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Abstract Purpose Formal coercion in psychiatry is widely studied yet much less is known about pressures patients may experience, partly because of the very few measures available. The goal of this study was to validate the P-PSY35 (Pressures in Psychiatry Scale) and provide a paper-and-pencil and a computerised adaptive test (CAT) to measure pressures experienced by patients in psychiatry. Methods The P-PSY35 items were developed with users. Patients were evaluated during psychiatric hospitalisation or through an online survey. Mokken scale analysis and Item response theory (IRT) were used to select and estimate the items parameters. A Monte-Carlo simulation was performed to evaluate the number of items needed to transform the paper-and-pencil test into a reliable psychometric CAT. Results A total of 274 patients were assessed. The P-PSY35 demonstrated good internal validity, internal consistency, convergent and divergent validity. The P-PSY35 could be substantially shortened while maintaining excellent reliability using the CAT procedure. Conclusion The P-PSY35 was developed in collaboration with users. It is a psychometrically rigorous tool designed to measure experienced pressures in French-language. The development and successful validation of the P-PSY35 represent a welcome step towards implementing and evaluating programs aimed at reducing negative consequences of coercion.

Abstract Background In low-middle income countries, healthcare providers primarily use paper health records for capturing data. Paper health records are utilized predominately due to the prohibitive cost of acquisition and maintenance of automated data capture devices and electronic medical records. Data recorded on paper health records is not easily accessible in a digital format to healthcare providers. The lack of real time accessible digital data limits healthcare providers, researchers, and quality improvement champions to leverage data to improve patient outcomes. In this project, we demonstrate the novel use of computer vision software to digitize handwritten intraoperative data elements from smartphone photographs of paper anesthesia charts from the University Teaching Hospital of Kigali. We specifically report our approach to digitize checkbox data, symbol-denoted systolic and diastolic blood pressure, and physiological data. Methods We implemented approaches for removing perspective distortions from smartphone photographs, removing shadows, and improving image readability through morphological operations. YOLOv8 models were used to deconstruct the anesthesia paper chart into specific data sections. Handwritten blood pressure symbols and physiological data were identified, and values were assigned using deep neural networks. Our work builds upon the contributions of previous research by improving upon their methods, updating the deep learning models to newer architectures, as well as consolidating them into a single piece of software. Results The model for extracting the sections of the anesthesia paper chart achieved an average box precision of 0.99, an average box recall of 0.99, and an mAP0.5-95 of 0.97. Our software digitizes checkbox data with greater than 99% accuracy and digitizes blood pressure data with a mean average error of 1.0 and 1.36 mmHg for systolic and diastolic blood pressure respectively. Overall accuracy for physiological data which includes oxygen saturation, inspired oxygen concentration and end tidal carbon dioxide concentration was 85.2%. Conclusions We demonstrate that under normal photography conditions we can digitize checkbox, blood pressure and physiological data to within human accuracy when provided legible handwriting. Our contributions provide improved access to digital data to healthcare practitioners in low-middle income countries.

Abstract Background In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. Main body Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. Conclusion Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

Abstract Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

Abstract Numerous researchers and institutions have been developing in ovo sexing technologies to improve animal welfare by identifying male embryos in an early embryonic stage and disposing of them before pain perception. This review gives a complete overview of the technological approaches reported in papers and patents by performing a thorough search using Web of Science and Patstat/Espacenet databases for papers and patents, respectively. Based on a total of 49 papers and 115 patent families reported until May 2023 worldwide, 11 technology categories were defined: 6 non-optical and 5 optical techniques. Every category was described for its characteristics while assessing its potential for application. Next, the dynamics of the publications of in ovo sexing techniques in both paper and patent fields were described through growth curves, and the interest or actual status was visualized using the number of paper citations and the actual legal status of the patents. When comparing the reported technologies in papers to those in patents, scientific gaps were observed, as some of the patented technologies were not reported in the scientific literature, e.g., ion mobility and mass spectrometry approaches. Generally, more diverse approaches in all categories were found in patents, although they do require more scientific evidence through papers or industrial adoption to prove their robustness. Moreover, although there is a recent trend for non-invasive techniques, invasive methods like analyzing DNA through PCR or hormones through immunosensing are still being reported (and might continue to be) in papers and patents. It was also observed that none of the technologies complies with all the industry requirements, although 5 companies already entered the market. On the one hand, more research and harmony between consumers, industry, and governments is necessary. On the other hand, close monitoring of the market performance of the currently available techniques will offer valuable insights into the potential and expectations of in ovo sexing techniques in the poultry industry.

Abstract Adverse Outcome Pathways (AOPs) have been proposed to facilitate mechanistic understanding of interactions of chemicals/materials with biological systems. Each AOP starts with a molecular initiating event (MIE) and possibly ends with adverse outcome(s) (AOs) via a series of key events (KEs). So far, the interaction of engineered nanomaterials (ENMs) with biomolecules, biomembranes, cells, and biological structures, in general, is not yet fully elucidated. There is also a huge lack of information on which AOPs are ENMs-relevant or -specific, despite numerous published data on toxicological endpoints they trigger, such as oxidative stress and inflammation. We propose to integrate related data and knowledge recently collected. Our approach combines the annotation of nanomaterials and their MIEs with ontology annotation to demonstrate how we can then query AOPs and biological pathway information for these materials. We conclude that a FAIR (Findable, Accessible, Interoperable, Reusable) representation of the ENM-MIE knowledge simplifies integration with other knowledge. Scientific contribution This study introduces a new database linking nanomaterial stressors to the first known MIE or KE. Second, it presents a reproducible workflow to analyze and summarize this knowledge. Third, this work extends the use of semantic web technologies to the field of nanoinformatics and nanosafety.

Abstract Background In line with the impetus traceable among the nursing staff, studies regarding the perception of Unfinished Care among students have increased in recent years as also recommended by some policy documents in the consideration that, as future members of the staff, they are expected to raise concerns about failures in the standards of care. However, no discussion of their methodological requirements has been provided to date. The aim of this study is to debate Unfinished Care explorations among nursing students and developing recommendations. Methods A Rapid Review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, followed by a scientific discussion based on empirical evidence that emerged from the review combined with expert knowledge. Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases were searched up to May 2022. Results In the last five years, seven studies have been conducted by researchers affiliated at the university level, involving from 18 to 737 undergraduate students across Europe. By critically analysing their key aspects, there are derived some recommendations in conducting investigations in this field as, (a) the hidden meaning of Unfinished Care investigations among students by also deciding which concept is mostly appropriate to investigate; (b) the need of establishing alliances with the clinical settings in order to involve them in such explorations; (c) more complex research methods capable of exploring this issue among students by promoting learning outcomes and not only a simple data collection; and (e) the influences of these explorations on students’ wellbeing, as well as on ethical implications and that regarding the relationship between the healthcare services and the universities. Conclusion Policymakers consider students to be key informants of the quality of nursing care issues witnessed during their clinical placements. The related emerging line of research is intriguing because of the underlying methodological, ethical and system complexities that need to be addressed according to some considerations.

