Miracle-dz/UniFAR-FTUs huggingface dataset:
Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to increased radiation-resistance. However, it is not yet fully understood how radiotherapy regulates the expression and subcellular localization of YAP in breast cancer cells experiencing different microenvironmental stiffnesses. To elucidate the role of extracellular matrix stiffness and ionizing radiations on YAP regulation, we explored the behaviour of two different mammary cell lines, a normal epithelial cell line (MCF10A) and a highly aggressive and invasive adenocarcinoma cell line (MDA-MB-231) interacting with polyacrylamide substrates mimicking the mechanics of both normal and tumour tissues (∼1 and ∼13 kPa). We report that X-ray radiation affected in a significant way the levels of YAP expression, density, and localization in both cell lines. After 24 h, MCF10A and MDA-MB-231 increased the expression level of YAP in both nucleus and cytoplasm in a dose dependent manner and particularly on the stiffer substrates. After 72 h, MCF10A reduced mostly the YAP expression in the cytoplasm, whereas it remained high in the nucleus of cells on stiffer substrates. Tumour cells continued to exhibit higher levels of YAP expression, especially in the cytoplasmic compartment, as indicated by the reduction of nuclear/cytoplasmic ratio of total YAP. Then, we investigated the existence of a correlation between YAP localization and the expression of the nuclear envelope protein lamin A/C, considering its key role in modulating nuclear deformability and changes in YAP shuttling phenomena. As supposed, we found that the effects of radiation on YAP nucleus/cytoplasmic expression ratio, increasing in healthy cells and decreasing in tumour ones, were accompanied by lower and higher lamin A/C levels in MCF10A and MDA-MB-231 cells, respectively. These findings point to obtain a deeper knowledge of the role of the extracellular matrix and the effects of X-rays on YAP and lamin A/C expression that can be used in the design of doses and timing of radiation therapy.
Protein disulfide isomerase A6 promotes the repair of injured nerve through interactions with spastin

The maintenance of appropriate endoplasmic reticulum (ER) homeostasis is critical to effective spinal cord injury (SCI) repair. In previous reports, protein disulfide isomerase A6 (PDIA6) demonstrated to serve as a reversible functional modulator of ER stress responses, while spastin can coordinate ER organization through the modulation of the dynamic microtubule network surrounding this organelle. While both PDIA6 and spastin are thus important regulators of the ER, whether they interact with one another for SCI repair still needs to be determined. Here a proteomics analysis identified PDIA6 as being related to SCI repair, and protein interaction mass spectrometry further confirmed the ability of PDIA6 and spastin to interact with one another. Pull-down and co-immunoprecipitation assays were further performed to validate and characterize the interactions between these two proteins. The RNAi-based knockdown of PDIA6 in COS-7 cells inhibited the activity of spastin-dependent microtubule severing. PDIA6 was also found to promote injured neuron repair, while spastin knockdown reversed this reparative activity. Together, these results thus confirm that PDIA6 and spastin function together as critical mediators of nerve repair, highlighting their potential value as validated targets for efforts to promote SCI repair.
Unpacking language teacher beliefs, agency, and resilience in the complex, unprecedented time: A mixed-method study

We conducted this mixed-method study by focusing on the influx relationship among teacher beliefs, agency, and resilience during the pandemic and exploring the relationships and tensions among these constructs or capacities. Specifically, we surveyed 93 language teachers across seven different regions in China and collected their perceptions and beliefs about challenges and solutions during the first wave of the pandemic. In a further step, we interviewed six participants, analyzed the transcripts of the interviews, and then explored how their agency and resilience emerged and developed during the pandemic. From the quantitative statistics, we reported teacher beliefs about emotional, physical, mentoring, and support challenges in emergency remote teaching and their adopted strategies to handle these challenges during the pandemic. We also reported significant correlations among different perceived challenges and solutions. From the qualitative analysis, we found that language teacher beliefs, agency, and resilience co-evolved from intrapersonal and interpersonal reflections through temporal and contextual affordances. Drawing from the sociocultural theory, we contributed a theoretical framework for studying language teacher beliefs, agency, and resilience. We discussed our findings around the global traits that language teachers are required to develop in the increasingly complex world and also offered implications for language teacher education programs.
Associations of chronic diarrheal symptoms and inflammatory bowel disease with sleep quality: A secondary analysis of NHANES 2005–2010

