bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstructive Sleep Apnoea and Cardiac Arrhythmias (OSCA) trial: a nested cohort study using injectable loop recorders and Holter monitoring in patients with obstructive sleep apnoea
Authors: He Hejie , Lachlan Thomas , Chandan Nakul , Lim Ven Gee , Kimani Peter , Ng G Andre , Ali Asad , Randeva Harpal , Osman Faizel
Published: February 2023

Introduction

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular mortality despite continuous positive airways pressure (CPAP) therapy. This excess risk may be related to increased arrhythmia risk, especially atrial fibrillation (AF). The true incidence of arrhythmia in patients with OSA is unknown. Implantable loop recorders (ILR) are powerful tools for detecting arrhythmias long-term. Cardiac autonomic function may be important in arrhythmogenesis in these patients but needs further study. We aim to identify the true incidence of arrhythmias (especially AF) using ILRs, assess cardiac autonomic function using Holter monitors in patients with OSA and explore cardiovascular outcomes.

Methods and analysis

A two-centre (University Hospital Coventry and St. Cross Hospital, Rugby) nested cohort study using Reveal LINQ (Medtronic, UK) ILR to identify precise arrhythmia (atrial/ventricular) incidence in patients with moderate–severe OSA. 200 patients will be randomised 1:1 to standard care alone or standard care+ILR (+Holter monitor at baseline and 12 months). The primary objective is to compare arrhythmia detection over 3 years between the two groups. Cardiac autonomic function will be assessed in the ILR-arm at baseline and 12 months post CPAP. Secondary objectives will explore the mechanisms linking OSA and arrhythmia using cardiac autonomic function parameters based on Holter recordings and circulating biomarkers (high sensitivity Troponin-T, N-terminal pro B-type natriuretic peptide, matrix metalloproteinase-9, fibroblast growth factor 23, high sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor-α) before and after CPAP initiation in the ILR-arm.

Ethics and dissemination

This study has been approved by the Health Research Authority after examination by the Solihull Research and Ethics Committee. The main ethical considerations was the minimally invasive nature of ILR insertion outside of usual care. Patient advisory groups were consulted with a positive outcome for this type of research. We plan on publishing papers in peer-reviewed journals based on the primary objective and any interesting findings from secondary objectives. We will endeavour to publish all relevant data.

Trial registration number

NCT03866148.
VILL: Toward Efficient and Automatic Visual Landmark Labeling
Authors: Niu Qun , Zhu Kunxin , He Suining , Cen Shaoqi , Chan S.-H. Gary , Liu Ning
Published: February 2023

Of all indoor localization techniques, vision-based localization emerges as a promising one, mainly due to the ubiquity of rich visual features. Visual landmarks, which present distinguishing textures, play a fundamental role in visual indoor localization. However, few researches focus on visual landmark labeling. Preliminary arts usually designate a surveyor to select and record visual landmarks, which is tedious and time-consuming. Furthermore, due to structural changes (e.g., renovation), the visual landmark database may be outdated, leading to degraded localization accuracy.

To overcome these limitations, we propose
VILL
, a user-friendly, efficient, and accurate approach for visual landmark labeling. VILL asks a user to sweep the camera to take a video clip of his/her surroundings. In the construction stage, VILL identifies unlabeled visual landmarks from videos adaptively according to the graph-based visual correlation representation. Based on the spatial correlations with selected anchor landmarks, VILL estimates locations of unlabeled ones on the floorplan accurately. In the update stage, VILL formulates an alteration identification model based on the judgments from different users to identify altered landmarks accurately. Extensive experimental results in two different trial sites show that VILL reduces the site survey substantially (by at least 65.9%) and achieves comparable accuracy.
On Protocols for Monotone Feasible Interpolation
Authors: Folwarczný Lukáš
Published: February 2023

Dag-like communication protocols, a generalization of the classical tree-like communication protocols, are useful objects in the realm of proof complexity (most importantly for monotone feasible interpolation) and circuit complexity. We consider three kinds of protocols in this article (
d
is the degree of a protocol):

—

IEQ-
d
-dags: feasible sets of these protocols are described by inequality which means that the feasible sets are combinatorial triangles; these protocols are also called triangle-dags in the literature,

—

EQ-
d
-dags: feasible sets are described by equality, and

—

c
-IEQ-
d
-dags: feasible sets are described by a conjunction of
c
inequalities.

Garg, Göös, Kamath, and Sokolov (Theory of Computing, 2020) mentioned all these protocols, and they noted that EQ-
d
-dags are a special case of
c
-IEQ-
d
-dags. The exact relationship between these types of protocols is unclear.

As our main contribution, we prove the following statement: EQ-2-dags can efficiently simulate
c
-IEQ-
d
-dags when
c
and
d
are constants. This implies that EQ-2-dags are at least as strong as IEQ-
d
-dags and that EQ-2-dags have the same strength as
c
-IEQ-
d
-dags for
c ≥ 2
(because 2-IEQ-2-dags can trivially simulate EQ-2-dags).

