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Abstract Kelps are vital for marine ecosystems, yet the genetic diversity underlying their capacity to adapt to climate change remains unknown. In this study, we focused on the kelp Macrocystis pyrifera a species critical to coastal habitats. We developed a protocol to evaluate heat stress response in 204 Macrocystis pyrifera genotypes subjected to heat stress treatments ranging from 21 °C to 27 °C. Here we show that haploid gametophytes exhibiting a heat-stress tolerant (HST) phenotype also produced greater biomass as genetically similar diploid sporophytes in a warm-water ocean farm. HST was measured as chlorophyll autofluorescence per genotype, presented here as fluorescent intensity values. This correlation suggests a predictive relationship between the growth performance of the early microscopic gametophyte stage HST and the later macroscopic sporophyte stage, indicating the potential for selecting resilient kelp strains under warmer ocean temperatures. However, HST kelps showed reduced genetic variation, underscoring the importance of integrating heat tolerance genes into a broader genetic pool to maintain the adaptability of kelp populations in the face of climate change.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Carcinoid heart disease is a rare complication of carcinoid syndrome, resulting in right-sided valvular heart disease and subsequent heart failure due to long-term exposure to vasoactive substances. The management of this condition is complex, often requiring surgical intervention. Current perioperative regimens entail the use of prophylactic somatostatin analogs to prevent carcinoid crisis; however, regimens vary widely among practitioners and evidence supporting their efficacy in this clinical setting is mixed. This case report describes the perioperative management of a 65-year-old man with carcinoid heart disease requiring tricuspid and pulmonary valve replacement surgery. As an adjunct to somatostatin analog therapy, the novel tyrosine hydroxylase inhibitor, telotristat, was initiated preoperatively. This combination resulted in normalization of preoperative urinary 5-HIAA levels. The patient successfully underwent tricuspid and pulmonic valve replacement without evidence of carcinoid crisis. This clinical case is the first published documenting the use of telotristat in the perioperative period in a patient with carcinoid syndrome and carcinoid heart disease and was associated with a good long-term outcome despite the high-risk nature of the case.

Abstract Background Children are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine–artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM). Methods An integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Introduction: Scientists use donated biospecimens to create organoids, miniature copies of patient tumors1 that are revolutionizing precision medicine2 and drug discovery. However, current biobanking platforms remove patient names to protect privacy, precluding communication of health information and research findings between bench and bedside3. We leverage tokenization, transparency, and privacy-preservation of blockchain technology to advance a decentralized biobanking prototype empowering patient engagement in organoid research. Methods: We design and develop a proof-of-concept NFT framework4 for a simulated human cancer model research network. Our implementation deployed multiple smart contracts on Ethereum test networks which minted NFTs representing each stakeholder, biospecimen, and organoid, a NodeJS server using a Metamask wallet to interact with blockchain through an Infura hosted node, and a Flutter mobile application connected to a Firebase Database to demonstrate biobanking activities. Results: Our prototype demonstrated the viability of NFTs representing patients, physicians, scientists, and organoids while preserving privacy, and displayed how decentralized biobanking could be integrated into existing biobanking platforms5. The application featured key activities for patients, including biospecimen tracking, the ability to view organoids, learn about ongoing studies, and peer-to-peer communications with scientists. Discussion: Our prototype demonstrates proof-of-concept for a web3 platform that engages patients, physicians and scientists in an privacy-preserving organoid community. Further research is needed to advance decentralized biobanking features, encapsulating complex organoid research activities, and to assess feasibility and acceptability of implementing our approach.

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center (MPTC) and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three-time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n=4) were compared to photon radiation (n=4). Additional control groups included healthy age- and sex-matched controls (n=5), head and neck cancer patients who never received radiation therapy (n=8), and patients with oral inflammatory disease (n=3). Results: Photon therapy patients presented with a lower microbial alpha diversity at all timepoints and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. Bacterial de novo pyrimidine biosynthesis pathway and nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for proliferation of pathogenic bacteria. Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status.