Objective Poor sleep quality is highly prevalent in patients with chronic diarrheal symptoms or inflammatory bowel disease (IBD). This study aimed to evaluate the associations of chronic diarrheal symptoms and IBD with sleep quality in the general US population. Methods 14,696 adults (≥20 years) from the National Health and Nutrition Examination Survey (2005–2010) were included in the study. Chronic diarrheal symptoms and IBD were defined by self-reports. Sleep quality was assessed by sleep disorder, sleep trouble, and sleep duration. Multivariable logistic regression models were used to examine the associations. Results After adjustment of a series of covariates, we found that participants with chronic diarrheal symptoms or IBD had higher odds of sleep disorder [chronic diarrheal symptoms: odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.04–1.38; IBD: OR = 3.86, 95% CI = 1.92–7.77] and sleep trouble (chronic diarrheal symptoms: OR = 1.19, 95% CI = 1.09–1.30; IBD: OR = 2.32, 95% CI = 1.30–4.14), respectively. Sleep duration for participants with IBD was significantly shorter than that for those without IBD (β = −0.39, 95% CI = −0.78 to 0.01, P = 0.045). Subgroup analyses revealed that the associations of chronic diarrheal symptoms and IBD with sleep disorder and sleep trouble were more pronounced among women. Conclusions In this large sample of US adults, we found that chronic diarrheal symptoms and IBD were significantly associated with sleep quality, particularly in women. The findings highlight the importance of managing bowel health to promote high quality of sleep; and thus, improve quality of life in this subpopulation.
Redesign, Development and Construction of Powered Burner Head

This paper presents the redesign of a burner mixing head that used on High Static Gas burner (HSG) product to mix the gas and air mixture before it is ignited. This burner operates in firing range of 60,000-400,000 Btu/hr. The objective of redesigning the burner mixing head is to improve the overall performance of the HSG burner. This design project deals with the mixing head of a powered gas burner utilizing both natural and propane gases. The mixing head’s function in a powered gas burner is to initiate the fuel gas into an air stream. The redesigned burner mixing head increases combustion efficiency by 3% compared to the original burner head. This new burner mixing head operates within a wider range of excess air of 5% on both the lean and rich side while still igniting reliably and keeping the CO levels under 400 ppm. The redesigned burner mixing head design meets all the criteria of the American National Standards Institute ANSI Z21.17 standard for domestic gas conversion burners. The redesigned burner mixing head was machined out of 304 stainless steel which makes the burner head have corrosion resistant properties this includes using corrosion resistant fasteners.
Association between frontal fibrosing Alopecia and Rosacea: Results from clinical observational studies and gene expression profiles

Background In recent years, frontal fibrosing alopecia (FFA), a type of scarring alopecia, has attracted increasing attention. Several studies have reported the frequent occurrence of rosacea in FFA; however, the association between FFA and rosacea and the underlying pathogenesis have not been thoroughly clarified. Thus, this study aimed to quantify these relationships and investigate their shared molecular mechanisms. Methods We evaluated the association between FFA and rosacea by analyzing clinical data from nine observational studies. We then analyzed the gene expression profiles of FFA and rosacea. First, differential expression analysis and weighted gene co-expression network analysis were used to identify the common differentially expressed genes (DEGs). Later, we conducted a functional enrichment analysis and protein-protein interaction network and used seven algorithms to identify hub genes. Then, we performed a correlation analysis between the hub genes and the gene set variation analysis scores of common pathways in the gene set enrichment analysis (GSEA). The results were validated using different datasets. Finally, transcription factors were predicted and verified, and CIBERSORT and single-sample GSEA were used to estimate the infiltrating immune cells. Results Patients with FFA had significantly higher odds for rosacea (pooled odds ratio [OR], 2.46; 95% confidence interval [CI], 1.78–3.40), and the pooled prevalence of rosacea in patients with FFA was 23% (95% CI, 14–23%). Furthermore, we identified 115 co-DEGs and 13 hub genes (CCR5, CCL19, CD2, CD38, CD83, CXCL8, CXCL9, CXCL10, CXCL11, CXCR4, IRF1, IRF8, and PTPRC). Seven pathways showed a high correlation with these hub genes. In addition, one TF, STAT1, was highly expressed in both diseases, and the results of the immune infiltration analysis indicated the importance of M1 macrophages and effector memory CD8+ T cells. Conclusion This study contributes to the understanding of the relationship between FFA and rosacea, and based on the hub genes, we reveal the potential pathologies shared by the two diseases. This finding provides new insights of underlying molecular mechanisms and it may inspire future research on this comorbidity.
Hope and life satisfaction among Chinese shadow education tutors: The mediating roles of positive coping and perceived social support