Hrubeš and Pudlák (Information Processing Letters, 2018) proved that IEQ-
d
-dags over the monotone Karchmer-Wigderson relation are equivalent to monotone real circuits which implies that we have exponential lower bounds for these protocols. Lower bounds for EQ-2-dags would directly imply lower bounds for the proof system R(LIN).
Domestic Animals as Potential Reservoirs of Zoonotic Viral Diseases
Authors: Tomori Oyewale , Oluwayelu Daniel O.
Published: February 2023

Zoonoses are diseases and infections naturally transmitted between humans and vertebrate animals. Over the years, zoonoses have become increasingly significant threats to global health. They form the dominant group of diseases among the emerging infectious diseases (EID) and currently account for 73% of EID. Approximately 25% of zoonoses originate in domestic animals. The etiological agents of zoonoses include different pathogens, with viruses accounting for approximately 30% of all zoonotic infections. Zoonotic diseases can be transmitted directly or indirectly, by contact, via aerosols, through a vector, or vertically in utero. Zoonotic diseases are found in every continent except Antarctica. Numerous factors associated with the pathogen, human activities, and the environment play significant roles in the transmission and emergence of zoonotic diseases. Effective response and control of zoonotic diseases call for multiple-sector involvement and collaboration according to the One Health concept.
Scientific Validation of Cannabidiol for Management of Dog and Cat Diseases
Authors: Corsato Alvarenga Isabella , Panickar Kiran S. , Hess Hannah , McGrath Stephanie
Published: February 2023

Cannabidiol (CBD) is a non-psychotropic phytocannabinoid of the plant Cannabis sativa L. CBD is increasingly being explored as an alternative to conventional therapies to treat health disorders in dogs and cats. Mechanisms of action of CBD have been investigated mostly in rodents and in vitro and include modulation of CB1, CB2, 5-HT, GPR, and opioid receptors. In companion animals, CBD appears to have good bioavailability and safety profile with few side effects at physiological doses. Some dog studies have found CBD to improve clinical signs associated with osteoarthritis, pruritus, and epilepsy. However, further studies are needed to conclude a therapeutic action of CBD for each of these conditions, as well as for decreasing anxiety and aggression in dogs and cats. Herein, we summarize the available scientific evidence associated with the mechanisms of action of CBD, including pharmacokinetics, safety, regulation, and efficacy in ameliorating various health conditions in dogs and cats.
Psychoneuroimmunology: An Introduction to Immune-to-Brain Communication and Its Implications for Clinical Psychology
Authors: Bower Julienne E. , Kuhlman Kate R.
Published: February 2023

Research conducted over the past several decades has revolutionized our understanding of the role of the immune system in neural and psychological development and function across the life span. Our goal in this review is to introduce this dynamic area of research to a psychological audience and highlight its relevance for clinical psychology. We begin by introducing the basic physiology of immune-to-brain signaling and the neuroimmune network, focusing on inflammation. Drawing from preclinical and clinical research, we then examine effects of immune activation on key psychological domains, including positive and negative valence systems, social processes, cognition, and arousal (fatigue, sleep), as well as links with psychological disorders (depression, posttraumatic stress disorder, anxiety, schizophrenia). We also consider psychosocial stress as a critical modulator of neuroimmune activity and focus on early life adversity. Finally, we highlight psychosocial and mind–body interventions that influence the immune system and may promote neuroimmune resilience.
Application of Potassium Ion Conducting KTiOPO4 as Effective Inner Solid-Contact Layer in All-Solid-State Potassium Ion-Selective Electrode
Authors: Tatara Ryoichi , Ishihara Kenta , Kosugi Motohiro , Aoki Kazuma , Takei Yuko , Matsui Takahiro , Takayama Toshiharu , Komaba Shinichi
Published: February 2023

Solid electrolytes used in all-solid-state batteries electronically separate the positive and negative electrodes in the battery and only allow the carrier ions to pass through. KTiOPO4 (KTP), a potassium ion-conducting solid electrolyte, was first applied as the inner solid contact layer of an all-solid-state potassium ion-selective electrode (ISE) to stabilize the membrane potential. Application of the KTP layer improved the long-term potential stability of the ISE by stabilizing the membrane potential. This can be further improved by adding acetylene black (AB) to the KTP layer which reduced the electrode resistance owing to its high double-layer capacitance.
Implications of the Thermal Stability of FEC-Based Electrolytes for Li-Ion Batteries
Authors: Teufl Tobias , Pritzl Daniel Josef , Hartmann Louis , Solchenbach Sophie , Mendez Manuel , Gasteiger Hubert
Published: February 2023

