bluuebunny/crossref_metadata_2025 huggingface dataset:
DEVELOPMENT OF MULTI FREQUENCY ELECTRICAL IMPEDANCE TOMOGRAPHY FOR RECTANGULAR GEOMETRY BY FINITE VOLUME METHODS
Authors: Ain Khusnul , Kurniadi Deddy , Ulum Mokhamad Fakhrul , Choridah Lina , Mukhayyar Utriweni , D. Garnadi Agah , Hendra Setyawan Nurhuda , Ariwanto Bayu
Published: February 2022

Electrical impedance tomography (EIT) is a non-invasive technique for imaging the electrical conductivity and permittivity in the body by measuring the electrical potential on the surface. One of the EIT applications in the medical field is breast cancer detection. The study proposed a rectangular geometry EIT multi-frequency device based on the Finite Volume Method (FVM) reconstruction method. This device can be used to complement mammography images into dual EIT-mammography modalities. The EIT device built of DDS AD9850 as a programmable multi-frequency sinusoidal generator, AD620 as instrument amplifier, AD536 as an AC converter, and ADS1115 as an ADC 16 bit. These devices can scan at the maximum frequency of 100 kHz. The device has been tested with a phantom of distilled water and carrots in the center and on the sides. The reconstruction methods one step different frequency produces a rectangular geometric image with anomalies in the depth and at the surface clearly.
OPTIMISATION OF BIOMASS, LIPID AND CARBOHYDRATE PRODUCTIVITIES IN Chlorella vulgaris FOR BIOFUEL PRODUCTION
Authors: Nordin Norazela , Yusoff Norjan , Md Nadzir Syafiqah , Kamari Azlan , Mohd Yusoff Mohd Zulkhairi
Published: February 2022

Synthesis of lipid and carbohydrate in microalgae simultaneously is essential for cost-effective microalgae-based biofuel production. Statistical optimisation approaches of the Plackett–Burman design (PBD) and central composite design (CCD) were applied to optimise the biomass, lipid, and carbohydrate productivities of the C. vulgaris UPSI-JRM01. The results obtained from PBD shown that NO3- concentration, light intensity and NaHCO3 concentration were the significant factors that affecting biomass productivity. Through CCD, optimum biomass, lipid, and carbohydrate productivities were obtained at 401.81 mg/L NO3–, 11238.20 lux light intensity, and 0.30 g/L NaHCO3, achieving the highest biomass productivity of 404.24 mg/L/day, highest lipid productivity of 65.3 mg/L/day, and highest carbohydrate productivity of 165.43 mg/L/day. The major fatty acid methyl esters (FAMEs) produced were palmitic acid (33.54%) and linoleic acid (30.29%), thus producing microalgae-based biodiesel with properties complying with international biodiesel standards.
ASSESSMENT OF RADIO TELECOMMUNICATION COVERAGE SIGNAL USING GEOSPATIAL ANALYSIS
Authors: Baharim Mohd Sharul Aikal , Sabri Nor Hazmin , Umar Roslan , Othman Ainon Nisa , Abdul Rahman Siti Nur Dianah
Published: February 2022

With the advancement in Information and Communications Technology (ICT), the importance of telecommunication sectors is irrefutable. Rapid growth in this sector requires a good network coverage so the application of the technology is accessible for all purpose from everywhere. In this study, the radio telecommunication coverage signal in Kg. Gong Badak, Universiti Malaysia Terengganu (UMT) and Universiti Sultan Zainal Abidin (UNISZA) have analysed to estimate the frequency (MHz) level using different interpolation techniques (IDW, Natural Neighbor, and Kriging) to select the best method. Then, the relationship between signal strength level (amplitude) and Land Use Land Cover (LULC) data was identified. Several statistical approaches such as Linear Regression Model and Rank Spearman Correlation Coefficient were implemented in this study. From the findings, we found that the Kriging method is the best technique to be applied for network coverage assessment.  We also found that the relationship between signal strength (amplitude) and LULC in Kg. Gong Badak exists either in environmental aspects or physical structures. Kg.Tok Jembal, UMT, Kg. Pak Tuyu and Kg. Jati show a strong positive linear relationship (p-value of < 1%) between signal strength received and a 100-meter interval for 1 kilometer from the base station tower (BST). This indicates that the distance from the BST determines the signal strength. This study can be beneficial for the government and the players in the telecommunication industry to monitor the network coverage in Malaysia to provide a better service.
Modified 3D-printed architectures: Effects of coating by alumina on acrylonitrile butadiene styrene
Authors: Varga Atilla C. , Barry Seán T.
Published: February 2022

3D-printed acrylonitrile butadiene styrene (ABS) polymer structures were coated with alumina (Al2O3) using the trimethylaluminum(III) and water atomic layer deposition (ALD) process at 80 °C, which resulted in a 203 nm thin film with a 1.35 Å growth per cycle. This thin film was a well-adhered protective overcoating on ABS to prevent reaction with acetone vapors in a solvent resistance experiment. Scratch tests were not able to remove the overcoating from the polymer surface, which provided a 50% and 32% increase in acetone vapor resistance before initial deformation and complete structure collapse, respectively. A more aggressive tape test caused delamination of the protective coating. This proof-of-concept experiment demonstrates how 3D printing combined with ALD overcoating can alter the chemical characteristics of complex polymer architectures.
Nanofabricating neural networks: Strategies, advances, and challenges
Authors: Luttge Regina
Published: February 2022