Abstract Background Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. Objective This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. Methods We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students’ perceptions and experiences. Results The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. Conclusions Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. Trial Registration Retrospectively registered.

Abstract Background Workers in pulp and paper factories are continuously exposed to paper dust. Excessive exposure to paper dust can cause respiratory disease. Information about the prevalence of chronic respiratory symptoms and dust exposure levels among workers in pulp and paper factories is not available in Ethiopia. The aim of this study was, therefore, to assess personal total dust exposure levels, the prevalence of chronic respiratory symptoms and their associated risk factors among workers in Ethiopian pulp and paper factories. Methods A comparative cross-sectional study was conducted. A total of 40 dust measurements were carried out on 20 randomly selected workers. To assess chronic respiratory symptoms and associated factors, 434 workers from two paper factories and controls were interviewed using a standard questionnaire adapted from the American Thoracic Society (ATS). Gravimetric analyses of the filters were undertaken using a standard microbalance. Poisson regression was performed for comparing the prevalence of symptoms and risk factors for the two groups. Multivariable analyses were conducted to identify factors associated with chronic respiratory symptoms. Result The arithmetic mean (AM) and geometric mean (GM) of dust exposure levels among the paper factories workers were 11.3 (± 7.7) and 10.2 (± 1.4) mg/m3 respectively. This exposure level exceeded the threshold limit value recommended for total dust (10 mg/m3). The prevalence of having at least one chronic respiratory symptom was about 51% among the workers in paper factories. The prevalence ratio of having chronic respiratory symptoms among paper factory workers was 5.6 times higher (PR = 6, 95% CI 3.5–10.3) than in the controls. Chronic respiratory symptoms were significantly associated with factors such as an educational status of less than grade 9, being employed in the work sections of the factories, having work experience of 5 years and above, working more than 8 h per day and having a past history of occupation and respiratory illnesses. Conclusion The dust concentration in the paper factories exceeded the acceptable recommended limit value of 10 mg/m3. The prevalence of chronic respiratory symptoms among paper factory workers was higher than among controls. The main determining factors for chronic respiratory symptoms among the workers were the specific work section such as production section, low income, having past history of respiratory illnesses, the number of years of working and low educational status. This finding indicated the need for improving the working conditions in paper factories in Ethiopia.

Abstract Background As the older population increases, the need for early detection of cognitive decline is also increasing. In this study, we examined whether our paper–pencil type group examination for cognitive assessment (PAPLICA) could detect the effects of years of education and aging. Methods PAPLICA was conducted on 829 older people. The inclusion criteria were age 60 years or older and the ability to come to the event site alone. The exclusion criteria were participants with a medical or psychiatric disorder or dementia.One examiner conducted the test on a group of approximately 10–20 people in approximately 25 min. Participants were instructed on tackling the issues projected on the projector, and their answers were recorded in a response booklet. Results An independent sample t-test was performed for years of education, and ANCOVA was performed for aging. Among the test items included in PAPLICA, the Speed I and Letter fluency tests were unable to detect the effects of aging. Furthermore, the age at which the effect of aging manifests varies depending on the test item. For instance, a decline in scores in the Speed I and Picture ECR Free recall tests was observed in the 70–74 age group; for that of Word DRT, Picture ECR cued recall, and Similarity, in the 75–79 age group; for CFT, in the 80–84 age group, and for CLOX, the decline was observed in the 85 ≤ age group. Conclusions PAPLICA, similar to other neuropsychological tests, was able to detect the effects of years of education and aging. Future testing should be conducted on different demographics to identify the differences in patterns of cognitive decline.

Abstract Kidney stones, a persistent urological condition, continue to affect people globally. In this critical review, we examine the work of Borghi et al. who evaluated patients with idiopathic stone formation and randomised 99 patients to increased water intake (≥ 2 L/day) and 100 patients to usual care in a 5-year randomized controlled trial. The study examined baseline urine volume in individuals with idiopathic calcium stones, recurrence rates, and relevant biochemical factors. The study found reduced recurrence rate (12.1% vs. 27% (p = 0.008)), and time to recurrence with increased water intake (38.7 ± 13.2 months) vs. (25 ± 16.4 months) (p = 0.016). These findings inform clinical practice, contributing to the guideline recommendations that kidney stone patients should aim for fluid intake of at least 2.5 L per day to prevent stone recurrence.

Abstract Background The advent of Personalized Medicine (PM) holds significant promise in revolutionizing healthcare by tailoring treatments to individual patients based on their data. However, its successful implementation requires the seamless integration of innovative technologies and presents formidable challenges in terms of sustainability. To tackle these challenges head-on, the International Consortium for Personalized Medicine (ICPerMed) was established, and the IC2PerMed project, as part of this consortium, seeks to foster collaboration between the European Union (EU) and China in the field of Personalized Medicine. Based on the results collected by the project, the objective of this study is to discern the key priorities for the implementation of Personalised Medicine concerning Information and Communication Technologies (ICT) and Big Data and digital solutions, with a particular emphasis on data management and protection. Methods A Delphi survey was conducted to gather expert’s consensus on the main priorities for actions on Information and Communication Technologies (ICT) and Big Data and digital solutions in the field of Personalized Medicine. Results The survey identified seven priorities in the area of Big Data and digital solutions, including data interoperability, standards, security measures, and international partnerships. Additionally, twelve priorities were identified for the innovation-to-market process, emphasizing cost-effectiveness, need assessment, and value definition in resource allocation. Conclusions The effective implementation of new technologies in Personalized Medicine research and practice is essential for the advancement of healthcare systems in both the European and Chinese contexts. The identified priorities play a pivotal role in promoting the sustainability of health systems and driving innovation in the implementation of Personalized Medicine. Addressing challenges related to data interoperability, standards, security, international collaboration, cost-effectiveness, and value assessment is of utmost importance in order to propel the progress of Personalized Medicine in healthcare systems.

Abstract In this critical review, we explore the study design, strengths and limitations of the paper: “Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial.” The paper reports 24 month follow-up data of the landmark ROSETTA trial. This multi-centre, open-labelled parallel randomised trial allocated females 1:1 to receive Sacral Neuromodulation (SNM) or OnabotulinumtoxinA(BTX) 200 units (U). The primary outcome was change in mean daily urinary urgency incontinence episodes (UUIE) over 24 months. The study did not demonstrate a difference between treatments (-3.88 vs. -3.50 episodes per day), however women treated with BTX were more satisfied; but reported higher rates of UTI. The two treatments provide comparable third-line treatment options for patients with refractory urgency urinary incontinence.

