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Abstract There is a growing need to evaluate the agreement between the field methods and integrate artificial intelligence (AI) using two-dimensional (2D) photos for enhanced real-world analysis. This study evaluated the agreement between AI-2D photos and the clinical reference method, dual-energy X-ray absorptiometry (DXA) to estimate the body fat percentage (BFP). Other methods were also investigated, including skinfolds, A-mode ultrasound, and bioelectrical impedance analysis (BIA). This cross-sectional study was conducted on 1273 adults of both sexes. The Bland–Altman plots, Lin’s Correlation Coefficient of Agreement (CCC), and error analyses were calculated. AI-2D photos demonstrated substantial agreement with DXA presenting the highest agreement (CCC ≥ 0.96) among all the investigated methods. InBody-270 and Omron HBF-514 BIA devices showed moderate agreement (CCC = 0.90 to 0.95) for all participants, age groups >30 years, and body mass index >25 kg/m2. AI-2D photos can be interchangeable with DXA, providing a practical, accessible alternative and an easy-to-use system for BFP estimation.

Abstract The relationship between weather and acute coronary syndrome (ACS) incidence has been the subject of considerable research, with varying conclusions. Harnessing machine learning techniques, our study explores the relationship between meteorological factors and ACS presentations in the emergency department (ED), offering insights into seasonal variations and inter-day fluctuations to optimize patient care and resource allocation. A retrospective cohort analysis was conducted, encompassing ACS presentations to Dutch EDs from 2010 to 2017. Temporal patterns were analyzed using heat-maps and time series plots. Multivariable linear regression (MLR) and Random Forest (RF) regression models were employed to forecast daily ACS presentations with prediction horizons of one, three, seven, and thirty days. Model performance was assessed using the coefficient of determination (R²), Mean Absolute Error (MAE), and Mean Absolute Percentage Error (MAPE). The study included 214,953 ACS presentations, predominantly unstable angina (UA) (94,272; 44%), non-ST-elevated myocardial infarction (NSTEMI) (78,963; 37%), and ST-elevated myocardial infarction (STEMI) (41,718; 19%). A decline in daily ACS admissions over time was observed, with notable inter-day (estimated median difference: 41 (95%CI = 37–43, p =

Summary: Background: Clinical decision-making is increasingly shifting towards data-driven approaches and requires large databases to develop state-of-the-art algorithms for diagnosing, detecting and predicting diseases. The intensive care unit (ICU), a data-rich setting, faces challenges with high-frequency, unstructured monitor data. Here, we showcase a successful example of a data pipeline to efficiently move patient data to the cloud environment for structured storage. This supports individual patient analysis, enables largescale retrospective research, and the development of data-driven algorithms. Methods: Since June 2021, ICU data of the Amsterdam UMC have been collected and stored in a third-party cloud environment which is hosted on large virtual servers. The feasibility of the pipeline will be demonstrated with the available data through research and clinical use cases. Furthermore, privacy, safety, data quality, and environmental impact are carefully considered in the cloud storage transition. Findings: Over two years, data from over 9000 patients have been stored in the cloud. The availability, agility, computational power, high uptime, and streaming data pipelines allow for large retrospective analyses as well as the opportunity to implement real-time prediction of critical events with machine learning algorithms. Critical events can be accessed by applying keyword search in the natural language data, annotated by the treating team. Besides, the cloud environment offers storage of institutional data enabling evaluation of healthcare. Interpretation: The combined data and features of cloud environments offer support for predictive algorithm development and implementation, healthcare evaluation, and improved individual patient care. Funding: University of Amsterdam Research Priority Agenda Program AI for Heath Decision-Making.

Objective: Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites – chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether RET and CCDC6 exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells. Methods: We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the RET and CCDC6 genes break following irradiation. Results: Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the RET gene. We discovered that both the RET and CCDC6 genes undergo late replication in thyroid cells. However, only RET’s replication rate is notably delayed after irradiation. Conclusion: The findings suggest that post-irradiation in the RET gene causes a breakage in the replication fork, which could potentially invade another genomic area, including CCDC6. As a result, this could greatly contribute to the high prevalence of chromosomal RET/PTC rearrangements seen in patients exposed to external radiation.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Background Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Methods and Results We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity–Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (β‐2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein–outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), or high‐sensitivity cardiac troponin. Conclusions Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON‐HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. Registration URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Abstract Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.

