bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjugated polymers based on metalla-aromatic building blocks
Authors: Chen Shiyan , Peng Lixia , Liu Yanan , Gao Xiang , Zhang Ying , Tang Chun , Zhai Zhenghao , Yang Liulin , Wu Weitai , He Xumin , Liu Liu Leo , He Feng , Xia Haiping
Published: July 2022

Conjugated polymers usually require strategies to expand the range of wavelengths absorbed and increase solubility. Developing effective strategies to enhance both properties remains challenging. Herein, we report syntheses of conjugated polymers based on a family of metalla-aromatic building blocks via a polymerization method involving consecutive carbyne shuttling processes. The involvement of metal
d
orbitals in aromatic systems efficiently reduces band gaps and enriches the electron transition pathways of the chromogenic repeat unit. These enable metalla-aromatic conjugated polymers to exhibit broad and strong ultraviolet–visible (UV–Vis) absorption bands. Bulky ligands on the metal suppress π–π stacking of polymer chains and thus increase solubility. These conjugated polymers show robust stability toward light, heat, water, and air. Kinetic studies using NMR experiments and UV–Vis spectroscopy, coupled with the isolation of well-defined model oligomers, revealed the polymerization mechanism.
In situ architecture of the lipid transport protein VPS13C at ER–lysosome membrane contacts
Authors: Cai Shujun , Wu Yumei , Guillén-Samander Andrés , Hancock-Cerutti William , Liu Jun , De Camilli Pietro
Published: July 2022

VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from electron microscopy (EM) studies in situ is still missing, however. Here, we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson’s disease–linked VPS13 paralog localized at contacts between the endoplasmic reticulum (ER) and endo/lysosomes. Such a model predicts an ∼30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER–endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused ion beam (cryo-FIB) milling and cryo–electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods, we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full-length VPS13C or its shorter truncated mutant, thus providing in situ evidence for a bridge model of VPS13 in lipid transport.
Genetic variation that determinesTAPBPexpression levels associates with the course of malaria in an HLA allotype-dependent manner
Authors: Walker-Sperling Victoria , Digitale Jean C. , Viard Mathias , Martin Maureen P. , Bashirova Arman , Yuki Yuko , Ramsuran Veron , Kulkarni Smita , Naranbhai Vivek , Li Hongchuan , Anderson Stephen K. , Yum Lauren , Clifford Robert , Kibuuka Hannah , Ake Julie , Thomas Rasmi , Rowland-Jones Sarah , Rek John , Arinaitwe Emmanuel , Kamya Moses , Rodriguez-Barraquer Isabel , Feeney Margaret E. , Carrington Mary
Published: July 2022

HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulateTAPBPmessenger RNA (mRNA) expression in Africans,rs111686073(G/C) andrs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively.rs111686073Gandrs59097151Ainduced significantly higherTAPBPmRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lowerPlasmodium falciparumparasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputedTAPBPmRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.
La regulación del español en contextos digitales
Authors: Rizzo María Florencia
Published: July 2022

Abstracta

El objetivo de este trabajo es analizar, desde el enfoque glotopolítico, las estrategias de intervención normativa
en contextos digitales, en particular, en la plataforma Twitter, que ha desarrollado la Fundación del Español Urgente (Fundéu).
Este organismo, creado en 2005 por la Agencia EFE con el patrocinio del Banco Bilbao Vizcaya Argentaria (BBVA), tiene como fin
promover, con el asesoramiento de la Real Academia Española, el buen uso del español en los medios de
comunicación y en Internet. Nuestro punto de partida es que la Fundéu ha configurado un dispositivo normativo dinámico en (y para)
entornos virtuales que produce un efecto de descentramiento respecto de la pauta académica. Esto obedece al propósito de situarse
como agente moderado y moderador en materia normativa con el objeto de captar un tipo de público
que, en el actual mundo globalizado, puede no sentirse convocado por el discurso académico.
Dissecting protein tyrosine phosphatase signaling by engineered chemogenetic control of its activity
Authors: Fauser Jordan , Huyot Vincent , Matsche Jacob , Szynal Barbara N. , Alexeev Yuri , Kota Pradeep , Karginov Andrei V.
Published: July 2022

Protein tyrosine phosphatases (PTPases) are critical mediators of dynamic cell signaling. A tool capable of identifying transient signaling events downstream of PTPases is essential to understand phosphatase function on a physiological time scale. We report a broadly applicable protein engineering method for allosteric regulation of PTPases. This method enables dissection of transient events and reconstruction of individual signaling pathways. Implementation of this approach for Shp2 phosphatase revealed parallel MAPK and ROCK II dependent pathways downstream of Shp2, mediating transient cell spreading and migration. Furthermore, we show that the N-SH2 domain of Shp2 regulates MAPK-independent, ROCK II-dependent cell migration. Engineered targeting of Shp2 activity to different protein complexes revealed that Shp2-FAK signaling induces cell spreading whereas Shp2-Gab1 or Shp2-Gab2 mediates cell migration. We identified specific transient morphodynamic processes induced by Shp2 and determined the role of individual signaling pathways downstream of Shp2 in regulating these events. Broad application of this approach is demonstrated by regulating PTP1B and PTP-PEST phosphatases.
Thermal transport in porous graphene with coupling effect of nanopore shape and defect concentration
Authors: Yin Hang , Zhao Ruisheng , Liu Kaidi , Yang Yi , Jiang Jin-Wu , Wan Jing
Published: July 2022

