Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Responses of Urinary Epinephrine and Norepinephrine to 24-h Shift-Work Stressor in Physicians

Multiple stressors, including 24-h-shifts characterise the working environment of physicians, influencing well-being, health and performance. We aimed to evaluate the effect of the stressor 24-h-shift on the adrenal medullary and sympathoneural system in physicians with the hypothesis that shift work might have different impacts on both systems. Twenty-two physicians collected two 12-h-urine samples (“daytime” and “nighttime”) during a 24-h shift (“on-duty”) and on a free weekend (“off-duty”), respectively. Urinary excretion rates per m2 body surface area were assessed for the catecholamines epinephrine, norepinephrine and their respective free O-methylated metabolites metanephrine and normetanephrine by LC-MS/MS-analysis. The stressor provoked differential responses of epinephrine and norepinephrine. Epinephrine excretion rates showed significant increases from off to on duty. The largest proportional change (off-duty to on-duty) for epinephrine was observed for nighttime (205%), the increase for daytime was 84%. An increase in norepinephrine from off to on duty was only visible for nighttime collections. For the catecholamine metabolites, normetanephrine paralleled norepinephrine and exhibited an increase in excretion from off to on duty during nighttime collections of 53% whereas there was no change during daytime collections (3%). In conclusion: Whilst the 24-h-shift-work stressor in physicians activates the sympatho-adrenomedullary system, represented by epinephrine, the sympathoneural response through norepinephrine reflects mainly an ambulatory position during working hours.
Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer accounting for 80% of all renal cancers as well as the majority of renal cancer-associated deaths. During the last decade, the treatment paradigm for ccRCC has radically changed. In particular, the recent development of immune checkpoint inhibitors (ICI) has led to an increased overall survival in the metastatic setting. Moreover, novel immune therapies targeting the tumor microenvironment have been developed. In this rapidly evolving treatment landscape, precise tools for personalized cancer therapy are needed. Here, we collected fresh tissue from 42 patients who underwent surgical resection for renal cell carcinoma. Part of the tissue was used to obtain formalin-fixed, paraffin-embedded samples or RNA. The remaining tissue was minced and cultured in a collagen-based three-dimensional, air-liquid interface (ALI) culture system. The generated patient-derived tumor organoids (ALI PDOs) were characterized by immunohistochemistry staining and RNA sequencing to validate their close similarity to the matched tumor. Immune cells and stromal cells within the microenvironment could be identified. Finally, we treated 10 ALI PDOs with the commonly used targeted cancer drug cabozantinib or the ICI nivolumab. Interestingly, we observed varying responses of ALI PDOs to these treatments and future studies are needed to investigate whether the ALI PDO approach could inform about treatment responses in patients. In conclusion, this three-dimensional ccRCC culture model represents a promising, facile tool for monitoring tumor responses to different types of therapies in a controlled manner, yet, still preserves the key features of the tumor of origin.
Establishment of National DRL For CT in Hybrid Imaging Studies(The Second Phase of the National NM CT (PET) Dose Audit For Kuwait Population -2019)

DRLs for CT part used in PET/CT examinations are limited. The aim was to execute the second phase of the national DRL for CT part of PET/CT imaging operating in KW, in support of optimisation and dose reduction as imaging technology is advancing. In this multicentre collaborative PET centers (No:8) audit, data collection was restricted to the adult oncology patients due to a limited number of the other studies and also due to the National MOH Ethical Committee recommendation. The CTDIvol, DLP and SL were recorded and the Median, Mean, SD, 75th, 25th percentiles as well as WB effective dose (ED) were calculated. Dose and scan length statistics for HB and WB scans (65% and 35% of total: 309) and the WB+HB presented together with the proposed NDRLs and the Achievable doses. Third quartile DLP (mGy x cm) and CTDIvol (mGy) values for the HB were (537, 5) which were higher than the UK NDRL (400, 4.3) but were lower than the Swiss NDRL (620, 6) and the France NDRL (762, 7.7). Comparatively, the Proposed NDRLs for (WB) were (684, 4.1) which were lower than Swiss National Data (720, 5.0). It is worth noted that, the Swiss had about 5000 (HB) & 706 (WB), the UK had 370 (HB) and France had 1000 (HB) entries. Calculated ED varied from 4.1 to 10.2 mSv, (mean values=6.9 mSv) for HB and from 2.6 to 7 mSv (mean value=4.6 mSv) for WB scans which were lower than the first phase (2018). Although, there was 9.1% improvement in NDRL, but the outcome suggested there is a continuous need for monitoring NDRL. KEY WORDS: PET/CT, NDRL, CTDvol, DLP, Molecular Imaging
Brain Atrophy Rates for Stable Multiple Sclerosis Patients on Long-Term Fingolimod versus Glatiramer Acetate

