Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep-learning and transfer learning identify new breast cancer survival subtypes from single-cell imaging data

Quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at population scale are currently missing. Here, we computationally extracted hundreds of features describing single-cell based cell-cell interactions and cellular phenotypes from a large, published cohort of cyto-images of breast cancer patients. We applied these features to a neural-network based Cox-nnet survival model and obtained high accuracy in predicting patient survival in test data (Concordance Index > 0.8). We identified seven survival subtypes using the top survival features, which present distinct profiles of epithelial, immune, fibroblast cells, and their interactions. We identified atypical subpopulations of TNBC patients with moderate prognosis (marked by GATA3 over-expression) and Luminal A patients with poor prognosis (marked by KRT6 and ACTA2 over-expression and CDH1 under-expression). These atypical subpopulations are validated in TCGA-BRCA and METABRIC datasets. This work provides important guidelines on bridging single-cell level information towards population-level survival prediction. STATEMENT OF TRANSLATIONAL RELEVANCE Our findings from a breast cancer population cohort demonstrate the clinical utility of using the single-cell level imaging mass cytometry (IMC) data as a new type of patient prognosis prediction marker. Not only did the prognosis prediction achieve high accuracy with a Concordance index score greater than 0.8, it also enabled the discovery of seven survival subtypes that are more distinguishable than the molecular subtypes. These new subtypes present distinct profiles of epithelial, immune, fibroblast cells, and their interactions. Most importantly, this study identified and validated atypical subpopulations of TNBC patients with moderate prognosis (GATA3 over-expression) and Luminal A patients with poor prognosis (KRT6 and ACTA2 over-expression and CDH1 under-expression), using multiple large breast cancer cohorts.
New SARS-CoV-2 Omicron Variant with Spike Protein Mutation Y451H, Kilifi, Kenya, March–May 2023

We report a newly emerged SARS-CoV-2 Omicron subvariant FY.4 that has mutations Y451H in spike and P42L in open reading frame 3a proteins. FY.4 emergence coincided with increased SARS-CoV-2 cases in coastal Kenya during April–May 2023. Continued SARS-CoV-2 genomic surveillance is needed to identify new lineages to inform COVID-19 outbreak prevention.
Prevalence and knowledge about acute mountain sickness in the Western Alps

Objective To assess the prevalence of acute mountain sickness (AMS) in 1370 mountaineers at four different altitudes in the Western Alps. We also examined the influence of potential risk factors and the knowledge about AMS on its prevalence. Methods In this observational cross-sectional study AMS was assessed on the day of ascent by the Lake Louise score (LLS, cut-off ≥3, version 2018) and the AMS-Cerebral (AMS-C) score of the environmental symptom questionnaire (cut-off ≥0,70). The latter was also obtained in the next morning. Knowledge regarding AMS and high-altitude cerebral edema (HACE) and the potential risk factors for AMS were evaluated by questionnaires. Results On the day of ascent, the prevalence of AMS assessed by the LLS and AMS-C score was 5.8 and 3.9% at 2850 m, 2.1 and 3.1% at 3050 m, 14.8 and 10.1% at 3650 m, and 21.9 and 15% at 4559 m, respectively. The AMS prevalence increased overnight from 10.1 to 14.5% and from 15 to 25.2% at 3650 m and 4559 m, respectively, and was unchanged at 2850 m and 3050 m. A history of AMS, higher altitude, lower degree of pre-acclimatization, and younger age were identified as risk factors for developing AMS. Slow ascent was weakly associated with AMS prevalence, and sex and knowledge about AMS and HACE were indistinct. Conclusion AMS is common at altitudes ≥ 3650 m and better knowledge about AMS and HACE was not associated with less AMS in mountaineers with on average little knowledge.
Effects of a 12 week community-based high-level mobility programme on sustained participation in physical activity by adolescents with cerebral palsy: a single subject research design study.

