Miracle-dz/UniFAR-FTUs huggingface dataset:
High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts

Mitochondria play a key role in metabolic transitions involved in the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), but the underlying molecular mechanisms remain largely unexplored. To obtain new insight into the mechanisms of cellular reprogramming, we studied the role of FAH domain-containing protein 1 (FAHD1) in the reprogramming of murine embryonic fibroblasts (MEFs) into iPSCs and their subsequent differentiation into neuronal cells. MEFs from wild type (WT) and Fahd1-knock-out (KO) mice were reprogrammed into iPSCs and characterized for alterations in metabolic parameters and the expression of marker genes indicating mitochondrial biogenesis. Fahd1-KO MEFs showed a higher reprogramming efficiency accompanied by a significant increase in glycolytic activity as compared to WT. We also observed a strong increase of mitochondrial DNA copy number and expression of biogenesis marker genes in Fahd1-KO iPSCs relative to WT. Neuronal differentiation of iPSCs was accompanied by increased expression of mitochondrial biogenesis genes in both WT and Fahd1-KO neurons with higher expression in Fahd1-KO neurons. Together these observations establish a role of FAHD1 as a potential negative regulator of reprogramming and add additional insight into mechanisms by which FAHD1 modulates mitochondrial functions.
Urinary Potassium and Kidney Function Decline in the Population—Observational Study

Background—Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods—Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983–1985), exam-2 (1989–1992), and exam-3 (2001–2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results—In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and −0.059/0.019) nor at exam-2 (0.024 and −0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR < 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion—In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.
Association of Family History and Life Habits in the Development of Colorectal Cancer: A Matched Case-Control Study in Mexico

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and, as such, is important for public health. The increased incidence of this neoplasm is attributed to non-modifiable controls such as family history and modifiable variable behavioral risk factors involved in lifestyle like diets in Mexico. The presence of these factors is unknown. Therefore, the aim of this study was to evaluate family history and lifestyle factors associated with developing colorectal cancer in a Mexican population. Descriptive statistics and multivariate logistic regression were used to estimate the adjusted odds ratios (OR), as well as the 95% confidence intervals (CI). In this paper, significant differences were demonstrated between cases and controls. A family history of cancer (FHC) increased the probability of CRC [OR = 3.19 (95% CI: 1.81–5.60)]. The area of urban residence was found to be a protective factor compared to the rural area. This was also the case for frequent consumption of fruits [OR = 0.49 (95% CI: 0.28–0.88)], the frequent consumption of beef [OR = 2.95 (95% CI: 1.05–8.26)], pork [OR = 3.26 (95% CI: 1.34–7.90)], and region-typical fried food [OR = 2.79 (95% CI (1.32–5.89)]. These results provide additional evidence supporting the association of some CRC risk factors with family history of cancer, low fruit consumption, high consumption of red meat, and fried foods typical of the region of México. It is important to establish intervention methods, as well as genetic counseling to relatives of patients with CRC.
Alpha-1 Antitrypsin Augmentation Inhibits Proteolysis of Neutrophil Membrane Voltage-Gated Proton Channel-1 in Alpha-1 Deficient Individuals

Background and Objectives: Alpha-1 antitrypsin is a serine protease inhibitor that demonstrates an array of immunomodulatory functions. Individuals with the genetic condition of alpha-1 antitrypsin deficiency (AATD) are at increased risk of early onset emphysematous lung disease. This lung disease is partly driven by neutrophil mediated lung destruction in an environment of low AAT. As peripheral neutrophil hyper-responsiveness in AATD leads to excessive degranulation and increased migration to the airways, we examined the expression of the membrane voltage-gated proton channel-1 (HVCN1), which is integrally linked to neutrophil function. The objectives of this study were to evaluate altered HVCN1 in AATD neutrophils, serine protease-dependent degradation of HVCN1, and to investigate the ability of serum AAT to control HVCN1 expression. Materials and Methods: Circulating neutrophils were purified from AATD patients (n = 20), AATD patients receiving AAT augmentation therapy (n = 3) and healthy controls (n = 20). HVCN1 neutrophil expression was assessed by flow cytometry and Western blot analysis. Neutrophil membrane bound elastase was measured by fluorescence resonance energy transfer. Results: In this study we demonstrated that HVCN1 protein is under-expressed in AATD neutrophils (p = 0.02), suggesting a link between reduced HVCN1 expression and AAT deficiency. We have demonstrated that HVCN1 undergoes significant proteolytic degradation in activated neutrophils (p < 0.0001), primarily due to neutrophil elastase activity (p = 0.0004). In addition, the treatment of AATD individuals with AAT augmentation therapy increased neutrophil plasma membrane HVCN1 expression (p = 0.01). Conclusions: Our results demonstrate reduced levels of HVCN1 in peripheral blood neutrophils that may influence the neutrophil-dominated immune response in the AATD airways and highlights the role of antiprotease treatment and specifically AAT augmentation therapy in protecting neutrophil membrane expression of HVCN1.
Association of Platelets and White Blood Cells Subtypes with Trauma Patients’ Mortality Outcome in the Intensive Care Unit

