Comparison of sleep quality, diet quality, and weight change between COVID-19-recovered patients and healthy controls: A matched case-control study.

Background and Aim: Literature suggests that individuals who have recovered from COVID-19 may experience post-COVID conditions, including sleep problems and alterations in smell or taste. Thus, this study aims to compare the sleep quality, diet quality, and weight change between COVID-19-recovered patients and healthy controls. Methods: A matched case-control study involving young adults aged 18-30 years was conducted in the Klang Valley of Malaysia. The young adults were matched in a 1:1 ratio based on their sociodemographic characteristics, including gender, age, marital status, ethnicity, educational attainment, employment status, and monthly earned income. The Pittsburgh Sleep Quality Index was utilized to evaluate sleep quality, and the Diet Quality for Malaysia was used to determine the diet quality of all young adults. The young adults retrospectively recalled their prepandemic body weight in February 2020, while their current body weight in February 2023 was measured using a TANITA HD-314 digital weighing scale. Results: Emerging findings suggest that sleep quality and weight change were comparable between COVID-19-recovered patients and healthy controls. However, healthy controls were reported to have a more diversified diet than COVID-19-recovered patients. Nevertheless, no significant main effects or interaction effects of sleep and diet quality on weight change were observed in COVID-19-recovered patients or healthy controls. In this study, young adults also reported suffering from sleep deprivation and deficiency due to the pandemic. Conclusion: Intervention programs that emphasize avoiding stimulants before bedtime for healthy controls, promoting the importance of having a diversified and balanced diet among the COVID-19-recovered patients, and achieving an ideal body weight for all young adults should be conducted after the COVID-19 pandemic.

Evaluation of the Fill-it-up-design to use historical control data in randomized clinical trials with two arm parallel group design.

PURPOSE: In the context of clinical research, there is an increasing need for new study designs that help to incorporate already available data. With the help of historical controls, the existing information can be utilized to support the new study design, but of course, inclusion also carries the risk of bias in the study results. METHODS: To combine historical and randomized controls we investigate the Fill-it-up-design, which in the first step checks the comparability of the historical and randomized controls performing an equivalence pre-test. If equivalence is confirmed, the historical control data will be included in the new RCT. If equivalence cannot be confirmed, the historical controls will not be considered at all and the randomization of the original study will be extended. We are investigating the performance of this study design in terms of type I error rate and power. RESULTS: We demonstrate how many patients need to be recruited in each of the two steps in the Fill-it-up-design and show that the family wise error rate of the design is kept at 5 % . The maximum sample size of the Fill-it-up-design is larger than that of the single-stage design without historical controls and increases as the heterogeneity between the historical controls and the concurrent controls increases. CONCLUSION: The two-stage Fill-it-up-design represents a frequentist method for including historical control data for various study designs. As the maximum sample size of the design is larger, a robust prior belief is essential for its use. The design should therefore be seen as a way out in exceptional situations where a hybrid design is considered necessary.

Normative Neuroimaging Library: Designing a Comprehensive and Demographically Diverse Dataset of Healthy Controls to Support Traumatic Brain Injury Diagnostic and Therapeutic Development.

