Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed. Objectives: To develop and validate a deep learning method to improve the management of IPNs. Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions. Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4–90.7%) and 91.9% (95% CI, 88.7–94.7%), compared with 78.1% (95% CI, 68.7–86.4%) and 81.9 (95% CI, 76.1–87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts. Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.
The Expression Profile of Dental Pulp-Derived Stromal Cells Supports Their Limited Capacity to Differentiate into Adipogenic Cells

Mesenchymal stromal cells (MSCs) can self-renew, differentiate into specialised cells and have different embryonic origins—ectodermal for dental pulp-derived MSCs (DPSCs) and mesodermal for adipose tissue-derived MSCs (ADSCs). Data on DPSCs adipogenic differentiation potential and timing vary, and the lack of molecular and genetic information prompted us to gain a better understanding of DPSCs adipogenic differentiation potential and gene expression profile. While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). To better understand this limitation in adipogenesis, transcriptome analysis in undifferentiated DPSCs was carried out, with the ADSC transcriptome used as a positive control. In total, 14,871 transcripts were common to DPSCs and ADSCs, some were unique (DPSCs: 471, ADSCs: 1032), and 510 were differentially expressed genes. Detailed analyses of overrepresented transcripts showed that DPSCs express genes that inhibit adipogenic differentiation, revealing the possible mechanism for their limited adipogenesis.
Tissue‐resident CD8+T memory cells with unique properties are present in human decidua during early pregnancy

Resident memory T (TRM) cells reside in the uterus during pregnancy may play an important role in balancing maternal‐fetal tolerance with anti‐infectious immunity. Although CD8+TRM and decidual CD8+T cells have been extensively characterized, the properties of decidual CD8+TRM (dTRM) cells remain poorly defined.
Variation in volumes and characteristics of trauma patients admitted to a level one trauma centre during national level 4 lockdown for COVID-19 in New Zealand.

AIM The aims of this study were to describe the variation in volumes and types of injuries admitted to a level one trauma centre in New Zealand over two 14-day periods before and during the national level 4 lockdown for COVID-19; and highlight communities at risk of preventable injury that may impact negatively on hospital resources. METHOD A retrospective, descriptive study of prospectively collected data in the Midland Trauma Registry in New Zealand. RESULTS Overall there was a reduction of 43% in all injury-related admissions with significant reductions seen in major injury (50% reduction), males (50% reduction) and children aged 0-14 years (48% reduction). Results for ethnicity and persons aged over 14 years were within 3% deviation of this overall 43% reduction. Injuries at home, particularly falls, predominate. CONCLUSION Despite the significant reduction in admissions during level 4 lockdown, hospitals should continue to provide full services until resource limitations are unavoidable. Immediate messaging is recommended to reduce rates of injury on the farm and at home, specifically falls prevention. Ongoing attention of road users to road safety is essential to reduce the incidence of preventable major injury. These immediate measures can potentially reduce unnecessary pressure on hospital beds and resources during the pandemic.
Study on Adsorption and Aggregation in the Mixed System of Polyacrylamide, Cu(II) Ions and Innovative Carbon–Silica Composite

The paper presents an original study on adsorption and aggregation phenomena in a mixed system consisting of a macromolecular compound, heavy metal ions and an innovative adsorbent. The authors used ionic polyacrylamides (PAM), Cu(II) ions and carbon–silica composite (C-SiO2) in the experiments. Such a system has not yet been described in the literature and therefore, the article is of significant novelty and great importance. The composite was prepared by mixing phenol–formaldehyde resin with silica and pyrolysis at 800 °C. The adsorbed amounts of Cu(II) ions and PAM were determined spectrophotometrically. C-SiO2 was characterized using potentiometric titration, microelecrophoresis and Fourier Transform Infrared Spectroscopy (FTIR) analysis. In turn, the C-SiO2 aggregation was established turbidimetrically as well as using a particle size analyzer. The obtained results indicated that both Cu(II) ions and ionic polyacrylamide were adsorbed on the composite surface at pH 6. The highest noted adsorbed amounts were 9.8 mg/g for Cu(II) and 35.72 mg/g for CT PAM-25%. Cu(II) ions increased the anionic PAM adsorbed and reduced the cationic PAM one. The adsorption of anionic PAM (50 ppm) stimulated the solid aggregation significantly. What is more, Cu(II) ions enhanced this process. The size of particles/aggregates formed without additives equaled 0.44 μm, whereas in the mixed Cu(II)/AN PAM system, they were even at 1.04 μm.
Sphingosine kills bacteria by binding to cardiolipin

