Miracle-dz/UniFAR-FTUs huggingface dataset:
Sociodemographic disparities in targeted therapy in ovarian cancer in a national sample

Background The treatment landscape for ovarian cancer has changed in recent years with the introduction of targeted therapies to treat patients with advanced disease. We investigated patient demographic and clinical factors associated with use of targeted therapies as a part of the first-line treatment for ovarian cancer. Methods This study included patients diagnosed with stage I–IV ovarian cancer between 2012 and 2019 from the National Cancer Database. Information on demographic and clinical characteristics were collected and described using frequency and percent across receipt of targeted therapy. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (CI) associating patient demographic and clinical factors with receipt of targeted therapy. Results Among 99,286 ovarian cancer patients (mean age 62 years), 4.1% received targeted therapy. The rate of targeted therapy receipt across racial and ethnic groups over the study period was fairly similar; however, non-Hispanic Black women were less likely to receive targeted therapy than their non-Hispanic White counterparts (OR=0.87, 95% CI: 0.76–1.00). Patients who received neoadjuvant chemotherapy were more likely to receive targeted therapy than those who received adjuvant chemotherapy (OR=1.26; 95% CI: 1.15–1.38). Moreover, among patients who received targeted therapy, 28% received neoadjuvant targeted therapy, with non-Hispanic Black women being most likely to receive neoadjuvant targeted therapy (34%) compared with other racial and ethnic groups. Conclusions We observed differences in receipt of targeted therapy by factors such as age at diagnosis, stage, and comorbidities present at diagnosis, as well as factors related to healthcare access—including neighborhood education level and health insurance status. Approximately 28% of patients received targeted therapy in the neoadjuvant setting, which could negatively impact treatment outcomes and survival due to the increased risk of complications associated with targeted therapies that may delay or prevent surgery. These results warrant further evaluation in a cohort of patients with more comprehensive treatment information.
Clinician and patient perspectives on the ontology of mental disorder: a qualitative study

Background Psychiatry may face an “identity crisis” regarding its very foundations. The lack of consensus regarding the theoretical grounds of psychiatry as a discipline has its epicenter in the discussion about the Diagnostic and Statistical Manual (DSM). A growing number of academics considers the manual broken and a growing number of patients voice concern. Despite the huge body of critique, 90% of Randomized Trials are based on DSM definitions of mental disorder. Therefore, the question regarding the ontology of mental disorder remains: what is a mental disorder, exactly? Aims We aim to identify ontologies that live among patients and clinicians, evaluate the degree of consistency and coherence between clinician and patient views and contribute to the establishment of a novel ontological paradigm of mental disorder that is aligned with patients’ and clinicians’ perspectives. Method Eighty participants (clinicians/patients/clinicians with lived experience) were interviewed using a semi-structured interview, exploring their ideas on the ontology of mental disorder. This question was approached from different angles which led to comprising the interview schedule into different topics: “concept of disorder,” “representation by DSM,” “what is treated,” “what is recovered,” and “the right outcome measure. ” Interviews were transcribed and analyzed using inductive Thematic Analysis. Results From all subthemes and main themes, a typology was constructed in which six, not necessarily mutually exclusive, ontological domains were identified: mental disorder as (1) disease, (2) functional impairment, (3) loss of adaptation, (4) existential problem, (5) highly subjective phenomenon, and (6) deviation from social norms. Common ground for the sample groups was that mental disorder is about functional impairment. Although about a fourth of sample clinicians holds an ontological concept of disease, only a small percentage of patients and none of the clinicians with lived experience adhered to an ontological concept of disease. The sample clinicians most often understand mental disorder to be a highly subjective phenomenon, and individuals with lived experience (patients and clinicians) most often understand mental (dis)order to be adaptational in nature: an (im)balance of burden in relation to strengths, skills, and recourses. Conclusion The ontological palette is more diverse than what is taught about mental disorder in dominant scientific and educational discourse. There is a need to diversify the current, dominant ontology and make room for other ontologies. Investment is required in the development, elaboration and coming of age of these alternative ontologies, allowing them to reach their full potential and act as drivers of a landscape of promising novel scientific and clinical approaches.
Improvement effect of biochar on soil microbial community structure and metabolites of decline disease bayberry

