Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineered colorectal cancer tissue recapitulates key attributes of a patient-derived xenograft tumor line

The development of physiologically relevant in vitro colorectal cancer (CRC) models is vital for advancing understanding of tumor biology. Although CRC patient-derived xenografts (PDXs) recapitulate key patient tumor characteristics and demonstrate high concordance with clinical outcomes, the use of this in vivo model is costly and low-throughput. Here we report the establishment and in-depth characterization of an in vitro tissue-engineered CRC model using PDX cells. To form the 3D engineered CRC-PDX (3D-eCRC-PDX) tissues, CRC PDX tumors were expanded in vivo, dissociated, and the isolated cells encapsulated within PEG-fibrinogen hydrogels. Following PEG-fibrinogen encapsulation, cells remain viable and proliferate within 3D-eCRC-PDX tissues. Tumor cell subpopulations, including human cancer and mouse stromal cells, are maintained in long-term culture (29 days); cellular subpopulations increase ratiometrically over time. The 3D-eCRC-PDX tissues mimic the mechanical stiffness of originating tumors. Extracellular matrix protein production by cells in the 3D-eCRC-PDX tissues resulted in approximately 57% of proteins observed in the CRC-PDX tumors also being present in the 3D-eCRC-PDX tissues on day 22. Furthermore, we show congruence in enriched gene ontology molecular functions and Hallmark gene sets in 3D-eCRC-PDX tissues and CRC-PDX tumors compared to normal colon tissue, while prognostic Kaplan–Meier plots for overall and relapse free survival did not reveal significant differences between CRC-PDX tumors and 3D-eCRC-PDX tissues. Our results demonstrate high batch-to-batch consistency and strong correlation between our in vitro tissue-engineered PDX-CRC model and the originating in vivo PDX tumors, providing a foundation for future studies of disease progression and tumorigenic mechanisms.
Continuance Intention to Use and Perceived Net Benefits as Perceived by Streaming Platform Users: An Application of the Updated IS Success Model

Video game streaming has become a popular leisure activity which, depending on content, level of skill, and user interest, reaches a wide array of audiences. Using streaming platforms, client users are able to broadcast their video gameplays and use chat rooms to interact with other viewers and game players in real time. This paper aimed to develop and examine a theoretical explanation concerning the formation of client users’ satisfaction with, perceived net benefits of, and continuance intention to use a particular streaming platform. The study employed the updated IS Success Model. An online questionnaire was designed for individuals who were game streaming users of a streaming platform. A total of 632 usable responses were used in the data analysis. The results pointed out that system quality, information quality, service quality, and user motivation all positively and significantly affected user satisfaction. User satisfaction had a positive and significant effect on perceived net benefits and continuance intention to use a streaming platform. Perceived net benefits positively and significantly related to continuance intention to use a particular streaming platform. The moderating effect of emotional involvement between user satisfaction and perceived net benefits was confirmed.
Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

Abstract Background An imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear. Objectives To examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs. Animals Twenty dogs with CKD and 10 healthy dogs. Methods In this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines. Results Serum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs. Conclusions and Clinical Importance leptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.
Erectile Problems in Polish Straight, Bisexual, and Gay Men: Does Sexual Identity Really Matter?

ABSTRACT Erectile dysfunction (ED) is one of the most common sexual health diagnoses in men. Previous studies demonstrated that ED can be even more prevalent among sexual minority men. This study investigated whether sexual identity is related to erectile function (EF) and explored variables possibly contributing to the differences between Polish straight and sexual minority men. The study sample included 1,246 gay, 838 straight, and 535 bisexual men who participated in an online survey. First, the psychometric qualities of the IIEF-2-EF scale used in the study were examined through confirmatory and exploratory factor analysis; a correction to account for potential bias in the questionnaire was also applied. Next, a series of univariate and multivariable models accounting for predictors possibly contributing to the observed differences between the groups of men were conducted. It was demonstrated that gay and bisexual men were more likely to show poorer EF. However, as demonstrated in the subgroup of men who were in relationships, sexual identity lost its significance when the unique characteristics of minority men’s sexuality (i.e., less focus on insertive penetrative sex in gay men and more frequent relational non-exclusivity in bisexual men) were controlled for. Erectile problems in minority men may benefit from clinical consideration in the unique context of their sexuality.
Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma

PURPOSE Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach. METHODS We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio). RESULTS Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003). CONCLUSION In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.
Cognitive Stimulation in Moderate Alzheimer’s Disease

Cognitive stimulation is one of the non-pharmacological therapies recommended for dementia intervention. The present study evaluated the efficacy of an intervention based on cognitive stimulation in people with moderate Alzheimer’s disease. Fifty-nine subjects with moderate dementia were randomly assigned to the stimulation group (N = 36) and the control group (N = 35). The treatment group received 16 intervention sessions cognitive tasks. All participants were evaluated with a battery of neuropsychological tests at three time points (pre, post, and follow-up). The treatment group showed significant increases in the three domains studied (memory, attention, and executive functions), although some of these effects were not maintained at follow-up. The control group progressively worsened. Cognitive stimulation was found to be an effective intervention for people with moderate Alzheimer’s disease because it helped to maintain memory function, executive functions, and attention. However, the effects were minimized at the 3-month follow-up.
The level of vitamin D in follicular fluid and ovarian reserve in an in vitro fertilization program: A pilot study