Background: White blood cell (WBC) subtypes have been suggested to reflect patients’ immune-inflammatory status. Furthermore, the derived ratio of platelets and WBC subtypes, including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), is proposed to be associated with patient outcome. Therefore, this study aimed to identify the association of platelets and white blood cells subtypes with the mortality outcome of trauma patients in the intensive care unit (ICU). Method: The medical information from 2854 adult trauma patients admitted to the ICU between 1 January 2009 and 31 December 2019 were retrospectively retrieved from the Trauma Registry System and classified into two groups: the survivors group (n = 2524) and the death group (n = 330). The levels of monocytes, neutrophils, lymphocytes, platelets, and blood-drawn laboratory data detected upon patient arrival to the emergency room and the derived MLR, NLR, and PLR were calculated. Multivariate logistic regression analysis was used to determine the independent effects of univariate predictive variables on mortality occurrence. Result: The results revealed the patients who died had significantly lower platelet counts (175,842 ± 61,713 vs. 206,890 ± 69,006/μL, p < 0.001) but higher levels of lymphocytes (2458 ± 1940 vs. 1971 ± 1453/μL, p < 0.001) than the surviving patients. However, monocyte and neutrophil levels were not significantly different between the death and survivor groups. Moreover, dead patients had a significantly lower PLR than survivors (124.3 ± 110.3 vs. 150.6 ± 106.5, p < 0.001). However, there was no significant difference in MLR or NLR between the dead patients and the survivors. Multivariate logistic regression revealed that male gender, old age, pre-existing hypertension, coronary artery disease and end-stage renal disease, lower Glasgow Coma Scale (GCS), higher Injury Severity Score (ISS), higher level of lymphocytes and lower level of red blood cells and platelets, longer activated partial thromboplastin time (aPTT), and lower level of PLR were independent risk factors associated with higher odds of trauma patient mortality outcome in the ICU. Conclusion: This study revealed that a higher lymphocyte count, lower platelet count, and a lower PLR were associated with higher risk of death in ICU trauma patients.
Entrepreneurship Education Meets FabLab: Lessons Learned with Teenagers

Digital fabrication, making and entrepreneurship education all have potential to empower children and increase their abilities to participate and shape the society and digitalization within, and act as active “protagonists” instead of passive consumers. While the potential of these educational trends has been acknowledged, they have mostly been studied separately and without specific focus on challenges involved. We have conducted a business innovation project with teenagers at school, combining elements of digital fabrication, making and entrepreneurship education. Our qualitative, data-driven analysis focused on the process and the challenges involved in the endeavor. As a result, we generate a list of lessons learned associated with teenagers adopting the role of a protagonist, driving business innovation. Our main findings relate to the lessons learned on the importance of balancing the making activities with the entrepreneurial aspects and negotiating the roles and responsibilities between the adult participants.
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Physiological and Pathological Processes within the Gastrointestinal Tract: A Review

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the central nervous system (CNS) and many peripheral organs, such as the digestive tract, endocrine, reproductive and respiratory systems, where it plays different regulatory functions and exerts a cytoprotective effect. The multifarious physiological effects of PACAP are mediated through binding to different G protein-coupled receptors, including PAC1 (PAC1-R), VPAC1 (VPAC1-R) and VPAC2 (VPAC2-R) receptors. In the gastrointestinal (GI) tract, PACAP plays an important regulatory function. PACAP stimulates the secretion of digestive juices and hormone release, regulates smooth muscle contraction, local blood flow, cell migration and proliferation. Additionally, there are many reports confirming the involvement of PACAP in pathological processes within the GI tract, including inflammatory states, neuronal injury, diabetes, intoxication and neoplastic processes. The purpose of this review is to summarize the distribution and pleiotropic action of PACAP in the control of GI tract function and its cytoprotective effect in the course of GI tract disorders.
Dispositional mindfulness predicting psychological adjustment among college students: the role of rumination and gender