Nanofabrication can help us to emulate natural intelligence. Forward-engineering brain gained enormous momentum but still falls short in human neurodegenerative disease modeling. Here, organ-on-chip (OoC) implementation of tissue culture concepts in microfluidic formats already progressed with the identification of our knowledge gap in toxicology and drug metabolism studies. We believe that the self-organization of stem cells and chip technology is a key to advance such complex in vitro tissue models, including models of the human nervous system as envisaged in this review. However, current cultured networks of neurons show limited resemblance with the biological functions in the real nervous system or brain tissues. To take full advantage of scaling in the engineering domain of electron-, ion-, and photon beam technology and nanofabrication methods, more research is needed to meet the requirements of this specific field of chip technology applications. So far, surface topographies, microfluidics, and sensor and actuator integration concepts have all contributed to the patterning and control of neural network formation processes in vitro. However, when probing the state of the art for this type of miniaturized three-dimensional tissue models in PubMed, it was realized that there is very little systematic cross-disciplinary research with biomaterials originally formed for tissue engineering purposes translated to on-chip solutions for in vitro modeling. Therefore, this review contributes to the formulation of a sound design concept based on the understanding of the existing knowledge and the technical challenges toward finding better treatments and potential cures for devastating neurodegenerative diseases, like Parkinson's disease. Subsequently, an integration strategy based on a modular approach is proposed for nervous system-on-chip (NoC) models that can yield efficient and informative optical and electronic NoC readouts in validating and optimizing these conceptual choices in the innovative process of a fast growing and exciting new OoC industry.
The Effect of Exercise Therapy Interventions on Shoulder Pain and Musculoskeletal Risk Factors for Shoulder Pain in Competitive Swimmers: A Scoping Review
Authors: Yoma Matias , Herrington Lee , Mackenzie Tanya A.
Published: February 2022

Context: Shoulder pain is the main cause of missed or modified training in competitive swimmers. Exercise therapy can improve the outcomes, yet uncertainty exists regarding the characteristics of these interventions. Objectives: The primary aim was to describe the evidence base relating to the effectiveness of exercise therapy interventions on shoulder pain and shoulder musculoskeletal risk factors for shoulder pain in swimmers. The secondary aim was to identify gaps in the literature and provide recommendations for future research and practice. Evidence Acquisition: A scoping review methodology was applied through the search of MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The authors included any research studies (except clinical commentaries and conference papers) that assess the effect of exercise therapy on shoulder pain and musculoskeletal risk factors for shoulder pain in swimmers. The literature was critically appraised using the Modified Down and Black checklist. Evidence Synthesis: From 452 papers identified, 14 studies were included in this review. An exercise program of 6 to 8 weeks, including strengthening exercises (shoulder external rotator and scapula retractor muscles) and stretches (pectoral muscles), can decrease the incidence of shoulder pain in swimmers. Furthermore, a combination of exercises and stretches with manual therapy techniques can help to decrease shoulder pain in injured swimmers. Regarding risk factors, a strengthening program of more than 12 weeks increased shoulder external rotation peak force, endurance, and external rotation/internal rotation ratio; however, this was not associated to decreases in pain. Finally, open kinetic chain exercises and a dry-land program are superior to close kinetic exercises and water training for improving shoulder external rotation strength and endurance. Conclusions: Exercise therapy has positive effects on reducing the incidence of shoulder pain, the management of shoulder pain, and improving shoulder musculoskeletal risk factors in competitive swimmers. However, due to methodological limitations of the studies, caution must be used when applying these results in practice. Future research should focus on high-quality randomized controlled trials for prevention and management of shoulder pain in swimmers.
Heusler-based synthetic antiferrimagnets
Authors: Filippou Panagiotis Ch. , Faleev Sergey V. , Garg Chirag , Jeong Jaewoo , Ferrante Yari , Topuria Teya , Samant Mahesh G. , Parkin Stuart S. P.
Published: February 2022

Antiferromagnet spintronic devices eliminate or mitigate long-range dipolar fields, thereby promising ultrafast operation. For spin transport electronics, one of the most successful strategies is the creation of metallic synthetic antiferromagnets, which, to date, have largely been formed from transition metals and their alloys. Here, we show that synthetic antiferrimagnetic sandwiches can be formed using exchange coupling spacer layers composed of atomically ordered RuAl layers and ultrathin, perpendicularly magnetized, tetragonal ferrimagnetic Heusler layers. Chemically ordered RuAl layers can both be grown on top of a Heusler layer and allow for the growth of ordered Heusler layers deposited on top of it that are as thin as one unit cell. The RuAl spacer layer gives rise to a thickness-dependent oscillatory interlayer coupling with an oscillation period of ~1.1 nm. The observation of ultrathin ordered synthetic antiferrimagnets substantially expands the family of synthetic antiferromagnets and magnetic compounds for spintronic technologies.
Logic operations with active topological defects
Authors: Zhang Rui , Mozaffari Ali , de Pablo Juan J.
Published: February 2022