Thermal conductivity of porous graphene can be affected by defect concentration, nanopore shape and distribution, and it is hard to clarify the effects due to the correlation of those factors. In this work, molecular dynamics simulation is used to compare the thermal conductivity of graphene with three shapes of regularly arranged nanopores. The results prove the dominant role of defect concentration under certain circumstances in reducing thermal conductivity, while the coupling effect of nanopore shape should be noticed. When the atoms at the local phonon scattering area around each nanopore are properly removed, the abnormal increment of thermal conductivity can be detected with the increase of defect concentration. Heat flux vector angles can effectively characterize the local phonon scattering area, which can be used to describe the effect of nanopore shape. The coupling effect of defect concentration and pore shape with similar heat flux path is clarified according to this process. By adjusting vertex angle of triangle defect, there is a balanced state of the effect factors between the variation of defect concentration and the same phonon scattering area. It provides a possible way to describe the weighing factors of the coupling effect. The results suggest a feasible approach to optimize and regulate thermal properties of porous graphene in nanodevice.
Rapid microwave hydrothermal processed spinel Co3O4 nanospheres infused N-doped graphene nanosheets for high-performance battery
Authors: Kanimozhi G , Naresh Nibagani , Babu Reshma S , Kumar V V Ravikanth , Satyanarayana N
Published: July 2022

Spinel Co3O4 nanospheres have been synthesized by the microwave-assisted hydrothermal method. The N-doped graphene nanosheets (NGN) were synthesized using Hummer’s method. The prepared spinel Co3O4 and NGN were mixed under certain proportions using an ultrasonication process and treated with microwave radiation to prepare a novel spinel Co3O4 nanospheres infused NGN. The synthesized samples were characterized by x-ray diffraction, Raman spectroscopy, Zetasizer, scanning electron microscope/transmission electron microscopy and x-ray photoelectron spectroscopy for identifying crystal structure and phase, particle size, and the morphology of the nanostructure and the elemental configuration, respectively. The prepared spinel Co3O4/NGN were used as anode material and lithium metal as a reference electrode to fabricate half cell using Swagelok cell components. The electrochemical properties were studied and found to exhibit a larger specific capacity of 575 mAh g−1 compared to traditional graphite electrodes, after 100 cycles under 0.1 C rate with a coulombic efficiency of ≈100%. The good electrochemical properties ascribe to the distinctive surface morphological nanostructures of nanoporous nanospheres of spinel Co3O4 nanospheres and nanosheets of N-doped graphene that reduce the lithium-ion diffusion pathway. The developed anode material would be a potential electrode for lithium ion battery applications.
A giant self-Kerr nonlinearity using phase-sensitive excitation in a closed three-level atomic system
Authors: J Ayyappan , T Beena
Published: July 2022

A third-order nonlinear response is investigated theoretically using a closed lambda system. In this scheme, a pair of optical fields and a microwave field connect three hyperfine levels in a cyclic fashion, rendering the atomic response sensitive to the relative phase of all three fields. Changing the relative phase, we can suppress the linear response of the probe field and enhance its third order self-Kerr nonlinear response using the underlying electromagnetically induced transparency (EIT) effect. The resultant giant self-Kerr nonlinear response is comparable to or exceeding that found in atomic systems at room temperature. Most importantly, we show that the self-Kerr nonlinear response at an optical frequency can be controlled using the phase and amplitude of a frequency-separated microwave field.
Experimental estimation of CO concentration in LN2 cooled CW CO laser operating with CO2 laser gas mixture
Authors: Dwivedi Tatsat , Ghosh Ayan , Sai Prasad M B , Nilaya Jonnalagadda Padma
Published: July 2022

The lasing medium of cryo-cooled CW-CO laser operated with CO2 laser gain medium (CO2–N2–He mixture) resulting in 5 µm emission is formed in-situ in the discharge and its composition, that is sensitively dependent on the discharge temperature, is not known a priori. The composition of the CO lasing gas mixture here was successfully arrived at by way of sampling the gas mixture at the exhaust and measuring the wavelength dependent absorbance by a Fourier Transform Infrared Spectrophotometer. This enabled us to determine the CO and CO2 concentrations in the lasing mixture accurately while the other major constituents were estimated from the initial partial pressures. The composition of the lasing gas mixture was studied for various discharge wall temperatures starting from no cooling condition (∼351 K) to LN2 cooled conditions (79 K). While the concentrations of both, CO2 and CO were found to decrease for temperatures below the freezing point of CO2 at the operating pressure of 11 mbar, the relative concentration of CO with respect to CO2 also increased with reducing temperature accompanied by a steady increase in the CO laser power output. The onset of lasing in 5 µm region was found to occur at a discharge wall temperature of 212 K.
Research status of sensor demodulation technology of fiber grating ultrasonic signal
Authors: Zhang Han , Meng Lijun
Published: July 2022