Abstract Objective This study examined rumination as a mediator of the relationship between dispositional mindfulness (DM) and depression, loneliness, and anxiety, while considering gender as a moderator of these mediation models. Participants Three hundred and nineteen undergraduate students (49.5% female; M = 18.90 years) participated with data collected from January 2018 to April 2019. Methods Self-report measures of DM, rumination, symptoms of anxiety and depression, loneliness, and social support were completed. Results Males scored significantly higher than females on DM, while females scored significantly higher than males on rumination and psychological distress. Rumination mediated the relationship between DM and all adjustment variables. The mediation model predicting depression was moderated by gender, showing stronger effects for females than males. Conclusion Results support rumination as a mechanism underlying the association between DM and psychological adjustment and suggest that targeting both DM and rumination could maximize the effectiveness of mindfulness-based interventions for college students’ well-being.
Mobile Phone Use during Gait: The Role of Perceived Prioritization and Executive Control

(1) Background: Mobile phone use during gait is associated with adverse health outcomes, namely increased risk of pedestrian injury. Healthy individuals can voluntarily prioritize concurrent task performance, but the factors underlying the impact of phone use during walking remain largely unknown. Thus, the objective of this work was to evaluate the relationship between subjective (perceived) prioritization, cognitive flexibility and dual-task performance when using a mobile phone during walking. (2) Methods: Thirty young participants walked for one minute with and without reading or texting on a mobile phone, as well as reading or texting while sitting. Walking performance (kinematics) was recorded, as well as phone use (text comprehension, text read/written), mental workload, perceived prioritization (visual analog scale), and cognitive flexibility (trail-making test). (3) Results: Texting while walking was associated with larger decreases in gait speed, larger gait variability, higher mental workload, and lower text comprehension compared to reading. Perceived prioritization was associated with walking dual-task costs (DTCs) (r = 0.39–0.42, p < 0.04) when texting, and better cognitive flexibility was associated with lower gait DTCs when texting (r = 0.55, p = 0.002) but not reading. (4) Conclusions: The context-dependent link between perceived prioritization, cognitive flexibility, and walking DTCs promotes our understanding of the factors underlying texting-while-walking performance. This could identify individuals who are more prone to dual-task interference in this increasingly common and dangerous task.
Antibacterial Polysiloxane Polymers and Coatings for Cochlear Implants

Within this study, new materials were synthesized and characterized based on polysiloxane modified with different ratios of N-acetyl-l-cysteine (NAC) and crosslinked via UV-assisted thiol-ene addition, in order to obtain efficient membranes able to resist bacterial adherence and biofilm formation. These membranes were subjected to in vitro testing for microbial adherence against S. pneumoniae using standardized tests. WISTAR rats were implanted for 4 weeks with crosslinked siloxane samples without and with NAC. A set of physical characterization methods was employed to assess the chemical structure and morphological aspects of the new synthetized materials before and after contact with the microbiological medium.
Smoflipid Is Better Than Lipofundin for Long-Term Neurodevelopmental Outcomes in Preterm Infants

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes −9 or −10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.
Muscle Work and Its Relationship with ACE and ACTN3 Polymorphisms Are Associated with the Improvement of Explosive Strength

Background: The potential influence of genetics in athletic performance allows the search for genetic profiles associated with muscular work for the orientation of strength training and sports selection. The purpose of the study was to analyze four muscular exercises for effectiveness in improving explosive strength variables, associated to the genetics in Angiotensin Converting Enzyme (ACE) and α-actinin-3 (ACTN3) polymorphisms. Methods: A randomized controlled trial was conducted on a sample of 80 subjects allocated into four groups: concentric muscle work (CMW), eccentric muscle work (EMW), concentric-eccentric muscle (C-EMW) work and isometric muscular work (IMW), by block and gender randomization. Vertical jump, long jump, power jump, and speed were measured to study explosive strength. Genotypic frequencies of ACE (rs4646994) and ACTN3 (rs1815739) were obtained by polymerase chain reaction. Results: ACE gen showed significant improvements regarding the DD genotype in the Sargent test (p = 0.003) and sprint velocity test (p = 0.017). In the ACTN3 gene, the RR variable obtained improvement results with regard to RX and XX variables in long jump (p < 0.001), Sargent test (p < 0.001) and power jump (p = 0.004). Conclusions: The selected genes demonstrated an influence on the muscle work and the improvement in explosive strength variables with a decisive role regarding the type of muscle work performed.
Risks and Function of Breast Cancer Susceptibility Alleles