Logic operations performed by semiconductor-based transistors are the basis of modern computing. There is considerable interest in creating autonomous materials systems endowed with the capability to make decisions. In this work, we introduce the concept of using topological defects in active matter to perform logic operations. When an extensile active stress in a nematic liquid crystal is turned on, +1/2 defects can self-propel, in analogy to electron transport under a voltage gradient. By relying on hydrodynamic simulations of active nematics, we demonstrate that patterns of activity, when combined with surfaces imparting certain orientations, can be used to control the formation and transport of +1/2 defects. We further show that asymmetric high- and low-activity patterns can be used to create effective defect gates, tunnels, and amplifiers. The proposed active systems offer the potential to perform computations and transmit information in active soft materials, including actin-, tubulin-, and cell-based systems.
Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
Authors: Nguyen Long Chi , Yang Dongbo , Nicolaescu Vlad , Best Thomas J. , Gula Haley , Saxena Divyasha , Gabbard Jon D. , Chen Shao-Nong , Ohtsuki Takashi , Friesen John Brent , Drayman Nir , Mohamed Adil , Dann Christopher , Silva Diane , Robinson-Mailman Lydia , Valdespino Andrea , Stock Letícia , Suárez Eva , Jones Krysten A. , Azizi Saara-Anne , Demarco Jennifer K. , Severson William E. , Anderson Charles D. , Millis James Michael , Dickinson Bryan C. , Tay Savaş , Oakes Scott A. , Pauli Guido F. , Palmer Kenneth E. ,   The National COVID Cohort Collaborative Consortium, Meltzer David O. , Randall Glenn , Rosner Marsha Rich
Published: February 2022

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ongoing coronavirus disease 2019 (COVID-19) pandemic underscores the need for new treatments. Here, we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α ribonuclease endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against current use of non-medical formulations as a preventative or treatment therapy.
Activation of PDGFRA signaling contributes to filamin C–related arrhythmogenic cardiomyopathy
Authors: Chen Suet Nee , Lam Chi Keung , Wan Ying-Wooi , Gao Shanshan , Malak Olfat A. , Zhao Shane Rui , Lombardi Raffaella , Ambardekar Amrut V. , Bristow Michael R. , Cleveland Joseph , Gigli Marta , Sinagra Gianfranco , Graw Sharon , Taylor Matthew R.G. , Wu Joseph C. , Mestroni Luisa
Published: February 2022

FLNC
truncating mutations (
FLNCtv
) are prevalent causes of inherited dilated cardiomyopathy (DCM), with a high risk of developing arrhythmogenic cardiomyopathy. We investigated the molecular mechanisms of mutant FLNC in the pathogenesis of arrhythmogenic DCM (a-DCM) using patient-specific induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs). We demonstrated that iPSC-CMs from two patients with different
FLNCtv
mutations displayed arrhythmias and impaired contraction. FLNC ablation induced a similar phenotype, suggesting that
FLNCtv
are loss-of-function mutations. Coimmunoprecipitation and proteomic analysis identified β-catenin (CTNNB1) as a downstream target. FLNC deficiency induced nuclear translocation of CTNNB1 and subsequently activated the platelet-derived growth factor receptor alpha (PDGFRA) pathway, which were also observed in human hearts with a-DCM and
FLNCtv
. Treatment with the PDGFRA inhibitor, crenolanib, improved contractile function of patient iPSC-CMs. Collectively, our findings suggest that PDGFRA signaling is implicated in the pathogenesis, and inhibition of this pathway is a potential therapeutic strategy in FLNC-related cardiomyopathies.
Human expandable pancreatic progenitor–derived β cells ameliorate diabetes
Authors: Ma Xiaojie , Lu Yunkun , Zhou Ziyu , Li Qin , Chen Xi , Wang Weiyun , Jin Yan , Hu Zhensheng , Chen Guo , Deng Qian , Shang Weina , Wang Hao , Fu Hongxing , He Xiangwei , Feng Xin-Hua , Zhu Saiyong
Published: February 2022

An unlimited source of human pancreatic β cells is in high demand. Even with recent advances in pancreatic differentiation from human pluripotent stem cells, major hurdles remain in large-scale and cost-effective production of functional β cells. Here, through chemical screening, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor I-BET151 can robustly promote the expansion of PDX1
+
NKX6.1
+
pancreatic progenitors (PPs). These expandable PPs (ePPs) maintain pancreatic progenitor cell status in the long term and can efficiently differentiate into functional pancreatic β (ePP-β) cells. Notably, transplantation of ePP-β cells rapidly ameliorated diabetes in mice, suggesting strong potential for cell replacement therapy. Mechanistically, I-BET151 activates Notch signaling and promotes the expression of key PP-associated genes, underscoring the importance of epigenetic and transcriptional modulations for lineage-specific progenitor self-renewal. In summary, our studies achieve the long-term goal of robust expansion of PPs and represent a substantial step toward unlimited supplies of functional β cells for biomedical research and regenerative medicine.
PTPN2 elicits cell autonomous and non–cell autonomous effects on antitumor immunity in triple-negative breast cancer
Authors: Goh Pei Kee , Wiede Florian , Zeissig Mara N. , Britt Kara L. , Liang Shuwei , Molloy Tim , Goode Nathan , Xu Rachel , Loi Sherene , Muller Mathias , Humbert Patrick O. , McLean Catriona , Tiganis Tony
Published: February 2022

