Miracle-dz/UniFAR-FTUs huggingface dataset:
Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma—Associations with Clinical Parameters and Patient Survival

Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the formation and progression of cancer. The aim of the study was to evaluate the expression of ephrin receptors EphA1, EphA5, and EphA7 in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. The study included 94 previously untreated patients who underwent enucleation due to uveal melanoma. High expression of EphA1 was positively correlated with a smaller tumor size, less frequent extra-scleral extension, lower mitotic activity, and more frequent vitreous hemorrhage. High expression of EphA5 was associated with less frequent chromosome 3 loss, absence of distant metastases, and more frequent vitreous hemorrhage. High expression of EphA7 was associated with a more frequent primary tumor location in the posterior pole. High EphA5 expression was associated with longer overall survival time. The above findings indicate that high expression of EphA1 and EphA5 can be considered a beneficial prognostic factor in uveal melanoma.
Reading High Breast Density Mammograms: Differences in Diagnostic Performance between Radiologists from Hong Kong SAR/Guangdong Province in China and Australia

Background: Variations in the performance of radiologists reading mammographic images are well reported, but key parameters explaining such variations in different countries are not fully explored. The main aim of this study is to investigate performances of Chinese (Hong Kong SAR and Guangdong Province) and Australian radiologists in interpreting dense breast mammographic images. Methods: A test set, contained 60 mammographic examinations with high breast density, was used to assess radiologists’ performance. Twelve Chinese and thirteen Australian radiologists read all the cases independently and were asked to identify all lesions and provide a grade from 1 to 5 to each lesion. Case sensitivity, specificity, lesion sensitivity, AUC and JAFROC were used to assess radiologists’ performances. Demographic information and reading experience were also collected from the readers. Performance scores were compared between the two populations and the relationships between performance scores and their reading experience were discovered. Results: For radiologists who were less than 40-year-old, lesion sensitivity, AUC and JAFROC were significantly lower in Chinese radiologists than those in Australian (52.10% vs 71.45%, p=0.043; 0.76 vs 0.84, p=0.031; 0.59 vs 0.72, p=0.045; respectively). Australian radiologists with less than 10 years of reading experience had higher AUC and JAFROC scores compared with their Chinese counterparts (0.83 vs 0.76, p=0.039; 0.70 vs 0.56, p=0.020, respectively). Conclusions: We found that younger Australian radiologists performed better at reading dense breast cases which is likely to be linked to intensive fellowship training, immersion in a screening program and exposure to the benefits of a performance-measuring education tool.
WD40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance of D. radiodurans

Abstract RqkA, a DNA damage responsive serine/threonine kinase, is characterized for its role in DNA repair and cell division in D. radiodurans. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β-propeller repeats held together via ‘tryptophan-docking motifs’ and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance in D. radiodurans and lacked γ radiation-mediated activation of kinase activity in vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate E. coli cells. Unlike wild-type enzyme, the kinase activity of its WD40 mutants was not stimulated by pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions in vivo, and thus, the role of WD40 domain in the regulation of any STPK is first time demonstrated in bacteria. Communicated by Ramaswamy H. Sarma
The Influence of Norm Perception on Pro-Environmental Behavior: A Comparison between the Moderating Roles of Traditional Media and Social Media

The activation of norm perception can promote pro-environmental behavior. How does media, as important variables in activating norm perception, affect pro-environmental behavior? Through an online survey of 550 randomly selected Chinese citizens, this study examines the roles of traditional media and social media in influencing the relationship between norm perception and pro-environmental behavior. Based on multi-level regression analysis of data, this study found that (1) compared with traditional media, social media play a more significant role in moderating the relationship between norm perception and pro-environmental behavior; (2) the promotion of the perception of injunctive norms by traditional media has a negative relationship with pro-environmental behaviors; (3) the activation of subjective norm perception by social media will promote pro-environmental behaviors. According to this research, in the current media environment, we should carefully release pro-environmental information on social media and encourage relevant discussions, and appropriately reduce environment-relevant injunctive normative information on traditional media. The study also discusses the role of media in regulating norm perception and pro-environmental behavior in different cultural contexts.
Rapid (FLASH-FLIM) imaging of protoporphyrin IX in a lipid mixture using a CMOS based widefield fluorescence lifetime imaging camera in real time for margin demarcation applications

