Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning coronary artery calcium scoring in coronary CTA from non-contrast CT using unsupervised domain adaptation

Deep learning methods have demonstrated the ability to perform accurate coronary artery calcium (CAC) scoring. However, these methods require large and representative training data hampering applicability to diverse CT scans showing the heart and the coronary arteries. Training methods that accurately score CAC in cross-domain settings remains challenging. To address this, we present an unsupervised domain adaptation method that learns to perform CAC scoring in coronary CT angiography (CCTA) from non-contrast CT (NCCT). To address the domain shift between NCCT (source) domain and CCTA (target) domain, feature distributions are aligned between two domains using adversarial learning. A CAC scoring convolutional neural network is divided into a feature generator that maps input images to features in the latent space and a classifier that estimates predictions from the extracted features. For adversarial learning, a discriminator is used to distinguish the features between source and target domains. Hence, the feature generator aims to extract features with aligned distributions to fool the discriminator. The network is trained with adversarial loss as the objective function and a classification loss on the source domain as a constraint for adversarial learning. In the experiments, three data sets were used. The network is trained with 1,687 labeled chest NCCT scans from the National Lung Screening Trial. Furthermore, 200 labeled cardiac NCCT scans and 200 unlabeled CCTA scans were used to train the generator and the discriminator for unsupervised domain adaptation. Finally, a data set containing 313 manually labeled CCTA scans was used for testing. Directly applying the CAC scoring network trained on NCCT to CCTA led to a sensitivity of 0.41 and an average false positive volume 140 mm3/scan. The proposed method improved the sensitivity to 0.80 and reduced average false positive volume of 20 mm3/scan. The results indicate that the unsupervised domain adaptation approach enables automatic CAC scoring in contrast enhanced CT while learning from a large and diverse set of CT scans without contrast. This may allow for better utilization of existing annotated data sets and extend the applicability of automatic CAC scoring to contrast-enhanced CT scans without the need for additional manual annotations. The code is publicly available at https://github.com/qurAI-amsterdam/CACscoringUsingDomainAdaptation.
Quantitative trait loci mapping reveals important genomic regions controlling root architecture and shoot biomass under nitrogen, phosphorus, and potassium stress in rapeseed (Brassica napus L.)

Plants rely on root systems for nutrient uptake from soils. Marker-assisted selection helps breeders to select desirable root traits for effective nutrient uptake. Here, 12 root and biomass traits were investigated at the seedling stage under low nitrogen (LN), low phosphorus (LP), and low potassium (LK) conditions, respectively, in a recombinant inbred line (RIL) population, which was generated from Brassica napus L. Zhongshuang11 and 4D122 with significant differences in root traits and nutrient efficiency. Significant differences for all the investigated traits were observed among RILs, with high heritabilities (0.43–0.74) and high correlations between the different treatments. Quantitative trait loci (QTL) mapping identified 57, 27, and 36 loci, explaining 4.1–10.9, 4.6–10.8, and 4.9–17.4% phenotypic variances under LN, LP, and LK, respectively. Through QTL-meta analysis, these loci were integrated into 18 significant QTL clusters. Four major QTL clusters involved 25 QTLs that could be repeatedly detected and explained more than 10% phenotypic variances, including two NPK-common and two specific QTL clusters (K and NK-specific), indicating their critical role in cooperative nutrients uptake of N, P, and K. Moreover, 264 genes within the four major QTL clusters having high expressions in roots and SNP/InDel variations between two parents were identified as potential candidate genes. Thirty-eight of them have been reported to be associated with root growth and development and/or nutrient stress tolerance. These key loci and candidate genes lay the foundation for deeper dissection of the NPK starvation response mechanisms in B. napus.
An appressorium membrane protein, Pams1, controls infection structure maturation and virulence via maintaining endosomal stability in the rice blast fungus

The rice blast fungus Magnaporthe oryzae spores differentiate and mature into functional appressoria by sensing the host surface signals. Environmental stimuli are transduced into cells through internalization during appressorium formation, such as in the cAMP-PKA pathway. Here, we describe a novel contribution to how appressoria mature on the surface of a leaf, and its connection to endosomes and the cAMP-PKA pathway. An appressorium membrane-specific protein, Pams1, is required for maintaining endosomal structure, appressorium maturation, and virulence in M. oryzae. During appressorium development, Pams1 was translocated from the cell membrane to the endosomal membrane. Deletion of PAMS1 led to the formation of two types of abnormal appressoria after 8 h post inoculation (hpi): melanized type I had a reduced virulence, while pale type II was dead. Before 8 hpi, Δpams1 formed appressoria that were similar to those of the wild type. After 8 hpi, the appressoria of Δpams1 was differentiated into two types: (1) the cell walls of type I appressoria were melanized, endosomes were larger, and had a different distribution from the wild type and (2) Type II appressoria gradually stopped melanization and began to die. The organelles, including the nucleus, endosomes, mitochondria, and endoplasmic reticula, were degraded, leaving only autophagic body-like vesicles in type II appressoria. The addition of exogenous cAMP to Δpams1 led to the formation of a greater proportion of type I appressoria and a smaller proportion of type II appressoria. Thus, defects in endosomal structure and the cAMP-PKA pathway are among the causes of the defective appressorium maturation and virulence of Δpams1.
Mu opioid receptor stimulation in the medial preoptic area or nucleus accumbens facilitates song and reward in flocking European starlings