The tumor-suppressor PTPN2 is diminished in a subset of triple-negative breast cancers (TNBCs). Paradoxically, PTPN2-deficiency in tumors or T cells in mice can facilitate T cell recruitment and/or activation to promote antitumor immunity. Here, we explored the therapeutic potential of targeting PTPN2 in tumor cells and T cells. PTPN2-deficiency in TNBC associated with T cell infiltrates and PD-L1 expression, whereas low
PTPN2
associated with improved survival. PTPN2 deletion in murine mammary epithelial cells TNBC models, did not promote tumorigenicity but increased STAT-1–dependent T cell recruitment and PD-L1 expression to repress tumor growth and enhance the efficacy of anti-PD-1. Furthermore, the combined deletion of PTPN2 in tumors and T cells facilitated T cell recruitment and activation and further repressed tumor growth or ablated tumors already predominated by exhausted T cells. Thus, PTPN2-targeting in tumors and/or T cells facilitates T cell recruitment and/or alleviates inhibitory constraints on T cells to combat TNBC.
A versatile hydrogel network–repairing strategy achieved by the covalent-like hydrogen bond interaction
Authors: Han Zilong , Wang Peng , Lu Yuchen , Jia Zheng , Qu Shaoxing , Yang Wei
Published: February 2022

Hydrogen bond engineering is widely exploited to impart stretchability, toughness, and self-healing capability to hydrogels. However, the enhancement effect of conventional hydrogen bonds is severely limited by their weak interaction strength. In nature, some organisms tolerate extreme conditions due to the strong hydrogen bond interactions induced by trehalose. Here, we report a trehalose network–repairing strategy achieved by the covalent-like hydrogen bonding interactions to improve the hydrogels’ mechanical properties while simultaneously enabling them to tolerate extreme environmental conditions and retain synthetic simplicity, which proves to be useful for various kinds of hydrogels. The mechanical properties of trehalose-modified hydrogels including strength, stretchability, and fracture toughness are substantially enhanced under a wide range of temperatures. After dehydration, the modified hydrogels maintain their hyperelasticity and functions, while the unmodified hydrogels collapse. This strategy provides a versatile methodology for synthesizing extremotolerant, highly stretchable, and tough hydrogels, which expand their potential applications to various conditions.
Coexistence of Ammonium Transporter and Channel Mechanisms in Amt-Mep-Rh Twin-His Variants Impairs the Filamentation Signaling Capacity of Fungal Mep2 Transceptors
Authors: Williamson Gordon , Brito Ana Sofia , Bizior Adriana , Tamburrino Giulia , Dias Mirandela Gaëtan , Harris Thomas , Hoskisson Paul A. , Zachariae Ulrich , Marini Anna Maria , Boeckstaens Mélanie , Javelle Arnaud
Published: February 2022

Fungal infections represent a significant threat to human health and cause huge damage to crop yields worldwide. The dimorphic switch between yeast and filamentous growth is associated with the virulence of pathogenic fungi.
Vaccine-Induced, High-Magnitude HIV Env-Specific Antibodies with Fc-Mediated Effector Functions Are Insufficient to Protect Infant Rhesus Macaques against Oral SHIV Infection
Authors: Curtis Alan D. , Saha Pooja T. , Dennis Maria , Berendam Stella J. , Ramasubramanian Pratamesh , Cross Kaitlyn A. , Alam S. Munir , Ferrari Guido , Kozlowski Pamela A. , Fouda Genevieve G. , Hudgens Michael G. , Van Rompay Koen K. A. , Pollara Justin , Permar Sallie R. , De Paris Kristina
Published: February 2022

Women of childbearing age are three times more likely to contract HIV infection than their male counterparts. Poor HIV testing rates coupled with low adherence to antiretroviral therapy (ART) result in a high risk of mother-to-infant HIV transmission, especially during the breastfeeding period.
Reduced Virulence and Enhanced Host Adaption during Antibiotics Therapy: a Story of a Within-Host Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Evolution in a Patient with a Serious Scrotal Abscess
Authors: Ye Meiping , Liao Chunjie , Shang Mengya , Zou Danyang , Feng Xin , Lu Xinying , Zhang Yixin , Yan Jingmin , Hu Zhixiang , Xu Xiaogang , Jiang Jianping , Zhou Pingyu
Published: February 2022

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) has disseminated worldwide and can cause life-threatening infections, including pneumonia, bloodstream infections, urinary tract infections, intraabdominal infection, liver abscess, and meningitis. CRKP infection is the leading cause of high mortality in hospitals.
Functional and Structural Characterization of Diverse NfsB Chloramphenicol Reductase Enzymes from Human Pathogens
Authors: Mullowney Michael W. , Maltseva Natalia I. , Endres Michael , Kim Youngchang , Joachimiak Andrzej , Crofts Terence S.
Published: February 2022