Abstract Background Diligent fluid management is an instrumental part of Enhanced Recovery After Surgery. However, the effect of a ward regimen to limit intravenous fluid administration on outcome remains unclear. We performed a meta-analysis investigating the effect of a restrictive versus a conventional fluid regimen on complications in patients after non-cardiac surgery in the postoperative period on the clinical ward. Study design We performed a systematic search in MEDLINE, Embase, Cochrane Library, and CINAHL databases, from the start of indexing until June 2022, with constraints for English language and adult human study participants. Data were combined using classic methods of meta-analyses and were expressed as weighted pooled risk ratio (RR) or odds ratio (OR) with 95% confidence interval (CI). Quality assessment and risk of bias analyses was performed according to PRISMA guidelines. Results Seven records, three randomized controlled trials, and four non-randomized studies were included with a total of 883 patients. A restrictive fluid regimen was associated with a reduction in overall complication rate in the RCTs (RR 0.46, 95% CI 0.23 to 0.95; P

Background: Intraoperative hypotension has been extensively studied for its association with adverse outcomes. However, small sample sizes and methodological issues limit the causal inference that can be drawn. Methods: In this multicentre, adaptive, randomised controlled trial, we will include 5000 adult inpatients scheduled for elective non-cardiac surgery under general or central neuraxial anaesthesia. Patients will be either randomly allocated to the intervention or care-as-usual group using computer-generated blocks of four, six, or eight, with an allocation ratio of 1:1. In the intervention arm patients will be divided into low-, intermediate-, and high-risk groups based on their likelihood to experience intraoperative hypotension, with resulting mean blood pressure targets of 70, 80, and 90 mm Hg, respectively. Anaesthesia teams will be provided with a clinical guideline on how to keep patients at their target blood pressure. During the first 6 months of the trial the intervention strategy will be evaluated and further revised in adaptation cycles of 3 weeks if necessary, to improve successful impact on the clinical process. The primary outcome is postoperative disability after 6 months measured with the World Health Organization Disability Assessment Score (WHODAS) 2.0 questionnaire. Ethics and dissemination: This study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht (20–749) and all protocol amendments will be communicated to the Medical Ethics Committee. The study protocol is in adherence with the Declaration of Helsinki and the guideline of Good Clinical Practice. Dissemination plans include publication in a peer-reviewed journal. Clinical trial registration: The Dutch Trial Register, NL9391. Registered on 22 March 2021.

Abstract Background As disease-modifying therapies do not reverse the course of multiple sclerosis (MS), assessment of therapeutic success involves documenting patient-reported outcomes (PROs) concerning health-related quality of life, disease and treatment-related symptoms, and the impact of symptoms on function. Interpreting PRO data involves going beyond statistical significance to calculate within-patient meaningful change scores. These thresholds are needed for each PRO in order to fully interpret the PRO data. This analysis of PRO data from the PROMiS AUBAGIO study, which utilized 8 PRO instruments in teriflunomide-treated relapsing-remitting MS (RRMS) patients, was designed to estimate clinically meaningful within-individual improvement thresholds in the same manner, for 8 PRO instruments. Results The analytical approach followed a triangulation exercise that considered results from anchor- and distribution-based methods and graphical representations of empirical cumulative distribution functions in PRO scores in groups defined by anchor variables. Data from 8 PRO instruments (MSIS-29 v2, FSMC, MSPS, MSNQ, TSQM v1.4, PDDS, HRPQ-MS v2, and HADS) were assessed from 434 RRMS patients. For MSIS-29 v2, FSMC, MSPS, and MSNQ total scores, available anchor variables enabled both anchor- and distribution-based methods to be applied. For instruments with no appropriate anchor available, distribution-based methods were applied. A recommended value for meaningful within-individual improvement was defined by comparing mean change in PRO scores between participants showing improvement of one or two categories in the anchor variable or those showing no change. A “lower bound” estimate was calculated using distribution-based methods. An improvement greater than the lower-bound estimate was considered “clinically meaningful”. Conclusion This analysis produced estimates for assessing meaningful within-individual improvements for 8 PRO instruments used in MS studies. These estimates should be useful for interpreting scores and communicating study results and should facilitate decision-making by regulatory and healthcare authorities where these 8 PROs are commonly employed.

IntroductionPrevious research suggests that altered experiences of agency are an underlying vulnerability in both schizophrenia and autism. Here, we explore agency as a potential transdiagnostic factor by conducting a systematic review of existing literature investigating agency in autism and schizophrenia individually and together.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted three systematic searches on PsycINFO, Embase, Medline, PubMed and Web of Science to identify studies that investigated (1) agency in schizophrenia, (2) agency in autism, and (3) agency in both schizophrenia and autism.ResultsA total of 31 articles met eligibility criteria for inclusion and data extraction, with 24 measuring agency in schizophrenia, 7 investigating agency in autism, and no articles comparing the two. Results show that, compared to control populations, agency is significantly different in every identified schizophrenia study and generally not significantly different in autism.DiscussionImportantly, we identified a lack of studies using common tasks and a disproportionate number of studies investigating different dimensions of agency across the two conditions, resulting in limited grounds for valid comparison.Systematic review registrationProspero, CRD42021273373.