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and socioeconomic categories. Clinicians can only use the results of imaging scans to support their decision-making if they know how the results for their patient compare with a normative standard. This potential for utilizing magnetic resonance imaging (MRI) in TBI diagnosis motivated the American College of Radiology and Cohen Veterans Bioscience to create a reference database of healthy individuals with neuroimaging, demographic data, and characterization of psychological functioning and neurocognitive data that will serve as a normative resource for clinicians and researchers for development of diagnostics and therapeutics for TBI and other brain disorders. The goal of this article is to introduce the large, well-curated Normative Neuroimaging Library (NNL) to the research community. NNL consists of data collected from ∼1900 healthy participants. The highlights of NNL are (1) data are collected across a diverse population, including civilians, veterans, and active-duty service members with an age range (18-64 years) not well represented in existing datasets; (2) comprehensive structural and functional neuroimaging acquisition with state-of-the-art sequences (including structural, diffusion, and functional MRI; raw scanner data are preserved, allowing higher quality data to be derived in the future; standardized imaging acquisition protocols across sites reflect sequences and parameters often recommended for use with various neurological and psychiatric conditions, including TBI, post-traumatic stress disorder, stroke, neurodegenerative disorders, and neoplastic disease); and (3) the collection of comprehensive demographic details, medical history, and a broad structured clinical assessment, including cognition and psychological scales, relevant to multiple neurological conditions with functional sequelae. Thus, NNL provides a demographically diverse population of healthy individuals who can serve as a comparison group for brain injury study and clinical samples, providing a strong foundation for precision medicine. Use cases include the creation of imaging-derived phenotypes (IDPs), derivation of reference ranges of imaging measures, and use of IDPs as training samples for artificial intelligence-based biomarker development and for normative modeling to help identify injury-induced changes as outliers for precision diagnosis and targeted therapeutic development. On its release, NNL is poised to support the use of advanced imaging in clinician decision support tools, the validation of imaging biomarkers, and the investigation of brain-behavior anomalies, moving the field toward precision medicine.

Analytical Methods for Comparing Uncontrolled Trials with External Controls from Real-World Data: a Systematic Literature Review and Comparison to European Regulatory and Health Technology Assessment Practice.

OBJECTIVES: To provide an overview of analytical methods in scientific literature for comparing uncontrolled medicine trials to external controls from individual patient-level real-world data (IPD-RWD). In addition, to compare these methods with recommendations made in guidelines from European regulatory and health technology assessment (HTA) organizations and with their evaluations described in assessment reports. METHODS: A systematic literature review (until March 1st 2023) in PubMed and Connected Papers was performed to identify analytical methods for comparing uncontrolled trials with external controls from IPD-RWD. These methods were compared descriptively to methods recommended in method guidelines and encountered in assessment reports of the European Medicines Agency (2015-2020) and four European HTA organizations (2015-2023). RESULTS: Thirty-four identified scientific articles described analytical methods for comparing uncontrolled trial data to IPD-RWD-based external controls. The various methods covered controlling for confounding and/or dependent censoring, correction for missing data; and analytical comparative modelling methods. Seven guidelines also focused on research design, RWD quality and transparency aspects, and four of those recommended analytical methods for comparisons with IPD-RWD. The methods discussed in regulatory (n=15) and HTA (n=35) assessment reports were often based on aggregate data and lacked transparency due to the few details provided. CONCLUSION: Literature and guidelines suggest a methodological approach to comparing uncontrolled trials with external controls from IPD-RWD similar to target trial emulation, using state-of-the-art methods. External controls supporting regulatory and HTA decision-making were rarely in line with this approach. Twelve recommendations are proposed to improve the quality and acceptability of these methods.

Essential/precursor chemical control research: Giommoni's review, understanding multi-replication interrupted time series analysis, and next steps.

Controls on essential/precursor chemicals from commercial companies have been associated with many large downturns in illicit drug markets and attendant problems. My colleagues and I brought this to light in the studies that are the subject of Giommoni's review. McKetin et al. in an earlier review considered several of our studies on chemical controls for methamphetamine, all centered in North America. Giommoni discusses not only those studies but also our later work on chemical controls for cocaine and heroin. This later work evaluates US essential/precursor chemical policies targeting illicit drug producers outside of North America, and it examines impacts on illicit drug availability and use (the studies reviewed by McKetin et al. predominantly focused on outcomes such as drug-related hospitalizations, arrests, and treatment). Giommoni's review is a new resource that will help make the varied topics in essential/precursor chemical control research more accessible to many readers. After noting this, I discuss some common methodological misconceptions about our studies. For example, our studies generally used multi-replication interrupted time series analysis, a research design among the most powerful of all quasi-experimental designs. Authors, however, typically discuss the studies as if they used single-intervention interrupted time series analysis, a less powerful design. Multi-replication and single-intervention interrupted time series analyses also differ regarding likely confounders; awareness of this is critical to accurately assessing our findings and critiquing alternative explanations. Finally, I note that commercial chemical companies function as the silent, albeit usually unwitting, partners in the large-scale production of several illicit drugs, including fentanyl. And many governments are implementing essential/precursor chemical controls to help stymie this partnership. But they are doing so largely without evaluation and study-a poor policy practice. To remedy this, I suggest establishing multi-disciplinary applied research teams to help assess, guide and improve essential/precursor chemical control efforts.