The question of how new enzyme activities evolve is of great biological interest and, in the context of antibiotic resistance, of great medical importance. Here, we have tested the hypothesis that new antibiotic resistance mechanisms may evolve from promiscuous housekeeping enzymes that have antibiotic modification side activities.
Differential Effects of Toll-Like Receptor Signaling on the Activation of Immune Responses in the Upper Respiratory Tract
Authors: Xu Meiyi , Li Ning , Fan Xin , Zhou Ya , Bi Shuai , Shen Adong , Wang Beinan
Published: February 2022

Agonists of TLRs are potential adjuvant candidates for mucosal vaccination. We demonstrated that the TLR-mediated inflammatory and antibody responses in the URT of SPF mice exposed to extracellular TLR agonists were substantially restricted.
Evaluation of Flow Cytometry for Cell Count and Detection of Bacteria in Biological Fluids
Authors: Dossou N. , Gaubert I. , Moriceau C. , Cornet E. , le Hello S. , Malandain D.
Published: February 2022

The analysis of biological fluids is crucial for the diagnosis and monitoring of diseases causing effusions and helps in the diagnosis of infectious diseases. The possibility of carrying out cytological and microbiological analyses of biological fluid samples on the same automated machine would simplify the sample circuit (addressing the sample in a single laboratory, 24/7).
Genome-Wide CRISPR-Cas9 Screen Does Not Identify Host Factors Modulating Streptococcus agalactiae β-Hemolysin/Cytolysin-Induced Cell Death
Authors: Shahi Ifrah , Llaneras Cristina N. , Perelman Sofya S. , Torres Victor J. , Ratner Adam J.
Published: February 2022

CRISPR-Cas9 forward genetic screens have been used to identify host cell targets required by bacterial toxins. They have been used successfully to both verify known targets and elucidate novel host factors required by toxins.
Investigation and Alteration of Organic Acid Synthesis Pathways in the Mammalian Gut Symbiont Bacteroides thetaiotaomicron
Authors: Porter Nathan T. , Larsbrink Johan
Published: February 2022

Both humans and animals host a large community of bacteria and other microorganisms in their gastrointestinal tracts. This community breaks down dietary fiber and produces organic acids that are used as an energy source by the body and can also help the host resist infection by various pathogens.
Dynamic Changes of the Blood Chemistry in Syrian Hamsters Post-Acute COVID-19
Authors: Hsu Chi-Ju , Lin Wen-Chin , Chou Yu-Ching , Yang Chuen-Mi , Wu Hsueh-Ling , Cheng Yun-Hsiang , Liu Ping-Cheng , Chang Jia-Yu , Chen Hsing-Yu , Sun Jun-Ren
Published: February 2022

COVID-19 is now considered a multiorgan disease with a wide range of manifestations. There are increasing reports of persistent and long-term effects after acute COVID-19, but the long-term health consequences of COVID-19 are not fully understood.
Emergency SARS-CoV-2 Variants of Concern: Novel Multiplex Real-Time RT-PCR Assay for Rapid Detection and Surveillance
Authors: Chung Hsing-Yi , Jian Ming-Jr , Chang Chih-Kai , Lin Jung-Chung , Yeh Kuo-Ming , Chen Chien-Wen , Hsieh Shan-Shan , Hung Kuo-Sheng , Tang Sheng-Hui , Perng Cherng-Lih , Chang Feng-Yee , Wang Chih-Hung , Shang Hung-Sheng
Published: February 2022

COVID-19 has spread globally. SARS-CoV-2 variants of concern (VOCs) are leading the next waves of the COVID-19 pandemic.
Estimating SARS-CoV-2 Seroprevalence in Canadian Blood Donors, April 2020 to March 2021: Improving Accuracy with Multiple Assays
Authors: Tuite Ashleigh R. , Fisman David , Abe Kento T. , Rathod Bhavisha , Pasculescu Adrian , Colwill Karen , Gingras Anne-Claude , Yi Qi-Long , O’Brien Sheila F. , Drews Steven J.
Published: February 2022

Here, we describe an approach to estimating seroprevalence in a low prevalence setting when multiple assays are available and yet no known gold standard exists. Because serological studies identify cases through both diagnostic testing and surveillance, and otherwise silent, unrecognized infections, serological data can be used to estimate the true infection fatality ratio of a disease.
A Genomic and Bioinformatics View of the Classification and Evolution of
Morganella
Species and Their Chromosomal Accessory Genetic Elements Harboring Antimicrobial Resistance Genes
Authors: Jing Ying , Yin Zhe , Wang Peng , Guan Jiayao , Chen Fangzhou , Wang Lingling , Li Xinyue , Mu Xiaofei , Zhou Dongsheng
Published: February 2022

This study presents a comprehensive genomic epidemiology analysis on global sequenced
Morganella
isolates. First, a genome sequence-based species classification scheme for
Morganella
is established with a higher resolution and accuracy than those of the conventional scheme.
Effect of asthma education on health outcomes in children: a systematic review
Authors: Liu Wen-Yi , Jiesisibieke Zhu Liduzi , Tung Tao-Hsin
Published: February 2022

Background

It remains unknown whether child-oriented asthma education is associated with better health outcomes. This meta-analysis investigated the effects of asthma education on hospitalisation and emergency department and clinic visits.