Previous studies of the relationship between hope and life satisfaction left the underlying mechanism of how hope predicts life satisfaction unexplored to scholars. This study thus investigates the two potential mediators in the relationship between hope and life satisfaction among a sample of Chinese shadow education institution (SEI) tutors who may be under immense professional development pressure from a cross-sectional approach. The main body of the study consists of an online survey in which 221 SEI tutors reported their hope, positive coping, perceived social support, and life satisfaction. The survey results were analyzed using mediation and moderation analysis via SPSS 23.0. The results indicated that positive coping improved the relationship between hope and life satisfaction, supporting the hypothesis regarding the serial mediating effect of positive coping and perceived social support. In other words, tutors with a high level of hope tend to adopt positive coping strategies, thus will receive more social support and improve life satisfaction. Our findings revealed the independent and accumulative mediating effects of positive coping and perceived social support on the relationship between hope and life satisfaction, and had implications for the psychological intervention of SEI tutors who are currently facing enormous industry pressure.
Does urinary metabolite signature act as a biomarker of post-stroke depression?

Background It is difficult to conduct the precise diagnosis of post-stroke depression (PSD) in clinical practice due to the complex psychopathology of depressive disorder. Several studies showed that gas chromatography–mass spectrometry (GC-MS)-identified urinary metabolite biomarkers could significantly discriminate PSD from stroke survivors. Methods A systematic review was performed for the keywords of “urinary metabolite” and “PSD” using Medline, Cochrane Library, Embase, Web of Science, PsycINFO, Wanfang, CNKI, CBM, and VIP database from inception to 31 March 2022. Results Four related studies were included in the review. Differential urinary metabolites including lactic acid, palmitic acid, azelaic acid, and tyrosine were identified in all the included studies. As a significant deviation in the metabolite biomarker panel, glyceric acid, azelaic acid, phenylalanine, palmitic acid, pseudouridine, and tyrosine were found in at least 2 included studies, which indicated good potential for the differentiation of PSD. Conclusion The systematic review provided evidence that differential urinary metabolites analyzed by the GC-MS-based approach might be used as a biomarker for the diagnosis and prognosis of PSD.
Clinical relevance of the combined analysis of circulating tumor cells and anti-tumor T-cell immunity in metastatic breast cancer patients