The fluorescence from protoporphyrin IX (PpIX) has been employed to characterise cellular activity and assist in the visualisation of tumour cells. Its formation can be induced by 5-aminolevulonic acid (5-ALA) which is metabolised by tumour cells to form PpIX. The PpIX is localised within the cells, rather than spreading into the vascular system. This, plus its photophysics, exhibits potential in photodynamic therapy. Hence its study and the ability to rapidly image its localisation is of importance, especially in the field of fluorescence guided surgery. This has led to investigations using tissue phantoms and widefield intensity imaging. Aggregation or the presence of photoproducts can alter PpIX emission, which has implications using widefield imaging and a broad wavelength range detection. The use of the fluorescence lifetime imaging (FLIM) is therefore advantageous as it can distinguish between the emissive species as they exhibit different fluorescence lifetimes. Here we use PpIX in a construct consisting of lipid mixture (Intralipid), employed to simulate fat content and optical scattering, in a gellan gum matrix. PpIX in intralipid in aqueous solution was injected into the gellan host to form inclusions. The samples are imaged using commercial widefield TCSPC camera based on a sensor chip with 192 × 128 pixels. Each pixel contains both detection and photon timing enabling the Fluorescence Lifetime Acquisition by Simultaneous Histogramming (FLASH). This ‘FLASH-FLIM’ approach enables widefield fluorescence lifetime images, displayed in real time to be acquired, which has potential for use in visualising tumour boundaries.
Anti-Acne Effects of Cembrene Diterpenoids from the Cultured Soft Coral Sinularia flexibilis

Acne is a skin disease common in adolescents and increasingly common in the adult population. The major pathologic events of acne vulgaris include increased sebum production, retention hyperkeratosis, carrying commensal skin microbiota, and inflammation. In recent years, more than 10,000 compounds have been isolated and identified from marine organisms. The aim of this study was to discover the potential anti-acne activity of fraction 9 + 10 (SF-E) of Sinularia flexibilis extract and six cembrene diterpenoids. We found that the SF-E significantly reduced Cutibacterium acnes-induced edema in Wistar rat ears. The cembrene diterpenoids including 11-dehydrosinulariolide (SC-2), 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (SC-7), and sinularin (SC-9) reduced nitric oxide (NO) production with 50% inhibitory concentration of 5.66 ± 0.19, 15.25 ± 0.25, and 3.85 ± 0.25 μM, respectively, and inducible NO synthase expression in RAW 264.7 cells. Moreover, treatment with SC-2, SC-7, and SC-9 significantly suppressed lipopolysaccharide- and heat-killed C. acnes-induced expression of proteins involved in mitogen-activated protein kinase pathway in both RAW 264.7 and HaCaT cells. After treatment with SC-2, SC-7, and SC-9, over-proliferation of HaCaT cells was significantly terminated. In summary, SC-2, SC-7, and SC-9 showed anti-inflammatory effects in RAW 264.7 cells, suggesting that these cembrene diterpenoids obtained from S. flexibilis are natural marine products with potential anti-acne activities.
Anthocyanin Intake and Physical Activity: Associations with the Lipid Profile of a US Working Population

While growing evidence exists on the independent associations between anthocyanins and physical activity on cardiovascular disease (CVD) risk determinants, the possible interaction between these exposures has not yet been studied. We aimed to study the potential synergism between anthocyanin intake and physical activity on lipid profile measures. This cross-sectional study was conducted among 249 US career firefighters participating in the Feeding America’s Bravest trial. Anthocyanin intake was calculated using a validated food frequency questionnaire (FFQ) and physical activity level by a validated questionnaire. Multivariable linear regression models determined the extent to which anthocyanin intake and physical activity predicted lipid parameters. Generalized linear models were used for joint effect and interaction analyses on the multiplicative and additive scales. Both anthocyanins and physical activity were independently inversely associated with total cholesterol:high density lipoprotein (HDL) cholesterol. Only physical activity was inversely associated with triglycerides, low density lipoprotein (LDL) cholesterol:HDL, and triglycerides (TG):HDL. Although the combined exposure of low anthocyanin intake and low physical activity was associated with lower (RR = 2.83; 95% CI: 1.42 to 5.67) HDL cholesterol <40 mg/dL, neither multiplicative (p = 0.72) nor additive interactions were detected (relative excess risk due to interaction (RERI): 0.02; 95% CI: −1.63 to 1.66; p = 0.98). Our findings provide insight on the potential synergism between anthocyanin intake and physical activity on the lipid profile.
Transcritption regulation of soybean ribulose-1,5-bisphosphate carboxylase small subunit gene by external factors

