Miracle-dz/UniFAR-FTUs huggingface dataset:
An Interpretable and Accurate Deep-Learning Diagnosis Framework Modeled With Fully and Semi-Supervised Reciprocal Learning

The deployment of automated deep-learning classifiers in clinical practice has the potential to streamline the diagnosis process and improve the diagnosis accuracy, but the acceptance of those classifiers relies on both their accuracy and interpretability. In general, accurate deep-learning classifiers provide little model interpretability, while interpretable models do not have competitive classification accuracy. In this paper, we introduce a new deep-learning diagnosis framework, called InterNRL, that is designed to be highly accurate and interpretable. InterNRL consists of a student-teacher framework, where the student model is an interpretable prototype-based classifier (ProtoPNet) and the teacher is an accurate global image classifier (GlobalNet). The two classifiers are mutually optimised with a novel reciprocal learning paradigm in which the student ProtoPNet learns from optimal pseudo labels produced by the teacher GlobalNet, while GlobalNet learns from ProtoPNet’s classification performance and pseudo labels. This reciprocal learning paradigm enables InterNRL to be flexibly optimised under both fully- and semi-supervised learning scenarios, reaching state-of-the-art classification performance in both scenarios for the tasks of breast cancer and retinal disease diagnosis. Moreover, relying on weakly-labelled training images, InterNRL also achieves superior breast cancer localisation and brain tumour segmentation results than other competing methods.
Spatial behaviour of wild boar

The spatial behaviour of an animal is influenced by decisions relating to foraging, movement, avoidance, resting, territorial activity, mating and rearing young. Many of these behaviours can be explained by the optimal foraging theory, exceptions being reproductive behaviours and predator avoidance. Predation risk and associated avoidance behaviors varies across the landscape, resulting in a divergence from patterns predicted by optimal foraging theory, instead optimizing fitness. Such risk effects can be large and affect both individuals and population demography. This thesis focus on external factors affecting movements and habitat selection of wild boar females (N=15-17 depending on the question) using data from GPS collared individuals (N>100.000 data points analyzed) over 4 years in the southern part of Sweden. My results show that habitat selection is affected by season and by risk effects, such as traffic and hunting. Intense traffic diverts wild boar from crossing roads, and reduce the number of traffic accidents when traffic intensity is high. Intense hunting results in fleeing while less intense hunting results in hiding. Hunts that results in flights affects habitat selection until wild boar returned to their homer range. Wild boar perceive crop fields as risky but rewarding habitats, and while using crop fields they prefer to be close to cover such as edges, hedges and ditches. Further, wild boar movement is affected by seasonal and temporal aspects and weather conditions. The most common reaction to stressful factors such as traffic, hunting and aversive weather was to reduce movement. The only exception was when wild boar were chased in drive hunts and fled. These results are important for understanding how weather conditions affect optimal foraging strategies and how the animals’ perception of risk affects movement patterns and habitat selection. From a management perspective, my results can be used to reduce crop damages and traffic accidents caused by wild boar. These findings are also useful in understanding how hunting as a management tool affects the space use of wild boar, and consequently can aid managers to select hunting methods that may reduce damages to crops.
Genetic Architecture of Flowering Time Differs Between Populations With Contrasting Demographic and Selective Histories

Abstract Understanding the evolutionary factors that impact the genetic architecture of traits is a central goal of evolutionary genetics. Here, we investigate how quantitative trait variation accumulated over time in populations that colonized a novel environment. We compare the genetic architecture of flowering time in Arabidopsis populations from the drought-prone Cape Verde Islands and their closest outgroup population from North Africa. We find that trait polygenicity is severely reduced in the island populations compared to the continental North African population. Further, trait architectures and reconstructed allelic histories best fit a model of strong directional selection in the islands in accord with a Fisher–Orr adaptive walk. Consistent with this, we find that large-effect variants that disrupt major flowering time genes (FRI and FLC) arose first, followed by smaller effect variants, including ATX2 L125F, which is associated with a 4-day reduction in flowering time. The most recently arising flowering time-associated loci are not known to be directly involved in flowering time, consistent with an omnigenic signature developing as the population approaches its trait optimum. Surprisingly, we find no effect in the natural population of EDI-Cvi-0 (CRY2 V367M), an allele for which an effect was previously validated by introgression into a Eurasian line. Instead, our results suggest the previously observed effect of the EDI-Cvi-0 allele on flowering time likely depends on genetic background, due to an epistatic interaction. Altogether, our results provide an empirical example of the effects demographic history and selection has on trait architecture.
The Additive Effect of Left Ventricular Filling Pressure and Renal Function on Long-Term Prognosis of High-Risk Patients Undergoing Coronary Angiography

