Miracle-dz/UniFAR-FTUs huggingface dataset:
Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers

Simple summary Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III–IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved. Background Low-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence. Methods We retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan–Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula. Results A total of 92 patients were included (median age was 47 years, IQR 35–64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1–10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1–10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1–10 mm (HR = 2.30, 95% CI 1.30–4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92–7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52–6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS. Conclusions Optimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.
Nonscattering solutions to the $L^{2}$-supercritical NLS Equations

We investigate the nonlinear Schr\"{o}dinger equation $iu_{t}+\Delta u+|u|^{p-1}u=0$ with $1+\frac{4}{N} \|Q\|_{2}^{\frac{1-s_{c}}{s_{c}}}\|\nabla Q\|_{2},$ then either $u(t)$~blows up in finite forward time, or $u(t)$ exists globally for positive time and there exists a time sequence $t_{n}\rightarrow+\infty$ such that $\|\nabla u(t_{n})\|_{2}\rightarrow+\infty. $ Here $Q$ is the ground state solution of $-Q+\Delta Q+|Q|^{p-1}Q=0. $ A similar result holds for negative time. This extend the result of the 3D cubic Schr\"{o}dinger equation in \cite{holmer10} to the general mass-supercritical and energy-subcritical case .
Rapid qualitative health research from the Global South: Reflections and learnings from Argentina, Brazil, Chile, and Mexico during the COVID-19 pandemic

The objective of this paper is to provide insights into our experiences undertaking qualitative rapid research in Latin American contexts based on fieldwork from Argentina, Brazil, Chile, and Mexico. We focus on the insights and learning processes that emerged from our research teamwork during the COVID-19 pandemic. Our research projects are part of an international collaboration led by the Rapid Research Evaluation and Appraisal Lab (RREAL) to explore the experiences of COVID-19 Frontline Healthcare Workers. The analyzed experiences not only rely on the local studies but also on our reflections as a group of Latin American researchers collaborating along with an international team. Qualitative research has an important and long-lasting tradition in Latin America. However, healthcare professionals are still reluctant to use these methods. We highlight tensions and dilemmas that have emerged from our own empirical experience: First, the time for research ethics committees to evaluate the protocols; second, the difficulties in accessing funding to undertake research due to the lack of financial opportunities; third, having to decide the language of our publications. That is just the tip of the iceberg that allows us to show inequalities in the conditions under which scientific knowledge is produced between the North and the Global South. Following these points, our text explores the tension between the urgency to conduct rapid research and the multiple difficulties when undertaking it during the pandemic. It is important to point out that the problems we faced already existed before the sanitary emergency, being magnified by the former. At last, our conclusions delve into the reflexive process we, as a team of female researchers, undertook to explore the differences and similarities of our experiences. This analysis allowed us to solve obstacles and dilemmas when doing research. The winding road we describe here serves as an example for other research teams when planning and undertaking rapid qualitative research during future pandemics.
Metabolic effects of prolactin

Over the last years, the metabolic role of PRL has emerged. PRL excess is known to promote weight gain, obesity, metabolic syndrome, and impairment in gluco-insulinemic and lipid profiles, likely due to the suppression of physiologic dopaminergic tone. Prolactin receptors and dopamine receptors type 2 have been demonstrated to be expressed on both human pancreatic β- cell and adipocytes, supporting a key role of prolactin and dopamine in peripheral metabolic regulation. Medical treatment with the dopamine agonists bromocriptine and cabergoline has been demonstrated to decrease the prevalence of metabolic syndrome and obesity, and significantly improve gluco-insulinemic and lipid profiles. In hyperprolactinemic men with concomitant hypogonadism, correction of hyperprolactinaemia and testosterone replacement has been proven to restore metabolic impairment. In turn, low prolactin levels have also been demonstrated to exert a detrimental effect on weight gain, glucose and lipid metabolism, thus leading to an increased prevalence of metabolic syndrome. Therefore, PRL values ranging from 25 to 100 mg/L, in absence of other recognizable pathological causes, have been proposed to represent a physiological response to the request for an increase in metabolic activity, and nowadays classify the so-called HomeoFIT- PRL as a promoter of metabolic homeostasis. The current review focuses mainly on the effects of hyperprolactinemia and its control by medical treatment with DAs on the modulation of food intake, body weight, gluco-insulinemic and lipid profile. Furthermore, it provides the latest knowledge about the metabolic impact of hypoprolactinemia.
Standard CBT versus integrative and multimodal CBT assisted by virtual-reality for generalized anxiety disorder

