Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular cloning, expression, and in situ hybridization analysis of MnGPx-3 and MnGPx-4 from oriental river prawn, Macrobrachium nipponense, in response to hypoxia and reoxygenation

Glutathione peroxidase (GPx) has been the focus of increased research because of its important role as an antioxidant and in reactive oxygen species (ROS) induced damage repair. Studies on GPxs have relevance with Macrobrachium nipponense because it has poor tolerance to hypoxia in Macrobrachium nipponense. The two subunits named as MnGPx-3 and MnGPx-4 according to the glutathione peroxidase nomenclature system. Both full-length cDNAs were cloned from the hepatopancreas. In this study, we analyzed the expression of two GPxs in Macrobrachium nipponense in response to changes in environmental oxygen. Expression levels of MnGPx-3 and MnGPx-4 indicated that both have strong responses to hypoxia. In situ hybridization showed that MnGPx-3 and MnGPx-4 were located in secretory and storage cells in hepatopancreas. These results suggest that GPx gene is expressed and released by secretory cells and released response to hypoxia. In the gill tissue, however, GPxs are located in blood cells, suggesting that they perform different functions in different tissues or organs. The results of in situ hybridization were consistent with those of quantitative Real-time PCR. This study provides a basis for understanding the oxidative stress response in M. nipponense under hypoxia.
Computational prediction of hemodynamical and biomechanical alterations induced by aneurysm dilatation in patient‐specific ascending thoracic aortas

The aim of the present work is to propose a robust computational framework combining computational fluid dynamics (CFD) and 4D flow MRI to predict the progressive changes in hemodynamics and wall rupture index (RPI) induced by aortic morphological evolutions in patients harboring ascending thoracic aortic aneurysms (ATAAs). An analytical equation has been proposed to predict the aneurysm progression based on age, sex, and body surface area. Parameters such as helicity, wall shear stress (WSS), time‐averaged WSS, oscillatory shear index, relative residence time, and viscosity were evaluated for two patients at different stages of aneurysm growth, and compared with age‐sex‐matched healthy subjects. The study shows that evolution of hemodynamics and RPI, despite being very slow in ATAAs, is strongly affected by morphological alterations and, in turn could impact biomechanical factors and aortic mechanobiology. An aspect of the current work is that the patient‐specific 4D MRI data sets were obtained with a follow‐up of 1 year and the measured time‐averaged velocity maps and flow eccentricity were compared with the CFD simulation for validation. The computational framework presented here is capable of capturing the blood flow patterns and the hemodynamic descriptors during the various stages of aneurysm growth. Further investigations will be conducted in order to verify these results on a larger cohort of patients and with long follow‐up times to finally elucidate the link between deranged hemodynamics, AA geometry, and wall mechanical properties in ATAAs.
Infrastructural Challenges Lead to Delay of Curative Radiotherapy in Nigeria

PURPOSE In low- and middle-income countries, there has been an exponential increase in cancer incidence. According to the International Atomic Energy Agency, the biggest gap in radiotherapy availability and need is in Nigeria, where each machine serves an estimated 25.7 million people. This study aimed to characterize the barriers to radiotherapy and to identify areas for intervention. METHODS This was a cross-sectional study conducted at the University College Hospital in Ibadan, Nigeria, from June 2017 to August 2017. Demographic, sociocultural, and infrastructural factors relating to radiotherapy were collected through a questionnaire (N = 186). Ordinal logistic regression was used to identify the factors leading to delays in referral and delays in treatment initiation. RESULTS Patients traveled from 20 of Nigeria’s 36 states. The median age was 50 years (range, 19-79 years). The most common cancers treated were breast (37.5%), cervical (16.3%), head and neck (11.9%), and prostate (10.9%). In ordinal logistic regression, sociocultural factors, including the inability to pay (odds ratio [OR], 1.99; P = .034), a bad hospital experience (OR, 7.05; P = .001), and travel time (OR, 1.36; P = .001), increased the odds of referral delay to radiotherapy. In contrast, there was no significant relationship between time to treatment initiation and sociocultural factors including age, education, and inability to pay. Infrastructural barriers, including machine breakdown (OR, 2.92; P = .001), worker strikes (OR, 2.64; P = .001), and power outages (OR, 2.81; P = .022), increased the odds of treatment delay. CONCLUSION Although delays caused by patient factors are reported extensively, patients overcame these barriers in the hopes of curative treatment. However, staff and equipment malfunctions prevented patients from receiving timely radiotherapy. Policies aimed at addressing machine maintenance, health care worker satisfaction, and the aging power grid in Nigeria must be implemented in the future to strengthen the health care system to care for patients with cancer.
The health status of transgender and gender nonbinary adults in the United States

