Miracle-dz/UniFAR-FTUs huggingface dataset:
JNK Signaling in Stem Cell Self-Renewal and Differentiation

C-JUN N-terminal kinases (JNKs), which belong to the mitogen-activated protein kinase (MAPK) family, are evolutionarily conserved kinases that mediate cell responses to various types of extracellular stress insults. They regulate physiological processes such as embryonic development and tissue regeneration, playing roles in cell proliferation and programmed cell death. JNK signaling is also involved in tumorigenesis and progression of several types of malignancies. Recent studies have shown that JNK signaling has crucial roles in regulating the traits of cancer stem cells (CSCs). Here we describe the functions of the JNK signaling pathway in self-renewal and differentiation, which are essential features of various types of stem cells, such as embryonic, induced pluripotent, and adult tissue-specific stem cells. We also review current knowledge of JNK signaling in CSCs and discuss its role in maintaining the CSC phenotype. A better understanding of JNK signaling as an essential regulator of stemness may provide a basis for the development of regenerative medicine and new therapeutic strategies against malignant tumors.
COVID-19 infections are also affected by human ACE1 D/I polymorphism

The number of victims of the COVID-19 pandemic shows important geographical differences. In this study, a number of human genetic polymorphisms were compared to the number of Covid-19 patients and Covid-19 mortality. Data from 33 countries were analyzed. Among the polymorphisms tested, the human angiotensine converting enzyme (ACE) polymorphism turned out to be a determinant factor in both prevalence and mortality. The present findings may partly explain why some countries are more affected than others by the Covid-19 pandemic.
Changes in P1 latencies of children with normal hearing and those with cochlear implants

Background/aim The aim of this study was to determine the age-related latency interval of P1 latencies of children with normal hearing, and to evaluate the P1 latency changes after surgery in children who underwent cochlear implantation. Materials and methods We evaluated 60 children with normal hearing and 16 children with cochlear implants aged 0–6 years using cortical auditory evoked potentials. P1 latencies were measured only once in the children with normal hearing, and on the postoperative first day, and the first, third, and sixth postoperative months in the children with cochlear implants. Results There was a statistically significant decrease in the P1 latencies as the age increased in children with normal hearing (P < 0.001). It was determined that when the external partof the cochlear implant was applied, the P1 latencies of children with cochlear implants were significantly longer than those of age-matched children with normal hearing (P < 0.001). This difference disappeared in 10 children with implants at the third and sixth months, but significant differences remained in 6 children. Conclusion P1 latency could be used as an objective tool to evaluate the normal development of auditory pathways, and may be helpful in the effective programming of children undergoing cochlear implantation.
18F-FDG PET Assessment of Malignant Pleural Mesothelioma: Total Lesion Volume and Total Lesion Glycolysis—The Central Role of Volume

Cancer survival is related to tumor volume. 18F-FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in 2 forms: the first is total lesion volume (TLV) based on the number of voxels in the tumor, and the second is total lesion glycolysis (TLG), which is the TLV multiplied by the average SUL (i.e., SUV normalized for lean mass) of the tumor (SULaverage). In this study, we measured tumor volume in patients with malignant pleural mesothelioma (MPM). Methods: A threshold-based program in Interactive Data Language was developed to measure tumor volume in 18F-FDG PET images. Nineteen patients with MPM were studied before and after 2 cycles (6 wk) of chemoimmunotherapy. Measurements included TLV, TLG, the sum of the SULs in the tumor (SULtotal, a measure of total 18F-FDG uptake), and SULaverage. Results: Baseline TLV ranged from 11 to 2,610 cm3. TLG ranged from 32 to 8,552 cm3 g/mL and correlated strongly with TLV. Although tumor volumes ranged over 3 orders of magnitude, SULaverage stayed within a narrow range of 2.4–5.3 units. Thus, TLV was the major component of TLG, whereas SULaverage was a minor component and was essentially constant. Further evaluation of SULaverage showed that in this cohort its 2 components, SULtotal and TLV, changed in parallel and were strongly correlated (r = 0.99, P < 0.01). Thus, whether the tumors were large or small, 18F-FDG uptake as measured by SULtotal was proportional to the TLV. Conclusion: TLG equals TLV multiplied by SULaverage, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of metabolic activity in tumors, is also in this cohort a measure of tumor volume. The constancy of SULaverage is due to the fact that 18F-FDG uptake is proportional to tumor volume. Thus, in this study, 18F-FDG uptake was also a measure of volume.
Clinical Consensus Statement: Ankyloglossia in Children