PURPOSE To assess if a high-level mobility programme (HLMP) can promote sustained participation in physical activity by adolescents with cerebral palsy. METHODS Eight adolescents with cerebral palsy, Gross Motor Function Classification System levels I-II, 11-16 years, participated in 24 community-based group HLMP sessions across 12 weeks. Participants set attendance, involvement, and physical performance goals, completed activity diaries over 58 weeks and undertook physical capacity tests. Measures of activity frequency and diversity (attendance) and involvement level were collected weekly across baseline (4-6 weeks), intervention (12 weeks), and nine months follow-up (including Covid lockdown). RESULTS Median attendance was 23 of 24 HLMP sessions. Attendance goal/s attainment was highest during COVID lockdown. Involvement goals were consistently attained throughout all phases. Physical performance goal/s attainment was highest during intervention phase but reduced during nine months follow-up. Frequency of participation in physical activities varied greatly across study phases (range 0-33 episodes/week) with stable variety of activities and generally high 'involvement. ' During the intervention, seven participants improved physical capacity and six maintained, or increased, the gains six months later. CONCLUSION Most participants improved physical capacity post-intervention but only some had sustained attendance and involvement in physical activity, highlighting the complexity of physical activity participation.
Burnout and fatigue amongst internal medicine residents: A cross-sectional study on the impact of alternative scheduling models on resident wellness

Background Fatigue and burnout are prevalent among resident physicians across Canada. Shifts exceeding 24 hours are commonly purported as detrimental to resident health and performance. Residency training programs have employed strategies towards understanding and intervening upon the complex issue of resident fatigue, where alternative resident scheduling models have been an area of active investigation. This study sought to characterize drivers and outcomes of fatigue and burnout amongst internal medicine residents across different scheduling models. Methods We conducted cross-sectional surveys were among internal medicine resident physicians at the University of Alberta. We collected anonymized socioeconomic demographics and medical education background, and estimated associations between demographic or work characteristics and fatigue and burnout outcomes. Results Sixty-nine participants competed burnout questionnaires, and 165 fatigue questionnaires were completed (response rate of 48%). The overall prevalence of burnout was 58%. Lower burnout prevalence was noted among respondents with dependent(s) (p = 0.048), who identified as a racial minority (p = 0.018), or completed their medical degree internationally (p = 0.006). The 1-in-4 model was associated with the highest levels of fatigue, reported increased risk towards personal health (OR 4.98, 95%CI 1.77–13.99) and occupational or household harm (OR 5.69, 95%CI 1.87–17.3). Alternative scheduling models were not associated with these hazards. Conclusions The 1-in-4 scheduling model was associated with high rates of resident physician fatigue, and alternative scheduling models were associated with less fatigue. Protective factors against fatigue are best characterized as strong social supports outside the workplace. Further studies are needed to characterize the impacts of alternative scheduling models on resident education and patient safety.
Changes in Mature Human Milk Macronutrient Composition over 45 years in an Urban Population in Indonesia

Background: With improvement in a population’s welfare, its food consumption patterns may change, including those of nursing mothers. This, in turn, could influence their human milk composition. Research Aim: To investigate the secular trend in macronutrient composition of mature human milk from mothers of healthy, full-term infants in urban populations in Indonesia from 1974 and 2019. Method: We compared the macronutrient composition of mature human milk of healthy full-term infants from 1974 and 2019. The data from 2019 used the Human Milk Analyzer MIRIS to quantify the milk’s carbohydrate, fat, and protein content, while the historical data used methods available at that time, that is, methods described by Benedict, Gerber and Kjeldahl, respectively. Results: There were no significant differences in carbohydrate, protein and fat content across categories of maternal nutritional status in the respective periods. However, the fat content of human milk from 2019 was significantly higher than that of 1974 (4.7 g/dl, SD = 1.7 g/dl vs. 3.3 g/dl, SD = 1.1 g/dl; p < 0.001), while its carbohydrate content was significantly lower (6.2 g/dl, SD = 2.1 g/dl vs. 7.1 g/dl, SD = 0.2 g/dl; p < 0.001). There was no difference in the protein content between the two periods (1.4 g/dl, SD = 0.5 g/dl vs. 1.6 g/dl, SD = 0.3 g/dl; p = 0.491). Conclusion: The mature human milk from 2019 has a higher fat and total energy content but lower carbohydrate content than those observed 4 decades ago. The protein content remained the same.
Embelin inhibits viability of cutaneous T cell lymphoma cell lines HuT78 and H9 by targeting inhibitors of apoptosis