Decoding Seafood: Multi-Marker Metabarcoding for Authenticating Processed Seafood.

Given the recognized nutritional value of fish and shifting consumer lifestyles, processed seafood has become increasingly prevalent, comprising a significant portion of global food production. Although current European Union labeling regulations do not require species declaration for these products, food business operators often voluntarily provide this information on ingredient lists. Next Generation Sequencing (NGS) approaches are currently the most effective methods for verifying the accuracy of species declarations on processed seafood labels. This study examined the species composition of 20 processed seafood products, each labeled as containing a single species, using two DNA metabarcoding markers targeting the mitochondrial cytochrome c oxidase I (COI) and 16S rRNA genes. The combined use of these markers revealed that the majority of the products contained multiple species. Furthermore, two products were found to be mislabeled, as the declared species were not detected. These findings underscore that NGS is a robust technique that could be adopted to support routine food industry activities and official control programs, thereby enhancing the 'From Boat to Plate' strategy and combating fraudulent practices in the complex fisheries supply chain.

A fractional-order model for optimizing combination therapy in heterogeneous lung cancer: integrating immunotherapy and targeted therapy to minimize side effects.

This research presents a novel approach to address the complexities of heterogeneous lung cancer dynamics through the development of a Fractional-Order Model. Focusing on the optimization of combination therapy, the model integrates immunotherapy and targeted therapy with the specific aim of minimizing side effects. Notably, our approach incorporates a clever fusion of Proportional-Integral-Derivative (PID) feedback controls alongside the optimization process. Unlike previous studies, our model incorporates essential equations accounting for the interaction between regular and mutated cancer cells, delineates the dynamics between immune cells and mutated cancer cells, enhances immune cell cytotoxic activity, and elucidates the influence of genetic mutations on the spread of cancer cells. This refined model offers a comprehensive understanding of lung cancer progression, providing a valuable tool for the development of personalized and effective treatment strategies. the findings underscore the potential of the optimized treatment strategy in achieving key therapeutic goals, including primary tumor control, metastasis limitation, immune response enhancement, and controlled genetic mutations. The dynamic and adaptive nature of the treatment approach, coupled with economic considerations and memory effects, positions the research at the forefront of advancing precision and personalized cancer therapeutics.

Analysis of Nonconcurrent Controls in Adaptive Platform Trials: Separating Randomized and Nonrandomized Information.

Adaptive platform trials allow treatments to be added or dropped during the study, meaning that the control arm may be active for longer than the experimental arms. This leads to nonconcurrent controls, which provide nonrandomized information that may increase efficiency but may introduce bias from temporal confounding and other factors. Various methods have been proposed to control confounding from nonconcurrent controls, based on adjusting for time period. We demonstrate that time adjustment is insufficient to prevent bias in some circumstances where nonconcurrent controls are present in adaptive platform trials, and we propose a more general analytical framework that accounts for nonconcurrent controls in such circumstances. We begin by defining nonconcurrent controls using the concept of a concurrently randomized cohort, which is a subgroup of participants all subject to the same randomized design. We then use cohort adjustment rather than time adjustment. Due to flexibilities in platform trials, more than one randomized design may be in force at any time, meaning that cohort-adjusted and time-adjusted analyses may be quite different. Using simulation studies, we demonstrate that time-adjusted analyses may be biased while cohort-adjusted analyses remove this bias. We also demonstrate that the cohort-adjusted analysis may be interpreted as a synthesis of randomized and indirect comparisons analogous to mixed treatment comparisons in network meta-analysis. This allows the use of network meta-analysis methodology to separate the randomized and nonrandomized components and to assess their consistency. Whenever nonconcurrent controls are used in platform trials, the separate randomized and indirect contributions to the treatment effect should be presented.