Methods

We searched the Cochrane Library, PubMed and EMBASE for relevant studies from inception to 4 July 2021, and selected studies that reported hospitalisation or emergency department or clinic visits as outcomes. The participants were only children. Two authors independently selected the studies, assessed the quality of the included studies and retrieved the data. A third senior author was engaged to resolve disagreements. Fifteen longitudinal studies were included for the systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 was used as the standard of reporting (PRISMA registration ID is 284509).

Findings

Compared with the control group, the asthma education group had 54% lower hospitalisation risk (95% CI 0.32 to 0.66), and 31% lower emergency department visit risk (95% CI 0.59 to 0.81). Sensitivity analysis showed that the asthma education group had a reduced clinic visit risk (risk ratio (RR)=0.80, 95% CI 0.67 to 0.97). Subgroup analysis showed that asthma education involving both children and parents/guardians was associated with fewer hospitalisations (RR=0.38, 95% CI 0.24 to 0.59) and emergency department visits (RR=0.69, 95% CI 0.57 to 0.83). Asthma education in hospitals or non-hospitals can reduce the risk of hospitalisation and emergency department visits. However, only education in the hospitals was associated with the reduction of clinical visits (RR=0.45, 95% CI 0.22 to 0.92).

Interpretation

Education is effective for controlling asthma, especially for reducing hospitalisation and emergency department and clinic visits. Education involving both children and parents/guardians is more effective than that involving only children. The setting of asthma education does not impact its effect to a large extent.
Current practice in the management of ocular toxoplasmosis
Authors: Yogeswaran Kengadhevi , Furtado João M , Bodaghi Bahram , Matthews Janet M ,   International Ocular Toxoplasmosis Study Group, Smith Justine R
Published: February 2022

Background

Ocular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.

Methods

192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.

Results

For 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.

Conclusion

Our report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.
Poor isometric neck extension strength as a risk factor for concussion in male professional Rugby Union players
Authors: Farley Theo , Barry Ed , Sylvester Richard , Medici Akbar De , Wilson Mathew G
Published: February 2022

Background

Concussion is one of the highest burden injuries within professional Rugby Union (‘rugby’) and comes with a high health and financial cost to players and teams. Limited evidence exists as to the existence of modifiable intrinsic risk factors for concussion, leaving athletes and clinicians with few options when developing prevention strategies.

Objective

To investigate whether neck strength is significantly associated with concussion incidence in professional male rugby players.

Methods

225 rugby players were assessed for neck strength at three time points throughout the 2018/2019 season using a method of isometric contraction. Associations with clinically diagnosed concussion injuries are presented as incidence rate ratios (IRRs) with 95% CIs.

Results

Thirty concussions occurred in 29 players during the study period; a rate of 13.7 concussions per 1000 hours played. Greater neck strength was observed at mid and end of season time points versus preseason across the study population. There was a significant association between extension strength and concussion; a 10% increase for extension strength was associated with a 13% reduction in concussion rate (adjusted IRR (95% CI) 0.87 (0.78 to 0.98). No other significant associations were observed between concussion incidence and any other unique neck strength range or composite score.

Conclusion

Higher neck extension strength is associated with lower concussion rates in male rugby players. Neck strength is a modifiable intrinsic risk factor for concussion and may be an important component of a strength and conditioning regime.
Educational online prevention programme (the SPRINT study) has no effect on the number of running-related injuries in recreational runners: a randomised-controlled trial
Authors: Cloosterman Kyra L A , Fokkema Tryntsje , de Vos Robert-Jan , Visser Edwin , Krastman Patrick , IJzerman John , Koes Bart W , Verhaar Jan A N , Bierma-Zeinstra Sita M A , van Middelkoop Marienke
Published: February 2022

Objectives

The aim of this study was to examine the effectiveness of an enhanced online injury prevention programme on the number of running-related injuries (RRIs) in recreational runners.

Methods

We conducted a randomised-controlled trial in runners who registered for running events (distances: 10–42.195 km) in the Netherlands. Adult runners who provided informed consent were randomised into the intervention or control group. Participants in the intervention group received access to the online prevention programme, which included items to prevent RRIs. Participants in the control group followed their regular preparation for the running event. The primary outcome measure was the number of new RRIs from baseline to 1 month after the running event. To determine differences between injury proportions, univariate and multivariate logistic regression analyses were performed.

Results

This study included 4050 recreational runners (63.5% males; mean (SD) age: 42.3 (12.1) years) for analyses. During follow-up, 35.5% (95% CI: 33.5 to 37.6) of the participants in the intervention group sustained a new RRI compared with 35.4% (95% CI: 33.3 to 37.5) of the participants in the control group, with no between-group difference (OR: 1.03; 95% CI: 0.90 to 1.17). There was a positive association between the number of items followed in the injury prevention programme and the number of RRIs (OR: 1.05; 95% CI: 1.00 to 1.11).

Conclusion

The enhanced online injury prevention programme had no effect on the number of RRIs in recreational runners, and being compliant with the programme paradoxically was associated with a slightly higher injury rate. Future studies should focus on individual targeted prevention with emphasis on the timing and application of preventive measures.