Compared with ordinary gratings, phase-shifted fiber gratings have better ultrasonic response sensitivity and higher upper response frequency. The application of phase-shifted fiber gratings in ultrasonic signal detection has gradually become a research hotspot. This paper mainly introduces the demodulation principle of tunable laser power scanning and wavelength feedback control techniques such as wavelength stabilization, frequency stabilization and laser tracking. Most of the existing demodulation techniques are only suitable for single optical channel, and the demodulation frequency is low. The development direction of fiber Bragg grating demodulation technology is multi-channel synchronous stable high frequency demodulation.
Scene Semantic Anomaly Detection of Multi-Sensor in Autonomous Driving
Authors: Zhao ZiQi , Yang Bin , Qian ChuiSheng , Zhang YuanGuang
Published: July 2022

Autonomous driving is an outstanding representative of artificial intelligence, and while it has unlimited opportunities, it also faces unprecedented challenges. The potential risks of autonomous vehicles cause a significant threat to our current traffic system. Multi-sensor data in autonomous vehicles will form scene semantics. When sensors are intruded, however, discordant elements of scene semantics will appear. Anomaly detection of scene semantics can improve the robustness of intrusion detection systems for autonomous driving. In this paper, we proposed a method for scene semantic anomaly detection. We obtain the scene semantic representation by performing a semantic-level fusion of sensor data. Then, to achieve a scene semantic anomaly detection, convert abnormal semantic detection to out-of-distribution detection. To test the effectiveness of our method, we performed experiments on a publicly available dataset of autonomous driving.
Research on a rectangular microwave filter with rectangular groove
Authors: Qian Jun , Hou Yifeng
Published: July 2022

In this paper, a rectangular microwave filter with rectangular groove is designed. The filter adopts symmetrical three-stage structure. The first section is the slot line waveguide section to realize the input / output of microwave signal, the second section is the transition section, which adopts the impedance gradient structure, and the third section is the sspps section composed of periodic symmetrical rectangular groove and 90 degree bending structure. By adjusting the geometric size of the rectangular groove and its air gap, the passband width and stopband characteristics of the filter can be adjusted, and its microwave sub wavelength binding effect can be further improved, making the anti space electromagnetic interference ability of sspps filter more excellent. The filter can be applied to L ∼ s Band civil microwave communication system.
Application Research on Sensors and Detection Technology in Mechatronics System
Authors: Lu Yujiao
Published: July 2022

Sensors and detection technology play a very important role in the industrial control industry. Sensors play a pivotal role in various intelligent equipment. Sensors are divided into a variety of sensors. Reasonable sensor components can be used according to the actual situation of the application. However, the application of sensors and detection technology in mechatronics systems is very common, so this research work aims to focus on the analysis of sensors and detection technology, and to study the application of this technology in mechatronics control systems. In the final phase of this research, a future analysis of the application status of sensors and detection technologies is carried out. It aims to provide the necessary theoretical basis for the improvement and innovation of modern sensors and detection technology.
NMPC-based trajectory tracking control strategy for unmanned surface vehicle
Authors: Liu Zhiqiang , Xiang Qing , Ye Xi
Published: July 2022

To solve the unmanned surface vehicle trajectory tracking control problem under model uncertainty and external environmental disturbance, a trajectory tracking control strategy based on nonlinear model predictive control (NMPC) has been proposed. Firstly, a hydrodynamic model considering the uncertainty of model parameters and the influence of external environmental disturbance has been established; then, the fourth-order Lundgren-Kutta method has been used to discretize the nonlinear state space model, and the control quantity, control increment and output quantity of the system have been used as constraints to solve the optimization problem by numerical computation; finally, the reference circle has been used as the preset trajectory, and the trajectory tracking experiment has been carried out under the uncertainty of the model and external environmental disturbance. The experimental results show that the trajectory tracking strategy based on NMPC can better track the preset trajectory and has better anti-interference ability and control effect.
Control and Dynamic Simulation of Wire-Driven Precise Spray Robotic Arm
Authors: Niu Yuxin , Li Yishu , Bao Xiulan , Ma Xiaojie , Xu Kailun , Xu Jiadong , Chen Mingjun
Published: July 2022

