A Compact Wearable Textile Antenna for NB-IoT and ISM Band Patient Tracking Applications.

This paper proposes a novel multi-band textile monopole antenna for patient tracking applications. The designed antenna has compact footprints (0.13λ02) and works in the narrow band-internet of things (NB-IoT) 1.8 GHz, radio frequency identification (RFID), and industrial, scientific, and medical (ISM) 2.45 GHz and 5.8 GHz bands. The impedance bandwidths and gain of the antenna at 1.8 GHz, 2.45 GHz, and 5.8 GHz are 310 MHz, 960 MHz, and 1140 MHz; 3.7 dBi, 5.3 dBi, and 9.6 dBi, respectively. Also, the antenna's behavior is checked on different body parts of the human body in various bending scenarios. As per the evaluated link budget, the designed antenna can easily communicate up to 100 m of distance. The specific absorption rate values of the designed antenna are also within acceptable limits as per the (FCC/ICNIRP) standards at the reported frequency bands. Unlike traditional rigid antennas, the proposed textile antenna is non-intrusive, enhancing user safety and comfort. The denim material makes it comfortable for extended wear, reducing the risk of skin irritation. It can also withstand regular wear and tear, including stretching and bending. The presented denim-based antenna can be seamlessly integrated into clothing and accessories, making it less obtrusive and more aesthetically pleasing.

Quad-Band 1 × 4 Linear MIMO Antenna for Millimeter-Wave, Wearable and Biomedical Telemetry Applications.

In this paper, we present the design of a millimeter-wave 1 × 4 linear MIMO array antenna that operates across multiple resonance frequency bands: 26.28-27.36 GHz, 27.94-28.62 GHz, 32.33-33.08 GHz, and 37.59-39.47 GHz, for mm-wave wearable biomedical telemetry application. The antenna is printed on a flexible substrate with dimensions of 11.0 × 44.0 mm2. Each MIMO antenna element features a modified slot-loaded triangular patch, incorporating 'cross'-shaped slots in the ground plane to improve impedance matching. The MIMO antenna demonstrates peak gains of 6.12, 8.06, 5.58, and 8.58 dBi at the four resonance frequencies, along with a total radiation efficiency exceeding 75%. The proposed antenna demonstrates excellent diversity metrics, with an ECC < 0.02, DG > 9.97 dB, and CCL below 0.31 bits/sec/Hz, indicating high performance for mm-wave applications. To verify its properties under flexible conditions, a bending analysis was conducted, showing stable S-parameter results with deformation radii of 40 mm (Rx) and 25 mm (Ry). SAR values for the MIMO antenna are calculated at 28.0/38.0 GHz. The average SAR values for 1 gm/10 gm of tissues at 28.0 GHz are found to be 0.0125/0.0079 W/Kg, whereas, at 38.0 GHz, average SAR values are 0.0189/0.0094 W/Kg, respectively. Additionally, to demonstrate the telemetry range of biomedical applications, a link budget analysis at both 28.0 GHz and 38.0 GHz frequencies indicated strong signal strength of 33.69 dB up to 70 m. The fabricated linear MIMO antenna effectively covers the mm-wave 5G spectrum and is suitable for wearable and biomedical applications due to its flexible characteristics.

Rational Design of Chimeric Antisense Oligonucleotides on a Mixed PO-PS Backbone for Splice-Switching Applications.

Synthetic antisense oligonucleotides (ASOs) are emerging as an attractive platform to treat various diseases. By specifically binding to a target mRNA transcript through Watson-Crick base pairing, ASOs can alter gene expression in a desirable fashion to either rescue loss of function or downregulate pathogenic protein expression. To be clinically relevant, ASOs are generally synthesized using modified analogs to enhance resistance to enzymatic degradation and pharmacokinetic and dynamic properties. Phosphorothioate (PS) belongs to the first generation of modified analogs and has played a vital role in the majority of approved ASO drugs, mainly based on the RNase H mechanism. In contrast to RNase H-dependent ASOs that bind and cleave target mature mRNA, splice-switching oligonucleotides (SSOs) mainly bind and alter precursor mRNA splicing in the cell nucleus. To date, only one approved SSO (Nusinersen) possesses a PS backbone. Typically, the synthesis of PS oligonucleotides generates two types of stereoisomers that could potentially impact the ASO's pharmaco-properties. This can be limited by introducing the naturally occurring phosphodiester (PO) linkage to the ASO sequence. In this study, towards fine-tuning the current strategy in designing SSOs, we reported the design, synthesis, and evaluation of several stereo-random SSOs on a mixed PO-PS backbone for their binding affinity, biological potency, and nuclease stability. Based on the results, we propose that a combination of PO and PS linkages could represent a promising approach toward limiting undesirable stereoisomers while not largely compromising the efficacy of SSOs.