Fluoroethylene-carbonate (FEC) is a common co-solvent for high-voltage cathodes and for silicon-based anodes in lithium-ion batteries. However, FEC has a limited thermal stability when used with LiPF6 as conductive salt, and its decomposition can trigger detrimental side reactions. Here, we will examine the reaction mechanism of FEC with LiPF6, confirming that vinylene-carbonate (VC) and HF are produced at elevated temperatures. By full-cell cycling at 45°C in a T-cell setup with a micro-reference electrode (µ-RE), we can show by electrochemical impedance spectroscopy that these side reactions not only lead to an impedance increase of the anode and the cathode, but also trigger transition metal dissolution. By comparison of FEC and ethylene-carbonate (EC) as cyclic carbonate, we demonstrate that FEC has no advantage at high-voltage operation compared to EC, when employing cathode materials or cathode potentials for which no lattice oxygen is evolved. Finally, we use multi-layer pouch-cells to analyze the gassing of an EC- and FEC-based electrolyte upon extended charge/discharge cycling at 45°C, showing that the latter leads to cell bulging upon extended charge/discharge cycling at 45°C due to the oxidation of the VC formed by the thermal decomposition of FEC above ~4.4-4.5 V vs. Li+/Li
Thrombospondin-1, CD47, and SIRPα display cell-specific molecular signatures in human islets and pancreata
Authors: Erdem Neslihan , Chen Kuan-Tsen , Qi Meirigeng , Zhao Yuqi , Wu Xiwei , Garcia Isaac , Ku Hsun Teresa , Montero Enrique , Al-Abdullah Ismail H. , Kandeel Fouad , Roep Bart O. , Isenberg Jeffrey S.
Published: February 2023

CD47 is a cell surface receptor with two primary ligands, soluble thrombospondin-1 (TSP1) and cell surface signal regulatory protein alpha (SIRPα). Both interactions provide checkpoints for immune cell activity. We determined that fresh human islets display CD47 and secrete TSP1. However, human islet endocrine cells lack SIRPα. These gene signatures are likely important given the increasing use of CD47 and SIRPα blocking molecules in individuals with cancer.
Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver
Authors: Surugihalli Chaitra , Muralidaran Vaishna , Ryan Caitlin E. , Patel Kruti , Zhao David , Sunny Nishanth E.
Published: February 2023

Branched-chain amino acids (BCAAs) have been shown to modulate lipid metabolic networks in various tissues, especially during insulin resistance. In this study we show that the dietary supplementation of BCAAs to normal, insulin-sensitive mice resulted in higher mitochondrial NADH:NAD+ ratios and AMPK activation in the liver. This change in the cellular redox status provided an optimal metabolic milieu to increase fatty acid oxidation while keeping the rates of de novo lipogenesis lower in the BCAA-supplemented mice livers.
Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids
Authors: Blackwood Sarah J. , Horwath Oscar , Moberg Marcus , Pontén Marjan , Apró William , Ekblom Maria M. , Larsen Filip J. , Katz Abram
Published: February 2023

Whether lipid-mediated insulin resistance occurs as a result of an increased or decreased capacity of skeletal muscle to oxidize lipids has been debated. We show that a 3-day fast results in increases in circulating lipids and insulin resistance in subjects expressing a high or low proportion of type I muscle fibers. High expression of type I is associated with a higher capacity to oxidize lipids and a greater loss of insulin sensitivity after starvation.
Interaction of dynamic error signals in saccade adaptation
Authors: Wagner Ilja , Schütz Alexander C.
Published: February 2023

Motor adaptation is typically studied in static environments, where all information that is required to evaluate movement accuracy is available simultaneously. Here, using saccadic eye movements as a model, we studied motor adaptation in a dynamic environment, where the availability of conflicting information about movement accuracy varied over time. We demonstrate that properties of the visual environment determine how dynamic movement errors are corrected.
Learning to Track Multiple Radar Targets with Long Short-Term Memory Networks
Authors: Song Fei , Li Yong , Cheng Wei , Dong Limeng
Published: February 2023

Radar multitarget tracking in a dense clutter environment remains a complex problem to be solved. Most existing solutions still rely on complex motion models and prior distribution knowledge. In this paper, a new online tracking method based on a long short-term memory (LSTM) network is proposed. It combines state prediction, measurement association, and trajectory management functions in an end-to-end manner. We employ LSTM networks to model target motion and trajectory associations, relying on their strong learning ability to learn target motion properties and long-term dependence of trajectory associations from noisy data. Moreover, to address the problem of missing appearance information of radar targets, we propose an architecture based on the LSTM network to calculate similarity function by extracting long-term motion features. And the similarity is applied to trajectory associations to improve their robustness. Our proposed method is validated in simulation scenarios and achieves good results.
Patient and Clinician Perspectives of Physical Therapy for Walking Difficulties in Multiple Sclerosis
Authors: Plummer Prudence , Stewart Andrea , Anderson Jessica N.
Published: February 2023

