Miracle-dz/UniFAR-FTUs huggingface dataset:
In-Depth Characterization of Stromal Cells within the Tumor Microenvironment Yields Novel Therapeutic Targets

Simple Summary This up-to-date and in-depth review describes fibroblast-derived cells and their role within the tumor microenvironment for tumor progression. Moreover, targets for future antitumor therapies are summarized and potential aspects for future translational research are outlined. Furthermore, this review discusses the challenges and possible obstacles related to certain treatment targets. Abstract Cells within the tumor stroma are essential for tumor progression. In particular, cancer-associated fibroblasts (CAF) and CAF precursor cells (resident fibroblasts and mesenchymal stromal cells) are responsible for the formation of the extracellular matrix in tumor tissue. Consequently, CAFs directly and indirectly mediate inflammation, metastasis, immunomodulation, angiogenesis, and the development of tumor chemoresistance, which is orchestrated by complex intercellular cytokine-mediated crosstalk. CAFs represent a strategic target in antitumor therapy but their heterogeneity hinders effective treatment regimes. In-depth understanding of CAF subpopulations and knowledge of specific functions in tumor progression will ultimately result in more specific and effective cancer treatments. This review provides a detailed description of CAFs and CAF precursor cells and summarizes possible treatment strategies as well as molecular targets of these cells in antitumor therapies.
Paving the Way to Food Grade Analytical Chemistry: Use of a Natural Deep Eutectic Solvent to Determine Total Hydroxytyrosol and Tyrosol in Extra Virgin Olive Oils

Extra virgin olive oil (EVOO) is well known for containing relevant amounts of healthy phenolic compounds. The European Food Safety Authority (EFSA) allowed a health claim for labelling olive oils containing a minimum amount of hydroxytyrosol (OHTyr) and its derivatives, including tyrosol (Tyr). Therefore, harmonized and standardized analytical protocols are required in support of an effective application of the health claim. Acid hydrolysis performed after extraction and before chromatographic analysis has been shown to be a feasible approach. Nevertheless, other fast, green, and easy methods could be useful for on-site screening and monitoring applications. In the present research, a natural deep eutectic solvent (NADES) composed of lactic acid and glucose was used to perform a liquid/liquid extraction on EVOO samples, followed by UV-spectrophotometric analysis. The spectral features of the extracts were related with the content of total OHTyr and Tyr, determined by the acid hydrolysis method. The second derivative of spectra allowed focusing on three single wavelengths (i.e., 299 nm, 290 nm, and 282 nm) significantly related with total OHTyr, total Tyr, and their sum, respectively. In particular, the sum of OHTyr and Tyr could be determined with a root mean square error of prediction of 29.5 mg kg−1, while the limits of quantitation and detection were respectively 11.8 and 4.9 mg kg−1. The proposed method, therefore, represents an easy screening tool, with the use of a green, food-derived solvent, and could be considered as an attempt to pave the way for food grade analytical chemistry.
A Mixed-Methods Evaluation of CARE (Cancer and Rehabilitation Exercise): A Physical Activity and Health Intervention, Delivered in a Community Football Trust

With increasing cancer survivorship has come an increased necessity to support people living with cancer (PLWC) to have a good quality of life including being physically active. Using mixed methods, the current study aimed to use the RE-AIM evaluation framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) to determine how the football community trust delivered CARE (Cancer and Rehabilitation Exercise) intervention was able to increase participants’ physical activity in order to improve their quality of life and regain physiological and psychological function. Quantitative outcome data were collected at baseline, 3 and 6 months using the Cancer Physical Activity Standard Evaluation Framework questionnaire. Semi-structured focus groups (n = 5) captured participants’ (n = 40) lived experience of the reach, effectiveness, adoption, implementation, and maintenance of CARE. Questionnaire data were analysed using repeated measures ANOVAs and qualitative data were thematically analysed. Following diagnosis, CARE was successful in providing participants with a unique and accessible opportunity to become or restart physically activity, by providing a local, socially supportive, and inclusive environment. This resulted in significant increases in physical activity (F(1.58, 23) = 5.98, p = 0.009), quality of life (QoL) (F(2,36) = 13.12, p = 0.000) and significant reductions in fatigue (F(1.57,31) = 11.19, p = 0.000) over 6 months. Participants also reported becoming more active, recovering physical function, regaining independence, and enhanced psychological well-being as a result of attending CARE. Key design features of CARE were also identified across RE-AIM. CARE, a football community trust delivered physical activity intervention was successful in significantly improving participants’ QoL and in regaining the physical and psychological functioning of people living with cancer. Results suggest that maintaining engagement in CARE for 6 months and beyond can support people to maintain these changes. Engaging in robust evaluations such as this can help organizations to successfully secure future funding for their programs.
Elastic Bioresorbable Polymeric Capsules for Osmosis-Driven Delayed Burst Delivery of Vaccines