Simple Summary Population-based genetic risk stratification and detection of early-stage breast cancers will improve approaches to prevent and reduce disease-associated mortalities. In this review, we summarize the latest discoveries in breast cancer susceptibility genetics and propose how these findings can be applied in the clinical arena to improve risk prediction and prevention of breast cancer. We also review the latest approaches and progress aimed at elucidating the functional consequences of both high and moderate penetrance genetic variation, which tend to lie in the protein coding regions of breast cancer susceptibility genes, and common low penetrance breast cancer risk alleles which tend to lie in non-protein coding DNA regions and affect gene regulation. For non-coding risk variation, there is no genetic code to interpret the function of common risk allele; and so, we provide the reader with an illustration of the step-by-step methods to understand their functional impact on breast cancer disease biology. Abstract Family history remains one of the strongest risk factors for breast cancer. It is well established that women with a first-degree relative affected by breast cancer are twice as likely to develop the disease themselves. Twins studies indicate that this is most likely due to shared genetics rather than shared epidemiological/lifestyle risk factors. Linkage and targeted sequencing studies have shown that rare high- and moderate-penetrance germline variants in genes involved in the DNA damage response (DDR) including BRCA1, BRCA2, PALB2, ATM, and TP53 are responsible for a proportion of breast cancer cases. However, breast cancer is a heterogeneous disease, and there is now strong evidence that different risk alleles can predispose to different subtypes of breast cancer. Here, we review the associations between the different genes and subtype-specificity of breast cancer based on the most comprehensive genetic studies published. Genome-wide association studies (GWAS) have also been used to identify an additional hereditary component of breast cancer, and have identified hundreds of common, low-penetrance susceptibility alleles. The combination of these low penetrance risk variants, summed as a polygenic risk score (PRS), can identify individuals across the spectrum of disease risk. However, there remains a substantial bottleneck between the discovery of GWAS-risk variants and their contribution to tumorigenesis mainly because the majority of these variants map to the non-protein coding genome. A range of functional genomic approaches are needed to identify the causal risk variants and target susceptibility genes and establish their underlying role in disease biology. We discuss how the application of these multidisciplinary approaches to understand genetic risk for breast cancer can be used to identify individuals in the population that may benefit from clinical interventions including screening for early detection and prevention, and treatment strategies to reduce breast cancer-related mortalities.
Predicting 1-Year Mortality after Hip Fracture Surgery: An Evaluation of Multiple Machine Learning Approaches

Postoperative death within 1 year following hip fracture surgery is reported to be up to 27%. In the current study, we benchmarked the predictive precision and accuracy of the algorithms support vector machine (SVM), naïve Bayes classifier (NB), and random forest classifier (RF) against logistic regression (LR) in predicting 1-year postoperative mortality in hip fracture patients as well as assessed the relative importance of the variables included in the LR model. All adult patients who underwent primary emergency hip fracture surgery in Sweden, between 1 January 2008 and 31 December 2017 were included in the study. Patients with pathological fractures and non-operatively managed hip fractures, as well as those who died within 30 days after surgery, were excluded from the analysis. A LR model with an elastic net regularization were fitted and compared to NB, SVM, and RF. The relative importance of the variables in the LR model was then evaluated using the permutation importance. The LR model including all the variables demonstrated an acceptable predictive ability on both the training and test datasets for predicting one-year postoperative mortality (Area under the curve (AUC) = 0.74 and 0.74 respectively). NB, SVM, and RF tended to over-predict the mortality, particularly NB and SVM algorithms. In contrast, LR only over-predicted mortality when the predicted probability of mortality was larger than 0.7. The LR algorithm outperformed the other three algorithms in predicting 1-year postoperative mortality in hip fracture patients. The most important predictors of 1-year mortality were the presence of a metastatic carcinoma, American Society of Anesthesiologists(ASA) classification, sex, Charlson Comorbidity Index (CCI) ≤ 4, age, dementia, congestive heart failure, hypertension, surgery using pins/screws, and chronic kidney disease.