Gait speed is frequently the primary efficacy endpoint in clinical trials of interventions targeting mobility in people with multiple sclerosis (MS). However, it is unclear whether increased gait speed is a meaningful outcome for people living with MS. The purpose of this study was to identify the most important aspects of mobility for people with MS and physical therapists and to explore how patients and clinicians perceive whether physical therapy has been effective. Forty-six people with MS and 23 physical therapy clinicians participated in a focus group, one-on-one interview, or electronic survey. The focus group and interview data were transcribed and coded to identify themes. Free-text survey responses were also coded, and multiple-choice options were analyzed for frequency. Among people with MS, falls and difficulties getting out into the community were identified as highly important mobility limitations. Clinicians also identified falls and safety as a priority. Walking speed was infrequently described as a problem, and although gait speed is often measured by clinicians, improving gait speed is rarely a treatment goal. Despite their emphasis on safety, clinicians lacked certainty about how to objectively measure improvements in safety. People with MS evaluated physical therapy effectiveness based on the ease by which they can do things and acknowledged that “not getting worse” is a positive outcome. Clinicians evaluated effectiveness based on the amount of change in objective outcome measures and by patient and caregiver reports of improved function. These findings indicate that gait speed is not of major importance to people with MS or physical therapy clinicians. People with MS want to be able to walk further and without an assistive device, and they want to avoid falls. Clinicians want to maximize safety while improving functional ability. Clinicians and patients may differ in their expected outcomes from physical therapy.
Long Noncoding RNA LINC00578 Inhibits Ferroptosis in Pancreatic Cancer via Regulating SLC7A11 Ubiquitination
Authors: Li Haoran , Wei Yijun , Wang Jie , Yao Jun , Zhang Chen , Yu Chengqing , Tang Yuchen , Zhu Dongming , Yang Jian , Zhou Jian
Published: February 2023

Background. Pancreatic cancer is a highly aggressive malignancy worldwide with rapid development and an exceedingly poor prognosis. lncRNAs play crucial roles in regulating the biological behaviors of tumor cells. In this study, we discovered that LINC00578 acted as a regulator of ferroptosis in pancreatic cancer. Methods. A series of loss- and gain-of-function experiments in vitro and in vivo were performed to explore the oncogenic role of LINC00578 in pancreatic cancer development and progression. Label-free proteomic analysis was performed to select LINC00578-related differentially expressed proteins. Pull-down and RNA immunoprecipitation assays were carried out to determine and validate the binding protein of LINC00578. Coimmunoprecipitation assays were used to investigate the association of LINC00578 with SLC7A11 in ubiquitination and to confirm the interaction between ubiquitin-conjugating enzyme E2 K (UBE2K) and SLC7A11. An immunohistochemical assay was used to confirm the correlation between LINC00578 and SLC7A11 in the clinic. Results. LINC00578 positively regulated cell proliferation and invasion in vitro and tumorigenesis in vivo in pancreatic cancer. LINC00578 can obviously inhibit ferroptosis events, including cell proliferation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) depolarization. In addition, the LINC00578-induced inhibitory effect on ferroptosis events was rescued by SLC7A11 knockdown. Mechanistically, LINC00578 directly binds UBE2K to decrease the ubiquitination of SLC7A11, thus accelerating SLC7A11 expression. In the clinic, LINC00578 is closely associated with clinicopathologic factors and poor prognosis and correlated with SLC7A11 expression in pancreatic cancer. Conclusions. This study elucidated that LINC00578 acts as an oncogene to promote pancreatic cancer cell progression and suppress ferroptosis by directly combining with UBE2K to inhibit the ubiquitination of SLC7A11, which provides a promising option for the diagnosis and treatment of pancreatic cancer.
A Fusion Recognition Method Based on Temporal Evidence Reasoning
Authors: Wang Haibin , Guan Xin , Yi Xiao , Liu Ying , Sun Guidong
Published: February 2023

In order to improve the effectiveness of system decision‐making, the use of the evidence theory to identify target intentions has always been a research hotspot. In information fusion using the evidence theory, there are relatively few research studies on temporal domain evidence information fusion. Due to the obvious dynamic, sequential, and real‐time characteristics of temporal domain information fusion, traditional spatial domain information fusion methods are not suitable. Therefore, it is very necessary to study new methods for the temporal evidence fusion problem. In this article, a temporal evidence fusion method under the framework of the evidence reasoning rule (the ER rule) is proposed. The method uses complementary reliability integration rules and the time‐series evidence distance function to obtain the reliability of evidence at adjacent moments. According to the temporal domain evidence credibility decay model, the evidence weight of the temporal domain evidence is determined. Then, through the integration of the ER rule, the temporal domain evidence reliability and evidence weight are used to combine the evidence. The capability of this method is verified by numerical experiments and compared with other methods. The results show that the proposed method can effectively deal with the temporal domain evidence combination problem, has strong anti‐interference ability, and can support target intent recognition.
Discovery and Validation of Traditional Chinese and Western Medicine Combination Antirheumatoid Arthritis Drugs Based on Machine Learning (Random Forest Model)
Authors: Sun Jijia , Ni Qinghua , Jiang Fengyan , Liu Baocheng , Wang Jianying , Zhang Lei , Huang Jihan
Published: February 2023