Introduction: Impaired relaxation is the earliest manifestation of ischemic cascade. Risk factors and renal function abnormalities are associated with coronary disease and diastolic dysfunction as well. We aimed to study the association of noninvasive assessment of left ventricular filling pressures and renal function with mortality in high-risk patients undergoing coronary angiography. Patients and Methods: An observational prospective study of 564 consecutive patients undergoing coronary angiography was conducted. The median follow-up was 2,293 days. Patients were categorized into 2 groups according to presence of significant diastolic dysfunction: group 1, 382 patients, with normal and group 2, 182 patients, with elevated filling pressure. Renal insufficiency was determined as calculated glomerular filtration rate <60 mL/min. Patients demographic, clinical, echocardiography, laboratory, and angiographic data were prospectively collected. Results: Fifty-three percent of patients underwent angiography due to acute coronary syndrome (ACS), 85.5% had coronary artery disease, 53.4% had reduced (<50%) left ventricular ejection fraction (LVEF), and 47.4% had abnormal renal function. The mortality during the follow-up period was 30.0%. Patients with elevated filling pressure had significantly higher mortality (50.5% vs. 20.2%, p < 0.0001). Impaired renal failure as well, was associated with higher mortality (48% vs. 15%, p < 0.001). The association remained significant in subgroups of patients with and without ACS and reduced and preserved LVEF. In Cox regression model which combined elevated filling pressure, renal insufficiency, age, diabetes mellitus, hypertension, presence of atrial fibrillation, LVEF, and anemia, elevated filling pressure and renal function impairment were independently associated with higher mortality (HR: 3.717, CI: 1.623–8.475, p < 0.0001 and HR: 0.972, CI: 0.958–0.985, p = 0.0001, respectively). There was an incremental prognostic value of elevated filling pressures and renal function impairment on mortality. Conclusions: Advanced diastolic dysfunction and impaired renal function are signals toward worse outcomes and are associated with mortality in high-risk patients undergoing coronary angiography.
ER and COX2 expression in endometrial hyperplasia processes

Endometrial hyperplastic processes (EHPs) encompass various morphological changes, characterized by an increased ratio of endometrial glands to stroma. These changes manifest as endometrial hyperplasia (EH) and endometrial polyps. The objective of this study was to investigate the expressions of ER and Cyclooxygenase-2 (COX2) in EH and endometrial polyps, and determine their correlation with histological and anthropometric parameters. Tissue samples were obtained during hysteroresectoscopy and divided into 3 groups: non-atypical EH, glandular EP, and glandular-fibrous EP. We examined the immunoprofile of epithelial and stromal cells using rabbit polyclonal anti-COX2 antibodies and rabbit monoclonal anti-ER antibodies (clone SP1). Our results indicate that there is no association between the expressions of ER and COX2 and the type of EHP. Furthermore, the expression levels of ER and COX2 are not influenced by the patients anthropometric parameters. However, tissues with EHPs exhibited significantly higher COX2 expression compared to intact tissues. We also observed a direct correlation between ER and COX2 expression in the endometrial epithelium. The variability in ER and COX2 expressions observed in hyperplastic processes of the endometrium potentially suggests their synergistic involvement in the initiation and progression of EHPs, as well as their potential role in subsequent tumor transformation.
Glucocorticoids regulate lipid mediator networks by reciprocal modulation of 15-lipoxygenase isoforms affecting inflammation resolution

Significance The specialized proresolving mediators (SPM) are potent immunoresolvents, formed from omega-3-fatty acids by lipoxygenases, which foster resolution of inflammation. Currently, no pharmacological treatments are approved to stimulate SPM biosynthesis for promoting inflammation resolution. Glucocorticoids are widely used anti-inflammatory drugs that dampen immune responses and excessive inflammation, but they also display inflammation-resolving features. However, by which mechanism glucocorticoids resolve inflammation and how they impact SPM biosynthesis remained elusive. We show that in human monocyte/macrophages, glucocorticoids strongly up-regulate 15-lipoxygenase-2/ALOX15B expression via the glucocorticoid receptor that binds to ALOX15B intron 3 but suppress 15-lipoxygenase-1/ALOX15 isoform induction with striking consequences for SPM biosynthesis. Conclusively, glucocorticoids mediate their inflammation-resolving effects via elevated SPM formation, and thus advance the understanding of how glucocorticoids manipulate immune responses.
CD133/Prom1 marks proximal mouse oviduct epithelial progenitors and adult epithelial cells with a low generative capacity

