bluuebunny/crossref_metadata_2025 huggingface dataset:
Echo intensity and gray-level co-occurrence matrix analysis of soft tissue grafting biomaterials and dental implants: an in vitro ultrasonographic pilot study
Authors: Mancini Leonardo , Khehra Anahat , Nguyen Tu , Barootchi Shayan , Tavelli Lorenzo
Published: July 2023

Objective:

To characterize different allogeneic and xenogeneic soft tissue graft substitutes and to assess their echo intensity and grayscale texture-related outcomes by using high-frequency ultrasonography (HFUS).

Methods:

Ten samples from each of the following biomaterials were scanned using HFUS: bilayered collagen matrix (CM), cross-linked collagen matrix (CCM), multilayered cross-linked collagen matrix (MCCM), human-derived acellular dermal matrix (HADM), porcine-derived acellular dermal matrix (PADM), collagen tape dressing (C) and dental implants (IMPs). The obtained images were then imported in a commercially available software for grayscale analysis. First-order grayscale outcomes included mean echo intensity (EI), standard deviation, skewness, and kurtosis, while second-order grayscale outcomes comprised entropy, contrast, correlation, energy and homogeneity derive from the gray-level co-occurrence matrix analysis. Descriptive statistics were performed for visualization of results, and one-way analysis of variance with Bonferroni post-hoc tests were performed to relative assessments of the biomaterials.

Results:

The statistical analysis revealed a statistically significant difference among the groups for EI (p < .001), with the group C showing the lowest EI, and the IMP group presenting with the greatest EI values. All groups showed significantly higher EI when compared with C (p < .001). No significant differences were observed for energy, and correlation, while a statistically significant difference among the groups was found in terms of entropy (p < 0.01), contrast (p < .001) and homogeneity (p < .001). IMP exhibited the highest contrast, that was significantly higher than C, HADM, PADM, CCM and CM.

Conclusions:

HFUS grayscale analysis can be applied to characterize the structure of different biomaterials and holds potential for translation to in-vivo assessment following soft tissue grafting-related procedures.
Automated detection of cephalometric landmarks using deep neural patchworks
Authors: Weingart Julia Vera , Schlager Stefan , Metzger Marc Christian , Brandenburg Leonard Simon , Hein Anna , Schmelzeisen Rainer , Bamberg Fabian , Kim Suam , Kellner Elias , Reisert Marco , Russe Maximilian Frederik
Published: July 2023

Objectives

This study evaluated the accuracy of deep neural patchworks (DNPs), a deep learning-based segmentation framework, for automated identification of 60 cephalometric landmarks (bone-, soft tissue- and tooth-landmarks) on CT scans. The aim was to determine whether DNP could be used for routine three-dimensional cephalometric analysis in diagnostics and treatment planning in orthognathic surgery and orthodontics.

Methods:

Full skull CT scans of 30 adult patients (18 female, 12 male, mean age 35.6 years) were randomly divided into a training and test data set (each n = 15). Clinician A annotated 60 landmarks in all 30 CT scans. Clinician B annotated 60 landmarks in the test data set only. The DNP was trained using spherical segmentations of the adjacent tissue for each landmark. Automated landmark predictions in the separate test data set were created by calculating the center of mass of the predictions. The accuracy of the method was evaluated by comparing these annotations to the manual annotations.

Results:

The DNP was successfully trained to identify all 60 landmarks. The mean error of our method was 1.94 mm (SD 1.45 mm) compared to a mean error of 1.32 mm (SD 1.08 mm) for manual annotations. The minimum error was found for landmarks ANS 1.11 mm, SN 1.2 mm, and CP_R 1.25 mm.

Conclusion:

The DNP-algorithm was able to accurately identify cephalometric landmarks with mean errors <2 mm. This method could improve the workflow of cephalometric analysis in orthodontics and orthognathic surgery. Low training requirements while still accomplishing high precision make this method particularly promising for clinical use.
Salix ×browiczii (Salicaceae) – a new nothospecies from northeastern Greece
Authors: Zieliński Jerzy , Tomaszewski Dominik , Kosiński Piotr
Published: July 2023

A hybrid between Salix triandra and S. xanthicola, occurring in the Rhodope Mountains in northeastern Greece, is described as a new nothospecies. It differs from S. triandra by having distinctly hairy young stems and more deeply serrate-dentate leaf margins, and from S. xanthicola by a smooth, unstructured (without conicoids) wax layer on the lower side of the leaves and the presence of subsessile glands on the petioles.
Evaluation of marginal and internal fit of metal crowns made from wax patterns made by conventional technique and CAD CAM milling technique: An in vivo study
Authors: Tawade Shubham , Dhamande Mithilesh , Sathe Seema
Published: July 2023

Introduction: Marginal and internal fit of a metal crown are very important for a successful metal crown prosthesis. This study will evaluate the marginal and internal fit of metal crowns produced from wax patterns that are formed by two different wax pattern fabrication procedures: conventional wax pattern fabrication and wax pattern milled using the computer-aided design and manufacture (CAD CAM) method.

Objectives: To evaluate the marginal and internal fit of metal crowns over prepared tooth made from wax patterns made by conventional technique and CAD CAM technique.

