Miracle-dz/UniFAR-FTUs huggingface dataset:
Study of the Relationship between Sigma Receptor Expression Levels and Some Common Sigma Ligand Activity in Cancer Using Human Cancer Cell Lines of the NCI-60 Cell Line Panel

Sigma (σ) receptors have attracted great interest since they are implicated in various cellular functions and biological processes and diseases, including various types of cancer. The receptor family consists of two subtypes: sigma-1 (σ1) and sigma-2 (σ2). Both σ receptor subtypes have been proposed as therapeutic targets for various types of cancers, and many studies have provided evidence that their selective ligands (agonists and antagonists) exhibit antiproliferative and cytotoxic activity. Still, the precise mechanism of action of both σ receptors and their ligands remains unclear and needs to be elucidated. In this study, we aimed to simultaneously determine the expression levels of both σ receptor subtypes in several human cancer cell lines. Additionally, we investigated the in vitro antiproliferative activity of some widely used σ1 and σ2 ligands against those cell lines to study the relationship between σ receptor expression levels and σ ligand activity. Finally, we ran the NCI60 COMPARE algorithm to further elucidate the cytotoxic mechanism of action of the selected σ ligands studied herein.
Adolescent Transitions in Self-Management Strategies and Young Adult Alcohol Use

Individuals use a variety of strategies to manage their thoughts, emotions, and behaviors across the lifespan. In this study, we used latent class analysis to derive distinct subtypes of self-management skills in early adolescence and latent transition analysis to examine whether movement between different classes was associated with later young adult alcohol use. Assessments of behavioral self-control, affective self-regulation, and cognitive self-reinforcement were obtained in the seventh and 10th grades from students participating in two independent drug prevention trials (control group participants only, N = 3,939). Assessment of alcohol use was obtained when participants were young adults (23–26). A model distinguishing four subtypes of self-management skills fit best for both the seventh and 10th grades. While findings indicated modest stability in class structure over time, maintaining class membership characterized by high cognitive self-reinforcement and high affective self-regulation was consistently protective in terms of young adult alcohol use relative to movement from this to other classes. Transitions in class membership involving an expansion of self-management strategies were protective and associated with lower levels of young adult alcohol use and transitions involving a contraction of self-management strategies associated with higher young adult alcohol use. This study illustrates the important use of person-centered techniques to exemplify how typologies of self-management during adolescence can play a protective role in young adult alcohol use.
Diagnostic performance of circulating cell-free DNA for hepatocellular carcinoma: a systematic review and meta-analysis.

Background: We aimed to assess the diagnostic performance of circulating cell-free DNA (cfDNA) in hepatocellular carcinoma (HCC). Materials & methods: After a systematic literature search bivariate linear mixed models were used to integrate sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio. The area under receiver operating characteristics curves of the included studies was used to estimate the diagnostic value. Results: Thirty-eight articles enrolled in quantitative synthesis. In overall analysis the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristics curves for cfDNA in distinguishing HCC patients from healthy controls were 0.54, 0.90, 5.23, 0.51, 10.27 and 0.82, respectively. Conclusion: This study suggests that cfDNA has a promising diagnostic accuracy in detection of HCC.
Management Strategies for Antipsychotic-Related Sexual Dysfunction: A Clinical Approach

Antipsychotic medication can be often associated with sexual dysfunction (SD). Given its intimate nature, treatment emergent sexual dysfunction (TESD) remains underestimated in clinical practice. However, psychotic patients consider sexual issues as important as first rank psychotic symptoms, and their disenchantment with TESD can lead to important patient distress and treatment drop-out. In this paper, we detail some management strategies for TESD from a clinical perspective, ranging from prevention (carefully choosing an antipsychotic with a low rate of TESD) to possible pharmacological interventions aimed at improving patients’ tolerability when TESD is present. The suggested recommendations include the following: prescribing either aripiprazole or another dopaminergic agonist as a first option antipsychotic or switching to it whenever possible. Whenever this is not possible, adjunctive treatment with aripiprazole seems to also be beneficial for reducing TESD. Some antipsychotics, like olanzapine, quetiapine, or ziprasidone, have less impact on sexual function than others, so they are an optimal second choice. Finally, a variety of useful strategies (such as the addition of sildenafil) are also described where the previous ones cannot be applied, although they may not yield as optimal results.
Quantitative Sensory Testing of Spinal Cord and Dorsal Root Ganglion Stimulation in Chronic Pain Patients