ABSTRACT The epithelium lining the oviduct or fallopian tube consists of multiciliated and secretory cells, which support fertilization and preimplantation development, however, its homeostasis remains poorly understood. CD133/Prom1 expression has been used as a marker to identify adult stem cell populations in various organs and often associated with cancer cells that have stem-like properties. Using an antibody targeted to CD133 and a Cre recombinase-based lineage tracing strategy, we found that CD133/Prom1 expression is not associated with a stem/progenitor population in the oviduct but marked predominantly multiciliated cells with a low generative capacity. Additionally, we have shown that CD133 is disparately localised along the oviduct during neonatal development, and that Prom1 expressing secretory cells in the ampulla rapidly transitioned to multiciliated cells and progressively migrated to the ridge of epithelial folds.
Pregnancy and Birth Outcomes in Patients With Multidrug-Resistant Tuberculosis Treated With Regimens That Include New and Repurposed Drugs

Abstract Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming neonates.
The Relationship Between Rape Myths, Revictimization by Law Enforcement, and Well-Being for Victims of Sexual Assault

Relationships between rape myths, revictimization, and postassault well-being were examined in a sample of adult victims of sexual assault (n = 88). Correlation, multiple regression, and path analyses investigated whether conformity to stereotypes of “real rape” or “real victim” was associated with revictimization and well-being. A possible mediating effect of revictimization on the relationship between rape myth conformity and well-being was assessed. The relationship between specific revictimization behaviors and emotions was also analyzed. Questioning victims’ resistance to the assault was correlated with revictimization emotions. “Real victim” characteristics were associated with well-being, but no mediating effect of revictimization was observed.
Two‐stage or not two‐stage? That is the question for IPD meta‐analysis projects

Individual participant data meta‐analysis (IPDMA) projects obtain, check, harmonise and synthesise raw data from multiple studies. When undertaking the meta‐analysis, researchers must decide between a two‐stage or a one‐stage approach. In a two‐stage approach, the IPD are first analysed separately within each study to obtain aggregate data (e.g., treatment effect estimates and standard errors); then, in the second stage, these aggregate data are combined in a standard meta‐analysis model (e.g., common‐effect or random‐effects). In a one‐stage approach, the IPD from all studies are analysed in a single step using an appropriate model that accounts for clustering of participants within studies and, potentially, between‐study heterogeneity (e.g., a general or generalised linear mixed model). The best approach to take is debated in the literature, and so here we provide clearer guidance for a broad audience. Both approaches are important tools for IPDMA researchers and neither are a panacea. If most studies in the IPDMA are small (few participants or events), a one‐stage approach is recommended due to using a more exact likelihood. However, in other situations, researchers can choose either approach, carefully following best practice. Some previous claims recommending to always use a one‐stage approach are misleading, and the two‐stage approach will often suffice for most researchers. When differences do arise between the two approaches, often it is caused by researchers using different modelling assumptions or estimation methods, rather than using one or two stages per se.
Outcomes of a respiratory therapist driven high flow nasal cannula management protocol for pediatric critical asthma patients

This study aimed to determine if a respiratory therapist (RT)‐driven high flow nasal cannula (HFNC) protocol could decrease duration of HFNC use, pediatric intensive care unit (PICU) and hospital length of stay (LOS), and duration of continuous albuterol use in pediatric patients with critical asthma.
Dorsal hippocampal CA1 NMDA receptors mediate the interactive effects of quetiapine and lithium on memory retention in male rats

Objective(s): Lithium and quetiapine are administered simultaneously as a treatment for bipolar disorder. The concurrent use of these two drugs has been observed to affect the neurobiological mechanisms underlying learning and memory. To clarify the precise mechanisms involved, we evaluated the possible role of the dorsal hippocampal CA1 NMDA receptors in the interactive effects of lithium and quetiapine in memory consolidation. Materials and Methods: The dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated, and a single-trial step-through inhibitory avoidance apparatus was used to assess memory consolidation. Results: Post-training administration of certain doses of lithium (20, 30, and 40 mg/kg, IP) diminished memory consolidation. Post-training administration of higher doses of quetiapine (5, 10, and 20 mg/kg, IP) augmented memory consolidation. Post-training administration of certain doses of quetiapine (2.5, 5, 10, and 20 mg/kg) dose-dependently restored lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10-5 and 10-4 µg/rat, intra-CA1) plus an ineffective dose of quetiapine (2.5 mg/kg) restored the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-801 (0.0625 and 0.0125 μg/rat, intra-CA1), diminished the quetiapine-induced (10 mg/kg) memory improvement in lithium-induced memory impairment. Conclusion: These findings suggest a functional interaction between lithium and quetiapine through hippocampal CA1 NMDA receptor mechanisms in memory consolidation.
IMPACT OF FOVEAL STATUS AND TIMING OF SURGERY ON VISUAL OUTCOME IN RHEGMATOGENOUS RETINAL DETACHMENT

