Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic ablation of Cullin-RING E3 ubiquitin ligase 7 restrains pressure overload-induced myocardial fibrosis

Fibrosis is a pathognomonic feature of structural heart disease and counteracted by distinct cardioprotective mechanisms, e.g. activation of the phosphoinositide 3-kinase (PI3K) / AKT pro-survival pathway. The Cullin-RING E3 ubiquitin ligase 7 (CRL7) was identified as negative regulator of PI3K/AKT signalling in skeletal muscle, but its role in the heart remains to be elucidated. Here, we sought to determine whether CRL7 modulates to cardiac fibrosis following pressure overload and dissect its underlying mechanisms. For inactivation of CRL7, the Cullin 7 (Cul7) gene was deleted in cardiac myocytes (CM) by injection of adeno-associated virus subtype 9 (AAV9) vectors encoding codon improved Cre-recombinase (AAV9-CMV-iCre) in Cul7flox/flox mice. In addition, Myosin Heavy Chain 6 (Myh6; alpha-MHC)-MerCreMer transgenic mice with tamoxifen-induced CM-specific expression of iCre were used as alternate model. After transverse aortic constriction (TAC), causing chronic pressure overload and fibrosis, AAV9-CMV-iCre induced Cul7-/- mice displayed a ~50% reduction of interstitial cardiac fibrosis when compared to Cul7+/+ animals (6.7% vs. 3.4%, p<0.01). Similar results were obtained with Cul7flox/flox Myh6-Mer-Cre-MerTg(1/0) mice which displayed a ~30% reduction of cardiac fibrosis after TAC when compared to Cul7+/+ Myh6-Mer-Cre-MerTg(1/0) controls after TAC surgery (12.4% vs. 8.7%, p<0.05). No hemodynamic alterations were observed. AKTSer473 phosphorylation was increased 3-fold (p<0.01) in Cul7-/- vs. control mice, together with a ~78% (p<0.001) reduction of TUNEL-positive apoptotic cells three weeks after TAC. In addition, CM-specific expression of a dominant-negative CUL71152stop mutant resulted in a 16.3-fold decrease (p<0.001) of in situ end-labelling (ISEL) positive apoptotic cells. Collectively, our data demonstrate that CM-specific ablation of Cul7 restrains myocardial fibrosis and apoptosis upon pressure overload, and introduce CRL7 as a potential target for anti-fibrotic therapeutic strategies of the heart.
OMIP 072: A 15‐color panel for immunophenotypic identification, quantification, and characterization of leukemic stem cells in children with acute myeloid leukemia

This panel was designed to identify, quantify and phenotypically characterize putative leukemic stem cells (LSCs) in bone marrow (BM) samples from individual pediatric patients diagnosed with acute myeloid leukemia (AML). Based on an aberrant expression on immunophenotypically defined hematopoietic stem cells (HSCs), several antigens have been proposed as LSC markers in AML research, using healthy adult BM samples as reference material. Generally, these antigens have been evaluated individually in smaller panels (e.g. 8‐color panels). This necessitates several tubes to characterize the LSC phenotype and compromises the ability to evaluate LSC heterogeneity. The present 15‐color OMIP incorporates nine suggested LSC markers to comprehensively capture LSC immunophenotypes and to explore heterogenic marker‐patterns within LSC populations in a single tube. Importantly, this single tube approach requires less input material, which is essential when sampling BM aspirates from pediatric patients where sample volumes often are sparse. As knowledge on normal expression levels of the included LSC markers in HSCs from hematologically healthy children are a prerequisite for labelling a phenotype as abnormal, we have evaluated the applicability of the panel on cryopreserved mononuclear cells (MNCs) isolated from BM samples from pediatric patients without hematological disorders as well as pediatric AML patients. The panel is optimized for cryopreserved BM MNCs, but could in principle, be utilized for LSC detection in any biological material containing human hematopoietic cells.
Simultaneous Determination of Anions and Cations in Mineral Water by Capillary Electrophoresis with a Chelating Agent