The presence of opportunistic bacteria such as coagulase-negative Staphylococcus (CoNS) in drinking water poses public health concerns because of its potential to cause human infection and due to its antimicrobial resistance (AMR) diversity. This study evaluated the occurrence, virulence markers and AMR of CoNS in 468 drinking water samples from 15 public fountains located in four urban parks of São Paulo city (Brazil). Out of 104 samples positive for the presence of Staphylococcus genus, we detected CoNS in 75 of them (16%), which did not meet the Brazilian sanitary standards for residual chlorine. All isolates were of concern to public health for being responsible for infection in humans from low to high severity, nine of them are considered the most of concern due to 63.6% being multiresistant to antimicrobials. The results demonstrated that CoNS in drinking water must not be neglected. It is concluded that the presence of resistant staphylococci in drinking water is a potential health risk, which urges feasible and quick control measures to protect human health, especially in crowded public places. HIGHLIGHTS Coagulase-negative Staphylococcus (CoNS) was detected in chlorinated drinking water.; High diversity of CoNs was found in drinking water.; Ten species of CoNS and 25 phylogenetic variations were identified.; High frequency of antibiotic-resistant CoNs was observed.; A strain of S. haemolyticus carrying mecA gene and resistant to oxacillin and cefoxitin (MRSH) was identified.;

Inland aquaculture is essential for the food and livelihoods of millions of small-scale producers across the global South. Very diverse actions from national governments, civil sector and international organizations have been seeking to enhance the performance of small-scale aquaculture systems. However, many of these efforts are constrained by the general lack of information about the status and characteristics of the sector. In many cases, data are unavailable, highly aggregated or outdated, thus failing to provide a clear picture of the situation on the ground to inform relevant efforts. Bangladesh is one such country, where, on the one hand, the aquaculture sector is extremely important for national economic growth, rural development and food and nutrition security, but on the other hand suffers from a general lack of quality data to inform relevant actions. In this study, we report the findings generated though eight workshops that engaged 215 stakeholders involved in the Bangladesh small-scale carp aquaculture sector. By leveraging the expertise of the participants, we obtain an overarching picture of the characteristics of small-scale carp production models around the country. The findings suggest a large variability of production models and levels of intensification, which are mainly based on polyculture involving species such as rohu, catla, and mrigal. These systems have been roughly categorized in four types characterized by different levels of intensification and dominant species, which are present across the country with varied socio-economic, infrastructure and environmental conditions. The study also identified an unfolding shift in the last years, from subsistence-based to commercially oriented production. In terms of market preference, quite different carp attributes are valued among small-scale producers across the country, with large size of carp, its rapid growth and the availability of improved strains being the most valued. As aquaculture, and particularly carp aquaculture, is important for rural development in Bangladesh by sustaining households’ income and livelihoods in different ways, we argue for the need to undertake more detailed studies to understand the characteristics and performance of these types of small-scale aquaculture systems. This will be indispensable for informing policies and actions that aim to target more effectively the different types of producers, and to improve the overall performance and sustainability of the sector.

Abstract Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg−1) or high-dose (15 mg kg−1) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose–response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9–11), + 3.9 (2.8–5.6) in the low-dose and 1.9 (− 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO.

Wong, Lee et al. analyse trajectory patterns in the neutralising antibody response to SARS-CoV-2 in convalescent COVID-19 patients. The authors identify two major classes of patients—high-persistent and waning—reporting specific clinical characteristics of each class, which could help with targeted vaccination strategies.

Introduction Hypotension is common during cardiac surgery and often persists postoperatively in the intensive care unit (ICU). Still, treatment is mainly reactive, causing a delay in its management. The Hypotension Prediction Index (HPI) can predict hypotension with high accuracy. Using the HPI combined with a guidance protocol resulted in a significant reduction in the severity of hypotension in four non-cardiac surgery trials. This randomised trial aims to evaluate the effectiveness of the HPI in combination with a diagnostic guidance protocol on reducing the occurrence and severity of hypotension during coronary artery bypass grafting (CABG) surgery and subsequent ICU admission.Methods and analysis This is a single-centre, randomised clinical trial in adult patients undergoing elective on-pump CABG surgery with a target mean arterial pressure of 65 mm Hg. One hundred and thirty patients will be randomly allocated in a 1:1 ratio to either the intervention or control group. In both groups, a HemoSphere patient monitor with embedded HPI software will be connected to the arterial line. In the intervention group, HPI values of 75 or above will initiate the diagnostic guidance protocol, both intraoperatively and postoperatively in the ICU during mechanical ventilation. In the control group, the HemoSphere patient monitor will be covered and silenced. The primary outcome is the time-weighted average of hypotension during the combined study phases.Ethics and dissemination The medical research ethics committee and the institutional review board of the Amsterdam UMC, location AMC, the Netherlands, approved the trial protocol (NL76236.018.21). No publication restrictions apply, and the study results will be disseminated through a peer-reviewed journal.Trial registration number The Netherlands Trial Register (NL9449), ClinicalTrials.gov (NCT05821647).

