Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Regulation of Betulinic Acid on α3β4 Nicotinic Acetylcholine Receptors

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor’s ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative.
Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.
Removal of Mn(II) from Acidic Wastewaters Using Graphene Oxide–ZnO Nanocomposites

Pollution due to acidic and metal-enriched waters affects the quality of surface and groundwater resources, limiting their uses for various purposes. Particularly, manganese pollution has attracted attention due to its impact on human health and its negative effects on ecosystems. Applications of nanomaterials such as graphene oxide (GO) have emerged as potential candidates for removing complex contaminants. In this study, we present the preliminary results of the removal of Mn(II) ions from acidic waters by using GO functionalized with zinc oxide nanoparticles (ZnO). Batch adsorption experiments were performed under two different acidity conditions (pH1 = 5.0 and pH2 = 4.0), in order to evaluate the impact of acid pH on the adsorption capacity. We observed that the adsorption of Mn(II) was independent of the pHPZC value of the nanoadsorbents. The qmax with GO/ZnO nanocomposites was 5.6 mg/g (34.1% removal) at pH = 5.0, while with more acidic conditions (pH = 4.0) it reached 12.6 mg/g (61.2% removal). In turn, the results show that GO/ZnO nanocomposites were more efficient to remove Mn(II) compared with non-functionalized GO under the pH2 condition (pH2 = 4.0). Both Langmuir and Freundlich models fit well with the adsorption process, suggesting that both mechanisms are involved in the removal of Mn(II) with GO and GO/ZnO nanocomposites. Furthermore, adsorption isotherms were efficiently modeled with the pseudo-second-order kinetic model. These results indicate that the removal of Mn(II) by GO/ZnO is strongly influenced by the pH of the solution, and the decoration with ZnO significantly increases the adsorption capacity of Mn(II) ions. These findings can provide valuable information for optimizing the design and configuration of wastewater treatment technologies based on GO nanomaterials for the removal of Mn(II) from natural and industrial waters.
A New Protocol of Computer-Assisted Image Analysis Highlights the Presence of Hemocytes in the Regenerating Cephalic Tentacles of Adult Pomacea canaliculata

In humans, injuries and diseases can result in irreversible tissue or organ loss. This well-known fact has prompted several basic studies on organisms capable of adult regeneration, such as amphibians, bony fish, and invertebrates. These studies have provided important biological information and helped to develop regenerative medicine therapies, but important gaps concerning the regulation of tissue and organ regeneration remain to be elucidated. To this aim, new models for studying regenerative biology could prove helpful. Here, the description of the cephalic tentacle regeneration in the adult of the freshwater snail Pomacea canaliculata is presented. In this invasive mollusk, the whole tentacle is reconstructed within 3 months. Regenerating epithelial, connective, muscular and neural components are already recognizable 72 h post-amputation (hpa). Only in the early phases of regeneration, several hemocytes are retrieved in the forming blastema. In view of quantifying the hemocytes retrieved in regenerating organs, granular hemocytes present in the tentacle blastema at 12 hpa were counted, with a new and specific computer-assisted image analysis protocol. Since it can be applied in absence of specific cell markers and after a common hematoxylin-eosin staining, this protocol could prove helpful to evidence and count the hemocytes interspersed among regenerating tissues, helping to unveil the role of immune-related cells in sensory organ regeneration.
Interdisciplinary Care Networks in Rehabilitation Care for Patients with Chronic Musculoskeletal Pain: A Systematic Review

This systematic review aims to identify what rehabilitation care networks, within primary care or between primary and other health care settings, have been described for patients with chronic musculoskeletal pain, and what their impact is on the Quadruple Aim outcomes (health; health care costs; quality of care experienced by patients; work satisfaction for health care professionals). Studies published between 1 January 1994 and 11 April 2019 were identified in PubMed, CINAHL, Web of Science, and PsycInfo. Forty-nine articles represented 34 interventions: 21 within primary care; 6 between primary and secondary/tertiary care; 1 in primary care and between primary and secondary/tertiary care; 2 between primary and social care; 2 between primary, secondary/tertiary, and social care; and 2 between primary and community care. Results on impact were presented in 19 randomized trials, 12 non-randomized studies, and seven qualitative studies. In conclusion, there is a wide variety of content, collaboration, and evaluation methods of interventions. It seems that patient-centered interdisciplinary interventions are more effective than usual care. Further initiatives should be performed for interdisciplinary interventions within and across health care settings and evaluated with mixed methods on all Quadruple Aim outcomes.
Insulin Resistance Is Not Sustained Following Denervation in Glycolytic Skeletal Muscle