Methodology: A total of 21 participants with endodontically restored mandibular first molar will be selected. Two all-metal crowns will be made for each participant, thus 42 metal crowns in total will be made. These 42 metal crowns will be divided into two groups based on the method used to create wax patterns: metal crowns made using conventional hand-carved wax pattern technique (Group I, n=21) and metal crowns made using CAD CAM-milled wax pattern technique (Group II, n=21). Then, the marginal and internal fit of metal crowns from both groups will be compared.

Expected results: It is expected that metal crowns made by CAD CAM milled wax pattern fabrication method will have better marginal and internal fit than those of conventional method. Conclusions: The clinical acceptability and success of the dental crown will be assessed by this study. Minimal marginal gap and better internal fit of all metal crown are key qualities.
ENERGY MATHEMATICAL MODEL OF A SPRAYER
Authors: Khafizov Kamil , Nurmiev Azat , Khafizov Ramil , Zalakov Nail , Zaycev Petr
Published: July 2023

The research was carried out in order to develop an energy mathematical model of a plant protection unit with a trailed sprayer, which makes it possible to optimize the parameters and operating modes, taking into account their influence on the size and loss of crop yield. For comparison with the tendencies of changes in the parameters of sprayers established in practice, computational experiments were performed using the developed mathematical model. The object of study is an analogue of MTZ-82 tractor, the main parameters of which (mass, engine power, kinematic length, etc.) can be changed, an analogue of a trailed sprayer with variable parameters (width, operating speed, tank volume, drawbar length, location of the center of mass, profile width and support wheel diameter, etc.). The optimization criterion was composite and included the sum of direct and indirect energy costs during the operation of the unit, taking into account the energy of the crop lost due to deviations from the optimal parameters and operating modes of the sprayer. Incorrect choice of unit parameters leads to yield losses, resulting from its decrease due to a violation of the deadline for performing a technological operation to protect crops from weeds, trampling down part of the crops by the unit's movers during processing, especially if there is no possibility of turning outside the field, due to soil compaction in the zone of growth and development of plant root systems. Computational experiments carried out using the developed energy mathematical model showed that an increase in sprayer coverage from 16 to 32 m at an aggregate speed of 12 km/h leads to a decrease in total energy costs from 3250 MJ/ha to 1692 MJ/ha, an increase in the unit speed from 7 to 12 km/h, with a working width of 32 m reduces the total energy costs from 1971 to 1692 MJ/ha. Reducing the width of the sprayer wheel tire profile from 0.6 to 0.2 m is accompanied by a decrease in total energy costs from 2793 MJ/ha to 1692 MJ/ha.
IMPROVEMENT OF ROLLING TECHNOLOGY AND FUEL INJECTION ADVANCE CLUTCH TEST
Authors: Ivanschikov Yuriy , Valiev Ayrat , Novikov Aleksey , Dobrohotov Yuriy , Kazakov Yuriy
Published: July 2023

The technology used for high-pressure fuel pumps running at fixed camshaft speeds does not provide running-in of friction pairs not only for the pump, but also for its fuel injection advance clutch. The purpose of the research is to develop a device that provides an equally variable angular velocity of the driven clutch half of the fuel injection advance clutch. The uneven speed of rotation of the driven half-coupling makes it possible to run the clutch in dynamic loading conditions by optimizing the stroke of the pushers, the radius of the rollers and the height of the programming washer, while ensuring optimal running-in modes with a combination of specified torsional vibrations in the range of amplitudes that overlap the operating angles of turn of the half-couplings. To achieve this goal, the work determined the range of sizes of the radii of the driven semi-shaft of the proposed device (6…12.5 mm) and its copying roller (5…9 mm), which provides an equally variable angular velocity of the driven half-coupling. For these values of the structural elements of the device, the height of the cam of the programming washer will be in the range of 2.99 ... 5.85 mm. In this range, it is possible to run commercially available fuel injection advance clutches in dynamic mode with an equally variable angular velocity, which improves the quality of running-in of the friction pairs of the pump and its clutch.
Gestational Diabetes: A Review
Authors: Barbach Abdelhaq , Chenguiti Anas Ansari , Charrah Yahya , Barkat Amina
Published: July 2023

Gestational diabetes (GD) is a disorder of glucose tolerance resulting in hyperglycemia first diagnosed during pregnancy. Its worldwide prevalence is estimated at 14% but varies regionally. In 2008, new diagnostic criteria were adopted, leading to an increase in diagnosed cases. Biomarkers could potentially serve as an alternative to the current diagnostic criteria in the future, enabling the realization of a universally applicable GD screening program. Risk factors associated with GD encompass a range of factors, including epigenetic factors, inadequate vitamin D levels, family history of diabetes, prediabetes, obesity, fetal death, polycystic ovary syndrome (PCOS), and advanced maternal age. GD can have consequences for maternal health, increasing the risk of hypertensive disorders, premature labor, cesarean delivery, metabolic disorders, and later type 2 diabetes. In children, it may be associated with macrosomia, shoulder dystocia, respiratory insufficiency, and hospitalization in the neonatal intensive care. Offspring born to mothers with GD face heightened susceptibility to childhood and adult obesity, alongside elevated cardiometabolic risk. The consequences and risk factors of GD are not fully understood to this day. Therefore, Additional research is warranted to gain a deeper comprehension of the pathophysiology underlying the disease and to ascertain efficacious preventive and therapeutic approaches. Nutritional therapy is often sufficient to achieve normoglycemia objectives. An individualized nutritional program is recommended, providing the necessary nutrients to promote maternal and infant health, attain optimal gestational weight gain and uphold glycemic regulation. However, in some cases, additional antidiabetic therapy is necessary. Insulin remains the most commonly used treatment, but metformin may be a safe and effective alternative. This still needs to be validated by in-depth studies leading to better evaluation of its long-term effects on offspring.
Evaluation of Safety Profile of Costus Pictus D Don Methanolic Leaf Extract on Albino Wistar Rats
Authors: Raj Jeneth Berlin , S Parthasarathy , K Manimekalai , AR Srinivasan
Published: July 2023