An overview of Synlab SDN Biobank's quality control system.

Biobanks are valuable service units that ensure the usage of high-quality biological samples. They contribute to translational research, and their support may improve future therapeutic approaches. They store biological samples that can be used to examine circulation biomarkers, immune cells, and immunohistochemistry aspects of illnesses and further in-depth examinations using NGS techniques. The IRCCS Synlab SDN Biobank has about 70,000 well-preserved cryopreserved human samples from various diseases, primarily oncological but also neurological and cardiovascular. These biospecimens were taken from 25,000 participants underwent imaging with a contrast agent. The goal is to propose quality control assays that meet the requirements of the international standard ISO 9001:2015 and ISO 20387:2020 accreditation. PBMCs viability was determined, and immune subset cells were analyzed by flow cytometry. Furthermore, the expression of ubiquitous miRNAs was used to assess plasma sample integrity. The quality controls demonstrated that the biological samples were correctly cryopreserved; the preservation of human biological samples did not affect the quality of the biological samples tested. Indeed, the cryopreserved PBMCs had a vitality of more than 80%, and the lymphocyte subsets could be selected for future immune cell investigations. Furthermore, miRNA expression was highest in thawed plasma samples compared to the positive and negative controls. We evaluated the quality of our randomly selected biobank-thawed human samples. Both PBMCs and plasma samples fulfill the high-quality standards needed for biomedical research, assuring their long-term preservation. However, further research is needed in the biobanking field to establish globally accepted procedures to confirm the quality of biological samples.

Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients.

Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44-0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69-2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54-0.60), hospitalizations (RR 0.40, 95% CI: 0.36-0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21-0.36). Conclusions: GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety.

Treatment Comparisons in Adaptive Platform Trials Adjusting for Temporal Drift.

An adaptive platform trial (APT) is a multi-arm trial in the context of a single disease where treatment arms are allowed to enter or leave the trial based on some decision rule. If a treatment enters the trial later than the control arm, there exist non-concurrent controls who were not randomized between the two arms under comparison. As APTs typically take long periods of time to conduct, temporal drift may occur, which requires the treatment comparisons to be adjusted for this temporal change. Under the causal inference framework, we propose two approaches for treatment comparisons in APTs that account for temporal drift, both based on propensity score weighting. In particular, to address unmeasured confounders, one approach is doubly robust in the sense that it remains valid so long as either the propensity score model is correctly specified or the time effect model is correctly specified. Simulation study shows that our proposed approaches have desirable operating characteristics with well controlled type I error rates and high power with or without unmeasured confounders.

Biogeochemical controls on methylmercury distribution in a subtropical wetland ecosystem.

Wetlands are widely regarded as biogeochemical hotspots of mercury methylation but little is known regarding such roles of mangrove forests. Here, we examined the detailed depth profile of mercury, methylmercury, and organic matter in surface sediments within an estuarine pond at Mai Po Nature Reserve in Hong Kong, China. There is a progressive enrichment of organic matter in sites closer to mangrove forests, and methylmercury showed a significantly positive correlation with organic matter content (p < 0.001). Methylmercury in sediments is significantly (p < 0.05) higher in the summertime when the temperature is elevated but salinity is reduced. Further, sediments at or near the mangrove forest have lower carbon to nitrogen ratio, which may imply more labile organic matter in these organic-rich sediments that can promote microbial mercury methylation. In summary, mangrove forests can enhance net methylmercury production and increase the risk to the migratory birds overwintering in this internationally important wetland.