Background Metastatic breast cancer (mBC) is a heterogeneous disease with varying responses to treatments and clinical outcomes, still requiring the identification of reliable predictive biomarkers. In this context, liquid biopsy has emerged as a powerful tool to assess in real-time the evolving landscape of cancer, which is both orchestrated by the metastatic process and immune-surveillance mechanisms. Thus, we investigated circulating tumor cells (CTCs) coupled with peripheral T-cell immunity to uncover their potential clinical relevance in mBC. Methods A cohort of 20 mBC patients was evaluated, before and one month after starting therapy, through the following liquid biopsy approaches: CTCs enumerated by a metabolism-based assay, T-cell responses against tumor-associated antigens (TAA) characterized by interferon-γ enzyme-linked immunosorbent spot (ELISpot), and the T-cell receptor (TCR) repertoire investigated by a targeted next-generation sequencing technique. TCR repertoire features were characterized by the Morisita’s overlap and the Productive Simpson Clonality indexes, and the TCR richness. Differences between groups were calculated by Fisher’s, Mann-Whitney or Kruskal-Wallis test, as appropriate. Prognostic data analysis was estimated by Kaplan-Meier method. Results Stratifying patients for their prognostic level of 6 CTCs before therapy, TAA specific T-cell responses were detected only in patients with a low CTC level. By analyzing the TCR repertoire, the highest TCR clonality was observed in the case of CTCs under the cut-off and a positive ELISpot response (p=0.03). Whereas, at follow-up, patients showing a good clinical response coupled with a low number of CTCs were characterized by the most elevated TCR clonality (p<0.05). The detection of CTCs≥6 in at least one time-point was associated with a lower TCR clonality (p=0.02). Intriguingly, by combining overall survival analysis with TCR repertoire, we highlighted a potential prognostic role of the TCR clonality measured at follow-up (p=0.03). Conclusion These data, whether validated in a larger cohort of patients, suggest that the combined analysis of CTCs and circulating anti-tumor T-cell immunity could represent a valuable immune-oncological biomarker for the liquid biopsy field. The clinical application of this promising tool could improve the management of mBC patients, especially in the setting of immunotherapy, a rising approach for BC treatment requiring reliable predictive biomarkers.
RPP40 is a prognostic biomarker and correlated with tumor microenvironment in uterine corpus endometrial carcinoma

Ribonuclease P/MRP Subunit P40 (RPP40), a component of ribonuclease P and multimeric ribonuclease P complex, was reported as one of the promoting factors for the chemoresistance of acute myeloid leukemia and a recurrence predictor of early-stage triple-negative breast cancer. However, the functional role of RPP40 in uterine corpus endometrial carcinoma (UCEC) is unclear. In this study, comprehensive bioinformatic analyses were conducted to explore the predictive role of RPP40 on UCEC diagnosis and prognosis, as well as the underlying mechanism. Differential analyses of multiple databases showed that both messenger RNA (mRNA) and the protein expression of RPP40 were significantly upregulated in UCEC tumor tissues. Furthermore, the RPP40 mRNA expression level was significantly correlated with the clinicopathological characteristics of UCEC patients, including the clinical stage, primary therapy outcome, histological type, histologic grade, overall survival event, disease-specific survival event, and progression-free interval event. Receiver operating characteristic (ROC) analysis showed that RPP40 was a reliable predictor for UCEC diagnosis with an area under the curve (AUC) of 0.775, a sensitivity of 0.829, and a specificity of 0.719. Kaplan–Meier, Cox regression, and nomogram analyses showed that high RPP40 expression was an independent prognostic factor for the 1-year, 3-year, and 5-year survival of UCEC patients. In addition, the enrichment analysis of RPP40-associated differentially expressed genes and correlation analyses showed that the expression of RPP40 was correlated with the regulation of extracellular matrix and immune cell infiltration. In conclusion, the upregulation of RPP40 is significantly correlated with the poor survival and tumor microenvironment of UCEC, suggesting that RPP40 is a promising biomarker of poor prognosis and a potential target of chemotherapy or immunotherapy in UCEC.
Age group differences in blubber fatty acid profiles in northern elephant seals (Mirounga angustirostris)