Electroporation (EP) stands out as a promising non-viral plasmid delivery strategy, although achieving optimal transfection efficiency in vivo remains a challenge. A noteworthy advancement in the field of in vivo EP is the application of hyaluronidase, an enzyme with the capacity to degrade hyaluronic acid in the extracellular matrix, which thereby enhances DNA transfer efficiency by 2- to 3-fold. This paper focuses on elucidating the mechanism of hyaluronidase’s impact on transfection efficiency. We demonstrate that hyaluronidase promotes a more uniform distribution of plasmid DNA (pDNA) within skeletal muscle. Additionally, our study investigates the effect of the timing of hyaluronidase pretreatment on EP efficiency by including time intervals of 0, 5, and 30 min between hyaluronidase treatment and the application of pulses. Serum levels of the pDNA-encoded transgene reveal a minimal influence of the hyaluronidase pretreatment time on the final serum protein levels following delivery in both mice and rabbit models. Leveraging bioimpedance measurements, we capture morphological changes in muscle induced by hyaluronidase treatment, which result in a varied pDNA distribution. Subsequently, these findings are employed to optimize EP electrical parameters following hyaluronidase treatment in animal models. This paper offers novel insights into the potential of hyaluronidase in enhancing the effectiveness of in vivo EP, as well as guides optimized electroporation strategies following hyaluronidase use.

Background: Left ventricular assist devices (LVADs) improve survival and quality of life, as either destination therapy or a bridge to transplantation. Although less-invasive hemisternotomy approaches for LVAD implantation are well studied, only a paucity of data is available in the literature on sternum-sparing bilateral minithoracotomy (BMT). Our centre has one of Canada’s most extensive experiences with the BMT approach. Herein, we compared LVAD implantation via BMT with patients who received full median sternotomy or hemisternotomy. Methods: A single-centre retrospective review of data from Foothills Medical Centre (Calgary, Canada) was performed. Patients underwent LVAD insertion from 2012 to 2019, receiving either BMT (n = 11) or sternotomy (full median sternotomy or upper hemisternotomy with left minithoracotomy; n = 38). Intraoperative and early postoperative outcomes were assessed. Results: Patients who received BMT had significantly fewer transfusions of red blood cells, fresh frozen plasma, and platelets. The BMT group had lower chest-tube output in the first 12 hours. No significant differences occurred in ventilation time, intensive care unit length of stay, mortality, stroke, or reoperation for bleeding. Conclusions: Outcomes suggest that sternum-sparing LVAD implantation is a feasible alternative to sternotomy, leading to less postoperative blood loss and transfusion in the early postoperative period. Less transfusion is particularly valuable in this patient population, to reduce antigen-related sensitization prior to transplantation. Additional study is needed to assess potential benefits related to right heart function, postoperative mobility, and re-entry for transplantation. Résumé: Introduction: Les dispositifs d’assistance ventriculaire gauche (DAVG) contribuent à améliorer la survie et la qualité de vie, soit en traitement définitif ou en attente d’une transplantation. Bien que des approches d’hémisternotomie moins invasives lors de l’implantation d’un DAVG font l’objet d’un bon nombre d’études, seules de rares données sont disponibles dans la littérature sur la minithoracotomie bilatérale (MTB) sans ouverture du sternum. Notre centre possède l’une des expériences les plus approfondies au Canada de l’approche par MTB. Dans le présent article, nous avons comparé l’implantation du DAVG par MTB chez les patients qui avaient subi une sternotomie médiane complète ou une hémisternotomie. Méthodes: Nous avons réalisé une revue rétrospective unicentrique des données du Foothills Medical Centre (Calgary, Canada). Les patients avaient subi l’insertion d’un DAVG de 2012 à 2019, soit par MTB (n = 11) ou par sternotomie (sternotomie médiane complète ou hémisternotomie supérieure associée à une minithoracotomie gauche ; n = 38). Nous avons évalué les résultats peropératoires et postopératoires précoces. Résultats: Les patients qui avaient subi une MTB avaient eu significativement moins de transfusions de globules rouges, de plasma frais congelé et de plaquettes. Le groupe de MTB avait un plus faible débit du drain thoracique dans les 12 premières heures. Aucune différence significative dans la durée de ventilation, la durée du séjour aux soins intensifs, la mortalité, l’accident vasculaire cérébral ou la réopération en raison d’un saignement n’a été observée. Conclusions: Les résultats montrent que l’implantation de DAVG sans ouverture du sternum est une alternative à la sternotomie, qui entraîne moins de pertes de sang postopératoires et de transfusions en phase postopératoire précoce. Un moins grand nombre de transfusions est particulièrement important au sein de cette population de patients afin de réduire la sensibilisation aux antigènes avant la transplantation. D’autres études sont nécessaires pour évaluer les avantages potentiels liés à la fonction du cœur droit, la mobilité après l’opération et la réadmission pour une transplantation.