The goal of this exploratory study was to delineate health differences among transgender subpopulations (transgender women/TW, transgender men/TM, gender nonbinary/GNB adults). 2015 Behavioral Risk Factor Surveillance System data were analyzed to compare the health of three groups (TW:N = 369; TM:N = 239; GNB:N = 156). Logistic regression and adjusted odds ratios were used to determine whether health outcomes (fair/poor health, frequent physical and mental unhealthy days, chronic health conditions, and health problems/impairments) are related to group and its interaction with personal characteristics and socioeconomic position. Group was a significant predictor of fair/poor health and frequent mental unhealthy days, revealing significant health differences between the transgender groups. The odds of poor/fair health were approximately 2.5 times higher in TM and GNB adults relative to TW. The odds of frequent mental unhealthy days for TM were approximately 1.5–2 times greater than TW and GNB adults. Among those with health insurance, the odds of fair/poor health for GNB adults was more than 1.5–2 times higher that of TM and TW. Among those without health insurance, TM had over 7 times greater odds of fair/poor health than TW. This study underscores the importance of classifying and examining the health of the transgender population as unique subpopulations, as notable health differences were discovered. TM and GNB adults have significant health concerns, requiring the attention of clinical interventions aimed at promoting health and preventing illness.
Evolution of Ty1 copy number control in yeast by horizontal transfer and recombination

Transposable elements constitute a large fraction of most eukaryotic genomes. Insertion of mobile DNA sequences typically has deleterious effects on host fitness, and thus diverse mechanisms have evolved to control mobile element proliferation. Mobility of the Ty1 retrotransposon in Saccharomyces yeasts is regulated by copy number control (CNC) mediated by a self-encoded restriction factor derived from the Ty1 gag capsid gene that inhibits virus-like particle function. Here, we survey a panel of wild and human-associated strains of S. cerevisiae and S. paradoxus to investigate how genomic Ty1 content influences variation in Ty1 mobility. We observe high levels of mobility for a tester element with a gag sequence from the canonical Ty1 subfamily in permissive strains that either lack full-length Ty1 elements or only contain full-length copies of the Ty1’ subfamily that have a divergent gag sequence. In contrast, low levels of canonical Ty1 mobility are observed in restrictive strains carrying full-length Ty1 elements containing a canonical gag sequence. Phylogenomic analysis of full-length Ty1 elements revealed that Ty1’ is the ancestral subfamily present in wild strains of S. cerevisiae, and that canonical Ty1 in S. cerevisiae is a derived subfamily that acquired gag from S. paradoxus by horizontal transfer and recombination. Our results provide evidence that variation in the ability of S. cerevisiae and S. paradoxus strains to repress canonical Ty1 transposition via CNC is regulated by the genomic content of different Ty1 subfamilies, and that self-encoded forms of transposon control can spread across species boundaries by horizontal transfer.
Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: A retrospective study

Background Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients. Methods We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors. Results A total of 455 patients were treated with cisplatin during the period. Of these, 34 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 43.1± 20.1%, respectively; P = 0.010]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 64%, respectively; P = 0.026). Conclusions DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients.
Correlating the passive response of eye and brain to head impact using MEMS IMUs on 3D-printed human head phantom

The eye may act as a surrogate for the brain in response to head acceleration during an impact. This paper reports the latest demonstration of the correlation between the passive human eye accelerations and the brain accelerations under head impacts using a model eye/brain/skull phantom. Experiments investigating rotational and linear accelerations were performed on a 3D-printed human head phantom, along with rotational experiments on a human volunteer. Data acquired during the passive eye response (PER) periods were processed and analysed using statistical methods including one-way normal analysis of variance, linear regression fit, and Pearson R correlation. The results have shown that, at least on the 3D-printed human head phantom, strong correlations can be found between the eye and the brain during the PER, which indicates a potential use of microelectromechanical systems inertial measurement units in real-time on-field monitoring and diagnosis of concussions or traumatic brain injuries. These discoveries pave the way for potential non-invasive wearable devices based on this technology to be applied in real-time on-field concussion monitoring, which is expected to provide vulnerable parties with instant alert thus timely treatment.
“Wonderful! We’ve just missed the bus.” – Parental use of irony and children’s irony comprehension

