Miracle-dz/UniFAR-FTUs huggingface dataset:
Draft genome sequence resource for Phyllachora maydis - an obligate pathogen that causes tar spot of corn with recent economic impacts in the United States.

Phyllachora maydis is an important fungal pathogen that causes tar spot of corn and has led to significant yield loss in the U.S. and other countries. P. maydis is an obligate biotroph belonging to Sordariomycetes class of Ascomycota. Due to the challenges posed by their obligate nature, there is no genome sequence available in the Phyllachora genus. P. maydis isolate PM01 was collected from a corn field in Indiana and the genome was determined by next-generation sequencing. The assembly size is 45.7 Mb, with 56.46% repetitive sequences. There are 5,992 protein-coding genes and 59 are predicted as effector proteins. This genome resource will increase our understanding of genomic features of P. maydis and will assist in studying the corn-P. maydis interaction and identifying potential resistant candidates for corn breeding programs.
Traffic‐Related Air Pollution and Carotid Plaque Burden in a Canadian City With Low‐Level Ambient Pollution

Background The association between fine particulate matter and cardiovascular disease has been convincingly demonstrated. The role of traffic‐related air pollutants is less clear. To better understand the role of traffic‐related air pollutants in cardiovascular disease development, we examined associations between NO2, carotid atherosclerotic plaque, and cardiometabolic disorders associated with cardiovascular disease. Methods and Results Cross‐sectional analyses were conducted among 2227 patients (62.9±13.8 years; 49.5% women) from the Stroke Prevention and Atherosclerosis Research Centre (SPARC) in London, Ontario, Canada. Total carotid plaque area measured by ultrasound, cardiometabolic disorders, and residential locations were provided by SPARC medical records. Long‐term outdoor residential NO2 concentrations were generated by a land use regression model. Associations between NO2, total carotid plaque area, and cardiometabolic disorders were examined using multiple regression models adjusted for age, sex, smoking, and socioeconomic status. Mean NO2 was 5.4±1.6 ppb in London, Ontario. NO2 was associated with a significant increase in plaque (3.4 mm2 total carotid plaque area per 1 ppb NO2), exhibiting a linear dose‐response. NO2 was also positively associated with triglycerides, total cholesterol, and the ratio of low‐ to high‐density lipoprotein cholesterol (P<0.05). Diabetes mellitus mediated the relationship between NO2 and total carotid plaque area (P<0.05). Conclusions Our results demonstrate that even low levels of traffic‐related air pollutants are linked to atherosclerotic plaque burden, an association that may be partially attributable to pollution‐induced diabetes mellitus. Our findings suggest that reducing ambient concentrations in cities with NO2 below current standards would result in additional health benefits. Given the billions of people exposed to traffic emissions, our study supports the global public health significance of reducing air pollution.
Design of non-equal-strut stent hoops for structural optimization of thoracic aortic stent-grafts

Abstract Background Endovascular aortic aneurysm repair (EVAR) with stent-grafts is used widely for the treatment of thoracic aortic aneurysms (TAA). Inappropriate design of stent-grafts may lead to complications such as endoleak, stent-graft migration and new entries, causes of which may be inappropriate radial support force or insufficient longitudinal flexibility of the stent-grafts. Material and methods To improve the mechanical performance of the stent-grafts, a type of non-equal-strut stent hoops was proposed, and the influence of structural parameters on the mechanical performance was studied. Results Results of numerical simulation and physical experiments show that by using the proposed non-equal-strut stent hoops, radial support force and longitudinal flexibility of stent-grafts can be reconciled and balanced. Conclusion Results of this study could be used to facilitate radial force control and longitudinal flexibility enhancement in the design of aortic stent-grafts.
Vertical Transmission of Gut Microbiome and Antimicrobial Resistance Genes in Infants Exposed to Antibiotics at Birth

Abstract Vertical transmission of maternal microbes is a major route for establishing the gut microbiome in newborns. The impact of perinatal antibiotics on vertical transmission of microbes and antimicrobial resistance is not well understood. Using a metagenomic approach, we analyzed the fecal samples from mothers and vaginally delivered infants from a control group (10 pairs) and a treatment group (10 pairs) receiving perinatal antibiotics. Antibiotic-usage had a significant impact on the main source of inoculum in the gut microbiome of newborns. The control group had significantly more species transmitted from mothers to infants (P = .03) than the antibiotic-treated group. Approximately 72% of the gut microbial population of infants at 3–7 days after birth in the control group was transmitted from their mothers, versus only 25% in the antibiotic-treated group. In conclusion, perinatal antibiotics markedly disturbed vertical transmission and changed the source of gut colonization towards horizontal transfer from the environment to the infants.
Proteome and Phosphoproteome Analysis of Brown Adipocytes Reveals That RICTOR Loss Dampens Global Insulin/AKT Signaling*