With the emerging trend of preferring naturopathy over modern medicine, common people are in more danger when consuming natural plant products without the knowledge of the toxic agents present in them. Aim and Objective: To evaluate the safety of methanolic leaf extract of Costus pictus D Don on albino Wistar rats. Methodology: The current study was designed strictly based on the organization for economic cooperation and development (OECD) guideline 423 for acute toxicity study to determine LD50 and guideline 407 for sub-acute toxicity study for hazard identification and risk assessment of the test solution. Methanolic leaf extract was prepared by soxhlation. 12 animals (each 12-week-old nulliparous, non-pregnant female Wistar rats with a mean weight of 142 ± 2 g), 3 per step were used for the acute toxicity study. The test was initiated with a single test dose of 300 mg/kg BW on three animals and continued till 2000 mg/kg BW. After ingesting the test dose each animal was observed individually for the first 4 hours and later every day for 2 weeks for signs of toxicity. For the sub-acute toxicity study, 30 adult Wistar rats (each 16-week-old rat weighing 250±12g) were randomized into 3 groups (1 control and 2 study groups) of 10 each consisting of five males and 5 females. Animals in the control group received 1% Carboxymethyl cellulose (CMC) at a dose of 10 ml/kg BW whereas the animals in the study group received 500 and 1000 mg/kg body weight (BW) of the extract respectively for 28 days. Later, all the animals were sacrificed and blood samples were studied for hematological and biochemical changes. Results: The lethal dose of Costus pictus D Don methanolic leaf extract was fixed as more than 2000 mg/kg Body weight. No obvious change was observed in feeding habits, weight, hematology, biochemical parameters, and histopathology. Conclusion: Methanolic leaf extract of Costus pictus D Don was observed to be absolutely safe when given orally in albino Wistar rats.
Support the education of your future employees
Authors: Monacelli Brian
Published: July 2023

Companies have long relied on academic programs to provide trained
employees. When trained with relevant, modern skills, graduates of
these programs can minimize costs to businesses, including recruiting
and on-the-job training expenses. Particularly in technical roles,
such as optics, a pipeline from academia to industry may be created
through partnerships among the academic program and the regional
industries. However, graduates can only be as informed as the academic
program that fosters their education. When industry members find ways
to influence this educational process, graduates earn useful,
in-demand skills, while industry members see applicants with the right
mix of these skills apply for their job openings. This paper discusses
some ways industry can impact the educational process to ensure that
their applicant pool is loaded with potential.
Fluorescence molecular tomography for quantum yield and lifetime
Authors: Cong Wenxiang , Wang Ge
Published: July 2023

Fluorescence molecular tomography (FMT) is a promising modality for noninvasive imaging of internal fluorescence agents in biological tissues, especially in small animal models, with applications in diagnosis, therapy, and drug design. In this paper, we present a fluorescent reconstruction algorithm that combines time-resolved fluorescence imaging data with photon-counting microcomputed tomography (PCMCT) images to estimate the quantum yield and lifetime of fluorescent markers in a mouse model. By incorporating PCMCT images, a permissible region of interest of fluorescence yield and lifetime can be roughly estimated as prior knowledge, reducing the number of unknown variables in the inverse problem and improving the image reconstruction stability. Our numerical experiments demonstrate the accuracy and stability of the proposed reconstruction method in the presence of data noise, achieving a reconstruction error of 0.02 ns for the fluorescence lifetime and an average relative error of 18% for quantum yield reconstruction.
Elimination of signal amplitude disturbance in ghost imaging using an auxiliary laser channel
Authors: Oparin Egor N. , Shumigai Vladimir S. , Sulimov Danil V. , Kalinichev Alexey A. , Tcypkin Anton N.
Published: July 2023

Ghost imaging can be used to detect objects in a nonstationary environment or in the presence of variable ambient light, making it attractive when conventional imaging methods are ineffective. However, the conventional ghost imaging algorithm is susceptible to temporal fluctuations in the detected signal. In this work, we propose a polarization-multiplexed auxiliary laser channel propagating along the same optical path with the main one. The signal in the auxiliary channel is used as a reference and allows the elimination of signal disturbance. A quantitative analysis and comparison of the proposed method’s performance to the high-pass filtering method are demonstrated. For an illumination pattern refresh rate of 10 Hz, effective suppression of bucket signal fluctuations has been experimentally demonstrated. For a disturbance frequency from 1 Hz to 10 Hz, the auxiliary channel method demonstrated a ghost image Pearson correlation coefficient (PCC) of not less than 0.70, while the high-pass filtering method showed a PCC sharp drop from 0.65 to 0.02.
Miniature side-view dual axes confocal endomicroscope for repetitive in vivo imaging
Authors: Shirazi Ahmad , Sahraeibelverdi Tayebeh , Lee Miki , Li Haijun , Yu Joonyoung , Jaiswal Sangeeta , Oldham Kenn R , Wang Thomas D
Published: July 2023

