No significant effects on between-network connectivity were found. In conclusion, genetic variation at the GLP-1R was differentially associated with brain functional connectivity in individuals with low versus high severity of alcohol use. Significant findings in the salience and default mode networks are particularly relevant, given their role in the neurobiology of AUD and addictive behaviors.
Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity
Authors: Visuthranukul Chonnikant , Chamni Supakarn , Kwanbunbumpen Tanisa , Saengpanit Puthita , Chongpison Yuda , Tepaamorndech Surapun , Panichsillaphakit Ekkarit , Uaariyapanichkul Jaraspong , Nonpat Natthapong , Chomtho Sirinuch
Published: July 2022

Inulin might improve body composition in obese children. We aimed to determine the effects of inulin supplementation on body composition and metabolic outcomes in obese children. A randomized, double-blinded placebo-controlled study was conducted in obese Thai children aged 7–15 years. Participants were assigned to 3 treatment groups for 6 months: 13 g of extracted inulin powder from Thai Jerusalem artichoke, isocaloric maltodextrin, and dietary fiber advice groups. Body composition was assessed by bioelectrical impedance analysis. One-hundred and fifty-five children completed the study (mean age 10.4 ± 2.2 years, BMI z-score 3.2 ± 1.0, 59% male). The drop-out rate was 6%. The inulin extract yielded more than 90% compliance without significant gastrointestinal side effects. All three groups demonstrated a significant decrease in BMI z-score, fat mass index (FMI), and trunk FMI, but the differences between groups were not observed. Fat-free mass index significantly increased only in the inulin group (16.18 ± 1.90 vs. 16.38 ± 1.98 kg/m2, P = 0.009). There were no significant differences in the metabolic profiles between groups. Despite showing no substantial effect on adiposity, inulin may increase fat-free mass in obese children. Further research in the change of gut microbiota composition is needed to determine inulin’s impact on host-microbe interaction in pediatric obesity.
N1-methyl-pseudouridine is incorporated with higher fidelity than pseudouridine in synthetic RNAs
Authors: Chen Tien-Hao , Potapov Vladimir , Dai Nan , Ong Jennifer L. , Roy Bijoyita
Published: July 2022

In vitro transcribed synthetic messenger RNAs (mRNAs) represent a novel therapeutic modality. To overcome the inherent immunogenicity, as well as to increase the therapeutic efficacy of the molecules, uridine analogs—such as pseudouridine (Ψ) and N1-methyl-pseudouridine (m1Ψ), are incorporated in the synthetic mRNA. To decipher the fidelity with which these modifications are incorporated during the in vitro transcription (IVT) process, we compared the incorporation fidelity of uridine analogs with different RNA polymerases. We demonstrate that m1Ψ is incorporated with higher fidelity than Ψ. The fidelity of nucleotide incorporation differs between RNA polymerases; however, the spectrum of mutations observed between the RNAPs is similar. We also show that the array of nucleotide misincorporation is not dependent on the template DNA sequence context and that the distribution of these misincorporated nucleotides is not localized to any specific region along the length of the RNA. Based on our findings, we introduce a novel method to improve uridine analog incorporation fidelity during IVT. Our proof-of-concept experiments for higher-fidelity incorporation of uridine analogs during IVT provide guidelines when choosing RNAPs for the generation of modified uridine-containing mRNAs in vitro.
Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
Authors: Sánchez Ricardo , Dorado Sara , Ruíz-Heredia Yanira , Martín-Muñoz Alejandro , Rosa-Rosa Juan Manuel , Ribera Jordi , García Olga , Jimenez-Ubieto Ana , Carreño-Tarragona Gonzalo , Linares María , Rufián Laura , Juárez Alexandra , Carrillo Jaime , Espino María José , Cáceres Mercedes , Expósito Sara , Cuevas Beatriz , Vanegas Raúl , Casado Luis Felipe , Torrent Anna , Zamora Lurdes , Mercadal Santiago , Coll Rosa , Cervera Marta , Morgades Mireia , Hernández-Rivas José Ángel , Bravo Pilar , Serí Cristina , Anguita Eduardo , Barragán Eva , Sargas Claudia , Ferrer-Marín Francisca , Sánchez-Calero Jorge , Sevilla Julián , Ruíz Elena , Villalón Lucía , del Mar Herráez María , Riaza Rosalía , Magro Elena , Steegman Juan Luis , Wang Chongwu , de Toledo Paula , García-Gutiérrez Valentín , Ayala Rosa , Ribera Josep-Maria , Barrio Santiago , Martínez-López Joaquín
Published: July 2022

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.
Characterization and anti-biofilm activity of bacteriophages against urinary tract Enterococcus faecalis isolates
Authors: El-Atrees Doaa M. , El-Kased Reham F. , Abbas Ahmad M. , Yassien Mahmoud A.
Published: July 2022

Strong biofilm-forming Enterococcus feacalis urinary tract pathogens (n = 35) were used to determine the lytic spectrum of six bacteriophages isolated from sewage samples. Only 17 Enterococcus feacalis isolates gave lytic zones with the tested bacteriophages from which five isolates were susceptible to all of them. The isolated enterococcal phages are characterized by wide range of thermal (30–90 °C) and pH (3–10) stability. They belong to order Caudovirales, from which four bacteriophages (EPA, EPB, EPD, EPF) belong to family Myoviridae and two (EPC, EPE) belong to family Siphoviridae. In addition, they have promising antibiofilm activity against the tested strong-forming biofilm E. faecalis isolates. The enterococcal phages reduced the formed and preformed biofilms to a range of 38.02–45.7% and 71.0–80.0%, respectively, as compared to the control. The same promising activities were obtained on studying the anti-adherent effect of the tested bacteriophages on the adherence of bacterial cells to the surface of urinary catheter segments. They reduced the number of adherent cells to a range of 30.8–43.8% and eradicated the pre-adherent cells to a range of 48.2–71.1%, as compared to the control. Overall, the obtained promising antibiofilm activity makes these phages good candidates for application in preventing and treating biofilm associated Enterococcus faecalis infections.