Single-administration vaccine delivery systems are intended to improve the efficiency and efficacy of immunisation programs in both human and veterinary medicine. In this work, an osmotically triggered delayed delivery device was developed that was able to release a payload after a delay of approximately 21 days, in a consistent and reproducible manner. The device was constructed out of a flexible poly(ε-caprolactone) photo-cured network fabricated into a hollow tubular shape, which expelled approximately 10% of its total payload within 2 days after bursting. Characterisation of the factors that control the delay of release demonstrated that it was advantageous to adjust material permeability and device wall thickness over manipulation of the osmogent concentration in order to maintain reproducibility in burst delay times. The photo-cured poly(ε-caprolactone) network was shown to be fully degradable in vitro, and there was no evidence of cytotoxicity after 11 days of direct contact with primary dermal fibroblasts. This study provides strong evidence to support further development of flexible biomaterials with the aim of continuing improvement of the device burst characteristics in order to provide the greatest chance of the devices succeeding with in vivo vaccine booster delivery.
Determinants of Population-Based Cancer Screening Performance at Primary Healthcare Institutions in China

Background: For a decade, most population-based cancer screenings in China are performed by primary healthcare institutions. To assess the determinants of performance of primary healthcare institutions in population-based breast, cervical, and colorectal cancer screening in China. Methods: A total of 262 primary healthcare institutions in Tianjin participated in a survey on cancer screening. The survey consisted of questions on screening tests, the number of staff members and training, the introduction of the screening programs to residents, the invitation of residents, and the number of performed screenings per year. Logistic regression models were used to analyze the determinants of performance of an institution to fulfil the target number of screenings. Results: In 58% and 61% of the institutions between three and nine staff members were dedicated to breast and cervical cancer screening, respectively, whereas in 71% of the institutions ≥10 staff members were dedicated to colorectal cancer screening. On average 60% of institutions fulfilled the target number of breast and cervical cancer screenings, whereas 93% fulfilled the target number for colorectal cancer screening. The determinants of performance were rural districts for breast (OR = 5.16 (95%CI: 2.51–10.63)) and cervical (OR = 4.17 (95%CI: 2.14–8.11)) cancer screenings, and ≥3 staff members dedicated to cervical cancer screening (OR = 2.34 (95%CI: 1.09–5.01)). Conclusions: Primary healthcare institutions in China perform better in colorectal than in breast and cervical cancer screening, and institutions in rural districts perform better than institutions in urban districts. Increasing the number of staff members on breast and cervical cancer screening could improve the performance of population-based cancer screening.
Pre-Surgery Cognitive Performance and Voxel-Based Lesion-Symptom Mapping in Patients with Left High-Grade Glioma