Developing an institutional control framework for contaminated sites in China: An analytical case study.

Institutional controls, as an important measure for risk management of contaminated sites, is widely used in site management by the United States, Canada and European countries. At present, some regions in China have also begun to explore the implementation of institutional controls, but its path, safeguard mechanism, and tracking evaluation are still unclear. Based on China's unique contaminated site remediation control system and land management system, this paper proposes a framework for the whole life cycle institutional controls of China's contaminated sites: (1) evaluate the need for institutional controls; (2) establish the objectives of institutional controls; (3) identify the restrictive requirements of institutional controls; (4) establish the implementation form of institutional controls; and (5) regularly review the effectiveness of institutional controls. To demonstrate the applicability of the institutional control framework, a case demonstration study was conducted at a petrochemical contaminated site in China. By analyzing the information on residual pollutants after the implementation of risk management measures at the site, the exposure pathways and hazards in case of re-release, and the engineering facilities, we proposed eight restrictive requirements, including the prohibition of disturbing and damaging the clean and planted soil layers of the site and the protection of long-term monitoring wells. At the same time, we constructed a multi-departmental pathway to implement institutional controls in conjunction with ecological environment, natural resources and housing departments to ensure effective implementation of institutional controls. Eventually, we summarized a set of replicable and generalizable institutional controls application models, which provide valuable theoretical and practical support for China and other local governments in the implementation of institutional controls at contaminated sites.

NLP-based ergonomics MSD risk root cause analysis and risk controls recommendation.

An ergonomics assessment of the physical risk factors in the workplace is instrumental in predicting and preventing musculoskeletal disorders (MSDs). Using Artificial Intelligence (AI) has become increasingly popular for ergonomics assessments because of the time savings and improved accuracy. However, most of the effort in this area starts and ends with producing risk scores, without providing guidance to reduce the risk. This paper proposes a holistic job improvement process that performs automatic root cause analysis and control recommendations for reducing MSD risk. We apply deep learning-based Natural Language Processing (NLP) techniques such as Part of Speech (PoS) tagging and dependency parsing on textual descriptions of the physical actions performed in the job (e.g. pushing) along with the object (e.g. cart) being acted upon. The action-object inferences provide the entry point to an expert-based Machine Learning (ML) system that automatically identifies the targeted work-related causes (e.g. cart movement forces are too high, due to caster size too small) of the identified MSD risk (e.g. excessive shoulder forces). The proposed framework utilises the root causes identified to recommend control strategies (e.g. provide larger diameter casters, minimum diameter 8" or 203 mm) most likely to mitigate risk, resulting in a more efficient and effective job improvement process.

We propose an ergonomics framework that identifies the root causes of MSD risk and recommends control actions. A key insight exploited using artificial intelligence is that when the estimated risk is high for a body joint, the actions of the worker in question and the associated objects constitute valuable information.

Metabolic syndrome and associated factors among H. pylori-infected and negative controls in Northeast Ethiopia: a comparative cross-sectional study.