It has been proposed that social cohesion in gregarious animals is reinforced both by a positive affective state induced by social interactions and by the prevention of a negative state that would be caused by social separation. Opioids that bind to mu opioid receptors (MORs) act in numerous brain regions to induce positive and to reduce negative affective states. Here we explored a potential role for MORs in affective states that may impact flocking behavior in mixed-sex flocks of nonbreeding European starlings, Sturnus vulgaris. Singing behavior, which is considered central to flock cohesion, and other social behaviors were quantified after infusions of the MOR agonist D-Ala2, N-Me-Phe4, glycinol5-ENK (DAMGO) into either the medial preoptic area (POM) or the nucleus accumbens (NAC), regions previously implicated in affective state and flock cohesion. We focused on beak wiping, a potential sign of stress or redirected aggression in this species, to provide insight into a presumed negative state. We also used conditioned place preference (CPP) tests to provide insight into the extent to which infusions of DAMGO into POM or NAC that stimulated song might be rewarding. We found that MOR stimulation in either POM or NAC dose-dependently promoted singing behavior, reduced beak wiping, and induced a CPP. Subtle differences in responses to MOR stimulation between NAC and POM also suggest potential functional differences in the roles of these two regions. Finally, because the location of NAC has only recently been identified in songbirds, we additionally performed a tract tracing study that confirmed the presence of dopaminergic projections from the ventral tegmental area to NAC, suggesting homology with mammalian NAC. These findings support the possibility that MORs in POM and NAC play a dual role in reinforcing social cohesion in flocks by facilitating positive and reducing negative affective states.
Associations between abdominal obesity and the risk of stroke in Chinese older patients with obstructive sleep apnea: Is there an obesity paradox?

Background and purpose Abdominal obesity (AO) is a well-known independent risk factor for stroke in the general population although it remains unclear in the case of the elderly, especially in Chinese older patients with obstructive sleep apnea (OSA), considering the obesity paradox. This study aimed to investigate the association between AO and stroke among Chinese older patients with OSA. Methods Data were collected from January 2015 to October 2017, and 1,290 older patients (age 60–96 years) with OSA (apnea–hypopnea index ≥ 5 events/h on polysomnography) were consecutively enrolled from sleep centers at six hospitals, evaluated for AO defined as waist circumference (WC) using the standardized criteria for the Chinese population, and followed up prospectively for a median period of 42 months. Logistic regression and Cox regression analyses were used to determine the cross-sectional and longitudinal associations between AO and stroke risk in these participants and different groups of the severity of OSA. Results Participants with AO had a higher prevalence of stroke at baseline. A higher incidence of stroke during a median follow-up period of 42 months in participants with AO than in participants without AO (12.4% vs. 6.8% and 8.3% vs. 2.4%, respectively; both P < 0.05) was predicted. Cross-sectional analysis revealed an association between AO and stroke (odds ratio [OR]1.96, 95% confidence interval [CI] 1.31–2.91), which was stronger among participants with moderate OSA only (OR 2.16, 95%CI 1.05–4.43). Cox regression analysis showed that, compared to participants without AO, participants with AO had a higher cumulative incidence of stroke (hazard ratio [HR] 2.16, 95% CI 1.12–4.04) during a median follow-up of 42 months, and this association was observed in patients with severe OSA only (HR 3.67, 95% CI 1.41–9.87) but not for individuals with mild OSA (HR = 1.84, 95% CI 0.43–6.23) and moderate OSA (HR = 1.98, 95% CI 0.73–6.45). Conclusion The risk of stroke is associated with AO among Chinese older patients who have OSA, both at baseline and during follow-up, and the strength of the association varied by OSA severity. Active surveillance for early detection of AO could facilitate the implementation of stroke-preventive interventions in the Chinese older OSA population.
Mechanism of tonifying-kidney Chinese herbal medicine in the treatment of chronic heart failure

