Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Analysis of Label-Free Microscale Collagen Gel Contraction Using Machine Learning-Aided Image Analysis

Pulmonary fibrosis is a deadly lung disease, wherein normal lung tissue is progressively replaced with fibrotic scar tissue. An aspect of this process can be recreated in vitro by embedding fibroblasts into a collagen matrix and providing a fibrotic stimulus. This work expands upon a previously described method to print microscale cell-laden collagen gels and combines it with live cell imaging and automated image analysis to enable high-throughput analysis of the kinetics of cell-mediated contraction of this collagen matrix. The image analysis method utilizes a plugin for FIJI, built around Waikato Environment for Knowledge Analysis (WEKA) Segmentation. After cross-validation of this automated image analysis with manual shape tracing, the assay was applied to primary human lung fibroblasts including cells isolated from idiopathic pulmonary fibrosis patients. In the absence of any exogenous stimuli, the analysis showed significantly faster and more extensive contraction of the diseased cells compared to the healthy ones. Upon stimulation with transforming growth factor beta 1 (TGF-β1), fibroblasts from the healthy donor showed significantly more contraction throughout the observation period while differences in the response of diseased cells was subtle and could only be detected during a smaller window of time. Finally, dose-response curves for the inhibition of collagen gel contraction were determined for 3 small molecules including the only 2 FDA-approved drugs for idiopathic pulmonary fibrosis.
‘Serious’ Disaster Video Games: An Innovative Approach to Teaching and Learning about Disasters and Disaster Risk Reduction

Abstract Scholars, practitioners and educators propose video games as innovative teaching methods to engage geography students. A methodological framework, informed by constructivist learning theory, explored the ability of ‘serious’ disaster video games to foster student participation in learning within four New Zealand schools. The findings indicate the utilization of video games within the classroom requires further consideration of the teaching and learning processes for both teachers and students. Ultimately, the alignment of video games to constructivism and pedagogical mechanisms of social science suggests the ability of geography to enable deeper discussions and engagement of the curriculum by both students and teachers.
Hindutva as a variant of right-wing extremism

ABSTRACT Leidig’s article addresses a theoretical and empirical lacuna by analysing Hindutva using the terminology of right-wing extremism. It situates the origins of Hindutva in colonial India where it emerged through sustained interaction with ideologues in Fascist Italy and Nazi Germany who, in turn, engaged with Hindutva to further their own ideological developments. Following India’s independence, Hindutva actors played a central role in the violence of nation-building and in creating a majoritarian identity. Yet Hindutva was not truly ‘mainstreamed’ until the election of the current prime minister, Narendra Modi, in 2014. In order to construct a narrative that furthered Hindu insecurity, Modi mobilized his campaign by appealing to recurring themes of a Muslim ‘threat’ to the Hindu majority. The result is that Hindutva has become synonymous with Indian nationalism. Leidig seeks to bridge the scholarly divide between, on the one hand, the study of right-wing extremism as a field dominated by western scholars and disciplines and, on the other, the study of Hindutva as a field that is of interest almost exclusively to scholars in South Asian studies. It provides an analytical contribution towards the conceptualization of right-wing extremism as a global phenomenon.
IL-12 DNA Displays Efficient Adjuvant Effects Improving Immunogenicity of Ag85A in DNA Prime/MVA Boost Immunizations

Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection.
Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors

Ovarian carcinoma is a heterogeneous disease with distinct molecular and histological profiles, ranging from low grade atypia to highly aggressive tumors associated with a poor prognosis. In the present study, glycosphingolipids were isolated from human high-grade serous ovarian carcinoma, whereby the novel stem cell marker Sialyl-lactotetra (S-Lc4) was characterized in two out of three cases. The presence and level of S-Lc4 was further evaluated immunohistochemically in a cohort of patients with ovarian tumors ranging from benign lesions to high grade serous carcinoma (n = 478). Its expression was assessed in association with tumor grade, stage, histology, and survival. The data showed that S-Lc4 is most common and highly expressed in borderline type tumors and carcinomas with low levels of aggressiveness, such as mucinous, endometrioid, and low grade serous. Accordingly, S-Lc4-positivity was associated with better disease-free survival. The expression of S-Lc4 was seemingly associated with lineage continuity and could be traced from premalignant lesions to carcinoma, suggesting inheritance by a stem cell lineage that gives rise to generally indolent tumors.
Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta‐analysis

