Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-talk between YAP and RAR-RXR Drives Expression of Stemness Genes to Promote 5-FU Resistance and Self-Renewal in Colorectal Cancer Cells

The mechanisms whereby the Hippo pathway effector YAP regulates cancer cell stemness, plasticity, and chemoresistance are not fully understood. We previously showed that in 5-fluorouracil (5-FU)–resistant colorectal cancer cells, the transcriptional coactivator YAP is differentially regulated at critical transitions connected with reversible quiescence/dormancy to promote metastasis. Here, we found that experimental YAP activation in 5-FU–sensitive and 5-FU–resistant HT29 colorectal cancer cells enhanced nuclear YAP localization and the transcript levels of the retinoic acid (RA) receptors RARα/γ and RAR target genes CYP26A1, ALDH1A3, and LGR5 through RA Response Elements (RARE). In these two cell models, constitutive YAP activation reinforced the expression of the stemness biomarkers and regulators ALDH1A3, LGR5, and OCT4. Conversely, YAP silencing, RAR/RXR inhibition by the pan-RAR antagonist BMS493, and vitamin A depletion downregulated stemness traits and self-renewal. Regarding the mechanisms engaged, proximity-dependent labeling, nuclear YAP pulldown coupled with mass spectrometry, and chromatin immunoprecipitation (ChIP)/re-ChIP experiments revealed: (i) the nuclear colocalization/interaction of YAP with RARγ and RXRs; and (ii) combined genomic co-occupancy of YAP, RARα/γ, and RXRα interactomes at proximal RAREs of LGR5 and ALDH1A3 promoters. Moreover, activation of the YAP/RAR-RXR cross-talk in colorectal cancer cells promoted RAR self-activation loops via vitamin A metabolism, RA, and active RAR ligands generated by ALDH1A3. Together, our data identify YAP as a bona fide RAR-RXR transcriptional coactivator that acts through RARE-activated stemness genes. Implications: Targeting the newly identified YAP/RAR-RXR cross-talk implicated in cancer cell stemness maintenance may lead to multitarget combination therapies for patients with colorectal cancer.
Use of Artificial Intelligence to understand adults’ thoughts and behaviours relating to COVID-19

Aims: The outbreak of severe acute respiratory syndrome coronavirus 2 (COVID-19) is a global pandemic that has had substantial impact across societies. An attempt to reduce infection and spread of the disease, for most nations, has led to a lockdown period, where people’s movement has been restricted resulting in a consequential impact on employment, lifestyle behaviours and wellbeing. As such, this study aimed to explore adults’ thoughts and behaviours in response to the outbreak and resulting lockdown measures. Methods: Using an online survey, 1126 adults responded to invitations to participate in the study. Participants, all aged 18 years or older, were recruited using social media, email distribution lists, website advertisement and word of mouth. Sentiment and personality features extracted from free-text responses using Artificial Intelligence methods were used to cluster participants. Results: Findings demonstrated that there was varied knowledge of the symptoms of COVID-19 and high concern about infection, severe illness and death, spread to others, the impact on the health service and on the economy. Higher concerns about infection, illness and death were reported by people identified at high risk of severe illness from COVID-19. Behavioural clusters, identified using Artificial Intelligence methods, differed significantly in sentiment and personality traits, as well as concerns about COVID-19, actions, lifestyle behaviours and wellbeing during the COVID-19 lockdown. Conclusions: This time-sensitive study provides important insights into adults’ perceptions and behaviours in response to the COVID-19 pandemic and associated lockdown. The use of Artificial Intelligence has identified that there are two behavioural clusters that can predict people’s responses during the COVID-19 pandemic, which goes beyond simple demographic groupings. Considering these insights may improve the effectiveness of communication, actions to reduce the direct and indirect impact of the COVID-19 pandemic and to support community recovery.
Nitrogen use efficiency in lowland rice genotypes