Simple Summary Studies on pre-surgery effects of high-grade glioma on cognition are few, and investigations mainly used general test batteries without specifically addressing selective neuropsychological functions. We studied the pre-surgery neuropsychological status of 85 patients with high-grade glioma, by administering several cognitive tasks to assess language, memory, executive functions, and praxis. We analyzed their lesion volumes to test anatomo-functional correlations. We found that high-grade glioma involving different sub-areas of the left temporal lobe selectively impacts cognitive functions, especially within the language domain. There was one small overlapping lesion area that was shared by all the tasks we examined, localized in the superior temporal cortex. Abstract (1) Background: The literature on the effects of high-grade glioma (HGG) growth on cognition is still scarce. (2) Method: A consecutive series of 85 patients with HGG involving the left hemisphere underwent an extended neuropsychological evaluation prior to surgery. Voxel-based lesion-symptom mapping (VLSM) was used to identify regions related to cognitive performance. (3) Results: The patients’ mean level of pre-surgery accuracy was overall high. They showed the greatest difficulties in language with tasks such as naming (42.1% of patients impaired on nouns and 61.4% on verbs), reading (36.3% on words and 32.7% on pseudo-words), auditory lexical decisions (43.9%) and writing (41.3%) being most frequently impaired. VLSM analysis revealed anatomically separated areas along the temporal cortex and the white matter related to impairments on the different tasks, with voxels commonly shared by all tasks restricted to a small region in the ventral superior and middle temporal gyrus. (4) Conclusions: High-grade glioma affects cognition; nonetheless, lesions do not cause diffuse deficits but selectively impact the different language sub-domains along the ventral stream and the dorsal stream for language processing.
Anti-Platelet Properties of Phenolic and Nonpolar Fractions Isolated from Various Organs of Elaeagnus rhamnoides (L.) A. Nelson in Whole Blood

Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) is a shrub growing in coastal areas. Its organs contain a range of bioactive substances including vitamins, fatty acids, various micro and macro elements, as well as phenolic compounds. Numerous studies of sea buckthorn have found it to have anticancer, anti-ulcer, hepatoprotective, antibacterial, and antiviral properties. Some studies suggest that it also affects the hemostasis system. The aim of the study was to determine the effect of six polyphenols rich and triterpenic acids rich fractions (A–F), taken from various organs of sea buckthorn, on the activation of blood platelets using whole blood, and to assess the effect of the tested fractions on platelet proteins: fraction A (polyphenols rich fraction from fruits), fraction B (triterpenic acids rich fraction from fruits), fraction C (polyphenols rich fraction from leaves), fraction D (triterpenic acids rich fraction from leaves), fraction E (polyphenols rich fraction from twigs), and fraction F (triterpenic acids rich fraction from twigs). Hemostasis parameters were determined using flow cytometry and T-TAS (Total Thrombus-formation Analysis System). Additionally, electrophoresis was performed under reducing and non-reducing conditions. Although all tested fractions inhibit platelet activation, the greatest anti-platelet activity was demonstrated by fraction A, which was rich in flavonol glycosides. In addition, none of the tested fractions (A–F) caused any changes in the platelet proteome, and their anti-platelet potential is not dependent on the P2Y12 receptor.
New Insights into the Mammalian Egg Zona Pellucida

Mammalian oocytes are surrounded by an extracellular coat called the zona pellucida (ZP), which, from an evolutionary point of view, is the most ancient of the coats that envelope vertebrate oocytes and conceptuses. This matrix separates the oocyte from cumulus cells and is responsible for species-specific recognition between gametes, preventing polyspermy and protecting the preimplantation embryo. The ZP is a dynamic structure that shows different properties before and after fertilization. Until very recently, mammalian ZP was believed to be composed of only three glycoproteins, ZP1, ZP2 and ZP3, as first described in mouse. However, studies have revealed that this composition is not necessarily applicable to other mammals. Such differences can be explained by an analysis of the molecular evolution of the ZP gene family, during which ZP genes have suffered pseudogenization and duplication events that have resulted in differing models of ZP protein composition. The many discoveries made in recent years related to ZP composition and evolution suggest that a compilation would be useful. Moreover, this review analyses ZP biosynthesis, the role of each ZP protein in different mammalian species and how these proteins may interact among themselves and with other proteins present in the oviductal lumen.
“Smartphone Apps Are Cool, But Do They Help Me?”: A Qualitative Interview Study of Adolescents’ Perspectives on Using Smartphone Interventions to Manage Nonsuicidal Self-Injury