Denervation rapidly induces insulin resistance (i.e., impairments in insulin-stimulated glucose uptake and signaling proteins) in skeletal muscle. Surprisingly, whether this metabolic derangement is long-lasting is presently not clear. The main goal of this study was to determine if insulin resistance is sustained in both oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles following long-term (28 days) denervation. Mouse hindlimb muscles were denervated via unilateral sciatic nerve resection. Both soleus and EDL muscles atrophied ~40%. Strikingly, while denervation impaired submaximal insulin-stimulated [3H]-2-deoxyglucose uptake ~30% in the soleus, it enhanced submaximal (~120%) and maximal (~160%) insulin-stimulated glucose uptake in the EDL. To assess possible mechanism(s), immunoblots were performed. Denervation did not consistently alter insulin signaling (e.g., p-Akt (Thr308):Akt; p-TBC1D1 [phospho-Akt substrate (PAS)]:TBC1D1; or p-TBC1D4 (PAS):TBC1D4) in either muscle. However, denervation decreased glucose transporter 4 (GLUT4) levels ~65% in the soleus but increased them ~90% in the EDL. To assess the contribution of GLUT4 to the enhanced EDL muscle glucose uptake, muscle-specific GLUT4 knockout mice were examined. Loss of GLUT4 prevented the denervation-induced increase in insulin-stimulated glucose uptake. In conclusion, the denervation results sustained insulin resistance in the soleus but enhanced insulin sensitivity in the EDL due to increased GLUT4 protein levels.
Trypsin Induced Degradation of Amyloid Fibrils

Proteolytic enzymes are known to be involved in the formation and degradation of various monomeric proteins, but the effect of proteases on the ordered protein aggregates, amyloid fibrils, which are considered to be extremely stable, remains poorly understood. In this work we study resistance to proteolytic degradation of lysozyme amyloid fibrils with two different types of morphology and beta-2-microglobulun amyloids. We showed that the proteolytic enzyme of the pancreas, trypsin, induced degradation of amyloid fibrils, and the mechanism of this process was qualitatively the same for all investigated amyloids. At the same time, we found a dependence of efficiency and rate of fibril degradation on the structure of the amyloid-forming protein as well as on the morphology and clustering of amyloid fibrils. It was assumed that the discovered relationship between fibrils structure and the efficiency of their degradation by trypsin can become the basis of a new express method for the analysis of amyloids polymorphism. Unexpectedly lower resistance of both types of lysozyme amyloids to trypsin exposure compared to the native monomeric protein (which is not susceptible to hydrolysis) was attributed to the higher availability of cleavage sites in studied fibrils. Another intriguing result of the work is that the cytotoxicity of amyloids treated with trypsin was not only failing to decline, but even increasing in the case of beta-2-microglobulin fibrils.
Cardiac Autonomic Response to Active Standing in Calcific Aortic Valve Stenosis

Aortic stenosis is a progressive heart valve disorder characterized by calcification of the leaflets. Heart rate variability (HRV) analysis has been proposed for assessing the heart response to autonomic activity, which is documented to be altered in different cardiac diseases. The objective of the study was to evaluate changes of HRV in patients with aortic stenosis by an active standing challenge. Twenty-two volunteers without alterations in the aortic valve (NAV) and twenty-five patients diagnosed with moderate and severe calcific aortic valve stenosis (AVS) participated in this cross-sectional study. Ten minute electrocardiograms were performed in a supine position and in active standing positions afterwards, to obtain temporal, spectral, and scaling HRV indices: mean value of all NN intervals (meanNN), low-frequency (LF) and high-frequency (HF) bands spectral power, and the short-term scaling indices (α1 and αsign1). The AVS group showed higher values of LF, LF/HF and αsign1 compared with the NAV group at supine position. These patients also expressed smaller changes in meanNN, LF, HF, LF/HF, α1, and αsign1 between positions. In conclusion, we confirmed from short-term recordings that patients with moderate and severe calcific AVS have a decreased cardiac parasympathetic supine response and that the dynamic of heart rate fluctuations is modified compared to NAV subjects, but we also evidenced that they manifest reduced autonomic adjustments caused by the active standing challenge.
AtWAKL10, a Cell Wall Associated Receptor-Like Kinase, Negatively Regulates Leaf Senescence in Arabidopsis thaliana

Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of AtWAKL10 increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of AtWAKL10 contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function atwakl10 mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing AtWAKL10 showed an opposite trend. Additionally, some defense and senescence related WRKY transcription factors could bind to the promoter of AtWAKL10. In addition, deletion and overexpression of AtWAKL10 caused several specific transcriptional alterations, including genes involved in cell extension, cell wall modification, defense response and senescence related WRKYs, which may be implicated in regulatory mechanisms adopted by AtWAKL10 in controlling leaf senescence. Taken together, these results revealed that AtWAKL10 negatively regulated leaf senescence.
Thermoelectric Generator Using Polyaniline-Coated Sb2Se3/β-Cu2Se Flexible Thermoelectric Films

Herein, Sb2Se3 and β-Cu2Se nanowires are synthesized via hydrothermal reaction and water evaporation-induced self-assembly methods, respectively. The successful syntheses and morphologies of the Sb2Se3 and β-Cu2Se nanowires are confirmed via X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), and field emission transmission electron microscopy (FE-TEM). Sb2Se3 materials have low electrical conductivity which limits application to the thermoelectric generator. To improve the electrical conductivity of the Sb2Se3 and β-Cu2Se nanowires, polyaniline (PANI) is coated onto the surface and confirmed via Fourier-transform infrared spectroscopy (FT-IR), FE-TEM, and XPS analysis. After coating PANI, the electrical conductivities of Sb2Se3/β-Cu2Se/PANI composites were increased. The thermoelectric performance of the flexible Sb2Se3/β-Cu2Se/PANI films is then measured, and the 70%-Sb2Se3/30%-β-Cu2Se/PANI film is shown to provide the highest power factor of 181.61 μW/m·K2 at 473 K. In addition, a thermoelectric generator consisting of five legs of the 70%-Sb2Se3/30%-β-Cu2Se/PANI film is constructed and shown to provide an open-circuit voltage of 7.9 mV and an output power of 80.1 nW at ΔT = 30 K. This study demonstrates that the combination of inorganic thermoelectric materials and flexible polymers can generate power in wearable or portable devices.
Water Sorption and Solubility of Flowable Giomers

The objective of this study is the characterization of a novel experimental flowable giomer (G) regarding water sorption, water solubility, and the microstructural characteristics, in comparison to three commercial giomers: Beautifil flow Plus X F00 (B-F00), Beautifil flow F02 (B-F02) and Beautifil flow Plus X F03 (B-F03), Shofu, Kyoto, Japan. Methods: Water sorption/solubility was performed by weighing the specimens before and after water immersion for 1, 2, 3, 14, 21 and 30 days. Data analysis was carried out with the software Origin2019b Graphing & Analysis using the ANOVA test and the Tukey test for post hoc comparison of the groups of materials. The microstructural analyses were done with a scanning electron microscope (SEM) and an atomic force microscope (AFM). The results showed significant differences between the tested materials (p < 0.05). For sorption, the Tukey test indicated differences between all four sample groups, except between B-F02 and B-F03, which exhibited no differences in any of the investigation days. The Tukey test also showed significant differences regarding solubility between all sample groups in the 30-day interval. SEM images and roughness showed that after 30 days of immersion in water, the experimental giomer G had the roughest surface.
Honey Phenolic Compound Profiling and Authenticity Assessment Using HRMS Targeted and Untargeted Metabolomics