Sphingosine is a long-chain sphingoid base that has been shown to have bactericidal activity against many pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. We have previously demonstrated that sphingosine is present in nasal, tracheal, and bronchial epithelial cells and constitutes a central element of the defense of the airways against bacterial pathogens. Here, using assorted lipid-binding and cell biology assays, we demonstrate that exposing P. aeruginosa and S. aureus cells to sphingosine results in a very rapid, i.e. within minutes, permeabilization of the bacterial plasma membrane, resulting in leakiness of the bacterial cells, loss of ATP, and loss of bacterial metabolic activity. These alterations rapidly induced bacterial death. Mechanistically, we demonstrate that the presence of the protonated NH2 group in sphingosine, which is an amino-alcohol, is required for sphingosine's bactericidal activity. We also show that the protonated NH2 group of sphingosine binds to the highly negatively–charged lipid cardiolipin in bacterial plasma membranes. Of note, this binding was required for bacterial killing by sphingosine, as revealed by genetic experiments indicating that E. coli or P. aeruginosa strains that lack cardiolipin synthase are resistant to sphingosine, both in vitro and in vivo. We propose that binding of sphingosine to cardiolipin clusters cardiolipin molecules in the plasma membrane of bacteria. This clustering results in the formation of gel-like or even crystal-like structures in the bacterial plasma membrane and thereby promotes rapid permeabilization of the plasma membrane and bacterial cell death.
Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity

Akkermansia muciniphila is a mucin-degrading bacterium that has shown the potential to provide anti-inflammatory and anti-obesity effects in mouse and man. We here focus on companion animals, specifically cats and dogs, and evaluate the microbial degradation of mucus and its health impact in the context of the worldwide epidemic of pet obesity. A literature survey revealed that the two presently known Akkermansia spp. , A. muciniphila and A. glycaniphila, as well as other members of the phylum of Verrucomicrobia seem to be neither very prevalent nor abundant in the digestive tract of cats and dog. While this may be due to methodological aspects, it suggests that bacteria related to Akkermansia are not the major mucus degraders in these pets and hence other mucus-utilizing taxa may deserve attention. Hence, we will discuss the potential of these endogenous mucus utilizers and dietary interventions to boost these as well as the use of Akkermansia spp. related bacteria or their components as strategies to target feline and canine obesity.
Hope, Loneliness and Sense of Coherence among Bereaved Parents

Coping with the loss of a child is a challenging and difficult experience that disrupts the lives of the surviving parents and the fabric of the family. Our goal is to identify the factors that help bereaved parents cope with this loss and introduce hope and future perspectives into their lives. Our sample consisted of 81 parents (30 fathers and 51 mothers), who completed questionnaires on the following topics: family climate, loneliness, sense of coherence and hope. In addition, interviews were conducted with six parents to further clarify the quantitative results. A moderated mediation model revealed that increased levels of loneliness among the parents predicted lower levels of hope. However, their emotional resources in terms of their sense of coherence mediated this relationship. In addition, the number of years since the loss moderated the negative relationship between loneliness and the parents’ emotional resources. It can be concluded that the negative impact of loneliness on parents’ sense of coherence declined over time. The interviews conducted extend the understanding of these results, as parents described their ability to continue with their lives and identified their goals in terms of the hope theory, alongside their ongoing pain. Finally, the therapeutic implications of the results we obtained are discussed.
Dysmetabolic Circulating Tumor Cells Are Prognostic in Metastatic Breast Cancer