We investigated the efficacy and safety of surgery and external beam radiotherapy (EBRT), in patients with hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) through a comparative meta‐analysis. A systematic search of PubMed, MEDLINE, EMBASE, and the Cochrane library was performed for entries until July 2020. Eighteen studies with 22 cohorts were included, encompassing 755 patients. The pooled median overall survival (OS) and 1‐ and 2‐year OS rates were 14.2 months, 55.6%, and 27.4%, respectively. The pooled median OS in the surgery and EBRT arms were 15.3 and 11.7 months, respectively. The pooled 1‐year OS rate in the surgery arm was significantly higher than that in the EBRT arm (62.4%, 95% CI: 53.8%‐70.3% vs 48.8%, 95% CI: 40.9‐56.8, respectively; P = .023), while the 2‐year OS rates were similar (27.5%, 95% CI: 19.7%‐37.1% vs 26.9%, 95% CI: 20.7‐34.2, respectively; P = .913). In the surgical arm, the perioperative mortality and grade ≥3 complication rates were 0%‐7.6% and 3.9%‐67%, respectively. Grade ≥3 complications and radiation‐induced liver disease were rarely observed in the EBRT arm. Surgery could be an effective local modality for achieving the best survival rate, though it requires efforts to minimize morbidities and careful patient selection. EBRT, as a noninvasive modality, is a valid palliative option, especially for high‐risk patients with a shorter life expectancy.
Potential Application of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Renal Cell Tumors

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CAR-T cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CAR-T cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CAR-T cell therapy in renal cell malignancies.
Disrupted Structural Brain Network Organization Behind Depressive Symptoms in Major Depressive Disorder

Major depressive disorder (MDD) is a severe and devastating condition. However, the anatomical basis behind the affective symptoms, cognitive symptoms, and somatic-vegetative symptoms of MDD is still unknown. To explore the mechanism behind the depressive symptoms in MDD, we used diffusion tensor imaging (DTI)–based structural brain connectivity analysis to investigate the network difference between MDD patients and healthy controls (CN), and to explore the association between network metrics and patients’ clinical symptoms. Twenty-six patients with MDD and 25 CN were included. A baseline 24-item Hamilton rating scale for depression (HAMD-24) score ≥ 21 and seven factors (anxiety/somatization, weight loss, cognitive disturbance, diurnal variation, retardation, sleep disturbance, hopelessness) scores were assessed. When compared with healthy subjects, significantly higher characteristic path length and clustering coefficient as well as significantly lower network efficiencies were observed in patients with MDD. Furthermore, MDD patients demonstrated significantly lower nodal degree and nodal efficiency in multiple brain regions including superior frontal gyrus (SFG), supplementary motor area (SMA), calcarine fissure, middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). We also found that the characteristic path length of MDD patients was associated with weight loss. Moreover, significantly lower global efficiency of MDD patients was correlated with higher total HAMD score, anxiety somatization, and cognitive disturbance. The nodal degree in SFG was also found to be negatively associated with disease duration. In conclusion, our results demonstrated that MDD patients had impaired structural network features compared to CN, and disruption of optimal network architecture might be the mechanism behind the depressive symptoms and emotion disturbance in MDD patients.
Who is not linked to primary care public health facilities for cardiovascular disease prevention, and why-not: A community based follow up study from urban slums in India

We designed and conducted a community based longitudinal study in 16 urban slum clusters in context of a community health worker (CHW) led screening and preventive therapy initiation initiative for CVD prevention. Linkage to public health systems primary care facilities was a key outcome indicator for this initiative. In this paper, we have investigated predictors and barriers to non-linkage. CHWs screened all adults aged 30 years through for hypertension as well as diabetes. Referrals were advised and facilitated to nearby Urban Primary Health Centre (PHC) clinic for either treatment initiation or continuation or optimization. CHWs screened a total of 6174 individuals, and physicians identified 1449 participants (23.46%; 95% CI 22.42-24.54) as high-risk who required linkage to public-health facilities for pharmacotherapy . Out of these, 943(65%) attended health facilities with 801(55.2 %) being adherent to pharmacotherapy. Those who were not linked were young men belonging to low socio-economic position, living farther from UPHC, engaged late by CHW and identified to be in denial mode and reported lack of family support. This study highlights importance of early engagement through CHWs after positive screening, necessity to address denial of newly diagnosed and increase male participation in order to reduce detection to treatment initiation gap. Keywords- hypertension, diabetes, adherence, community health worker, cardio vascular diseases, population-based screening
EFFECTS OF AMINO ACIDS AND YEAST EXTRACT ON GLUTATHIONE PRODUCTION