Irony is one of the linguistic means in which intended and expressed meaning diverge. It serves social-communicative functions, requires the understanding of the speaker's mental state and its comprehension takes place at an advanced stage of language acquisition. In the present study, we investigated 8-year old’s irony comprehension and social skills and asked their parents about their preferred use of irony towards their children. We then compared children with the highest scores in irony comprehension test with those with lower scores. The full sample included 46 families from Poland. Results show positive associations between children’s levels of irony comprehension and levels of mothers irony use. No such relations were found for fathers. No differences were found in ToM scores between proficient and non-proficient irony comprehenders. Our findings provide a base for future studies to study the use of irony in child-parent talk in more diverse culturally and linguistically diverse populations.
Ribose-cysteine protects against the development of atherosclerosis in apoE-deficient mice

Ribose-cysteine is a synthetic compound designed to increase glutathione (GSH) synthesis. Low levels of GSH and the GSH-dependent enzyme, glutathione peroxidase (GPx), is associated with cardiovascular disease (CVD) in both mice and humans. Here we investigate the effect of ribose-cysteine on GSH, GPx, oxidised lipids and atherosclerosis development in apolipoprotein E-deficient (apoE-/-) mice. Female 12-week old apoE-/- mice (n = 15) were treated with 4–5 mg/day ribose-cysteine in drinking water for 8 weeks or left untreated. Blood and livers were assessed for GSH, GPx activity and 8-isoprostanes. Plasma alanine transferase (ALT) and lipid levels were measured. Aortae were quantified for atherosclerotic lesion area in the aortic sinus and brachiocephalic arch and 8-isoprostanes measured. Ribose-cysteine treatment significantly reduced ALT levels (p<0.0005) in the apoE-/- mice. Treatment promoted a significant increase in GSH concentrations in the liver (p<0.05) and significantly increased GPx activity in the liver and erythrocytes of apoE-/-mice (p<0.005). The level of 8-isoprostanes were significantly reduced in the livers and arteries of apoE-/- mice (p<0.05 and p<0.0005, respectively). Ribose-cysteine treatment showed a significant decrease in total and low density lipoprotein (LDL) cholesterol (p<0.05) with no effect on other plasma lipids with the LDL reduction likely through upregulation of scavenger receptor-B1 (SR-B1). Ribose-cysteine treatment significantly reduced atherosclerotic lesion area by >50% in both the aortic sinus and brachiocephalic branch (p<0.05). Ribose-cysteine promotes a significant GSH-based antioxidant effect in multiple tissues as well as an LDL-lowering response. These effects are accompanied by a marked reduction in atherosclerosis suggesting that ribose-cysteine might increase protection against CVD.
Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma

Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity.
Electrolyte-Dependent Supercapacitor Performance on Nitrogen-Doped Porous Bio-Carbon from Gelatin

The carbon supercapacitance strongly relies upon the electrolyte’s nature, but the clear-cut structure–performance nexus remains elusive. Herein, a series of bio-carbons with gradually varied pore structure and surface chemistry are derived using a new salt template protocol (with eco-benign KNO3 as the template, activator, and porogen, and cheap gelatin as the carbon precursor), and are used as model systems to probe the dependence of the electrochemical mechanism of such nanocarbons on two typical electrolytes (KOH and EMIBF4). By only adjusting the KNO3 dosage, two pivotal figures of merit of biochar—multiscale porosity and surface functionalization—were finely modulated to construct electric double layers. Electrochemical data clarify that the combined porosity and doping effects all contribute to enhanced supercapacitance, but with only one of the two factors playing the leading role in different electrolytes. Kinetic analysis corroborates the fact that ample heteroatom doping can effectively compensate capacitance by intensive surface redox insertion in KOH, while a suitable pore size dispersion plays a preponderant part in self-amplifying the ion partitioning, and thus dictating a good charge separation in EMIBF4. A quasi-quantitative model of performance–structure relevance in EMIBF4 is judiciously conjectured to hint at a superb ion–pore-size compatibility, in which the bi- and mono-layer ion confinement coupling in integrated single and double ion-sized pores is found to be more useful for curbing notorious over-screening effects and for changing the coordination number, Coulombic ordering, and phase conformation of EMIBF4 in several nm-sized nanopores. This unique energy storage fashion in ion-matching pores promotes the energy density of optimal samples to a novel level of 88.3 Wh kg−1 at 1 kW kg−1, which rivals the overwhelming majority of the reported carbon materials. In short, the comparison case study here reveals a valuable correlation of carbon’s figure of merit and electrolyte type, which may act as a vital rudder to design electrolyte-contingent state-of-the-art supercapacitor materials.
Efficacy, Safety, and Biomarkers of Toripalimab in Patients with Recurrent or Metastatic Neuroendocrine Neoplasms: A Multiple-Center Phase Ib Trial

