Miracle-dz/UniFAR-FTUs huggingface dataset:
Neighbourhood characteristics as a predictor of adherence to dietary recommendations: A population-based cohort study of Finnish adults

Aims: To investigate the association of six-year cumulative level of socioeconomic neighbourhood disadvantage and population density with subsequent adherence to dietary recommendations, controlling for preceding dietary adherence, in adults in Finland. Methods: Population-based Health and Social Support (HeSSup) study participants from four age groups (20–24, 30–34, 40–44 and 50–54 years at baseline in 1998). Data on diet and alcohol consumption were obtained from the 2003 and 2012 surveys and information on neighbourhoods from Statistics Finland Grid database (n = 10,414 men and women). Participants diet was measured as adherence to Nordic Nutrition recommendation (score range 0–100). Neighbourhood disadvantage was measured by median household income, proportion of those with primary education only and unemployment rate, and population density by the number of adult population between years 2007 and 2012. Linear models were used to assess the associations of neighbourhood characteristics with the score for adherence to dietary recommendations in 2012. Results: Cumulative neighbourhood socioeconomic disadvantage was associated with slightly weaker (1.49 (95% confidence interval (CI) −1.89 to −1.09) point decrease in dietary score) adherence while higher population density was associated with better (0.70 (95% CI 0.38−1.01) point increase in dietary score) adherence to dietary recommendations. These associations remained after controlling for prior dietary habits, sociodemographic, chronic cardio-metabolic diseases, and severe life events. Conclusions: These longitudinal findings support the hypothesis that neighbourhood characteristics affect dietary habits.
From Chip Size to Wafer-Scale Nanoporous Gold Reliable Fabrication Using Low Currents Electrochemical Etching

We report a simple, scalable route to wafer-size processing for fabrication of tunable nanoporous gold (NPG) by the anodization process at low constant current in a solution of hydrofluoric acid and dimethylformamide. Microstructural, optical, and electrochemical investigations were employed for a systematic analysis of the sample porosity evolution while increasing the anodization duration, namely the small angle X-ray scattering (SAXS) technique and electrochemical impedance spectroscopy (EIS). Whereas the SAXS analysis practically completes the scanning electronic microscopy (SEM) investigations and provides data about the impact of the etching time on the nanoporous gold layers in terms of fractal dimension and average pore surface area, the EIS analysis was used to estimate the electroactive area, the associated roughness factor, as well as the heterogeneous electron transfer rate constant. The bridge between the analyses is made by the scanning electrochemical microscopy (SECM) survey, which practically correlates the surface morphology with the electrochemical activity. The results were correlated to endorse the control over the gold film nanostructuration process deposited directly on the substrate that can be further subjected to different technological processes, retaining its properties. The results show that the anodization duration influences the surface area, which subsequently modifies the properties of NPG, thus enabling tuning the samples for specific applications, either optical or chemical.
Production of recombinant butyrylcholinesterase from transgenic rice cell suspension cultures in a pilot‐scale bioreactor

Producing recombinant proteins in transgenic plant cell suspension cultures in bioreactors provides controllability, reproducibility, scalability, and low‐cost production, although low yields remain the major challenge. The studies on scaling‐up to pilot‐scale bioreactors, especially in conventional stainless‐steel stirred tank bioreactors (STB), to produce recombinant proteins in plant cell suspension cultures are very limited. In this study, we scaled‐up the production of rice recombinant butyrylcholinesterase (rrBChE), a complex hydrolase enzyme that can be used to prophylactically and therapeutically treat against organophosphorus nerve agents and pesticide exposure, from metabolically regulated transgenic rice cell suspension cultures in a 40‐L pilot‐scale STB. Employing cyclical operation together with a simplified‐process operation (controlling gas sparging rate rather than dissolved oxygen and allowing natural sugar depletion) identified in lab‐scale (5 L) bioreactor studies, we found a consistent maximum total active rrBChE production level of 46–58 µg/g fresh weight in four cycles over 82 days of semicontinuous operation. Additionally, maintaining the overall volumetric oxygen mass transfer coefficient (kLa) in the pilot‐scale STB to be equivalent to the lab‐scale STB improves the maximum total active rrBChE production level and the maximum volumetric productivity to 85 µg/g fresh weight and 387 µg L−1 day−1, respectively, which are comparable to the lab‐scale culture. Here, we demonstrate pilot‐scale bioreactor performance using a metabolically regulated transgenic rice cell culture for long‐term, reproducible, and sustained production of rrBChE.
TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.
C Protein Is Essential for Canine Distemper Virus Virulence and Pathogenicity in Ferrets