The effects of amino acids and yeast extract on glutathione (GSH) production by yeast were investigated.The results showed that various amino acids could enhance the growth of yeast but couldn't greatly improve the biosynthesis of GSH,while cysteine showed a property of significantly increasing the GSH content but inhibiting the growth.The highest specific GSH production rate (3.7 mg·g cell -1 ·h -1 ) was obtained when the initial cysteine concentration was 5 mmol/L.Both the growth of yeast and the biosynthesis of GSH could be remarkably improved by addition of yeast extract.When the glucose concentration was 3% without yeast extract addition the GSH content was only 50% compared with that in 1% glucose concentration,while with 0.6% yeast extract addition the GSH content was approximately twice as much as the control;and the total GSH in broth (92.5 mg/L) with suppling glucose operation was 48% higher than that in 1% glucose concentration.
The Role of Nerves in Skeletal Development, Adaptation, and Aging

The skeleton is well-innervated, but only recently have the functions of this complex network in bone started to become known. Although our knowledge of skeletal sensory and sympathetic innervation is incomplete, including the specific locations and subtypes of nerves in bone, we are now able to reconcile early studies utilizing denervation models with recent work dissecting the molecular signaling between bone and nerve. In total, sensory innervation functions in bone much as it does elsewhere in the body—to sense and respond to stimuli, including mechanical loading. Similarly, sympathetic nerves regulate autonomic functions related to bone, including homeostatic remodeling and vascular tone. However, more study is required to translate our current knowledge of bone-nerve crosstalk to novel therapeutic strategies that can be effectively utilized to combat skeletal diseases, disorders of low bone mass, and age-related decreases in bone quality.
The Role of Milk Components, Pro-, Pre-, and Synbiotic Foods in Calcium Absorption and Bone Health Maintenance

Increasing peak bone mass during adolescence and reducing bone loss in later life are two approaches to reduce the risk of osteoporosis with aging. Osteoporosis affects a large proportion of the elderly population worldwide and the incidence is increasing. Milk consumption is an accepted strategy in building peak bone mass and therefore may reduce the risk of osteoporosis. In childhood calcium, phosphorous, and growth factors are the important components to support bone growth but in adults the positive influence on bone density/maintenance may also be due to other bioactive proteins/peptides or lipids in milk acting directly in the gastrointestinal tract (GIT). Lactose has been known to increase calcium absorption; galactooligosaccharides (GOS) are derived from lactose and are non-digestible oligosaccharides. They have been shown to improve mineral balance and bone properties as well as causing increases in bifidobacteria in the gut, therefore a prebiotic effect. Supplementation with fortified milk and dairy products with added prebiotics, increased both calcium and magnesium absorption and caused some modulation of gut microbiota in animals and humans. Fermented milk is now also recognized to contain highly active components such as vitamins, peptides, oligosaccharides, and organic acids. In this review, the role of milk and milk components in improving calcium absorption and thereby supporting bone health is discussed. In addition, some reference is made to the significance of combining the inherent beneficial components from milk with fortificants/nutrients that will support bone health through adulthood. Novel data suggesting differences in diversity of the microbiota between healthy and osteoporotic women are provided.
Social Feedback During Sensorimotor Synchronization Changes Salivary Oxytocin and Behavioral States