The spraying of citrus to kill insects is a necessary part of the citrus planting process. Most of the currently used sprayers are cover sprays, which cannot achieve accurate and low-consumption spraying. Causing a lot of pesticide waste and environmental pollution. Aiming at the difficulty of precise spraying of citrus leaves, this paper proposes a soft spraying manipulator with good bending characteristics and flexible operation ability. The robotic arm consists of 6 joints and 2 arm segments. The two arm segments of the robotic arm are driven by two wire ropes and move in two orthogonal planes respectively. The PD controller design is designed. The joint state observers are constructed to predict joint angles, angular velocities, and other information. The dynamic simulation experiment is carried out, and the relationship between the wire rope tension and the spring elastic force changes with time, and the relationship between each joint angle changes with time. These make the wire-driven precise spray robotic arm potentially useful in agricultural spraying.
The resolution property holds away from codimension three
Authors: Mathur Siddharth , Schröer Stefan
Published: July 2022

The purpose of this paper is to verify a conjecture of Gross under mild hypotheses: all reduced, separated, and excellent schemes have the resolution property away from a closed subset of codimension

≥
3

\geq 3

. Our technique uses formal-local descent and the existence of affine flat neighborhoods to reduce the problem to constructing certain modules over commutative rings. Once in the category of modules we exhibit enough locally free sheaves directly, thereby establishing the resolution property for a specific class of algebraic spaces. A crucial step is showing it suffices to resolve a single coherent sheaf.
A New Ensemble Approach for Congestive Heart Failure and Arrhythmia Classification Using Shifted One-Dimensional Local Binary Patterns with Long Short-Term Memory
Authors: Çalışkan Abidin
Published: July 2022

The electrocardiogram (ECG) is a vital diagnostic tool for identifying a variety of cardiac disorders, including cardiac arrhythmia (ARR), sinus rhythms and heart failure. However, rapid interpretation of ECG recordings is quite important in the diagnosis of heart-related diseases. Many patients can be saved using the systems developed for the rapid and accurate analysis of ECG signals. A novel ensemble method based on shifted one-dimensional local binary patterns (S-1D-LBP) and long short-term memory (LSTM) is presented for the prognosis of ARR, normal sinus rhythm (NSR) and congestive heart failure (CHF) in this study. The ECG signals were first subjected to the S-1D-LBP method. Depending on the R and L parameters of this method, nine different signals are generated. Each of the histograms of these signals is given to LSTM models with the same hyperparameters. ECG signals are classified according to the common decisions of LSTM models with nine different input signals. The suggested method was tested using ECG signals (ARR, NSR and CHF) from the MIT-BIH and BIDMC datasets. Considering the results obtained in the applications carried out with various scenarios, it was observed that a high (99.6%) success rate was attained by the proposed approach. The suggested S-1D-LBP + ELSTM (Ensemble LSTM) model is expected to be safe to employ in the classification of various signals.
Hospital procedural volume and outcomes with catheter-directed intervention for pulmonary embolism: a nationwide analysis
Authors: Sedhom Ramy , Elbadawi Ayman , Megaly Michael , Jaber Wissam A , Cameron Scott J , Weinberg Ido , Mamas Mamas A , Elgendy Islam Y
Published: July 2022

Aims

There is limited data on the association between hospital catheter-directed intervention (CDI) volume and outcomes among patients with acute pulmonary embolism (PE).

Methods and results

The Nationwide Readmissions Database years 2016–2019 was utilized to identify hospitalizations undergoing CDI for acute PE. Hospitals were divided into tertiles based on annual CDI volume; low-volume (1–3 procedures), moderate-volume (4–12 procedures) and high-volume (>12 procedures). The primary outcome was all-cause in-hospital mortality. Among 1 436 382 PE admissions, 2.6% underwent CDI; 5.6% were in low-volume, 17.3% in moderate-volume and 77.1% in high-volume hospitals. There was an inverse relationship between hospital CDI volume and in-hospital mortality (coefficient  −0.344, P < 0.001). On multivariable regression analysis, hospitals with high CDI volume were associated with lower in-hospital mortality compared with hospitals with low CDI volume (adjusted odds ratio [OR] 0.71; 95% confidence interval [CI] 0.53, 0.95). Additionally, there was an inverse association between CDI volume and length of stay (LOS) (regression coefficient −0.023, 95% CI −0.027, −0.019) and cost (regression coefficient −74.6, 95% CI −98.8, −50.3). There were no differences in major bleeding and 30-day unplanned readmission rates between the three groups.

Conclusion

In this contemporary observational analysis of PE admissions undergoing CDI, there was an inverse association between hospital CDI volume and in-hospital mortality, LOS, and cost. Major bleeding and 30-day unplanned readmission rates were similar between the three groups.
On the effects of COVID-19 on food prices in India: a time-varying approach
Authors: Emediegwu Lotanna E , Nnadozie Obianuju O
Published: July 2022

Since the inception of the novel coronavirus, immense research efforts have been made to understand how several economic indicators, including food security, would be affected. With India racing behind the United States in terms of daily infection rate and being a country with challenging food security issues, it is important to investigate how the presence of the pandemic has influenced the dynamics of food prices in the country. This paper considers seven price series from 167 markets across the five regions in India as well as the growth rate of COVID-19 infection. The paper uses a time-varying autoregressive model to investigate the nonlinear dynamics of food prices in relation to the pandemic in India. The resultant models reveal strong asymmetric properties with shock-inflicted persistence, which appear not to converge over the simulation period. Moreover, in terms of the location of the burden of the pandemic impact, we find a food product divide.
We can’t mitigate what we don’t monitor: using informatics to measure and improve healthcare systems’ climate impact and environmental footprint
Authors: Smith Carolynn L , Zurynski Yvonne , Braithwaite Jeffrey
Published: July 2022

