Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic analysis of cystine uptake and inhibition pattern of sulfasalazine in A549 cells

Cystine/glutamate transporter (xCT) is an antiporter involved in cystine uptake and glutamate efflux. However, there are very few reports regarding the kinetic analysis of xCT for cystine uptake using cancer cell lines, as well as the inhibition pattern of sulfasalazine, an inhibitor of xCT, for cystine uptake. Therefore, the purpose of this study was to clarify the kinetics of xCT in A549 cells, human lung cancer cells, and to reveal the inhibition pattern of sulfasalazine. Cystine uptake occurred in a time‐dependent manner, with linear cystine uptake observed for 5 min. Additionally, sulfasalazine inhibited cystine uptake in a concentration‐dependent manner, presenting an IC50 value of 24.7 ± 5.6 μM. Cystine uptake was saturated with increasing concentration, demonstrating Km and Vmax values of 179.4 ± 26.7 μM and 30.4 ± 2.3 nmol/min/mg protein, respectively. Moreover, during cystine uptake with sulfasalazine, Km and Vmax were >300 μM and 8.0 ± 1.5 nmol/min/mg protein, respectively, suggesting that sulfasalazine might demonstrate a mixed inhibition pattern. Furthermore, xCT siRNA decreased the xCT mRNA level and reduced cystine uptake. In conclusion, xCT was involved in the cystine uptake in A549 cells and sulfasalazine showed a mixed inhibition pattern to xCT.
Evaluation of the Sensitivity of Proteomics Methods Using the Absolute Copy Number of Proteins in a Single Cell as a Metric

Proteomic technology has improved at a staggering pace in recent years, with even practitioners challenged to keep up with new methods and hardware. The most common metric used for method performance is the number of peptides and proteins identified. While this metric may be helpful for proteomics researchers shopping for new hardware, this is often not the most biologically relevant metric. Biologists often utilize proteomics in the search for protein regulators that are of a lower relative copy number in the cell. In this review, I re-evaluate untargeted proteomics data using a simple graphical representation of the absolute copy number of proteins present in a single cancer cell as a metric. By comparing single-shot proteomics data to the coverage of the most in-depth proteomic analysis of that cell line acquired to date, we can obtain a rapid metric of method performance. Using a simple copy number metric allows visualization of how proteomics has developed in both sensitivity and overall dynamic range when using both relatively long and short acquisition times. To enable reanalysis beyond what is presented here, two available web applications have been developed for single- and multi-experiment comparisons with reference protein copy number data for multiple cell lines and organisms.
Dental Plaque Microbial Resistomes of Periodontal Health and Disease and Their Changes after Scaling and Root Planing Therapy

The emergence and development of resistance to antibiotics in periodontal pathogens have affected the success rate of treatment for periodontitis. The development of new antibacterial strategies is urgently needed to help control and treat periodontal disease, and dental plaque microbiome studies offer a promising new angle of attack. ABSTRACT The human oral microbial community has been considered a reservoir of antibiotic resistance. Currently, the effects of periodontitis and the scaling and root planing (SRP) treatment on the performance of antibiotic-resistant genes (ARGs) and metal-resistant genes (MRGs) in the dental plaque microbiota are not well characterized. To explore this issue, we selected 48 healthy-state (HS), 40 periodontitis-state (PS; before treatment), and 24 resolved-state (RS; after SRP treatment) metagenomic data of dental plaque samples from the Sequence Read Archive (SRA) database. NetShift analysis identified Fretibacterium fastidiosum, Tannerella forsythia, and Campylobacter rectus as key drivers during dental plaque microbiota alteration in the progression of periodontitis. Periodontitis and SRP treatment resulted in an increase in the number of ARGs and MRGs in dental plaque and significantly altered the composition of ARG and MRG profiles. Bacitracin, beta-lactam, macrolide-lincosamide-streptogramin (MLS), tetracycline, and multidrug resistance genes were the main classes of ARGs with high relative abundance, whereas multimetal, iron, chromium, and copper resistance genes were the primary types of MRGs in dental plaque microbiota. The cooccurrence of ARGs, MRGs, and mobile genetic elements (MGEs) indicated that a coselection phenomenon exists in the resistomes of dental plaque microbiota. Overall, our data provide new insights into the standing of the distribution of ARGs and MRGs in oral microbiota of periodontitis patients, and it was possible to contribute to the understanding of the complicated correlations among microorganisms, resistomes, and MGEs. IMPORTANCE The emergence and development of resistance to antibiotics in periodontal pathogens have affected the success rate of treatment for periodontitis. The development of new antibacterial strategies is urgently needed to help control and treat periodontal disease, and dental plaque microbiome studies offer a promising new angle of attack. In this study, we investigated the dental plaque microbiota and resistomes in periodontal health and disease states and their changes after SRP therapy. This is the first analysis of the profile of the microbial community and antibiotic and metal resistance genes in dental plaque by the metagenomic approach, to the best of our knowledge. Monitoring the profile of these resistomes has huge potential to provide reference levels for proper antibiotics use and the development of new antimicrobial strategies in periodontitis therapy and thereby improve actual efficacy of the treatment regimens.
Predicting the Membrane Permeability of Fentanyl and Its Analogues by Molecular Dynamics Simulations