Abstract Anions and cations in mineral water were simultaneously measured by capillary electrophoresis with a chelating agent. Ions studied were chloride, sulfate, sulfite, nitrate, nitrite, fluoride, formate, and acetate for anions, and magnesium, calcium, copper, lead and zinc for cations. They were separated in a fused-silica capillary (50 cm × 50 μm i.d.) filled with 300 mM borate buffer (pH 9.0) containing a cationic surfactant and a chelating agent as the electro-osmotic flow modifier and chelator, respectively. The method was successfully applied to the determination of ions in mineral water.
Parenting intentions of young sexual minority men living with HIV in Mexico City, Mexico

Abstract Young sexual minority men are disproportionately affected by HIV in Mexico. Little is known about their thoughts about childbearing, an issue complicated by sexual identity and HIV serostatus. We conducted 16 in-depth qualitative interviews to explore the parenting desires of young sexual minority men living with HIV in Mexico City. Domains of the questionnaire included (1) parenting desires, (2) preferences about different methods (e.g. adoption, in-vitro fertilisation), and (3) perceived barriers to becoming a father. A modified grounded theory approach was used for qualitative analysis. Participants ranged in age from 17 to 21 years and had been living with HIV for an average of 15 months. Most expressed the desire to have a child in the future but were uninformed as to their options for doing so. Participants largely preferred adoption, citing the perceived risk of HIV transmission as a deterrent to using assisted reproductive technologies. Some participants expressed the desire to have a child that was genetically their own, but shared doubts as to the feasibility. The majority of participants stated that the topic of childbearing had never come up during the course of their HIV care.
Characterizing the Feeding Injury Caused by Phylloscelis rubra (Hemiptera: Dictyopharidae) to Cranberries

Abstract Due to changes in pest management practices, farmers’ reports of severe feeding injury to cranberries, Vaccinium macrocarpon Aiton Ericales: Ericaceae, caused by the cranberry toad-bug, Phylloscelis rubra Ball, have increased in recent years in New Jersey (United States). Currently, however, limited information is available on the effects of P. rubra feeding or density of individuals needed to cause injury to cranberry vines and fruit. In 2015‒2017, we conducted studies to characterize injury to cranberry at a range of P. rubra densities by using cages in a screen-house and field, to establish a correlation between P. rubra density and crop injury in an open field experiment, and to measure the effects of P. rubra injury on the nutritional content (i.e., amounts of macro- and microelements) of cranberry vines. Phylloscelis rubra feeding on cranberry vines produced typical injury symptoms at relatively low densities (i.e., 2 individuals per vine in field cages or <10 individuals per sweep net sample in open fields), which included discolored (yellowish or reddish) or dead (brown) vines. This vine injury could lead to reductions in fruit mass and total fruit number. However, P. rubra injury to cranberry vines did not alter their nutritional composition. In general, this study highlights the ability of P. rubra to cause substantial injury to cranberry vines even when population densities were relatively low, which could result in declines in fruit production (quality and quantity). Therefore, infestations by P. rubra in cranberries must be considered when making pest management decisions in regions where this insect is present.
1/f noise in ohmic silicon JFET channels

Measurements have been made of the excess noise in silicon. The specimens were ohmic, uniform cross-section JFET channels with no active oxide interfaces. The gate voltage was used to deplete the channel and change one transverse linear dimension. The temperature was varied between 77K and 368K to change the dominant scattering mechanism. The carrier density and mobility profiles across the channel were measured. At low temperatures one excess noise component was identified as due to donor occupation fluctuation. The observed excess noise component with a 1/f spectrum has been compared with the predictions of various models. The magnitude of the noise and its dependence on the scattering mechanism do not agree with the mobility fluctuation model.
Systematic review and meta-analysis of sex-based differences for concussion incidence in soccer