Climate change, human health, and healthcare systems are inextricably linked. As the climate warms due to greenhouse gas (GHG) emissions, extreme weather events, such as floods, fires, and heatwaves, will drive up demand for healthcare. Delivering healthcare also contributes to climate change, accounting for ∼5% of the global carbon emissions. To rein in healthcare’s carbon footprint, clinicians and health policy makers must be able to measure the GHG contributions of healthcare systems and clinical practices. Herein, we scope potential informatics solutions to monitor the carbon footprint of healthcare systems and to support climate-change decision-making for clinicians, and healthcare policy makers. We discuss the importance of methods and tools that can link environmental, economic, and healthcare data, and outline challenges to the sustainability of monitoring efforts. A greater understanding of these connections will only be possible through further development and usage of models and tools that integrate diverse data sources.
Chemometric-Based AQbD and Green Chemistry Approaches to Chromatographic Analysis of Remogliflozin Etabonate and Vildagliptin
Authors: Prajapati Pintu , Ahir Hetal , Prajapati Bhumika , Shah Shailesh
Published: July 2022

Background

According to the green chemistry approach, during method development, the usage of toxic and carcinogenic organic solvents should be avoided or minimized for the safety of the environment and analysts. The chromatographic methods such as reverse-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) include the usage of class 2 organic solvents as per the International Council for Harmonization (ICH) Q3C (R6) guideline. The chromatographic analysis by HPTLC requires less organic solvent compared to the RP-HPLC method.

Objective

Hence, HPTLC-based chromatographic analysis of vildagliptin (VIL) and remogliflozin etabonate (RMG) has been carried out using green chemistry and analytical quality by design (AQbD) approaches.

Method

The principal component analysis (PCA)-based chemometric analysis was applied for the identification of critical method variables (CMV) for the development of the method. The design of experiments (DoE)-based Box-Behnken design (BBD) was applied for response surface modeling (RSM) and optimization of CMV. The analytical design space (ADS) and analytical control point were navigated for the development of the HPTLC method as per the quality target analytical profile.

Results

The chromatographic analysis of VIL and RMG was carried out using silica gel G60 F254 as the stationary phase and acetone–ethyl acetate–water–triethylamine (7.0 + 2.5 + 0.3 + 0.2, v/v) as the mobile phase. The HPTLC method was validated as per the ICH Q2 (R1) guideline. The HPTLC method was applied for the assay of fixed-dose combinations (FDCs) of VIL and RMG, and the results were found to comply with their labeled claim.

Conclusions

The developed method included the usage of organic solvents that belong to the class 3 category as per the ICH Q3C (R6) guideline. Hence, the developed method can be used as an eco-friendly alternative to published chromatographic methods for quality control and routine analysis of FDCs of VIL and RMG in the pharmaceutical industry.

Highlights

Chromatographic analysis of VIL and RMG using green chemistry and AQbD approaches. Application of the method for assay of drugs in their combined pharmaceutical dosage forms.
Judicial Discomfort over ‘Innovative’ Treatment for Adolescents with Gender Dysphoria
Authors: Taylor-Sands Michelle M , Dimopoulos Georgina
Published: July 2022

Medical treatment for adolescents with gender dysphoria has attracted considerable attention in recent years, with continuing court involvement in Australia and recent judicial review proceedings in the UK. In Re Imogen [No 6], the Family Court of Australia held that an application to the Family Court is mandatory if a parent or a medical practitioner of an adolescent diagnosed with gender dysphoria disputes the diagnosis, the adolescent’s capacity to consent, or the proposed treatment. In this article, we examine the Family Court’s rationale for preserving its welfare jurisdiction in gender dysphoria cases. We analyse case law developments in Australia and more recently in the UK and identify a thread of judicial discomfort in gender dysphoria jurisprudence about adolescents consenting to medical treatment that the court perceives to be ‘innovative’, ‘experimental’, ‘unique’, or ‘controversial’. We explore whether treatment for gender dysphoria can be characterised as ‘innovative’ and identify four factors that appear to be influencing courts in Australia and the UK. We also consider how such a characterisation might impact (if at all) on an adolescent’s capacity to consent to gender dysphoria treatment. We critique the ongoing role of courts in these cases and recommend a robust decision-making framework for gender dysphoria treatment to minimise court involvement in the future.
Army Health Systems Doctrine and Training in Relation to Antibiotics: A Systematic Review
Authors: Nichols Ryoma , Horstman Jordan , Nitz Iver
Published: July 2022

Introduction

In the early 2000s when Tactical Combat Casualty Care was developed, the adoption of prophylactic antibiotic use was not mainstream. Back then, guidelines were derivative of civilian trauma guidelines which did not include widespread prophylactic antibiotic use. Current protocols across the DoD have embraced the use of prophylactic antibiotic use before reaching a military treatment facility as evidenced by Tactical Combat Casualty Care guidelines and several Joint Trauma System Clinical Practice Guidelines.