Abstract Cutaneous T cell lymphoma (CTCL) is a varied group of neoplasms that affects the skin. Acquired resistance against chemotherapeutic drugs and associated toxic side effects are limitations that warrant search for novel drugs against CTCL. Embelin (EMB) is a naturally occurring benzoquinone derivative that has gained attention owing to its anticancer pharmacological actions and nontoxic nature. We assessed the anticancer activity of EMB against CTCL cell lines, HuT78, and H9. EMB inhibited viability of CTCL cells in a dose-dependent manner. EMB activated extrinsic and intrinsic pathways of apoptosis as shown by the activation of initiator and executioner caspases. EMB-induced apoptosis also involved suppression of inhibitors of apoptosis, XIAP, cIAP1, and cIAP2. PARP cleavage and upregulation of pH2AX indicated DNA damage induced by EMB. In conclusion, we characterized a novel apoptosis-inducing activity of EMB against CTCL cells, implicating EMB as a potential therapeutic agent against CTCL.
Barriers and facilitators of access to sexual and reproductive health services among migrant, internally displaced, asylum seeking and refugee women: A scoping review

Introduction Migrant, internally displaced, asylum seeking and refugee women experience ongoing risks of having their reproductive healthcare rights violated. This ever-increasing population also has limited access to sexual and reproductive health services. We conducted a scoping review to identify the barriers and facilitating factors when accessing sexual and reproductive health services for this specific population. Methods We searched the grey literature and queried eight bibliographic databases (Embase, Medline, Cinahl, Scopus, Science Direct, Web of Science, Hinari, and Cochrane Library) to extract articles published between January, 2000, and October, 2021. The extracted data were organized in a framework adapted from Peters et al. and then categorized as facilitators or barriers. We followed the Arksey and O’Malley framework and wrote the report according to the PRISMA-Scr recommendations. Results The search identified 4,722 records of which forty-two (42) met eligibility criteria and were retained for analysis. Ten (10) groups of factors facilitating and/or limiting access to sexual and reproductive health care emerged from the synthesis of the retained articles. The main barriers were lack of knowledge about services, cultural unacceptability of services, financial inaccessibility, and language barriers between patients and healthcare providers. Facilitators included mobile applications for translation and telehealth consultations, patients having a wide availability of information sources, the availability health promotion representatives, and healthcare providers being trained in cultural sensitivity, communication and person-centered care. Conclusion Ensuring the sexual and reproductive rights of migrant, internally displaced, asylum-seeking and refugee women requires that policymakers and health authorities develop intervention strategies based on barriers and facilitators identified in this scoping review. Therefore, considering their mental health in future studies would enable a better understanding of the barriers and facilitators of access to sexual and reproductive health services.
Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712

Outcomes for children with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are poor, and new therapies are needed. Pevonedistat is an inhibitor of the NEDD‐8 activating enzyme, a key regulator of the ubiquitin proteasome system that is responsible for protein turnover, with protein degradation regulating cell growth and survival.
Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis

RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast–like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC.
Bailout clipping of a leaflet perforation during mitral transcatheter edge-to-edge repair using a larger clip size: a case report

Abstract Background Leaflet tear and perforation are serious complications of transcatheter edge-to-edge repair (TEER) using the MitraClip system for severe mitral regurgitation (MR). However, no optimal bailout strategy has been established. Case summary An 80-year-old woman developed heart failure due to acute ischaemic severe MR after primary percutaneous coronary intervention. Given the requirement for inotropic drugs and an intra-aortic balloon pump to stabilize her heart failure, we decided to perform TEER using the MitraClip G4 system. The NTW clip was selected considering the limited posterior leaflet, wide central MR, and delivery to the central A2/P2. The leaflet was successfully grasped, and the MR jet dramatically decreased while the clip was closed. However, the MR jet suddenly appeared after completely closing the clip arm. A new eccentric jet was detected coming from the mid-portion of the posterior leaflet, indicating leaflet perforation. We decided to manage the leaflet perforation by covering the perforated portion with a longer type of clip. An XTW clip was then carefully delivered to the previously grasped portion, after which we confirmed that the tip of the clip arm was positioned more posteriorly to the leaflet perforation. After slowly closing the clip, MR decreased to mild, with transoesophageal echocardiography showing no eccentric MR. After her haemodynamics stabilized, she was discharged 28 days after the procedure. Discussion This case details a successful bailout clipping of a leaflet perforation using an XTW clip. Leaflet anatomy evaluation is important to ensure that the injured portion is covered by the longer clip arm.
Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response