The measles (MeV) and canine distemper (CDV) viruses express accessory proteins that regulate the host’s immune response and enhance replication. The MeV C protein is critical in preventing the generation of excess immunostimulatory double-stranded RNA. ABSTRACT Paramyxoviruses, including members of the genus Morbillivirus, express accessory proteins with ancillary functions during viral replication. One of these, the C protein, is expressed from an alternative open reading frame (ORF) located in the P gene. The measles virus (MeV) C protein has been implicated in modulation of interferon signaling, but has more recently been shown to play a vital role in regulation of viral transcription and replication, preventing the excessive production of double-stranded RNA. Failure to do so, as seen with C-deficient MeV, leads to early activation of innate immune responses resulting in restriction of viral replication and attenuation in the host. One puzzling aspect of morbillivirus C protein biology has been the finding that a C-deficient canine distemper virus (CDV) generated by a similar mutagenesis strategy displayed no attenuation in ferrets, an animal model commonly used to evaluate CDV pathogenesis. To resolve how virus lacking this protein could maintain virulence, we revisited the CDV C protein and found that truncated C proteins are expressed from the CDV gene using alternative downstream start codons, even when the first start codon has been disrupted. We introduced an additional point mutation abrogating expression of these truncated C proteins. A new CDV with this mutation was attenuated in vitro and led to increased activation of protein kinase R. It was also strongly attenuated in ferrets, inducing only mild disease in infected animals, thus replicating the phenotype of C-deficient MeV. Our results demonstrate the crucial role of morbillivirus C proteins in pathogenesis. IMPORTANCE The measles (MeV) and canine distemper (CDV) viruses express accessory proteins that regulate the host’s immune response and enhance replication. The MeV C protein is critical in preventing the generation of excess immunostimulatory double-stranded RNA. C protein-deficient MeV is strongly attenuated compared to wild-type virus, whereas CDV with a similarly disrupted C open reading frame is fully pathogenic. Here, we show that CDV can compensate for the disrupting mutations by expression of truncated, but apparently functional, C proteins from several alternative start codons. We generated a new recombinant CDV that does not express these truncated C proteins. This virus was attenuated both in cell culture and in ferrets and finally resolves the paradox of the MeV and CDV C proteins, showing that both in fact have similar functions important for viral pathogenesis.
Adenosine A2A and A3 Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy

Diabetic nephropathy (DN) and hypertension are prime causes for end-stage renal disease (ESRD) that often coexist in patients, but are seldom studied in combination. Kidney adenosine levels are markedly increased in diabetes, and the expression and function of renal adenosine receptors are altered in experimental diabetes. The aim of this work is to explore the impact of endogenous and exogenous adenosine on the expression/distribution profile of its receptors along the nephron of hypertensive rats with experimentally-induced diabetes. Using spontaneously hypertensive (SHR) rats rendered diabetic with streptozotocin (STZ), we show that treatment of SHR-STZ rats with an agonist of adenosine receptors increases A2A immunoreactivity in superficial glomeruli (SG), proximal tubule (PCT), and distal tubule (DCT). Differently, treatment of SHR-STZ rats with a xanthinic antagonist of adenosine receptors decreases adenosine A3 immunoreactivity in SG, PCT, DCT, and collecting duct. There is no difference in the immunoreactivity against the adenosine A1 and A2B receptors between the experimental groups. The agonist of adenosine receptors ameliorates renal fibrosis, probably via A2A receptors, while the antagonist exacerbates it, most likely due to tonic activation of A3 receptors. The reduction in adenosine A3 immunoreactivity might be due to receptor downregulation in response to prolonged activation. Altogether, these results suggest an opposite regulation exerted by endogenous and exogenous adenosine upon the expression of its A2A and A3 receptors along the nephron of hypertensive diabetic rats, which has a functional impact and should be taken into account when considering novel therapeutic targets for hypertensive-diabetic nephropathy.
No Change in Medial Olivocochlear Efferent Activity during an Auditory or Visual Task: Dual Evidence from Otoacoustic Emissions and Event-Related Potentials

