Exploring novel immunotherapy biomarker candidates induced by cancer deformation

by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.

Xinnaotongluo liquid protects H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3

by Jiankun Cui, Qinwen Wang, Minghao Li

Xinnaotongluo liquid has been used to improve the clinical symptoms of patients with myocardial infarction. However, the molecular mechanism of Xinnaotongluo liquid is not completely understood. H9c2 cells exposed to hypoxia/reoxygenation (H/R) was used to simulate damage to cardiomyocytes in myocardial infarction in vitro. The biological indicators of H9c2 cells were measured by cell counting kit-8, enzyme linked immunoabsorbent assay, and western blot assay. In H/R-induced H9c2 cells, a markedly reduced murine double minute 2 (MDM2) was observed. However, the addition of Xinnaotongluo liquid increased MDM2 expression in H/R-induced H9c2 cells. And MDM2 overexpression strengthened the beneficial effects of Xinnaotongluo liquid on H9c2 cells from the perspective of alleviating oxidative damage, cellular inflammation, apoptosis and ferroptosis of H/R-induced H9c2 cells. Moreover, MDM2 overexpression reduced the protein expression of p53 and Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). Whereas, STEAP3 overexpression hindered the function of MDM2-overexpression in H/R-induced H9c2 cells. Our results insinuated that Xinnaotongluo liquid could protect H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3, which provide a potential theoretical basis for further explaining the working mechanism of Xinnaotongluo liquid.

Self-administration medication errors at home and its predictors among illiterate and low-literate community-dwelling older adults with polypharmacy: A negative binomial hierarchical regression

by Nafiseh Ghassab-Abdollahi, Haidar Nadrian, Elnaz Shaseb, Narges Kheirollahi, Mina Hashemiparast

Background

Older adults with polypharmacy are more prone to medication errors. People with low educational attainment have more difficulties in taking their medications.

Objectives

This study aimed to identify the extent of medication self-administration errors (MSEs) and the contributing factors among illiterate and low-literate community-dwelling older adults with polypharmacy.

Method

The present cross-sectional study was conducted among people aged 60 and above. The data were collected using the sociodemographic, clinical, and Belief about Medicines Questionnaires (BMQ). To determine the extent of MSE, a medication error checklist was used. The negative binomial hierarchical regression model in the five blocks was performed.

Results

The final sample size was 276 people. The frequency of MSEs in the last 6 months was 69.2%. Sixteen percent of participants had made four or more mistakes. The most common MSEs were forgetting, improper taking of medications with food, improper timing, incorrect dosage (lower dose), and forgetting the doctor’s instructions. Near 18% of participants reported adverse events following their mistakes. The significant predictors of MSEs were being completely illiterate (p = 0.021), the higher number of doctor visits per year (p = 0.014), irregularly seeing doctors (p Conclusion

Despite the high prevalence of MSEs among older patients, practical strategies to deal with them at their homes have not been established among health systems. MSE as a multifactorial event can be caused by a collection of internal and external factors. Further studies to identify the role of patients, clinicians, procedures, and systems in developing MSEs as interconnected components are needed.

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells

by Mina Baek, Minjae Kim, Hae In Choi, Bert Binas, Junho Cha, Kyoung Hwa Jung, Sungkyoung Choi, Young Gyu Chai

The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected. Acute Rego treatment of these cells reversed the expression of genes involved in TGF-beta signaling but further increased the expression of genes involved in PI3K-Akt signaling. Additionally, Rego reversed the expression of genes involved in nucleosome assembly and epigenetic gene expression. Weighted gene co-expression network analysis (WGCNA) revealed four differentially expressed long non-coding RNA (DElncRNA) modules that were associated with the effectiveness of Rego on SR cells. Eleven putative DElncRNAs with distinct expression patterns were identified. We associated each module with DEmRNAs of the same pattern, thus obtaining DElncRNA/DEmRNA co-expression modules. We discuss the potential significance of each module. These findings provide insights and resources for further investigation into the potential mechanisms underlying the response of SR HCC cells to Rego.

Accessible luminal interface of bovine rectal organoids generated from cryopreserved biopsy tissues

by Minae Kawasaki, Yoko M. Ambrosini

Developing precise species-specific in vitro models that closely resemble in vivo intestinal tissues is essential for advancing our understanding of gastrointestinal physiology and associated diseases. This is especially crucial in examining host-pathogen interactions, particularly in bovines, a known reservoir for microbes and pathogens posing substantial public health threats. This research investigated the viability of producing bovine rectal organoids from cryopreserved tissues. We compared two cryopreservation methods with a traditional technique using fresh tissues, evaluating their effectiveness through growth rates, long-term viability, and comprehensive structural, cellular, and genetic analyses. These assessments utilized phase-contrast imaging, immunofluorescence imaging, and RT-qPCR assays. Additionally, the study developed a sophisticated method for forming a functional epithelial barrier from organoid-derived bovine rectal monolayers, incorporating a wide range of epithelial cells. This methodology employed transepithelial electrical resistance (TEER), parallel artificial membrane permeability assay (P_app), confocal microscopy, and advanced imaging techniques like scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our findings decisively show that bovine rectal organoids can be effectively generated from cryopreserved biopsy tissues. Moreover, we formulated a robust and optimized protocol for creating functional rectal monolayers from these organoids. This significant progress is particularly relevant given the susceptibility of the bovine rectum to various enteric pathogens of public health concern, marking a vital step forward in veterinary and biomedical research. The creation of accurate species specific in vitro models that faithfully mimic in vivo intestinal tissues is critical for enhancing our understanding of gut physiology and related pathologies. This is particularly relevant in studying the interactions between hosts and microbes or pathogens with significant public health risks where bovine can be the major reservoir.

AE-GPT: Using Large Language Models to extract adverse events from surveillance reports-A use case with influenza vaccine adverse events

by Yiming Li, Jianfu Li, Jianping He, Cui Tao

Though Vaccines are instrumental in global health, mitigating infectious diseases and pandemic outbreaks, they can occasionally lead to adverse events (AEs). Recently, Large Language Models (LLMs) have shown promise in effectively identifying and cataloging AEs within clinical reports. Utilizing data from the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2016, this study particularly focuses on AEs to evaluate LLMs’ capability for AE extraction. A variety of prevalent LLMs, including GPT-2, GPT-3 variants, GPT-4, and Llama2, were evaluated using Influenza vaccine as a use case. The fine-tuned GPT 3.5 model (AE-GPT) stood out with a 0.704 averaged micro F1 score for strict match and 0.816 for relaxed match. The encouraging performance of the AE-GPT underscores LLMs’ potential in processing medical data, indicating a significant stride towards advanced AE detection, thus presumably generalizable to other AE extraction tasks.

Effect of the red uniform on the judgment of position or movement used in Wushu Routine, evaluated by practitioners of the modality

by Jinkun Li, Jingmin Zhang, Shuo Tao, Xiaoying Zeng, Rong Zou, Xiaobin Hong

In the artistic sports program, the referee’ scores directly determine the final results of the athletes. Wushu is a artistic sport that has a Chinese characteristic and has the potential to become an official competition at the Summer Olympic. In this study we tested whether a red uniform color affects Wushu Routine practitioners’ ratings of athletes’ position or movement of Wushu Routine. We also tested whether the effect varied depending on the gender of the athlete and the practitioner, and depending on whether female practitioners were in the ovulation phase of their menstrual cycle. Male (Experiment 1: N = 72) and female (Experiment 1: N = 72; Experiment 2: N = 52) participants who major in Wushu Routine were recruited to take a referee’s perspective and rate the movement quality of male and female athletes wearing red or blue uniforms. The results of Experiment 1 showed that both male and female athletes wearing red uniform (compared to blue uniform) received higher ratings (p = .002, η2 = .066; p = .014, η2 = .043), and the red effect was especially strong when male practitioners rated female athletes (p = .002, η2 = .069). The results of Experiment 2, in an all-female sample, showed that in most cases there was no difference in ratings made by women in the ovulation and non-ovulation phases of their menstrual cycle, with the exception of their ratings of male athletes wearing red; in this condition, women gave higher ratings when they were in the ovulation phase of their cycle (p = .026). The results suggest that there is a red effect in an artistic sport like Wushu Routine, in which gender and the female menstrual cycle play an important role.

Institutional capacity assessment in the lens of implementation research: Capacity of the local institutions in delivering WASH services at Cox’s Bazar district, Bangladesh

by Mahbubur Rahman, Mahbub-Ul Alam, Sharmin Khan Luies, Sharika Ferdous, Zahidul Mamun, Musarrat Jabeen Rahman, Debashish Biswas, Tazrina Ananya, Asadullah, Abul Kamal, Ritthick Chowdhury, Eheteshamul Russel Khan, Dara Johnston, Martin Worth, Umme Farwa Daisy, Tanvir Ahmed

Background

The influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox’s Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies.

Methods

We used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis.

Results

The majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders.

Conclusion

Research evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area.

Inflammatory markers in world trade center workers with asthma: Associations with post traumatic stress disorder

by Juan P. Wisnivesky, Nikita Agrawal, Jyoti Ankam, Adam Gonzalez, Alex Federman, Steven B. Markowitz, Janette M. Birmingham, Paula J. Busse

Background

Post-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site.

Research question

Do WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity?

Study design and methods

We collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants.

Results

Of the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses.

Interpretation

Our results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.

Lightweight high-precision SAR ship detection method based on YOLOv7-LDS

by Shiliang Zhu, Min Miao

The current challenges in Synthetic Aperture Radar (SAR) ship detection tasks revolve around handling significant variations in target sizes and managing high computational expenses, which hinder practical deployment on satellite or mobile airborne platforms. In response to these challenges, this research presents YOLOv7-LDS, a lightweight yet highly accurate SAR ship detection model built upon the YOLOv7 framework. In the core of YOLOv7-LDS’s architecture, we introduce a streamlined feature extraction network that strikes a delicate balance between detection precision and computational efficiency. This network is founded on Shufflenetv2 and incorporates Squeeze-and-Excitation (SE) attention mechanisms as its key elements. Additionally, in the Neck section, we introduce the Weighted Efficient Aggregation Network (DCW-ELAN), a fundamental feature extraction module that leverages Coordinate Attention (CA) and Depthwise Convolution (DWConv). This module efficiently aggregates features while preserving the ability to identify small-scale variations, ensuring top-quality feature extraction. Furthermore, we introduce a lightweight Spatial Pyramid Dilated Convolution Cross-Stage Partial Channel (LSPHDCCSPC) module. LSPHDCCSPC is a condensed version of the Spatial Pyramid Pooling Cross-Stage Partial Channel (SPPCSPC) module, incorporating Dilated Convolution (DConv) as a central component for extracting multi-scale information. The experimental results show that YOLOv7-LDS achieves a remarkable Mean Average Precision (mAP) of 99.1% and 95.8% on the SAR Ship Detection Dataset (SSDD) and the NWPU VHR-10 dataset with a parameter count (Params) of 3.4 million, a Giga Floating Point Operations Per Second (GFLOPs) of 6.1 and an Inference Time (IT) of 4.8 milliseconds. YOLOv7-LDS effectively strikes a fine balance between computational cost and detection performance, surpassing many of the current state-of-the-art object detection models. As a result, it offers a more resilient solution for maritime ship monitoring.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial

by Afsoon Dadvar, Melika Jameie, Mehdi Azizmohammad Looha, Mohammadamin Parsaei, Meysam Zeynali Bujani, Mobina Amanollahi, Mahsa Babaei, Alireza Khosravi, Hamed Amirifard

Objectives

Caffeine’s potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS).

Methods

This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient’s perspective on MS-related QoL (MS-QoL), and Patients’ Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1).

Results

Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value Conclusions

Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time.

Trial registration

This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Unraveling implicit human behavioral effects on dynamic characteristics of Covid-19 daily infection rates in Taiwan

by Ting-Li Chen, Elizabeth P. Chou, Min-Yi Chen, Fushing Hsieh

We investigate the dynamic characteristics of Covid-19 daily infection rates in Taiwan during its initial surge period, focusing on 79 districts within the seven largest cities. By employing computational techniques, we extract 18 features from each district-specific curve, transforming unstructured data into structured data. Our analysis reveals distinct patterns of asymmetric growth and decline among the curves. Utilizing theoretical information measurements such as conditional entropy and mutual information, we identify major factors of order-1 and order-2 that influence the peak value and curvature at the peak of the curves, crucial features characterizing the infection rates. Additionally, we examine the impact of geographic and socioeconomic factors on the curves by encoding each of the 79 districts with two binary characteristics: North-vs-South and Urban-vs-Suburban. Furthermore, leveraging this data-driven understanding at the district level, we explore the fine-scale behavioral effects on disease spread by examining the similarity among 96 age-group-specific curves within urban districts of Taipei and suburban districts of New Taipei City, which collectively represent a substantial portion of the nation’s population. Our findings highlight the implicit influence of human behaviors related to living, traveling, and working on the dynamics of Covid-19 transmission in Taiwan.

Factors affecting young doctors’ choice of medical specialty—A qualitative study

by Beniamin Michalik, Mateusz Kulbat, Alicja Domagała

Background

Young doctors’ choice of medical specialty is essential to maintaining a sufficient health workforce and developing a sustainable healthcare system. The choice of specialization is the result of numerous factors, including doctors’ preferences, population needs, and the number of available residency slots. The aim of this article is to explore the factors taken into consideration by young Polish physicians in choosing their future specialty.

Methods

We have conducted 30 structured interviews with randomly selected recent medical school graduates (17 female and 13 male). The study was conducted from December 2022 until February 2023 using online platforms. Data from in-depth interviews were coded using NVivo Release 1.6.1. Then thematic analysis was performed.

Results

Respondents indicated remuneration and career-associated factors as the main determinants, emphasizing that work-life balance, personal motivations, and the flexibility to choose the type of workplace (hospital vs. outpatient clinic) were even more important. Young doctors expect flexibility in working hours and better working conditions in future work, and these factors are important when choosing a medical specialty. Significant difficulties during the selection of medical specialty include limited residency slots in preferred specializations and lack of knowledge concerning the everyday aspects of work in a particular specialty.

Conclusions

Factors and limitations influencing the choice of medical specialty should be taken into account by policymakers to address the shortages of doctors in deficit specialties. Knowledge about doctors’ preferences regarding their medical specialty could support the development of targeted policies to increase the attractiveness of deficit specialties and reduce the uneven distribution of medical staff.

Assessing the basic knowledge and awareness of dengue fever prevention among migrant workers in Klang Valley, Malaysia

by Maryam N. Chaudhary, Voon-Ching Lim, Erwin Martinez Faller, Pramod Regmi, Nirmal Aryal, Siti Nursheena Mohd Zain, Adzzie Shazleen Azman, Norhidayu Sahimin

Background

Globally, 390 million dengue virus infections occur per year. In Malaysia, migrant workers are particularly vulnerable to dengue fever (DF) due to mosquito breeding sites exposure and poor health literacy. Therefore, this study aimed to (i) assess the current DF knowledge, attitudes and practices (KAP), and (ii) identify strategies to promote DF awareness, among migrant workers in Klang Valley.

Method

A survey was conducted with 403 Nepali, Filipino and Indonesian migrant workers through phone interviews and online self-administered questionnaires. Piecewise structural equation modelling was applied to identify predictor variables for DF KAP.

Results

Most respondents were male, working in the services industry, had completed high school, aged between 30–39 years and with less than ten years work experience in Malaysia. Overall, respondents’ knowledge was positively correlated with attitude but negatively with practices. Older respondents, who had completed higher education, obtained higher knowledge scores. Similarly, those with working experience of >20 years in Malaysia obtained higher attitude scores. Respondents with a previous history of DF strongly considered the removal of mosquito breeding sites as their own responsibility, hence tended to frequently practise DF preventive measures. Respondents’ knowledge was also positively correlated to their understanding of DF information sourced from social media platforms.

Conclusion

These findings highlighted: (i) the need for targeted DF educational intervention among younger and newly arrived workers with lower levels of education and (ii) maximising the usage of social media platforms to improve DF public awareness.

Distress, multimorbidity, and complex multimorbidity among Chinese and Korean American older adults

by Hannah Oh, Brittany N. Morey, Yuxi Shi, Sunmin Lee

Background

Studies suggest that distress is associated with various health conditions such as hypertension, asthma, diabetes, and coronary heart disease. However, only few studies focused on Asian Americans and little is known about the association with multiple comorbidity.

Methods

We conducted a cross-sectional analysis among 400 Chinese and Korean American participants (aged 50–75 years) of the STOP CRC randomized controlled trial. Perceived distress was assessed using the distress thermometer scale (range 0–10). Disease diagnosis was self-reported by the participants. Multimorbidity (MM) was defined as having ≥2 chronic conditions. Complex multimorbidity (CMM) was defined as having ≥3 of the following body system disorders: circulation disorder, endocrine-metabolic disorder, cancer, anxiety or depression, breathing problem, and other health problems. We performed logistic regression for CMM and Poisson regression with robust error variance for MM to estimate associations with distress, adjusting for potential confounders.

Results

The mean age was 58.4 years and mean distress score was 3.65. One-unit increase in distress score was associated with a 1.22-fold increase in the odds of having CMM (95% CI: 1.04–1.42). The magnitude of association slightly increased after additional adjustment for socioeconomic factors and health insurance status (OR: 1.29; 95% CI: 1.10–1.52). Higher distress score was positively associated with MM but the association was only marginally significant (PR: 1.04; 95% CI: 0.99–1.10), adjusting for socioeconomic factors and health insurance status.

Conclusion

Our data suggest that higher perceived distress may be associated with simultaneous dysfunction of multiple distinct body systems among Chinese and Korean American older adults.

Causal relationship between diet and knee osteoarthritis: A Mendelian randomization analysis

by Xiaofeng Lv, Fangqi Liang, Shanshan Liu, Xinmin Deng, Rui Lai, Jihang Du, Jian Luo

Background

Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR).

Methods

We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394–462, 342), and KOA (n = 403, 124). We selected 6–77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis.

Results

We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy.

Conclusions

Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.

Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan

by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama

Objective

Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan.

Design

The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET^® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan.

Participants

Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021.

Exposures

The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine.

Results

We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period.

Conclusions and relevance

This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks

by Josh Williams, Haavard Ahlqvist, Alexander Cunningham, Andrew Kirby, Ira Katz, John Fleming, Joy Conway, Steve Cunningham, Ali Ozel, Uwe Wolfram

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.

Automatic classification of sleep stages using EEG signals and convolutional neural networks

by Ihssan S. Masad, Amin Alqudah, Shoroq Qazan

Sleep stages classification is one of the new topics in studying human life quality because it plays a crucial role in getting a healthy lifestyle. Abnormal changes or absence of normal sleep may lead to different diseases such as heart-related diseases, diabetes, and obesity. In general, sleep staging analysis can be performed using electroencephalography (EEG) signals. This study proposes a convolutional neural network (CNN) based methodology for sleep stage classification using EEG signals taken by six channels and transformed into time-frequency analysis images. The proposed methodology consists of three major steps: (i) segment the EEG signal into epochs with 30 seconds in length, (ii) convert epochs into 2D representation using time-frequency analysis, and (iii) feed the 2D time-frequency analysis to the 2D CNN. The results showed that the proposed methodology is robust and achieved a very high accuracy of 99.39% for channel C4-A1. All other channels have accuracy values above 98.5%, which indicates that any channel can be used for sleep stage classification with high accuracy. The proposed methodology outperformed the methods in the literature in terms of overall accuracy or single channel accuracy. It is expected to provide a great benefit for physicians, especially neurologists; by providing them with a new powerful tool to support the clinical diagnosis of sleep-related diseases.

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression

by Karim S. Ladha, Jiwon Lee, Gabriella F. Mattina, Janneth Pazmino-Canizares, Duminda N. Wijeysundera, Fatemeh Gholamali Nezhad, Kaylyssa Philip, Vanessa K. Tassone, Fathima Adamsahib, Venkat Bhat, on behalf of the SMILE Study Investigators

Background

Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.

Methods

In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score Discussion

This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression.

Trial registration

ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.