Over the past two decades, researchers have searched for methods to better understand the relationship between coral hosts and their microbiomes. Data on how coral-associated bacteria are involved in their host’s responses to stressors that cause bleaching, disease, and other deleterious effects can elucidate how they may mediate, ameliorate, and exacerbate interactions between the coral and the surrounding environment. At the same time tracking coral bacteria dynamics can reveal previously undiscovered mechanisms of coral resilience, acclimatization, and evolutionary adaptation. Although modern techniques have reduced the cost of conducting high-throughput sequencing of coral microbes, to explore the composition, function, and dynamics of coral-associated bacteria, it is necessary that the entire procedure, from collection to sequencing, and subsequent analysis be carried out in an objective and effective way. Corals represent a difficult host with which to work, and unique steps in the process of microbiome assessment are necessary to avoid inaccuracies or unusable data in microbiome libraries, such as off-target amplification of host sequences. Here, we review, compare and contrast, and recommend methods for sample collection, preservation, and processing (e.g., DNA extraction) pipelines to best generate 16S amplicon libraries with the aim of tracking coral microbiome dynamics. We also discuss some basic quality assurance and general bioinformatic methods to analyze the diversity, composition, and taxonomic profiles of the microbiomes. This review aims to be a generalizable guide for researchers interested in starting and modifying the molecular biology aspects of coral microbiome research, highlighting best practices and tricks of the trade.

BRAFV600E represents the most common BRAF mutation in all human cancers. Among central nervous system (CNS) tumors, BRAFV600E is mostly found in pediatric low-grade gliomas (pLGG, ~20%) and, less frequently, in pediatric high-grade gliomas (pHGG, 5-15%) and adult glioblastomas (GBM, ~5%). The integration of BRAF inhibitors (BRAFi) in the treatment of patients with gliomas brought a paradigm shift to clinical care. However, not all patients benefit from treatment due to intrinsic or acquired resistance to BRAF inhibition. Defining predictors of response, as well as developing strategies to prevent resistance to BRAFi and overcome post-BRAFi tumor progression/rebound growth are some of the main challenges at present in the field. In this review, we outline current achievements and limitations of BRAF inhibition in gliomas, with a special focus on potential mechanisms of resistance. We discuss future directions of targeted therapy for BRAFV600E mutated gliomas, highlighting how insights into resistance to BRAFi could be leveraged to improve outcomes.

Purpose: This study aims to delve into the evolution, trends and implications of scientific production related to service learning (SL) and community engagement for sustainability in higher education institutions (HEIs). Because HEIs play a crucial role in achieving the sustainable development goals (SDGs), experiential learning approaches are needed to actively involve students in sustainable development. Design/methodology/approach: In total, 869 publications from Web of Science and Scopus databases were analysed using a bibliometric approach that included performance analysis and science mapping. Subsequently, a systematic literature review was conducted on 118 publications, focusing on their contribution to SDGs and alignment with United Nations Educational Scientific and Cultural Organisation's fields of expertise. Findings: The findings reveal two significant trends: a substantial shift from curriculum development (2000-2010) to education for sustainable development (2011-2022), and the effectiveness of experiential learning teaching approaches, such as the integration of SL with community engagement and the use of innovative research methods in promoting the acquisition of sustainable development competencies. Additionally, community-based research, participatory action research and capacity development emerged as the primary topics. Research limitations/implications: While this research is based on publications from two prominent databases, it may not include significant studies published in other databases. Practical implications: These findings suggest that stakeholders should incorporate experiential learning activities and innovative research approaches to enhance education in, for and from sustainability. Originality/value: This study offers a fresh perspective on the intellectual framework of experiential learning teaching approaches concerning sustainability in HEIs.