The lack of community-relevant flood informational resources and tools often results in inadequate and divergent understandings of flood risk and can impede communities' ability to function cohesively in the face of increasing flood threats. The current study reports on a set of workshops that the authors conducted with various groups (citizens, city engineers and planners, realtors and builders, and media representatives) within a flood prone community to evaluate how novel hydroinformatic tools that include hydrodynamic modeling, geospatial visualization, and socioeconomic analysis can enhance understanding of flood risk and engagement in flood risk mitigation among diverse community members. The workshops were designed to help identify stakeholder preferences regarding key functionality needed for integrated hydroinformatic technologies and socioeconomic analyses for flood risk reduction. Workshop participants were asked to use and comment on examples of prototype flood risk informational tools, such as: (1) flood damage estimation tool, (2) drivability and emergency accessibility tool, and (3) community-scale social and economic metrics tool. Data gathered from workshops were analyzed using qualitative analysis based on a grounded-theory approach. Data were coded by hand based on themes identified by the research team and incorporated deviant case analysis to ensure minority opinions was represented. The study results are focused on the following main themes and how flood tools can address them: (1) improving the understanding of flood risk and engagement in flood risk mitigation, (2) reducing the gap between individual and community risk, (3) challenges in communicating flood risk information, (4) enhancing relevance to and engagement of the community, and (5) enabling actionable information. Our research demonstrates the need for community-anchored tools and technologies that can illustrate local context, include local historical and simulated events at multiple levels of community impact, enable analyses by flood professionals while also providing simplified tools of use by citizens, and allow individuals to expand their knowledge beyond their homes, businesses, and places of work.

Summary: Background: This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19. Methods: This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18–65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population. Findings: The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ). Interpretation: There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated. Funding: Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

A new patient satisfaction measure called the Radiation Oncology Patient Satisfaction (ROPS) questionnaire is used in this study to measure satisfaction data for radiation oncology in private practice. Limitations of existing literature on patient satisfaction demonstrated a need to develop a questionnaire that was more tailored to analyze patient satisfaction among those utilizing private oncology centers within the U.S. healthcare system. This need was met by this study’s development of the ROPS questionnaire, which was a variation of 2 existing constructs that are presented in the text. The questionnaire was fielded among patients at a private cancer radiation treatment clinic in Florida (n = 950). Data analysis tested the psychometric properties of our revised construct and its predictive validity for 2 patient satisfaction outcomes: (1) likelihood of recommending this treatment center to family members/close friends and (2) overall satisfaction with treatment. Each of the ROPS variables were found to make a legitimate contribution to evaluating patients’ overall satisfaction with radiation treatment. Findings indicated organizational setting was of vital importance when conducting patient- centered research on satisfaction. Treatment factors in ROPS can be adjusted to measure satisfaction with chemotherapy or other modalities in addition to radiation treatment. Authors recommend radiation oncology clinics regularly monitor patient satisfaction, especially if/when they experience organizational changes, such as when a new physician joins the practice or if/when the national or local landscape undergoes significant shifts in norms and expectations like we have seen happen with COVID-19.

