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Abstract Introduction Although cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, research describing the patient experience is limited. This study sought to create a conceptual model of non-metastatic disease, to assess patient-reported outcome (PRO) instruments commonly used in CSCC against this model, and to develop a patient-relevant measurement strategy for evaluating the benefit of new therapies. Methods Researchers conducted a literature review, a review of patient blogs, and interviews with dermatologists to draft the conceptual model. A total of 22 patients with CSCC participated in 60-min phone interviews, which were subsequently transcribed, coded, and analyzed; the conceptual model was then updated. PRO instruments used in CSCC were assessed for content validity on the basis of this. Results The CSCC patient experience includes physical symptoms, psychological impacts, and behavior changes. Existing PRO instruments were assessed against the conceptual model using targeted subdomains considered to be relevant for assessing clinical benefit. Four modules of the FACE-Q® Skin Cancer instrument, plus de novo items developed for concepts not assessed by the FACE-Q® [lesion symptoms, negative treatment effects (including symptomatic), and experience of care], provide the best coverage for the concepts of interest hypothesized to show the benefit of novel treatments. Conclusions This research provides a comprehensive understanding of the experience of patients with non-metastatic CSCC, and the effects of its treatment. It also identifies unmet needs in a subgroup of patients reporting negative treatment experiences. Further cognitive debriefing and psychometric analysis of de novo items are warranted for applications in clinical research.

Abstract Background Acne vulgaris is a chronic inflammatory skin condition with a multifactorial pathogenesis. The clinical appearance of acne and its sequelae may differ according to phototypes. Data regarding the potential benefit of dermocosmetics (DC) regardless of phototype are lacking and assessing acne improvement can be difficult, given the lack of visual support in people with skin of colour. A DC regimen, combining a cleanser and a cream, both containing thermal spring water, has been developed for the management of mild‐to‐moderate acne, for all skin phototypes studied. Objectives To assess the efficacy and local tolerance of a DC routine in mild‐to‐moderate acne and to visualize the clinical improvement in all skin phototypes. Methods In an open‐labelled, multicentre clinical study, subjects of any phototype aged above 11 years and above with mild (N = 48, 55.2%) or moderate (N = 39, 44.8%) facial acne applied the DC twice daily for 56 days. No other acne care was allowed. Acne severity, as well as inflammatory and noninflammatory lesion counts, were assessed at baseline, Days 28 and 56. Photographs were taken using a novel imaging tool based on multimodal acquisition, to show clinical improvement over time. Results Eighty‐seven subjects, 41 adults and 46 adolescents, were included; 59.8% were female and were aged between 11 and 44 years. The total acne lesion count decreased by 34%, the noninflammatory lesion count by 28%, and the inflammatory lesion count by 52% at Day 56. All % changes were statistically significant (p

Abstract Fusobacterium necrophorum is a Gram-negative anaerobic bacterium responsible for localized infections of the oropharynx that can evolve into bacteremia and/or septic thrombophlebitis of the jugular vein or peritonsillar vein, called Lemierre’s syndrome. To identify microbial genetic determinants associated with the severity of this life-threatening disease, 70 F. necrophorum strains were collected and grouped into two categories according to the clinical presentation: (i) localized infection, (ii) bacteremia with/without Lemierre’s syndrome. Comparative genomic analyses revealed two clades with distinct genetic content, one clade being significantly enriched with isolates from subjects with bacteremia. To identify genetic determinants contributing to F. necrophorum pathogenicity, genomic islands and virulence factor orthogroups (OVFs) were predicted. The presence/absence profiles of OVFs did not group isolates according to their clinical category, but rather according to their phylogeny. However, a variant of lktA, a key virulence factor, with a frameshift deletion that results in two open reading frames, was associated with bacteremia. Moreover, a genome-wide association study identified three orthogroups associated with bacteremic strains: (i) cas8a1, (ii) a sodium/solute symporter, and (iii) a POP1 domain-containing protein. Further studies must be performed to assess the functional impact of lktA mutation and of these orthogroups on the physiopathological mechanisms of F. necrophorum infections.