Honey consumption is attributed to potentially advantageous effects on human health due to its antioxidant capacity as well as anti-inflammatory and antimicrobial activity, which are mainly related to phenolic compound content. Phenolic compounds are secondary metabolites of plants, and their content in honey is primarily affected by the botanical and geographical origin. In this study, a high-resolution mass spectrometry (HRMS) method was applied to determine the phenolic profile of various honey matrices and investigate authenticity markers. A fruitful sample set was collected, including honey from 10 different botanical sources (n = 51) originating from Greece and Poland. Generic liquid–liquid extraction using ethyl acetate as the extractant was used to apply targeted and non-targeted workflows simultaneously. The method was fully validated according to the Eurachem guidelines, and it demonstrated high accuracy, precision, and sensitivity resulting in the detection of 11 target analytes in the samples. Suspect screening identified 16 bioactive compounds in at least one sample, with abscisic acid isomers being the most abundant in arbutus honey. Importantly, 10 markers related to honey geographical origin were revealed through non-targeted screening and the application of advanced chemometric tools. In conclusion, authenticity markers and discrimination patterns were emerged using targeted and non-targeted workflows, indicating the impact of this study on food authenticity and metabolomic fields.
Condom-Protected Sex and Minority Stress: Associations with Condom Negotiation Self-Efficacy, “Passing” Concerns, and Experiences with Misgendering among Transgender Men and Women in Brazil

This cross-sectional exploratory study aims to verify associations between condom-protected sex, condom negotiation self-efficacy, self-esteem, and four minority stressors (experiences with misgendering, “passing” concerns, anticipated prejudice, and perceived prejudice) among transgender men (TM) and transgender women (TW). 260 individuals (192 TW and 68 TM) residing in two Brazilian states participated in the study. Data was collected online and in two hospital programs for transgender people and included sociodemographic data, condom-protected sex, the Trans-Specific Condom/Barrier Negotiation Self-Efficacy (T-Barrier) Scale, the Rosenberg Self-Esteem Scale, and four minority stressors. Measures that were significantly associated with condom-protected sex were tested as independent variables in a linear regression model. The main results suggest that lower condom negotiation self-efficacy, higher “passing” concerns, and higher experiences with misgendering were predictors of lower frequency of condom-protected sex. These negative outcomes were found among both TM and TW, which justifies their inclusion in public health policies. Structural strategies and clinical interventions are suggested to address condom negotiation self-efficacy and “passing” concerns in transgender populations.
Diagnostic Accuracy of 10/66 Dementia Protocol in Fijian-Indian Elders Living in New Zealand

The 10/66 dementia protocol was developed as a language and culture-fair instrument to estimate the prevalence of dementia in non-English speaking communities. The aim of this study was to validate the 10/66 dementia protocol in elders of Indian ethnicity born in the Fiji Islands (Fijian-Indian) living in New Zealand. To our knowledge, this is the first time a dementia diagnostic tool has been evaluated in the Fijian-Indian population in New Zealand. We translated and adapted the 10/66 dementia protocol for use in in Fijian-Indian people. Individuals (age ≥ 65) who self-identified as Fijian-Indian and had either been assessed for dementia at a local memory service (13 cases, eight controls) or had participated in a concurrent dementia prevalence feasibility study (eight controls) participated. The sensitivity, specificity, positive predictive value, and Youden’s index were obtained by comparing the 10/66 diagnosis and its sub-components against the clinical diagnosis (reference standard). The 10/66 diagnosis had a sensitivity of 92.3% (95% CI 70.3–99.5), specificity of 93.8% (95% CI 75.3–99.6), positive predictive value of 92.3% (95% CI 70.3–99.5), and negative predictive value of 93.8% (95% CI 75.3–99.6). The study results show that the Fijian-Indian 10/66 dementia protocol has adequate discriminatory abilities to diagnose dementia in our sample. This instrument would be suitable for future dementia population-based studies in the Fijian-Indian population living in Aotearoa/New Zealand or the Fiji-Islands.
Body Composition in Elite Soccer Players from Youth to Senior Squad

There is a strong relationship between body composition and performance in male soccer players. This study aimed to display an optimal body height and weight, and body composition profile of male soccer players for four competitive age groups. This cross-sectional study included four groups: U-15 (n = 152), U-17 (n = 154), U-19 (n = 61), and seniors (n = 27). Body height and weight were measured under standard conditions, and the bioelectrical impedance analyzer (BIA) analyzed body composition. On average, soccer players in the U-15 group had significantly lower body height, weight, body mass index, skeletal muscle mass, fat-free mass, total body water and basal metabolic rate than U-17, U-19 and seniors, but a higher percentage of body fat than U-17 and U-19, p < 0.05. In addition, the results show significant non-linear increases in body height, weight and body composition as the age of soccer players increases, with the exception of the percentage of body fat mass, which tends to significantly decrease with age. The main findings of this study are that body fat mass remains stable and similar across all age groups, including in the senior squad.