Purpose: Patients with recurrent or metastatic neuroendocrine neoplasms (NEN) had a poor prognosis and few treatment options. Toripalimab, a humanized IgG4 antibody specific for human PD-1 receptor, was first approved to treat second-line metastatic melanoma in China in 2018. Patients and Methods: The multiple-center phase Ib trial enrolled patients with NENs (Ki-67 ≥ 10%) after failure of first-line therapy received 3 mg/kg toripalimab once every two weeks. The primary objective was objective response rate (ORR) and safety. PD-L1 expression and whole-exome sequencing were performed on tumor biopsies. Secondary objectives included duration of response (DOR), disease control rate (DCR), and progression-free survival and overall survival. Results: Of 40 patients included from April 2017 to December 2018, 8 partial responses and 6 stable diseases were observed, for a 20% ORR and a 35% DCR. The median DOR was 15.2 months. Patients with PD-L1 expression (≥10%) or high tumor mutational burden (TMB) had better ORR than PD-L1 <10% (50.0% vs. 10.7%, P = 0.019) and TMB-low patients (75.0% vs. 16.1%, P = 0.03). Three of 8 (37.5%) responders harbored ARID1A mutations, whereas only 1 of 27 nonresponders had mutations (P = 0.03). Of note, 1 exceptional responder with TMB-L, microsatellite stable (MSS), and PD-L1–negative had multiple genomic arrangements with high prediction score for neoantigens. Conclusions: Toripalimab had antitumor activity and safety in treating recurrent or metastatic NENs. Patients with positive PD-L1 expression, TMB-H (top 10%), and/or microsatellite instable (MSI-H) might preferentially benefit from the treatment. The genomic mutation of ARID1A and high genomic rearrangements might be correlated with clinical benefit.
Dietary Habits and Dietary Antioxidant Intake Are Related to Socioeconomic Status in Polish Adults: A Nationwide Study

The aim of this study was to estimate dietary habits and dietary antioxidant intake in a Polish adult population in relation to socioeconomic status. The subjects (4774) were participants in the Polish National Multi-Centre Health Examination Survey (the WOBASZ II study) performed in 2013–2014. Socioeconomic status (SES) scores were calculated by multiplying ordinal numerical values assigned to consecutive categories of education level and monthly income per capita in a family. In the Polish adult population, a higher socioeconomic status was significantly associated with a better lifestyle (more physical activity and less smoking), a better health status (lower occurrence of overweight individuals and metabolic syndrome in both genders, and lower occurrence of central obesity, hypertension, and diabetes in women), and better dietary habits, including a higher intake of dietary antioxidants.
Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study

A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with survival in nivolumab-treated metastatic non-small cell lung cancer (NSCLC) patients. Plasma biomarkers were assayed at baseline and after two cycles of nivolumab. A cut-off of positivity for sPD-1, sPD-L1 and sCD40L expressions was defined as a plasma level above the lower limit of quantification. Baseline sPD-1 and sPD-L1 levels were subsequently analyzed in a control group of EGFR-mutated (Epidermal Growth Factor Receptor) NSCLC patients. Association between survival and biomarkers was investigated using Cox proportional hazard regression model. Eighty-seven patients were included (51 nivolumab-treated patients, 36 in EGFR-mutated group). In nivolumab group, baseline sPD-1, sPD-L1 and sCD40L were positive for 15(29.4%), 27(52.9%) and 18(50%) patients, respectively. We defined a composite criteria (sCombo) corresponding to sPD-1 and/or sPD-L1 positivity for each patient. In nivolumab group, baseline sCombo positivity was associated with shorter median progression-free survival (PFS) (78 days 95%CI (55–109) vs. 658 days (222-not reached); HR: 4.12 (1.95–8.71), p = 0.0002) and OS (HR: 3.99(1.63–9.80), p = 0.003). In multivariate analysis, baseline sCombo independently correlated with PFS (HR: 2.66 (1.17–6.08), p = 0.02) but not OS. In EGFR-mutated group, all patients were baseline sCombo positive; therefore this factor was not associated with survival. After two cycles of nivolumab, an increased or stable sPD-1 level independently correlated with longer PFS (HR: 0.49, 95%CI (0.30–0.80), p = 0.004) and OS (HR: 0.39, 95%CI (0.21–0.71), p = 0.002). VEGFA, sCD40L and sCD44 did not correlate with survival. We propose a composite biomarker using sPD-1and sPDL-1 to predict nivolumab efficacy in NSCLC patients. A larger validation study is warranted.