ABSTRACT Objective To compare concussion incidence in male and female soccer players due to the specific concussion-causing activity. Methods/Data Sources PubMed, EMBASE, and Cochrane Library were searched for studies published between January 2000 and February 2020. Search terms included ‘sex,’ ‘gender,’ ‘sex differences,’ ‘brain injury,’ ‘sports,’ ‘athletes,’ ‘incidence,’ ‘epidemiology,’ ‘symptoms,’ and ‘injury rate. ’ Studies that contained data on concussion incidence in soccer and featured comparisons by sex and soccer activity were included. Studies that were not written in English, contained data on non-sports-related concussions, or were conference abstracts were excluded. Results Six studies were included in this meta-analysis, each of which contributed the number of concussions in males and females for a specific soccer activity. Concussion incidence rates were calculated using athlete-exposures as the denominator and a rate ratio was measured by dividing the concussion rate among female soccer players by the rate among male soccer players. Female soccer players were shown to have a greater rate of concussions from heading [1.65 (95% CI: 1.35, 2.03, p < 0.001)] and goalkeeping [1.63 (95% CI: 1.22, 2.17, p = 0.001)]. There were 3 studies comparing sex differences for general play. While the pooled rate ratio was statistically significant [1.51 (95% CI: 1.12, 2.04), p = 0.007], this result was largely driven by 1 study. Conclusion Concussion incidence rates were significantly higher in female soccer players compared to male players while heading. There is also some evidence to suggest that the incidence is higher for female goalkeepers. Soccer coaches and health care providers need to recognize this sex difference when coaching or treating players.
Allergen immunotherapy and biologics in respiratory allergy: friends or foes?

Purpose of review Allergen-specific immunotherapy has established as an indispensable disease-modifying treatment in allergy practice but its safety and efficacy might be furtherly improved by combining it with other drugs or therapeutic intervention that co-modulate immune type 2 immune networks Recent findings In the past two decades, clinical research focused on AIT and omalizumab co-treatment to improve both safety and long-term efficacy of allergic disease treatment. Recently, combination of AIT with other biologicals targeting different mediators of type 2 inflammation has been set up with interesting preliminary results. Moreover, AIT current contraindication might be overcome by contemporarily controlling underlying type 2 inflammation in severe atopic patients. Summary AIT--biological combination treatment can realize a complex multitargeted treatment strategy allowing for consistently improving disease control and sparing steroid administration.
Lattice Models for Thermotropic Liquid Crystals

Abstract The utility of the DiMarzio-Alben lattice model for investigating thermotropic liquid crystals is evaluated, using a system of straight, inflexible rods with hard cores and nearest neighbor attractions on a simple cubic lattice. In the most general case, treated in the Bragg-Williams approximation, the rods, of length-to-breadth ratio x, are divided into a core portion of c segments and two “tail” portions of (x - c)/2 segments each and there are seven different segmental attractive energies: w cc, w ct, w tt, w ee, w cc, w ct, w tt, where c and t denote core and tail segments, respectively, unprimed and primed energies are for interactions between parallel and perpendicular rods, respectively, and w ee is for the end-to-end interaction between the last segments of two parallel rods. In addition, a special case of the model is also treated in the quasi-chemical or Bethe approximation and the Bragg-Williams approach is extended to simple mixtures of hard rods of two different lengths with solvent-.
MEK Inhibition Reverses Aberrant Signaling in Melanoma Cells through Reorganization of NRas and BRAF in Self Nanoclusters