Nitrogen (N) is one of the most yield-limiting nutrients in lowland rice production around the world. Use of N efficient genotypes is an important complementary strategy in improving rice yield and reducing cost of production. A greenhouse experiment was conducted at the Embrapa Rice & Beans, Santo Antonio de Goiás, Brazil, with the objective to evaluate N use efficiency of eight lowland (Oryza sativa L.) genotypes. The soil used in the experiment was an Inceptisol and two N levels used were without N application (low level) and an application of 304 mg N kg−1 of soil (high level). Grain yield and yield components and N uptake parameters were significantly affected by genotype and N treatments except the N uptake in shoot. On the basis of N-use efficiency (mg grain weight/mg N accumulated in shoot and grain) and grain yield at zero N, genotypes were classified as efficient and responsive (ER), efficient and nonresponsive (ENR), nonefficient and responsive (NER), and nonefficient and nonresponsive (NENR). Genotypes Rio Formoso, CNA 7550, and CNA 7556 were classified as ER, and genotypes Javaé and CNA 6343 were classified as ENR. In the group, NER was classified genotype CNA 7857. In the group, NENR were falled genotypes CNA 8319 and CNA 8619. From a practical point of view, genotypes which produce high grain yield in a low level of N and respond well to added N are the most desirable because they are able to express their high yield potential in a wide range of N environment. Correlation analysis showed that shoot dry weight, number of panicles, number of grains per panicle, grain harvest index, N uptake in shoot and grain, N harvest index, and N use efficiency having significant positive association with grain yield.
Cortical Tracking of Speech: Toward Collaboration between the Fields of Signal and Sentence Processing

Abstract In recent years, a growing number of studies have used cortical tracking methods to investigate auditory language processing. Although most studies that employ cortical tracking stem from the field of auditory signal processing, this approach should also be of interest to psycholinguistics—particularly the subfield of sentence processing—given its potential to provide insight into dynamic language comprehension processes. However, there has been limited collaboration between these fields, which we suggest is partly because of differences in theoretical background and methodological constraints, some mutually exclusive. In this paper, we first review the theories and methodological constraints that have historically been prioritized in each field and provide concrete examples of how some of these constraints may be reconciled. We then elaborate on how further collaboration between the two fields could be mutually beneficial. Specifically, we argue that the use of cortical tracking methods may help resolve long-standing debates in the field of sentence processing that commonly used behavioral and neural measures (e.g., ERPs) have failed to adjudicate. Similarly, signal processing researchers who use cortical tracking may be able to reduce noise in the neural data and broaden the impact of their results by controlling for linguistic features of their stimuli and by using simple comprehension tasks. Overall, we argue that a balance between the methodological constraints of the two fields will lead to an overall improved understanding of language processing as well as greater clarity on what mechanisms cortical tracking of speech reflects. Increased collaboration will help resolve debates in both fields and will lead to new and exciting avenues for research.
Performance in Major League Baseball Pitchers After Surgical Treatment of Thoracic Outlet Syndrome

Objectives: Thoracic outlet syndrome (TOS) can be a career threatening injury for baseball pitchers. The purpose of this study is to determine the efficacy of surgical management for TOS as a function of return to play and quantitative pitching metrics. Methods: Twenty-seven major league baseball pitchers underwent surgical treatment for TOS between January 2001 and December 2017. Analysis of pre and postoperative pitching metrics were used to assess the effect of surgery on 20 pitchers who returned to pitch in Major League Baseball (MLB). All pitching metrics were compared via assessing performance two years prior to surgery and two years after surgery. For 20 pitchers who returned to pitch, MLB pitching metrics of earned run average (ERA), walks plus hits per innings pitched (WHIP), wins above replacement (WAR), strikeouts per nine innings (K/9), average fastball velocity, and strike percentage, were used to assess a pitcher’s ability to return to preoperative performance level. Results: Of the 27 pitchers, 20 pitchers were diagnosed with neurogenic thoracic outlet syndrome (NTOS) and seven with venous thoracic outlet syndrome (VTOS). The average age of onset of TOS was 28.6 years. There was no significant difference between the age of onset between the NTOS and VTOS populations (p=0.272). Of the 27 pitchers, 20 (74.1%) were able to return to MLB play at a mean of 297 days (range, 105-638 days) after surgery. Pitching metrics demonstrated that pitcher ERA remained inferior postoperatively compared to baseline preoperative performance (3.66 vs 4.50, p=0.03). Fastball velocity (p=0.94), strike percentage (p=0.50), and K/9 (p=0.878) were equivalent to pre-injury performance. There was no difference in preoperative pitching metrics between pitchers who were able to return and pitchers who were unable to return to the MLB. Conclusions: About 3/4 of professional pitchers who undergo surgical intervention for TOS are able to return to play at the MLB level. With regards to performance, the majority of metrics were unchanged from prior to surgery, indicating return at a similar functional level.
Cyclophanes. Part LII: Ethynyl[2.2]paracyclophanes: New building blocks for molecular scaffolding