Abstract Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients’ outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

Abstract Background Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a ‘forgotten drug’ and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common “misconceptions” and “stereotypes” associated with lithium treatment; we also provide a list of “good reasons” for using lithium in ordinary clinical practice to overcome those false myths. Main text A narrative search of the available literature has been performed entering the following keywords: “bipolar disorder”, “lithium”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding”. The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients’ groups suffering from bipolar disorder; (3) Drug–drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. Conclusions In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Abstract The South West Oncology Group’s 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear. Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy. Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35–49) RFS at five years in the control arm and 60% RFS (53–67 95% CI) in the maintenance arm (p

Abstract Impact Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes. Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease. Methods An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics. Results Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value

Abstract Background Broussonetia papyrifera (L.) L’Hér. ex Vent. has the characteristics of strong stress resistance, high crude protein content, and pruning tolerance. It is an ecological, economic, and medicinal plant. Polyploid plants usually perform better than their corresponding diploid plants in terms of nutrients, active substances, and stress resistance. Results In this study, the leaves, calli, and seeds of diploid B. papyrifera were used for tetraploid induction by colchicine. The induction effect of colchicine on B. papyrifera was summarized through the early morphology, chromosome count and flow cytometry. It was concluded that the best induction effect (18.6%) was obtained when the leaves of B. papyrifera were treated in liquid MS (Murashige and Skoog) medium containing 450 mg·L-1 colchicine for 3 d. The comparative analysis of the growth characteristics of diploid and tetraploid B. papyrifera showed that tetraploid B. papyrifera has larger ground diameter, larger stomata, thicker palisade tissue and thicker sponge tissue than diploid B. papyrifera. In addition, the measurement of photosynthetic features also showed that tetraploids had higher chlorophyll content and higher photosynthetic rates. Conclusion This study showed that tetraploid B. papyrifera could be obtained by treating leaves, callus and seeds with liquid and solid colchicine, but the induction efficiency was different. Moreover, there were differences in stomata, leaf cell structure and photosynthetic features between tetraploid B. papyrifera and its corresponding diploid. The induced tetraploid B. papyrifera can provide a technical basis and breeding material for the creation of B. papyrifera germplasm resources in the future.

Abstract Background An estimated 11 million individuals are released from U.S. jails and prisons each year. Individuals with a history of incarceration have higher rates of cardiovascular disease (CVD) events and mortality compared to the general population, especially in the weeks following release from carceral facilities. Healthy sleep, associated with cardiovascular health, is an underexplored factor in the epidemiology of CVD in this population. Incarcerated people may have unique individual, environmental, and institutional policy-level reasons for being sleep deficient. The social and physical environment within carceral facilities and post-release housing may synergistically affect sleep, creating disparities in sleep and cardiovascular health. Since carceral facilities disproportionately house poor and minoritized groups, population-specific risk factors that impact sleep may also contribute to inequities in cardiovascular outcomes. Methods This study is ancillary to an ongoing prospective cohort recruiting 500 individuals with known cardiovascular risk factors within three months of release from incarceration, the Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE) study. The Sleep Justice study will measure sleep health among participants at baseline and six months using three validated surveys: the Pittsburgh Sleep Quality Index (PSQI), the STOP-Bang, and the Brief Index of Sleep Control. In a subsample of 100 individuals, we will assess sleep over the course of one week using wrist actigraphy, a validated objective measure of sleep that collects data on rest-activity patterns, sleep, and ambient light levels. Using this data, we will estimate and compare sleep health and its association with CVD risk factor control in individuals recently released from carceral facilities. Discussion The incarceration of millions of poor and minoritized groups presents an urgent need to understand how incarceration affects CVD epidemiology. This study will improve our understanding of sleep health among people released from carceral facilities and its potential relationship to CVD risk factor control. Using subjective and objective measures of sleep will allow us to identify unique targets to improve sleep health and mitigate cardiovascular risk in an otherwise understudied population.

Abstract Network meta-analysis compares multiple interventions and estimates the relative treatment effects between all interventions, combining both direct and indirect evidence. Recently, a framework was developed to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) which is part of the more comprehensive framework to evaluate the Confidence In the evidence for Network Meta-Analysis (CINeMA). To produce an overall risk of bias judgement for each network estimate, ROB-MEN: performs an assessment of the bias due to missing evidence in each possible pairwise comparison; combines the assessment with the contribution from the direct pairwise comparisons; considers the potential for small-study effects. To facilitate and semi-automate this process, ROB-MEN has been implemented in a user-friendly web-application ( https://cinema.ispm.unibe.ch/rob-men ). Here we provide a tutorial detailing the functionality and use of the application consisting of data upload, analysis configuration, output visualisation, and production of the tool’s output tables for recording the risk of bias assessment. We also illustrate an example application using the demo dataset available for download on the application’s homepage. The ROB-MEN web-application is open-source and freely available ( https://github.com/esm-ispm-unibe-ch/rob-men ).

Abstract Background Laccase-based biosensors are efficient for detecting phenolic compounds. However, the instability and high cost of laccases have hindered their practical utilization. Results In this study, we developed hierarchical manganese dioxide–copper phosphate hybrid nanoflowers (H–Mn–Cu NFs) as excellent laccase-mimicking nanozymes. To synthesize the H–Mn–Cu NFs, manganese dioxide nanoflowers (MnO2 NFs) were first synthesized by rapidly reducing potassium permanganate using citric acid. The MnO2 NFs were then functionalized with amine groups, followed by incubation with copper sulfate for three days at room temperature to drive the coordination interaction between the amine moieties and copper ions and to induce anisotropic growth of the petals composed of copper phosphate crystals, consequently yielding H–Mn–Cu NFs. Compared with those of free laccase, at the same mass concentration, H–Mn–Cu NFs exhibited lower K m (~ 85%) and considerably higher V max (~ 400%), as well as significantly enhanced stability in the ranges of pH, temperature, ionic strength, and incubation periods evaluated. H–Mn–Cu NFs also catalyzed the decolorization of diverse dyes considerably faster than the free laccase. Based on these advantageous features, a paper microfluidic device incorporating H–Mn–Cu NFs was constructed for the convenient visual detection of phenolic neurotransmitters, including dopamine and epinephrine. The device enabled rapid and sensitive quantification of target neurotransmitters using an image acquired using a smartphone. Conclusions These results clearly show that H–Mn–Cu NFs could be potential candidates to replace natural laccases for a wide range of applications in biosensing, environmental protection, and biotechnology. Graphical Abstract