Background: Clinically stable multiple sclerosis (MS) patients on long-term therapy often have negligible acute inflammation on MRI. Brain atrophy may provide insight into subclinical disease progression in such populations. Objective: This study aims to compare brain atrophy for age- and gender-matched MS patients treated for >2 years with fingolimod (FTY) or glatiramer acetate (GA), examining brain volume, cognition, and patient-reported outcomes (PROs). Methods: Stable relapsing-MS patients, age 18–60, on FTY or GA for >2 years were followed up for 2 years. MRI brain and lesion volumes, cognitive measures, and PROs were collected at baseline and annually. Results: Forty-four FTY and forty-three GA patients completed baseline and year 2 visits. No differences in age, gender, or education were observed. Median EDSS was 2.0GA and 2.5FTY (p = 0.22). Treatment duration was longer for GA, 6.50GA vs. 3.73FTY years (p < 0.001). Baseline geometric mean T2LV were different, GA = 1,009.29 cm3 vs. FTY = 2,404.67 cm3 (p = 0.0071). Baseline brain volumes were similar, GA = 1,508 cm3 vs. FTY = 1,489 cm3 (p = 0.2381). Annualized atrophy rates, adjusted for baseline and at mean baseline value, were GA = −0.2775% vs. FTY = −0.2967% (p = 0.7979). No differences in cognitive measures or PROs were observed. Conclusions: Stable MS patients on long-term treatment with FTY and GA have similar brain volume loss rates. Differences in baseline disease severity may suggest patients with more aggressive disease treated with FTY may achieve similar brain volume loss rates as patients with milder baseline disease on GA.
UPLC-HRMS Analysis Revealed the Differential Accumulation of Antioxidant and Anti-Aging Lignans and Neolignans in In Vitro Cultures of Linum usitatissimum L

Over the last few decades, methods relating to plant tissue culture have become prevalent within the cosmetic industry. Forecasts predict the cosmetic industry to grow to an annual turnover of around a few hundred billion US dollars. Here we focused on Linum usitatissimum L. , a plant that is well-known for its potent cosmetic properties. Following the a) establishment of cell cultures from three distinct initial explant origins (root, hypocotyl, and cotyledon) and b) selection of optimal hormonal concentrations, two in vitro systems (callus vs cell suspensions) were subjected to different light conditions. Phytochemical analysis by UPLC-HRMS not only confirmed high (neo)lignan accumulation capacity of this species with high concentrations of seven newly described (neo)lignans. Evaluation over 30 days revealed strong variations between the two different in vitro systems cultivated under light or dark, in terms of their growth kinetics and phytochemical composition. Additionally, antioxidant (i.e. four different in vitro assays based on hydrogen-atom transfer or electron transfer mechanism) and anti-aging (i.e. four in vitro inhibition potential of the skin remodeling enzymes: elastase, hyaluronidase, collagenase and tyrosinase) properties were evaluated for the two different in vitro systems cultivated under light or dark. A prominent hydrogen-atom transfer antioxidant mechanism was illustrated by the DPPH and ABTS assays. Potent tyrosinase and elastase inhibitory activities were also observed, which was strongly influenced by the in vitro system and light conditions. Statistical treatments of the data showed relationship of some (neo)lignans with these biological activities. These results confirmed the accumulation of flax (neo)lignans in different in vitro systems that were subjected to distinct light conditions. Furthermore, we showed the importance of optimizing these parameters for specific applications within the cosmetic industry.
The Role of Imaging Biomarkers Derived From Advanced Imaging and Radiomics in the Management of Brain Tumors