The combination of traditional Chinese medicine (TCM) and Western medicine is a promising method for treating rheumatoid arthritis (RA). Combining the two fully exploits the advantages of Western and TCM to treat RA and has the potential to greatly improve the therapeutic effect on RA. In this study, we developed a combination drug training set by using 16 characteristic variables based on the characteristics of small molecules of TCM ingredients and Food and Drug Administration‐certified combination drug data downloaded from the DrugCombDB database. Furthermore, we compared the prediction and classification abilities of five models: the k‐nearest neighbors, naive Bayes, support vector machine, random forest, and AdaBoost algorithms. The random forest model was selected as the classification and prediction model for Western and TCM and Western combination drugs. We collected data for 41 small molecules of TCM ingredients from the Traditional Chinese Medicine Systems Pharmacology database and 10 small molecule drugs commonly used in anti‐RA treatment from the DrugBank database. Combinations of Western and TCM for anti‐RA treatment were screened. Finally, the CellTiter‐Glo method was used to determine the synergy of these combinations, and the 15 most predicted drug combinations were carried out experimental verification. Myricetin, rhein, nobiletin, and fisetin had high synergy with celecoxib, and rhein had high synergy with hydroxychloroquine. The preliminary findings of this study can be further applied for practical clinical anti‐RA combined treatment strategies and serve as a reference for clinical treatment of RA with integrated Western and TCM.
A Study of Lithium Ferrite and Vanadium-Doped Lithium Ferrite Nanoparticles Based on the Structural, Optical, and Magnetic Properties
Authors: Malathi S. , Sridhar B. , Wayessa Shiferaw Garoma
Published: February 2023

Lithium ferrite and vanadium-doped lithium ferrite have been extensively studied in recent research because of their potential applications in thermochromic materials, optoelectronic devices, and as a cathode material for rechargeable lithium batteries. In the present investigation, lithium ferrite and lithium vanadium ferrite are synthesized by sol–gel process. According to the Scherrer formula, the average particle size of lithium ferrite is 22 nm and that of vanadium-doped lithium ferrite is 29 nm. The lattice parameters and dislocation density are calculated from the X-ray diffraction results. According to the Fourier transform infrared spectroscopy analysis, ferrites were formed that exhibit strong absorption bands. According to the energy-dispersive X-ray analysis spectrum, the predicted elements are present in the sample. With the use of a vibrating sample magnetometer (VSM), the materials’ magnetic behavior is investigated.
Pomegranate Peel in the Amelioration of High-Altitude Disease: A Network Pharmacology and Molecular Docking Study of Underlying Mechanisms
Authors: Yeerjiang Alimire , Maimaitiyiming Dilinuer , Yang Tao , Fang Lei , Aihemaitituoheti Adilai , Aimaiti Mutalifu , Zhang Xiangyang , Nijiati Yiliyaer
Published: February 2023

High-altitude disease (HAD) describes the failure to adapt to the lack of oxygen found at high altitudes and therapeutic antioxidant effects have been attributed to pomegranate peel (PP) extract. Network pharmacology, molecular docking, and experimental validation were used to study mechanisms responsible for the alleviation of HAD by PP. The aim was to establish a reference for future research and aid technological development, particularly in clinical settings. Network pharmacology analysis showed that PP affected many targets in HAD via the active ingredients, luteolin 7-O-glycoside, punicalagin, and ellagic acid. HNRNPA1, HSPA1B, HSPA1A, CUL4B, CLTC, PPP1CA, PARP1, RACK1, NEDD8, and MAP3K1 were all targets, responsible for effects on ribosomes, apoptosis, cell cycle, mRNA surveillance pathway, and the MAPK signaling pathway. PP had an antiapoptosis effect on H9c2 cells damaged by hypoxia, as shown by annexinV-FITC/PI double staining. Practical Applications. HAD comprises a group of diseases caused by failure to adapt to a low-oxygen environment. PP extract has previously been shown to have antioxidant effects. PP attenuated damage to H9c2 cells and reduced the apoptosis rate. The current results lay the foundation for further experimental investigations.
Optimization of a Semiflexible Demand-Responsive Feeder System in Suburban Areas Using a Memetic Algorithm
Authors: Sartori Vieira Fabio , Sorensen Kenneth , Vansteenwegen Pieter
Published: February 2023

Traditional bus operations in suburban areas are inefficient due to their fixed routes and timetables. Since suburban operations deal with low demand spread in a large area, the service stays underused for most off-peak hours. In order to render the operation profitable and increase the number of passengers on each bus, operators reduce the frequency of the service, which results in an increase of passenger waiting time for the service. As a solution to this problem, this paper introduces a demand-responsive public bus system that aims to adjust routes and timetables of a semiflexible system to the demand for transportation. The operation still offers a reliable service like the traditional system but aims to reduce the passenger travel time. A memetic algorithm is developed to optimize this demand-responsive system. For a network with 25 bus stops served hourly by three lines and with an average demand of 20 requests per hour, the memetic algorithm is demonstrated to reduce the passenger waiting time with almost 50% in comparison with a traditional system operating in the same network with fixed routes and timetable.
Perceptions of Family Caregivers in the Caring for COVID-19 Patient: Self-Sacrificing Management, Fear, and Loneliness to Protect the Patient—A Qualitative Content Analysis
Authors: Faghani Safieh , Ahmadi Fazlollah , Mohammadi Eesa
Published: February 2023