Abstract Background The prevalence and death rate arising from malaria infection, and emergence of other diseases showing similar symptoms to malaria require the development of malaria-specific and sensitive devices for its diagnosis. To address this, the design and fabrication of low-cost, rapid, paper-based analytical devices (µPAD) using surface-immobilized aptamers to detect the presence of a recombinant malarial biomarker—Plasmodium falciparum lactate dehydrogenase (rPfLDH)—is reported in this study. Methods Test zones on paper surfaces were created by covalently immobilizing streptavidin to the paper, subsequently attaching biotinylated aptamers to streptavidin. Aptamers selectively bound rPfLDH. The measurement of captured rPfLDH enzyme activity served as the means of detecting this biomarker. Enzyme activity across three replicate sensors was digitally quantified using the colorimetric Malstat assay. Results Screening of several different aptamers reported in the literature showed that aptamers rLDH7 and 2008s immobilized in this manner specifically recognised and captured PfLDH. Using rLDH7, the sensitivity of the µPAD sensor was evaluated and the µPAD sensor was applied for preferential detection of rPfLDH, both in buffered solutions of the protein and in spiked serum and red blood cell lysate samples. In buffered solutions, the test zone of the µPAD sensor exhibited a K D of 24 ± 11 nM and an empirical limit of detection of 17 nM, respectively, a limit similar to commercial antibody-based sensors exposed to rPfLDH. The specific recognition of 133 nM rPfLDH in undiluted serum and blood samples was demonstrated by the µPAD. Conclusion The reported µPAD demonstrates the potential of integrating aptamers into paper-based malarial rapid diagnostic tests. Graphical Abstract The assembly of µPAD sensors using APTEC assay principles for the detection the malarial biomarker, lactate dehydrogenase enzymes from Plasmodium falciparum (PfLDH). The aptamers immobilized at the test zones capture the PfLDH in samples. After washing the unbound sample components from the zones, Malstat assay reagents are added for colour development, proportional to the amount of captured PfLDH.

Abstract Background People with severe mental illness (e.g. psychosis, bipolar disorder) experience poor oral health compared to the general population as shown by more decayed, missing and filled teeth and a higher prevalence of periodontal disease. Attending dental services allows treatment of oral health problems and support for prevention. However, people with severe mental illness face multiple barriers to attending routine dental appointments and often struggle to access care. Link work interventions use non-clinical support staff to afford vulnerable populations the capacity, opportunity, and motivation to navigate use of services. The authors have co-developed with service users a link work intervention for supporting people with severe mental illness to access routine dental appointments. The Mouth Matters in Mental Health Study aims to explore the feasibility and acceptability of this intervention within the context of a feasibility randomised controlled trial (RCT) measuring outcomes related to the recruitment of participants, completion of assessments, and adherence to the intervention. The trial will closely monitor the safety of the intervention and trial procedures. Methods A feasibility RCT with 1:1 allocation to two arms: treatment as usual (control) or treatment as usual plus a link work intervention (treatment). The intervention consists of six sessions with a link worker over 9 months. Participants will be adults with severe mental illness receiving clinical input from secondary care mental health service and who have not attended a planned dental appointment in the past 3 years. Assessments will take place at baseline and after 9 months. The target recruitment total is 84 participants from across three NHS Trusts. A subset of participants and key stakeholders will complete qualitative interviews to explore the acceptability of the intervention and trial procedures. Discussion The link work intervention aims to improve dental access and reduce oral health inequalities in people with severe mental illness. There is a dearth of research relating to interventions that attempt to improve oral health outcomes in people with mental illness and the collected feasibility data will offer insights into this important area. Trial registration The trial was preregistered on ISRCTN (ISRCTN13650779) and ClinicalTrials.gov (NCT05545228).

Abstract Background South Africa is reporting higher rates of adolescent pregnancy as compared to other countries. There are different types of interventions that are in place to address teenage pregnancy. However, these interventions were developed using top-down strategy without the inclusion of different stakeholders and adolescents which makes it hard to implement those interventions particularly in countries like South Africa. Hence, this study aimed to develop strategies to enhance sexual health education for prevention of teenage pregnancy in Vhembe District, Limpopo Province of South Africa. Methods The research design of this study will be Co-operative Inquiry.The study will take place in Vhembe District in Limpopo province of South Africa through collaborating with a Non-governmental Organisation (NGO). The study population will be the teenagers and all the different stakeholders caring for teenagers in their areas of specialization. Purposive sampling will be used to sample the targeted participants of the study. The data collection method will be done in phases and focus group discussions will be used to collect data. Content analysis will be used to analyse data. Discussion This study will add to the body of knowledge regarding the strategies that maybe used to enhance sexual health education for prevention of teenage pregnancy.

Abstract Background Successful aging is often linked to individual’s ability to demonstrate resilience: the maintenance or quick recovery of functional ability, well-being, and quality of life despite losses or adversity. A crucial element of resilience is behavioral adaptability, which refers to the adaptive changes in behavior in accordance with internal or external demands. Age-related degradation of executive functions can, however, lead to volition problems that compromise flexible adjustment of behavior. In contrast, the reliance on habitual control has been shown to remain relatively intact in later life and may therefore provide an expedient route to goal attainment among older adults. In the current study, we examine whether a metacognitive self-help intervention (MCSI), aimed at facilitating goal striving through the gradual automatization of efficient routines, could effectively support behavioral adaptability in favor of resilience among older adults with and without (sub-clinical) mental health problems. Methods This metacognitive strategy draws on principles from health and social psychology, as well as clinical psychology, and incorporates elements of established behavioral change and activation techniques from both fields. Additionally, the intervention will be tailored to personal needs and challenges, recognizing the significant diversity that exist among aging individuals. Discussion Despite some challenges that may limit the generalizability of the results, our MCSI program offers a promising means to empower older adults with tools and strategies to take control of their goals and challenges. This can promote autonomy and independent functioning, and thereby contribute to adaptability and resilience in later life. Trial registration Pre-registered, partly retrospectively. This study was pre-registered before the major part of the data was collected, created, and realized. Only a small part of the data of some participants (comprising the baseline and other pre-intervention measures), and the full dataset of the first few participants, was collected prior to registration, but it was not accessed yet. See: https://osf.io/5b9xz