The synthesis of seven ethynyl[2.2]paracyclophanes is described. The five diethynyl derivatives 4,5-diethynyl[2.2]paracyclophane (12), pseudo-gem- (13), pseudo-ortho- (14), pseudo-meta(15), and pseudo-para-diethynyl[2.2]paracyclophane (16), the tetraethynyl compound 4,7,13,16-tetraethynyl[2.2]paracyclophane (17), and for comparison the mono-ethynylated hydrocarbon 4-ethynyl[2.2]paracyclophane (11) have been prepared. The structures of these new building blocks for carbon rich systems were determined by the usual analytical and spectroscopic methods.
Highly Water Soluble C60 Derivatives: A New Synthesis

Abstract Unprecedented protocol, consisting in reduction of Buckminsterfullerene with Na/K alloy and successive stirring in presence of O2, affords polyhydroxylated fullerenols which are highly water soluble, from strongly basic to medium acidic conditions. The products have been characterized by means of cross polarization magic angle spinning (CPMAS) NMR, 1H‐NMR, electron, FT‐IR, Raman and mass spectroscopies. Possible paths of reaction and the role of molecular oxygen in fullerene cage‐oxidation are discussed.
Impact of plasma IP-10/CXCL10 and RANTES/CCL5 levels on neurocognitive function in HIV treatment naïve patients.

BACKGROUND Immune activation, which is accompanied by the production of proinflammatory cytokines, is a strong predictor of disease progression in HIV infection. Inflammation is critical in neuronal damage linked to HIV-associated neurocognitive disorders. METHODS We examined the relationship between plasma cytokine levels and deficits in neurocognitive function. Multiplex profiling by Luminex ® technology was used to quantify 27 cytokines/chemokines from 139 plasma samples of PLWH. The relationship of plasma cytokine markers, clinical parameters and cognitive impairment, was assessed using Spearman correlations. Partial least squares (PLS) regression and Variable importance in projection (VIP) scores were used for further evaluation of the association. RESULTS Forty-nine (35.3%) participants exhibited neurocognitive impairment based on a GDS of at least 0.5 and 90 (64.7%) were classified as non-impaired. 23 (16.5%) initiated on cART for 4 weeks prior to cognitive assessment and 116 (83.5%) were not on treatment. We identified 5 proinflammatory cytokines that were significant predictors of GDS namely, IP10 (β = 0.058; p = 0.007), RANTES (β = 0.049; p = 0.005), IL2 (β = 0.047, p = 0.006), Eotaxin (β = 0.042, p = 0.003), and IL7 (β = 0.039, p = 0.003). IP10 and RANTES were the strongest predictors of GDS. Both cytokines correlated with plasma viral load and lymphocyte proviral load and were inversely correlated with CD4+ T cell counts. IP-10 and RANTES formed a separate cluster with highest proximity Conclusion: Study findings describe novel associations between IP-10, RANTES, cognitive status, plasma viral load and cell-associated viral load.
Respectful maternity care delivered within health facilities in Bangladesh, Ghana and Tanzania: a cross-sectional assessment preceding a quality improvement intervention

Objective To assess respectful maternity care (RMC) in health facilities. Design Cross-sectional study. Setting Forty-three (43) facilities across 15 districts in Bangladesh, 16 in Ghana and 12 in Tanzania. Participants Facility managers; 325 providers (nurses/midwives/doctors)—Bangladesh (158), Ghana (86) and Tanzania (81); and 849 recently delivered women—Bangladesh (295), Ghana (381) and Tanzania (173)—were interviewed. Observation of 641 client–provider interactions was conducted—Bangladesh (387), Ghana (134) and Tanzania (120). Assessment Trained social scientists and clinicians assessed infrastructure, policies, provision and women’s experiences of RMC (emotional support, respectful care and communication). Primary outcome RMC provided and/or experienced by women. Results Three (20%) facilities in Bangladesh, four (25%) in Ghana and three (25%) in Tanzania had no maternity clients’ toilets and one-half had no handwashing facilities. Policies for RMC such as identification of client abuses were available: 81% (Ghana), 73% (Bangladesh) and 50% (Tanzania), but response was poor. Ninety-four (60%) Bangladeshi, 26 (30%) Ghanaian and 20 (25%) Tanzanian providers were not RMC trained. They provided emotional support during labour care to 107 (80%) women in Ghana, 95 (79%) in Tanzania and 188 (48.5%) in Bangladesh, and were often courteous with them—236 (61%) in Bangladesh, 119 (89%) in Ghana and 108 (90%) in Tanzania. Due to structural challenges, 169 (44%) women in Bangladesh, 49 (36%) in Ghana and 77 (64%) in Tanzania had no privacy during labour. Care was refused to 13 (11%) Tanzanian and 2 Bangladeshi women who could not pay illegal charges. Twenty-five (7%) women in Ghana, nine (6%) in Bangladesh and eight (5%) in Tanzania were verbally abused during care. Providers in all countries highly rated their care provision (95%–100%), and 287 (97%) of Bangladeshi women, 368 (97%) Ghanaians and 152 (88%) Tanzanians reported ‘satisfaction’ with the care they received. However, based on their facility experiences, significant (p<0.001) percentages—20% (Ghana) to 57% (Bangladesh)—will not return to the same facilities for future childbirth. Conclusions Facilities in Bangladesh, Ghana and Tanzania have foundational systems that facilitate RMC. Structural inadequacies and policy gaps pose challenges. Many women were, however, unwilling to return to the same facilities for future deliveries although they (and providers) highly rated these facilities.
Rational Design of Organic Semiconductors for Texture Control and Self‐Patterning on Halogenated Surfaces