The lipid membrane is considered a crucial component of opioid general anesthesia. The main drug used for the induction and maintenance of opioid anesthesia is fentanyl and its various analogues. However, these drugs have different clinical effects, and detailed atomic-level insight into the drug–membrane interactions could lead to a better understanding how these drugs exert their anesthetic properties. In this study, we have used extensive umbrella sampling molecular dynamics simulations to study the permeation process of fentanyl and three of its analogues into a variety of simple phospholipid membrane models. Our simulations show that we can accurately predict the permeability coefficients of these drug molecules, which is an important process in understanding how pharmaceuticals reach their molecular targets. We were also able to show that one phospholipid provides more accurate predictions than other lipids commonly used in these types of permeation studies, which will aid future studies of these types of processes.
The effects of lower body compression on left ventricular rotational mechanics in lymphoedema (from the MAGYAR‐Path Study)

Lower body half compression of bilateral secondary leg lymphoedema (LE) without relevant cardiac insufficiency gives rise to whether external leg compression may influence left ventricular (LV) function. Patients with LE were subjected to baseline two‐dimensional transthoracic echocardiography (2DTTE) for general assessment then three‐dimensional speckle‐tracking echocardiography (3DSTE) before and 1 h after lower body half external compression for LV torsion analysis.
Off-gassing plasticware to decrease the toxicity effect in embryo culture

Objective: To determine if reproductive toxicity might be reduced by off-gassing plasticware before use in in vitro fertilization culture. Methods: Petri dishes were grouped according to the off-gassing days before use for testing as follow: 0 day (Group A); 3 days (Group B); 7 days (Group C). Two bioassays were run: Human survival sperm assay (HSSA) at 24 hours for all groups and mouse embryo assay (MEA) to evaluate the effect of the off-gassing procedure. Sperm motility and sperm motility index values were examined and blastocyst formation was calculated on Days 4 and 5. Results: HSSA revealed decreased sperm motility in Group A (84%) compared to Groups B (94%) and C (93%) (p<0.5). MEA showed no statistical difference in blastocyst formation for the off-gassing groups (79.6%, 84.4%, 80%, Group A, B, and C, respectively; p>0.5). Hatching blastocyst formation on Day 5 was decreased in the non-off-gassing group (49% vs. 56.7%, p>0.5). Conclusions: Off-gassing for at least 72 hours decreases the toxicity of plasticware before use in in vitro fertilization cultures for HSSA. Further investigation needs to be done in order to standardize the bioassays used to evaluate this procedure.
Application of principal component analysis with instrumental analysis and sensory evaluation for assessment of chicken breast meat juiciness

ABSTRACT 1. The objectives of this study were to use principal component analysis (PCA) to analyse the variability of the three instrumental and 14 descriptive sensory properties of chicken breast meat. The meat was cooked until the internal temperature reached 85°C and further cooked for 0, 20, and 40 min. The second objective was to identify the most critical variables for assessing meat juiciness. 2. Cooking loss and moisture content exhibited high correlation with sensorial moisture release and mouth feel. 3. The distribution of objects on the axes of the first two principal components (PCs) enabled the identification of three groups undergoing different cooking durations. The four major PCs explained 80.0% of the total variability. 4. Cooking loss, moisture content, water-holding capacity, sensorial moisture release and mouth feel were demonstrated as the most effective variables for the first two PCs. PCA with instrumental and sensory analyses proved an effective procedure for systematically and comprehensively judging chicken meat juiciness.
Feasibility of bone marrow sparing volumetric modulated arc therapy to spare active bone marrow in cervical and vaginal cancer patients: a retrospective dosimetric analysis

Chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical and vaginal cancer. It is associated with high haematological toxicity (HT) that can lead to treatment interruptions and cancelled chemotherapy cycles, reducing the potential effectiveness of this regimen. Bone marrow sparing (BMS) utilising volumetric modulated arc therapy (VMAT) is one method to reduce dose to the active bone marrow (ABM) so that HT rates are reduced. The aim of this paper was to assess whether BMS‐VMAT can effectively spare the ABM whilst maintaining clinically acceptable target and organ‐at‐risk (OAR) doses.
Is neutral genetic diversity related to quantitative variation in semen traits in bulls?

Conservation decisions based on neutral genetic diversity have been observed to promote retention of useful quantitative variation in biological populations. An experiment was undertaken to determine the association between microsatellite marker polymorphisms and phenotypic variation in semen production and cryosurvival traits in bulls. Thirty-five ejaculates were collected from ten bulls of two breeds and evaluated before and after cryopreservation for several semen traits. The bulls were also genotyped using a set of sixteen bovine-specific microsatellite marker loci. Fixation indices (FST ), heterozygosity and Nei's genetic distance measures were computed from allele frequency data for each of the bulls. Molecular and phenotypic data were used to compute tri-distance matrices for the ten bulls and correlated using Mantel's test in GenAIEx 6.5. The study revealed extensive heterogeneity in semen traits, heterozygosity and FST values among the bulls. Large pairwise phenotypic and genetic distances were also observed. Correlation between pairwise genetic distances and phenotypic distances was significant and highly positive for sperm viability (r = 0.61, P < 0.001) and moderately positive for sperm motility (r = 0.40-42, P < 0.05) variables. For sperm morphology, ejaculate volume and sperm concentration, correlation with genetic distances was positive, low and not significantly different from zero (P > 0.05). A tendency for a triangular-shaped relationship between genetic and phenotypic distances for post-thaw motility and viability traits was also observed. Accordingly, association with neutral genetic diversity was absent for semen production traits and moderate to highly positive for sperm cryosurvival traits. Given these findings, conservation decisions based on neutral genetic diversity may capture variation in some adaptive traits, but not others.
ASSESSMENT OF RECURRENT ANAL FISTULAS TREATMENT WITH PLATELET-RICH PLASMA.

BACKGROUND Surgical treatment of recurrent anal fistulas can lead to numerous complications, including fecal incontinence. Therefore, sphincter preserving techniques are gaining more popularity. OBJECTIVE The aim of the study was to assess effectiveness of platelet-rich plasma (PRP) therapy in the patients with recurrent cryptoglandular anal fistulas. METHODS A cohort of 18 patients with anal fistulas was enrolled into a preliminary and prospective trial. They were divided into two groups consisting of eight and ten patients respectively. PRP was injected locally in all patients, however in the group II it was applied after 7 days drainage of fistulas with polyurethane foam or negative pressure wound therapy. On average, three doses of PRP were administered, but with the opportunity to double the number of applications if it was clinically justified. The patients were evaluated in an out-patient department after fortnight and then in 1, 6, and 12 months following the last PRP application. RESULTS Anal fistulas were closed in 4 (50%) patients from the group I and in 7 (70%) patients form the group II. Although, the difference between both groups was not statistically significant, PRP therapy should be preceded with fistulous tract drainage in all patients. Summarizing, that successful result was achieved in 11 (60%) patients from the entire group of 18 participants. CONCLUSION The rate of recurrent cryptoglandular anal fistulas closure reaching 60%, after topical treatment with PRP, exceeds the results of other sphincter-saving methods of treatment. Therefore, it might become a novel method of anal fistulas therapy.
Social participation and depressive symptoms in older African American cancer survivors: a comparison with non-cancer subjects