Antibody-drug conjugates (ADCs) have emerged as a revolutionary therapeutic class, combining the precise targeting ability of monoclonal antibodies with the potent cytotoxic effects of chemotherapeutics. Notably, ADCs have rapidly advanced in the field of breast cancer treatment. This innovative approach holds promise for strengthening the immune system through antibody-mediated cellular toxicity, tumor-specific immunity, and adaptive immune responses. However, the development of upfront and acquired resistance poses substantial challenges in maximizing the effectiveness of these therapeutics, necessitating a deeper understanding of the underlying mechanisms. These mechanisms of resistance include antigen loss, derangements in ADC internalization and recycling, drug clearance, and alterations in signaling pathways and the payload target. To overcome resistance, ongoing research and development efforts are focused on urgently identifying biomarkers, integrating immune therapy approaches, and designing novel cytotoxic payloads. This Review provides an overview of the mechanisms and clinical effectiveness of ADCs, and explores their unique immune-boosting function, while also highlighting the complex resistance mechanisms and safety challenges that must be addressed. A continued focus on how ADCs impact the tumor microenvironment will help to identify new payloads that can improve patient outcomes.
SCN-MLTPP: A Multi-Label Classifier for Predicting Therapeutic Properties of Peptides Using the Stacked Capsule Network

Identifying the function of therapeutic peptides is an important issue in the development of novel drugs. To reduce the time and labor costs required to identify therapeutic peptides, computational methods are increasingly required. However, most of the existing peptide therapeutic function prediction models are used for predicting a single therapeutic function, ignoring the fact that a bioactive peptide might simultaneously consist of multi-activities. Furthermore, in the few existing multi-label classification models, the feature extraction procedures are still rough. We propose a multi-label framework, called SCN-MLTPP, with a stacked capsule network for predicting the therapeutic properties of peptides. Instead of using peptide sequence vectors alone, SCN-MLTPP extracts different view representation vectors from the therapeutic peptides and learns the contributions of different views to the properties of therapeutic peptides based on the dynamic routing mechanism. Benchmarking results show that as compared with existing multi-label predictors, SCN-MLTPP achieves better and more robust performance for different peptides. In addition, some visual analyses and case studies also demonstrate the model can reliably capture features from multi-view data and predict different peptides.
Conditional Poisson Regression with Random Effects for the Analysis of Multi-site Time Series Studies

The analysis of time series studies linking daily counts of a health indicator with environmental variables (e.g., mortality or hospital admissions with air pollution concentrations or temperature; or motor vehicle crashes with temperature) is usually conducted with Poisson regression models controlling for long-term and seasonal trends using temporal strata. When the study includes multiple zones, analysts usually apply a two-stage approach: first, each zone is analyzed separately, and the resulting zone-specific estimates are then combined using meta-analysis. This approach allows zone-specific control for trends. A one-stage approach uses spatio-temporal strata and could be seen as a particular case of the case–time series framework recently proposed. However, the number of strata can escalate very rapidly in a long time series with many zones. A computationally efficient alternative is to fit a conditional Poisson regression model, avoiding the estimation of the nuisance strata. To allow for zone-specific effects, we propose a conditional Poisson regression model with a random slope, although available frequentist software does not implement this model. Here, we implement our approach in the Bayesian paradigm, which also facilitates the inclusion of spatial patterns in the effect of interest. We also provide a possible extension to deal with overdispersed data. We first introduce the equations of the framework and then illustrate their application to data from a previously published study on the effects of temperature on the risk of motor vehicle crashes. We provide R code and a semi-synthetic dataset to reproduce all analyses presented.
Secure Traversable Event logging for Responsible Identification of Vertically Partitioned Health Data

We aim to provide a solution for the secure identification of sensitive medical information. We consider a repository of de-identified medical data that is stored in the custody of a Healthcare Institution. The identifying information that is stored separately can be associated with the medical information only by a subset of users referred to as custodians. This paper intends to secure the process of associating identifying information with sensitive medical information. We also enforce the responsibility of the custodians by maintaining an immutable ledger documenting the events of such information identification. The paper proposes a scheme for constructing ledger entries that allow the custodians and patients to browse through the entries which they are associated with. However, in order to respect their privacy, such traversal requires appropriate credentials to ensure that a user cannot gain any information regarding the other users involved in the system unless they are both involved in the same operation.