Decline disease is a new disease that has recently caused severe damage in bayberry industry. The effect of biochar on decline disease was determined by investigating the changes in the vegetative growth and fruit quality of bayberry trees as well as soil physical and chemical properties, microbial community structure, and metabolites. Results indicated that the application of biochar could improve the vigor and fruit quality of diseased trees, and rhizosphere soil microbial diversity at the levels of phyla, orders, and genera. The relative abundance of Mycobacterium, Crossiella, Geminibasidium, and Fusarium were significantly increased, while Acidothermus, Bryobacter, Acidibacter, Cladophialophora, Mycena, and Rickenella were significantly decreased by biochar in rhizosphere soil of decline diseased bayberry. Analysis of redundancies (RDA) of microbial communities and soil characteristics revealed that the composition of bacterial and fungal communities was significantly affected by the pH, organic matter, alkali hydrolyzable nitrogen, available phosphorus, available potassium, exchangeable calcium and exchangeable magnesium in bayberry rhizosphere soil, and the contribution rates to fungi were larger than those to bacteria at the genus level. Biochar greatly influenced the metabolomics distribution of rhizosphere soils of decline disease bayberry. One hundred and nine different metabolites from both the presence and absence of biochar, mainly include acid, alcohol, ester, amine, amino acid, sterol, sugar, and other secondary metabolites, of which the contents of 52 metabolites were increased significantly such as aconitic acid, threonic acid, pimelic acid, epicatechin, and lyxose. The contents of 57 metabolites decreased significantly, such as conduritol β-expoxide, zymosterol, palatinitol, quinic acid, and isohexoic acid. There was a great difference between the absence and presence of biochar in 10 metabolic pathways, including thiamine metabolism, arginine and proline metabolism, glutathione metabolism, ATP-binding cassette (ABC) transporters, butanoate metabolism, cyanoamino acid metabolism, tyrosine metabolism, phenylalanine metabolism, phosphotransferase system (pts), and lysine degradation. There was a significant correlation between the relative content of microbial species and the content of secondary metabolites in rhizosphere soil at the levels of bacterial and fungal phyla, order, and genus. Overall, this study highlighted the significant influence of biochar in decline disease by regulating soil microbial community, physical and chemical properties, and secondary metabolites in rhizosphere soil, which provided a novel strategy for managing bayberry decline disease.
In their own words: deception detection by victims and near victims of fraud

Aim Research on deception detection has usually been executed in experimental settings in the laboratory. In contrast, the present research investigates deception detection by actual victims and near victims of fraud, as reported in their own words. Materials and methods Our study is based on a nationally representative survey of 11 types of (mostly) online fraud victimization (N = 2,864). We used qualitative information from actual victims and near victims on why they didn’t fall for the fraud, or how, in hindsight, it could have been prevented. Results The main detection strategies mentioned by near victims (N = 958) were 1) fraud knowledge (69%): these near victims clearly recognized fraud. Other strategies related to fraud knowledge were: noticing mistakes (27.9%), rules and principles about safe conduct (11.7%), and personal knowledge (7.1%). A second type of strategy was distrust (26.1%). A third strategy was ‘wise through experience’ (1.6%). Finally, a limited number of respondents (7.8%) searched for additional information: they contacted other people (5.5%), sought information online (4%), contacted the fraudster (2.9%), contacted their bank or credit card company (2.2%), or contacted the police (0.2%). Using knowledge as a strategy decreases the probability of victimization by a factor of 0.43. In contrast, all other strategies increased the likelihood of victimization by a factor of 1.6 or more. Strategies generally were uncorrelated, several strategies differed by type of fraud. About 40% of the actual victims (N = 243) believed that their victimization might have been prevented by: 1) seeking information (25.2%), 2) paying more attention (18.9%), 3) a third party doing something (16.2%), 4) following safety rules or principles, like using a safer way of paying or trading (14.4%), or by 5) ‘simply not going along with it’ (10.8%). Most of these strategies were associated with a higher, not lower, likelihood of victimization. Conclusion Clearly, knowledge of fraud is the best strategy to avoid fraud victimization. Therefore, a more proactive approach is needed to inform the public about fraud and attackers’ modus operandi, so that potential victims already have knowledge of fraud upon encountering it. Just providing information online will not suffice to protect online users.
Research on the fluid dynamics interaction between submarine sand waves and seawater by seismic oceanography