Abstract Objectives African Americans are differentially affected by most cancers compared to other racial groups. Social participation has demonstrated beneficial effects on mental health in older adults with a history of cancer. The purpose of the present study is to examine and compare the effects of specific social participation activities on depressive symptoms among older African Americans with and without a history of cancer. Method The study sample included 2,000 older African Americans selected from the National Health and Aging Trends Study. Waves from 2011 to 2018 were used. Mixed-effects logistic regressions were applied to examine the effects of four social participation activities on depressive symptoms among older African Americans with or without a history of cancer. Results Among older African American who had a history of cancer, visiting family and friends and attending religious services were related to lower odds of depressive symptoms. However, among older African Americans without a history of cancer, joining organized activities and going out for enjoyment predicted lower odds of depressive symptoms. Conclusion Older African Americans with a history of cancer tend to benefit from visiting family and friends and attending religious services in coping with depressive symptoms. Mental health services for this group could focus interventions on promoting social participation activities with family, friends, and religious congregants.
Removable Partial Dentures with Polyetheretherketone Framework: The Influence on Residual Ridge Stability.

PURPOSE To provide, in a clinical case-control study, 1-year data on edentulous residual ridge dimensional changes for patients wearing removable partial dentures (RPD) with Polyetheretherketone (PEEK) framework, fabricated with a digital workflow, and a control group of untreated patients. MATERIALS AND METHODS Ten patients treated with PEEK RPD, and 6 controls were studied. Intraoral scans at baseline (T0) and after a median period of one year (T1) were superimposed, trimmed, and reoriented (T0r and T1r), moved to a metrology software, and re-aligned. A curve (C0) was then traced on T0r, along the residual ridge crest; its projection (C1) on T1r was obtained. The mean distance C0-C1 was the dependent variable of interest and represented the 1-year changes in the height of the edentulous ridge. In addition, mean 3D distance between T0 and T1 at each edentulous area was measured. Differences in these outcomes measured between RPD treated and control groups were statistically assessed. RESULTS Twenty-six and 14 edentulous areas were investigated in the RPD treated and control groups, respectively. No significant differences were observed for potentially confounding variables, such as median follow-up time (12.5 vs 13 months, respectively), the alignment accuracy between T0r and T1r (0.01 mm vs 0 mm, respectively), the median number of remaining teeth (6 vs 8.5, respectively), and the median length of edentulous areas (25.5 mm vs 22.8 mm, respectively). For the outcomes of interest, no statistically significant difference was seen in the mean distance between C0 and C1 (i.e. changes in residual ridge height: -0.39 ±0.52 mm vs -0.52 ±0.54 mm, respectively) or in the mean 3D distance at corresponding points of the denture bearing areas (-0.3 ±0.46 mm vs -0.4 ±0.35, respectively). CONCLUSIONS Although 1 year is a relatively short observation period, this clinical study shows that there are no short term differences in edentulous residual ridge height and overall dimensions between patients wearing PEEK RPD, fabricated with a digital workflow, and controls without a RPD. This article is protected by copyright. All rights reserved.
Serum Contactin-1 in CIDP

Objective To investigate whether serum levels of contactin-1, a paranodal protein, correlate with paranodal injury as seen in patients with CIDP with antibodies targeting the paranodal region. Methods Serum contactin-1 levels were measured in 187 patients with CIDP and 222 healthy controls. Paranodal antibodies were investigated in all patients. Results Serum contactin-1 levels were lower in patients (N = 41) with paranodal antibodies compared with patients (N = 146) without paranodal antibodies (p < 0.01) and showed good discrimination between these groups (area under the curve 0.84; 95% CI: 0.76–0.93). Conclusions These findings suggest that serum contactin-1 levels have the potential to serve as a possible diagnostic biomarker of paranodal injury in CIDP. Classification of Evidence This study provides class II evidence that serum contactin-1 levels can discriminate between patients with CIDP with or without paranodal antibodies with a sensitivity of 71% (95% CI: 56%–85%) and a specificity of 97% (95% CI: 83%–100%).
GD2-directed bispecific trifunctional antibody outperforms dinutuximab beta in a murine model for aggressive metastasized neuroblastoma