Circulating tumor cells (CTCs) belong to a heterogeneous pool of rare cells, and a unequivocal phenotypic definition of CTC is lacking. Here, we present a definition of metabolically-altered CTC (MBA-CTCs) as CD45-negative cells with an increased extracellular acidification rate, detected with a single-cell droplet microfluidic technique. We tested the prognostic value of MBA-CTCs in 31 metastatic breast cancer patients before starting a new systemic therapy (T0) and 3–4 weeks after (T1), comparing results with a parallel FDA-approved CellSearch (CS) approach. An increased level of MBA-CTCs was associated with: i) a shorter median PFS pre-therapy (123 days vs. 306; p < 0.0001) and during therapy (139 vs. 266 days; p = 0.0009); ii) a worse OS pre-therapy (p = 0.0003, 82% survival vs. 20%) and during therapy (p = 0.0301, 67% survival vs. 38%); iii) good agreement with therapy response (kappa = 0.685). The trend of MBA-CTCs over time (combining data at T0 and T1) added information with respect to separate evaluation of T0 and T1. The combined results of the two assays (MBA and CS) increased stratification accuracy, while correlation between MBA and CS was not significant, suggesting that the two assays are detecting different CTC subsets. In conclusion, this study suggests that MBA allows detection of both EpCAM-negative and EpCAM-positive, viable and label-free CTCs, which provide clinical information apparently equivalent and complementary to CS. A further validation of proposed method and cut-offs is needed in a larger, separate study.
Central American Immigrant Parents’ Awareness, Acceptability, and Willingness to Vaccinate Their Adolescent Children Against Human Papillomavirus: A Pilot Cross-Sectional Study

Despite increasing interest in understanding the factors influencing awareness and acceptability of the human papillomavirus (HPV) vaccine among Latino parents, to date limited information is available specific to Central American parents living in the United States (US). Therefore, this pilot cross-sectional study was designed to explore and assess Central American immigrant parents’ awareness, acceptability, and willingness to vaccinate their children against HPV, and interest in participating in future HPV-associated cancer prevention study. Fifty-six Central American parents, majority immigrant (96.4%; n = 54) from four countries, El Salvador—50% (n = 27); Guatemala—25.9% (n = 14); Honduras—22.2% (n = 12); and Panama—1.9% (n = 1) participated in this study. Participants completed an interviewer-administered questionnaire survey in their preferred language (i.e., Spanish or English). A little over half of the participants were mothers (57.1%; n = 32) and parents’ mean age was 43.2 years (SD = 6.4). The majority was married or cohabitating (76.8%, n = 43), and 39.3% (n = 22) reported having two children. Seventy-five percent (n = 42) of parents reported they had heard of the HPV vaccine. Fewer fathers were aware of the HPV vaccine (58.3%; n = 14 vs.87.5%, n = 28; p = 0.01) than mothers. Among parents who had heard of the HPV vaccine (n = 42), 85.7% (n = 36) reported their children had received at least one dose of the HPV vaccine. Fewer fathers reported their child had been vaccinated against HPV (64.3%, n = 9 vs. 96.4%, n = 27; p = 0.06) than mothers. Moreover, 90% of parents (n = 18) whose children were unvaccinated reported willingness to vaccinate their adolescent children against HPV if recommended by their child’s physician. Findings indicate parents’ low to moderate awareness of the HPV vaccine, and high willingness to vaccinate their adolescent children if recommended by their child’s physician. Findings also demonstrate fathers’ lower awareness and acceptability of the HPV vaccine than mothers. Despite limitations and the need for more research, findings of this pilot study serve as a valuable first step toward building a knowledge foundation that is needed for developing future studies and interventions targeting Central American immigrant parents living in the US. Future studies can build on the findings of this exploratory study with other research designs and address its limitations by having a larger sample size and accounting for additional factors associated with Central American immigrant parents’ HPV awareness, knowledge, beliefs, attitudes, and vaccine acceptability from other communities across the US.
Contribution of executive functions to eating behaviours in obesity and eating disorders

Abstract Background: Patients with eating disorders (ED) or obesity show difficulties in tasks assessing decision-making, set-shifting abilities and central coherence. Aims: The aim of this study was to explore executive functions in eating and weight-related problems, ranging from restricting types of ED to obesity. Method: Two hundred and eighty-eight female participants (75 with obesity; 149 with ED: 76 with restrictive eating, 73 with bingeing-purging symptoms; and 64 healthy controls) were administered the Wisconsin Card Sorting Test, the Iowa Gambling Task, and the Group Embedded Figures Test to assess set-shifting, decision-making and central coherence, respectively. Results: Participants with either obesity or ED performed poorly on tests measuring executive functioning compared with healthy controls, even after controlling for age and intelligence. Both participants with obesity and participants with ED showed a preference for global information processing. Conclusions: The findings suggest that treatments for obesity and ED would benefit from addressing difficulties in cognitive functioning, in addition to the more evident clinical symptoms related to eating, body weight and shape.
Not all disengagement coping strategies are created equal: positive distraction, but not avoidance, can be an adaptive coping strategy for chronic life stressors