Revision is a complex cognitive task and an integral component of the writing process. Students benefit from understanding the value of and how to revise their own writing. The purpose of this study was to turn to students to investigate their understandings of revision. We posed the following question: What are 7th graders' perceptions and understandings of revision following a unit of study on revision? Using Qualtrics, we surveyed 345 seventh grade students (52% male, 48% female) about their understanding of revision after revising a piece of writing they had previously composed and considered "finished." Within the unit, students were taught to replace, add, delete, and reorder their writing. Findings indicate that prior to the unit students confused editing tasks for revision moves. Following the unit, students' understanding of the purpose of and how to revise grew and they felt their knowledge and use of revision strategies improved their writing. In addition, students found that distance from their piece helped them to see their writing in more critical ways. Student voices and experiences are needed to shed light on what students really know and understand about revision.

Background: A decade ago, it became possible to derive mean systemic filling pressure (MSFP) at the bedside using the inspiratory hold maneuver. MSFP has the potential to help guide hemodynamic care, but the estimation is not yet implemented in common clinical practice. In this study, we assessed the ability of MSFP, vascular compliance (Csys), and stressed volume (Vs) to track fluid boluses. Second, we assessed the feasibility of implementation of MSFP in the intensive care unit (ICU). Exploratory, a potential difference in MSFP response between colloids and crystalloids was assessed.Methods: This was a prospective cohort study in adult patients admitted to the ICU after cardiac surgery. The MSFP was determined using 3–4 inspiratory holds with incremental pressures (maximum 35 cm H2O) to construct a venous return curve. Two fluid boluses were administered: 100 and 500 ml, enabling to calculate Vs and Csys. Patients were randomized to crystalloid or colloid fluid administration. Trained ICU consultants acted as study supervisors, and protocol deviations were recorded.Results: A total of 20 patients completed the trial. MSFP was able to track the 500 ml bolus (p < 0.001). In 16 patients (80%), Vs and Csys could be determined. Vs had a median of 2029 ml (IQR 1605–3164), and Csys had a median of 73 ml mmHg−1 (IQR 56–133). A difference in response between crystalloids and colloids was present for the 100 ml fluid bolus (p = 0.019) and in a post hoc analysis, also for the 500 ml bolus (p = 0.010).Conclusion: MSFP can be measured at the bedside and provides insights into the hemodynamic status of a patient that are currently missing. The clinical feasibility of Vs and Csys was judged ambiguously based on the lack of required hemodynamic stability. Future studies should address the clinical obstacles found in this study, and less-invasive alternatives to determine MSFP should be further explored.Clinical Trial Registration:ClinicalTrials.gov Identifier NCT03139929.

BackgroundRegular HIV and sexually transmitted infection (STI) testing for men who have sex with men (MSM) is an important means of infection prevention, the adoption of which remains suboptimal in the community. ObjectiveOn the hypothesis that engagement plays an important role in sexual health monitoring, this study aimed to pilot-test internet-based HIV and STI testing with self-sampling to enhance engagement of MSM with regular testing. MethodsThis 1-year cohort study was conducted on HIV-negative MSM aged 18 years or older. A designated website was set up to enable participants to make appointments for baseline and follow-up visits at 3-monthly intervals. On-site blood sampling was performed for HIV and syphilis tests, along with self-collection of pharyngeal swabs, rectal swabs, and urine samples for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing. Full engagement, as defined by having made at least 3 visits over a 6-12 months’ follow-up period, was compared with partial engagement in the bivariable logistic regression model. ResultsBetween August 2019 and October 2020, 204 MSM were recruited, after the exclusion of 2 baseline HIV-positive MSM. The majority (189/204, 92.7%) were Chinese, the median age was 31 (IQR 26-39) years, and 58.0% (116/200) had experience with pre-exposure prophylaxis (PrEP) at baseline. Full engagement (146/204, 71.6%) was associated with incident STI during the follow-ups (odds ratio [OR] 4.23, 95% CI 1.63-10.94), seeking a medical referral after STI detection (OR 10.25, 95% CI 3.25-29.79), and a synchronized schedule of HIV and STI testing with PrEP visits (OR 51.85, 95% CI 19.30-139.34). No incident HIV was detected in the follow-up period. At baseline, the overall STI (CT, NG, or syphilis) prevalence was 30%, with CT at 18%, NG at 13%, and syphilis at 5%. During follow-up, the incidences were 59.08/100 person-years (py) for any STI, 33.05/100 py for CT, 29.86/100 py for NG, and 10.4/100 py for syphilis. The detection rates of CT and NG in urine samples were lower than with pharyngeal swabs and rectal swabs. The scores for convenience, confidence of correct sampling, and accuracy of self-sampling were high (7 to 8 out of 10). ConclusionsBoth baseline prevalence and incidence of STI were high among MSM engaged in regular testing. A high degree of engagement in regular STI and HIV testing was positively associated with incident STI, history of health-seeking behaviors, and perceived convenience of self-sampling. Self-sampling could be introduced as a means of enhancing engagement in regular HIV and STI testing.