Introduction Generalized Anxiety Disorder (GAD) is a prevalent emotional disorder associated with increased dysfunctionality, which has a lasting impact on the individual’s quality of life. Besides medication, Cognitive-Behavioral Therapy (CBT) represents the golden standard psychotherapeutic approach for GAD, integrating multilevel techniques and various delivery formats that enable the development of tailored treatment protocols. The objective of this study was to compare the efficiency of a standard CBT protocol targeting worries, dysfunctional beliefs, and intolerance of uncertainty with an integrative and multimodal CBT intervention augmented with Virtual Reality (VR). Materials and methods This study included 66 participants (Mage = 22.53 years; SD = 2.21) with moderate GAD symptoms that were randomized to the standard CBT group (CBTs; N = 32) and the Integrative and Multimodal CBT augmented with VR (IM-VRCBT; N = 34) group. The interventions comprised 10 weekly sessions conducted by trained CBT therapists, including cognitive restructuring, problem-solving, behavioral exposure, and relaxation techniques. Baseline and post-assessments were conducted with both groups. Primary outcome measures included the Hamilton Anxiety Rating Scale (HARS) and Penn-State Worry Questionnaire (PSWQ) to evaluate the severity of GAD symptoms and worries, respectively. Secondary outcomes involved the administration of Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitudes Scale (DAS) and Unconditional Self-Acceptance Questionnaire (USAQ). Results Both interventions determined statistically significant effects on both primary and secondary outcomes (ps < 0.001) in the expected direction. However, CBTs was associated with higher effect sizes for anxiety (Cohen’s d = 2.76) and worries (Cohen’s d = 1.85), in contrast to IM-VRCBT. Also, secondary analyses revealed positive correlations between changes in anxiety and worries level and the reduction of dysfunctional cognitive processes. Conclusion This research emphasized the effectiveness of CBT interventions for treating adults with moderate GAD symptomatology. Specifically, both interventions were efficient for reducing anxiety symptomatology present at individuals with GAD. However, regarding cognitive dysfunctions like worries, the standard CBT protocol performed better, as compared to the IM-VRCBT. In addition, we conclude that VR could be integrated within CBT interventions in a single protocol for GAD treatment.
Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.
Septate junction proteins are required for cell shape changes, actomyosin reorganization and cell adhesion during dorsal closure in Drosophila

Septate junctions (SJs) serve as occluding barriers in invertebrate epithelia. In Drosophila, at least 30 genes are required for the formation or maintenance of SJs. Interestingly, loss-of-function mutations in core SJ components are embryonic lethal, with defects in developmental events such as head involution and dorsal closure (DC) that occur prior to the formation of a mature SJ, indicating a role for these proteins in mid-embryogenesis independent of their occluding function. To understand this novel function in development, we examined loss-of-function mutations in three core SJ proteins during the process of DC. DC occurs during mid-embryogenesis to seal a dorsal gap in the epidermis following germ band retraction. Closure is driven by contraction of the extraembryonic amnioserosa cells that temporarily cover the dorsal surface and by cell shape changes (elongation) of lateral epidermal cells that bring the contralateral sheets together at the dorsal midline. Using live imaging and examination of fixed tissues, we show that early events in DC occur normally in SJ mutant embryos, but during later closure, coracle, Macroglobulin complement-related and Neurexin-IV mutant embryos exhibit slower rates of closure and display aberrant cells shapes in the dorsolateral epidermis, including dorsoventral length and apical surface area. SJ mutant embryos also show mild defects in actomyosin structures along the leading edge, but laser cutting experiments suggest similar tension and viscoelastic properties in SJ mutant versus wild type epidermis. In a high percentage of SJ mutant embryos, the epidermis tears free from the amnioserosa near the end of DC and live imaging and immunostaining reveal reduced levels of E-cadherin, suggesting that defective adhesion may be responsible for these tears. Supporting this notion, reducing E-cadherin by half significantly enhances the penetrance of DC defects in coracle mutant embryos.
Genome-wide association, RNA-seq and iTRAQ analyses identify candidate genes controlling radicle length of wheat