Northern elephant seals (Mirounga angustirostris), like many marine mammals, rely on internal lipid stores, specifically fatty acids (FAs) stored in the blubber layer, to meet metabolic needs. The energetic demands of northern elephant seals vary with ontogeny, as each life-history stage experiences different metabolic requirements due to development, growth, and breeding. To date, no comprehensive study has reported on changes in blubber FA profiles across northern elephant seal age groups or sex. Therefore, our objective was to determine how blubber FAs differ across ontogeny and sex in northern elephant seals. As a sexually dimorphic mammal, northern elephant seals go through sex-specific ontogenetic changes in morphology and physiology; we hypothesized that these changes would be reflected in their FAs profiles. To determine this, FAs profiles were compared from full blubber cores collected from 79 northern elephant seals across four age groups. We provide the first evidence of blubber fatty acids differing across ontogeny as NES transition from young, developing seals to mature fully developed adults. However, we did not find differences in blubber FAs profiles between the sexes. Monounsaturated fatty acids (MUFAs) are found in the highest proportions across all NES age classes and sexes, followed by SFAs and PUFAs; this highlights the important role MUFAs play in maintaining fluidity of the blubber layer and in thermoregulation. The individual FAs with the highest concentrations (C16:1, C18:1n9 and C16:0) in northern elephant seal blubber are similar to those in other marine mammals. Weaned pup FAs profiles were significantly different from all other age classes; adults and juveniles also showed age-specific differences. Specifically, weaned pups had the highest proportions of SFAs and the lowest proportions of PUFA, suggesting use of PUFAs to aid development. Each life history stage of NES is interconnected to previous and future stages, making FA accumulation, mobilization, and storage an important process throughout an individual’s life. Further, any changes to this process can have cascading consequences throughout ontogeny in this species. Future monitoring of the FA composition of blubber across age classes could potentially indicate the costs of different environmental changes on blubber storage in NES.
HEAD: an FHE-based Privacy-preserving Cloud Computing Protocol with Compact Storage and Efﬁcient Computation

—Fully homomorphic encryption (FHE) provides a natural solution for privacy-preserving cloud computing, but a straightforward FHE protocol may suffer from high computational overhead and a large ciphertext expansion rate, especially for computation-intensive tasks over large data, which are the main obstacles toward practical privacy-preserving cloud computing. In this paper, we present HEAD, a generic privacy-preserving cloud computing protocol that can be based on most mainstream (typically a BGV or GSW style scheme) FHE schemes with more compact storage and less computational costs than the straightforward FHE counterpart. In particular, our protocol enjoys a ciphertext/plaintext expansion rate of 1 (i.e., no expansion) in a cloud computing server, instead of a factor of hundreds of thousands. This is achieved by means of “pseudoran-domly masked” ciphertexts, and the efﬁcient transformations of them into FHE ciphertexts to facilitate privacy-preserving cloud computing. Depending on the underlying FHE in use, our HEAD protocol can be instantiated with the three masking techniques, namely modulo-subtraction-masking, modulo-division-masking, and XOR-masking, to support the decimal integer, real, or binary messages. Thanks to these masking techniques, various homomorphic computation tasks are made more efﬁcient and less prone to noise accumulation. Furthermore, our multi-input masking and unmasking operations are more ﬂexible than the FHE SIMD-batching, by supporting an on-demand conﬁguration of FHE during each cloud computing request. We evaluate the performance of HEAD protocols on BFV, BGV, CKKS, and FHEW schemes based on the PALISADE
The Rise of Safe Seats and Party Indiscipline in the U.S. Congress

Scholarly work has missed the key reason for the extraordinary levels of political polarization and poor governance in American politics in recent years. Contrary to the appearance that strong party leaders dictate member behavior, we argue that weak party discipline produces polarizing rhetoric in lieu of actionable policy proposals. We attribute this weak discipline to the rising number of safe House districts that play into the hands of extreme primary electorates. First, we provide comprehensive historical evidence of the rise of safe seats in U.S. House districts and show that this trend coincides with the greater divergence of legislators’ preferences not just between but also within parties. Second, we demonstrate that representatives from safer districts—and especially those from the GOP—have more ideologically extreme and divergent preferences across multiple alternative measures. We then use redistricting as a plausible source of exogenous variation in electoral competition and corroborate that seat safety causes ideological extremism. Finally, we explore the potential mechanisms behind this relationship, showing that the more-extreme ideological tendencies in safer seats are likely present due to a combination of more extreme electorates, primary challengers, and donor influence there, which can all undermine legislators’ willingness to support their party agendas.