Abstract Background RNA sequencing analysis focus on the detection of differential gene expression changes that meet a two-fold minimum change between groups. The variability present in RNA sequencing data may obscure the detection of valuable information when specific genes within certain samples display large expression variability. This paper develops methods that apply variance and dispersion estimates to intra-group data to identify genes with expression values that diverge from the group envelope. STRING database analysis of the identified genes characterize gene affiliations involved in physiological regulatory networks that contribute to biological variability. Individuals with divergent gene groupings within network pathways can thereby be identified and judiciously evaluated prior to standard differential analysis. Results A three-step process is presented for evaluating biological variability within a group in RNA sequencing data in which gene counts were: (1) scaled to minimize heteroscedasticity; (2) rank-ordered to detect potentially divergent “trendlines” for every gene in the data set; and (3) tested with the STRING database to identify statistically significant pathway associations among the genes displaying marked trendline variability and dispersion. This approach was used to identify the “trendline” profile of every gene in three test data sets. Control data from an in-house data set and two archived samples revealed that 65–70% of the sequenced genes displayed trendlines with minimal variation and dispersion across the sample group after rank-ordering the samples; this is referred to as a linear trendline. Smaller subsets of genes within the three data sets displayed markedly skewed trendlines, wide dispersion and variability. STRING database analysis of these genes identified interferon-mediated response networks in 11–20% of the individuals sampled at the time of blood collection. For example, in the three control data sets, 14 to 26 genes in the defense response to virus pathway were identified in 7 individuals at false discovery rates ≤1.92 E-15. Conclusions This analysis provides a rationale for identifying and characterizing notable gene expression variability within a study group. The identification of highly variable genes and their network associations within specific individuals empowers more judicious inspection of the sample group prior to differential gene expression analysis.

Abstract Background Osteoarthritis (OA) is a common condition that is often associated with chronic pain. Pain often leads patients to seek healthcare advice and treatment. In this retrospective cohort analysis of German longitudinal healthcare claims data, we aimed to explore the healthcare resource utilisation (HRU) and related healthcare costs for patients with OA who develop chronic pain. Methods Patient-level data was extracted from the German Institut für Angewandte Gesundheitsforschung (InGef) database. Insured persons (≥18 years) were indexed between January 2015 and December 2017 with a recent (none in the last 2 years) diagnosis of OA. HRU and costs were compared between patients categorised as with (identified via diagnosis or opioid prescription) and without chronic pain. Unweighted HRU (outpatient physician contacts, hospitalisations, prescriptions for physical therapy or psychotherapy, and incapacity to work) and healthcare costs (medication, medical aid/remedy, psychotherapy, inpatient and outpatient and sick pay in Euros [quartile 1, quartile 3]) were calculated per patient for the year following index. Due to potential demographic and comorbidity differences between the groups, inverse probability of treatment weighting (IPTW) was used to estimate weighted costs and rate ratio (RR; 95% confidence interval) of HRU by negative binomial regression modelling. Results Of 4,932,543 individuals sampled, 238,306 patients with OA were included in the analysis: 80,055 (34%) categorised as having chronic pain (24,463 via opioid prescription) and 158,251 (66%) categorised as not having chronic pain. The chronic pain cohort was slightly older, more likely to be female, and had more comorbidities. During the year following index, unweighted and IPTW-weighted HRU risk and healthcare costs were higher in patients with chronic pain vs those without for all categories. This led to a substantially higher total annual healthcare cost ─ observed mean; €6801 (1439, 8153) vs €3682 (791, 3787); estimated RR = 1.51 (1.36, 1.66). Conclusions German patients with chronic pain and OA have higher healthcare costs and HRU than those with OA alone. Our findings suggest the need for better prevention and treatment of OA in order to reduce the incidence of chronic pain, and the resultant increase in disease burden experienced by patients.

Purpose: Poor nutrition is highly implicated in the pathogenesis of cancer and affects the survival of patients during and after completion of definitive therapies. Mechanistic evidence accumulated over the last century now firmly places dysregulated cellular energetics within the emerging hallmarks of cancer. Nutritional intervention studies often aim to either enhance treatment effect or treat nutritional deficiencies that portend poor prognoses. Patients living within food priority areas have a high risk of nutritional need and are more likely to develop comorbidities, including diabetes, hypertension, renal disease, and cardiovascular risk factors. Unfortunately, there is currently a paucity of data analyzing the impact of food priority areas on cancer outcomes. Methods: Therefore, we performed a review of the literature focusing on the molecular and clinical interplay of cancer and nutrition, the importance of clinical trials in elucidating how to intervene in this setting and the significance of including citizens who live in food priority areas in these future prospective studies. Conclusions: Given the importance of nutrition as an emerging hallmark of cancer, further research must be aimed at directing the optimal nutrition strategy throughout oncologic treatments, including the supplementation of nutritious foods to those that are otherwise unable to attain them