Nanoscale dynamic organization of WT and mutant NRas relative to BRAF serves as a regulatory mechanism for NRas signaling and may be a viable therapeutic target for its sensitivity to MEKi. Hotspot mutations of the oncogenes BRAF and NRas are the most common genetic alterations in cutaneous melanoma. Still, the nanoscale organization and signal coupling of these proteins remain incompletely understood, particularly upon expression of oncogenic NRas mutants. Here we employed single-molecule localization microscopy to study the nanoscale organization of NRas and BRAF at the plasma membrane (PM) of melanoma cells. NRas and BRAF resided in self-clusters that did not associate well in resting cells. In EGF-activated cells, NRas clusters became more diffused while overall protein levels at the PM increased; thus allowing enhanced association of NRas and BRAF and downstream signaling. In multiple melanoma cell lines, mutant NRas resided in more pronounced self-clusters relative to wild-type (WT) NRas yet associated more with the clustered and more abundant BRAF. In cells resistant to trametinib, a clinical MEK inhibitor (MEKi), a similar coclustering of NRas and BRAF was observed upon EGF activation. Strikingly, treatment of cells expressing mutant NRas with trametinib reversed the effect of mutant NRas expression by restoring the nonoverlapping self-clusters of NRas and BRAF and by reducing their PM levels and elevated pERK levels caused by mutant NRas. Our results indicate a new mechanism for signal regulation of NRas in melanoma through its nanoscale dynamic organization and a new mechanism for MEKi function in melanoma cells carrying NRas mutations but lacking MEK mutations. Significance: Nanoscale dynamic organization of WT and mutant NRas relative to BRAF serves as a regulatory mechanism for NRas signaling and may be a viable therapeutic target for its sensitivity to MEKi.
Impact of Early and Regular Mobilization on Vital Signs and Oxygen Saturation in Patients Undergoing Open-Heart Surgery

Introduction This quasi-experimental study aimed to evaluate the impact of early and regular mobilization on vital signs and oxygen saturation in open-heart surgery patients. Methods The study universe comprised patients undergoing open-heart surgery in the cardiovascular intensive care unit of a heart center. The study sample consisted of patients who underwent open-heart surgery from November 2016 to April 2017, met the inclusion criteria, and voluntarily agreed to participate in the study. The study included 75 patients. Of these, 67 completed the mobilization program in two days, starting on the first postoperative day. Each patient was mobilized three times: twice on the first postoperative day and once on the second postoperative day. Vital signs and oxygen saturation for each patient were measured 10 minutes before and 20 minutes after each mobilization. Results The difference between pulse and systolic blood pressure values measured before and after the first mobilization was statistically significant (P<0.05). In addition, the difference between the mean systolic blood pressure values before the first mobilization and after the third mobilization (123.43±14.09 mmHg and 117.94±14.05 mmHg, respectively) was statistically significant (P<0.05). The other parameters measured in relation to the mobilizations were in the normal range. Conclusion Early and frequent mobilization did not cause vital signs and oxygen saturation to deviate from normal limits in open-heart surgery patients.
“Out of the Depths Have I Called Thee”: Jewish Israeli Undertakers’ Management of Death Anxiety

According to Terror Management Theory, there are three common buffers that minimize the anxiety of mortality salience: affirmation of one’s cultural worldview, the self and one’s personal values, and one’s significance in the context of close personal relationships. The current study aimed to explore the manner by which Jewish Israeli undertakers manage their constant exposure to death and buffer against death anxiety. A deductive and inductive thematic analysis captured a dialectical movement between, and within, two conflicting worldviews participants were engaged in, in their attempt to manage the mortality salience effect they experience and buffer against death anxiety.
Generation and age of immigration on later life cognitive performance in KHANDLE

ABSTRACT Objectives: We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. Design: Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. Setting: Older adults in Northern California. Participants: Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). Measurements: We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. Results: Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (β = −0.96; 95% CI: −1.12, −0.81) than immigration in adolescence (β = −0.68; 95% CI: −0.96, −0.41) or childhood (β = −0.28; 95% CI: −0.49, −0.06). Moreover, immigration in adulthood was associated with lower executive function (β = −0.63; 95% CI: −0.78, −0.48) than immigration in adolescence (β = −0.49; 95% CI: −0.75, −0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. Conclusions: Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.
Lineage analysis of human papillomavirus types 31 and 45 in cervical samples of Iranian women