A side-view dual axes confocal endomicroscope is demonstrated that can
be inserted repetitively in hollow organs of genetically engineered
mice for in vivo real-time imaging in horizontal and vertical planes.
Near infrared (NIR) excitation at λex =
785 nm was used. A monolithic 3-axis parametric resonance scan
mirror was fabricated using micro-electro-mechanical systems (MEMS)
technology to perform post-objective scanning in the distal end of a
4.19 mm diameter instrument. Torsional and serpentine springs were
designed to “switch” the mode of imaging between
vertical and horizontal planes by tuning the actuation frequency. This
system demonstrated real-time in-vivo images in horizontal and
vertical planes with 310 µm depth and 1.75 and 7.5 µm
lateral and axial resolution. Individual cells and discrete mucosal
structures could be identified.
Noise analysis in direct detection and coherent detection phase-sensitive optical time-domain reflectometry systems
Authors: Vidal-Moreno Pedro J. , Becerril Carlos , Fernández-Ruiz María R. , Martins Hugo , Martin-Lopez Sonia , Gonzalez-Herraez Miguel
Published: July 2023

This study compares noise and signal-to-noise ratio (SNR) in direct detection and coherent detection fiber-based distributed acoustic sensing (DAS) systems. Both detection schemes employ the dynamic analysis of Rayleigh-backscattered light in phase-sensitive optical time-domain reflectometry (ΦOTDR) systems. Through theoretical and experimental analysis, it is determined that for photodetection filters with a sufficiently narrow bandwidth, the SNR performance of both detection schemes is comparable. However, for filters with poor selectivity, coherent detection was found to exhibit superior performance. These findings provide crucial guidelines for the design of high-performance time-domain DAS systems.
SWAP and Fredkin gates for OAM optical beams via the sandwich of anisotropic optical fibers
Authors: Barshak E. V. , Lapin B. P. , Vikulin D. V. , Yu Fedorov A. , Alexeyev C. N. , Yavorsky M. A.
Published: July 2023

We study the propagation of circularly-polarized optical vortices of higher order topological charges ℓ ≥ 2 in a sandwich of multihelical - anisotropic - multihelical fibers on the basis of the Jones formalism for modes with orbital angular momentum. We demonstrate that such a system can operate as the all - fiber two - bit SWAP as well as universal tree - bit controlled-SWAP (Fredkin) gates over states of optical vortices, in which the mode radial number carries the control bit, while circular polarization and topological charge are the controlled bits.
Scalar vortex beams produced by Pancharatnam–Berry phase optical elements that utilize polarization holography
Authors: Ye Tian , Wang Jinyu , Liu Jie , Qi Peiliang , Zheng Shujun , Yang Yi , Lin Xiao , Huang Zhiyun , Tan Xiaodi
Published: July 2023

We discuss the appearance of the Pancharatnam–Berry phase in polarization holography, and confirm the possibility of generating scalar vortex beams by using the Pancharatnam–Berry phase. The polarization holograms used to generate scalar vortex beams are produced in phenanthrenequinone-doped polymethylmethacrylate (PQ/PMMA), where each radial direction consists of an equivalent half-wave plate hologram with gradually changing directions. The spin angular momentum carried by a circular polarization reading wave is converted into orbital angular momentum in a reconstruction process, resulting in the formation of scalar vortex beams with positive and negative topological charges controlled by the reading polarization.
A high-precision thermometry strategy by replacing the infrared with visible light for detection
Authors: Peng Lixin , Qin Feng , Wang Changwen , Li Leipeng , Zhang Zhiguo
Published: July 2023

We have developed a high-precision thermometry strategy based on 4I9/2–4I15/2 (I800 nm) and 4S3/2–4I15/2 (I551 nm) transitions of Er3+, after replacing the measurement of the 4I11/2–4I15/2 (I1000 nm) transition with the 4S3/2–4I15/2 transition, i.e., using visible light for detection instead of infrared. Through rate equation model analysis, (I1000 nm)2 and I551 nm can be substituted for each other under certain conditions. Further, because the 4I9/2 and 4I11/2 levels of Er3+ are thermally coupled, a new idea of ratiometric thermometry is proposed based on the ratio of (I800 nm)2 and I551 nm, which has the advantages of anti-interference of excitation light source fluctuation and background-free detection. The feasibility of the idea was verified by researching the power-dependent emission spectra at different temperatures and temperature-dependent emission spectra of a CaWO4:Er3+,Yb3+ sample under 980-nm laser excitation. The maximum relative sensitivity for the new ratiometric thermometry reaches up to 7.4% K−1 and the optimal temperature uncertainty calculated is 0.03 K at 303 K. This study provides guidance for solving the problem of a weak response of an infrared detector.
Hollow-waveguide-based light-induced thermoelastic spectroscopy sensing
Authors: Chen Weipeng , Qiao Shunda , Lang Ziting , Jiang Jiachen , He Ying , Shi Yiwei , Ma Yufei
Published: July 2023