This study aimed to evaluate the perception of family caregivers in the care process of patients with COVID-19. This study was conducted on 19 family caregivers, who were selected using purposive sampling from 2021 to 2022. Unstructured interviews were used to collect data. The data were analyzed using the Kyngas conventional content analysis approach. The analysis of data led to three main themes, including unremitting efforts in physical care in the light of traditional medicine, accuracy, and intelligence in psychological attention and trying to maintain environmental health. According to the results, family caregivers provide high levels of self-sacrificing, continuous, and comprehensive, combined with fear and loneliness care in different dimensions with little or no support from the family, community, and health team.
CHR vs. Human-Computer Interaction Design for Emerging Technologies: Two Case Studies
Authors: Murad Sharefa , Qusef Abdallah , Muhanna Muhanna
Published: February 2023

Recent years have seen a surge in interest in the multifaceted topic of human-computer interaction (HCI). Since the advent of the Fourth Industrial Revolution, the significance of human-computer interaction in the field of safety risk management has only grown. There has not been a lot of focus on developing human-computer interaction for identifying potential hazards in buildings. After conducting a comprehensive literature review, we developed a study framework for the use of human-computer interaction in the identification of construction-related hazards (CHR-HCI). Future studies will focus on the intersection of computer vision, VR, and ergonomics. In this research, we have built a theoretical foundation for past studies’ findings and connections and offered concrete recommendations for the improvement of HCI in danger identification in the future. Moreover, we analyzed two cases studies related to the domain of CHR-HCI in terms of wearable vibration-based systems and context aware navigation.
Use of Antiepileptic Drugs and Risk of Prostate Cancer: A Nationwide Case-Control Study in Prostate Cancer Data Base Sweden
Authors: George Gincy , Garmo Hans , Adolfsson Jan , Elf Kristin , Gedeborg Rolf , Holmberg Lars , Stattin Pär , Styrke Johan , Van Hemelrijck Mieke
Published: February 2023

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87–0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81–0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.
Highway Traffic Crash Risk Prediction Method considering Temporal Correlation Characteristics
Authors: Zhao Liping , Li Feng , Sun Dongye , Dai Fei
Published: February 2023

Crash risk analysis and prediction are considered the premise of highway traffic safety control, which directly affects the accuracy and effectiveness of traffic safety decisions. A highway traffic crash risk prediction method considering temporal correlation characteristics is proposed in this research. Firstly, the case-control sample analysis method is used to extract 6 time series sample data composed of crash traffic flow data and corresponding non-crash traffic flow data for crash risk analysis and prediction. Secondly, the multiparameter fusion clustering analysis method is used to indicate that the sample data of different time series have different effects on the crash risk. Then, the random forest model is used to screen several traffic flow variables that affect the highway crash risk. Thereafter, the downstream mean speed (ASD1D2), the upstream mean occupancy (AOU1U2), and the speed difference (DSU1D1) on the nearest detector were determined as the explanatory variables of the crash risk prediction model. Finally, based on the three variables, the dynamic Bayesian network model for highway traffic crash risk prediction is proposed. The overall prediction accuracy of this model is 84.9%, the crash prediction accuracy is 60.8%, and the non-crash prediction accuracy is 92.3%. Also, the prediction results show that the dynamic Bayesian model has better prediction effect than the static Bayesian model for the same sample data.
Distinct Mutagenic Activity of APOBEC3G Cytidine Deaminase Identified in Bladder Cancer
Authors: Caswell Deborah , Swanton Charles
Published: February 2023

The APOBEC cytidine deaminase enzyme family is linked to mutational signatures identified in cancer. While previous work has provided insights into the role of APOBEC3A and APOBEC3B in mutational processes in cancer, understanding of the mutational signatures induced by other APOBEC family members is limited. In this issue of Cancer Research, Liu and colleagues investigated the role of APOBEC3G (A3G) in bladder cancer. The authors revealed that transgenic expression of A3G in a murine bladder cancer model promotes tumorigenesis and induces a unique mutational signature distinct from previously identified APOBEC signatures. Expression of this A3G-related mutational signature correlated with significantly worse survival in patients with urothelial bladder carcinoma, and A3G expression was identified in 21 different cancer types. These findings suggest that different APOBEC3 enzymes induce unique mutation signatures and play distinct roles in cancer evolution. More complete understanding of the function of each APOBEC3 enzyme will improve anticancer therapy.

See related article by Liu et al., p. 506
Site-Specific Cancer Incidence by Race and Immigration Status in Canada 2006–2015: A Population-Based Data Linkage Study
Authors: Malagón Talía , Morais Samantha , Tope Parker , El-Zein Mariam , Franco Eduardo L.
Published: February 2023

Background:

The Canadian Cancer Registry (CCR) does not collect demographic data beyond age and sex, making it difficult to monitor health inequalities. Using data linkage, we compared site-specific cancer incidence rates by race.