The physiological mechanisms underlying the pain‐modulatory effects of clinical neurostimulation therapies, such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS), are only partially understood. In this pilot prospective study, we used patient‐reported outcomes (PROs) and quantitative sensory testing (QST) to investigate the physiological effects and possible mechanisms of action of SCS and DRGS therapies.
Poor oral health and the association with diet quality and intake in older people in two studies in the UK and USA

Abstract We aimed to investigate the associations of poor oral health cross-sectionally with diet quality and intake in older people. We also examined whether change in diet quality is associated with oral health problems. Data from the British Regional Heart Study (BRHS) comprising British males aged 71–92 years and the Health, Aging and Body Composition (HABC) Study comprising American males and females aged 71–80 years were used. Dental data included tooth loss, periodontal disease, dry mouth and self-rated oral health. Dietary data included diet quality (based on Elderly Dietary Index (BRHS) and Healthy Eating Score (HABC Study)) and several nutrients. In the BRHS, change in diet quality over 10 years (1998–2000 to 2010–2012) was also assessed. In the BRHS, tooth loss, fair/poor self-rated oral health and accumulation of oral health problems were associated with poor diet quality, after adjustment. Similar associations were reported for high intake of processed meat. Poor oral health was associated with the top quartile of percentage of energy content from saturated fat (self-rated oral health, OR 1·34, 95 % CI 1·02, 1·77). In the HABC Study, no significant associations were observed for diet quality after adjustment. Periodontal disease was associated with the top quartile of percentage of energy content from saturated fat (OR 1·48, 95 % CI 1·09, 2·01). In the BRHS, persistent low diet quality was associated with higher risk of tooth loss and accumulation of oral health problems. Older individuals with oral health problems had poorer diets and consumed fewer nutrient-rich foods. Persistent poor diet quality was associated with oral health problems later in life.
Estimating FST and kinship for arbitrary population structures

FST and kinship are key parameters often estimated in modern population genetics studies in order to quantitatively characterize structure and relatedness. Kinship matrices have also become a fundamental quantity used in genome-wide association studies and heritability estimation. The most frequently-used estimators of FST and kinship are method-of-moments estimators whose accuracies depend strongly on the existence of simple underlying forms of structure, such as the independent subpopulations model of non-overlapping, independently evolving subpopulations. However, modern data sets have revealed that these simple models of structure likely do not hold in many populations, including humans. In this work, we analyze the behavior of these estimators in the presence of arbitrarily-complex population structures, which results in an improved estimation framework specifically designed for arbitrary population structures. After generalizing the definition of FST to arbitrary population structures and establishing a framework for assessing bias and consistency of genome-wide estimators, we calculate the accuracy of existing FST and kinship estimators under arbitrary population structures, characterizing biases and estimation challenges unobserved under their originally-assumed models of structure. We then present our new approach, which consistently estimates kinship and FST when the minimum kinship value in the dataset is estimated consistently. We illustrate our results using simulated genotypes from an admixture model, constructing a one-dimensional geographic scenario that departs nontrivially from the independent subpopulations model. Our simulations reveal the potential for severe biases in estimates of existing approaches that are overcome by our new framework. This work may significantly improve future analyses that rely on accurate kinship and FST estimates.
The Effects of PEI Hollow Fiber Substrate Characteristics on PDMS/PEI Hollow Fiber Membranes for CO2/N2 Separation

The CO2 separation from flue gas based on membrane technology has drawn great attention in the last few decades. In this work, polyetherimide (PEI) hollow fibers were fabricated by using a dry-jet-wet spinning technique. Subsequently, the composite hollow fiber membranes were prepared by dip coating of polydimethylsiloxane (PDMS) selective layer on the outer surface of PEI hollow fibers. The hollow fibers spun from various spinning conditions were fully characterized. The influence of hollow fiber substrates on the CO2/N2 separation performance of PDMS/PEI composite membranes was estimated by gas permeance and ideal selectivity. The prepared composite membrane where the hollow fiber substrate was spun from 20 wt% of dope solution, 12 mL/min of bore fluid (water) flow rate exhibited the highest ideal selectivity equal to 21.3 with CO2 permeance of 59 GPU. It was found that the dope concentration, bore fluid flow rate and bore fluid composition affect the porous structure, surface morphology and dimension of hollow fibers. The bore fluid composition significantly influenced the gas permeance and ideal selectivity of the PDMS/PEI composite membrane. The prepared PDMS/PEI composite membranes possess comparable CO2/N2 separation performance to literature ones.
Serotonin in the Pathogenesis of Lymphocytic Colitis