Objective To identify and seek consensus on issues and controversies related to ankyloglossia and upper lip tie in children by using established methodology for American Academy of Otolaryngology–Head and Neck Surgery clinical consensus statements. Methods An expert panel of pediatric otolaryngologists was assembled with nominated representatives of otolaryngology organizations. The target population was children aged 0 to 18 years, including breastfeeding infants. A modified Delphi method was used to distill expert opinion into clinical statements that met a standardized definition of consensus, per established methodology published by the American Academy of Otolaryngology–Head and Neck Surgery. Results After 3 iterative Delphi method surveys of 89 total statements, 41 met the predefined criteria for consensus, 17 were near consensus, and 28 did not reach consensus. The clinical statements were grouped into several categories for the purposes of presentation and discussion: ankyloglossia (general), buccal tie, ankyloglossia and sleep apnea, ankyloglossia and breastfeeding, frenotomy indications and informed consent, frenotomy procedure, ankyloglossia in older children, and maxillary labial frenulum. Conclusion This expert panel reached consensus on several statements that clarify the diagnosis, management, and treatment of ankyloglossia in children 0 to 18 years of age. Lack of consensus on other statements likely reflects knowledge gaps and lack of evidence regarding the diagnosis, management, and treatment of ankyloglossia. Expert panel consensus may provide helpful information for otolaryngologists treating patients with ankyloglossia.
Survival among patients with glioma in the US Military Health System: A comparison with patients in the Surveillance, Epidemiology, and End Results program

Glioma is the most common malignant brain cancer. Accessibility to health care is an important factor affecting cancer outcomes in the US general population. The US Military Health System (MHS) provides universal health care to its beneficiaries. It is unknown whether this universal health care has translated into improved survival outcomes among MHS beneficiaries with glioma. This study compared the overall survival of patients with glioma in the MHS with the overall survival of patients with glioma in the general population.
Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

Background: non-alcoholic steatohepatitis (NASH) recently headlined hepatocellular carcinoma (HCC) worldwide. This study aims to unveil the role of some unaddressed critical players that might aid in understanding, predicting, and targeting NASH and NASH-HCC. Methods: Serum interleukin 13 (IL-13) levels and single nucleotide polymorphisms (SNPs) within interleukin (IL)-13 rs20541, IL-13 receptors (IL-13R1) rs2248841, (IL-13R2) rs5946040, signal transducer activator of transcription 6 (STAT6) rs167769, yes-associated protein (YAP1) rs11225163, programmed death-ligand 1 (PD-L1) rs2282055, and programmed death-ligand 2 (PD-L2) rs7854413 genes were analyzed by qRT-PCR. Multiple stepwise regression analysis was performed on a cohort of 134 Egyptian male patients diagnosed with NASH and NASH-HCC. RESULTS: higher serum alpha-fetoprotein (AFP) and higher serum IL-13 levels were directly associated with HCC development in NASH (odds ratio (OR) 19.6 and 1.9 p < 0.01). Reversibly, the presence of the C/C genotype in STAT6 rs167769 and the C allele carrier YAP1 rs11225163 were inversely associated with HCC in NASH patients (OR 0.015 and 0.047 p < 0.01). A predictive model was formulated with 97.5% specificity, 90.9% sensitivity, and 94.8% accuracy. Moreover, higher serum IL-13 levels and the presence of PD-L2 rs7854413 C allele carriers were associated with advanced fibrosis progression in NASH patients (OR 1.432 and 3.797 p < 0.01). Serum levels of IL-13 and C/C genotype in STAT6 rs167769 significantly increased the predictive capacity of serum AFP to predict HCC in F1–F2 and in F3–F4 fibrosis grades NASH patients. Conclusion: association between serum IL-13 and PD-L2 rs7854413 polymorphism successfully predict advanced fibrosis in NASH. However, HCC development in NASH is associated with higher serum AFP, IL-13 levels, and STAT6 rs167769, YAP1 rs11225163 polymorphisms.
Investigation of Heterologously Expressed Glucose-6-Phosphate Dehydrogenase Genes in a Yeast zwf1 Deletion

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme of the oxidative part of the pentose phosphate pathway and serves as the major source of NADPH for metabolic reactions and oxidative stress response in pro- and eukaryotic cells. We here report on a strain of the model yeast Saccharomyces cerevisiae which lacks the G6PD-encoding ZWF1 gene and displays distinct growth retardation on rich and synthetic media, as well as a strongly reduced chronological lifespan. This strain was used as a recipient to introduce plasmid-encoded heterologous G6PD genes, synthesized in the yeast codon usage and expressed under the control of the native PFK2 promotor. Complementation of the hypersensitivity of the zwf1 mutant towards hydrogen peroxide to different degrees was observed for the genes from humans (HsG6PD1), the milk yeast Kluyveromyces lactis (KlZWF1), the bacteria Escherichia coli (EcZWF1) and Leuconostoc mesenteroides (LmZWF1), as well as the genes encoding three different plant G6PD isoforms from Arabidopsis thaliana (AtG6PD1, AtG6PD5, AtG6PD6). The plastidic AtG6PD1 isoform retained its redox-sensitive activity when produced in the yeast as a cytosolic enzyme, demonstrating the suitability of this host for determination of its physiological properties. Mutations precluding the formation of a disulfide bridge in AtG6PD1 abolished its redox-sensitivity but improved its capacity to complement the yeast zwf1 deletion. Given the importance of G6PD in human diseases and plant growth, this heterologous expression system offers a broad range of applications.
3D Printing of Piezoelectric Barium Titanate-Hydroxyapatite Scaffolds with Interconnected Porosity for Bone Tissue Engineering