In this observational study, fovea-on and fovea-split cases demonstrated comparable visual outcomes which were not affected by length of time to surgery if performed within 7 days. By contrast, cases presenting fovea-off demonstrated worse visual outcomes, which declined further when surgery was delayed by two or more days. Purpose: To investigate the impact of surgical timing on visual acuity outcomes in retinal detachments based on the preoperative foveal status. Methods: A retrospective multicenter cohort study was conducted. Cases were stratified into fovea-on, fovea-split, and fovea-off groups. Days to surgery was defined as the time between the preoperative examination and surgery. The main outcome measure was the final postoperative visual acuity. Results: 1,675 cases were studied. More than 80% of fovea-on/fovea-split and fovea-off cases had surgery within 1 and 3 days, respectively. The mean final postoperative visual acuity did not differ significantly between the fovea-on and fovea-split groups (Snellen equivalent [SE] 20/33 ± 20/49 and 20/32 ± 20/39, P = 1.000) and did not change significantly based on days to surgery in either group. The mean final postoperative visual acuity was lowest in the fovea-off group (Snellen equivalent = 20/56 ± 20/76, P < 0.001) and was significantly lower in cases where surgery was performed after two or more days when compared with cases performed within 1 day (Snellen equivalent 20/74 ± 20/89 vs. 20/46 ± 20/63, P < 0.001). Conclusion: Fovea-on and fovea-split retinal detachments demonstrated comparable visual outcomes. Fovea-off RDs demonstrated worse visual outcomes, which declined further when surgery was delayed by two or more days.
A spotlight on intestinal permeability and inflammatory bowel diseases

ABSTRACT Introduction The intestinal barrier is a multi-faced structure lining the surface of the intestinal mucosa of the GI tract. To exert its main functions as a physical and immunological defense barrier, several components of the intestinal barrier act in a concerted and cooperative manner. Areas covered Herein, we first introduce to the basic organization of the intestinal barrier and then summarize different methods to assess barrier function in and ex vivo. Finally, we provide an in-depth overview of the relevance of intestinal barrier dysfunction in inflammatory bowel diseases. Expert opinion In parallel to a more fundamental understanding of the intestinal barrier as a key component for intestinal integrity is the notion that intestinal barrier defects are associated with a variety of diseases such as inflammatory bowel diseases. Recent research has fueled and perpetuated the concept that barrier defects are critical components of disease development, disease behavior, and potentially also an area of therapeutic intervention in IBD patients. Although being far away from standard, new technologies can be used to easily assess barrier healing in IBD and to derive clinical consequences from these findings such as more accurate forecasting of future disease behavior or the identification of novel therapeutic targets.
Multimodal fusion of multiple rest fMRI networks and MRI gray matter via parallel multilink joint ICA reveals highly significant function/structure coupling in Alzheimer's disease

In this article, we focus on estimating the joint relationship between structural magnetic resonance imaging (sMRI) gray matter (GM), and multiple functional MRI (fMRI) intrinsic connectivity networks (ICNs). To achieve this, we propose a multilink joint independent component analysis (ml‐jICA) method using the same core algorithm as jICA. To relax the jICA assumption, we propose another extension called parallel multilink jICA (pml‐jICA) that allows for a more balanced weight distribution over ml‐jICA/jICA. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer's disease (AD) versus controls. The results of the pml‐jICA yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for AD versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to GM components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.
Safety and pharmacodynamic efficacy of eculizumab in aneurysmal subarachnoid hemorrhage (CLASH): A phase 2a randomized clinical trial

Introduction: Complement C5 antibodies reduce brain injury after experimental subarachnoid hemorrhage. Patients and methods: In this randomized, controlled, open-label, phase 2a clinical trial with blinded-outcome assessment, we included adult aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to a tertiary referral center ⩽11 h after ictus. Patients were randomized (1:1) to eculizumab plus care as usual or to care as usual. Eculizumab (1200 mg) was administered <12 h, and on days 3 and 7 after ictus. In the intervention group, all patients received prophylactic antibiotics and, after a protocol amendment, fluconazole if indicated. Primary outcome was C5a concentration in cerebrospinal fluid (CSF) on day 3 after ictus. Safety was monitored during 4 weeks. In each group, 13 patients with CSF assessments were needed to detect a 55% reduction in CSF C5a concentration. Results: From October 2018 to May 2021, we enrolled 31 patients of whom 26 with CSF samples, 13 per group. Median C5a concentration in CSF on day 3 was 251 pg/ml [IQR: 103–402] in the intervention group and 371 pg/ml [IQR: 131–534] in the control group (p = 0.29). Infections occurred in two patients in the intervention group and four patients in the control group. One patient in the intervention group developed a C. albicans meningitis prior to the protocol amendment. Discussion and conclusion: One dose of eculizumab did not result in a ⩾ 55% decrease in C5a concentration in CSF on day 3 after aSAH. The study did not reveal new safety concerns, except for a C. albicans drain-related infection prior to antifungal monitoring and treatment. Trial registration: EudraCT 2017-004307-51, https://www.clinicaltrialsregister. eu/