In this Letter, a hollow waveguide (HWG)-based light-induced thermoelastic spectroscopy (LITES) gas sensing is proposed. An HWG with a length of 65 cm and inner diameter of 4 mm was used as the light transmission medium and gas chamber. The inner wall of the HWG was coated with a silver (Ag) film to improve reflectivity. Compared with the usually used multi-pass cell (MPC), the HWG has many advantages, such as small size, simple structure and fast filling. Compared with a hollow-core anti-resonant fiber (HC-ARF), the HWG has the merits of easy optical coupling, high system stability, and wide transmission range. A diode laser with output wavelength of 1.53 µm and a quantum cascade laser (QCL) with output wavelength of 4.58 µm were selected as the sources of excitation to target acetylene (C2H2) and carbon monoxide (CO), respectively, to verify the performance of the HWG-based LITES sensor in the near-infrared and mid-infrared regions. The experimental results showed that the HWG-based LITES sensor had a great linear responsiveness to the target gas concentration. The minimum detection limit (MDL) for C2H2 and CO was 6.07 ppm and 98.66 ppb, respectively.
Three-dimensional coherent diffraction snapshot imaging using extreme-ultraviolet radiation from a free electron laser
Authors: Fainozzi Danny , Ippoliti Matteo , Bille Fulvio , De Angelis Dario , Foglia Laura , Masciovecchio Claudio , Mincigrucci Riccardo , Pancaldi Matteo , Pedersoli Emanuele , Günther Christian M. , Pfau Bastian , Schneider Michael , Von Korff Schmising Clemens , Eisebitt Stefan , Kourousias George , Bencivenga Filippo , Capotondi Flavio
Published: July 2023

The possibility of obtaining a three-dimensional (3D) representation of a single object with sub-µm resolution is crucial in many fields, from material science to clinical diagnostics. This is typically achieved through tomography, which combines multiple 2D images of the same object captured with different orientations. However, this serial imaging method prevents single-shot acquisition in imaging experiments, a mandatory feature for the development of time-resolved 3D imaging. In the present experiment, we report on an approach for extracting information on the 3D structure of an object by using extreme-ultraviolet (EUV) radiation. In this method, two EUV pulses hit an isolated 3D object simultaneously from different directions, generating independent coherent diffraction patterns, resulting in two distinct bidimensional projections after phase retrieval. These views are then used, in combination with a ray tracing algorithm, to retrieve information on the 3D structure. This EUV stereoscopic imaging approach, similar to the natural process of binocular vision, provides sub-µm spatial resolution and single-shot capability. Moreover, ultrafast time resolution and spectroscopy can be readily implemented, and a further extension to x-ray wavelengths can be envisioned as well.
Linear and nonlinear photonic spin Hall effect induced by analog circular birefringence of Bessel-like beams
Authors: Li Yanke , Zou Yu , Liu Sheng , Li Peng , Wei Bingyan , Zhao Jianlin
Published: July 2023

The spin Hall effect of a light beam is essentially a product of circular birefringence but is rarely demonstrated. Here, we provide a scheme for initiating off-axis circular birefringence based on the spin-dependent wave vector bifurcation of Bessel beams via a single liquid crystal Pancharatnam–Berry phase element. The tilted Bessel beam shows a detectable photonic spin Hall effect. By introducing the nonlinear propagation trajectories, the spin Hall effect is greatly enhanced. More surprisingly, the two spin states exactly propagate along the scaled trajectories, enabling flexible control of the spin separation. This phenomenon is also applicable to other Bessel-like beams with nonlinear trajectories, which have been already reported.
Image-based flow simulation of platelet aggregates under different shear rates
Authors: Hao Yue , Závodszky Gábor , Tersteeg Claudia , Barzegari Mojtaba , Hoekstra Alfons G.
Published: July 2023

Hemodynamics is crucial for the activation and aggregation of platelets in response to flow-induced shear. In this paper, a novel image-based computational model simulating blood flow through and around platelet aggregates is presented. The microstructure of aggregates was captured by two different modalities of microscopy images of in vitro whole blood perfusion experiments in microfluidic chambers coated with collagen. One set of images captured the geometry of the aggregate outline, while the other employed platelet labelling to infer the internal density. The platelet aggregates were modelled as a porous medium, the permeability of which was calculated with the Kozeny-Carman equation. The computational model was subsequently applied to study hemodynamics inside and around the platelet aggregates. The blood flow velocity, shear stress and kinetic force exerted on the aggregates were investigated and compared under 800 s−1, 1600 s−1 and 4000 s−1 wall shear rates. The advection-diffusion balance of agonist transport inside the platelet aggregates was also evaluated by local Péclet number. The findings show that the transport of agonists is not only affected by the shear rate but also significantly influenced by the microstructure of the aggregates. Moreover, large kinetic forces were found at the transition zone from shell to core of the aggregates, which could contribute to identifying the boundary between the shell and the core. The shear rate and the rate of elongation flow were investigated as well. The results imply that the emerging shapes of aggregates are highly correlated to the shear rate and the rate of elongation. The framework provides a way to incorporate the internal microstructure of the aggregates into the computational model and yields a better understanding of the hemodynamics and physiology of platelet aggregates, hence laying the foundation for predicting aggregation and deformation under different flow conditions.
Sequential mutations in exponentially growing populations
Authors: Nicholson Michael D. , Cheek David , Antal Tibor
Published: July 2023