This review intends to find trends associated with the use of antibiotics in the military setting and answer the research question: Do current Army doctrine and practices address these issues and how can they be reworked to address them if needed?

Materials and Methods

Methods were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary author utilized four databases to locate articles: MEDLINE (EBSCOhost), Cochrane Central Register of Controlled Trials (Wiley), CINAHL Complete (EBSCOhost), and Embase (Elsevier). The following keywords were utilized: “Combat casualty,” “antibiotic,” “trauma,” and “prehospital.” This ultimately led to 19 articles included in the review.

Results

Nineteen articles were included in the final review and placed into one of the following categories: Overall antibiotic use, guideline adherence and practices, strains, and infection risk factors. Overall, the Army Health System has shown that there is room for improvement in terms of antibiotic stewardship and training regarding antibiotics.

Conclusion

Infectious diseases pose a substantial risk to combat wounded. The Army Health System must anticipate encountering challenges with delivering care to patients suffering infections in addition to serious combat injuries. A systematic review of the literature highlights several areas for improvement, primarily areas involving pathogen surveillance, treatment of pediatric populations, and the Army’s operational domain of training.
Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Results from a 24-week post-marketing surveillance study
Authors: Kameda Hideto , Nishida Keiichiro , Nanki Toshihiro , Watanabe Akira , Oshima Yukiya , Momohara Shigeki
Published: July 2022

Objectives

To report 24-week safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a post-marketing surveillance study.

Methods

Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and European Alliance of Associations for Rheumatology (EULAR) response. Missing data were imputed using the last observation carried forward.

Results

3727 patients were enrolled; safety and effectiveness were evaluated in 3586 and 1794 patients, respectively. 24.9% of patients reported AEs (893/3586), 14.7% reported ADRs (528/3586), 8.3% (298/3586) reported serious AEs and 5.3% (190/3586) reported serious ADRs. Selected serious ADRs of interest: infections (110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%), and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases, or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response.

Conclusions

These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.
Increased mtDNA mutation frequency in oocytes causes epigenetic alterations and embryonic defects
Authors: Han Longsen , Chen Yujia , Li Ling , Ren Chao , Wang Haichao , Wu Xinghan , Ge Juan , Shu Wenjie , Chen Minjian , Wang Qiang
Published: July 2022

Mitochondria are essential for female reproductive processes, yet the function of mitochondrial DNA (mtDNA) mutation in oocytes remains elusive. By employing an mtDNA mutator (Polgm) mouse model, we found the fetal growth retardation and placental dysfunction in post-implantation embryos derived from Polgm oocytes. Remarkably, Polgm oocytes displayed the global loss of DNA methylation; following fertilization, zygotic genome experienced insufficient demethylation, along with dysregulation of gene expression. Spindle–chromosome exchange experiment revealed that cytoplasmic factors in Polgm oocytes are responsible for such a deficient epigenetic remodeling. Moreover, metabolomic profiling identified a significant reduction in the α-ketoglutarate (αKG) level in oocytes from Polgm mice. Importantly, αKG supplement restored both DNA methylation state and transcriptional activity in Polgm embryos, consequently preventing the developmental defects. Our findings uncover the important role of oocyte mtDNA mutation in controlling epigenetic reprogramming and gene expression during embryogenesis. αKG deserves further evaluation as a potential drug for treating mitochondrial dysfunction-related fertility decline.
RNA editing of ion channels and receptors in physiology and neurological disorders
Authors: Zhai Jing , Koh Joanne Huifen , Soong Tuck Wah
Published: July 2022

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modification that diversifies protein functions by recoding RNA or alters protein quantity by regulating mRNA level. A-to-I editing is catalyzed by adenosine deaminases that act on RNA. Millions of editing sites have been reported, but they are mostly found in non-coding sequences. However, there are also several recoding editing sites in transcripts coding for ion channels or transporters that have been shown to play important roles in physiology and changes in editing level are associated with neurological diseases. These editing sites are not only found to be evolutionary conserved across species, but they are also dynamically regulated spatially, developmentally and by environmental factors. In this review, we discuss the current knowledge of A-to-I RNA editing of ion channels and receptors in the context of their roles in physiology and pathological disease. We also discuss the regulation of editing events and site-directed RNA editing approaches for functional study that offer a therapeutic pathway for clinical applications.
KARRIKIN UPREGULATED F-BOX 1 negatively regulates drought tolerance in Arabidopsis
Authors: Tian Hongtao , Watanabe Yasuko , Nguyen Kien Huu , Tran Cuong Duy , Abdelrahman Mostafa , Liang Xiaohan , Xu Kun , Sepulveda Claudia , Mostofa Mohammad Golam , Van Ha Chien , Nelson David C , Mochida Keiichi , Tian Chunjie , Tanaka Maho , Seki Motoaki , Miao Yuchen , Tran Lam-Son Phan , Li Weiqiang
Published: July 2022