A flexible dual-band 4 × 4 MIMO antenna for 5G mm-wave 28/38 GHz wearable applications.

This paper presents a novel, dual-band, four-port multi-input-multi-output (MIMO) antenna for 28/38 GHz millimeter wave 5G wearable applications. In the proposed work, we have used a novel design approach to get the dual-band behavior from a MIMO design with a small footprint of 18 × 8.5 × 0.25 mm3. For this purpose, each MIMO element is designed as a composite form of a circular and elliptical structure connected with a narrow strip and fed by a tapered feedline. The peak realized gains and total efficiencies of the antenna, evaluated in free space, are 4.15 dBi, 7.73 dBi and 80.13%, 85.44% at 28 GHz and 38 GHz frequencies, respectively. To appraise the thorough behavior of the MIMO antenna, we have evaluated all the parameters of the antenna: Envelope Correlation Coefficient (ECC), Diversity Gain (DG), Mean Effective Gain (MEG), Channel Capacity Loss (CCL), and Total Active Reflection Coefficient (TARC), and found them satisfactory. Channel capacity of the antenna at SNR = 20 dB is found to be 21.61 bps/Hz. For wearable applications, the proposed 4-port MIMO antenna is designed on a flexible Rogers 3003 substrate, and the performance is checked by evaluating bending analysis. The safety of the antenna is verified by analyzing the 1 g/10 g SAR at 28/38 GHz and the corresponding average SAR values are 0.11/0.08 W/kg and 0.05/0.04 W/kg, respectively. All the average SAR values for the proposed MIMO antenna are within the acceptable limits according to FCC/ICNIRP standards.

Inhibition of survivin by 2'-O-methyl phosphorothioate-modified steric-blocking antisense oligonucleotides.

Chemically modified antisense oligonucleotide (ASO) has been established as a successful therapeutic strategy for treating various human diseases. To date, ten ASO drugs, which are capable of either inducing mRNA degradation via RNase H recruitment (fomivirsen, mipomersen, inotersen, volanesorsen and tofersen) or splice modulation (eteplirsen, nusinersen, golodirsen, viltolarsen and casimersen), have been approved by the regulatory agencies for market entry. Nonetheless, none of these approved drugs are prescribed as cancer therapy. Towards this, we have developed steric-blocking ASOs targeting BIRC5 - a well-validated oncogene. Initial screening was performed by transfection of HepG2 cells with seven BIRC5 exon-2 targeting, uniformly 2'-OMe-PS modified ASOs at 400 nM respectively, leading to the identification of two best-performing candidates ASO-2 and ASO-7 in reducing the production of BIRC5 mRNA. Subsequent dose-response assay was conducted via transfection of HepG2 cells by different concentrations (400, 200, 100, 50, 25 nM) of ASO-2 and ASO-7 respectively, showing that both ASOs consistently and efficiently inhibited BIRC5 mRNA expression in a dose-dependent manner. Furthermore, western blot analysis confirmed that ASO-7 could significantly repress survivin production on protein level. Based on our preliminary results, we believe that ASO-7 could be a useful BIRC5 inhibitor for both research purpose and therapeutic development.

Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

Metallic nanostructure-based aptasensors for robust detection of proteins.