Abstract Background Law enforcement frequently responds to substance abuse and mental health crises. Crisis stabilization units (CSUs) operate as a public-receiving facility to provide short-term stabilization services for individuals experiencing these crises and offer law enforcement an important alternative to arrest. However, there is limited understanding about how and when law enforcement decides to use CSUs. There is also the challenge of retaining individuals in treatment after CSU stabilization to prevent future crises and persistent engagement with police. This study will respond to these gaps by exploring CSU procedures and examining the feasibility and acceptability of a technology-assisted mobile aftercare intervention designed for individuals brought to a CSU by law enforcement. Methods This study will consist of three aims. Aim 1 will include qualitative interviews with law enforcement and CSU-affiliated mental health staff (n=80) regarding CSU utilization and collaboration logistics between the groups. Findings from Aim 1 will be synthesized for the development of an implementation guide of our intervention, mobile, and technology-assisted aftercare, designed for individuals brought to a CSU by law enforcement, during Aim 2. During Aim 2, intervention services will be pilot-tested for 6 months through a small sample (n=24), randomized control trial (RCT). Control participants will receive standard services available for individuals discharging from a CSU. Treatment participants will receive the mobile aftercare intervention. Qualitative and quantitative data will be collected at 2 weeks, 3 months, and 6 months post-recruitment for all study participants. Aims 1 and 2 will inform the design of a multi-site RCT to compare CSUs with and without mobile and technology-assisted aftercare (Aim 3). Discussion The study will offer decision making and procedural insight into law enforcement use of CSUs as an alternative to jail and provide opportunities to inform that process. This research will provide outcome trends for those who go through standard CSU services compared to those who receive mobile and technology-assisted aftercare services. The current study will inform a larger RCT efficacy study of CSUs with and without technology-assisted aftercare services. Trial registration This study was registered on ClinicalTrials.gov (reference #NCT04899934) on May 25, 2021.

Abstract Background Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. Methods A bibliographic search using major databases was performed using the terms “emergency surgery” “diaphragmatic hernia,” “traumatic diaphragmatic rupture” and “congenital diaphragmatic hernia.” GRADE methodology was used to evaluate the evidence and give recommendations. Results CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. Conclusions Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.

Abstract Background Misinformation regarding COVID-19 pandemic and vaccination is damaging COVID-19 vaccine trust and acceptance in Low- and Middle-Income Countries (LMIC). Identification of misinformation and designing locally acceptable solutions are needed to improve COVID-19 vaccine acceptance. This study aimed to utilize community-led co-design methodology to evaluate misinformation regarding COVID-19 and develop contextual interventions to address misinformation in a marginalized peri urban slum communities of Landhi town Karachi, Pakistan. Methods This study was conducted between January and December 2021, in marginalized peri-urban slum dwellers of Muslimabad Colony, Landhi Town Karachi, Pakistan. We used a community-centred co-design methodology embedded within mixed study design to identify misinformation, co-design, test and implement locally acceptable solutions. The co-design methodology involved five stages of the design thinking model: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype, and (5) Test. The project involved active engagement and participation of wide range of stakeholders and community beneficiaries (end users) including local EPI vaccinators, informal healthcare workers, religious leaders (male and female), schoolteachers (male and female), local government representatives, community leaders, housewives, youth, and general population. To develop a trusting relationship, and understand local culture, values, practices, and traditions, we allowed one month of observation period (observe, engage, watch, and listen) in the beginning, followed by door-to-door survey along with focus group discussions (FGD) and in-depth interviews (IDI) at baseline. Co-design workshops (separate for male and female) were conducted at each stage of co-design methodology to design and test locally acceptable solutions. Conclusion Community-centred co-design methodology was not only successful in designing, testing, and evaluating locally acceptable solutions but it also actively engaged and empowered the marginalized population living in peri urban slum communities of Karachi, Pakistan.

Abstract Introduction The Ministry of Public Health in Lebanon is in the process of converting the surveillance reporting from a cumbersome paper-based system to a web-based electronic platform (DHIS-2) to have real-time information for early detection of alerts and outbreaks and for initiating a prompt response. Objectives This paper aimed to document the Lebanese experience in implementing DHIS-2 for the disease surveillance system. It also targets to assess the improvement of reporting rates and timeliness of the reported data and to disclose the encountered challenges and opportunities. Methodology This is a retrospective description of processes involved in the implementation of the DHIS-2 tool in Lebanon. Initially, it was piloted for the school-based surveillance in 2014; then its use was extended in May 2017 to cover other specific surveillance systems. This included all surveillance programs collecting aggregate data from hospitals, medical centers, dispensaries, or laboratories at the first stage. As part of the national roll-out process, the online application was developed. The customized aggregated-based datasets, organization units, user accounts, specific and generic dashboards were generated. More than 80 training sessions were conducted throughout the country targeting 1290 end-users including health officers at the national and provincial levels, focal persons who were working in all public and private hospitals, laboratories, and medical centers as well. Completeness and timeliness of reported data were compared before and after the implementation of DHIS-2. The unveiled challenges and the main lessons learned during the roll-out process were discussed. Results For laboratory-based surveillance, completeness of reporting increased from 70.8% in May to 89.6% in October. Timeliness has improved from 25 to 74%. For medical centers, an improvement of 8.1% for completeness and 9.4% in timeliness was recorded before and after training sessions. For zero reporting, completeness remains the same (88%) and timeliness has improved from 74 to 87%. The main challenges faced during the implementation of DHIS-2 were mainly infrastructural and system-related in addition to poor internet connectivity, limited workforce, and frequent changes to DHIS-2 versions. Conclusion Implementation of DHIS-2 improved timeliness and completeness for aggregated data reporting. Continued on-site support, monitoring, and system enhancement are needed to improve the performance of DHIS-2.

Abstract This letter concerns retracted papers published in the Journal of Diagnostic Pathology, where my name was misused as the author or corresponding author without my permission or knowledge. Considering that all misconducts were directed by an author during initial manuscripts’ submissions, I opened a case in Iran’s Cyber Police (FATA) to unravel the true identity of the submitting author. After Cyber Police’s report revealed the true identity of the submitting author, the court started a thorough investigation and finally convicted the submitting author for identity fraud and data forgery through creating and using fake email addresses.

Abstract Many countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty—an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions.