Background The level of vitamin D in follicular fluid (FF) according to the ovarian reserve has never been investigated, and the effect of FF vitamin D on the outcome of assisted reproductive technology (ART) remains controversial. The aim of this study is to evaluate the association between FF vitamin D levels and baseline anti-Müllerian hormone (AMH) / ART outcomes. Methods Forty-seven patients who underwent controlled ovarian stimulation at the fertility clinic of an academic tertiary care center were enrolled for a prospective observational study. FF was collected from the first aspirated leading follicle of each ovary and assayed by an enzyme-linked immunosorbent assay. Multivariable linear regression analysis was used to assess the association between baseline AMH and FF vitamin D levels with adjustment for basal FSH and serum vitamin D levels. Results Both the AMH and serum vitamin D were significant predictors for FF vitamin D. The estimated marginal mean of FF vitamin D level was higher in women with decreased ovarian reserve (DOR) than those with normal ovarian reserve (24.1 ± 2.1 vs. 18.8 ± 1.4 ng/ml, p = 0.048). However, FF vitamin D did not demonstrate any significant associations with cycle outcomes, including fertilization rate and the number and proportion of good embryos at day three. Conclusion We observed significantly higher FF vitamin D levels in women with DOR. However, FF vitamin D did not demonstrate any significant associations with the outcome of ART. A larger prospective study is needed to investigate the effect of FF vitamin D on the clinical pregnancy rate and live birth rate.
Insomnia Symptoms Among Hospice Family Caregivers: Prevalence and Association with Caregiver Mental and Physical Health, Quality of Life, and Caregiver Burden

Background Poor sleep exacerbates mental health problems and reduces quality-of-life (QOL) but prevalence of insomnia symptoms among hospice family caregivers and associations of poor sleep with caregiver health and QOL outcomes are not known. Objective To describe prevalence of insomnia symptoms among hospice family caregivers and compare anxiety, depression, self-rated health, QOL, and caregiver burden between hospice family caregivers with and without insomnia symptoms. Methods Descriptive sub-study using data collected during baseline interviews of hospice family caregivers involved in a randomized clinical trial in Midwestern United States (xxxxxxxx). Caregivers were dichotomized based on Insomnia Severity Index (ISI) scores (8+ indicated insomnia symptoms). Results Among 57 hospice family caregivers, the mean ISI score was 8.2; nearly half (49.1%) experienced insomnia symptoms. Compared to caregivers without insomnia symptoms, caregivers with insomnia symptoms reported 2.4 times greater mean anxiety scores (4.7 vs 11.4); 3.5 times greater mean depression scores (3.1 vs 10.7); 2.1 times greater caregiver burden scores (5.6 vs 11.8); and 1.3 times lower self-rated health (3.5 vs 2.8); 1.3 times lower total QOL scores (29.3 vs 22.6); including differences in emotional QOL (7.9 vs 2.2), social QOL (7.2 vs 3.0), and physical QOL (7.4 vs 5.3). Conclusions Hospice family caregivers experience high prevalence of insomnia symptoms; caregivers with insomnia symptoms report worse anxiety, depression, caregiver burden, QOL, self-rated health. Clinicians must screen hospice caregivers for poor sleep and mental health and offer supportive interventions that improve their sleep and health. Policy makers must expand hospice benefits to better support family caregivers.
Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections—A prospective cohort study

Background Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. Objective We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. Materials and methods Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. Results Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850–0.948]; AUC for CRP 0.922 [95%CI 0.879–0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694–0.894]; AUC for CRP 0.807 [95%CI 0.721–0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. Conclusion In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.
KIF11 manipulates SREBP2‐dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma

Cholesterol metabolism is highly correlated with risks of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the underlying mechanisms of activation of cholesterol biogenesis remain inconclusive. KIF11 is a key component of the bipolar spindle and expresses highly in various malignancies. However, its functional role in PDAC tumorigenesis is still unclear. This study aims to elucidate the oncogenic functions of KIF11 in stimulating cholesterol metabolism, thereby driving PDAC progression. We utilized bioinformatics analysis to identify that KIF11 expressed highly in tumor samples versus paired normal tissues and high KIF11 correlated with high clinical stages of patients. Patients with high KIF11 had worse survival outcomes relative to those with low KIF11. Gene set enrichment analysis (GSEA) revealed that KIF11 correlated intensively with the mevalonate (MVA) metabolic pathway. Positive associations were observed between KIF11 and MVA‐signature (HMGCR, FDFT1, SQLE, and MSMO1). KIF11 could elevate the free cholesterol content of PDAC cells and targeting MVA inhibited the in vitro growth of KIF11‐overexpressing cells. Mechanistically, we found KIF11 could interact with SREBP2, the master regulator of MVA. High KIF11 could increase SREBP2 proteins, but not alter their mRNA levels. KIF11 could attenuate the ubiquitination‐mediated degradation of SREBP2, thereby enhancing its stability and accumulation. Accordingly, KIF11 stimulated the expressions of MVA‐signature and free cholesterol contents depending on SREBP2. In addition, KIF11 depended on SREBP2 to promote cell growth, migration, stemness, and colony formation abilities. The subcutaneous xenograft models indicated that targeting MVA biogenesis (atorvastatin) is effective to restrict the in vivo growth of KIF11high PDAC. Taken together, our study identified that KIF11 could activate the MVA cross talk to drive PDAC progression and inhibiting the KIF11/MVA axis provided a therapeutic vulnerability in the treatment of PDAC.
Invasive Salmonella Infections Among Children in Shenzhen, China: A Five-year Retrospective Review

Background: Invasive Salmonella infections are highly prevalent worldwide. Clinical data of childhood invasive Salmonella infections from China are limited. Methods: Data of hospitalized children <18 years old with invasive Salmonella infections from 2016 to 2020 in Shenzhen Children’s Hospital in Shenzhen were retrospectively collected. Serotypes and antimicrobial susceptibility tests of the invasive Salmonella isolates were performed. Results: Sixty-three cases were enrolled during the 5-year study period including 8 in 2016, 11 in 2017, 16 in 2018, 6 in 2019 and 22 in 2020. The median age was 15 months (interquartile range, 11–22 months), and 79.4% (50 cases) were <2 years of age. Underlying diseases were found in 28.6% (18 cases) of the patients with a great variety, but no cases of malaria or HIV infection were identified. Most of the invasive Salmonella cases were bloodstream infections (84.1%), followed by osteoarthritis (11.1%) and meningitis (4.8%). Gastroenteritis (49.2%) and pneumonia (28.6%) were found to be the major manifestations among the patients. Furthermore, invasive Salmonella infections resulted in the death of 3 children (4.8%). Salmonella enteritis (12 cases; 15.9%) and Salmonella typhimurium (9 cases; 19.0%) as the most common serovars were identified. The resistance rates of Salmonella strains to ceftriaxone, ceftazidime and cefepime were also measured to be 17.5%, 17.5% and 9.5%, respectively. Conclusions: An increasing number of childhood invasive Salmonella infections with a broad range of serotypes was observed in Shenzhen, China. It is critical to pay attention to the antimicrobial resistance of the isolates taken from children with invasive Salmonella infections.
Predictive Factors for Molecular Response in Chronic Myeloid Leukemia: Reduction Ratio and Halving Time of BCR::ABL1 IS Transcript Levels

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important thanBCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.
Managing Uncertainty for and With Family: Communication Strategies and Motivations in Familial Uncertainty Management for Hereditary Cancer

The management of uncertainty is integral to health and illness. Individuals manage uncertainty about their health through communication enmeshed in family systems, but existing theorizing focuses on individuals without accounting for family processes. An iterative qualitative analysis of 42 dyadic, family interviews (N = 84) revealed (a) moments in the context of hereditary cancer that involved individual-centered and familial uncertainty appraisal and management, (b) family members’ communication strategies to prompt relatives to engage familial uncertainty, and (c) the communicative (re)creation and negotiation of family models for uncertainty management. The findings illuminate tensions that individuals encounter across their lifespan as they appraise and manage uncertainty about hereditary cancer risks. This study extends uncertainty management theory to encompass familial uncertainty management and contributes insights useful for the management of hereditary cancer.
Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections

Significance BET bromodomain inhibition is therapeutic in multiple diseases; however, pan-BET inhibitors have induced significant myelosuppression and gastrointestinal toxicity, perhaps due to inhibition of both tandem bromodomains (BD) of all BET family members. However, selective inhibition of just the first BD (BD1) phenocopies pan-BET inhibitor activity in preclinical models of cancer, other diseases, and, for BRDT, in the testes for a contraceptive effect. Here, we leveraged our multibillion-molecule collection of DNA-encoded chemical libraries (DECLs) to identify BET BD1-selective inhibitors of specific chirality with high potency, stability, and good cellular activity. Our findings highlight the robustness and efficiency of the DECL platform to identify specific, potent protein binders that have promise as potential anticancer and anti-inflammatory agents and as male contraceptives.
Det norske måltidsmønsteret - ideal og praksis

Dette er en studie om det norske maltidsmonsteret. Hensikten med prosjektet var a oke kunnskapen om hvilken rolle og verdi maltidet har i den moderne hverdagen. Studien har vaert delt i to overordnede problemomrader. Pa den ene siden ble det sett pa hvordan maltidsmonsteret utformes og gjennomfores, og pa den annen side ble det sett pa den mening og betydning maltidet tillegges. Det har blitt benyttet bade kvalitative og kvantitative materialer.