Abstract Background The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID‑19 (SE-LC19), and establish its content validity. Methods The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID. A 2-part mixed-method approach was employed. Part 1: Qualitative interviews with a purposive sample of 41 patients with confirmed long COVID were conducted for the content validation of SE-LC19. During cognitive debriefing interviews, patients were asked to describe their understanding of the instrument’s instructions, specific symptoms, response options, and recall period to ensure its relevance and comprehensiveness. Five clinicians of different medical specialties who regularly treated patients with long COVID were also interviewed to obtain their clinical expert opinions on SE-LC19. Part 2: Exploratory Rasch Measurement Theory (RMT) analysis was conducted to evaluate the psychometric properties of the SE-LC19 data collected during the interviews. Results Overall, patients reported that the instructions, questions, recall period, and response options for SE-LC19 were comprehensive and relevant. Minor conceptual gaps reported by patients captured nuances in the experience of some symptoms that could be considered in future studies. Some patients suggested a revision of the recall period from 24 h to 7 days to be able to capture more symptoms given the waxing and waning nature of some symptoms. Clinicians found the instrument comprehensive with minimal suggestions regarding its content. Exploratory RMT analyses provided evidence that the SE-LC19 questionnaire performed as intended. Conclusion The present mixed-methods study in patients with confirmed long COVID supports the content validity and applicability of the SE-LC19 instrument to evaluate the symptoms of patients with long COVID. Further research is warranted to explore the psychometric properties of the instrument and refine a meaningful and robust patient-relevant endpoint for use in different settings such as clinical trials and clinical practice to track the onset, severity, and recovery of long COVID.

While social location substantially impacts faculty experiences on university campuses, comparatively little research has explored the experiences of undergraduate and graduate teaching assistants (TAs). Drawing on semi-structured interviews, this study explores how TAs at one Canadian university construct their identities as they teach. We employ the concepts of self-presentation and performativity to consider the interplay between TAs' socially-influenced enactments of self and how these are read and interpreted by students. Our findings suggest that TAs have markedly different experiences in the classroom based on their social location and that they engage in processes of impression management. Ultimately, our findings point toward a need to develop institutional initiatives that support TAs in navigating complex processes of embodiment, self-presentation, and disclosure in the classroom.

This research considers the ways in which digital agriculture (DA) technologies (like robotic machinery, big data applications, farm management software platforms and drones) fit into discourses of sustainable agriculture in the Canadian political and media landscape. To undertake this research, I conducted a discourse analysis of relevant government and media materials published between 2016 and 2022. What became evident was an ideology of optimization, which works to communicate that environmental sustainability needs to and will be optimized using DA technologies. I then consider how these findings are related to the federal fertilizer emissions reduction target, aiming to reduce emissions arising from fertilizer application in agricultural contexts by 30% below 2020 levels by 2030. I argue that discourse regarding this target deploys the ideology of optimization to keep current systems of fertilizer use in place, solidifying further the industrial and productivist paradigm of agriculture in Canada.

Objective: To present the first surgical video of robotic radical cystectomy with intracorporeal neobladder in a renal transplant recipient. Patient and surgical procedure: A 29-year-old solitary kidney male who previously underwent double renal transplants (2016 right and 2020 left iliac fossa) presented to our attention a wide urothelial carcinoma of the distal part of the right graft ureter extending to the bladder. At the transurethral resection, a muscle-invasive high-grade urothelial carcinoma was diagnosed. At the CT scan, the right renal graft appeared functionally excluded while the left one was well-vascularized and functioning, and no lymph node involvement or metastatic disease was reported. The patient was planned for surgery with curative intent. Robotic radical cystectomy, right graft radical nephroureterectomy, prophylactic bilateral native ureterectomy and Florence robotic intracorporeal neobladder (FloRIN) were performed. Results: The procedure was successfully completed. Technical aspects of the surgery are illustrated in the video. No intra- and postoperative complications were recorded. Blood losses were 200 mL. Operative time was 420 min. The mono J placed to protect the left renal graft was removed after two weeks, while the urinary catheter three weeks after a negative cystogram. The final pathology revealed a bladder pT2a G3 high-grade urothelial carcinoma and a pelvis and ureteral pT1 G3 high-grade urothelial carcinoma with carcinoma in situ. At one year after surgery, the patient was continent, potent, with insignificant residual volume and an unchanged renal function, and disease-free. Conclusions: In renal transplant recipients, robotic radical cystectomy with intracorporeal neobladder in renal transplant recipients is a safe and feasible procedure, guaranteeing optimal surgical and functional outcomes and a low complications rate.

AbstractOur recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.