Lymphocytic colitis (LC) is a chronic inflammatory disease associated with watery diarrhea, abdominal pain, and colonic intraepithelial lymphocytosis. Serotonin (5-hydroxytryptamine, 5-HT) is reported to increase in certain colon diseases; however, little is known regarding its metabolism in LC. In the present work, the level of 5-HT in serum and the number of enteroendocrine cells (EECs) as well as the expression of the 5-HT rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) in colonic biopsies and urine 5-hydroxyindoeoacetic acid (5-HIAA) were determined in 36 LC patients that were treated with budesonide and 32 healthy controls. The 5-HT serum and 5-HIAA urine levels were measured using ELISA, the EEC number was determined immunohistochemically, and the colonic TPH1 mRNA expression was determined using RT-PCR. The levels of 5-HT and 5-HIAA and the number of EECs were higher in LC patients than in the controls, and positive correlations were observed between the 5-HT and 5-HIAA levels, 5-HT and EEC number, TPH1 mRNA and EEC number, as well as the severity of disease symptoms and 5-HIAA. Budesonide decreased the levels of 5-HT, 5-HIAA, and TPH1 expression and the number of EECs to values that did not differ from those for controls. In conclusion, the serotonin metabolism may be important for LC pathogenesis, and the urinary level of 5-HIAA may be considered as a non-invasive marker of this disease activity.
Factors Associated with Decisions for Initial Dosing, Up-Titration of Propiverine and Treatment Outcomes in Overactive Bladder Syndrome Patients in a Non-Interventional Setting

Two doses of propiverine ER (30 and 45 mg/d) are available for the treatment of overactive bladder (OAB) syndrome. We have explored factors associated with the initial dosing choice (allocation bias), the decision to adapt dosing (escalation bias) and how dosing relative to other factors affects treatment outcomes. Data from two non-interventional studies of 1335 and 745 OAB patients, respectively, receiving treatment with propiverine, were analyzed post-hoc. Multivariate analysis was applied to identify factors associated with dosing decisions and treatment outcomes. Several parameters were associated with dose choice, escalation to higher dose or treatment outcomes, but only few exhibited a consistent association across both studies. These were younger age for initial dose choice and basal number of urgency and change in incontinence episodes for up-titration. Treatment outcome (difference between values at 12 weeks vs. baseline) for each OAB system was strongly driven by the respective baseline value, whereas no other parameter exhibited a consistent association. Patients starting on the 30 mg dose and escalating to 45 mg after 4 weeks had outcomes comparable with those staying on a starting dose of 30 or 45 mg. We conclude that dose escalation after 4 weeks brings OAB patients with an initially limited improvement to a level seen in initially good responders. Analysis of underlying factors yielded surprisingly little consistent insight.
Chlorite topography and dissolution of the interlayer studied with atomic force microscopy

Abstract The weathering of rocks is a process important for the understanding of soil formation as well as a general understanding of the interaction between litho- and hydrosphere. Phyllosilicates in general are of special importance for the understanding of weathering processes due to their abundance in rocks and soils. A common phyllosilicate in soils is chlorite, which has a structure composed of a combination of two distinct layers, the tetrahedral-octahedral-tetrahedral (TOT) and the interlayer (i.e., the octahedral layer between TOT layers). In this study, the morphology and dissolution of chlorite in pure water has been visualized using atomic force microscopy. Upon cleavage, the TOT layer shows atomically flat terraces and steps, while the interlayer presents strips and voids. In pure water, dissolution channels and equilateral, mono-oriented triangular etch pits form in the interlayer and lead to progressively increased solubilization. Dissolution channels are proposed to originate from structural defects, while a conceptual model is discussed to explain the presence of triangular etch pits. In this model, their formation is driven by the different reactivity of the two octahedral configurations along the etch pits. It is not currently known which of these is the most stable configuration, however we propose arguments that point toward a specific orientation. The conceptual model is supported by experimental data and is potentially applicable to all mineral structures constituted by continuous octahedral layers.
Posture and gait in the early course of schizophrenia

While correlations between postural stability deficits and schizophrenia are well documented, information on dynamic motor alterations in schizophrenia are still scarce, and no data on their onset are available yet. Therefore, the aim of this study was i) to measure gait pattern(s) in patients with schizophrenia; ii) to identify posture and gait alterations which could potentially be used as a predictive clinical tool of the onset of the disorder. Body composition, posture and gait parameters were assessed in a group of 30 patients with schizophrenia and compared to 25 healthy subjects. Sway area was significantly higher in the schizophrenia group compared to controls regardless of whether the participants were in eyes open or eyes closed condition. Gait cadence and speed were significantly lower in patients with schizophrenia, while stride length was similar. We concluded that the combination of an increased sway area (independent from eye closure) and a gait cadence reduction—in the presence of normal gait speed and stride length—might be considered peculiar postural and gait profile characteristic of early schizophrenia.
Chronic kidney disease and the outcomes of fibrinolysis for ST-segment elevation myocardial infarction: A real-world study