Knowing the regional lineages/sublineages of human papillomavirus 31 (HPV 31) and 45 would be of great importance for further evolutionary, epidemiological, and biological analysis. In this regard, to characterize more common lineages and sublineages of HPV 31 and 45, the sequence variations of E6 gene were investigated in normal, premalignant, and malignant samples collected from the cervix in Iran. In total, 54 HPV 31‐ and 24 HPV 45‐positive samples were analyzed by hemi‐nested polymerase chain reaction (PCR) and nested‐PCR, respectively. All PCR products were subjected to direct sequencing analysis. The results indicated that all three lineages A, B, and C were detected in HPV 31‐positive samples; among which HPV 31 lineage A was dominant as it was found in 66.7% of all samples. HPV 31 lineages B and C were identified in 5.5% and 27.8% of samples, respectively. In HPV 45‐infected samples, lineage B comprised of 62.5% of all samples and the remaining 37.5% belonged to lineage A. In conclusion, our findings showed that lineage A of HPV 31 was predominant in Iran. Lineage B of HPV 45 was also dominant among Iranian women. However, further studies with larger sample size should be addressed to estimate the pathogenicity risk of HPV 31 or HPV 45 lineages/sublineages in the development of cervical cancer among Iranian women.
Use of tranexamic acid is not associated with complications following bipolar hemiarthroplasty for metastatic disease

Advances in the care of cancer patients have resulted in increased survival. The proximal femur is a common site for metastatic disease, often requiring surgical intervention. Tranexamic acid (TXA) has proven to be safe in elective and traumatic femoral hemiarthroplasty; however, its use has not been investigated in oncologic patients.
PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review

PET/CT combines imaging at the molecular level along with imaging at the anatomic level, which, with the administration of a hypoxia-sensitive radiopharmaceutical, allows evaluation of tissue oxygenation. Methods: This work consisted of a systematic literature review that included websites, books, and articles dated from July 1997 to December 2019. The aim was to identify the PET radiopharmaceuticals best suited to the detection of cell hypoxia and to recognize the benefits for planning intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT). Results: Hypoxia affects the likelihood of cure for head and neck tumors, reducing the success rate. Radiopharmaceuticals such as 18F-fluoromisonidazole, 18F-fluoroerythronitromidazole, and 18F-HX4 (18F-3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol) allow the delineation of hypoxic subvolumes within the target volume to optimize IMRT/VMAT. Conclusion: Identification of hypoxic areas with PET/CT imaging and use of subsequent IMRT/VMAT allows for possible escalation of radiation dose in radioresistant subvolumes, with a consequent decrease in relapses and an increased likelihood of disease-free survival.
Separation and Quantification of Phospholipid and Neutral Lipid Classes by HPLC–CAD: Application to Egg Yolk Lipids

In this paper the methods of different lipid classes analysis using high performance liquid chromatography (HPLC) with charged aerosol detector (CAD) are presented. The methods allowed base-line separation of all investigated egg yolk phospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; sphingomyelin, SM; and their lyso forms) and neutral lipid classes (triacylglycerol, TAG; cholesterol, Chol). Total lipids extraction was carried out by the Folch method. The polar and neutral lipid classes were separated by using normal-phase (silica) SPE cartridges. Two different HPLC methodologies (one for polar and one for neutral lipids) for the separation and quantification of lipid classes on a diol column were applied. The methods were optimized and the response and sensitivity of CAD was studied. In terms of linearity, precision, and sensitivity the methods were validated.
Post‐exercise intramuscular O2 supply is tightly coupled with a higher proximal‐to‐distal ATP synthesis rate in human tibialis anterior

The post‐exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle. To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise. We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate. Taken together, the findings of this study suggest that the post‐exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally.