bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term rate of ventricular arrhythmia in autoimmune disease
Authors: Sun Guoli , Fosbøl Emil L , Schou Morten , Faurschou Mikkel , Yafasova Adelina , Petersen Jeppe K , Haugan Ketil J , Mogensen Ulrik Madvig , Svendsen Jesper H , Køber Lars , Butt Jawad H
Published: March 2024

Aims

Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of this study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs.

Methods and results

Individuals diagnosed with an AID (2005–18) were identified through Danish nationwide registries. Each patient with an AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. In total, 186 733 patients diagnosed with AIDs were matched with 746 932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals {hazard ratio (HR) 1.39 [95% confidence interval (CI), 1.29–1.49]}. The highest HR was observed in patients with systemic sclerosis [3.86 (95% CI, 1.92–7.75)]. The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischaemic heart disease or heart failure/cardiomyopathy compared with those with these conditions (Pinteraction <0.05).

Conclusion

Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.
Cost-effectiveness of Mediterranean diet and physical activity in secondary cardiovascular disease prevention: results from the UCC-SMART cohort study
Authors: Bonekamp Nadia E , Visseren Frank L J , van der Schouw Yvonne T , van der Meer Manon G , Teraa Martin , Ruigrok Ynte M , Geleijnse Johanna M , Koopal Charlotte ,   UCC-SMART study group, Cramer M J , Nathoe H M , van der Harst P , van de Meer M G , de Borst G J , Teraa M , Bots M L , van Smeden M , Emmelot-Vonk M H , de Jong P A , Lely A T , van der Kaaij N P , Kappelle L J , Ruigrok Y M , Verhaar M C , Dorresteijn J A N , Visseren F L J
Published: March 2024

Aims

The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess whether Mediterranean diet and physical activity are also cost-effective in patients with established CVD.

Methods and results

A cost–utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in patients with CVD. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100 000 patients with CVD sampled from the Utrecht Cardiovascular Cohort—Secondary Manifestations of ARTerial disease study (n = 8947, mean age 62 ± 8.7 years, and 74% male). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of €1236 per person compared with usual care, resulting in an ICER of €−626/QALY [95% confidence interval (CI) −1929 to 2673]. At a willingness-to-pay of €20 000/QALY, INHB was 2.04 (95% CI 0.99–3.58) QALYs and INMB was €40 757 (95% CI 19 819–71 605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs.

Conclusion

In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared with usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all patients with CVD.
Increased mortality in socioeconomic disadvantaged municipalities during the first phase of the COVID-19 pandemic in Lombardy region
Authors: Alicandro Gianfranco , Gerli Alberto , La Vecchia Carlo
Published: March 2024

Background

Lombardy was the first European region most severely affected by the coronavirus disease 2019 pandemic in the spring of 2020. During that period, a substantial increase in socioeconomic inequality in total mortality was observed. This study aims to evaluate mortality data in the region up to September 2023 to verify whether the increased disparities between the poorest and the wealthiest municipalities persisted in the subsequent phases of the pandemic.

Methods

This study analyzed mortality data from January 2019 to September 2023 in Lombardy's municipalities by month and pandemic phases characterized by the predominance of the different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Municipalities were grouped according to the average income or pension of their residents. Age-standardized mortality rates (ASMRs) and the ASMR ratio between the poorest and the wealthiest municipalities were compared throughout the study period.

Results

In the pre-pandemic period (January 2019 - February 2020), the ASMR ratio at all ages between the poorest and the wealthiest municipalities fluctuated between 1.12 [95% confidence interval (CI): 1.07–1.16] and 1.29 (95% CI: 1.25–1.34). In March 2020, the ASMR ratio increased to 1.49 (95% CI: 1.45–1.52 95%) and returned to values registered before the pandemic thereafter. A similar pattern was observed in the analysis of mortality ≥ 65, using the average pension for group municipalities.

Conclusions

During the dramatic circumstances that the region faced in March 2020, pre-existing socioeconomic inequalities substantially widened. With the reorganization of the health system and the availability of vaccines, these disparities returned to the levels recorded before the pandemic.
Nanobody-based food allergen surveillance: current status and prospects
Authors: Wang Yi , Wu Sihao , Li Ang , Lv Huan , Ji Xuemeng , Hu Yaozhong , Wang Shuo
Published: March 2024

The incidence of food allergy has increased in recent decades, posing drastic risks to sensitive individuals, leading to mild to severe allergic symptoms. There is still no effective immune therapeutic strategy for food allergy that addresses accurate analytical methods to indicate the presence of allergens to prevent exposure of sensitive individuals. Currently, the most commonly applied detection method is immunoassay developed with food allergen-specific antibodies, especially the conventional formats of monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs), which serve as dominant detection reagents for food allergen analysis, although with the disadvantages of being labor-intensive, costly, batch differences, and significant cross-reaction, etc. Camelid-derived nanobodies (Nbs) have attracted tremendous attention to explore their application in food hazard analysis because of robust characteristics like unique paratopes, high stability and affinity that strongly contribute to the beneficial effect. However, extensive analysis is needed to validate the potential use of Nbs as detection reagents and the advantages for food allergen surveillance. Previous reports have demonstrated the potential of Nbs for immunoassay development against food allergens, such as macadamia allergen Mac i 1, peanut allergens Ara h 1 and Ara h 3, lupin allergen Lup an 1, milk allergen β-lactoglobulin, etc. In this review, we comprehensively summarize the structural and biochemical properties of Nbs that benefit the application of Nb-based immunoassay, as well as the representative detection strategies, to provide research data for newly developed Nb formats for food allergen analysis, and investigate the future establishment of Nb-based surveillance against major food allergens.
Decomposition of medical imaging spending growth between 2010 and 2021 in the US employer–insured population
Authors: Horný Michal , Chang Daniel , Christensen Eric W , Rula Elizabeth Y , Duszak Richard
Published: March 2024

Medical imaging, identified as a potential driver of unsustainable US health care spending growth, was subject to policies to reduce prices and use in low-value settings. Meanwhile, the Affordable Care Act increased access to preventive services—many involving imaging—for employer-sponsored insurance (ESI) beneficiaries. We used a large insurance claims database to examine imaging spending trends in the ESI population between 2010 and 2021—a period of considerable policy and benefits changes. Nominal spending on imaging increased 35.9% between 2010 and 2021, but as a share of total health care spending fell from 10.5% to 8.9%. The 22.5% growth of nominal imaging prices was below inflation, 24.3%, as measured by the Consumer Price Index. Other key contributors to imaging spending growth were increased use (7.4 percentage points [pp]), shifts toward advanced modalities (4.0 pp), and demographic changes (3.5 pp). Shifts in care settings and provider network participation resulted in 2.5-pp and 0.3-pp imaging spending decreases, respectively. In sum, imaging spending decreased as a share of all health care spending and relative to inflation, as intended by concurrent cost-containment policies.
Interaction among homeodomain transcription factors mediates ethylene biosynthesis during pear fruit ripening
Authors: Cao Su-Hao , Guo Zhi-Hua , Liu Hong , Wang Guo-Ming , Qi Kai-Jie , Wang Ze-Wen , Tian Rui-Ping , Sha Shou-Feng , Zhang Shao-Ling , Gu Chao
Published: March 2024

Fruit ripening is manipulated by the plant phytohormone ethylene in climacteric fruits. While the transcription factors (TFs) involved in ethylene biosynthesis and fruit ripening have been extensively studied in tomato, their identification in pear remains limited. In this study, we identified and characterized a HOMEODOMAIN TF, PbHB.G7.2, through transcriptome analysis. PbHB.G7.2 could directly bind to the promoter of the ethylene biosynthetic gene, 1-aminocyclopropane-1-carboxylic acid synthase (PbACS1b), thereby enhancing its activity and resulting in increased ethylene production during pear fruit ripening. Yeast-two-hybrid screening revealed that PbHB.G7.2 interacted with PbHB.G1 and PbHB.G2.1. Notably, these interactions disrupted the transcriptional activation of PbHB.G7.2. Interestingly, PbHB.G1 and PbHB.G2.1 also bind to the PbACS1b promoter, albeit different regions from those bound by PbHB.G7.2. Moreover, the regions of PbHB.G1 and PbHB.G2.1 involved in their interaction with PbHB.G7.2 differ from the regions responsible for binding to the PbACS1b promoter. Nonetheless, these interactions also disrupt the transcriptional activation of PbHB.G1 and PbHB.G2.1. These findings offer a new mechanism of ethylene biosynthesis during climacteric fruit ripening.
Windows of opportunity in integrating mental health into care of neglected tropical diseases: the Nigeria experience
Authors: Ojo Tunde M , Afolayan Oluwole G , Alex-Okoh Morenike O
Published: March 2024

In this invited commentary, the Mental Health and the Neglected Tropical Diseases(NTDs) Program leads in the Nigerian Federal Ministry of Health and Social Welfare share the opportunities that have arisen from recent global progress in normative guidance and political interest in the intersection of mental health and NTDs. They describe the new collaboration that has taken place between their programs, e.g. contributing to the World Health Organization Essential Care Package for Mental Health, Stigma and NTDs and integration of mental health for the first time into the new National NTD Masterplan.
Prevalence, assessment and correlates of mental health problems in neglected tropical diseases: a systematic review
Authors: Adjorlolo Samuel , Adimado Emma Efua , Setordzi Mawuko , Akorli Vincent Valentine
Published: March 2024

Neglected tropical diseases (NTDs) are a group of disease conditions that affect the world's poorest people in low- and middle-income countries. NTDs are associated with negative behavioural experiences, including discrimination, rejection and stigmatization, that predisposes those affected to mental health problems. Consequently, researchers have shown profound interest in elucidating the mental health burden associated with NTDs. To address pertinent issues in the burgeoning literature relating to the prevalence, assessment and correlates of mental health problems in NTDs, a systematic review methodology was used. Underpinned by the PRISMA guidelines, a search was conducted of electronic databases, individual journals and bibliographies for articles that were screened and subjected to predetermined inclusion and exclusion criteria. Sixteen articles from African, Asian and South American countries were included in the review. Depression was the most widely investigated mental health issue, followed by stress and anxiety, with prevalence estimates of 7–54%, 8–43% and 19–53%, respectively. The PHQ-9 and GAD-7 and Self-Reporting Questionnaire were the most widely administered mental health screening tools. The major correlates of mental health problems are lower education and economic status and female gender. We recommend multisectoral and multilayered mental health and related interventions to address the increasing burden of mental health in NTDs.
Leprosy in Colombia: A look from life experience
Authors: Mora Julián Andrés Uribe , Angarita Patricia Devia
Published: March 2024

Leprosy continues to be stigmatized, causing harm to fundamental rights, pain and hopelessness in those who have suffered from it and their families. From its relationship with public and mental health, effective strategies must be implemented to reduce stigma and unlearn myths and wrong perceptions, support families, and improve quality of life through early care and detection. This article shows that those affected by leprosy are capable, functional people with much to contribute to society anywhere in the world.
Antimicrobial resistance of clinical bacterial isolates in China: current status and trends
Authors: Qin Xiaohua , Ding Li , Hao Min , Li Pei , Hu Fupin , Wang Minggui
Published: March 2024

Antimicrobial resistance surveillance systems have been established in China. Two representative national surveillance networks are the China Antimicrobial Surveillance Network (CHINET) and China Antimicrobial Resistance Surveillance System (CARSS), both of which were established in 2005. For all clinical isolates collected in both of these surveillance networks, the ratio of Gram-negative bacilli to Gram-positive cocci was approximately 7:3 during the past 18 years. Generally, Gram-negative bacilli have a higher antimicrobial resistance profile in China. The prevalence of ESBLs in Escherichia coli is as high as approximately 50%. Acinetobacter baumannii-calcoaceticus complex (ABC) has a high antimicrobial resistance profile, with a carbapenem resistance rate of approximately 66%. However, the prevalence of carbapenem-resistant ABC has also shown a decreasing trend from 2018 to 2022. The prevalence of vancomycin-resistant Enterococcus was low, and the prevalence of MRSA and carbapenem-resistant Pseudomonas aeruginosa showed decreasing trends from 2005 to 2022. CHINET surveillance data demonstrated that the prevalence of carbapenem-resistant Klebsiella pneumoniae showed a remarkable increasing trend from 2.9% (imipenem resistance) in 2005 to 25.0% in 2018, and then slightly decreased to 22.6% in 2022. The decreasing trends may reflect the antimicrobial stewardship efforts in China: a professional consensus on the rational clinical use of carbapenems was issued by the National Health Commission of China and was well implemented nationally; after that, the clinical use of carbapenems decreased slightly in China.
An Image-Rich Educational Review of Breast Pain
Authors: Bui Anthony H , Smith Gretchen J , Dyrstad Sara W , Robinson Kathryn A , Herman Cheryl R , Owusu-Brackett Nicci , Fowler Amy M
Published: March 2024

Breast pain is extremely common, occurring in 70% to 80% of women. Most cases of breast pain are from physiologic or benign causes, and patients should be reassured and offered treatment strategies to alleviate symptoms, often without diagnostic imaging. A complete clinical history and physical examination is key for distinguishing intrinsic breast pain from extramammary pain. Breast pain without other suspicious symptoms and with a negative history and physical examination result is rarely associated with malignancy, although it is a common reason for women to undergo diagnostic imaging. When breast imaging is indicated, guidelines according to the American College of Radiology Appropriateness Criteria should be followed as to whether mammography, US, or both are recommended. This review article summarizes the initial clinical evaluation of breast pain and evidence-based guidelines for imaging. Additionally, the article reviews cyclical and noncyclical breast pain and provides an image-rich discussion of the imaging presentation and management of benign and malignant breast pain etiologies.
Reimagining space layout design through deep reinforcement learning
Authors: Kakooee Reza , Dillenburger Benjamin
Published: March 2024

Space layout design is a critical aspect of architectural design, influencing functionality and aesthetics. The inherent combinatorial nature of layout design poses challenges for traditional planning approaches; thus, it demands the exploration of novel methods. This paper presents a novel framework that leverages the potential of deep reinforcement learning (RL) algorithms to optimize space layouts. RL has demonstrated remarkable success in addressing complex decision-making problems, yet its application in the design process remains relatively unexplored. We argue that RL is particularly well-suited for the design process due to its ability to accommodate offline tasks and seamless integration with existing computer-aided design software, effectively acting as a simulator for design exploration. Framing space layout design as an RL problem and employing RL methods allows for the automated exploration of the expansive design space, thereby enhancing the discovery of innovative solutions. This paper also elucidates the synergy between the design process and the RL problem, which opens new avenues for exploring the potential of RL algorithms in design. We aim to foster experimentation and collaboration within the RL and architecture communities. To facilitate our research, we have developed SpaceLayoutGym, an environment specifically designed for space layout design tasks. SpaceLayoutGym serves as a customizable environment that encapsulates the essential elements of the layout design process within an RL framework. To showcase the effectiveness of SpaceLayoutGym and the capabilities of RL as an artificial space layout designer, we employ the Proximal Policy Optimization (PPO) algorithm to train the RL agent in selected design scenarios with both geometrical constraints and topological objectives. The study further extends to contrast the effectiveness of PPO agents with that of genetic algorithms, and also includes a comparative analysis with existing layouts. Our results demonstrate the potential of RL to optimize space layouts, offering a promising direction for the future of artificial intelligence-aided design.
Racial differences in postpandemic trends in prostate-specific antigen screening
Authors: Qian Zhiyu , Alexander Jameshisa , Daniels Danesha , Abdollah Firas , Cole Alexander P , Iyer Hari S , Trinh Quoc-Dien
Published: March 2024

Our study investigates the trends in prostate cancer screening amid the COVID-19 pandemic, particularly focusing on racial disparities between Black and White men. Utilizing data from the Behavioral Risk Factor Surveillance System from 2018, 2020, and 2022, we analyzed prostate-specific antigen screening rates in men aged 45-75 years. Our findings reveal initial declines in screening rates for both groups during the pandemic, with subsequent recovery; however, the pace of rebound differed statistically significantly between races. Whereas White men showed a notable increase in screening rates postpandemic, Black men’s rates recovered more slowly. This disparity underscores the impact of socioeconomic factors, health-care access, and possibly systemic biases affecting health-care delivery. Our study highlights the need for targeted interventions to address these inequalities and ensure equitable access to prostate cancer preventive care in the aftermath of COVID-19.
Carpal tunnel syndrome, spinal canal stenosis, cardiomyopathy, renal insufficiency, enteropathy, and diffuse myopathy as an expression of systemic ATTR amyloidosis - diagnostics and therapy
Authors: Radmer Sebastian , Andresen Julian Ramin
Published: March 2024

Systemic amyloidosis is an incurable multisystem disease, caused by fibrillar protein deposits with resulting dysfunction of affected organ systems. It mostly affects patients > 60 years. Diagnosis is often delayed because the symptoms are nonspecific and highly variable. We report on an elderly patient with multi-organ involvement with proven wild-type transthyretin amyloidosis. The initial manifestation involved bilateral carpal tunnel syndrome and lumbar spinal canal stenosis. The occurrence of ligament and tendon disorders, unexplained muscle pain and polyneuropathy in elderly patients should be considered as a possible first manifestation of systemic amyloidosis.
Successful surgical correction of an incomplete atrioventricular septal defect in a 76-year-old female patient
Authors: Shirakura Kentaro , Akasaka Nobuyuki , Mizushima Daichi , Narita Masahiko , Okubo Ryo , Nakatsu Tomoki , Kobayashi Daita , Kamiya Hiroyuki
Published: March 2024

We report the case of a 76-year-old woman with an incomplete atrioventricular septal defect and severe congestive heart failure who underwent surgical repair. Surgical intervention involved mitral valve repair and patch closure of the ostium primum defect, resulting in a favorable postoperative course. Successful outcomes support surgery as a reasonable treatment option owing to its significant improvement in postoperative quality of life, even in elderly patients with left atrioventricular valve degeneration.
Early gastro-oesophageal junction perforation repaired using through-the-scope clips following Nissen fundoplication
Authors: Anthony Phelopatir , Andrawis Nagy
Published: March 2024

Early gastric and oesophageal perforations are rare following laparoscopic fundoplications, with an incidence of 0.9%. If managed operatively, omentopexy or redo-fundoplication may be employed. Here, we present the case of a septic 21 year old patient who presented with an early gastro-oesophageal perforation 7 days following laparoscopic Nissen fundoplication, which was successfully repaired endoscopically using haemostatic clips. To date, this technique of perforation repair in the setting of fundoplication has yet to be reported.
Optimal Predictors of General Small Area Parameters Under an Informative Sample Design Using Parametric Sample Distribution Models
Authors: Cho Yanghyeon , Guadarrama-Sanz María , Molina Isabel , Eideh Abdulhakeem , Berg Emily
Published: March 2024

Two challenges in small area estimation occur when (i) the sample selection mechanism depends on the outcome variable and (ii) the parameter of interest is a nonlinear function of the response variable in the assumed model. If, given the values of the model covariates, the sample selection mechanism depends on the model response variable, the design is said to be informative for the model. Pfeffermann and Sverchkov (2007) develop a small area estimation procedure for informative sampling, focusing on the prediction of small area means. Molina and Rao (2010) develop a small area estimation procedure for general parameters that are nonlinear functions of the model response variable. The method of Molina and Rao assumes noninformative sampling. We combine these two approaches to develop a procedure for the estimation of general parameters in small areas under informative sampling. We introduce a parametric bootstrap MSE estimator that is appropriate for an informative sample design. We evaluate the validity of the proposed procedures through extensive simulation studies and illustrate the procedures utilizing Mexico’s income data.
Modelling Chinese contemporary calligraphy: the WRITE data model
Authors: Pasqual Valentina , Lučić Katarina , Bisceglia Marta Rosa , Merenda Martina , Iezzi Adriana , Tomasi Francesca
Published: March 2024

This article presents the WRITE data model and dataset, a comprehensive collection of Chinese contemporary calligraphic data, utilizing Linked Open Data (LOD) principles. Calligraphy plays a pivotal role in Chinese culture, reflecting national identity and cultural transformations. The objective of this study is to enhance understanding and provide new tools for exploring Chinese contemporary calligraphy through LOD. The WRITE data model comprises artistic, linguistic, and socio-political-economic aspects. The WRITE data model, developed collaboratively with domain specialists, represents four collections: Contemporary Visual Art, Performance, Graffiti, and Decorative and Applied Arts. Metadata describing the artworks is structured by reusing and extending the Wikidata model. Complex relations are established between artworks and contextual elements, (e.g. people, exhibition history, organizations, and literary works). The artistic and linguistic metadata recorded over the ‘calli-writing units’ provide insights into shared and diverging characteristics with traditional calligraphy. Traditional and contemporary calligraphy practices are compared, highlighting how contemporary calligraphy challenges traditional rules. Two case studies demonstrate the formalization of specific items in the WRITE collection, showcasing the study of graffiti art’s socio-political meaning in China and the multidimensional nature of musicalligraphy performance. The WRITE dataset and data model contribute to advancing knowledge and understanding of Chinese contemporary calligraphy, offering valuable resources for artistic analysis and interdisciplinary research.
Recent advances in enzyme-free and enzyme-mediated single-nucleotide variation assay in vitro
Authors: Xiong Erhu , Liu Pengfei , Deng Ruijie , Zhang Kaixiang , Yang Ronghua , Li Jinghong
Published: March 2024

Single-nucleotide variants (SNVs) are the most common type variation of sequence alterations at a specific location in the genome, thus involving significant clinical and biological information. The assay of SNVs has engaged great awareness, because many genome-wide association studies demonstrated that SNVs are highly associated with serious human diseases. Moreover, the investigation of SNV expression levels in single cells are capable of visualizing genetic information and revealing the complexity and heterogeneity of single-nucleotide mutation-related diseases. Thus, developing SNV assay approaches in vitro, particularly in single cells, is becoming increasingly in demand. In this review, we summarized recent progress in the enzyme-free and enzyme-mediated strategies enabling SNV assay transition from sensing interface to the test tube and single cells, which will potentially delve deeper into the knowledge of SNV functions and disease associations, as well as discovering new pathways to diagnose and treat diseases based on individual genetic profiles. The leap of SNV assay achievements will motivate observation and measurement genetic variations in single cells, even within living organisms, delve into the knowledge of SNV functions and disease associations, as well as open up entirely new avenues in the diagnosis and treatment of diseases based on individual genetic profiles.
Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients
Authors: Kudriavtsev Andrei , Pastor Brice , Mirandola Alexia , Pisareva Ekaterina , Gricourt Yann , Capdevila Xavier , Thierry Alain R , Cuvillon Philippe
Published: March 2024

Objectives

Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular trap (NETs) markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients.

Methods

We examined the plasma levels of two NETs protein markers [myeloperoxidase (MPO) and neutrophil elastase (NE)], as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origin in 29 colon, prostate, and breast cancer patients and in 114 healthy individuals (HI).

Results

The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer [r = 0.60 (P < 0.001) and r = 0.53 (P < 0.01), respectively], but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI.

Conclusion

Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.
Mortality, bone density and grip strength: lessons from the past and hope for the future?
Authors: Westbury Leo D , Laskou Faidra , Patel Harnish P , Cooper Cyrus , Dennison Elaine M
Published: March 2024

Objectives

Therapeutic advances in the management of osteoporosis and sarcopenia have occurred at different rates over the last 2 decades. Here we examine associations between grip strength and BMD with subsequent all-cause and cause-specific mortality in a UK community-dwelling cohort.

Methods

Data from 495 men and 414 women from the Hertfordshire Cohort Study were analysed. Grip strength was assessed by grip dynamometry, femoral neck BMD was ascertained using DXA and deaths were recorded from baseline (1998–2004) until 31 December 2018. Grip strength and BMD in relation to mortality outcomes (all-cause, cardiovascular-related, cancer-related and mortality due to other causes) were examined using Cox regression with adjustment for age and sex.

Results

The mean baseline age of participants was 64.3 years (s.d. 2.5) and 65.9 years (s.d. 2.6) in men and women, respectively. Lower grip strength was associated with increased risk of all-cause mortality [hazard ratio (HR) 1.30 (95% CI 1.06, 1.58), P = 0.010] and cardiovascular-related mortality [HR 1.75 (95% CI 1.20, 2.55), P = 0.004]. In contrast, BMD was not associated with any of the mortality outcomes (P > 0.1 for all associations).

Conclusion

We report strong relationships between grip strength and mortality compared with BMD. We hypothesize that this may reflect better recognition and treatment of low BMD in this cohort.
A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy
Authors: Zhang Nan , Sun Qiqi , Li Junhua , Li Jing , Tang Lei , Zhao Quan , Pu Yuji , Liang Gaofeng , He Bin , Gao Wenxia , Chen Jianlin
Published: March 2024

Immune checkpoint blockade therapy provides a new strategy for tumor treatment; however, the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects. Herein, we reported a lipid/PLGA nanocomplex (RDCM) co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1MT to improve immunotherapy of colon cancer. Arginine–glycine–aspartic acid (RGD) as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol (PEG), and programmed cell death-ligand 1 (PD-L1) peptide inhibitor DPPA (sequence: CPLGVRGK-GGG-d(NYSKPTDRQYHF)) was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker. The Ce6 and 1MT were encapsulated in PLGA nanoparticles. The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes. When the nanocomplexes were delivered to tumor, DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding. RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin. Strong immunogenic cell death was induced by 1O2 generated from Ce6 irradiation under 660 nm laser. 1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment. The RDCM facilitated the maturation of dendritic cells, inhibited the activity of IDO, and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice, triggering a robust immunological memory effect, thus effectively preventing tumor metastasis. The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.
Sleep behavioral outcomes of school-based interventions for promoting sleep health in children and adolescents aged 5 to 18 years: a systematic review
Authors: Gaskin Cadeyrn J , Venegas Hargous Carolina , Stephens Lena D , Nyam Gunchmaa , Brown Victoria , Lander Natalie , Yoong Serene , Morrissey Bridget , Allender Steven , Strugnell Claudia
Published: March 2024

Study Objectives

Insufficient sleep is common among children and adolescents, and can contribute to poor health. School-based interventions potentially could improve sleep behavior due to their broad reach, but their effectiveness is unclear. This systematic review focused on the effects of school-based interventions on sleep behavior among children and adolescents aged 5 to 18 years.

Methods

Five electronic databases were searched for randomized controlled trials of sleep health interventions initiated or conducted in school settings and in which behavioral sleep outcomes were measured. Cochrane risk of bias tools were used to assess study quality.

Results

From the 5303 database records and two papers from other sources, 21 studies (22 papers) met the inclusion criteria for this review. These studies involved 10 867 children and adolescents at baseline from 13 countries. Most studies (n = 15) were conducted in secondary schools. Sleep education was the most common intervention, either alone (n = 13 studies) or combined with other initiatives (stress management training, n = 2; bright light therapy, n = 1; health education, n = 1). Interventions were typically brief in terms of both the intervention period (median = 4 weeks) and exposure (median = 200 minutes). Behavioral outcomes included actigraphy-measured and self-reported sleep patterns, and sleep hygiene. All outcomes had high risk of bias or some concerns with bias. Sleep education interventions were typically ineffective. Later school start times promoted longer sleep duration over 1 week (1 study, high risk of bias).

Conclusions

Current evidence does not provide school-based solutions for improving sleep health, perhaps highlighting a need for complex, multi-component interventions (e.g. whole-of-school approaches) to be trialed.
Pluripotent stem cells for target organ developmental toxicity testing
Authors: Wu Xian , Chen Yichang , Kreutz Anna , Silver Brian , Tokar Erik J
Published: March 2024

Prenatal developmental toxicity research focuses on understanding the potential adverse effects of environmental agents, drugs, and chemicals on the development of embryos and fetuses. Traditional methods involve animal testing, but ethical concerns and the need for human-relevant models have prompted the exploration of alternatives. Pluripotent stem cells (PSCs) are versatile cells with the unique ability to differentiate into any cell type, serving as a foundational tool for studying human development. Two-dimensional (2D) PSC models are often chosen for their ease of use and reproducibility for high-throughput screening. However, they lack the complexity of an in vivo environment. Alternatively, three-dimensional (3D) PSC models, such as organoids, offer tissue architecture and intercellular communication more reminiscent of in vivo conditions. However, they are complicated to produce and analyze, usually requiring advanced and expensive techniques. This review discusses recent advances in the use of human PSCs differentiated into brain and heart lineages and emerging tools and methods that can be combined with PSCs to help address important scientific questions in the area of developmental toxicology. These advancements and new approach methods align with the push for more relevant and predictive developmental toxicity assessment, combining innovative techniques with organoid models to advance regulatory decision-making.
Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility
Authors: Vincent Melissa J , Fitch Seneca , Bylsma Lauren , Thompson Chad , Rogers Sarah , Britt Janice , Wikoff Daniele
Published: March 2024

Formaldehyde is recognized as carcinogenic for the portal of entry sites, though conclusions are mixed regarding lymphohematopoietic (LHP) cancers. This systematic review assesses the likelihood of a causal relationship between formaldehyde and LHP cancers by integrating components recommended by NASEM. Four experimental rodent bioassays and 16 observational studies in humans were included following the implementation of the a priori protocol. All studies were assessed for risk of bias (RoB), and meta-analyses were conducted on epidemiological studies, followed by a structured assessment of causation based on GRADE and Bradford Hill. RoB analysis identified systemic limitations precluding confidence in the epidemiological evidence due to inadequate characterization of formaldehyde exposure and a failure to adequately adjust for confounders or effect modifiers, thus suggesting that effect estimates are likely to be impacted by systemic bias. Mixed findings were reported in individual studies; meta-analyses did not identify significant associations between formaldehyde inhalation (when measured as ever/never exposure) and LHP outcomes, with meta-SMRs ranging from 0.50 to 1.51, depending on LHP subtype. No associations with LHP-related lesions were reported in reliable animal bioassays. No biologically plausible explanation linking the inhalation of FA and LHP was identified, supported primarily by the lack of systemic distribution and in vivo genotoxicity. In conclusion, the inconsistent associations reported in a subset of the evidence were not considered causal when integrated with the totality of the epidemiological evidence, toxicological data, and considerations of biological plausibility. The impact of systemic biases identified herein could be quantitatively assessed to better inform causality and use in risk assessment.
Parents’ Views on Prolonged Maternal Hospital Stay With Sick Newborn Infants in a Tertiary Neonatal Unit in Sri Lanka
Authors: Rodrigo Ranmali , Amir Lisa H. , Forster Della A.
Published: March 2024

Background:

Mothers of infants in most Sri Lankan neonatal units are required to be “inpatients” during the entirety of their infant’s stay. This traditional practice is closely aligned to the relatively newer model of family-integrated care.

Purpose:

Exploration of parent’s views regarding the expectation for mothers to remain in hospital for the entire duration of their infant’s neonatal unit stay.

Methods:

Cross-sectional study of parents of infants admitted to the University neonatal unit of Colombo North Teaching Hospital, Ragama, Sri Lanka, using self-administered questionnaires in 2017.

Results:

We found that 40% (19/48) of mothers and 43% (16/37) of fathers preferred that mothers traveled from home, rather than being inpatients continuously, in order to care for older children, receive psychological support from family, and also due to other practical inconveniences of living in the hospital. The main barriers to women being able to travel from home were the need to safely provide expressed human milk for their hospitalized infants and current hospital administrative and societal attitudes.

Implications for Practice and Research:

We found that a considerable number of parents with infants in the neonatal intensive care unit in Sri Lanka would like the option of the mother being able travel from home, rather than being confined to hospital. To facilitate this option, changes in hospital protocols and further research into storage and transportation of expressed mother’s milk will be required. Improving facilities in hospital and providing more opportunities for families to interact with infants in neonatal intensive care unit will encourage mothers to remain in hospital continuously.
Hypothesis Tests for Continuous Audiometric Threshold Data
Authors: Liu Zechen , Wei Zhuoran , Li Jiaxuan , Curhan Gary , Curhan Sharon , Wang Molin
Published: March 2024

Objectives:

Hypothesis tests for hearing threshold data may be challenging due to the special structure of the response variable, which consists of the measurements from the participant’s two ears at multiple frequencies. The commonly-used methods may have inflated type I error rates for the global test that examines whether exposure-hearing threshold associations exist in at least one of the frequencies. We propose using both-ear methods, including all frequencies in the same model for hypothesis testing.

Design:

We compared the both-ear method to commonly used single-ear methods, such as the worse-ear, better-ear, left/right-ear, average-ear methods, and both-ear methods that evaluate individual audiometric frequencies in separate models, through both theoretical consideration and a simulation study. Differences between the methods were illustrated using hypothesis tests for the associations between the Dietary Approaches to Stop Hypertension adherence score and 3-year change in hearing thresholds among participants in the Conservation of Hearing Study.

Results:

We found that (1) in the absence of ear-level confounders, the better-ear, worse-ear and left/right-ear methods have less power for frequency-specific tests and for the global test; (2) in the presence of ear-level confounders, the better-ear and worse-ear methods are invalid, and the left/right-ear and average-ear methods have less power, with the power loss in the left/right-ear much greater than the average-ear method, for frequency-specific tests and for the global test; and (3) the both-ear method with separate analyses for individual frequencies is invalid for the global test.

Conclusions:

For hypothesis testing to evaluate whether there are significant associations between an exposure of interest and audiometric hearing threshold measurements, the both-ear method that includes all frequencies in the same model is the recommended analytic approach.
Is the Ankle Fusion the Single Salvage Procedure and the Best Result for the Massive Distal Tibial Loss: Surgical Techniques and Clinical Results
Authors: Lerner Alexander , Jakusonoka Ruta , Jumtins Andris , Rothem David
Published: March 2024

Background:

Management of high-energy injuries with extensive soft tissue damage and massive distal tibial loss is challenging and often lead to severe dysfunction. In these complex situations ankle fusion procedure is the most commonly performed surgery. Publications devoted to treatment options and outcomes in these surgical challenging conditions are relatively rare.

Objective:

The purpose of this work is to present our clinical experience in using staged external fixation protocol in the treatment of six patients who suffered from complex open fractures of the distal tibial segment with severe bone and soft tissue loss due to high-energy trauma.

Methods:

The retrospective analysis of six patients (Gustilo-Anderson III B and III C fractures) with massive distal tibial loss and treated using a staged protocol of external fixation between 1998 and 2010, was carried out. Mean bone loss was 11.5 cm (range, 9 – 15 cm).

Results:

All patients had reconstructive surgery using circular external fixation frames. The outcome in three of them was solid ankle fusion – two patients had acute distal shortening and proximal tibial elongation by distraction osteogenesis and one had acute fibular transfer to replace distal tibial loss with fixation using Ilizarov circular frame. In other three patients, the functional and the radiological outcome was pain-free ankle joint pseudoarthrosis – one had proximal tibial elongation, one had a combination of bone transport with distal fibular transfer and one had acute limb shortening without tibial elongation. All six patients were pain-free and satisfied with functional outcomes, regardless of the final solid bone fusion or pseudoarthrosis.

Conclusions:

The method of circular external fixation combined with proximal tibial elongation by distraction histogenesis is recommended for limb reconstruction in high-energy injuries with massive distal tibial loss including articular surface.

Level of Evidence:

Diagnostic Level Ⅳ.
Combined Morphine and Methadone Treatment: Two Case Reports
Authors: Srivastava Anita , Kahan Meldon
Published: March 2024

Background:

The vast majority of accidental opioid toxicity deaths in Canada were fentanyl-related in 2022. The strongest evidence-based treatment defense against such deaths is opioid agonist treatment. In the hope of increasing treatment retention in opioid agonist treatment, recent guidelines have endorsed the addition of slow-release oral morphine (SROM) to methadone maintenance treatment (MMT) as a long-term option and anecdotally, the practice is starting to take hold in some medical practices.

Case Reports:

Two case reports of patients who were prescribed both SROM and MMT concurrently for ongoing maintenance are presented and examined here.

Discussion:

These case reports demonstrate the possible benefit of combining SROM with MMT for long-term opioid agonist maintenance. Clinician and patient self-report narratives included an improved sense of well-being, stability, and reduced fentanyl and other opioid use.

Contexte:

La grande majorité des décès accidentels dus à l’intoxication aux opioïdes au Canada étaient liés au fentanyl en 2022. Le traitement par agoniste opioïde est le meilleur moyen de défense fondé sur des données probantes contre ces décès. Dans l’espoir d’accroître la rétention du traitement par agoniste opioïde (TAO), des lignes directrices récentes ont approuvé l’ajout de morphine orale à libération lente (MOLL) au traitement d’entretien à la méthadone (TEM) comme option à long terme et, de façon non officielle, la pratique commence à s’implanter dans certains cabinets médicaux.

Rapports de cas:

Deux rapports de cas de patients à qui l’on a prescrit simultanément de la MOLL et le TEM pour un traitement d’entretien continu sont présentés et examinés ici.

Discussion:

Ces rapports de cas démontrent les avantages possibles de la combinaison de la MOLL et du TEM pour l’entretien à long terme des agonistes opioïdes. Les récits des cliniciens et des patients comprennent une amélioration du sentiment de bien-être et de stabilité, ainsi qu’une réduction de la consommation de fentanyl et d’autres opioïdes.