Ribulose-1,5-bisphosphate carboxylase small subunit gene (rbcS) is present with multi-gene family in plant genome. In Glycine max, the rbcS polypeptide (EC4.1.1.39) is encoded by a gene family containing 4–8 members. Three full-length rbcS cDNA clones were isolated and characterized from soybean seedlings, and both of their nucleotide and amino acid sequences showed high similarity. Differential accumulation of the rbcS mRNA was observed among roots, hypocotyls, cotyledons, epicotyls and leaves. The rbcS genes were up-regulated by various external factors such as salicylic acid (SA), salt stress and drought stress. The expression level of rbcS genes after being treated by 2.0 mmol/L SA and 0.4% NaCl, respectively, is 2.5–3.0-fold as high as that of control sample. Moreover, soybean rbcS mRNA was accumulated with diurnal variation but easily influenced by light and low temperature.
AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions

As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 (AQP2) plays an essential role in water reabsorption along osmotic gradients. The capacity to accumulate AQP2 in the apical plasma membrane in response to decreased fluid volume or increased plasma osmolality is critically regulated by the antidiuretic hormone AVP and its receptor 2 (AVPR2). Mutations in AVPR2 result in X-linked recessive NDI, the most common form of inherited NDI. Genetic defects in AQP2 cause autosomal recessive or dominant NDI. In this review, we provide an updated overview of the genetic and molecular mechanisms of congenital NDI, with a focus on the potential disease-causing mutations in AVPR2 and AQP2, the molecular defects in the AVPR2 and AQP2 mutants, post-translational modifications (i.e., phosphorylation, ubiquitination, and glycosylation) and various protein-protein interactions that regulate phosphorylation, ubiquitination, tetramerization, trafficking, stability, and degradation of AQP2.
Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial.

Importance The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials. Objective To determine the effect of 16:8-hour time-restricted eating on weight loss and metabolic risk markers. Interventions Participants were randomized such that the consistent meal timing (CMT) group was instructed to eat 3 structured meals per day, and the time-restricted eating (TRE) group was instructed to eat ad libitum from 12:00 pm until 8:00 pm and completely abstain from caloric intake from 8:00 pm until 12:00 pm the following day. Design, Setting, and Participants This 12-week randomized clinical trial including men and women aged 18 to 64 years with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 to 43 was conducted on a custom mobile study application. Participants received a Bluetooth scale. Participants lived anywhere in the United States, with a subset of 50 participants living near San Francisco, California, who underwent in-person testing. Main Outcomes and Measures The primary outcome was weight loss. Secondary outcomes from the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure. Results Overall, 116 participants (mean [SD] age, 46.5 [10.5] years; 70 [60.3%] men) were included in the study. There was a significant decrease in weight in the TRE (-0.94 kg; 95% CI, -1.68 to -0.20; P = .01), but no significant change in the CMT group (-0.68 kg; 95% CI, -1.41 to 0.05, P = .07) or between groups (-0.26 kg; 95% CI, -1.30 to 0.78; P = .63). In the in-person cohort (n = 25 TRE, n = 25 CMT), there was a significant within-group decrease in weight in the TRE group (-1.70 kg; 95% CI, -2.56 to -0.83; P < .001). There was also a significant difference in appendicular lean mass index between groups (-0.16 kg/m2; 95% CI, -0.27 to -0.05; P = .005). There were no significant changes in any of the other secondary outcomes within or between groups. There were no differences in estimated energy intake between groups. Conclusions and Relevance Time-restricted eating, in the absence of other interventions, is not more effective in weight loss than eating throughout the day. Trial Registration ClinicalTrials.gov Identifiers: NCT03393195 and NCT03637855.
Use of Hyaluronic Acid (HA) in Chronic Airway Diseases

Hyaluronic acid (HA) is a key component of the extracellular matrix of the lungs. A unique attribute of HA is its water-retaining properties, so HA has a major role in the regulation of fluid balance in the lung interstitium. Hyaluronic acid has been widely used in the treatment of eyes, ears, joints and skin disorders, but in the last years, it has been also proposed in the treatment of certain lung diseases, including airway diseases, due to its anti-inflammatory and water-binding capacities. Hyaluronic acid aerosol decreases the severity of elastase-induced emphysema in murine models, prevents bronchoconstriction in asthmatics and improves some functional parameters in chronic obstructive pulmonary disease (COPD) patients. Due to the protection of HA against bronchoconstriction and its hydration properties, inhaled HA would increase the volume of airway surface liquid, resulting in mucus hydration, increased mucous transport and less mucous plugging of the airways. In addition, it has been seen in human studies that the treatment with nebulised HA improves the tolerability of nebulised hypertonic saline (even at 6% or 7% of concentration), which has been demonstrated to be an effective treatment in bronchial secretion management in patients with cystic fibrosis and bronchiectasis. Our objective is to review the role of HA treatment in the management of chronic airway diseases.
Characterization and engineering of a two-enzyme system for plastics depolymerization