The medial olivocochlear (MOC) system is thought to be responsible for modulation of peripheral hearing through descending (efferent) pathways. This study investigated the connection between peripheral hearing function and conscious attention during two different modality tasks, auditory and visual. Peripheral hearing function was evaluated by analyzing the amount of suppression of otoacoustic emissions (OAEs) by contralateral acoustic stimulation (CAS), a well-known effect of the MOC. Simultaneously, attention was evaluated by event-related potentials (ERPs). Although the ERPs showed clear differences in processing of auditory and visual tasks, there were no differences in the levels of OAE suppression. We also analyzed OAEs for the highest magnitude resonant mode signal detected by the matching pursuit method, but again did not find a significant effect of task, and no difference in noise level or number of rejected trials. However, for auditory tasks, the amplitude of the P3 cognitive wave negatively correlated with the level of OAE suppression. We conclude that there seems to be no change in MOC function when performing different modality tasks, although the cortex still remains able to modulate some aspects of MOC activity.
AL Amyloidosis: The Effect of Maintenance Therapy on Autologous Stem Cell Transplantation Outcomes

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.
EMT Transcription Factor ZEB1 Represses the Mutagenic POLθ-Mediated End-Joining Pathway in Breast Cancers

These findings uncover an original mechanism of TMEJ regulation, highlighting ZEB1 as a key player in genome stability during cancer progression via its repression of POLQ. A characteristic of cancer development is the acquisition of genomic instability, which results from the inaccurate repair of DNA damage. Among double-strand break repair mechanisms induced by oncogenic stress, the highly mutagenic theta-mediated end-joining (TMEJ) pathway, which requires DNA polymerase theta (POLθ) encoded by the POLQ gene, has been shown to be overexpressed in several human cancers. However, little is known regarding the regulatory mechanisms of TMEJ and the consequence of its dysregulation. In this study, we combined a bioinformatics approach exploring both Molecular Taxonomy of Breast Cancer International Consortium and The Cancer Genome Atlas databases with CRISPR/Cas9-mediated depletion of the zinc finger E-box binding homeobox 1 (ZEB1) in claudin-low tumor cells or forced expression of ZEB1 in basal-like tumor cells, two triple-negative breast cancer (TNBC) subtypes, to demonstrate that ZEB1 represses POLQ expression. ZEB1, a master epithelial-to-mesenchymal transition–inducing transcription factor, interacted directly with the POLQ promoter. Moreover, downregulation of POLQ by ZEB1 fostered micronuclei formation in TNBC tumor cell lines. Consequently, ZEB1 expression prevented TMEJ activity, with a major impact on genome integrity. In conclusion, we showed that ZEB1 directly inhibits the expression of POLQ and, therefore, TMEJ activity, controlling both stability and integrity of breast cancer cell genomes. Significance: These findings uncover an original mechanism of TMEJ regulation, highlighting ZEB1 as a key player in genome stability during cancer progression via its repression of POLQ. See related commentary by Carvajal-Maldonado and Wood, p. 1441
Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke

Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This review systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms: “precondition” or “pretreatment” and “neural stem cell” and “ischemic stroke”. The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future.
Role of gender, age and BMI in prognosis of heart failure

The prognostic stratification of heart failure remains an urgent need for correct clinical management of the affected patients. In fact, due to the high mortality and morbidity rates, heart failure constantly requires an updated and careful management of all aspects that characterise the disease. In addition to the well-known clinical, laboratory and instrumental characteristics that affect the prognosis of heart failure, gender, age and body mass index have a different impact and deserve specific insights and clarifications. At this scope, the metabolic exercise cardiac kidney index score research group has produced several works in the past, trying to identify the role of these specific factors on the prognosis of heart failure. In particular, the different performances in the cardiopulmonary exercise test of specific categories of heart failure patients, such as women, elderly and obese or overweight individuals, have requested dedicated evaluations of metabolic exercise cardiac kidney index score power.
The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions

SNX10 is a member of the phox homology domain‐containing family of phosphoinositide‐binding proteins. Intracellularly, SNX10 localizes to endosomes where it mediates intracellular trafficking, endosome organization, and protein localization to the centrosome and cilium. It is highly expressed in bone and the gut where it participates in bone mineral and calcium homeostasis through the regulation of osteoclastic bone resorption and gastric acid secretion, respectively. Not surprisingly, patients harboring mutations in SNX10 mutation manifest a phenotype of autosomal recessive osteopetrosis or malignant infantile osteopetrosis, which is clinically characterized by dense bones with increased cortical bone into the medullary space with bone marrow occlusion or depletion, bone marrow failure, and anemia. Accordingly, SNX10 mutant osteoclasts exhibit impaired bone resorptive capacity. Beyond the skeleton, there is emerging evidence implicating SNX10 in cancer development, metabolic disorders, inflammation, and chaperone‐mediated autophagy. Understanding the structural basis through which SNX10 exerts its diverse biological functions in both cell and tissue‐specific manners may therefore inform new therapeutic opportunities toward the treatment and management of SNX10‐related diseases.
The Influence of Sagittal Plane Hip Position on Lower-Extremity Muscle Activity and Torque Output.

CONTEXT Hip muscle strength has previously been evaluated in various sagittal plane testing positions. Altering the testing position appears to have an influence on hip muscle torque during hip extension, abduction, and external rotation. However, it is unknown how altering the testing position influences hip muscle activity during these commonly performed assessments. OBJECTIVES To evaluate how hip sagittal plane position influences hip muscle activation and torque output. STUDY DESIGN Cross-sectional. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 22 healthy females (age = 22.1 [1.4] y; mass = 63.4 [11.3] kg; height = 168.4 [6.2] cm) were recruited. INTERVENTION None. MAIN OUTCOME MEASURES Participants completed isometric contractions with surface electromyography on the superior and inferior gluteus maximus; anterior, middle, and posterior gluteus medius; biceps femoris, semitendinosus, adductor longus, and tensor fascia latae. Extension and external rotation were tested in 0°, 45°, and 90° of hip flexion and abduction was tested in -5°, 0°, and 45° of hip flexion. Repeated-measures analysis of variances were used for statistical analysis (P ≤ .01). RESULTS Activation of gluteal (P < .007), semitendinosus (P = .002), and adductor longus (P = .001) muscles were lesser for extension at 90° versus less flexed positions. Adductor longus activity was greatest during 90° of hip flexion for external rotation torque testing (P < .001). Tensor fascia latae (P < .001) and gluteus maximus (P < .001) activities were greater in 45° of hip flexion. Significant differences in extension (P < .001) and abduction (P < .001) torque were found among positions. CONCLUSIONS Position when assessing hip extension and abduction torque has an influence on both muscle activity and torque output but only muscle activity for hip external rotation torque. Clinicians should be aware of the influence of position on hip extension, abduction, and external rotation muscle testing and select a position most in line with their clinical goals.