Methods:

The 2006 and 2011 Canadian Census Health and Environment Cohorts are population-based probabilistically linked datasets of 5.9 million respondents of the 2006 long-form census and 6.5 million respondents of the 2011 National Household Survey. Race was self-reported. Respondent data were linked with the CCR up to 2015. We calculated age-standardized incidence rate ratios (ASIRR), comparing group-specific rates to the overall population rate with bootstrapped 95% confidence intervals (CI). We used negative binomial regressions to adjust for socioeconomic variables and assess interactions with immigration status.

Results:

The age-standardized overall cancer incidence rate was lower in almost all non-White racial groups than in the overall population, except for White and Indigenous peoples who had higher incidence rates than the overall population (ASIRRs, 1.03–1.04). Immigrants had substantially lower age-standardized overall cancer incidence rates than nonimmigrants (ASIRR, 0.83; 95% CI, 0.82–0.84). Stomach, liver, and thyroid cancers and multiple myelomas were the sites where non-White racial groups had consistently higher site-specific cancer incidence rates than the overall population. Immigration status was an important modifier of cancer risk in the interaction model.

Conclusions:

Differences in cancer incidence between racial groups are likely influenced by differences in lifestyles, early life exposures, and selection factors for immigration.

Impact:

Data linkage can help monitor health inequalities and assess progress in preventive interventions against cancer.

See related commentary by Withrow and Gomez, p. 876
Intratumoral CD16+ Macrophages Are Associated with Clinical Outcomes of Patients with Metastatic Melanoma Treated with Combination Anti-PD-1 and Anti-CTLA-4 Therapy
Authors: Lee Hansol , Ferguson Angela L. , Quek Camelia , Vergara Ismael A. , Pires daSilva Ines , Allen Ruth , Gide Tuba Nur , Conway Jordan W. , Koufariotis Lambros T. , Hayward Nicholas K. , Waddell Nicola , Carlino Matteo S. , Menzies Alexander M. , Saw Robyn P.M. , Shklovskaya Elena , Rizos Helen , Lo Serigne , Scolyer Richard A. , Long Georgina V. , Palendira Umaimainthan , Wilmott James S.
Published: February 2023

Purpose:

This study characterizes intratumoral macrophage populations within baseline melanoma biopsies from patients with advanced melanoma who received either anti-PD-1 monotherapy or a combination with anti-CTLA-4. Particularly, FcγRIIIa (CD16)-expressing macrophage densities were investigated for associations with response and progression-free survival.

Experimental Design:

Patients with advanced melanoma who received either anti-PD-1 monotherapy or combination anti-PD-1 and anti-CTLA-4 were retrospectively identified. Macrophage populations were analyzed within baseline melanoma biopsies via multiplex IHC in relation to treatment outcomes.

Results:

Patients who responded to combination immune checkpoint inhibitor contained higher CD16+ macrophage densities than those who did not respond (196 vs. 7 cells/mm2; P = 0.0041). There was no diffidence in CD16+ macrophage densities in the PD-1 monotherapy-treated patients based on response (118 vs. 89 cells/mm2; P = 0.29). A significantly longer 3-year progression-free survival was observed in combination-treated patients with high intratumoral densities of CD16+ macrophages compared with those with low densities (87% vs. 42%, P = 0.0056, n = 40). No association was observed in anti-PD-1 monotherapy-treated patients (50% vs. 47%, P = 0.4636, n = 50). Melanoma biopsies with high densities of CD16+ macrophages contained upregulated gene expression of critical T-cell recruiting chemokines (CXCL9, CXCL10, and CXCL11).

Conclusions:

Our data demonstrate that tumor microenvironments enriched with CD16+ macrophages are favorable for response to combination anti-PD-1 and anti-CTLA-4 therapy but not anti-PD-1 monotherapy. These data provides a potential biomarker of response for combination immunotherapies in patients with metastatic melanoma.

See related commentary by Smithy and Luke, p. 2345
The Diagnostic Value of Multifrequency Tympanometry in Patients with Ménière’s Disease: A Prospective Analysis
Authors: de Jong Marrigje A. , van Esch Babette F. , van Benthem Peter Paul G. , van der Zaag-Loonen Hester J. , Bruintjes Tjasse D. , Thomeer Hans G.X.M.
Published: February 2023