BackgroundThe COVID-19 pandemic has prompted significant changes in healthcare, particularly affecting psychiatric and psychological Consultation-Liaison (CL) services in general hospital settings.AimTo assess the effects of COVID-19-related restrictions on utilization of psychiatric and psychological CL services in Northeast Italy during 2020, and to compare it to the use of services in the previous year (2019).MethodsThe study collected data on psychiatric and psychological consultations in 2019 and 2020 from a hospital database. It categorizes consultations by type of patient (inpatient or outpatient) and referral source (hospital wards, general practitioners, other specialists). Pandemic-related restrictions were classified as “lockdown,” “intermediate restrictions,” and “no or reduced restrictions” based on the Covid Stringency Index (CSI). Poisson regression models were employed to analyze the data.ResultsThe findings reveal a significant 28% increase in the number of psychiatric and psychological consultations in 2020. Consultations for outpatients increased by 51%, while those for inpatients decreased by 11%. However, the lockdown and intermediate restriction phases were deemed responsible of a decrease of 42.9% and 19.5% in consultations respectively.DiscussionThis study highlights the persistent psychological burden during the COVID-19 pandemic, alongside reduced CL services due to lockdown measures. Integrating telemedicine into these types of services becomes imperative for meeting patient needs during restrictions. These findings can inform policies and practices to improve effective mental health care delivery during and beyond pandemics. Future research should explore the impact of pandemic-related restrictions on mental healthcare across settings and clinical factors affecting service accessibility.

Abstract Longitudinal studies that continuously generate data enable the capture of temporal variations in experimentally observed parameters, facilitating the interpretation of results in a time-aware manner. We propose IL-VIS (incrementally learned visualizer), a new machine learning pipeline that incrementally learns and visualizes a progression trajectory representing the longitudinal changes in longitudinal studies. At each sampling time point in an experiment, IL-VIS generates a snapshot of the longitudinal process on the data observed thus far, a new feature that is beyond the reach of classical static models. We first verify the utility and correctness of IL-VIS using simulated data, for which the true progression trajectories are known. We find that it accurately captures and visualizes the trends and (dis)similarities between high-dimensional progression trajectories. We then apply IL-VIS to longitudinal multi-electrode array data from brain cortical organoids when exposed to different levels of quinolinic acid, a metabolite contributing to many neuroinflammatory diseases including Alzheimer’s disease, and its blocking antibody. We uncover valuable insights into the organoids’ electrophysiological maturation and response patterns over time under these conditions.

The Bosniak classification of renal cysts aims to provide a probabilistic risk assessment indicating the likelihood of malignancy from imaging findings. Originally designed to classify adult renal cysts based on computed tomography findings, the Bosniak classification has been extended to pediatric patients, with some adjustments made with the aim of accommodating magnetic resonance imaging (MRI) and ultrasonography (US). Bosniak IV lesions are rare in adolescents, indicating localized renal cell carcinoma and requiring surgical intervention. In contrast, Bosniak III lesions can be treated conservatively, although there is a lack of specific guidelines on their management. We present a case of a 14-year-old boy with a Bosniak III lesion, which was incidentally detected during the US evaluation of a left varicocele. After a 12-month follow-up, MRI revealed progression to a Bosniak IV cyst. Robot-assisted tumor enucleation was performed with selective artery clamping when the patient was 15. Histopathology showed tubulocystic renal cell carcinoma without adverse features. Immunocytochemistry supported a favorable prognosis of this rare tumor (

Abstract The coronary angiogram is the gold standard for evaluating the severity of coronary artery disease stenoses. Presently, the assessment is conducted visually by cardiologists, a method that lacks standardization. This study introduces DeepCoro, a ground-breaking AI-driven pipeline that integrates advanced vessel tracking and a video-based Swin3D model that was trained and validated on a dataset comprised of 182,418 coronary angiography videos spanning 5 years. DeepCoro achieved a notable precision of 71.89% in identifying coronary artery segments and demonstrated a mean absolute error of 20.15% (95% CI: 19.88–20.40) and a classification AUROC of 0.8294 (95% CI: 0.8215–0.8373) in stenosis percentage prediction compared to traditional cardiologist assessments. When compared to two expert interventional cardiologists, DeepCoro achieved lower variability than the clinical reports (19.09%; 95% CI: 18.55–19.58 vs 21.00%; 95% CI: 20.20–21.76, respectively). In addition, DeepCoro can be fine-tuned to a different modality type. When fine-tuned on quantitative coronary angiography assessments, DeepCoro attained an even lower mean absolute error of 7.75% (95% CI: 7.37–8.07), underscoring the reduced variability inherent to this method. This study establishes DeepCoro as an innovative video-based, adaptable tool in coronary artery disease analysis, significantly enhancing the precision and reliability of stenosis assessment.