There is a significant need for fast, cost-effective, and highly sensitive protein target detection, particularly in the fields of food, environmental monitoring, and healthcare. The integration of high-affinity aptamers with metal-based nanomaterials has played a crucial role in advancing the development of innovative aptasensors tailored for the precise detection of specific proteins. Aptamers offer several advantages over commonly used molecular recognition methods, such as antibodies. Recently, a variety of metal-based aptasensors have been established. These metallic nanomaterials encompass noble metal nanoparticles, metal oxides, metal-carbon nanotubes, carbon quantum dots, graphene-conjugated metallic nanostructures, as well as their nanocomposites, metal-organic frameworks (MOFs), and MXenes. In general, these materials provide enhanced sensitivity through signal amplification and transduction mechanisms. This review primarily focuses on the advancement of aptasensors based on metallic materials for the highly sensitive detection of protein targets, including enzymes and growth factors. Additionally, it sheds light on the challenges encountered in this field and outlines future prospects. We firmly believe that this review will offer a comprehensive overview and fresh insights into metallic nanomaterials-based aptasensors and their capabilities, paving the way for the development of innovative point-of-care (POC) diagnostic devices.

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices.

AIMS: There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact ('remote') or via in-person appointments in primary care and explored impact of age on screening outcomes. METHODS AND RESULTS: People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1-4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. CONCLUSION: Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over.

Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.

The last decade (2013-2023) has seen unprecedented successes in the clinical translation of therapeutic antisense oligonucleotides (ASOs). Eight such molecules have been granted marketing approval by the United States Food and Drug Administration (US FDA) during the decade, after the first ASO drug, fomivirsen, was approved much earlier, in 1998. Splice-modulating ASOs have also been developed for the therapy of inborn errors of metabolism (IEMs), due to their ability to redirect aberrant splicing caused by mutations, thus recovering the expression of normal transcripts, and correcting the deficiency of functional proteins. The feasibility of treating IEM patients with splice-switching ASOs has been supported by FDA permission (2018) of the first "N-of-1" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing to the rarity of individual disease and/or pathogenic mutation, only a low number of patients may be treated by ASOs that specifically suppress the aberrant splicing pattern of mutant precursor mRNA (pre-mRNA), splice-switching ASOs represent superior individualized molecular therapeutics for IEM. In this work, we first summarize the ASO technology with respect to its mechanisms of action, chemical modifications of nucleotides, and rational design of modified oligonucleotides; following that, we precisely provide a review of the current understanding of developing splice-modulating ASO-based therapeutics for IEM. In the concluding section, we suggest potential ways to improve and/or optimize the development of ASOs targeting IEM.

Implementation of a Heparin Infusion Calculator in the Electronic Health Record System as a Risk-Mitigation Strategy in a Community Teaching Hospital Emergency Department.

INTRODUCTION: According to the Institute for Safe Medication Practices, unfractionated heparin is a high-risk medication due to the potential for medication errors and adverse events. Unfractionated heparin is often started in the emergency department for patients with acute coronary syndromes or coagulopathies. Risk-mitigation strategies should be implemented to ensure appropriate initiation and monitoring of this high-risk medication. In 2019, an unfractionated heparin calculator was built into the electronic health record at a community medical center. The purpose of this study was to evaluate the impact of the calculator as a risk-mitigation strategy. METHODS: Patients ≥18 years old admitted between January 1, 2020, and December 31, 2020, were included if they were administered an unfractionated heparin infusion in the emergency department. Patient encounters were excluded if unfractionated heparin order was discontinued before administration. Patient encounters were classified into the unfractionated heparin calculator arm if the unfractionated heparin calculator was used to determine initial dosing, and the remaining patient encounters were classified into the unfractionated heparin no calculator arm. Unfractionated heparin orders were reviewed if a baseline activated partial thromboplastin time was collected and if the correct initial bolus dose and infusion rate were administered. The primary objective is to determine whether the use of unfractionated heparin initiation calculator reduced the rate of medication administration errors. Medication administration errors are defined as baseline activated partial thromboplastin time not collected or incorrectly collected or the administration of incorrect initial bolus dose and infusion rate. RESULTS: A total of 356 patient encounters with unfractionated heparin orders were included in the primary analysis. There were 13.9% errors (39 of 279) present when the calculator was used and 23.3% (18 of 77) when the calculator was not used (P = .046). There was 86% correct administration of heparin (240 of 279) when the calculator was used and 76% correct administrations (59 of 77) when the calculator was not used. DISCUSSION: The use of the unfractionated heparin infusion calculator in the emergency department led to decrease in medication administration errors. This is the first study to evaluate the integration of an unfractionated heparin calculator into the electronic health record.