Introduction: Diagnosing Ménière’s disease (MD) by its characteristics such as episodes of vertigo, fluctuating hearing loss, and tinnitus with aural fullness remains challenging. Available tests evaluating the presence of endolymphatic hydrops (EH) are often expensive or time assuming. An in-office quick and simple non-invasive diagnostic test is multifrequency tympanometry (MFT). It can measure conductance at 2 kHz probe tones, which was demonstrated to reflect variations in cochlear pressure. Previous studies investigating MFT as a diagnostic test for MD showed conflicting outcomes possibly biased by their retrospective design. Methods: We prospectively collected MFT results (Y width) in patients with dizziness and compared MFT test results in affected (group 1) and unaffected (group 2) ears of 37 MD subjects and in control ears of 33 non-MD subjects (group 3). Results: The mean value of the Y width in affected ears was 315.6 ± 70.2 daPa compared to 292.3 ± 98.6 daPa in unaffected ears in MD subjects and 259.4. ± 60.6 daPa in the non-MD group. A positive test result (i.e., a Y width of 235 daPa or more) was found in 35 ears in the MD group, 21 times involving the affected ear and 14 times involving the unaffected ear, compared to 16 in the non-MD group. No significant differences between the three groups could be demonstrated (p > 0.05). We found a sensitivity of 58.3% and specificity of 66.3% for detecting EH in an affected ear in MD subjects. Conclusion: There is a trend towards increased conductance tympanometry in affected ears. However, we noticed a high false positive rate of MFT and do not support standardized use of MFT as an additional diagnostic tool for detecting EH in MD patients. A negative test result on the contrary is unlikely related to EH.
Fulminant Skin Abscesses and Hepatic Failure: A Notorious Disease Hidden in Plain Sight
Authors: Mir Fatima Farid , Rafaqat Azka , Butt Fahad Fayyaz , Elmiaari Mira Sedki , AlRomaithi Layla , Alzarawani Fatma , Hashimy Faizah Azim
Published: February 2023

We present a one-month-old male brought in with diffuse large skin abscesses, failure to thrive, and hepatic failure. His status depreciated rapidly, requiring intensive care unit admission as a result of septic shock and multiple incision and drainage surgeries for skin abscesses. Wound site cultures yielded Staphylococcus aureus and urine culture positive for Candida albicans; however, extensive further investigations for causative infectious versus immune-related etiologies remained unfruitful. Despite broad-spectrum antibiotic, antifungal, and antituberculosis coverage, the child’s condition deteriorated further. Within a month of admission, parents were informed of an abnormal neonatal screening report from the hospital where he was born, as presumptively positive for galactosemia. Feeds were immediately shifted to non-lactose formulation, and diagnosis was then confirmed via genetic testing. Jaundice, coagulopathy, inflammatory markers, and weight gain all steadily improved thereafter, and the child was repatriated for continuity of care. Our case demonstrates a unique disease manifestation of a well-known, often forgotten disorder and reemphasizes the importance of rapid institution of lactose-free formula milk.
European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update
Authors: Sweet David G. , Carnielli Virgilio P. , Greisen Gorm , Hallman Mikko , Klebermass-Schrehof Katrin , Ozek Eren , te Pas Arjan , Plavka Richard , Roehr Charles C. , Saugstad Ola D. , Simeoni Umberto , Speer Christian P. , Vento Maximo , Visser Gerry H.A. , Halliday Henry L.
Published: February 2023

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).
Age Gap between Stroke Patients Included in Randomized Clinical Trials of Acute Revascularization Therapy and Those in Population-Based Studies: A Review
Authors: Béjot Yannick
Published: February 2023

Background: The ongoing aging population in high-income countries is responsible for a dramatic rise in the number of elderly stroke patients in whom many questions remain regarding the use of acute revascularization therapy. This review aimed to compare stroke patients from population-based studies to those included in RCTs in terms of age. Summary: Population-based incidence studies conducted in high income that complied with the defined quality criteria were reviewed (period 1985–2020). RCTs of acute ischemic stroke therapy including intravenous thrombolysis (IVT) with either alteplase or tenecteplase and mechanical thrombectomy (MT) were retrieved from systematic reviews performed in recent guidelines from the European Stroke Organisation. When available, information on either mean and/or median age was extracted from each selected article. As a result, 36 population-based registries were included, 34 of which recorded patients with first-ever stroke over 63 distinct time periods with a total of 38,188 patients. Twenty-nine RCTs enrolling 11,666 patients were identified including 13 RCTs related to IVT with alteplase, 11 RCTs about MT, and 5 RCTs on IVT with tenecteplase. A gap in age between stroke patients in the RCTs and those in population-based studies was observed. With few exceptions, mean age of patients in the RCTs was about 4 years younger than in population-based studies, while the median age was approximately 7 years younger. Thirty-five (83%) population-based incidence studies and 8 RCTs (32%) reported a mean age of patients >70 years old. Mean age ≥75 years was observed in 9 (21%) population-based studies and in only 1 (4%) RCT. All population-based studies and half of the RCTs reported a median age >70 years. Key Messages: The gap in age between patients enrolled in acute stroke therapy RCTs and those from population-based studies highlights an under-representation of elderly stroke patients in RCTs. With the current aging of the population, this trend is likely to increase in the coming years, and there is a need to promote the inclusion of older patients, particularly those with disabilities, in future trials to reflect the true population of stroke patients and to help clinicians have evidence-based data to guide their decision-making.