The prevalence of large bone defects is still a major problem in surgical clinics. It is, thus, not a surprise that bone-related research, especially in the field of bone tissue engineering, is a major issue in medical research. Researchers worldwide are searching for the missing link in engineering bone graft materials that mimic bones, and foster osteogenesis and bone remodeling. One approach is the combination of additive manufacturing technology with smart and additionally electrically active biomaterials. In this study, we performed a three-dimensional (3D) printing process to fabricate piezoelectric, porous barium titanate (BaTiO3) and hydroxyapatite (HA) composite scaffolds. The printed scaffolds indicate good cytocompatibility and cell attachment as well as bone mimicking piezoelectric properties with a piezoelectric constant of 3 pC/N. This work represents a promising first approach to creating an implant material with improved bone regenerating potential, in combination with an interconnected porous network and a microporosity, known to enhance bone growth and vascularization.
Elucidating Specificity Opens a Window to the Complexity of Both the Innate and Adaptive Immune Systems

Science is a tedious and painstaking business. Many discoveries are considered incremental, individually not necessarily earth shattering, but collectively providing the critical broad framework on which pivotal insights can emerge. Transformational discoveries spring from this knowledge legacy of others and spur a fervent discovery process, often driven by technological developments. The seminal discovery of major histocompatibility class restriction I (MHCI) and its role in antiviral infections by Doherty and Zinkernagel in 1974 was one such discovery—the key that unlocked the treasure chest to the rich tapestry of the diversity of the immune system. An army of researchers have teased apart the different elements of the immune response, which now brings us to a deeper understanding of immune memory and protective immunity. In this process, it has uncovered a multitude of cell types that bridge the innate and adaptive arms of the immune system—blurring the line between these two branches—and ultimately fortifying the development of long-term immune protection.
Between-limb asymmetry in kinetic and temporal characteristics during bilateral plyometric drop jumps from different heights

ABSTRACT This study investigated the between-limb asymmetry in kinetic and temporal characteristics during bilateral plyometric drop jumps from different heights. Seventeen male basketball players performed drop jumps from 3 heights on two platforms in randomized orders. Vertical ground reaction force data were analysed with respect to the lead limb (i.e. the limb stepping off the raised platform first) and trail limb. Peak forces and loading rates of each limb were calculated. The absolute time differential between the two limbs at initial ground contact and takeoff were determined. The frequency of symmetrical landing and taking off with “both limbs together” were counted using 3 time windows. Results showed that the lead limb displayed higher peak forces and loading rates than the trail limb across all heights (p <.05). As drop height increased, the absolute time differentials decreased at initial ground contact (p <.001) but increased at takeoff (p =.035). The greater the preset time window, the more landings and takeoffs were classified as bilaterally symmetrical. In conclusion, higher drop heights allowed subjects to become more bilaterally symmetrical in the timing of landing but this reduction in temporal asymmetry did not accompany with any reduction in kinetic asymmetry.
Improving the coverage of credible sets in Bayesian genetic fine-mapping

Genome Wide Association Studies (GWAS) have successfully identified thousands of loci associated with human diseases. Bayesian genetic fine-mapping studies aim to identify the specific causal variants within GWAS loci responsible for each association, reporting credible sets of plausible causal variants, which are interpreted as containing the causal variant with some “coverage probability”. Here, we use simulations to demonstrate that the coverage probabilities are over-conservative in most fine-mapping situations. We show that this is because fine-mapping data sets are not randomly selected from amongst all causal variants, but from amongst causal variants with larger effect sizes. We present a method to re-estimate the coverage of credible sets using rapid simulations based on the observed, or estimated, SNP correlation structure, we call this the “adjusted coverage estimate”. This is extended to find “adjusted credible sets”, which are the smallest set of variants such that their adjusted coverage estimate meets the target coverage. We use our method to improve the resolution of a fine-mapping study of type 1 diabetes. We found that in 27 out of 39 associated genomic regions our method could reduce the number of potentially causal variants to consider for follow-up, and found that none of the 95% or 99% credible sets required the inclusion of more variants—a pattern matched in simulations of well powered GWAS. Crucially, our method requires only GWAS summary statistics and remains accurate when SNP correlations are estimated from a large reference panel. Using our method to improve the resolution of fine-mapping studies will enable more efficient expenditure of resources in the follow-up process of annotating the variants in the credible set to determine the implicated genes and pathways in human diseases.
Comorbidity in patients with chronic coronary syndromes: prevalence and assessment.

