A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS

PurposeTo identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation.MethodsWe employed the preferred term (PT) “electrocardiogram QT prolonged” from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004–2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs.ResultsWe listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis.ConclusionsOur study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation

Revealing unusual bandgap shifts with temperature and bandgap renormalization effect in phase-stabilized metal halide perovskites

Hybrid organic-inorganic metal halide perovskites are emerging materials in photovoltaics, whose bandgap is one of the most crucial parameters governing their light harvesting performance. Here we present temperature and photocarrier density dependence of the bandgap in two phase-stabilized perovskite thin films (MA0.3FA0.7PbI3 and MA0.3FA0.7Pb0.5Sn0.5I3) using photoluminescence and absorption spectroscopy. Contrasting bandgap shifts with temperature are observed between the two perovskites. By utilizing X-ray diffraction and in situ high pressure photoluminescence spectroscopy, we show that the thermal expansion plays only a minor role on the large bandgap blueshift due to the enhanced structural stability in our samples. Our first-principles calculations further demonstrate the significant impact of thermally induced lattice distortions on the bandgap widening and reveal that the anomalous trends are caused by the competition between the static and dynamic distortions. Additionally, both the bandgap renormalization and band filling effects are directly observed for the first time in fluence-dependent photoluminescence measurements and are employed to estimate the exciton effective mass. Our results provide new insights into the basic understanding of thermal and charge-accumulation effects on the band structure of hybrid perovskites

Inhibition of RhoA-Subfamily GTPases Suppresses Schwann Cell Proliferation Through Regulating AKT Pathway Rather Than ROCK Pathway

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway

Ascorbic Acid Facilitates Neural Regeneration After Sciatic Nerve Crush Injury

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA’s bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Secure D2D Group Authentication Employing Smartphone Sensor Behavior Analysis

Nowadays, with rapid advancement of both the upcoming 5G architecture construction and emerging Internet of Things (IoT) scenarios, Device-to-Device (D2D) communication provides a novel paradigm for mobile networking. By facilitating continuous and high data rate services between physically proximate devices without interconnection with access points (AP) or service network (SN), spectral efficiency of the 5G network can be drastically increased. However, due to its inherent open wireless communicating features, security issues and privacy risks in D2D communication remain unsolved in spite of its benefits and prosperous future. Hence, proper D2D authentication mechanisms among the D2D entities are of great significance. Moreover, the increasing proliferation of smartphones enables seamlessly biometric sensor data collecting and processing, which highly correspond to the user’s unique behavioral characteristics. For the above consideration, we present a secure certificateless D2D authenticating mechanism intended for extreme scenarios in this paper. In the assumption, the key updating mechanism only requires a small modification in the SN side, while the decryption information of user equipment (UEs) remains constant as soon as the UEs are validated. Note that a symmetric key mechanism is adopted for the further data transmission. Additionally, the user activities data from smartphone sensors are analyzed for continuous authentication, which is periodically conducted after the initial validation. Note that in the assumed scenario, most of the UEs are out of the effective range of cellular networks. In this case, the UEs are capable of conducting data exchange without cellular connection. Security analysis demonstrates that the proposed scheme can provide adequate security properties as well as resistance to various attacks. Furthermore, performance analysis proves that the proposed scheme is efficient compared with state-of-the-art D2D authentication schemes

RSU-Aided Remote V2V Message Dissemination Employing Secure Group Association for UAV-Assisted VANETs

Nowadays, the research on vehicular ad hoc networks (VANETs) remains a hot topic within the Internet of Things (IoT) scenarios. Diverse studies and techniques regarding all aspects of VANETs have been investigated thoroughly. Particularly, the wireless characteristic of heterogeneous vehicular communication, along with the complicated and dynamic connection topology among participating VANET entities, have severely affected the secure and stable data exchange. Specifically, the spontaneous vehicle-to-vehicle (V2V) message dissemination, as the essential functionality of VANET, plays a significant role for instant and real-time data sharing for vehicles within a certain vicinity. However, with the short-time interaction and high mobilization of vehicular connections, the remote V2V message delivery intended for long-distance vehicles in the range of different roadside units (RSUs) has not been properly researched. Meanwhile, both V2V and V2R (Vehicle-to-RSU) communication are highly restricted by environmental factors such as physical obstructions or signal interferences, thus drastically reducing the wireless connectivity in practical VANET implementations. In this case, the unmanned aerial vehicles (UAVs), as the auxiliary facilities, can provide the VANET with substitute wireless routes, so that the transmission quality and availability can be improved. In this paper, the authenticated UAV group association design is proposed at first. On this basis, the remote V2V message dissemination method is enabled, where the decentralized V2V connections involving all RSUs along the way are provided. The analysis regarding crucial security properties is presented accordingly, where the formal proofs and comparison are conducted. Moreover, the performance evaluation in terms of storage and time consumption during RSU authentication process is illustrated, respectively. Comparison results with the state-of-the-art prove that superiority on the major performance factors can be achieved

A Secure and Efficient Group Key Management Protocol with Cooperative Sensor Association in WBANs

The wireless body area network (WBAN) is considered as one of the emerging wireless techniques in the healthcare system. Typical WBAN sensors, especially implantable sensors, have limited power capability, which restricts their wide applications in the medical environment. In addition, it is necessary for the healthcare center (HC) to broadcast significant notifications to different patient groups. Considering the above issues, in this paper, the novel practical WBAN system model with group message broadcasting is built. Subsequently, a secure and efficient group key management protocol with cooperative sensor association is proposed. In the proposed protocol, the Chinese remainder theorem (CRT) is employed for group key management between HC and the personal controller (PC), which also supports batch key updating. The proposed sensor association scheme is motivated by coded cooperative data exchange (CCDE). The formal security proofs are presented, indicating that the proposed protocol can achieve the desired security properties. Moreover, performance analysis demonstrates that the proposed protocol is efficient compared with state-of-the-art group key management protocols

A secure authentication and key agreement scheme with dynamic management for vehicular networks

The development of 5G communication, big data technology and intelligent transportation system has driven the rapid development of vehicle network (VANET). However, with the rapid development of vehicle networks, it will be invaded by various security problems, such as privacy disclosure, session key security, forward security, etc. To eliminate the security threats faced by the vehicle network and ensure privacy and secure communication between vehicles and roadside units(RSU), it is necessary to introduce a secure, reliable, and efficient authentication key agreement scheme. Therefore, based on the principle of challenge authentication handshake protocol, we propose a novel security authentication and key agreement scheme for the vehicle networks. The scheme meets mutual authentication, and is the session key of communication protocol between vehicle and roadside unit to resist common attacks. In addition, compared with other schemes, our scheme has the advantage that we can flexibly set time keys to constrain vehicle behaviour and achieve dynamic vehicle management. We also give a formal security proof of the scheme under the random oracle model (ROM). Finally, the efficiency of the protocol is evaluated, and the computing and communication overhead of our scheme is about 35% lower than that of the existing scheme. So, our scheme is more practical