Stochastic models of sequential mutation acquisition are widely used to quantify cancer and bacterial evolution. Across manifold scenarios, recurrent research questions are: how many cells are there with n alterations, and how long will it take for these cells to appear. For exponentially growing populations, these questions have been tackled only in special cases so far. Here, within a multitype branching process framework, we consider a general mutational path where mutations may be advantageous, neutral or deleterious. In the biologically relevant limiting regimes of large times and small mutation rates, we derive probability distributions for the number, and arrival time, of cells with n mutations. Surprisingly, the two quantities respectively follow Mittag-Leffler and logistic distributions regardless of n or the mutations’ selective effects. Our results provide a rapid method to assess how altering the fundamental division, death, and mutation rates impacts the arrival time, and number, of mutant cells. We highlight consequences for mutation rate inference in fluctuation assays.
The oxidative stress response, in particular the katY gene, is temperature-regulated in Yersinia pseudotuberculosis
Authors: Scheller Daniel , Becker Franziska , Wimbert Andrea , Meggers Dominik , Pienkoß Stephan , Twittenhoff Christian , Knoke Lisa R. , Leichert Lars I. , Narberhaus Franz
Published: July 2023

Pathogenic bacteria, such asYersinia pseudotuberculosisencounter reactive oxygen species (ROS) as one of the first lines of defense in the mammalian host. In return, the bacteria react by mounting an oxidative stress response. Previous global RNA structure probing studies provided evidence for temperature-modulated RNA structures in the 5’-untranslated region (5’-UTR) of various oxidative stress response transcripts, suggesting that opening of these RNA thermometer (RNAT) structures at host-body temperature relieves translational repression. Here, we systematically analyzed the transcriptional and translational regulation of ROS defense genes by RNA-sequencing, qRT-PCR, translational reporter gene fusions, enzymatic RNA structure probing and toeprinting assays. Transcription of four ROS defense genes was upregulated at 37°C. ThetrxAgene is transcribed into two mRNA isoforms, of which the most abundant short one contains a functional RNAT. Biochemical assays validated temperature-responsive RNAT-like structures in the 5’-UTRs ofsodB,sodCandkatA. However, they barely conferred translational repression inY.pseudotuberculosisat 25°C suggesting partially open structures available to the ribosome in the living cell. Around the translation initiation region ofkatYwe discovered a novel, highly efficient RNAT that was primarily responsible for massive induction of KatY at 37°C. By phenotypic characterization of catalase mutants and through fluorometric real-time measurements of the redox-sensitive roGFP2-Orp1 reporter in these strains, we revealed KatA as the primary H2O2scavenger. Consistent with the upregulation ofkatY, we observed an improved protection ofY.pseudotuberculosisat 37°C. Our findings suggest a multilayered regulation of the oxidative stress response inYersiniaand an important role of RNAT-controlledkatYexpression at host body temperature.
Nuclear elongation during spermiogenesis depends on physical linkage of nuclear pore complexes to bundled microtubules by Drosophila Mst27D
Authors: Li Pengfei , Messina Giovanni , Lehner Christian F.
Published: July 2023

Spermatozoa in animal species are usually highly elongated cells with a long motile tail attached to a head that contains the haploid genome in a compact and often elongated nucleus. In Drosophila melanogaster, the nucleus is compacted two hundred-fold in volume during spermiogenesis and re-modeled into a needle that is thirty-fold longer than its diameter. Nuclear elongation is preceded by a striking relocalization of nuclear pore complexes (NPCs). While NPCs are initially located throughout the nuclear envelope (NE) around the spherical nucleus of early round spermatids, they are later confined to one hemisphere. In the cytoplasm adjacent to this NPC-containing NE, the so-called dense complex with a strong bundle of microtubules is assembled. While this conspicuous proximity argued for functional significance of NPC-NE and microtubule bundle, experimental confirmation of their contributions to nuclear elongation has not yet been reported. Our functional characterization of the spermatid specific Mst27D protein now resolves this deficit. We demonstrate that Mst27D establishes physical linkage between NPC-NE and dense complex. The C-terminal region of Mst27D binds to the nuclear pore protein Nup358. The N-terminal CH domain of Mst27D, which is similar to that of EB1 family proteins, binds to microtubules. At high expression levels, Mst27D promotes bundling of microtubules in cultured cells. Microscopic analyses indicated co-localization of Mst27D with Nup358 and with the microtubule bundles of the dense complex. Time-lapse imaging revealed that nuclear elongation is accompanied by a progressive bundling of microtubules into a single elongated bundle. In Mst27D null mutants, this bundling process does not occur and nuclear elongation is abnormal. Thus, we propose that Mst27D permits normal nuclear elongation by promoting the attachment of the NPC-NE to the microtubules of the dense complex, as well as the progressive bundling of these microtubules.
A survey of patient and public perceptions and awareness of SARS-CoV-2-related risks among participants in India and South Africa
Authors: Mbamalu Oluchi , Surendran Surya , Nampoothiri Vrinda , Bonaconsa Candice , Edathadathil Fabia , Zhu Nina , Carter Vanessa , Lambert Helen , Tarrant Carolyn , Ahmad Raheelah , Brink Adrian , Steenkamp Ebrahim , Holmes Alison , Singh Sanjeev , Charani Esmita , Mendelson Marc
Published: July 2023