According to traditional Chinese medicine (TCM), chronic heart failure has the basic pathological characteristics of “heart-kidney yang deficiency. ” Chronic heart failure with heart- and kidney-Yang deficiency has good overlap with New York Heart Association (NYHA) classes III and IV. Traditional Chinese medicine classical prescriptions for the treatment of chronic heart failure often take “warming and tonifying kidney-Yang” as the core, supplemented by herbal compositions with functions of “promoting blood circulation and dispersing blood stasis. ” Nowadays, there are still many classical and folk prescriptions for chronic heart failure treatment, such as Zhenwu decoction, Bushen Huoxue decoction, Shenfu decoction, Sini decoction, as well as Qili Qiangxin capsule. This review focuses on classical formulations and their active constituents that play a key role in preventing chronic heart failure by suppressing inflammation and modulating immune and neurohumoral factors. In addition, given that mitochondrial metabolic reprogramming has intimate relation with inflammation, cardiac hypertrophy, and fibrosis, the regulatory role of classical prescriptions and their active components in metabolic reprogramming, including glycolysis and lipid β-oxidation, is also presented. Although the exact mechanism is unknown, the classical TCM prescriptions still have good clinical effects in treating chronic heart failure. This review will provide a modern pharmacological explanation for its mechanism and offer evidence for clinical medication by combining TCM syndrome differentiation with chronic heart failure clinical stages.
Handel-Miller theory and finite depth foliations

We make a detailed study of the unpublished work of M. Handel and R. Miller on the classification, up to isotopy, of endperiodic homeomorphisms of surfaces. We generalize this theory to surfaces with infinitely many ends and we axiomatize the theory for the important case in which the laminations cannot be assumed to be geodesic. We set the stage for projected applications to foliations of depth greater than one. Using the axioms, we provide a completely new proof of the so-called “transfer theorem”, namely that, if two depth one foliations F and F′ are transverse to a common one-dimensional foliation L which induces Handel-Miller monodromy on the noncompact leaves of F, then L also induces Handel-Miller monodromy on the noncompact leaves of F′. An earlier published proof was very complicated and contained some errors. Finally, the axioms also let us smooth the Handel-Miller map.
Identification of protein–protein interaction associated functions based on gene ontology and KEGG pathway

Protein–protein interactions (PPIs) are extremely important for gaining mechanistic insights into the functional organization of the proteome. The resolution of PPI functions can help in the identification of novel diagnostic and therapeutic targets with medical utility, thus facilitating the development of new medications. However, the traditional methods for resolving PPI functions are mainly experimental methods, such as co-immunoprecipitation, pull-down assays, cross-linking, label transfer, and far-Western blot analysis, that are not only expensive but also time-consuming. In this study, we constructed an integrated feature selection scheme for the large-scale selection of the relevant functions of PPIs by using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations of PPI participants. First, we encoded the proteins in each PPI with their gene ontologies and KEGG pathways. Then, the encoded protein features were refined as features of both positive and negative PPIs. Subsequently, Boruta was used for the initial filtering of features to obtain 5684 features. Three feature ranking algorithms, namely, least absolute shrinkage and selection operator, light gradient boosting machine, and max-relevance and min-redundancy, were applied to evaluate feature importance. Finally, the top-ranked features derived from multiple datasets were comprehensively evaluated, and the intersection of results mined by three feature ranking algorithms was taken to identify the features with high correlation with PPIs. Some functional terms were identified in our study, including cytokine–cytokine receptor interaction (hsa04060), intrinsic component of membrane (GO:0031224), and protein-binding biological process (GO:0005515). Our newly proposed integrated computational approach offers a novel perspective of the large-scale mining of biological functions linked to PPI.
A multi-center, randomized, double-blinded, parallel, placebo-controlled study to assess the efficacy and safety of Shenqisuxin granule in complex coronary artery disease after PCI: Study protocol