Background: Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent purinergic receptor type Y, subtype 12 (P2Y12) inhibitors remains a challenge in the management of acute coronary syndrome (ACS). Methods: We conducted a systematic review and meta-analysis following a 2-stage process consisting of searching for systematic reviews published between 2019 and November 2022. We included randomized controlled trials (RCTs) of ACS patients treated with percutaneous coronary intervention comparing (i) ticagrelor- vs prasugrel-based DAPT and (ii) P2Y12 inhibitor de-escalation strategies. Outcomes of interest were major adverse cardiovascular events (MACE), all-cause death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Eight RCTs (n = 5571) compared ticagrelor to prasugrel. Ticagrelor was associated with an increased risk of MACE compared to prasugrel (RR 1.23, 95% CI 1.01-1.49, moderate certainty), without significant differences in death, stent thrombosis, or major bleeding. In 2 RCTs (n = 3343) comparing clopidogrel-based DAPT de-escalation after 1 month to potent P2Y12 inhibitor–based DAPT continuation, clopidogrel de-escalation did not significantly alter the incidence of MACE, death, or stent thrombosis, but reduced that of major bleeding (RR 0.51, 95% CI 0.28-0.92, high certainty). The effect of prasugrel dose de-escalation was inconclusive for all outcomes based on one trial. Conclusions: Ticagrelor was associated with an increase in MACE compared with prasugrel, based on low-certainty evidence, whereas de-escalation to clopidogrel after 1 month of potent P2Y12 inhibitor was associated with a decrease in incidence of major bleeding without increasing thrombotic outcomes in ACS patients post-percutaneous coronary intervention. Résumé: Contexte: Équilibrer les effets de la bithérapie antiplaquettaire (BTAP) à l’ère des puissants inhibiteurs du récepteur purinergique de type Y, sous-type 12 (P2Y12) demeure un défi dans la prise en charge du syndrome coronarien aigu (SCA). Méthodologie: Nous avons procédé à un examen systématique et à une méta-analyse, tout d’abord en recherchant les revues systématiques publiées entre 2019 et 2022, puis en mettant à jour la recherche la plus complète de ces revues jusqu’en novembre 2022. Nous avons inclus des essais contrôlés randomisés (ECR) menés chez des patients ayant subi un SCA traité par intervention coronarienne percutanée qui comparaient i) une BTAP comportant du ticagrélor à une BTAP à base de prasugrel, et ii) les stratégies de réduction graduelle de la dose de l’inhibiteur de P2Y12. Les résultats d’intérêt comprenaient les événements cardiovasculaires indésirables majeurs (ECIM), les décès toutes causes confondues, les thromboses de l’endoprothèse et les saignements majeurs. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l’aide d’un modèle à effets aléatoires. Résultats: Huit ECR (n = 5 571) ont comparé le ticagrélor au prasugrel. Le ticagrélor était associé à un risque accru d’ECIM comparativement au prasugrel (RR de 1,23, IC à 95 % de 1,01 à 1,49, certitude modérée), sans différence significative quant au décès, à la thrombose de l’endoprothèse ou au saignement majeur. Dans deux ECR (n = 3 343) comparant la réduction graduelle de la BTAP à base de clopidogrel après 1 mois à la poursuite de la BTAP comportant un inhibiteur puissant de P2Y12, la réduction graduelle de la dose de clopidogrel n’a pas modifié de manière significative la fréquence des ECIM, des décès ou des thromboses de l’endoprothèse, mais a réduit celle des saignements majeurs (RR de 0,51, IC à 95 % de 0,28 à 0,92, certitude élevée). L’effet de la réduction graduelle de la dose de prasugrel n’a pas été concluant pour tous les résultats sur la base d’un seul essai. Conclusions: Si l’on se fie aux données probantes de faible certitude, le ticagrélor a été associé à une augmentation des ECIM comparativement au prasugrel, tandis que la réduction graduelle de la dose de clopidogrel après 1 mois d’administration d’un puissant inhibiteur de P2Y12 a été associée à une diminution de la fréquence des saignements majeurs sans augmentation des événements thrombotiques chez les patients ayant subi une intervention coronarienne percutanée pour traiter un SCA.

Background: Ongoing debate remains regarding optimal antithrombotic therapy in patients with atrial fibrillation (AF) and coronary artery disease. Methods: We performed a systematic review and meta-analysis to synthesize randomized controlled trials (RCTs) comparing the following: (i) dual-pathway therapy (DPT; oral anticoagulant [OAC] plus antiplatelet) vs triple therapy (OAC and dual-antiplatelet therapy) after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS), and (iii) OAC monotherapy vs DPT at least 1 year after PCI or ACS. Following a 2-stage process, we identified systematic reviews published between 2019 and 2022 on these 2 clinical questions, and we updated the most comprehensive search for additional RCTs published up to October 2022. Outcomes of interest were major adverse cardiovascular events (MACE), death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Based on 6 RCTs (n = 10,435), DPT reduced major bleeding (RR 0.62, 95% CI 0.52-0.73) and increased stent thrombosis (RR 1.55, 95% CI 1.02-2.36), vs triple therapy after PCI or medically-managed ACS, with no significant differences in MACE and death. In 2 RCTs (n = 2905), OAC monotherapy reduced major bleeding (RR 0.66, 95% CI 0.49-0.91) vs DPT in AF patients with remote PCI or ACS, with no significant differences in MACE or death. Conclusions: In patients with AF and coronary artery disease, using less-aggressive antithrombotic treatment (DPT after PCI or ACS, and OAC alone after remote PCI or ACS) reduced major bleeding, with an increase in stent thrombosis with recent PCI. These results support a minimalist yet personalized antithrombotic strategy for these patients. Résumé: Contexte: La question du traitement antithrombotique optimal chez les personnes présentant une fibrillation auriculaire (FA) et une coronaropathie demeure controversée. Méthodologie: Nous avons réalisé une revue systématique et une méta-analyse pour synthétiser les essais contrôlés randomisés ayant comparé i) la bithérapie (anticoagulant oral et antiplaquettaire) et la trithérapie (anticoagulant oral et bithérapie antiplaquettaire) après une intervention coronarienne percutanée (ICP) ou un syndrome coronarien aigu (SCA), et ii) un anticoagulant oral en monothérapie et la bithérapie au moins 1 an après une ICP ou un SCA. Nous avons procédé en 2 temps, d’abord en répertoriant les revues systématiques publiées entre 2019 et 2022 sur ces 2 questions cliniques, puis en effectuant la recherche la plus exhaustive possible pour trouver d’autres essais contrôlés randomisés publiés jusqu’en octobre 2022. Les paramètres qui nous intéressaient étaient les événements cardiovasculaires indésirables majeurs (ECIM), le décès, la thrombose de l’endoprothèse et l’hémorragie majeure. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l’aide d’un modèle à effets aléatoires. Résultats: D’après 6 essais contrôlés randomisés (n = 10 435), la bithérapie a réduit les hémorragies majeures (RR : 0,62; IC à 95 % : 0,52 à 0,73) et augmenté les thromboses de l’endoprothèse (RR : 1,55; IC à 95 % : 1,02 à 2,36), comparativement à la trithérapie après une ICP ou un SCA ayant fait l’objet d’une prise en charge médicale, tandis qu’aucune différence significative n’a été observée quant aux ECIM et aux décès. Dans 2 essais contrôlés randomisés (n = 2 905), un anticoagulant oral en monothérapie a réduit les hémorragies majeures (RR : 0,66; IC à 95 % : 0,49 à 0,91) comparativement à la bithérapie chez des patients présentant une FA après une ICP ou un SCA plus lointain, sans différence significative quant aux ECIM et aux décès. Conclusions: Chez les patients présentant une FA et une coronaropathie, l’utilisation d’un traitement antithrombotique moins agressif (bithérapie après un ICP ou un SCA, et anticoagulant oral en monothérapie après une ICP ou un SCA plus lointain) réduit les hémorragies majeures, mais s’accompagne d’une augmentation des thromboses de l’endoprothèse en cas d’ICP récente. Ces résultats plaident en faveur d’une stratégie antithrombotique minimaliste, mais personnalisée chez ces patients.

Persistent inequities in access to and experiences of learning in postsecondary education have been well documented. In line with efforts to redress these inequities and develop more just institutions, this study explores the potential for pedagogical partnerships in which students and faculty collaborate on teaching and learning initiatives to contribute to classroom equity. We investigate this issue by drawing on qualitative interviews with students who have participated in extracurricular pedagogical partnership programs in institutions in Canada and the United States, and who identify as members of marginalized groups (e.g., racialized students, 2SLGBTQ+ students, students from religious minorities, disabled students). While much existing research on equity and student-faculty partnership primarily focuses on the outcomes of partnership for participating students, we instead investigate students' perceptions of the extent to which their partnership efforts contributed to wider impacts--such as developments in faculty thinking and teaching practice and student experiences in the classroom. We also consider challenges students noted connected to power imbalances and faculty resistance, which influence partnership's capacity to contribute to equity and raise important considerations for those interested in partnership practice.

**Background:** People living with hemophilia A face challenges impacting their daily lives despite treatment innovations. Previous studies have explored perceptions and treatment experiences; however, there is a lack of an evidence-based, comprehensive model to identify concepts (clinical, physical, and psychological functioning) relevant for people with hemophilia A (PwHA). **Objectives:** The aim of this qualitative study was to address the question: What is the humanistic and symptomatic experience of adolescents, adults, and children living with hemophilia A and what is the impact of hemophilia A on their quality of life? **Methods:** Participants, identified through patient associations in the UK, were male PwHA and caregivers of male PwHA receiving prophylactic treatment. Qualitative research was conducted involving semistructured telephone interviews with PwHA and caregivers between April 2020 and September 2020 in the UK. Standard analytical techniques of conceptual model development were used. **Results:** Of 30 participants, 23 were PwHA and 7 were caregivers. A conceptual model was produced describing patient experience of symptoms, physical functioning, treatment experiences, and the impact of symptoms and treatment on daily lives. Participants reported hemophilia-related symptoms, including bleeding, pain, and joint stiffness, as well as difficulties engaging with social and leisure activities. They also reported protection from bleeds provided by their treatment, relief from symptoms, and the resultant sense of normality. Concepts were broadly relevant across all age groups; however, psychological impacts were reported only by adult PwHA, and caregivers reported impacts related to outdoor activities, play, and education. Participants indicated that their ideal treatment would be delivered orally. **Discussion:** This study highlights the range of symptoms experienced by PwHA across a broad range of age groups, thus enabling the evaluation of relevant concepts across different stages of life. The research supports development of a conceptual model documenting symptoms, impacts, and treatment experience relevant to PwHA. **Conclusion:** Insights gathered through the interviews and resulting conceptual model support development of new therapies to address the physical and social challenges identified by PwHA and highlight a need for novel hemophilia A treatments that can ease treatment administration, provide adequate level of protection, and enable life to be lived normally.

Objectives To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD).Design A secondary analysis of the randomised controlled trial ADAPTABLE was performed.Setting The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA.Participants Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%).Interventions Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months.Primary and secondary outcomes measures The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion.Results Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints.Conclusion Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race.Trial registration number NCT02697916.

This paper presents the results of a one-year study of undergraduate business students' preference and level of satisfaction with online instruction at one university. A questionnaire was voluntarily completed by 305 undergraduate business students during the 2019-2020 academic year. Multiple regression analysis revealed that prior experience with online courses, ease of communication, personal benefits--convenience of taking online courses and expectation of improving GPA were positively associated with satisfaction in online courses relative to face-to-face courses. Learning benefits from online courses such as availability of course materials did not have a significant relationship. Satisfaction was positively related to preference for online courses. Demographic factors such as age and gender had no significant effect on satisfaction with online courses.

A recent measure was developed to assess the Quality of Life (QoL) of young people with advanced cancer and is available for parents and professionals (Advance QoL). The present study aimed to elaborate self-reported versions for children and adolescents with advanced cancer. We adopted a four-phase research plan: (1) to elaborate the Advance QoL questionnaire for youth (8–12 and 13–18 years old) with a team of young research partners; (2) to evaluate the understandability of these versions in a sample of 12 young patients from the target population using cognitive interviews; (3) to assess social validity in the same group using a questionnaire and the content validity index (CVI); and (4) to refine the questionnaires according to these results. Four major themes were identified: (1) issues affecting the understanding of the tool; (2) issues that did not affect the understanding of the tool; (3) modifications to improve the tool; and (4) positive features of the tool. Advance QoL was well received, and feedback was positive. Adjustments were made according to young people’s comments and two self-reported versions are now available. It is essential to measure the key domains of QoL in advanced cancer. Advance QoL self-report versions will help target the specific needs of young people with this condition and their families.

The viscous–plastic (VP) rheology with an elliptical yield curve and normal flow rule is implemented in a Lagrangian modelling framework using the smoothed particle hydrodynamics (SPH) meshfree method. Results show, from a perturbation analysis of SPH sea-ice dynamic equations, that the classical SPH particle density formulation expressed as a function of sea-ice concentration and mean ice thickness leads to incorrect plastic wave speed. We propose a new formulation for particle density that gives a plastic wave speed in line with theory. In all cases, the plastic wave in the SPH framework is dispersive and depends on the smoothing length (i.e., the spatial resolution) and on the SPH kernel employed in contrast to its finite-difference method (FDM) implementation counterpart. The steady-state solution for the simple 1D ridging experiment is in agreement with the analytical solution within an error of 1 %. SPH is also able to simulate a stable upstream ice arch in an idealized domain representing the Nares Strait in a low-wind regime (5.3 m s−1) with an ellipse aspect ratio of 2, an average thickness of 1 m and free-slip boundary conditions in opposition to the FDM implementation that requires higher shear strength to simulate it. In higher-wind regimes (7.5 m s−1) no stable ice arches are simulated – unless the thickness is increased – and the ice arch formation showed no dependence on the size of particles, in contrast to what is observed in the discrete-element framework. Finally, the SPH framework is explicit, can take full advantage of parallel processing capabilities and shows potential for pan-Arctic climate simulations.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs. Résumé: Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d’apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d’apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l’anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l’hôpital entre les femmes et les hommes. Nous avons comparé les taux d’événements indésirables cliniques nets, le critère composite de mortalité, d’infarctus du myocarde, d’accident vasculaire cérébral ou d’accident ischémique transitoire, la thromboembolie systémique ou l’hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l’analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l’hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n’a été notée dans le risque d’événements hémorragiques et d’événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d’ordonnances d’ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d’apparition récente.

Abstract Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.e., substantia nigra, ventral tegmental area, and caudate nucleus) had remarkable enrichment of common mtDNA deletions.

Over the last decade, online learning has grown to become an important part of higher education. However, hybrid formats that blend online learning with direct face-to-face contact with instructors have emerged as a popular course delivery format. These hybrids format aims to take full advantages of the benefits of both online and face-to-face course offerings. This study examines the factors that influence college students' attitudes toward hybrid courses. Data from 300 students at a college of business is used to examine relationships between their perceptions of hybrid course formats and their attitudes and preference for such formats. Specifically, perceptions of flexibility afforded by hybrid formats, improvement in attendance through such formats, expectations of GPA in online formats, requirement to participate in online web conferencing through technologies like Zoom, and availability of course material online were analyzed. The results show that hybrid formats are preferable because they allow students to have flexible schedules, likely improve their attendance, and have online course material for anytime access. Expectations of earning a higher GPA in online environments and required participation were not found to be significant. There was no significant difference between demographics based on gender or age for hybrid formats.

This study builds upon previous research that explores the pedagogical use of film and video by explicitly asking instructors about their attitudes towards and motivations for employing such texts in their teaching, as well as the challenges they face in the process. Data were gathered through an anonymous, online survey of instructors across disciplines at seven Ontario universities. Commonalities were found amongst participants in the purposes cited for using film and video as well as in the challenges that accompany use of this pedagogical tool. For example, instructors in four of our six Faculty groupings commonly noted drawing on film and video to engage student attention, and the two most frequently selected challenges in five of our six Faculty groupings were 'technical difficulties screening films' and 'problems finding appropriate materials'. We consider the implications of these findings for teaching and learning and suggest areas for future research.