A cross-sectional survey among participants in India and South Africa to explore perceptions and awareness of SARS-CoV-2-related risks. Main outcome measures–proportion of participants aware of SARS-CoV-2, and their perception of infection risks as it related to their views and perceptions on vaccination, i.e., using COVID-19 vaccine uptake as proxy for awareness level. Self-administered questionnaires were used to collect data via web- and paper-based surveys over three months. Pearson’s Chi-squared test assessed relationships between variables; a p-value less than 0.05 was considered significant. There were 844 respondents (India: n = 660, South Africa: n = 184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of pandemic information were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively; reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness. In South Africa, vaccine acceptance was associated with improved hand hygiene practices since the pandemic and flu vaccination in the preceding year. No relationship was noted between awareness and practice of infection prevention measures (such as hand hygiene) and socio-demographic factors such as employment status or availability of amenities. Pandemic response and infection prevention and control measures through vaccination campaigns should consider robust public engagement and contextually-fit communication strategies with multimodal, participatory online and offline initiatives to address public concerns, specifically towards vaccines developed for this pandemic and general vaccine hesitancy.
A Phase-I pharmacokinetic, safety and food-effect study on flubentylosin, a novel analog of Tylosin-A having potent anti-Wolbachia and antifilarial activity
Authors: Alami Negar , Carter David C. , Kwatra Nisha V. , Zhao Weihan , Snodgrass Linda , Porcalla Ariel R. , Klein Cheri E. , Cohen Daniel E. , Gallenberg Loretta , Neenan Melina , Carr Robert A. , Marsh Kennan C. , Kempf Dale J.
Published: July 2023

Background

The parasitic filariae responsible for onchocerciasis and lymphatic filariasis are host to an endosymbiotic bacterium, Wolbachia, which is essential to the fertility and development of the parasites. We performed a Phase-I pharmacokinetic, safety and food-effect study on single and multiple ascending doses of flubentylosin (ABBV-4083), a macrolide antibacterial with activity against Wolbachia, intended to sterilize and eliminate the parasites.

Methods

Seventy-eight healthy adults were exposed to flubentylosin; 36 were exposed to single ascending 40, 100, 200, 400 or 1000 mg doses; 12 received 1000 mg in the food-effect part; and 30 received multiple ascending daily doses of 100 mg for 7 days, 200 mg for 7 or 14 days, or 400 mg for 7 or 14 days. Twenty-two subjects received placebo.

Results

Maximum concentrations (Cmax) of flubentylosin were reached after 1–2 hours, with a half-life < 4 hours at doses ≤ 400 mg. Cmax and AUC increased in a more than dose-proportional manner, with similar exposure after multiple dose administration. The most frequently reported adverse events were nausea (8/78, 10%) and headache (6/78, 8%).

Two subjects given a single dose of flubentylosin 1000 mg in the food-effect part experienced reversible asymptomatic ALT and AST elevations at Grade 2 or Grade 4, with no elevation in bilirubin, deemed related to study drug. The effect of food on exposure parameters was minimal. No treatment-related serious adverse events were reported.

Discussion

Flubentylosin 400 mg for 14 days was the maximum tolerated dose in this first-in-human, Phase-I study in healthy adults. Based on preclinical pharmacokinetic/pharmacodynamic modeling, flubentylosin 400 mg once daily for 7 or 14 days is expected to be an effective dose. A Phase-II, proof-of-concept study with flubentylosin using these regimens is currently ongoing in patients with onchocerciasis in Africa.
Phase 1b study on the repurposing of meclizine hydrochloride for children with achondroplasia
Authors: Matsushita Masaki , Kitoh Hiroshi , Mishima Kenichi , Kamiya Yasunari , Kato Daisaku , Takemoto Genta , Sawamura Kenta , Ueno Shinji , Yasuhiro Nakai , Nishida Kazuki , Imagama Shiro
Published: July 2023

Achondroplasia (ACH) is a common skeletal dysplasia characterized by a disproportionately short stature. We found that meclizine, which is an over-the-counter drug for motion sickness, inhibited the fibroblast growth factor receptor 3 (FGFR3) gene using a drug repositioning strategy, and meclizine 1 and 2 mg/kg/day promoted bone growth in a mouse model of ACH. A previous phase 1a clinical trial for children with ACH demonstrated that a single dose of meclizine 25 and 50 mg was safe and that the simulated plasma concentration achieved steady state approximately 10 days after the first dose. The current study aimed to evaluate the safety and pharmacokinetics (PK) of meclizine in children with ACH after a 14-day-repeated dose of meclizine. Twelve patients with ACH aged 5–10 years were enrolled. Meclizine 12.5 (cohort 1) and 25 mg/day (cohort 2) were administered after meals for 14 days, and adverse events (AEs) and PK were evaluated. No patient experienced serious AEs in either group. The average (95% confidential interval [CI]) maximum drug concentration (Cmax), peak drug concentration (Tmax), area under the curve (AUC) from 0 to 24 h, and terminal elimination half-life (t1/2) after a 14-day-repeated administration of meclizine (12.5 mg) were 167 (83–250) ng/mL, 3.7 (3.1–4.2) h, 1170 (765–1570) ng·h/mL, and 7.4 (6.7–8.0) h, respectively. The AUC0-6h after the final administration was 1.5 times that after the initial dose. Cmax and AUC were higher in cohort 2 than in cohort 1 in a dose-dependent manner. Regarding the regimen of meclizine 12.5 and 25 mg in patients < 20 kg and ≥ 20 kg, respectively, the average (95% CI) AUC0-24h was 1270 (1100–1440) ng·h/mL. Compartment models demonstrated that the plasma concentration of meclizine achieved at a steady state after the 14th administration. Long-term administration of meclizine 12.5 or 25 mg/day is recommended for phase 2 clinical trials in children with ACH.
Anxiety classification in virtual reality using biosensors: A mini scoping review
Authors: Mevlevioğlu Deniz , Tabirca Sabin , Murphy David
Published: July 2023