Background: Patients with acute febrile illness need to be screened for malaria and coronavirus disease 2019 (COVID-19) in malaria-endemic areas to reduce malaria mortality rates and to prevent the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: To estimate the frequency of children and adolescents with COVID-19 and/or malaria among febrile patients attending for malaria diagnosis Method: This cross-sectional study was conducted in a sentinel site for malaria surveillance during the SARS-CoV-2 pandemic (Omicron variant), from October 2021 to December 2021 in Gabon. All febrile patients were tested for malaria using microscopy. Severe acute respiratory syndrome coronavirus 2 was detected by real time polymerase chain reaction (RT-PCR) and rapid antigen tests developed by Sansure Biotech®. Results: A total of 135 patients were screened. Their median age was 6 (interquartile range [IQR]: 3–14) years. Malaria was confirmed for 49 (36.3%) patients, 29 (32.5%) children, 13 (59.0%) adolescents and 7 (29.2%) adults. The frequency of COVID-19 cases was 7.4% (n = 10/135), and it was comparable between children (n = 6; 6.7%), adolescents (n = 2; 9.1%) and adults (n = 2; 8.3%) (p = 0.17). Malaria and COVID-19 co-infections were diagnosed in 3 (6.1%) patients from all the age groups. Participants with a co-infection had a higher median temperature, a higher median parasitaemia, and were mostly infected with non-falciparum malaria. Conclusion: COVID-19 cases and cases of malaria/COVID-19 co-infections were found in febrile children and adolescents. SARS-CoV-2 testing should be included in the screening of suspected malaria cases. Contribution: This study highlights the presence of malaria-COVID-19 coinfection among children and adolescents who should also be screened for both diseases, like for adults.

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

BackgroundTAVI has shown to result in immediate and sustained hemodynamic alterations and improvement in health-related quality of life (HRQoL), but previous studies have been suboptimal to predict who might benefit from TAVI. The relationship between immediate hemodynamic changes and outcome has not been studied before. This study sought to assess whether an immediate hemodynamic change, reflecting myocardial contractile reserve, following TAVI is associated with improved HRQoL. Furthermore, it assessed whether pre-procedural cardiac power index (CPI) and left ventricular ejection fraction (LVEF) could predict these changes.MethodsDuring the TAVI procedure, blood pressure and systemic hemodynamics were prospectively collected with a Nexfin® non-invasive monitor. HRQoL was evaluated pre-procedurally and 12 weeks after the procedure, using the EQ-5D-5L classification tool.ResultsOverall, 97/114 (85%) of the included patients were eligible for analyses. Systolic, diastolic and mean arterial pressure, heart rate, and stroke volume increased immediately after TAVI (all p < 0.005), and left ventricular ejection time (LVET) immediately decreased with 10 ms (95%CI = −4 to −16, p < 0.001). Overall HRQoLindex increased from 0.810 [0.662–0.914] before to 0.887 [0.718–0.953] after TAVI (p = 0.016). An immediate decrease in LVET was associated with an increase in HRQoLindex (0.02 index points per 10 ms LVET decrease, p = 0.041). Pre-procedural CPI and LVEF did not predict hemodynamic changes or change in HRQoL.ConclusionTAVI resulted in an immediate hemodynamic response and increase in HRQoL. Immediate reduction in LVET, suggesting unloading of the ventricle, was associated with an increase in HRQoL, but neither pre-procedural CPI nor LVEF predicted these changes.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03088787

When and how to survey potential respondents is often determined by budgetary and external constraints, but choice of survey modality may have enormous implications for data quality. Different survey modalities may be differentially susceptible to measurement error attributable to interviewer assignment, known as interviewer effects. In this paper, we leverage highly similar surveys, one conducted face-to-face (FTF) and the other via phone, to examine variation in interviewer effects across survey modality and question type. We find that while there are no cross-modality differences for simple questions, interviewer effects are markedly higher for sensitive questions asked over the phone. These findings are likely explained by the enhanced ability of in-person interviewers to foster rapport and engagement with respondents. We conclude with a thought experiment that illustrates the potential implications for power calculations, namely, that using FTF data to inform phone surveys may substantially underestimate the necessary sample size for sensitive questions.