Background In low-resource regions, fibrinolytic therapy is often the only option for ST-elevation myocardial infarction (STEMI) patients as primary percutaneous coronary intervention (PCI) is often not available and patients are hardly transferred to a medical center with PCI capacity within the first 120 minutes. Chronic kidney disease (CKD) is one of the most frequently encountered complications of STEMI. However, the evidence for the efficacy of fibrinolytic therapy in STEMI patients with CKD is still limited. The aim of this study is to test whether CKD modifies the association between fibrinolytic therapy and short-term major adverse cardiovascular events (MACEs) among patients with STEMI. Methods and findings This is a real-world study analyzing the data from 9508 STEMI patients (mean age: 64.0±12.4 years; male: 70.1%) in the third phase of Clinical Pathways in Acute Coronary Syndromes program (CPACS-3), which is a large study of the management of acute coronary syndromes (ACS) in 101 county hospitals without PCI capacity in China. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1·73 m2 at the admission. The primary outcome is short-term MACEs, including all-cause death, recurrent myocardial infarction, or nonfatal stroke. Patients were recruited consecutively between October 2011 and November 2014. Out of them, 1282 patients (13.5%) were classified as having CKD. Compared with non-CKD patients, CKD patients were less likely to receive fibrinolytic therapy than non-CKD patients (26.4% vs. 38.9%, P<0.001), more likely to experience a failed fibrinolytic therapy (32.8% vs. 16.9%), and had a higher risk of short-term MACEs (19.7% vs. 5.6%). After full adjustment, use of fibrinolytic therapy was associated with a significantly lower risk of short-term MACEs in non-CKD patients (relative risk [RR] = 0.87, 95% confidence interval [CI]: 0.76–0.99), but not in CKD patients (P for interaction = 0.026). Further analysis stratified by the success of fibrinolysis showed that compared with patients who did not receive fibrinolytic therapy, patients with successful fibrinolysis had a lower risk of short-term MACEs that was similar between patients with (RR = 0.71, 95% CI: 0.55–0.82) and without CKD (RR = 0.67, 95% CI: 0.55–0.92), while patients with unsuccessful fibrinolysis had a similarly higher risk in CKD patients (RR = 1.25, 95% CI: 1.09–1.43) and non-CKD patients (RR = 1.30, 95% CI: 1.13–1.50). Conclusions CKD reduced the likelihood of successful fibrinolysis and increased the risk of short-term MACEs in patients with STEMI. Attention should be paid to how to improve the success rate of fibrinolytic therapy for STEMI patients with CKD. Trial registration The CPACS-3 study was registered on www.clinicaltrials. gov (NCT01398228).
Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.
Effects of Different Nitrogen Forms and Exogenous Application of Putrescine on Heat Stress of Cauliflower: Photosynthetic Gas Exchange, Mineral Concentration and Lipid Peroxidation

This study examines the effect of the exogenous application of polyamine putrescine together with the application of different ratios of nitrate/ammonium (NO3−/NH4+), on the physiology of cauliflower subjected to heat stress. The 50:50 NO3−/NH4+ ratio was the best ratio against heat stress. As a result of the joint application of these compounds, a higher photosynthetic rate, a higher accumulation of both photosynthesis-related compounds and pigments, total proteins, and a change in the status of nutrients were obtained. Particularly, the decrease in content of calcium, chloride and sulphate in plants under heat stress is ameliorated by the ammonium effect. Additionally, it is important to highlight that cauliflower waste contains a higher content of mineral nutrients than floret cauliflower. These effects were more marked in young leaves. Furthermore, a synergistic effect for coping with heat stress between the polyamine and the nutritional treatment was observed. For this, both the application of putrescine and the feeding of plants with a 50:50 NO3−/NH4+ ratio before heat stress is proposed for the first time as an agricultural practice for increasing the thermotolerance of cauliflower cv Moonshine. On the other hand, due to the lower lipid peroxidation rate obtained in cauliflower leaves, these plants could be used for health purposes as ointments or other nutraceutical products, making the cultivation of this kind of cruciferous more sustainable.