Introduction The seafloor is an important interface between the lithosphere and the hydrosphere, where processes related to circulation and energy exchange happen along with various marine processes widely developed in the water column near the seafloor. These processes are still not yet completely understood as there are constraints of submarine detection technology and the interdisciplinary nature of these complex environments. Seismic reflection data have been a preferable tool to study and image these processes due to their characteristics in terms of spatial resolution. In seismic reflection data, submarine sand waves show hair-like reflection configurations with low continuity and wearing-hair style, appearing with an angle with the seafloor. Investigation of the relationship between the characteristics of submarine sand waves induced hair-like reflection configuration and hydrodynamics is crucial for understanding hair-like reflection configuration generation and spatiotemporal evolution. Methods This study combines fluid dynamics numerical simulation and seismic oceanography to discuss the seismic response characteristics and formation mechanisms of the hair-like reflection configuration. First, we create a seawater time-variant fluid-dynamical model followed by the numerical simulation of seismic oceanography data. This procedure results in seismic oceanography numerical simulation sections with hair-like reflection configurations for different constant flow conditions forced on the boundary. Optimal matching method is then applied to interpret field seismic reflection sections given the results obtained with the numerical experiments. Results and discussion As consequence, the fluid dynamic explanation for the formation mechanism of the hair-like reflection configuration due to differences in seawater thermohaline is proposed. The study provides additional comprehension and further insights into the dynamic process of submarine sand waves induced hair-like reflection configuration using the seismic oceanography method.
Research progress of interleukin-15 in cancer immunotherapy

Interleukin-15 (IL-15) is a cytokine that belongs to the interleukin-2 (IL-2) family and is essential for the development, proliferation, and activation of immune cells, including natural killer (NK) cells, T cells and B cells. Recent studies have revealed that interleukin-15 also plays a critical role in cancer immunotherapy. Interleukin-15 agonist molecules have shown that interleukin-15 agonists are effective in inhibiting tumor growth and preventing metastasis, and some are undergoing clinical trials. In this review, we will summarize the recent progress in interleukin-15 research over the past 5 years, highlighting its potential applications in cancer immunotherapy and the progress of interleukin-15 agonist development.
Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy

The development of novel analgesics for chronic pain in the last 2 decades has proven virtually intractable, typically failing due to lack of efficacy and dose-limiting side effects. Identified through unbiased gene expression profiling experiments in rats and confirmed by human genome-wide association studies, the role of excessive tetrahydrobiopterin (BH4) in chronic pain has been validated by numerous clinical and preclinical studies. BH4 is an essential cofactor for aromatic amino acid hydroxylases, nitric oxide synthases, and alkylglycerol monooxygenase so a lack of BH4 leads to a range of symptoms in the periphery and central nervous system (CNS). An ideal therapeutic goal therefore would be to block excessive BH4 production, while preventing potential BH4 rundown. In this review, we make the case that sepiapterin reductase (SPR) inhibition restricted to the periphery (i.e., excluded from the spinal cord and brain), is an efficacious and safe target to alleviate chronic pain. First, we describe how different cell types that engage in BH4 overproduction and contribute to pain hypersensitivity, are themselves restricted to peripheral tissues and show their blockade is sufficient to alleviate pain. We discuss the likely safety profile of peripherally restricted SPR inhibition based on human genetic data, the biochemical alternate routes of BH4 production in various tissues and species, and the potential pitfalls to predictive translation when using rodents. Finally, we propose and discuss possible formulation and molecular strategies to achieve peripherally restricted, potent SPR inhibition to treat not only chronic pain but other conditions where excessive BH4 has been demonstrated to be pathological.
Adaptive immunology of Cryptococcus neoformans infections—an update

The fungal genus Cryptococcus comprises a group of pathogens with considerable phenotypic and genotypic diversity that can lead to cryptococcosis in both healthy and immunocompromised individuals. With the emergence of the HIV pandemic, cryptococcosis, mainly meningoencephalitis, afflicts HIV-infected patients with severe dysfunction of T cells. It has also been reported in recipients of solid organ transplantation and in patients with autoimmune diseases who take immunosuppressive agents long-term, as well as in those with unidentified immunodeficiency. The clinical outcome of the disease is primarily determined by the immune response resulting from the interplay between the host immune system and the pathogen. Most human infections are caused by Cryptococcus neoformans, and nearly all immunological studies have focused on C. neoformans. This review provides an updated understanding of the role of adaptive immunity during infection with C. neoformans in human and animal models over the past half-decade.
Functional-oriented, portable brain–computer interface training for hand motor recovery after stroke: a randomized controlled study