Significant advances have been made in the realm of medical image analysis in the past few decades, aimed at improving our understanding of the disease—how it develops, behaves, and responds to treatment. Advanced imaging strategies using magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional phenotypic biomarkers that correlate with key disease processes. Radiomics-based biomarkers provide a deeper analysis of pathophysiologic processes and insights to better diagnose, classify, stratify, and prognosticate brain tumors, and to assess their response to therapy.
Effectiveness of the Boston University Approach to Psychiatric Rehabilitation in Improving Social Participation in People With Severe Mental Illnesses: A Randomized Controlled Trial

Background People with severe mental illnesses (SMIs) have difficulty participating in society through work or other daily activities. Aims To establish the effectiveness with which the Boston University Approach to Psychiatric Rehabilitation (BPR) improves the level of social participation in people with SMIs, in the Netherlands. Method In a randomized controlled trial involving 188 people with SMIs, we compared BPR (n = 98) with an Active Control Condition (ACC, n = 90) (Trial registration ISRCTN88987322). Multilevel modeling was used to study intervention effects over two six-month periods. The primary outcome measure was level of social participation, expressed as having participated in paid or unpaid employment over the past six months, as the total hours spent in paid or unpaid employment, and as the current level of social participation. Secondary outcome measures were clients’ views on rehabilitation goal attainment, Quality of Life (QOL), personal recovery, self-efficacy, and psychosocial functioning. Results During the study, social participation, QOL, and psychosocial functioning improved in patients in both groups. However, BPR was not more effective than ACC on any of the outcomes. Better social participation was predicted by previous work experience and a lower intensity of psychiatric symptoms. Conclusions While ACC was as effective as BPR in improving the social participation of individuals with SMIs, much higher percentages of participants in our sample found (paid) work or other meaningful activities than in observational studies without specific support for social participation. This suggests that focused rehabilitation efforts are beneficial, irrespective of the specific methodology used.
Father Involvement in Infant Parenting in an Ethnically Diverse Community Sample: Predicting Paternal Depressive Symptoms

Early paternal involvement in infant care is beneficial to child and maternal health, and possibly for paternal mental health. The purpose of the present study was to examine the relationship between fathers’ involvement in early infant parenting and their depressive symptoms during the infant’s first year in a sample of 881 low-income Black, Hispanic, and White fathers recruited from five sites in the United States (urban, mixed urban/suburban, rural). Home interviews at 1 month after birth assessed three concepts based on prior research and community input: (1) time spent with the infant, (2) parenting self-efficacy, (3) material support for the baby. Paternal depressive symptoms at 1, 6, and 12 months after the birth of a child were assessed with the Edinburgh Postpartum Depression Scale. Generalized estimating equations tested whether the three indicators of father involvement at 1 month after birth predicted lower subsequent paternal depressive symptoms controlling for social and demographic variables. For fathers, greater time spent with the infant, parenting self-efficacy, and material support were all significantly associated with lower paternal depressive symptoms during the first year. When risk of depression (scores > 9) was examined, only parenting self-efficacy among fathers was associated with higher likelihood of clinical depression. Findings have implications for future research on mechanisms linking paternal involvement and paternal mental health, and for possible paid paternal leave policies in the future.
MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation

Current treatment of T-cell acute lymphoblastic leukemia (T-ALL) is primarily based on high-intensity combination chemotherapy, which has serious side effects. Therefore, developments of novel targeted therapeutics are urgently needed for treatment of T-ALL. In this study, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a novel promising therapeutic target for treatment of T-ALL. MALT1 inhibitor MI-2 significantly suppressed the cell growth, proliferation, and colony formation of T-ALL cells. Furthermore, MI-2 induced cell apoptosis of T-ALL via a mitochondrial-dependent pathway. In a T-ALL mouse model, MI-2 significantly reduced leukemic burden and prolonged the survival of leukemia-bearing mice. Mechanistically, MALT1 inhibition effectively blocked both baseline and Notch1-induced activation of nuclear factor κB pathway, which mediates T-ALL cell survival. In conclusion, our results highlight the potential role of MALT1 as an attractive target for treatment of T-ALL and support the potential of MI-2 or other MALT1 inhibitors to clinical trials in T-ALL.
Essentialist Biases in Reasoning About Emotions