Significance Deconstruction of recalcitrant polymers, such as cellulose or chitin, is accomplished in nature by synergistic enzyme cocktails that evolved over millions of years. In these systems, soluble dimeric or oligomeric intermediates are typically released via interfacial biocatalysis, and additional enzymes often process the soluble intermediates into monomers for microbial uptake. The recent discovery of a two-enzyme system for polyethylene terephthalate (PET) deconstruction, which employs one enzyme to convert the polymer into soluble intermediates and another enzyme to produce the constituent PET monomers (MHETase), suggests that nature may be evolving similar deconstruction strategies for synthetic plastics. This study on the characterization of the MHETase enzyme and synergy of the two-enzyme PET depolymerization system may inform enzyme cocktail-based strategies for plastics upcycling. Plastics pollution represents a global environmental crisis. In response, microbes are evolving the capacity to utilize synthetic polymers as carbon and energy sources. Recently, Ideonella sakaiensis was reported to secrete a two-enzyme system to deconstruct polyethylene terephthalate (PET) to its constituent monomers. Specifically, the I. sakaiensis PETase depolymerizes PET, liberating soluble products, including mono(2-hydroxyethyl) terephthalate (MHET), which is cleaved to terephthalic acid and ethylene glycol by MHETase. Here, we report a 1.6 Å resolution MHETase structure, illustrating that the MHETase core domain is similar to PETase, capped by a lid domain. Simulations of the catalytic itinerary predict that MHETase follows the canonical two-step serine hydrolase mechanism. Bioinformatics analysis suggests that MHETase evolved from ferulic acid esterases, and two homologous enzymes are shown to exhibit MHET turnover. Analysis of the two homologous enzymes and the MHETase S131G mutant demonstrates the importance of this residue for accommodation of MHET in the active site. We also demonstrate that the MHETase lid is crucial for hydrolysis of MHET and, furthermore, that MHETase does not turnover mono(2-hydroxyethyl)-furanoate or mono(2-hydroxyethyl)-isophthalate. A highly synergistic relationship between PETase and MHETase was observed for the conversion of amorphous PET film to monomers across all nonzero MHETase concentrations tested. Finally, we compare the performance of MHETase:PETase chimeric proteins of varying linker lengths, which all exhibit improved PET and MHET turnover relative to the free enzymes. Together, these results offer insights into the two-enzyme PET depolymerization system and will inform future efforts in the biological deconstruction and upcycling of mixed plastics.
Activity and Metabolism in the Mussel Mytilus edulis L. during Intertidal Hypoxia and Aerobic Recovery

Coordinated calorimetric and respirometric measurements revealed differences in heat dissipation during exposure to air (tq̇air) and its partitioning into aerobic and anaerobic components in intertidally and subtidally acclimatized specimens of Mytilus edulis. Variations in air-gaping behavior were associated with these differences. There appeared to be a minimum (anaerobic) tq̇air and a constant overshoot in heat dissipation associated with recovery metabolism in aerated seawater; superimposed on this anaerobic rate in air was individual variability in air-gaping behavior, which produced a fivefold range of tq̇air. There was a positive relationship between the volume of air enclosed by individual mussels and maximum tq̇air. Those individuals which gaped less in air showed more shell valve movements during recovery. Exceptionally active mussels accumulated more strombine in their posterior adductor muscles and had a higher anaerobic contribution to muscular activity during recovery. Differences between intertidal and subtidal mussels in the time course of reoxygenation of the hemolymph on reimmersion were associated with differences in the time required to achieve maximum rates of aerobic heat dissipation. Differences between these groups of mussels in aquatic heat dissipation and oxygen consumption following recovery were related more to differences in ration than to aerial exposure per se.
The relationship between parental factors, child symptom profile, and persistent postoperative pain interference and analgesic use in children

Both parental and child factors have been previously associated with persistent or recurrent postoperative pain in children. Yet, little is known about the relative contribution of parent factors or whether child symptom factors might impact the association between parent factors and long‐term pain. The aim of this study was to explore the associations between parent factors, child symptomology, and the child's long‐term pain outcomes after surgery.