Background Neuroblastoma is the most common extracranial solid tumor of childhood. Patients with high-risk disease undergo extremely aggressive therapy and nonetheless have cure rates below 50%. Treatment with the ch14.18 monoclonal antibody (dinutuximab beta), directed against the GD2 disialoganglioside, improved 5-year event-free survival in high-risk patients when administered in postconsolidation therapy and was recently implemented in standard therapy. Relapse still occurred in 57% of these patients, necessitating new therapeutic options. Bispecific trifunctional antibodies (trAbs) are IgG-like molecules directed against T cells and cancer surface antigens, redirecting T cells (via their CD3 specificity) and accessory immune cells (via their functioning Fc-fragment) toward tumor cells. We sought proof-of-concept for GD2/CD3-directed trAb efficacy against neuroblastoma. Methods We used two GD2-specific trAbs differing only in their CD3-binding specificity: EKTOMUN (GD2/human CD3) and SUREK (GD2/mouse Cd3). This allowed trAb evaluation in human and murine experimental settings. Tumor-blind trAb and the ch14.18 antibody were used as controls. A coculture model of human peripheral blood mononuclear cells (PBMCs) and neuroblastoma cell lines was established to evaluate trAb antitumor efficacy by assessing expression of T-cell surface markers for activation, proinflammatory cytokine release and cytotoxicity assays. Characteristics of tumor-infiltrating T cells and response of neuroblastoma metastases to SUREK treatment were investigated in a syngeneic immunocompetent neuroblastoma mouse model mimicking minimal residual disease. Results We show that EKTOMUN treatment caused effector cell activation and release of proinflammatory cytokines in coculture with neuroblastoma cell lines. Furthermore, EKTOMUN mediated GD2-dependent cytotoxic effects in human neuroblastoma cell lines in coculture with PBMCs, irrespective of the level of target antigen expression. This effect was dependent on the presence of accessory immune cells. Treatment with SUREK reduced the intratumor Cd4/Cd8 ratio and activated tumor infiltrating T cells in vivo. In a minimal residual disease model for neuroblastoma, we demonstrated that single-agent treatment with SUREK strongly reduced or eliminated neuroblastoma metastases in vivo. SUREK as well as EKTOMUN demonstrated superior tumor control compared with the anti-GD2 antibody, ch14.18. Conclusions Here we provide proof-of-concept for EKTOMUN preclinical efficacy against neuroblastoma, presenting this bispecific trAb as a promising new agent to fight neuroblastoma.
NUTRITIONAL MANAGEMENT OF LIVER CIRRHOSIS AND ITS COMPLICATIONS IN HOSPITALIZED PATIENTS.

BACKGROUND Cirrhosis is a chronic and progressive liver disease that occurs from prolonged hepatocellular injury. Malnutrition causes complications in cirrhosis patients that worsen the condition to liver failure. Both are closely linked and increase the chances of morbidity and mortality. Regular nutritional screening and monitoring is prime concern for such patients including comprehensive dietary history, laboratory tests, and evaluation of muscle loss and strength capabilities to determine the degree of frailty. For efficient assessment of liver cirrhosis patients Subjective Global Assessment has been used worldwide. The nutritional objectives for such individuals should be to regain liver functions, to prevent complications associated, and to overcome nutritional deficiencies causing malnutrition. METHODS We conducted a literature review using PubMed, Google Scholar and Science Direct for this purpose, a total of 130 articles were reviewed out of which 80 (from the past 5 years) including originally published research, review articles and abstracts were also included. Exclusion criteria of the selected studies was year of publication, irrelevancy and animal studies based on the purpose of current study. The aim of this study was to check nutritional management in patients having complications of liver cirrhosis. RESULTS According to the guidelines, for the conservation of normal nutritional status of the malnourished patients', energy should be provided 35 kcal/kg/day while to prevent hypoalbuminemia and maintain the protein stores in the body, 1.5 g/kg/day protein has been recommended. Carbohydrates and fats for cirrhosis patients are recommended 50% to 60% and 10% to 20% of the total dietary intake respectively. CONCLUSION Initial identification and prevention of malnutrition have the probability to lead to better health outcomes, prevention of complications of the disease, and improving quality of life.