ABSTRACT The analysis and comparison of genomes rely on different tools for tasks such as annotation, orthology prediction, and phylogenetic inference. Most tools are specialized for a single task, and additional efforts are necessary to integrate and visualize the results. To fill this gap, we developed zDB, an application integrating a Nextflow analysis pipeline and a Python visualization platform built on the Django framework. The application is available on GitHub (https://github.com/metagenlab/zDB) and from the bioconda channel. Starting from annotated Genbank files, zDB identifies orthologs and infers a phylogeny for each orthogroup. A species phylogeny is also constructed from shared single-copy orthologs. The results can be enriched with Pfam protein domain prediction, Cluster of Orthologs Genes and Kyoto Encyclopedia of Genes and Genomes annotations, and Swissprot homologs. The web application allows searching for specific genes or annotations, running Blast queries, and comparing genomic regions and whole genomes. The metabolic capacities of organisms can be compared at either the module or pathway levels. Finally, users can run queries to examine the conservation of specific genes or annotations across a chosen subset of genomes and display the results as a list of genes, Venn diagram, or heatmaps. Those features make zDB useful for both bioinformaticians and researchers more accustomed to laboratory research.IMPORTANCEGenome comparison and analysis rely on many independent tools, leaving to scientists the burden to integrate and visualize their results for interpretation. To alleviate this burden, we have built zDB, a comparative genomics tool that includes both an analysis pipeline and a visualization platform. The analysis pipeline automates gene annotation, orthology prediction, and phylogenetic inference, while the visualization platform allows scientists to easily explore the results in a web browser. Among other features, the interface allows users to visually compare whole genomes and targeted regions, assess the conservation of genes or metabolic pathways, perform Blast searches, or look for specific annotations. Altogether, this tool will be useful for a broad range of applications in comparative studies between two and hundred genomes. Furthermore, it is designed to allow sharing of data sets easily at a local or international scale, thereby supporting exploratory analyses for non-bioinformaticians on the genome of their favorite organisms.

Climate change is expected to increase the frequency and intensity of winter thaws, which could affect leaf phenology. Phenology could either be advanced through the acceleration of forcing accumulation or chilling completion, or be postponed through a reduction in chilling associated with warming air temperature. We tested the influence of winter thaws on budburst phenology by exposing 300 tree cuttings of sugar maple and yellow birch trees to five different frequencies and durations of winter thaws in the lab. In spring, half of the cuttings were exposed to air temperature in two cities representing an air temperature gradient of + 2.0 °C to mimic the ongoing climate warming and bud phenology was monitored three times a week. Irrespective of thaw treatment, yellow birch bud phenology occurred earlier in the warmer city, showing the importance of spring temperature in triggering budburst. The treatment with the highest frequency and duration of thawing increased bud mortality and delayed the onset of spring budburst whereas low frequency treatments did not, thereby identifying a tipping point (3 days twice a month) in the impact of winter thaws on bud phenology. Past this point, winter thaws could slow down bud phenology induced by warmer spring temperature and limit carbon uptake by delaying the closure of the canopy. Climate change simulations projected by the CMIP6 Canadian downscaled climate scenario show that winter thaws will increase in frequency Hence the expected advance in spring leaf emergence associated with warmer spring is not necessarily as straightforward as previously thought.

The Contamination Sanitization Inspection and Disinfection (CSI-D) device is a handheld fluorescence-based imaging system designed to disinfect food contact surfaces using ultraviolet-C (UVC) illumination. This study aimed to determine the optimal CSI-D parameters (i.e., UVC exposure time and intensity) for the inactivation of the following foodborne bacteria plated on non-selective media: generic Escherichia coli (indicator organism) and the pathogens enterohemorrhagic E. coli, enterotoxigenic E. coli, Salmonella enterica, and Listeria monocytogenes. Each bacterial strain was spread-plated on non-selective agar and exposed to high-intensity (10 mW/cm2) or low-intensity (5 mW/cm2) UVC for 1–5 s. Control plates were not exposed to UVC. The plates were incubated overnight at 37 °C and then enumerated. Three trials for each bacterial strain were conducted. Statistical analysis was carried out to determine if there were significant differences in bacterial growth between UVC intensities and exposure times. Overall, exposure to low or high intensity for 3–5 s resulted in consistent inhibition of bacterial growth, with reductions of 99.9–100 % for E. coli, 96.8–100 % for S. enterica, and 99.2–100 % for L. monocytogenes. The 1 s exposure time showed inconsistent results, with a 66.0–100 % reduction in growth depending on the intensity and bacterial strain. When the results for all strains within each species were combined, the 3–5 s exposure times showed significantly greater (p 0.05) in growth inhibition between the high and low UVC intensities. The results of this study show that, in pure culture conditions, exposure to UVC with the CSI-D device for ≥3 s is required to achieve consistent reduction of E. coli, S. enterica, and L. monocytogenes.