Trial registration number

NL7694.
National application of the European visual field standards for driving: a survey study
Authors: Sudmann Thea Melsen , Jonsdottir Thora Elisabet , Rowe Fiona J , Jørstad Øystein Kalsnes
Published: February 2022

Aims

To provide an overview of how the European visual field standards for driving (specified in Commission Directive 2009/113/EC) are applied and determine whether individuals with visual field defects are treated equally across Europe.

Methods

One ophthalmic expert from each of 32 European countries was invited to participate in an electronic survey. They were presented with threshold and Esterman perimetry results of 15 cases of visual field defects and asked to classify each case as either passed or failed in reference to their national standards. The results were compared with the European Driving Test Group 1 (EDT1), which is a new perimetry algorithm that adheres to the recommendations by the Eyesight Working Group. Fleiss’ kappa was used to determine the inter-rater agreement.

Results

Twenty-five countries responded. Three of 15 cases were passed by all. Full agreement on a failed case was not reached. Denmark graded most leniently and passed 12 cases. Bulgaria, Romania and Slovakia graded most strictly and passed five cases. The Fleiss’ kappa score was 0.52 (95% CI 0.49 to 0.55). Only Slovenia was in full agreement with the EDT1. Fifteen countries endorsed specific perimetric tests for assessing fitness to drive. Five of these also defined pass/fail criteria.

Conclusion

The directive fails to establish a uniform approach to the visual field requirements, as evident by moderate pass/fail agreement between the national experts. Because the visual standards for driving are enforced differently, identical visual field loss can result in either revocation or approval of a driving license.
A game for all shapes and sizes? Changes in anthropometric and performance measures of elite professional rugby union players 1999–2018
Authors: Bevan Trystan , Chew Stephen , Godsland Ian , Oliver Nick S , Hill Neil E
Published: February 2022

Background

Rugby union player size has increased since the game turned professional in 1995. Changes in physical and performance capability over this period have yet to be fully described.

Hypothesis

Increases in player momentum would result from changes in body mass.

Methods

Within-player rates of change in anthropometric and kinetic variables with season played were sampled in three successively studied professional rugby union club cohorts playing at the highest level of European competition between 1999 and 2019. Data comprised 910 seasons of observation for 291 elite male players. Most players had 2, 3 or 4 seasons of observation. Mixed-effects modelling distinguished changes independent of position played, club and international status.

Results

With each season played, player body mass, fat-free mass and maximum speed increased significantly, while per cent fat decreased. The mean maximal velocity of a rugby player in 1999 was 8.2 (±0.18) m/s, which in 2019 had risen to 9.1 (±0.10) m/s. Player’s momentum in 2019 was 14% more than those playing in 1999. In the Front Five, momentum increased in this period by >25%, mainly driven by greater running speed, disproving our hypothesis.

Conclusions

The momentum of players, particularly forwards, increased markedly over 20 seasons of professional rugby. The resulting forces generated in collisions are thus significantly greater, although these may be mitigated by better player conditioning. Proactive regulation to address player safety may be required to address the changing nature of anthropometric measures and physical performance, minimising injury rates and potential long-term sequelae.
Consensus on potential biomarkers developed for use in clinical tests for schizophrenia
Authors: Lin Ping , Sun Junyu , Lou Xiaoyan , Li Dan , Shi Yun , Li Zhenhua , Ma Peijun , Li Ping , Chen Shuzi , Jin Weifeng , Liu Shuai , Chen Qing , Gao Qiong , Zhu Lili , Xu Jie , Zhu Mengyuan , Wang Mengxia , Liang Kangyi , Zhao Ling , Xu Huabin , Dong Ke , Li Qingtian , Cheng Xunjia , Chen Jinghong , Guo Xiaokui
Published: February 2022

Background

Schizophrenia is a serious mental illness affecting approximately 20 million individuals globally. Both genetic and environmental factors contribute to the illness. If left undiagnosed and untreated, schizophrenia results in impaired social function, repeated hospital admissions, reduced quality of life and decreased life expectancy. Clinical diagnosis largely relies on subjective evidence, including self-reported experiences, and reported behavioural abnormalities followed by psychiatric evaluation. In addition, psychoses may occur along with other conditions, and the symptoms are often episodic and transient, posing a significant challenge to the precision of diagnosis. Therefore, objective, specific tests using biomarkers are urgently needed for differential diagnosis of schizophrenia in clinical practice.

Aims

We aimed to provide evidence-based and consensus-based recommendations, with a summary of laboratory measurements that could potentially be used as biomarkers for schizophrenia, and to discuss directions for future research.

Methods

We searched publications within the last 10 years with the following keywords: ‘schizophrenia’, ‘gene’, ‘inflammation’, ‘neurotransmitter’, ‘protein marker’, ‘gut microbiota’, ‘pharmacogenomics’ and ‘biomarker’. A draft of the consensus was discussed and agreed on by all authors at a round table session.

Results

We summarised the characteristics of candidate diagnostic markers for schizophrenia, including genetic, inflammatory, neurotransmitter, peripheral protein, pharmacogenomic and gut microbiota markers. We also proposed a novel laboratory process for diagnosing schizophrenia in clinical practice based on the evidence summarised in this paper.