Abstract Background Problem-based learning (PBL) remains a valid and effective tool for small-group medical education. Using Virtual patients (VP) case simulation in PBL is a recognizable educational method that has successfully prepared students to focus learning on core information that uses realistic patient-based cases relating to everyday clinical scenarios. Using other modalities as the virtual patient in PBL instead of the paper-based methods remains debatable. This study aimed to evaluate the effectiveness of using VP case simulation mannequin in PBL versus the PBL in paper-based cases in improving the cognitive skills by comparing the grades of a multiple-choice question test and assess its ability to reach students' satisfaction using questionnaire with Likert survey instrument. Methods The study was conducted on 459 fourth-year medical students studying in the pulmonology module of the internal medicine course, Faculty of Medicine, October 6 University. All students were divided into 16 PBL classes and randomly divided into groups A and B by simple manual randomization. The groups were parallel with a controlled cross-over study between paper-based and virtual patient PBL. Results The pre-test showed no significant difference between both, while post-test scores were significantly higher in both VP PBL cases 1 discussing COPD (6.25 ± 0.875) and case 2 discussing pneumonia (6.56 ± 1.396) compared to paper-based PBL (5.29 ± 1.166, 5.57 ± SD1.388, respectively) at p

Abstract Background The number of citations a paper receives reflects its impact on the scientific community. We aimed to identify and explore the characteristics of the most cited papers on total anomalous pulmonary venous connection (TAPVC). Methods Web of Science Core Collection Expanded Science Citation Index (1900 to present) was searched and papers on TAPVC were reviewed. Articles were ranked by the number of citations and the 100 most cited papers were analyzed. Results The 100 most cited papers were published between 1952 and 2018 with a mean number of citations of 52 (range 26 to 148). The 1990s was the most productive decade. All articles except one were written in English. The 100 most cited articles were published in 24 journals, led by Journal of Thoracic and Cardiovascular Surgery (21 articles), followed by Annals of Thoracic Surgery (20 articles), and Circulation (16 articles). The United States of America contributed most of the 100 most cited papers (60 articles). Hospital for Sick Children, Toronto led the list of citation classics with six papers. Christopher A. Caldarone, John W. Kirklin, and P. E. F. Daubeney were the most productive authors with 3 articles each. More than half of the papers were cohort studies (51 articles). Surgery, radiology and etiology were the main topics. Thirty-one articles were funded by public foundations, and none received support from commercial companies. Conclusions The bibliometric analysis gives a historical perspective on scientific progress in the field of TAPVC and lays the foundation for future research.

Abstract This paper presents the case of an adjunct university professor to illustrate the dilemma of using artificial intelligence (AI) technology to grade student papers. The hypothetical case discusses the benefits of using a commercial AI service to grade student papers—including discretion, convenience, pedagogical merits of consistent feedback for students, and advances made in the field that yield high-quality work—all of which are achieved quickly. Arguments against using AI to grade student papers involve cost, privacy, legality, and ethics. The paper discusses career implications for faculty members in both situations and concludes with implications for researchers within the discourse on academic integrity.

Abstract Background Personalised medicine (PM) has been fostered by technological and medical advances, but all stakeholders, including healthcare professionals, citizens and policy makers, should achieve adequate health literacy to promote PM implementation. The “Integrating China in the International Consortium for Personalised Medicine” (IC2PerMed) project, funded by the International Consortium for Personalised Medicine, focuses on this issue by highlighting the need to educate healthcare professionals and empower citizens. Within the aforementioned project, building on a mapping of European and Chinese policies in PM, experts in the field of PM participated in an online workshop and a following two-round Delphi survey, in order to identify the priority areas of intervention for healthcare professionals’ education and curricula, engagement and empowerment of citizens and patients. Results Nine experts completed the survey and reached a consensus on seventeen priorities: seven were related to health professionals’ education and curricula, whereas ten on citizen and patients’ awareness and empowerment. Conclusion These priorities emphasized the importance of education and health literacy, multidisciplinary and international collaboration, public trust, and consideration of ethical, legal, and social issues. The present experience highlights the relevance of the involvement of stakeholders in informing decision-makers, developing appropriate national plans, strategies, and policies, and ensuring the adequate implementation of PM in health systems.

Abstract Background Childhood apraxia of speech (CAS) is a pediatric motor-based speech sound disorder that requires a specialized approach to intervention. The extant literature on the treatment of CAS commonly recommends intensive treatment using a motor-based approach, with some of the best evidence supporting the use of Dynamic Temporal and Tactile Cueing (DTTC). To date, a rigorous and systematic comparison of high and low dose frequency (i.e., frequency of therapy sessions) has not been undertaken for DTTC, resulting in a lack of evidence to guide decisions about the optimal treatment schedule for this intervention. The current study aims to fill this gap in knowledge by comparing treatment outcomes when dose frequency is varied. Methods A randomized controlled trial will be conducted to examine the efficacy of low versus high dose frequency on DTTC treatment outcomes in children with CAS. A target of 60 children, 2;6–7;11 years of age, will be recruited to participate in this study. Treatment will be provided in the community setting by speech-language pathologists who have completed specialized training administering DTTC in a research reliable manner. True randomization with concealed allocation will be used to assign children to either the low or high dose frequency group. Treatment will be administered in 1-h sessions either 4 times per week over a 6-week period (high dose) or 2 times per week over a 12-week period (low dose). To measure treatment gains, probe data will be collected before treatment, during treatment, and 1 day, 1 week, 4 weeks, and 12 weeks post-treatment. Probe data will consist of customized treated words and a standard set of untreated words to assess generalization of treatment gains. The primary outcome variable will be whole word accuracy, encompassing segmental, phonotactic, and suprasegmental accuracy. Discussion This will be the first randomized controlled trial to evaluate dose frequency for DTTC treatment in children with CAS. Trial registration ClinicalTrials.gov identifier NCT05675306, January 6, 2023.

Abstract In this critical review, we explore the study design, strengths, and limitations of landmark trial “Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence”. This trial was the first to directly compare two key treatment options for urge urinary incontinence – anticholinergic medication and intravesical botox, and still influences clinical guidelines a decade after publication. This non-inferiority, double-blinded, multi-centre randomised controlled trial administered Solifenacin or intra-detrusor botox to women, measuring outcomes six months post-treatment. Non-inferiority of the treatments was established, though Botox had a higher rate of retention and infection, with side effect profile rising as the key discriminator in selecting first-line therapy.

Abstract Objectives The aim of this bibliometric analysis was twofold: to identify the 100 most cited research articles on thymoma and to highlight future research opportunities in light of past and current research efforts. Methods The Web of Science database was queried to identify the 100 most cited articles on thymoma. Imformations relevant to scientific research were extracted and analyzed: first author, journal, impact factor, type of article, year of publication, country, organization and keywords. Results The publication year of the top 100 most cited articles ranged from 1981 to 2018, and the number of citations ranged from 97 to 1182. Most of the included articles are original (75/100) and are mainly retrospective studies (52/75). The United States has the most published articles and citations, and the Annals of Thoracic Surgery is the most sourced journal (n = 16). Through VOSviewer analysis, high-density keywords mainly come from thymic carcinoma/invasive thymoma management, immune-related diseases, and laboratory research. Conclusions To our knowledge, this is the first bibliometric study on thymoma. We found most of the top 100 most cited articles are original and retrospective research. The United States has the published and cited works. Presently, the hot keywords for thymoma research has gradually tilted towards immune-related diseases and laboratory research.