Background

Anxiety prediction can be used for enhancing Virtual Reality applications. We aimed to assess the evidence on whether anxiety can be accurately classified in Virtual Reality.

Methods

We conducted a scoping review using Scopus, Web of Science, IEEE Xplore, and ACM Digital Library as data sources. Our search included studies from 2010 to 2022. Our inclusion criteria were peer-reviewed studies which take place in a Virtual Reality environment and assess the user’s anxiety using machine learning classification models and biosensors.

Results

1749 records were identified and out of these, 11 (n = 237) studies were selected. Studies had varying numbers of outputs, from two outputs to eleven. Accuracy of anxiety classification for two-output models ranged from 75% to 96.4%; accuracy for three-output models ranged from 67.5% to 96.3%; accuracy for four-output models ranged from 38.8% to 86.3%. The most commonly used measures were electrodermal activity and heart rate.

Conclusion

Results show that it is possible to create high-accuracy models to determine anxiety in real time. However, it should be noted that there is a lack of standardisation when it comes to defining ground truth for anxiety, making these results difficult to interpret. Additionally, many of these studies included small samples consisting of mostly students, which may bias the results. Future studies should be very careful in defining anxiety and aim for a more inclusive and larger sample. It is also important to research the application of the classification by conducting longitudinal studies.
The role of photobehaviour in sponge larval dispersal and settlement
Authors: Whalan Steve
Published: July 2023

Deciphering the behavioural ecology of adult (sessile) sponges is challenging. However, their motile larval stages afford opportunities to investigate how behaviour contributes to dispersal and selection of habitat. Light is a fundamental cue contributing to larval sponge dispersal where photoreceptive cells contribute to this process. But how universal is light as a cue to sponge larval dispersal and settlement? Behavioural choice experiments were used to test the effect of light on dispersal and settlement behaviours. Larvae of the tropical sponge species Coscinoderma mathewsi, Luffariella variabilis, Ircinia microconnulosa, and Haliclona sp., from deep (12–15 m) and shallower-water habitats (2–5 m), were used in experiments. Dispersal experiments provided a light-gradient-choice where light represented light attenuation with depth. Light treatments included white light and the spectral components of red and blue light. Settlement experiments comprised a choice between illuminated and shaded treatments. Fluorescence microscopy was used to establish the presence of fluorescent proteins associated with posterior locomotory cilia. Deeper-water species, C. mathewsi and I. microconnulosa discriminate light spectral signatures. Both species changed dispersal behaviour to light spectra as larvae aged. For C. mathewsi positive phototaxis to blue light changed to photophobic responses (all light treatments) after six hours and behaviours in I. microconnulosa changed from positive to negative phototaxis (white light) after six hours. L. variabilis, also a deeper-water species, was negatively phototactic to all light treatments. Larvae from the shallow-water species, Haliclona sp., moved towards all light wavelengths tested. There was no effect of light on settlement of the shallow-water Haliclona sp., but larvae in all three deeper-water species showed significantly higher settlement in shaded treatments. Fluorescence microscopy showed discrete fluorescent bands contiguous to posterior tufted cilia in all four species. These fluorescent bands may play a contributory role in larval photobehaviour.
What does the demographic profile of convicts tell us about social equity in India?
Authors: Mukhopadhyay Pranab , Desouza Shaila , Lolayekar Aparna P.
Published: July 2023

Social equity is a critical component of social justice and is measured in multiple ways. Conventionally, researchers use literacy levels, workforce participation, political participation and representation, corporate presence, and demographic parity as indicators of social and economic equity. We add law enforcement outcomes to this literature by examining the demographic profiles of convicts in prisons in India for each state and compare it with that of the population of the respective state. To test whether entrenched social inequities have permeated into the law enforcement system, we use three indicators of social identity–religion, caste, and domicile–to create a social equity index (SEI). This is a composite index combining caste, religion and domicile similar in method to the Human Development Index which combines income, education and health. Our indicators are not considered in other popular development indices and is a conceptual innovation. Our paper innovates by combining prison data and census data at the state level over the two latest census rounds (2001 and 2011). We use a spatial panel analysis as well as a distributional dynamics approach to test for bias and transitions over time at the state level. We find that entrenched social hierarchies are mirrored in conviction outcomes and that social identities influence law enforcement. In contrast to earlier studies, we find that states that are conventionally considered to perform poorly in terms of economic and human development have done better in terms of social equity than economically advanced states.