La production de ce numéro a été motivée par le peu d'attention accordé aux oeuvres "mineures" de Maryse Condé. Les contributeurs se sont penchés notamment sur les ouvrages de Condé destinés à la jeunesse ainsi qu'à ses pièces de théâtre. Ils ont fait ressortir non seulement la richesse et diversité que ces ouvrages apportent à l'ensemble du discours condéen, mais aussi les problèmes et préoccupations qui sous-tendent la façon particulière dont Condé a conçu son rôle d'écrivaine francophone dans un contexte postcolonial.

Introduction: Obstructive sleep apnea (OSA) is a common condition in the United States that is strongly linked to metabolic disease, cardiovascular disease, and increased mortality. Uninsured populations experience sleep health disparities, including delayed recognition, diagnosis, and treatment of OSA due to barriers accessing and affording care. Partnerships between primary care clinics and sleep medicine specialists for sleep apnea management have the potential to increase screening, testing, and treatment among underserved populations. Here, we present an integrated and cost-effective model that is easier to navigate for patients while maintaining high quality care. Methods: We designed and implemented a specialty sleep clinic at Shade Tree Clinic, Vanderbilt’s student-run, free primary care clinic. Patients with signs and symptoms of OSA were identified at primary care appointments and screened using the STOP-BANG questionnaire. Clinic visits took place over telehealth with a medical student and sleep specialist. Patients were diagnosed using a home sleep test, and if indicated, were prescribed and given a CPAP device for treatment. CPAP adherence was monitored using a cloud-based remote monitoring system. Results: From December 2020 through August 2021, we hosted 6 telehealth Sleep Clinics, seeing a total of 28 patients across these visits. We have received a total of 37 referrals and have coordinated sleep evaluations and diagnostic testing for 18 of these patients so far. Prior to initiation of the sleep clinic, there were 17 patients on our primary care panel at Shade Tree with a diagnosis of OSA. These patients were using donated equipment and many had been lost to follow-up or had broken parts. We were able to replace 10 of these patient’s CPAP devices and plan to replace the remaining seven. Conclusions: We have created a model of integrated specialty care that is efficient and cost-effective. This paradigm can be replicated for the many specialties that are typically overlooked and undertreated when working with uninsured patients. As awareness of this sleep medicine program becomes more widespread at Shade Tree Clinic, we anticipate reaching more primary care patients with signs and symptoms of sleep apnea through student education, cost-effective diagnostics, and partnership with sleep specialists.

BackgroundAtrial fibrillation (AF) burden on patients and healthcare systems warrants innovative strategies for screening asymptomatic individuals.ObjectiveWe sought to externally validate a predictive model originally developed in a German population to detect unidentified incident AF utilising real-world primary healthcare databases from countries in Europe and Australia.MethodsThis retrospective cohort study used anonymized, longitudinal patient data from 5 country-level primary care databases, including Australia, Belgium, France, Germany, and the UK. The study eligibility included adult patients (≥45 years) with either an AF diagnosis (cases) or no diagnosis (controls) who had continuous enrolment in the respective database prior to the study period. Logistic regression was fitted to a binary response (yes/no) for AF diagnosis using pre-determined risk factors.ResultsAF patients were from Germany (n = 63,562), the UK (n = 42,652), France (n = 7,213), Australia (n = 2,753), and Belgium (n = 1,371). Cases were more likely to have hypertension or other cardiac conditions than controls in all validation datasets compared to the model development data. The area under the receiver operating characteristic (ROC) curve in the validation datasets ranged from 0.79 (Belgium) to 0.84 (Germany), comparable to the German study model, which had an area under the curve of 0.83. Most validation sets reported similar specificity at approximately 80% sensitivity, ranging from 67% (France) to 71% (United Kingdom). The positive predictive value (PPV) ranged from 2% (Belgium) to 16% (Germany), and the number needed to be screened was 50 in Belgium and 6 in Germany. The prevalence of AF varied widely between these datasets, which may be related to different coding practices. Low prevalence affected PPV, but not sensitivity, specificity, and ROC curves.ConclusionsAF risk prediction algorithms offer targeted ways to identify patients using electronic health records, which could improve screening number and the cost-effectiveness of AF screening if implemented in clinical practice.

Les multiples références à l’œuvre d’Aimé Césaire dans Un Plat de porc aux bananes vertes (1967) d’André et Simone Schwarz-Bart suggèrent un dialogue, parfois implicite, entre la narratrice/protagoniste Mariotte et son compatriote martiniquais. Cet intertexte dialogique se reflète dans la composition des sept cahiers de Mariotte qui tente d’expliquer aux lecteurs sa lutte pour reconstituer la mémoire de son pays natal dans des conditions dictées, au milieu du XXe siècle, par un système social raciste, oppressif et déshumanisant. Deux figures en particulier de l’œuvre de Césaire se détachent des cahiers de Mariotte, à savoir le Rebelle qu’elle associe à un homme qu’elle a connu quand elle était enfant, et le « vieux nègre dans le tramway », personnage du Cahier d’un retour au pays natal (1939). Mais avant d’assumer elle-même ces deux rôles, Mariotte adresse une prière à « Saint-Césaire », lui demandant de la rejoindre dans son chant mémorial. Dans des notes placées à la fin du texte, les auteurs semblent dire que Mariotte a cité Césaire de façon plutôt cavalière, ce qui crée une certaine ambiguïté au sujet de ce rapport intertextuel.

Data from five sites of the International Long Term Ecological Research (ILTER) network in the North-Eastern Pacific, Western Arctic Ocean, Northern Baltic Sea, South-Eastern North Sea and in the Western Mediterranean Sea were analyzed by dynamic factor analysis (DFA) to trace common multi-year trends in abundance and composition of phytoplankton, benthic fauna and temperate reef fish. Multiannual trends were related to climate and environmental variables to study interactions. Two common trends in biological responses were detected, with temperature and climate indices as explanatory variables in four of the five LTER sites considered. Only one trend was observed at the fifth site, the Northern Baltic Sea, where no explanatory variables were identified. Our findings revealed quasi-synchronous biological shifts in the different marine ecosystems coincident with the 2000 climatic regime shift and provided evidence on a possible further biological shift around 2010. The observed biological modifications were coupled with abrupt or continuous increase in sea water and air temperature confirming the key-role of temperature in structuring marine communities.

Mobile computing devices (MCDs), such as smartphones and tablets, are revolutionizing medical practice. These devices are almost universally available and offer a multitude of capabilities, including online features, streaming capabilities, high-quality cameras, and numerous applications. Within the surgical field, MCDs are increasingly being used for simulations. Microsurgery is an expanding field of surgery that presents unique challenges to both trainees and trainers. Simulation-based training and assessment in microsurgery currently play an integral role in the preparation of trainee surgeons in a safe and informative environment. MCDs address these challenges in a novel way by providing valuable adjuncts to microsurgical training, assessment, and clinical practice through low-cost, effective, and widely accessible solutions. Herein, we present a review of the capabilities, accessibility, and relevance of MCDs for technical skills acquisition, training, and clinical microsurgery practice, and consider the possibility of their wider use in the future of microsurgical training and education.

BackgroundIn Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.Methods and findingsThis single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.ConclusionsPyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria.Trial registrationClinicalTrials.gov NCT03201770.

Abstract Background When discussing results medical research articles often tear substantive and statistical (methodical) contributions apart, just as if both were independent. Consequently, reasoning on bias tends to be vague, unclear and superficial. This can lead to over-generalized, too narrow and misleading conclusions, especially for causal research questions. Main body To get the best possible conclusion, substantive and statistical expertise have to be integrated on the basis of reasonable assumptions. While statistics should raise questions on the mechanisms that have presumably created the data, substantive knowledge should answer them. Building on the related principle of Bayesian thinking, we make seven specific and four general proposals on writing a discussion section. Conclusion Misinterpretation could be reduced if authors explicitly discussed what can be concluded under which assumptions. Informed on the resulting conditional conclusions other researchers may, according to their knowledge and beliefs, follow a particular conclusion or, based on other conditions, arrive at another one. This could foster both an improved debate and a better understanding of the mechanisms behind the data and should therefore enable researchers to better address bias in future studies.