A large literature debates whether emotions are universal and innate. Here, we ask whether reasoning about such matters is shaped by intuitive Essentialist biases that link innateness to the material body. To gauge the perception of innateness, we asked laypeople to evaluate whether emotion categories will be recognized spontaneously by hunter–gatherers who have had no contact with Westerners. Experiment 1 shows that participants believe that emotions are innate and embodied (facially and internally) and these two properties correlate reliably. Experiment 2 demonstrates that the link is causal. When told that emotions are localized in specific brain areas (i.e., embodied), participants concluded that emotions are innate. Experiment 3 shows that this naïve view persists even when participants are explicitly informed that these emotions are acquired. Our results are the first to suggest that laypeople incorrectly believe that, if emotions are embodied, then they must be innate. We suggest that people’s failure to grasp the workings of their psyche arises from the human psyche itself.
Pure Zirconium: Type II Nodal Line and Nodal Surface States

Type II nodal line states have novel properties, such as direction-reliant chiral anomalies and high anisotropic negative magneto-resistance. These type II nodal line states have been widely investigated. Compared to nodal line materials, there are far fewer proposed nodal surface materials, and furthermore, a very recent challenge is to find a realistic material that co-exhibits both nodal line and nodal surface states. In this manuscript, we present the study of the electronic and topological states of pure zirconium within the density functional theory. We found that pure Zr is an interesting material that rarely exhibits both the type II nodal line state (in kz = 0 plane) and nodal surface state (in kz = π plane). The nontrivial topological states are explained based on the orbital-resolved band structures. Our study shows that pure Zr can serve as a new platform to investigate the interplay between the nodal line state and the nodal surface state.
Downregulation of DUSP9 Promotes Tumor Progression and Contributes to Poor Prognosis in Human Colorectal Cancer

Background Dual-specificity phosphatase 9 (DUSP9) belongs to the dual-specificity protein phosphatase subfamily. Recently, increasing attention has been paid on the role of DUSP9 in a variety of cancers. However, its functional role in tumor development is still unclear, especially in colorectal cancer (CRC). Methods The functional role of DUSP9 in inhibiting the progression of CRC was verified using colony formation assay, wound healing assay, nude mice xenograft model, etc. RNA-seq was performed to assess the gene expression profiling in SW480 cells with DUSP9 stable knockdown and shControl cells. Bisulfite sequencing (BSE) was performed to reveal the methylation status of CpG island in the promoter of DUSP9. Results DUSP9 was significantly downregulated in tumor tissues compared with peritumor tissues. Mechanistically, the high methylation status of CpG island in the promoter of DUSP9 may lead to the downregulation of DUSP9 in CRC. Clinically, low DUSP9 expression in CRC was closely associated with depth of invasion, metastasis (TNM) stage, and poor survival, indicating that DUSP9 may be involved in the progression of CRC. Functional study revealed that DUSP9 inhibited proliferation, migration, invasion, and epithelial–mesenchymal transition of CRC cells both in vitro and in vivo. Transcriptome profiling studies revealed that Erk signaling was involved in the tumor progression mediated by DUSP9 silencing, which is confirmed by cell experiments and clinical tissue sample staining analysis. Conclusion Our findings demonstrate that DUSP9 plays a critical role in the progression of CRC, and therapeutic intervention to increase the expression or activity of DUSP9 may be a potential target for CRC treatment in the future.
Parents’ labour force participation and children’s involvement in work activities: evidence from Thailand