The karrikin (KAR) receptor and several related signaling components have been identified by forward genetic screening, but only a few studies have reported on upstream and downstream KAR signaling components and their roles in drought tolerance. Here, we characterized the functions of KAR UPREGULATED F-BOX 1 (KUF1) in drought tolerance using a reverse genetics approach in Arabidopsis (Arabidopsis thaliana). We observed that kuf1 mutant plants were more tolerant to drought stress than wild-type (WT) plants. To clarify the mechanisms by which KUF1 negatively regulates drought tolerance, we performed physiological, transcriptome, and morphological analyses. We found that kuf1 plants limited leaf water loss by reducing stomatal aperture and cuticular permeability. In addition, kuf1 plants showed increased sensitivity of stomatal closure, seed germination, primary root growth, and leaf senescence to abscisic acid (ABA). Genome-wide transcriptome comparisons of kuf1 and WT rosette leaves before and after dehydration showed that the differences in various drought tolerance-related traits were accompanied by differences in the expression of genes associated with stomatal closure (e.g. OPEN STOMATA 1), lipid and fatty acid metabolism (e.g. WAX ESTER SYNTHASE), and ABA responsiveness (e.g. ABA-RESPONSIVE ELEMENT 3). The kuf1 mutant plants had higher root/shoot ratios and root hair densities than WT plants, suggesting that they could absorb more water than WT plants. Together, these results demonstrate that KUF1 negatively regulates drought tolerance by modulating various physiological traits, morphological adjustments, and ABA responses and that the genetic manipulation of KUF1 in crops is a potential means of enhancing their drought tolerance.
Compliance in Non-Clinical Development of Cell-, Gene-, and Tissue-Based Medicines: Good Practice for Better Therapies
Authors: Lopez-Navas Luis , Torrents Sílvia , Sánchez-Pernaute Rosario , Vives Joaquim
Published: July 2022

The development of cell-, gene- and tissue engineering (CGT)-based therapies must adhere to strict pharmaceutical quality management standards, as for any other biological or small-molecule drug. However, early developments often failed to fully comply with good laboratory practices (GLP) in non-clinical safety studies. Despite an upward trend of positive opinions in marketing authorization applications, evidence of adherence to the principles of GLP is not openly reported; therefore, their relative impact on the overall quality of the product development program is unknown. Herein we investigated the actual degree of GLP implementation and the underlying factors impeding full compliance in non-clinical developments of CGT-based marketed medicines in the EU and USA, including (i) the co-existence of diverse quality management systems of more strategic value for small organizations, particularly current Good Manufacturing Practices n(GMP); (ii) lack of regulatory pressure to pursue GLP certification; and (iii) the involvement of public institutions lacking a pharmaceutical mindset and resources. As a final reflection, we propose conformity to good research practice criteria not as a doctrinaire impediment to scientific work, but as a facilitator of efficient clinical translation of more effective and safer innovative therapies.
Probing the interaction of superparamagnetic iron oxide nanoparticles with lipase and their interacting consequences at the molecular level
Authors: Yang Bin , Jia Rui , Fang Mengke , Wang Siyi , Lv Zhe , Wang Jing
Published: July 2022

Background

Although superparamagnetic iron oxide nanoparticles (SPIONs) are used as carriers for candida rugosa lipase (CRL) in biomedical fields, their interactions and the influences on CRL are still unknown. Consequently, SPIONs were synthesized, characterized, and incubated with CRL to explore their molecular interactions and interacting consequences in this study.

Methods

The toxic effects of SPIONs on CRL and their molecular interactions were explored through transmission electron microscope, isothermal titration calorimetry, zeta potential measurements, multi-spectroscopic techniques, and biological enzyme activity tests.

Results

Results revealed the adsorption of SPIONs to CRL and the reduction of CRL aggregation. The unfolding and loosening of CRL structure as well as the change of secondary structure with the decrease of α-helix were found under SPIONs exposure. Moreover, higher SPIONs concentrations contributed to larger conformational changes and less aggregation of CRL. Meanwhile, it showed that hydrophobic forces were the dominant driving forces in the binding process, with the participation of electrostatic forces. CRL binds to SPIONs with the stoichiometry of 20.7 and the binding constant of 9.9 × 106 M−1. No obvious changes were found in CRL activity due to no interference to Ser-209, Glu-341, and His-449 residues.