The radicle, present in the embryo of a seed, is the first root to emerge at germination, and its rapid growth is essential for establishment and survival of the seedling. However, there are few studies on the critical mechanisms underlying radicle and then radicle length in wheat seedlings, despite its importance as a food crop throughout the world. In the present study, 196 wheat accessions from the Huanghuai Wheat Region were screened to measure radicle length under 4 hydroponic culture environments over 3 years. Different expression genes and proteins (DEGs/DEPs) between accessions with extremely long [Yunong 949 (WRL1), Zhongyu 9,302 (WRL2)] and short roots [Yunong 201 (WRS1), Beijing 841 (WRS2)] were identified in 12 sets of root tissue samples by RNA-seq and iTRAQ (Isobaric tags for relative and absolute quantification). Phenotypic results showed that the elongation zone was significantly longer in root accessions with long roots compared to the short-rooted accessions. A genome-wide association study (GWAS) identified four stable chromosomal regions significantly associated with radicle length, among which 1A, 4A, and 7A chromosomes regions explained 7.17% to12.93% of the phenotypic variation. The omics studies identified the expression patterns of 24 DEGs/DEPs changed at both the transcriptional and protein levels. These DEGs/DEPs were mainly involved in carbon fixation in photosynthetic organisms, photosynthesis and phenylpropanoid biosynthesis pathways. TraesCS1A02G104100 and TraesCS2B02G519100 were involved in the biosynthesis of tricin-lignins in cell walls and may affect the extension of cell walls in the radicle elongation zone. A combination of GWAS and RNA-seq analyses revealed 19 DEGs with expression changes in the four accessions, among which, TraesCS1A02G422700 (a cysteine-rich receptor-like protein kinase 6, CRK6) also showed upregulation in the comparison group by RNA-seq, iTRAQ, and qRT-PCR. BSMV-mediated gene silencing also showed that TaCRK6 improves root development in wheat. Our data suggest that TaCRK6 is a candidate gene regulating radicle length in wheat.
Factors that determine mental health professionals’ decision to support home-based video consultations – A qualitative study

Introduction Using videoconferencing for consulting with patients in the mental health services has been shown in interventions to be similarly effective as when meeting in person. In practice, it often makes more sense to use video consultations with patients in a more flexible way than interventions permit. The aim of this study was to investigate what constitutes a professional video consultation from the perspectives of mental health professionals and explore what is of importance for the establishment and realization of video consultations in practice. Materials and methods A Grounded Theory methodology approach based on Corbin and Strauss was used. Data collection consisted of participant observations of introductory events followed by individual interviews with mental health professionals who had used video consultations with patients. Findings Mental health professionals believed that a professional video consultation was one that was not inferior to an in-person consultation but offered something else, such as more and easier access, accommodating patients’ needs and wishes. At the same time, it should not interfere with the treatment quality, e.g., by hampering communication and therapeutic tasks. The expected treatment quality was based on an individual assessment of the patient and varied from clinician to clinician. The implementation process and support which the organization provided affected the clinicians’ attitudes as well as the clinicians’ experiences and hence how the clinicians assessed the quality of the service. Conclusion Perceived usefulness, patient demands, and close IT support will positively impact the establishment and realization of video consultations whereas high workload and technical problems would hamper it.
‘Say Cheese!': Humane halos from environmental practices in dairy production