Conclusions

Further efforts are needed to identify schizophrenia-specific genetic and epigenetic markers for precise diagnosis, differential diagnosis and ethnicity-specific markers for the Chinese population. The development of novel laboratory techniques is making it possible to use these biomarkers clinically to diagnose disease.
Prospective analysis of gender-related characteristics in relation to cardiovascular disease
Authors: Bolijn Renee , Kunst Anton E , Appelman Yolande , Galenkamp Henrike , Moll van Charante Eric P , Stronks Karien , Tan Hanno L , van Valkengoed Irene GM
Published: February 2022

Objective

Differences in cardiovascular disease (CVD) incidence between men and women have been widely reported. Next to sex-related (biological) characteristics, gender-related (sociocultural) characteristics may partly explain how these differences arise. In this exploratory study, we examined the associations between selected gender-related characteristics and CVD incidence.

Methods

We linked baseline data of 18 058 participants without CVD from the population-based, multiethnic HEalthy LIfe in an Urban Setting study (Amsterdam, the Netherlands) to CVD incidence data, based on hospital admission and death records from Statistics Netherlands in 2013–2018. Using Cox regression analyses, we studied associations of time spent on household work, doing home repairs, primary earner status, type of employment, working in a male-dominated or female-dominated occupation and desire for emotional support with CVD incidence, stratified by sex. Analyses were adjusted for age, ethnicity and socioeconomic status.

Results

In men, gender-related characteristics were not associated with higher CVD incidence. In women, homemakers had a higher hazard for CVD compared with full-time workers (HR 2.34, 95% CI 1.35 to 4.04), whereas those spending a moderate amount of time on household work had a lower hazard for CVD than those spending little time (HR 0.56, 95% CI 0.34 to 0.95).

Conclusion

Although we found no evidence for associations between gender-related characteristics and CVD incidence in men, being the homemaker and moderate time spent on household work appeared to be associated with CVD incidence in women. Thus, attention to gender-related characteristics might in future help to identify subgroups that may benefit from additional prevention strategies.
Effectiveness of child burn prevention campaigns in Mongolia
Authors: Gunsmaa Gerelmaa , Inada Haruhiko , Badarch Tumen-Ulzii , Erdenetsetseg Galbadrakh , Ichikawa Masao
Published: February 2022

Objective

To evaluate the effects of child burn prevention campaigns on medically attended burn injuries in Ulaanbaatar, Mongolia.

Methods

We conducted an interrupted time-series analysis using data on patients aged<5 years who were treated for burn injuries at the Emergency Department of the National Trauma and Orthopaedic Center from January 2009 to December 2018. Since the campaigns focused on scald prevention, we calculated the monthly rate of scald injuries per 10 000 children aged<5 years by sex and injury severity, regressing it on the number of months after January 2009 (the beginning of the study), after June 2014 (the first nationwide campaign started) and after January 2017 (the second facility-based campaign started).

Results

During the 10-year study period, there were 23 459 patients, of whom 18 433 (79%) were treated for scald injuries, including 6920 severe injuries. The monthly rate of overall scald injuries started to decrease after the first campaign, with a relative change of −32% at the end of the intervention. However, the rate started increasing before the initiation of the second campaign; this trend continued during and after the campaign. The rate of severe scald injuries did not show any significant changes throughout the study period. The results were consistent for both sexes.

Conclusions

The nationwide burn prevention campaign was effective in reducing non-severe burn injuries among young children. Since the campaign was primarily aimed at increasing public awareness of child burn injury risks, further interventions should be considered with passive measures to prevent severe burn injuries.
Waiting for JAK inhibitor safety data
Authors: Kragstrup Tue Wenzel , Glintborg Bente , Svensson Annemarie L , McMaster Christopher , Robinson Philip C , Deleuran Bent , Liew David FL
Published: February 2022

The US Food and Drug Administration (FDA) has recently added a new ‘black box warning’ on all currently approved Janus kinase (JAK) inhibitors indicated for the treatment of arthritis and other inflammatory conditions based on results from the ORAL Surveillance study of tofacitinib versus tumour necrosis factor alpha inhibitors in rheumatoid arthritis. This is a warning difficult to ignore because the data, being from a randomised controlled trial, are of high fidelity and hard to reproach. It is especially problematic because safety data for all the other JAK inhibitors will be pending for several years. So how might we proceed, without being bound by our stasis? The lack of absolute certainty seems to require a pragmatic approach to the routine care use of JAK inhibitors. The patients who were at greatest risk were older and had other risk factors for the corresponding adverse events, in keeping with effect modification. This highlights the need to focus on risk stratification when tailoring therapy. In this viewpoint, we propose a simple illustration to guide clinical decision-making. First, identify general risk factors for venous thromboembolic event (VTE), major adverse cardiac event (MACE) and cancer (age>65 years and smoking) and whether there is a previous history of VTE, MACE or cancer. Then, evaluate risk based on the number of other risk factors for VTE and the number of other risk factors for MACE. Ultimately, ‘treat-to-target’ will in the end always be ‘treat-to-agreement’. As we have done in the past, and will do in the future, the optimal treatment strategy will have to be tailored based on individual patient risk factors and preferences in a shared-decision process.