ABSTRACT This study provides a better understanding of children’s engagement in economic work and housework by examining its relationship with parents’ labour force participation. It also explores how parents’ employment type is associated with children’s involvement in work activities. Using Thailand’s Labour Force and Time Use Surveys, our multivariate probit regression results show that girls actively participate in economic activities when their mothers are employed, while boys’ involvement in such work is positively correlated to both parents’ employment. Girls’ housework participation is also positively associated with parents’ employment, suggesting that their assistance in household chores enable their parents to stay in the labour market. These positive relationships are prevalent particularly among children with either mothers or fathers working informally. Hence, the findings suggest that anti-poverty or expansionary policies aimed at increasing labour force participation without attention to job quality, social protection and care needs can adversely affect children by increasing their need to work.
A Semiquantitative Non-invasive Measurement of PcomA Patency in C57BL/6 Mice Explains Variance in Ischemic Brain Damage in Filament MCAo

Numerous studies on experimental ischemic stroke use the filament middle cerebral artery occlusion (fMCAo) model in C57BL/6 mice, but lesion sizes in this strain are highly variable. A known contributor is variation in the posterior communicating artery (PcomA) patency. We therefore aimed to provide a semiquantitative non-invasive in vivo method to routinely assess PcomA patency. We included 43 male C57BL/6 mice from four independent studies using a transient 45 min fMCAo model. Edema-corrected lesion sizes were measured by magnetic resonance (MR) imaging 24 h after reperfusion. Time-of-flight MR angiography was performed 7 days before and 24 h after fMCAo. Scores of PcomA size measured 24 h after, but not scores measured 7 days before fMCAo were negatively correlated with lesion size. Variability in PcomA patency explained 30% of the variance in our cohort (p < 0.0001, coefficient of determination r2 = 0.3). In a simulation using parameters typical for experimental stroke research, the power to detect a true effect of d = 1 between two groups increased by 15% when an according covariate was included in the statistical model. We have demonstrated that in vivo measurement of PcomA size is feasible and can lead to increased accuracy in assessing the effect of treatments.
Scoping Review Supporting decision-making on allocation of ICU beds and ventilators in pandemics

As the world struggles with the COVID-19 pandemic, health service demands have increased to a point where healthcare resources may prove inadequate to meet demand. Guidelines and tools on how to best allocate intensive care beds and ventilators developed during previous epidemics can assist clinicians and policy-makers to make consistent, objective and ethically sounds decisions about resource allocation when healthcare rationing is inevitable. This scoping review of 62 published guidelines, triage protocols, consensus statements and prognostic tools from crisis and non-crisis situations sought to identify a multiplicity of objective factors to inform healthcare rationing of critical care and ventilator care. It also took ethical considerations into account. Prognostic indicators and other decision tools presented here can be combined to create locally-relevant triage algorithms for clinical services and policy makers deciding about allocation of ICU beds and ventilators during a pandemic. Community awareness of the triage protocol is recommended to build trust and alleviate anxiety among the public. This review provides a unique resource and is intended as a discussion starter for clinical services and policy makers to consider formalising an objective triage consensus document that fits the local context.
Dual Effects of Lipid Metabolism on Osteoblast Function

The skeleton is a dynamic and metabolically active organ with the capacity to influence whole body metabolism. This newly recognized function has propagated interest in the connection between bone health and metabolic dysfunction. Osteoblasts, the specialized mesenchymal cells responsible for the production of bone matrix and mineralization, rely on multiple fuel sources. The utilization of glucose by osteoblasts has long been a focus of research, however, lipids and their derivatives, are increasingly recognized as a vital energy source. Osteoblasts possess the necessary receptors and catabolic enzymes for internalization and utilization of circulating lipids. Disruption of these processes can impair osteoblast function, resulting in skeletal deficits while simultaneously altering whole body lipid homeostasis. This article provides an overview of the metabolism of postprandial and stored lipids and the osteoblast's ability to acquire and utilize these molecules. We focus on the requirement for fatty acid oxidation and the pathways regulating this function as well as the negative impact of dyslipidemia on the osteoblast and skeletal health. These findings provide key insights into the nuances of lipid metabolism in influencing skeletal homeostasis which are critical to appreciate the extent of the osteoblast's role in metabolic homeostasis.