Background: The prevalence of metabolic syndrome (MetS) in patients infected with Helicobacter pylori, and the factors associated with it are not well understood. This study evaluates MetS and its associated factors among both H pylori-positive and H pylori-negative individuals in Northeast Ethiopia. Methods: A cross-sectional study was conducted between 1 March 2022 to 30 May 2022. A semi-structured questionnaire was used to collect data on sociodemographic, behavioral, and clinical variables. A total of 228 subjects were randomly selected. Blood and stool samples were collected from each subject to measure fasting blood glucose and lipid profiles, and to identify H. pylori infection. Data were entered into Epi. Data 3.1 and analyzed using SPSS version 25. Logistic regression analysis and the Mann-Whitney U-test were performed to determine associated factors and compare median and interquartile ranges. Results: Of the 228 participants, 114 were H. pylori positive, and 114 were H. pylori negative. Participants (50.9% female) ranged in age from 18 years to 63 years, with a median age of 31 (IQR, 22, 40) years. The overall prevalence of MetS among the participants was 23.2%. We found a statistically significant association between MetS and fasting blood glucose level (AOR, 15.965; 95% CI, 7.605-33.515, p<0.001). Furthermore, there was a statistically significant difference in the median serum levels of low-density lipoprotein cholesterol (p<0.001), triglycerides (p=0.036), systolic blood pressure (<0.001), and total cholesterol (p<0.001) between H. pylori-positive and H. pylori-negative participants. Conclusion: MetS was prevalent among study participants. There was also a statistically significant association between fasting blood sugar and MetS. In addition, systolic blood pressure, total cholesterol, triglycerides, and low-density lipoprotein levels were significantly different between H. pylori-positive and H. pylori-negative individuals.

Optimal control analysis for the Nipah infection with constant and time-varying vaccination and treatment under real data application.

In the last two decades, Nipah virus (NiV) has emerged as a significant paramyxovirus transmitted by bats, causing severe respiratory illness and encephalitis in humans. NiV has been included in the World Health Organization's Blueprint list of priority pathogens due its potential for human-to-human transmission and zoonotic characteristics. In this paper, a mathematical model is formulated to analyze the dynamics and optimal control of NiV. In formulation of the model we consider two modes of transmission: human-to-human and food-borne. Further, the impact of contact with an infected corpse as a potential route for virus transmission is also consider in the model. The analysis identifies the model with constant controls has three equilibrium states: the NiV-free equilibrium, the infected flying foxes-free equilibrium, and the NiV-endemic equilibrium state. Furthermore, a theoretical analysis is conducted to presents the stability of the model equilibria. The model fitting to the reported cases in Bangladesh from 2001 to 2015, and the estimation of parameters are performed using the standard least squares technique. Sensitivity analysis of the model-embedded parameters is provided to set the optimal time-dependent controls for the disease eradication. The necessary optimality conditions are derived using Pontryagin's maximum principle. Finally, numerical simulation is performed to determine the most effective strategy for disease eradication and to confirm the theoretical results.

Considerations on Design and Analysis of External Control in Pediatric Oncology.

Pediatric cancer consists of a diverse group of rare diseases. Due to limited patient populations, standard randomized and controlled trials are often infeasible. As a result, single-arm trials are common in pediatric oncology and the use of external controls is often desirable or necessary to help generate actionable evidence and contextualize trial results. In this paper, we illustrate unique features in pediatric oncology clinical trials and describe their impact on the use of external controls. Various types of relevant external control data sources are described in terms of their utility and drawbacks. Statistical methodologies and design implications with external control are discussed. Two recent case studies using external controls to support pediatric oncology drug development are described in detail.

The Total Worker Health® (TWH) approach: a systematic review of its application in different occupational settings.

BACKGROUND: The National Institute for Occupational Safety and Health (NIOSH), in 2011, developed the "Total Worker Health®" (TWH) as a holistic approach to protect and promote the workers' safety, health, and well-being. After over ten years from the TWH development, the aim of the present systematic review is to provide a comprehensive overview of the worldwide TWH initiatives. METHODS: PubMed, Scopus and ISI Web of Science were searched for TWH studies published up to the 31st of July 2023, and 43 investigations could be included. The review was registered on the International prospective register of systematic reviews PROSPERO with the reference number CRD42023416972. RESULTS: Issues that emerged as relevant for the TWH operationalization were the awareness about the TWH approach and fundamentals, the leadership commitment, and a participatory engagement of the workforce: these aspects all contributed to acceptable and effective setting oriented TWH plans, specifically tailored on the peculiarities of the workplace, including small enterprises and multiemployer worksites. Evaluation and continual improvement were reported as fundamental for the successful implementation of TWH initiatives. Limited resources for safety and health initiatives, in terms of time, people, and funds, together with difficulties in the identification of safety and health priorities and a poor participatory culture were recognized as obstacles to the TWH application. Training resulted the core component of the TWH leadership and workforce preparedness, with beneficial results in terms of safety culture and adoption of preventive measures. CONCLUSIONS: Although interesting aspects emerged from our review, future longitudinal investigations should confirm the effectiveness, easy integration, and long-term sustainability of TWH models in different workplaces, in order to effectively support safe and health-enhancing works able to improve innovation and productivity.