Abstract The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK.

Abstract Background Huntington’s disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person’s functioning. It begins after a healthy start in life and leads through the relentless progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory. Discussion The position paper outlines current knowledge and experience alongside the experience and consensus of a recognised group of HD multidisciplinary experts. Additionally the patient’s voice is clear and calls for health care providers with a holistic view on patient and family. Building long-term trust is a cornerstone of the network around the patient. This paper describes a managed care network comprising all the needed professionals and services. In the health care system, the role of a central coordinator or case manager is of key importance but lacks an appropriate guideline. Other disciplines currently without guidelines are general practitioners, nurses, psychologists, and social workers. Guidelines for neurologists, psychiatrists, geneticists, occupational therapists, speech and language therapists, physiotherapists, dieticians, and dentists are being discussed. Apart from all these profession-specific guidelines, distinctive inter- and multidisciplinary collaboration requirements must be met. Conclusions and recommendations The complex nature of Huntington's disease demands multidisciplinary treatment and care endorsed by international regulations and the lay association. Available guidelines as reviewed in this paper should be used, made available by a central body, and updated every 3–5 years. Time needs to be invested in developing missing guidelines but the lack of this ‘proof’ should not prevent the ‘doing’ of good care.

Abstract Background Great variation has been observed in the composition of the normal microbiota of the ocular surface, and therefore, in addition to differences in detection techniques, the method of collecting ocular surface specimens has a significant impact on the test results.The goal of this study is to ascertain whether the eye surface microbial communities detected by two different sampling methods are consistent and hence explore the feasibility of using tear test paper instead of conjunctival swabs to collect eye surface samples for microbial investigation. Materials and methods From July 15, 2021, to July 30, 2021, nonirritating tear test strips and conjunctival swabs of both eyes were used in 158 elderly people (> 60 years old) (79 diabetic and 79 nondiabetic adults) in Xinjing Community for high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The composition of the microbial communities in tear test paper and conjunctival swab samples was analyzed. Results There was no statistically significant difference in Alpha diversity of ocular surface microorganisms represented by tear strip and conjunctival swab in diabetic group (P > 0.05), but there was statistically significant difference in Alpha diversity of ocular surface microorganisms detected by tear strip and conjunctival swab in nondiabetic group (P 0.05). Conclusions Tear test paper and conjunctival swabs detect different compositions of microbes through two different techniques of eye surface microbe sampling. Tear test paper cannot completely replace conjunctival swab specimens for the study of microbes related to eye surface diseases.

Abstract Background Minimally invasive surgery (MIS), including laparoscopic and robotic approaches, is widely adopted in elective digestive surgery, but selectively used for surgical emergencies. The present position paper summarizes the available evidence concerning the learning curve to achieve proficiency in emergency MIS and provides five expert opinion statements, which may form the basis for developing standardized curricula and training programs in emergency MIS. Methods This position paper was conducted according to the World Society of Emergency Surgery methodology. A steering committee and an international expert panel were involved in the critical appraisal of the literature and the development of the consensus statements. Results Thirteen studies regarding the learning curve in emergency MIS were selected. All but one study considered laparoscopic appendectomy. Only one study reported on emergency robotic surgery. In most of the studies, proficiency was achieved after an average of 30 procedures (range: 20–107) depending on the initial surgeon’s experience. High heterogeneity was noted in the way the learning curve was assessed. The experts claim that further studies investigating learning curve processes in emergency MIS are needed. The emergency surgeon curriculum should include a progressive and adequate training based on simulation, supervised clinical practice (proctoring), and surgical fellowships. The results should be evaluated by adopting a credentialing system to ensure quality standards. Surgical proficiency should be maintained with a minimum caseload and constantly evaluated. Moreover, the training process should involve the entire surgical team to facilitate the surgeon’s proficiency. Conclusions Limited evidence exists concerning the learning process in laparoscopic and robotic emergency surgery. The proposed statements should be seen as a preliminary guide for the surgical community while stressing the need for further research.

Abstract Background Novel survey methods are needed to tackle declining response rates. The 2020 National Maternity Survey included a randomised controlled trial (RCT) and social media survey to compare different combinations of sampling and data collection methods with respect to: response rate, respondent representativeness, prevalence estimates of maternity indicators and cost. Methods A two-armed parallel RCT and concurrent social media survey were conducted. Women in the RCT were sampled from ONS birth registrations and randomised to either a paper or push-to-web survey. Women in the social media survey self-selected through online adverts. The primary outcome was response rate in the paper and push-to-web surveys. In all surveys, respondent representativeness was assessed by comparing distributions of sociodemographic characteristics in respondents with those of the target population. External validity of prevalence estimates of maternity indicators was assessed by comparing weighted survey estimates with estimates from national routine data. Cost was also compared across surveys. Results The response rate was higher in the paper survey (n = 2,446) compared to the push-to-web survey (n = 2,165)(30.6% versus 27.1%, difference = 3.5%, 95%CI = 2.1–4.9, p

Abstract Background Microfluidic chip detection technology is considered a potent tool for many bioanalytic applications. Rapid detection of foodborne pathogens in the early stages is imperative to prevent the outbreak of foodborne diseases, known as a severe threat to human health. Conventional bacterial culture methods for detecting foodborne pathogens are time-consuming, laborious, and lacking in pathogen diagnosis. To overcome this problem, we have created an embedded paper-based microchip based on isothermal loop amplification (LAMP), which can rapidly and sensitively detect foodborne pathogens. Results We embed paper impregnated with LAMP reagent and specific primers in multiple reaction chambers of the microchip. The solution containing the target pathogen was injected into the center chamber and uniformly distributed into the reaction chamber by centrifugal force. The purified DNA of Escherichia coli O157:H7, Salmonella spp., Staphylococcus aureus, and Vibrio parahaemolyticus has been successfully amplified and directly detected on the microchip. The E. coli O157:H7 DNA was identified as low as 0.0134 ng μL− 1. Besides, the potential of this microchip in point-of-care testing was further tested by combining the on-chip sample purification module and using milk spiked with Salmonella spp.. The pyrolyzed milk sample was filtered through a polydopamine-coated paper embedded in the inside of the sample chamber. It was transported to the reaction chamber by centrifugal force for LAMP amplification. Then direct chip detection was performed in the reaction chamber embedded with calcein-soaked paper. The detection limit of Salmonella spp. in the sample measured by the microchip was approximately 12 CFU mL− 1. Conclusion The paper embedded LAMP microchip offers inexpensive, user-friendly, and highly selective pathogen detection capabilities. It is expected to have great potential as a quick, efficient, and cost-effective solution for future foodborne pathogen detection.