Nonsuicidal self-injury (NSSI) is a major mental health problem associated with negative psychosocial outcomes and it most often starts in early adolescence. Despite this, adolescents are rarely involved in informing the development of interventions designed to address their mental health problems. This study aimed to (1) assess adolescents’ needs and preferences about future interventions that are delivered through smartphones and (2) develop a framework with implications for designing engaging digital mental health interventions. Fifteen adolescent girls, aged 12–18 years, who met diagnostic criteria for a current NSSI disorder and were in contact with mental health services, participated in semi-structured interviews. Following a reflexive thematic analysis approach, this study identified two main themes: (1) Experiences of NSSI (depicts the needs of young people related to their everyday experiences of managing NSSI) and (2) App in Context (portrays preferences of young people about smartphone interventions and reflects adolescents’ views on how technology itself can improve or hinder engaging with these interventions). Adolescent patients expressed interest in using smartphone mental health interventions if they recognize them as helpful, relevant for their life situation and easy to use. The developed framework suggests that digital mental health interventions are embedded in three contexts (i.e., person using the intervention, mental health condition, and technology-related factors) which together need to inform the development of engaging digital resources. To achieve this, the cooperation among people with lived experience, mental health experts, and human computer interaction professionals is vital.
Potential Well in Poincaré Recurrence

From a physical/dynamical system perspective, the potential well represents the proportional mass of points that escape the neighbourhood of a given point. In the last 20 years, several works have shown the importance of this quantity to obtain precise approximations for several recurrence time distributions in mixing stochastic processes and dynamical systems. Besides providing a review of the different scaling factors used in the literature in recurrence times, the present work contributes two new results: (1) For ϕ-mixing and ψ-mixing processes, we give a new exponential approximation for hitting and return times using the potential well as the scaling parameter. The error terms are explicit and sharp. (2) We analyse the uniform positivity of the potential well. Our results apply to processes on countable alphabets and do not assume a complete grammar.
Low Carb and Ketogenic Diets Increase Quality of Life, Physical Performance, Body Composition, and Metabolic Health of Women with Breast Cancer

Breast cancer (BC) patients often ask for a healthy diet. Here, we investigated a healthy standard diet (SD), a low carb diet (LCD), and a ketogenic diet (KD) for BC patients during the rehabilitation phase. KOLIBRI was an open-label non-randomized one-site nutritional intervention trial, combining inpatient and outpatient phases for 20 weeks. Female BC patients (n = 152; mean age 51.7 years) could select their diet. Data collected were: Quality of life (QoL), spiroergometry, body composition, and blood parameters. In total 30, 92, and 30 patients started the KD, LCD, and SD, respectively. Of those, 20, 76, and 25 completed the final examination. Patients rated all diets as feasible in daily life. All groups enhanced QoL, body composition, and physical performance. LCD participants showed the most impressive improvement in QoL aspects. KD participants finished with a very good physical performance and muscle/fat ratio. Despite increased cholesterol levels, KD patients had the best triglyceride/high-density lipoprotein (HDL) ratio and homeostatic model assessment of insulin resistance index (HOMA-IR). Most metabolic parameters significantly improved in the LCD group. SD participants ended with remarkably low cholesterol levels but did not improve triglyceride/HDL or HOMA-IR. In conclusion, both well-defined KDs and LCDs are safe and beneficial for BC patients and can be recommended during the rehabilitation phase.
Eating Disorders in Top Elite Beach Handball Players: Cross Sectional Study

(1) Background: The preoccupation with the increasing appearance of eating disorders (ED) in athletes continues to grow, especially in athletes who practice team sports. ED severely affects the eating habits of the athletes, who tend to use unhealthy approaches to control their body weight. The development of nutritional education and early interventions by training staff is essential, and these factors are widely perceived as beneficial in sports medicine. This study evaluates the frequency at which beach handball (BH) players develop ED, also comparing the differences by sex and age (junior: adolescents vs. senior: young adults). In addition, the relation between body composition variables and ED was studied. (2) Methods: A descriptive and cross-sectional study was carried out in 69 top elite handball players (36 males and 33 females) from the Spanish National BH Team; who were separated by age (junior: adolescents and senior: young adults). The athletes completed the Eating Attitudes Test in its 26 item version (EAT-26). (3) Results: The prevalence of ED indicated that 11% of females had a high possibility of developing an ED, and 3% of males. Regarding the EAT-26 total score and subscales, no significant differences were found between female and male participants, or between the junior and senior categories. The correlations showed an association between body composition, in terms of body mass index, and the EAT-26 total score in both males and females. In the case of males, the correlation was negative. (4) Conclusions: Although there are no significant differences between sex or categories, it has been found that elite athletes are a population that is at high risk of developing ED.
MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification

Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis.
Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.