Abstract Background For uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children ≤ 5 years) and Asia. Methods The study was a randomized, double-blind, single-dose, multi-arm clinical trial in patients aged > 6 months to 5 years and 20 Asian patients. None of the treatment arms met the target efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine dose. Efficacy rates were low in Vietnamese patients, ranging from 20 to 40%. A clear relationship was found between drug exposure (artefenomel and ferroquine concentrations at Day 7) and efficacy (primary endpoint), with higher concentrations of both drugs resulting in higher efficacy. Six distinct kelch-13 mutations were detected in parasite isolates from 10/272 African patients (with 2 mutations known to be associated with artemisinin resistance) and 18/20 Asian patients (all C580Y mutation). Vomiting within 6 h of initial artefenomel administration was common (24.6%) and associated with lower drug exposures. Conclusion The efficacy of artefenomel/ferroquine combination was suboptimal in African children aged ≤ 5 years, the population of interest, and vomiting most likely had a negative impact on efficacy. Trial registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612&draw=2&rank=1

Objective: This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs). Methods: The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts. Results: Of 1647 individuals with OC recorded in the Brazilian Database of Craniofacial Anomalies, 100 individuals were selected for chromosome microarray analysis (CMA). Among these, 44 individuals were clinically classified as NSOC and 56 as SOC. CMA was performed for both groups, and abnormal CMA was identified in 9%, all previously classified as SCO. The clinical and CMA data analyses showed a significant predominance of abnormal CMA in individuals classified as SOC (p = 0.0044); prematurity, weight, length, and head circumference at birth were significantly lower in the group with abnormal CMA. Besides, minor signs were significantly higher in this group (p = 0.0090). Conclusion: The rigorous selection of cases indicates that the significant variables could help in early recognition of SOC. This study reinforces the importance of applying the CMA technique to establish the diagnosis of SOC. This is an important and universal issue in clinical practice for intervention, care, and genetic counseling.

Abstract Background Beginning in the last century, coral reefs have suffered the consequences of anthropogenic activities, including oil contamination. Chemical remediation methods, such as dispersants, can cause substantial harm to corals and reduce their resilience to stressors. To evaluate the impacts of oil contamination and find potential alternative solutions to chemical dispersants, we conducted a mesocosm experiment with the fire coral Millepora alcicornis, which is sensitive to environmental changes. We exposed M. alcicornis to a realistic oil-spill scenario in which we applied an innovative multi-domain bioremediator consortium (bacteria, filamentous fungi, and yeast) and a chemical dispersant (Corexit® 9500, one of the most widely used dispersants), to assess the effects on host health and host-associated microbial communities. Results The selected multi-domain microbial consortium helped to mitigate the impacts of the oil, substantially degrading the polycyclic aromatic and n-alkane fractions and maintaining the physiological integrity of the corals. Exposure to Corexit 9500 negatively impacted the host physiology and altered the coral-associated microbial community. After exposure, the abundances of certain bacterial genera such as Rugeria and Roseovarius increased, as previously reported in stressed or diseased corals. We also identified several bioindicators of Corexit 9500 in the microbiome. The impact of Corexit 9500 on the coral health and microbial community was far greater than oil alone, killing corals after only 4 days of exposure in the flow-through system. In the treatments with Corexit 9500, the action of the bioremediator consortium could not be observed directly because of the extreme toxicity of the dispersant to M. alcicornis and its associated microbiome. Conclusions Our results emphasize the importance of investigating the host-associated microbiome in order to detect and mitigate the effects of oil contamination on corals and the potential role of microbial mitigation and bioindicators as conservation tools. Chemical dispersants were far more damaging to corals and their associated microbiome than oil, and should not be used close to coral reefs. This study can aid in decision-making to minimize the negative effects of oil and dispersants on coral reefs. Video abstract

Abstract This nutrition consensus document is the first to coordinate the efforts of three professional organizations - the Brazilian Association of Nutrition (Asbran), the Brazilian Society of Nephrology (SBN), and the Brazilian Society of Parenteral and Enteral Nutrition (Braspen/SBNPE) - to select terminology and international standardized tools used in nutrition care. Its purpose is to improve the training delivered to nutritionists working with adult patients with chronic kidney disease (CKD). Eleven questions were developed concerning patient screening, care, and nutrition outcome management. The recommendations set out in this document were developed based on international guidelines and papers published in electronic databases such as PubMed, EMBASE(tm), CINHAL, Web of Science, and Cochrane. From a list of internationally standardized terms, twenty nutritionists selected the ones they deemed relevant in clinical practice involving outpatients with CKD. The content validity index (CVI) was calculated with 80% agreement in the answers. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to assess the strength of evidence and recommendations. A total of 107 terms related to Nutrition Assessment and Reassessment, 28 to Diagnosis, nine to Intervention, and 94 to Monitoring and Evaluation were selected. The list of selected terms and identified tools will be used in the development of training programs and the implementation of standardized nutrition terminology for nutritionists working with patients with chronic kidney disease in Brazil.