Background Brain–computer interfaces (BCIs) have been proven to be effective for hand motor recovery after stroke. Facing kinds of dysfunction of the paretic hand, the motor task of BCIs for hand rehabilitation is relatively single, and the operation of many BCI devices is complex for clinical use. Therefore, we proposed a functional-oriented, portable BCI equipment and explored the efficiency of hand motor recovery after a stroke. Materials and methods Stroke patients were randomly assigned to the BCI group and the control group. The BCI group received BCI-based grasp/open motor training, while the control group received task-oriented guidance training. Both groups received 20 sessions of motor training in 4 weeks, and each session lasted for 30 min. The Fugl–Meyer assessment of the upper limb (FMA-UE) was applied for the assessment of rehabilitation outcomes, and the EEG signals were obtained for processing. Results The progress of FMA-UE between the BCI group [10.50 (5.75, 16.50)] and the control group [5.00 (4.00, 8.00)] was significantly different (Z = −2.834, P = 0.005). Meanwhile, the FMA-UE of both groups improved significantly (P < 0.001). A total of 24 patients in the BCI group achieved the minimal clinically important difference (MCID) of FMA-UE with an effective rate of 80%, and 16 in the control group achieved the MCID, with an effective rate of 51.6%. The lateral index of the open task in the BCI group was significantly decreased (Z = −2.704, P = 0.007). The average BCI accuracy for 24 stroke patients in 20 sessions was 70.7%, which was improved by 5.0% in the final session compared with the first session. Conclusion Targeted hand movement and two motor task modes, namely grasp and open, to be applied in a BCI design may be suitable in stroke patients with hand dysfunction. The functional-oriented, portable BCI training can promote hand recovery after a stroke, and it is expected to be widely used in clinical practice. The lateral index change of inter-hemispheric balance may be the mechanism of motor recovery. Trial registration number ChiCTR2100044492.
Relative importance of ENSO and IOD on interannual variability of Indonesian Throughflow transport

Introduction The Indonesian Throughflow (ITF) connects the Pacific Ocean and the Indian Ocean. It plays an important role in the global ocean circulation system. The interannual variability of ITF transport is largely modulated by climate modes, such as Central-Pacific (CP) and Eastern-Pacific (EP) El Niño and Indian Ocean Dipole (IOD). However, the relative importance of these climate modes importing on the ITF is not well clarified. Methods Dominant roles of the climate modes on ITF in specific periods are quantified by combining a machine learning algorithm of the random forest (RF) model with a variety of reanalysis datasets. Results The results reveal that during the period from 1993 to 2019, the average ITF transport derived from high-resolution reanalysis datasets is -14.97 Sv with an intensification trend of -0.06 Sv year-1, which mainly occurred in the upper layer. Four periods, which are 1993–2000, 2002–2008, 2009–2012 and 2013–2019, are identified as Niño 3.4, Dipole Mode Index (DMI), no significant dominant index, and DMI dominated, respectively. Discussion The corresponding sea surface height differences between the Northwest Tropical Pacific Ocean (NWP) and Southeast Indian Ocean (SEI) in these three periods when exist dominant index are -0.50 cm, 0.99 cm and -3.22 cm, respectively, which are responsible for the dominance of the climate modes. The study provides a new insight to quantify the response of ITF transport to climate drivers.
Modulation of innate immunity in airway epithelium for host-directed therapy

Innate immunity of the mucosal surfaces provides the first-line defense from invading pathogens and pollutants conferring protection from the external environment. Innate immune system of the airway epithelium consists of several components including the mucus layer, mucociliary clearance of beating cilia, production of host defense peptides, epithelial barrier integrity provided by tight and adherens junctions, pathogen recognition receptors, receptors for chemokines and cytokines, production of reactive oxygen species, and autophagy. Therefore, multiple components interplay with each other for efficient protection from pathogens that still can subvert host innate immune defenses. Hence, the modulation of innate immune responses with different inducers to boost host endogenous front-line defenses in the lung epithelium to fend off pathogens and to enhance epithelial innate immune responses in the immunocompromised individuals is of interest for host-directed therapy. Herein, we reviewed possibilities of modulation innate immune responses in the airway epithelium for host-directed therapy presenting an alternative approach to standard antibiotics.
Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice

The involvement of mitochondrial dysfunction in cystatin B (CSTB) deficiency has been suggested, but its role in the onset of neurodegeneration, myoclonus, and ataxia in the CSTB-deficient mouse model (Cstb−/−) is yet unknown. CSTB is an inhibitor of lysosomal and nuclear cysteine cathepsins. In humans, partial loss-of-function mutations cause the progressive myoclonus epilepsy neurodegenerative disorder, EPM1. Here we applied proteome analysis and respirometry on cerebellar synaptosomes from early symptomatic (Cstb−/−) mice to identify the molecular mechanisms involved in the onset of CSTB-deficiency associated neural pathogenesis. Proteome analysis showed that CSTB deficiency is associated with differential expression of mitochondrial and synaptic proteins, and respirometry revealed a progressive impairment in mitochondrial function coinciding with the onset of myoclonus and neurodegeneration in (Cstb−/−) mice. This mitochondrial dysfunction was not associated with alterations in mitochondrial DNA copy number or membrane ultrastructure. Collectively, our results show that CSTB deficiency generates a defect in synaptic mitochondrial bioenergetics that coincides with the onset and progression of the clinical phenotypes, and thus is likely a contributor to the pathogenesis of EPM1.