Conclusion

This study examined the biological compatibility of SPIONs at the molecular level and provided important information about the structure and function of CRL upon binding to SPIONs. Our work might contribute to comprehend the molecular toxicity of SPIONs and the risks of engineered nanoparticles to human health.
Traces of Hymenoscyphus fraxineus in Northeastern Europe Extend Further Back in History than Expected
Authors: Agan Ahto , Tedersoo Leho , Hanso Märt , Drenkhan Rein
Published: July 2022

Herbaria are a promising but still poorly applied information source for retrospective microbiological studies. In order to find any evidence of the virulent European origin of ash dieback agent Hymenoscyphus fraxineus and other fungal pathogens, we analyzed 109 leaf samples from three different Estonian botanical herbaria, sampled during 171 years from 20 ash species and cultivars, using a PacBio third-generation sequencing of the fungal internal transcribed spacer ITS1-5.8S-ITS2 ribosomal DNA region. We identified a large amount of saprotrophic fungi naturally colonizing ash leaves. Hymenoscyphus fraxineus colonized a Fraxinus chinensis subsp. rhynchophylla specimen and a F. chinensis specimen collected from Tallinn Botanic Garden in July 1978 and July 1992, respectively. The samples originated from trees grown in this garden from seeds collected from Shamora, Far-East Russia, in 1961 and from a Beijing botanical garden in eastern China in 1985, respectively. Repeated subsequent DNA extraction, real-time quantitative PCR, and Sanger and Illumina sequencing confirmed our findings of these apparently oldest cases of the ash dieback agent in Europe. These results show that H. fraxineus evidently was present in Estonia 19 years earlier than our previous data from fungal herbaria documented and 14 years before the first visible damage of ash trees was registered in Poland. Because we found no evidence of the saprotrophic H. albidus from earlier mycological and botanical herbarium specimens, the presence of H. albidus in Estonia remains questionable.
Association of Vancomycin Trough Concentration and Clearance With Febrile Neutropenia in Pediatric Patients
Authors: Amano Erino , Tanaka Ryota , Ono Hiroyuki , Tatsuta Ryosuke , Hashimoto Takehiro , Hiramatsu Kazufumi , Itoh Hiroki
Published: July 2022

Background:

Febrile neutropenia promotes renal drug excretion. Adult and pediatric patients with febrile neutropenia exhibit a lower vancomycin concentration/dose (relative to bodyweight) ratio than those with other infections. In pediatric patients, renal function relative to bodyweight varies depending on age, and vancomycin clearance is age dependent. This study aimed to analyze the effects of febrile neutropenia on the pharmacokinetics of vancomycin in age-stratified pediatric patients.

Methods:

This retrospective, single-center, observational cohort study analyzed 112 hospitalized pediatric patients who met the selection criteria and intravenously received vancomycin at the Department of Pediatrics of the Oita University Hospital between April 2011 and October 2019.

Results:

The febrile neutropenia (n = 46) cohort exhibited a significantly higher estimated glomerular filtration rate than the nonfebrile neutropenia (n = 66) cohort. Compared with those in the nonfebrile neutropenia cohort, the daily vancomycin dose relative to bodyweight and vancomycin clearance were significantly higher, and the vancomycin trough concentration and vancomycin concentration/dose ratio were significantly lower in the febrile neutropenia cohort. In the age groups of 1–6 and 7–12 years, compared with those in the nonfebrile neutropenia cohort, the vancomycin concentration/dose ratio was significantly lower, and vancomycin clearance was significantly higher in the febrile neutropenia cohort. Univariate and multivariate analyses identified febrile neutropenia as the independent factor influencing vancomycin concentration/dose ratio and clearance only in pediatric patients aged 1–6 years.

Conclusions:

Increased initial dosage and therapeutic drug monitoring-guided dose optimization are critical for the therapeutic efficacy of vancomycin in pediatric patients with febrile neutropenia, especially in those aged 1–6 years.
Medial Canthus Reconstruction with the Paramedian Forehead Flap
Authors: Gupta Rohun , John Jithin , Hart Justin , Chaiyasate Kongkrit
Published: July 2022

Background:

The medial canthus represents the medial confluence of the upper and lower eyelid margins and plays an integral role in the lacrimal duct system. Various flaps have been utilized for the reconstruction of the lower eyelid in the medial canthal region. Our institution primarily utilizes the paramedian forehead flap for the reconstruction of medial canthus defects. Our study looked to evaluate the work of a single plastic surgeon and identify their postoperative outcomes.

Methods:

A retrospective chart review was conducted at Beaumont Health System, Royal Oak, for patients who underwent medial canthal repair by the lead surgeon between the years 2014 and 2018. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively gathered and analyzed.

Results:

A total of five patients were isolated. Patients underwent paramedian forehead flap medial canthal repair by the lead surgeon and were found to tolerate the procedure well. All patients had clinically viable flaps with aesthetically pleasing results.

Conclusions:

Utilization of the paramedian forehead flap leads to successful medial canthal repair with adequate coverage. Although the paramedian forehead flap requires three stages to complete, the procedure leaves patients with aesthetically pleasing results. In addition, the paramedian forehead flap has limited cases of ectropion. With the right expertise and patient population, the paramedian forehead flap can be highly successful in the repair of medial canthal defects.