Introduction: Point-of-care ultrasound (POCUS) is a rapid bedside tool, particularly in undifferentiated emergency department patients. Point-of-care ultrasound can investigate potential intra-abdominal infections in febrile patients, especially in the elderly, who often present atypically without abdominal pain or localizing symptoms.Case Report: We highlight the important POCUS findings of cholecystoduodenal fistula and staghorn calculus in a febrile, elderly patient with dementia.Conclusion: Early recognition of cholecystoduodenal fistula and staghorn calculus using POCUS can expedite appropriate antibiotic and interventional treatment for improved patient outcomes.

PurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P

Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.

In the United States, over 2 million individuals openly identify with a gender that differs from their sex assigned at birth. A cancer diagnosis is physically and psychologically taxing-and, in some, traumatic. However, for transgender and gender-diverse (TGD) people, many of whom have experienced discrimination in myriad health care settings, the challenges may be even greater. These recommendations focus on how best to deliver quality cancer care to transgender men (individuals who identify as men but were assigned female sex at birth), transgender women (individuals who identify as women but were assigned male sex at birth), and people who identify somewhere beyond this gender spectrum as nonbinary or using other terms, based on the available, albeit sparse, literature. This review broaches: (1) the epidemiology of cancer in TGD individuals, including the incidence of cancer and cancer-related mortality; (2) cancer center practices that are welcoming and affirming to TGD patients; (3) the need for awareness and intentionality in the spaces of diagnosis and treatment for cancer; (4) the inevitable conclusion that gender differences exist but much more needs to be learned about the impact of gender-affirming therapy, consisting of gender-affirming surgeries and gender-affirming hormone therapy, on cancer therapy; and (5) the efficacy and perceived safety of antineoplastic therapy and gender-affirming hormone therapy.

Microbial metabolomics studies are a common approach for identifying microbial strains that have a capacity to produce new chemistries both in vitro and in situ. A limitation to applying microbial metabolomics to the discovery of new chemical entities is the rediscovery of known compounds, or known unknowns. One factor contributing to this rediscovery is that the majority of laboratories use one ionization source─electrospray ionization (ESI)─to conduct metabolomics studies. Although ESI is an efficient, widely adopted ionization method, its widespread use may contribute to the reidentification of known metabolites. Here, we present the use of a dielectric barrier discharge ionization (DBDI) for microbial metabolomics applications through the use of soft ionization chemical reaction in-transfer (SICRIT). Additionally, we compared SICRIT to ESI using two different Vibrio species: Vibrio fischeri, a symbiotic marine bacterium, and Vibrio cholerae, a pathogenic bacterium. Overall, we found that the SICRIT source ionizes a different set of metabolites than ESI, and it has the ability to ionize lipids more efficiently than ESI in the positive mode. This work highlights the value of using more than one ionization source for the detection of metabolites.

White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating brain health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. Lesion network mapping (LNM) enables us to infer if brain networks are connected to lesions and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed LNM to test the following hypotheses: (i) LNM-informed markers surpass WMH volumes in predicting cognitive performance; and (ii) WMH contributing to cognitive impairment map to specific brain networks. We analysed cross-sectional data of 3485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in four cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity to 480 atlas-based grey and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. We compared the capacity of total and regional WMH volumes and LNM scores in predicting cognitive function using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention/executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater connectivity to WMH, in grey and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network integrity, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Climate change is shifting the timing of organismal life-history events. Although consequential food-web mismatches can emerge if predators and prey shift at different rates, research on phenological shifts has traditionally focused on single trophic levels. Here, we analysed >2000 long-term, monthly time series of phytoplankton, zooplankton, and fish abundance or biomass for the San Francisco, Chesapeake, and Massachusetts bays. Phenological shifts occurred in over a quarter (28%) of the combined series across all three estuaries. However, phenological trends for many taxa (ca. 29-68%) did not track the changing environment. While planktonic taxa largely advanced their phenologies, fishes displayed broad patterns of both advanced and delayed timing of peak abundance. Overall, these divergent patterns illustrate the potential for climate-driven trophic mismatches. Our results suggest that even if signatures of global climate change differ locally, widespread phenological change has the potential to disrupt estuarine food webs.

SignificanceFAK inhibitors are in combinatorial clinical testing with agents that prevent Ras-Raf-MAPK pathway activation in various cancers. This study suggests that nuclear FAK limits ERK/MAPK activation in supporting HGSOC cell survival to cisplatin stress. Overall, it is likely that targets of FAK-mediated survival signaling may be tumor type- and context-dependent.