Integrated On-Slide Positive Controls for Immunocytochemistry on Cytology Slides.

INTRODUCTION: Integrated on-slide positive controls are a standard quality assurance and quality control measure for immunohistochemistry on formalin-fixed paraffin-embedded tissue sections. They ensure identical analytical conditions for the control and patient samples. Our aim was to develop a procedure for preparing integrated on-slide positive controls for immunocytochemistry (ICC) on methanol-fixed cytospins. METHODS: Leftover diagnostic cytology samples with sufficient cells and confirmed expression of Calretinin, MOC31, TTF1, and hormone receptors were used as control samples. Cells from the control samples were deposited on the peripheral part of objective slides using standard cytocentrifuge equipment. Cytospins were immediately fixed in methanol for at least 30 min and then covered with polyethylene glycol (PEG). Completely dry and solid PEG was removed from the central part of the objective slides and stored at room temperature. Patient samples were subsequently added to the central part of a PEG-protected slide, with an appropriate positive control placed on the peripheral part, and then fixed in methanol. ICC was performed on the Ventana/Roche automated platform ULTRA, using optimized and validated protocols for TTF1, hormone receptors, and double immunostaining for Calretinin/MOC31. The quality of ICC reactions for both deposits on the same slide and potential cell carryover was evaluated retrospectively. RESULTS: In the period from October 2021 to December 2023, the majority of integrated positive controls (364/368, 99%) consistently exhibited unequivocally positive reactions for TTF-1 (n = 93), hormone receptors (n = 84), and double staining for Calretinin/MOC31 (n = 191), with easily interpretable ICC reactions on corresponding patient samples. No obvious carryover of cells from the control sample to the patient sample was observed during this period. CONCLUSION: A novel approach developed for preparing integrated on-slide positive controls for ICC on methanol-fixed cytospins using standard cytocentrifugation is low-cost and can be widely applied in diagnostic cytology laboratories. Simultaneous ICC procedures for the control and patient samples on the same slide ensure identical analytical conditions for both samples, providing the highest level of quality control while reducing costs. Interpreting both ICC reactions on the same slide is time-efficient and convenient.

High-Performance Bifunctional Electrocatalysts for Flexible and Rechargeable Zn-Air Batteries: Recent Advances.

Flexible rechargeable Zn-air batteries (FZABs) exhibit high energy density, ultra-thin, lightweight, green, and safe features, and are considered as one of the ideal power sources for flexible wearable electronics. However, the slow and high overpotential oxygen reaction at the air cathode has become one of the key factors restricting the development of FZABs. The improvement of activity and stability of bifunctional catalysts has become a top priority. At the same time, FZABs should maintain the battery performance under different bending and twisting conditions, and the design of the overall structure of FZABs is also important. Based on the understanding of the three typical configurations and working principles of FZABs, this work highlights two common strategies for applying bifunctional catalysts to FZABs: 1) powder-based flexible air cathode and 2) flexible self-supported air cathode. It summarizes the recent advances in bifunctional oxygen electrocatalysts and explores the various types of catalyst structures as well as the related mechanistic understanding. Based on the latest catalyst research advances, this paper introduces and discusses various structure modulation strategies and expects to guide the synthesis and preparation of efficient bifunctional catalysts. Finally, the current status and challenges of bifunctional catalyst research in FZABs are summarized.