Abstract Background Lysine succinylation is a naturally occurring post-translational modification (PTM) that is ubiquitous in organisms. Lysine succinylation plays important roles in regulating protein structure and function as well as cellular metabolism. Global lysine succinylation at the proteomic level has been identified in a variety of species; however, limited information on lysine succinylation in plant species, especially paper mulberry, is available. Paper mulberry is not only an important plant in traditional Chinese medicine, but it is also a tree species with significant economic value. Paper mulberry is found in the temperate and tropical zones of China. The present study analyzed the effects of lysine succinylation on the growth, development, and physiology of paper mulberry. Results A total of 2097 lysine succinylation sites were identified in 935 proteins associated with the citric acid cycle (TCA cycle), glyoxylic acid and dicarboxylic acid metabolism, ribosomes and oxidative phosphorylation; these pathways play a role in carbon fixation in photosynthetic organisms and may be regulated by lysine succinylation. The modified proteins were distributed in multiple subcellular compartments and were involved in a wide variety of biological processes, such as photosynthesis and the Calvin-Benson cycle. Conclusion Lysine-succinylated proteins may play key regulatory roles in metabolism, primarily in photosynthesis and oxidative phosphorylation, as well as in many other cellular processes. In addition to the large number of succinylated proteins associated with photosynthesis and oxidative phosphorylation, some proteins associated with the TCA cycle are succinylated. Our study can serve as a reference for further proteomics studies of the downstream effects of succinylation on the physiology and biochemistry of paper mulberry.

Abstract The indiscriminate use of herbicides in agriculture contributes to soil and water pollution, with important endangering consequences on the ecosystems. Among the available analytical systems, algal biosensors have demonstrated to be valid tools thanks to their high sensitivity, cost-effectiveness, and eco-design. Herein, we report the development of a dual electro-optical biosensor for herbicide monitoring, based on Chlamydomonas reinhardtii whole cells immobilised on paper-based screen-printed electrodes modified with carbon black nanomaterials. To this aim, a systematic study was performed for the selection and characterisation of a collection among 28 different genetic variants of the alga with difference response behaviour towards diverse herbicide classes. Thus, CC125 strain was exploited as case study for the study of the analytical parameters. The biosensor was tested in standard solutions and real samples, providing high sensitivity (detection limit in the pico/nanomolar), high repeatability (RSD of 5% with n = 100), long lasting working (10 h) and storage stability (3 weeks), any interference in the presence of heavy metals and insecticides, and low matrix effect in drinking water and moderate effect in surface one.

Abstract Background Patient referral is a process in which a healthcare provider decides to seek assistance due to the limitations of available skills, resources and services offered locally. Paper-based referrals predominantly used in low-income countries hardly follow any procedure. This causes a major gap in communication, coordination, and continuity of care between primary and specialized levels, leading to poor access, delay, duplication and unnecessary costs. The goal of this study is to assess the formats and completeness of existing paper-based referral letters in order to improve health information exchange, coordination, and continuity of care. Methods A retrospective exploratory research was conducted in eight public and three private healthcare facilities in the city of Kigali from May to October 2021. A purposive sampling method was used to select hospitals and referral letters from patients’ files. A data capture sheet was designed according to the contents of the referral letters and the resulting responses were analyzed descriptively. Results In public hospitals, five types of updated referral letters were available, in total agreement with World Health Organization (WHO) standards of which two (neonatal transfer form and patient monitoring transfer form) were not used. There was also one old format that was used by most hospitals and another format designed and used by a district hospital (DH) separately. Three formats were designed and used by private hospitals (PH) individually. A total of 2,304 referral letters were perused and the results show that “external transfer” forms were completed at 58.8%; “antenatal, delivery, and postnatal external transfer” forms at 47.5%; “internal transfer” forms at 46.6%; “Referral/counter referral” forms at 46.0%; district hospital referrals (DH2) at 73.4%. Referrals by private hospitals (PH1, PH2 and PH3) were completed at 97.7%, 70.7%, and 0.0% respectively. The major completeness deficit was observed in counter referral information for all hospitals. Conclusion We observed inconsistencies in the format of the available referral letters used by public hospitals, moreover some of them were incompatible with WHO standards. Additionally, there were deficits in the completeness of all types of paper-based referral letters in use. There is a need for standardization and to disseminate the national patient referral guideline in public hospitals with emphasis on referral feedback, referral registry, triage, archiving and a need for regular training in all organizations.

Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder associated with increased immune activity and severe, progressive heterotopic ossification. We previously described a cohort of 32 patients with FOP who were either exposed to SARS-CoV-2 or received a COVID-19 vaccine1 and showed that these patients did not develop heterotopic ossification after COVID-19 vaccination. Here, we present additional clinical data from new subjects and additional long-term follow-up from the first cohort. We enrolled 15 new subjects between August 24th, 2021 and May 17th, 2022 and collected additional self-reported outcomes. The larger cohort with 47 individuals encompassing 49 events showed that patients with FOP exhibited no additional change in FOP disease activity or flare activity resulting from COVID-19 infection or after receipt of a SARS-CoV-2 vaccine. Thus, although any vaccination carries a risk of inducing heterotopic ossification in patients with FOP, our results show that patients with FOP who choose to receive a COVID-19 vaccination may be able to tolerate the procedure without a high risk of heterotopic ossification when following the published guidelines.

Abstract Background In recent years, significant advances have been made in the field of rare diseases (RDs). However, there is a large number of RDs without specific treatment and half of these treatments have public funding in Spain. The aim of the FINEERR project was to carry out a multidisciplinary strategic discussion on the challenge of funding and access to RD-targeted drugs in Spain, in order to agree on specific proposals for medium-term improvement and hence support decision-making in the Spanish National Healthcare System (SNHS). Results The FINEERR Project was organized around a CORE Advisory Committee, which provided an overview, agreed on the design and scope of the project, and selected the members within each of four working groups (WG). Overall, 40 experts discussed and reached a consensus on different relevant aspects, such as conditioning factors for initial funding and access, evaluation and access to RD-targeted therapies, funding of these therapies, and implementation of a new funding and access model. From these meetings, 50 proposals were defined and classified by their level of relevance according to the experts. A descriptive analysis of responses was performed for each proposal. Thereafter, experts completed another questionnaire where they ranked the 25 most relevant proposals according to their level of feasibility of being implemented in the SNHS. The most relevant and feasible proposals were to improve: process of referral of patients with RDs, control over monitoring mechanisms, and communication between healthcare professionals and patients. Conclusions The FINEERR project may provide a starting point for stakeholders involved in the process of funding and access to RD-targeted therapies in Spain to provide the necessary resources and implement measures to improve both the quality of life and life expectancy of patients with RDs.