Understanding the interactions at interfaces between the materials constituting consecutive layers within organic thin‐film transistors (OTFTs) is vital for optimizing charge injection and transport, tuning thin‐film microstructure, and designing new materials. Here, the influence of the interactions at the interface between a halogenated organic semiconductor (OSC) thin film and a halogenated self‐assembled monolayer on the formation of the crystalline texture directly affecting the performance of OTFTs is explored. By correlating the results from microbeam grazing incidence wide angle X‐ray scattering (μGIWAXS) measurements of structure and texture with OTFT characteristics, two or more interaction paths between the terminating atoms of the semiconductor and the halogenated surface are found to be vital to templating a highly ordered morphology in the first layer. These interactions are effective when the separating distance is lower than 2.5 dw, where dw represents the van der Waals distance. The ability to modulate charge carrier transport by several orders of magnitude by promoting “edge‐on” versus “face‐on” molecular orientation and crystallographic textures in OSCs is demonstrated. It is found that the “edge‐on” self‐assembly of molecules forms uniform, (001) lamellar‐textured crystallites which promote high charge carrier mobility, and that charge transport suffers as the fraction of the “face‐on” oriented crystallites increases.
The Condensation Reactions of Lignin Model Compounds in Alkaline Pulping Liquors

Abstract The significance of condensation reactions at the 5-position of the aromatic ring of lignin to the overall pulping process has been evaluated using lignin model compounds. Reactions of 5-hydroxymethylcreosol, as a model for 5-substituted lignins formed when formaldehyde is released during pulping, have shown that such groups will react via ortho-quinonemethides to give alkali-stable carbon-carbon bonded condensation products. The amount of condensation depends on the type of pulping liquor used, with less formed in the kraft and soda-anthraquinone (AQ) processes than in the soda process. In these liquors the hydrosulphide or anthrahydroquinone (AHQ) ions present can compete effectively with phenoxide ion for the reactive o-quinonemethide intermediate. Reduced AQ reacts with the o-quinonemethide to form oxanthrone- and anthrone-adducts which are still detectable at 170°C. Such reactions, particularly the reduction of AQ to its anthrone oxidation state, may be one of the reasons why AQ is consumed .
Using electronic health records and claims data to identify high-risk patients likely to benefit from palliative care.

OBJECTIVES Palliative care has been demonstrated to have positive effects for patients, families, health care providers, and health systems. Early identification of patients who are likely to benefit from palliative care would increase opportunities to provide these services to those most in need. This study predicted all-cause mortality of patients as a surrogate for patients who could benefit from palliative care. STUDY DESIGN Claims and electronic health record (EHR) data for 59,639 patients from a large integrated health care system were utilized. METHODS A deep learning algorithm-a long short-term memory (LSTM) model-was compared with other machine learning models: deep neural networks, random forest, and logistic regression. We conducted prediction analyses using combined claims data and EHR data, only claims data, and only EHR data, respectively. In each case, the data were randomly split into training (80%), validation (10%), and testing (10%) data sets. The models with different hyperparameters were trained using the training data, and the model with the best performance on the validation data was selected as the final model. The testing data were used to provide an unbiased performance evaluation of the final model. RESULTS In all modeling scenarios, LSTM models outperformed the other 3 models, and using combined claims and EHR data yielded the best performance. CONCLUSIONS LSTM models can effectively predict mortality by using a combination of EHR data and administrative claims data. The model could be used as a promising clinical tool to aid clinicians in early identification of appropriate patients for palliative care consultations.
Association of Metformin Use With Age-Related Macular Degeneration: A Case-Control Study.

Importance Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD. Objective To determine whether metformin use is associated with reduced odds of developing AMD. Design, Setting, and Participants This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020. Exposures Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims. Main Outcomes and Measures Risk of developing AMD. Results A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]). Conclusion and Relevance In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.