In humans and animal models, oxytocin increases social closeness, attachment and prosocial behaviors, while decreasing anxiety and stress levels. Efficiently triggering the release of endogenous oxytocin could serve as a powerful therapeutic intervention for disorders of social behavior and for anxiety. We designed a new version of a social sensorimotor synchronization task to investigate the role of social approval in inducing biochemical and psychological changes following behavioral synchrony in a sample of 80 college students. Social approval in the form of real time positive feedback increased well-being only in women, while increasing social closeness in both genders. Social disapproval in the form of real time negative feedback prevented a decrease in stress levels that otherwise women reported following engagement in either social or non-social synchronization. Surprisingly, for certain personality traits, negative social feedback during sensorimotor synchronization was psychologically beneficial irrespective of gender. Salivary oxytocin levels increased only in women after the social but not the non-social synchronization tasks. Oxytocin dynamics were independent of the type of real time feedback that subjects received, indicating the existence of distinct mechanisms for hormonal versus behavioral changes following synchronization. Nevertheless, changes in salivary oxytocin after positive social feedback correlated with changes in well-being and predicted changes in prosocial attitudes. Our findings show evidence of distinct mechanisms for behavioral versus hormonal changes following social sensorimotor synchronization, and indicate that gender and personality traits should be carefully considered when designing behavioral therapies for improving social attitudes and for stress management.
Comparison of T2N0M0 and T3aN0M0 in Predicting the Prognosis of Patients With Renal Cell Carcinoma

Background: To investigate the prognostic role of tumor size in patients with pathological T2N0M0 and T3aN0M0 renal cell carcinoma (RCC) treated by radical surgery. Methods: A total of 3,662 cases were retrospectively analyzed from the Surveillance, Epidemiology and End Results (SEER) from 2010 to 2012. Overall survival (OS) and cancer-specific survival (CSS) data were obtained. The log-rank test was used to compare survival distributions and Cox proportional hazards model was used for univariate and multivariate analyses, respectively. Results: In the low-risk T3aN0M0 (perinephric fatty infiltration or sinus fatty infiltration only) group, patients with tumor size ≤ 7 cm were associated with a better OS (P = 0.009) and CSS (P < 0.001) than those with tumor size >7 cm. However, there was no difference in OS (P = 0.129) and CSS (P = 0.539) between T2bN0M0 patients and low-risk T3aN0M0 patients with tumor size ≤ 7 cm. A new T classification grouping patients with both T2bN0M0 and T3aN0M0 with tumor diameter ≤ 7 cm into the same staging category (pT2aN0M0, pT2bN0M0+low-risk pT3aN0M0 [tumor diameter ≤ 7cm], low-risk pT3aN0M0 [tumor diameter >7 cm], high-risk pT3aN0M0) was proposed and it was found as an independent predictive variable for OS and CSS. Conclusions: Findings from the present study suggest that the reclassification of pT2N0M0 and pT3aN0M0 RCC can lead to better prediction of OS and CSS.
Hypertension Risk in Young Women With Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Objective: A number of publications have assessed the prevalence of hypertension in polycystic ovary syndrome (PCOS) patients with inconclusive results. Since in general populations the occurrence of hypertension is related to age and comorbidities, we investigated the incidence rate and hazard ratios (HRs) of hypertension between healthy subjects and young women with PCOS as well as comorbidities. Methods: We conducted a population-based retrospective cohort study by using the National Health Insurance Research Database in Taiwan. The cohort included women with the diagnosis of PCOS between 2000 and 2012. Those without PCOS were selected as the control group at a ratio of 4:1 by an age-matched systematic random-sampling method. Cox proportional hazard regression analysis was used to determine the effects of PCOS on the risks of developing hypertension. Stratification analysis was performed to elucidate the interaction among PCOS and the comorbidities, which affect the incidence of hypertension. Results: The PCOS cohort consisted of 20,652 patients with PCOS and the comparison cohort consisted of 82,608 matched patients without PCOS. There was no difference in the distribution of age between the PCOS cohort and the comparison cohort (29.1 ± 6.8 vs. 29.0 ± 6.5, p = 0.32). The incidence rates of hypertension were 7.85 and 4.23 per 1,000 person-years in the PCOS and comparison groups, respectively. A statistically significant higher risk of hypertension was found in the PCOS cohort (adjusted HR = 1.62, 95% confidence interval = 1.48–1.76) than in the comparison cohort. After a joint analysis of comorbidities, the adjusted HR of hypertension was 9.44 (95% confidence interval = 7.27–12.24) for PCOS patients with comorbidities of diabetes mellitus (DM) and hyperlipidemia compared with women with neither PCOS nor DM and hyperlipidemia. Conclusion: The risk of developing hypertension in young women with PCOS was higher than in controls in this cohort study. The comorbidities of DM and hyperlipidemia could interact with PCOS patients and further increase the risk of hypertension. An earlier screening for hypertension and comorbidities in patients with PCOS may be warranted, even in young women.