OBJECTIVE The aim: To carry out an evaluation of comorbidities in CCS patients having undergone PCI for stable coronary artery diseases (planned) or PCI in myocardial infarction (urgent) with the aim of justifying the best management strategies. PATIENTS AND METHODS Materials and methods: We carried out an analysis of comorbid pathology spreading and the evaluation of multiple comorbidities using of Combined Age Charlson Comorbidity Index (CA-CCI) - in 138 patients below 75 yrs having undergone urgent and planned PCI. These patients were divided into two groups; the Ist one included 60 patients with urgent PCI (angioplasty with stent), the 2nd group - 78 patients with planned PCI. RESULTS Results: We found a high prevalence of comorbidity in CCS patients: the mean number of diseases in patients of the 1st and 2nd groups were 8.2±0.3 and 9.3±0.4, and the CACCI values - 7.3±0.3 and 7.5±0.2, respectively (p>0.05). Ten and more diseases were found in (28.3±5.8%) patients from the 1st group and in (43.6±5.6%) patients from the 2nd group (p=0.06). The most frequent comorbidities were arterial hypertension, cerebrovascular diseases, peripheral arterial disease, type 2 diabetes mellitus, and impaired glucose metabolism. CONCLUSION Conclusions: Comprehensive assessment and management of patients with CCS who undergo PCI remains a current problem in modern medicine, given the high prevalence of comorbid pathology.
Identifying patterns in foraging-area origins in breeding aggregations of migratory species: Loggerhead turtles in the Northwest Atlantic

Population assessments conducted at reproductive sites of migratory species necessitate understanding the foraging-area origins of breeding individuals. Without this information, efforts to contextualize changes in breeding populations and develop effective management strategies are compromised. We used stable isotope analysis of tissue samples collected from loggerhead sea turtles (Caretta caretta) nesting at seven sites in the Northern Recovery Unit (NRU) of the eastern United States (North Carolina, South Carolina and Georgia) to assign females to three separate foraging areas in the Northwest Atlantic Ocean (NWA). We found that the majority of the females at NRU nesting sites (84.4%) use more northern foraging areas in the Mid-Atlantic Bight, while fewer females use more proximate foraging areas in the South Atlantic Bight (13.4%) and more southerly foraging areas in the Subtropical Northwest Atlantic (2.2%). We did not find significant latitudinal or temporal trends in the proportions of NRU females originating from different foraging areas. Combining these findings with previous data from stable isotope and satellite tracking studies across NWA nesting sites showed that variation in the proportion of adult loggerheads originating from different foraging areas is primarily related differences between recovery units: individuals in the NRU primarily use the Mid-Atlantic Bight foraging area, while individuals from the three Florida recovery units primarily use the Subtropical Northwest Atlantic and Eastern Gulf of Mexico foraging areas. Because each foraging area is associated with its own distinct ecological characteristics, environmental fluctuations and anthropogenic threats that affect the abundance and productivity of individuals at nesting sites, this information is critical for accurately evaluating population trends and developing effective region-specific management strategies.
Role of Parents in Body Mass Reduction in Children with Obesity—Adherence and Success of 1-Year Participation in an Intervention Program

Background and Objectives: Obesity in children and adolescents results in a number of serious health-related consequences necessitating early treatment. Support from family members and family-focused lifestyle interventions can improve effectiveness of the treatment. The aim of the study was to assess the effects of parental characteristics and family-based dietary habits on the adherence and success of a body mass reduction program in children with obesity included in a lifestyle intervention program after 1 year. Materials and Methods: The program included dietetic, psychosocial, and endocrine counseling given to individuals either alone or in groups and was conducted by a multidisciplinary team (consisting of endocrinologists, nurses, psychologists, social counselors, dietitians, and physiotherapists). A total of 113 children aged 10–17 years (mean age 12.9 ± 2.0; 60 girls, 53 boys) were included in the program. After 1 year of participation, the rate of adherence and success were assessed. The effect of the participants’ general characteristics, including anthropometric data, as well as parental characteristics (marital status, employment, education, body mass index (BMI), duration of breastfeeding) and the circumstances of meal consumption (eating at home or outside, fast food consumption), was analyzed. Results: The most important factors predicting body mass reduction success were baseline BMI (p < 0.0001) and waist–hip ratio (WHR) (p = 0.04), but they did not predict body mass reduction adherence. Conclusions: The meal consumption habits and support from family members may be among the determinants of adherence to a body mass reduction program for preadolescents and adolescents with obesity. However, the results of the presented study suggested that baseline BMI and WHR are the most important determinants of the body mass reduction success.