ABSTRACT Background: Positive distraction involves distracting oneself from a stressor by thinking about or engaging in activities that induce positive emotion. We hypothesized that although it is a disengagement coping strategy, which have been historically viewed as maladaptive (e.g., avoidance), positive distraction can be an adaptive version that predicts positive outcomes. Design: To test this hypothesis, we developed a scale to measure positive and neutral distraction (distracting oneself by engaging in daily activities) in response to chronic stressors in 3 samples (MTurk1, N = 206; undergraduate, N = 376; MTurk2, N = 200). We then correlated the use of these strategies with outcomes in these samples and another undergraduate sample (N = 370). Results: Exploratory SEM confirmed that the scale consists of two factors corresponding to positive and neutral distraction, which were positively correlated with avoidance. However, unlike avoidance, positive distraction (and to a lesser degree neutral distraction) was related to positive outcomes such as higher well-being and positive emotions, and fewer depressive symptoms especially when controlling for avoidance. Conclusions: Our results suggest that positive distraction can be an adaptive disengagement coping strategy for chronic stressors when controlling for avoidance and should be incorporated into coping studies and interventions.
Experience-Dependent Coding of Time-Dependent Frequency Trajectories by Off Responses in Secondary Auditory Cortex

Time-dependent frequency trajectories are an inherent feature of many behaviorally relevant sounds, such as species-specific vocalizations. Dynamic frequency trajectories, even in short sounds, often convey meaningful information, which may be used to differentiate sound categories. However, it is not clear what and where neural responses in the auditory cortical pathway are critical for conveying information about behaviorally relevant frequency trajectories, and how these responses change with experience. Here, we uncover tuning to subtle variations in frequency trajectories in auditory cortex of female mice. We found that auditory cortical responses could be modulated by variations in a pure tone trajectory as small as 1/24th of an octave, comparable to what has been reported in primates. In particular, late spiking after the end of a sound stimulus was more often sensitive to the sound's subtle frequency variation compared with spiking during the sound. Such “Off” responses in the adult A2, but not those in core auditory cortex, were plastic in a way that may enhance the representation of a newly acquired, behaviorally relevant sound category. We illustrate this with the maternal mouse paradigm for natural vocalization learning. By using an ethologically inspired paradigm to drive auditory responses in higher-order neurons, our results demonstrate that mouse auditory cortex can track fine frequency changes, which allows A2 Off responses in particular to better respond to pitch trajectories that distinguish behaviorally relevant, natural sound categories. SIGNIFICANCE STATEMENT A whistle's pitch conveys meaning to its listener, as when dogs learn that distinct pitch trajectories whistled by their owner differentiate specific commands. Many species use pitch trajectories in their own vocalizations to distinguish sound categories, such as in human languages, such as Mandarin. How and where auditory neural activity encodes these pitch trajectories as their meaning is learned but not well understood, especially for short-duration sounds. We studied this in mice, where infants use ultrasonic whistles to communicate to adults. We found that late neural firing after a sound ends can be tuned to how the pitch changes in time, and that this response in a secondary auditory cortical field changes with experience to acquire a pitch change's meaning.
The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

Copper plays an important role as a regulator in many pathologies involving the angiogenesis process. In cancerogenesis, tumor progression, and angiogenic diseases, copper homeostasis is altered. Although many details in the pathways involved are still unknown, some copper-specific ligands have been successfully used as therapeutic agents. Copper-binding peptides able to modulate angiogenesis represent a possible way to value new drugs. We previously reported that a fragment (VEGF73-101) of vascular endothelial growth factor (VEGF165), a potent angiogenic, induced an apoptotic effect on human umbilical vein endothelial cells. The aim of this study was to investigate the putative copper ionophoric activity of VEGF73-101, as well as establish a relationship between the structure of the peptide fragment and the cytotoxic activity in the presence of copper(II) ions. Here, we studied the stoichiometry and the conformation of the VEGF73-101/Cu(II) complexes and some of its mutated peptides by electrospray ionization mass spectrometry and circular dichroism spectroscopy. Furthermore, we evaluated the effect of all peptides in the absence and presence of copper ions by cell viability and cytofuorimetric assays. The obtained results suggest that VEGF73-101 could be considered an interesting candidate in the development of new molecules with ionophoric properties as agents in antiangiogenic therapeutic approaches.