Awareness of the negative impacts of our food choices on planetary, human and animal health is growing. Research shows an increasing number of consumers consider ethical consequences when purchasing food. A new market sector has emerged which caters to the demands of these value-driven consumers. However, attempts to change the market through ethical purchases may be thwarted by advertising strategies which exploit the ‘halo effect', a cognitive bias which manifests when first impressions of one attribute influence subsequent evaluations of unknown attributes. This research investigates how two ethical domains, environmentalism and animal welfare, interact to influence consumer choice. In an online experiment, we recruited 267 participants and randomly assigned them to read either a pro-environmental, anti-environmental, or ethically neutral vignette about a cheese company. After being asked to rate the dairy on how well it treats its cows—an issue on which no information had been provided—participants indicated how frequently they would recommend the cheese compared to other brands. Results confirm that information about the company's environmental practices influenced perceptions of its animal welfare practices: a ‘humane halo' effect. Further, humane ratings predicted product consumption recommendations, indicating the humane halo acted as a mediator. Exploratory analyses suggest the strength of this mediated relationship depends on participants' environmental protection values, particularly if they received negative information. Our findings establish the existence of a cross-domain halo in food ethics and shed light on ways to increase the effectiveness of policies designed to shift consumers to more sustainable diets.
The inverse problem for the local ray transform

In this paper we consider the local X-ray transform for general flows. We extend the results on the local and global invertibility of the geodesic ray transform proved by Uhlmann and Vasy \cite{UV} to the X-ray transform for a general flow. The key improvement is that our argument for the ellipticity of the conjugated operator $A_F$ (which is defined in Section 2) can be applied to flows other than the geodesic flow.
Centers of value and the quest for meaning in faith development: A measurement approach

James Fowler’s model of faith development conceptualized “faith” as the quest for and maintenance of meaning oriented around centers of value which may or may not be religious or spiritual in nature. Although this model foreshadowed later work in meaning in life, substantial bodies of literature have developed in each area, almost entirely independently of the other. Integration has been hindered by measurement difficulties in faith development work. Fowler’s stages of faith development and their reformulation as Streib’s religious styles are usually measured through either a lengthy Faith Development Interview or short measures that do not assess the breadth of domains covered in the interview. These short measures are in many cases oriented around religious faith and impossible for a non-believer to answer. Embedded within the original model and the interview are aspects of faith development including perspective taking, social horizon, morality, locus of authority, form of world coherence, and symbolic function. A new Centers of Value and Quest for Meaning Scale is proposed to assess the aspects, allow non-believers to respond, tap centers of value that are not religious, and eventually address the theoretical assumption of structural wholeness across aspects. In a series of exploratory factor analyses, factors for each adult stage/style emerged for most of the aspects. This supports the potential importance of assessing the aspects and allows for more than one methodology to assess them.
Integration of three machine learning algorithms identifies characteristic RNA binding proteins linked with diagnosis, immunity and pyroptosis of IgA nephropathy

Objective: RNA-binding proteins (RBPs) are essential for most post-transcriptional regulatory events, which exert critical roles in nearly all aspects of cell biology. Here, characteristic RBPs of IgA nephropathy were determined with multiple machine learning algorithms. Methods: Our study included three gene expression datasets of IgA nephropathy (GSE37460, GSE73953, GSE93798). Differential expression of RBPs between IgA nephropathy and normal samples was analyzed via limma, and hub RBPs were determined through MCODE. Afterwards, three machine learning algorithms (LASSO, SVM-RFE, random forest) were integrated to determine characteristic RBPs, which were verified in the Nephroseq database. Immune cell infiltrations were estimated through CIBERSORT. Utilizing ConsensusClusterPlus, IgA nephropathy were classified based on hub RBPs. The potential upstream miRNAs were predicted. Results: Among 388 RBPs with differential expression, 43 hub RBPs were determined. After integration of three machine learning algorithms, three characteristic RBPs were finally identified (DDX27, RCL1, and TFB2M). All of them were down-regulated in IgA nephropathy than normal specimens, with the excellent diagnostic efficacy. Additionally, they were significantly linked to immune cell infiltrations, immune checkpoints, and pyroptosis-relevant genes. Based on hub RBPs, IgA nephropathy was stably classified as two subtypes (cluster 1 and 2). Cluster 1 exhibited the relatively high expression of pyroptosis-relevant genes and characteristic RBPs. MiR-501-3p, miR-760, miR-502-3p, miR-1224-5p, and miR-107 were potential upstream miRNAs of hub RBPs. Conclusion: Collectively, our findings determine three characteristic RBPs in IgA nephropathy and two RBPs-based subtypes, and thus provide a certain basis for further research on the diagnosis and pathogenesis of IgA nephropathy.