Introduction The Shenqisuxin granule (SQSX), a novel Chinese herbal formula, has the effect of preventing in-stent restenosis and improving angiogenesis. We intend to evaluate the efficacy and safety of SQSX to provide a possible therapeutic strategy for complex coronary artery disease (CCAD) after percutaneous coronary intervention (PCI). Methods/design The study is a multi-center, randomized, double-blinded, parallel, placebo-controlled trial. A total of 120 participants will be randomized 1:1 into the intervention group and the control group. Based on standardized treatment, the intervention group and control group will receive SQSX and placebo for 2 months, respectively. The primary outcomes, metabolic equivalents (METS) and peak oxygen uptake (Peak VO2), and the secondary outcomes, including other indicators of cardiorespiratory fitness (CRF), the European Quality of Life Questionnaire (EQ-5D-5L), the Seattle Angina Scale (SAQ), etc., will be assessed at baseline and 2 months ± 3 days. In addition, the survey scales will also be tested at 1 month ± 3 days. Trimethylamine N-oxide (TMAO), high-sensitivity C-reactive protein (hs-CRP), and gut microbiota features will be assessed at baseline and 2 months ± 3 days to probe possible mechanism. The major adverse cardiac and cerebrovascular events (MACCE) and bleeding events will be monitored until the 12-month follow-up. Discussion This study is launched to assess the efficacy and safety of SQSX in CCAD after PCI and probe the possible mechanism. Clinical trial registration China Clinical Trial Registry, ChiCTR2200060979, Registered on June 14, 2022.
Transcriptome analysis provides insight into adaptive mechanisms of scallops under environmental stress

High temperature and hypoxia greatly threaten marine life and aquaculture. Scallops, a diverse and ecologically important group of high economic value, mostly thrive in fluctuating environments, and are vulnerable to environmental stress. In the present study, the molecular response mechanism of scallops to a combination of environmental stressors was investigated via transcriptome analysis of the gill tissues in three scallop species, the Yesso scallop (Patinopecten yessoensis), Zhikong scallop (Chlamys farreri) and bay scallop (Argopecten irradians) that were exposed to transient heat, hypoxia and a combination thereof. The Yesso scallop had the most differentially expressed genes (DEGs) compared with the other two scallop species, indicating the highest sensitivity of the Yesso scallop to environmental stress. With increased temperature and decreased dissolved oxygen, the number of DEGs was greatly increased in the three scallop species, indicative of the enhancement in gene expression regulation in scallops in response to severe environmental changes. Heat and hypoxia had a synergistic effect on scallops. GO and KEGG enrichment analysis of DEGs under different stressors revealed overlapping molecular mechanisms of response in scallops following exposure to heat and hypoxia. Several immune and apoptosis-related pathways were highly enriched in the upregulated DEGs of the three scallops, suggesting that immune system activation and apoptosis promotion occurred in scallops in response to environmental stress. Heat shock proteins (HSPs) were significantly upregulated under heat and hypoxia, which likely assisted in correct protein folding to facilitate the adaption of the scallops to the altered environment. Additionally, the HIF-1 signaling pathway—the key pathway associated with hypoxia response—was triggered by extremely acute environmental changes. Comparative transcriptome analysis revealed 239 positively selected genes among the different scallops, including those involved in immune system and environmental adaptation, suggesting a long-term mechanism of environmental adaptation. The present study provides new insights into the molecular response mechanism in scallops to multiple environmental stressors and improves our understanding of the adaptive mechanisms of marine organisms under changing global climate conditions.
Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme

Breast and ovarian cancers are among the most common malignancies in the female population, with approximately 5–10% of cases being hereditary. BRCA1 and BRCA2 with other homologous recombination genes are the most tested genes in hereditary breast and ovarian cancer (HBOC) patients. As next-generation sequencing (NGS) has become a standard and popular technique, such as for HBOC, it has greatly simplified and accelerated molecular diagnosis of cancer. The study group included 3,458 HBOC patients or their relatives from Lower Silesia (Poland) (a voivodeship located in south-west Poland inhabited by 2.9 million people). All patients were tested according to the recommendations from the National Cancer Control Programme of the Ministry of Health for the years 2018–21. We tested 3,400 patients for recurrent pathogenic variants for the Polish population: five BRCA1 founder variants (c.5266dup, c.181T>G, c.4035del, c.3700_3704del, and c.68_69del), two PALB2 variants (c.509_510del, c.172_175del) and three CHEK2 variants [c.1100del, c.444+1G>A, g.27417113-27422508del (del5395)]. Next 260 patients from the study group were chosen for the BRCA1/2 NGS panel, and additionally selected marker pathogenic variants were tested using Sanger sequencing and MLPA methods in 45 and 13 individuals, respectively. The analysis of BRCA1/2 in the 3,458 patients with HBOC or their relatives revealed 144 carriers of 37 different pathogenic variants (22 in BRCA1 and 15 in BRCA2). Among all detected variants, 71.53% constituted founder pathogenic BRCA1 variants. Our study has revealed that for the Lower Silesian population, the first-line BRCA1/2 molecular test may be limited to only three variants in BRCA1—c.5266dup, c.181T>G, and c.4035del—but the aim should be to provide a full screening test of HBOC critical genes. The key and still growing role of molecular diagnostics of neoplasms, which includes HBOC, is undeniable. Therefore, it is necessary to provide complete and optimal therapeutic and prophylactic algorithms in line with current medical knowledge.