We applied DDA proteomics along with DDA and PRM phosphoproteomics to study brown adipocytes lacking RICTOR, an essential subunit of mTOR complex 2, over a time series of insulin stimulation. RICTOR loss caused many protein abundance changes, including increased levels of interferon response proteins. The insulin phosphoproteome response in RICTOR-deficient cells was dampened, including known functional sites ACLY S455, VIM S39, and EIF4B S422, potentially helping to bridge the gap between the acute and chronic effects of RICTOR loss. Graphical Abstract Highlights Global and targeted phosphoproteomics in RICTOR-deficient brown adipocytes. RICTOR loss leads to higher levels of many interferon response-associated proteins. RICTOR loss dampens the dynamic insulin-dependent phosphoproteome response. ACLY S455, VIM S39, and EIF4B S422 are among the most dampened phosphosites. Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-min time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation because of chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.
Therapeutic hypothermia reduces cortical inflammation associated with utah array implants

Objective. Neuroprosthetics hold tremendous promise to restore function through brain-computer interfaced devices. However, clinical applications of implantable microelectrodes remain limited given the challenges of maintaining neuronal signals for extended periods of time and with multiple biological mechanisms negatively affecting electrode performance. Acute and chronic inflammation, oxidative stress, and blood brain barrier disruption contribute to inconsistent electrode performance. We hypothesized that therapeutic hypothermia (TH) applied at the microelectrode insertion site will positively modulate both inflammatory and apoptotic pathways, promoting neuroprotection and improved performance in the long-term. Approach. A custom device and thermoelectric system were designed to deliver controlled TH locally to the cortical implant site at the time of microelectrode array insertion and immediately following surgery. The TH paradigm was derived from in vivo cortical temperature measurements and finite element modeling of temperature distribution profiles in the cortex. Male Sprague-Dawley rats were implanted with non-functional Utah microelectrodes arrays (UMEA) consisting of 4 × 4 grid of 1.5 mm long parylene-coated silicon shanks. In one group, TH was applied to the implant site for two hours following the UMEA implantation, while the other group was implanted under normothermic conditions without treatment. At 48 h, 72 h, 7 d and 14 d post-implantation, mRNA expression levels for genes associated with inflammation and apoptosis were compared between normothermic and hypothermia-treated groups. Main results. The custom system delivered controlled TH to the cortical implant site and the numerical models confirmed that the temperature decrease was confined locally. Furthermore, a one-time application of TH post UMEA insertion significantly reduced the acute inflammatory response with a reduction in the expression of inflammatory regulating cytokines and chemokines. Significance. This work provides evidence that acutely applied hypothermia is effective in significantly reducing acute inflammation post intracortical electrode implantation.
Women With Congenital Hypofibrinogenemia/Afibrinogenemia: From Birth to Death

Congenital fibrinogen disorders are a group of most frequent rare coagulation disorder, characterized by deficiency and/or defects in the fibrinogen molecule. Quantitative disorders include hypofibrinogenemia and afibrinogenemia. Due to their specific physiological characteristics, female patients tend to have congenital hypofibrinogenemia/afibrinogenemia, such as spontaneous recurrent abortion, menorrhagia, infertility, antepartum and postpartum hemorrhage, and so on. Current studies of congenital hypofibrinogenemia/afibrinogenemia mainly focus on different types of fibrinogen mutations, etiology/pathogenesis, and some rare case reports of the diseases. So far, there is no study available to systematically review the specific features of female patients with congenital bleeding disorders. This review aims to deal with hematological, gynecologic and obstetric issues, and relevant clinical management of congenital hypofibrinogenemia/afibrinogenemia at different life stages of female patients. We believe this review provides valuable reference for clinicians in the field of hematology, obstetrics, as well as gynecology.
Metastatic Melanoma Patient–Derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition

Purpose: Over 60% of patients with melanoma respond to immune checkpoint inhibitor (ICI) therapy, but many subsequently progress on these therapies. Second-line targeted therapy is based on BRAF mutation status, but no available agents are available for NRAS, NF1, CDKN2A, PTEN, and TP53 mutations. Over 70% of melanoma tumors have activation of the MAPK pathway due to BRAF or NRAS mutations, while loss or mutation of CDKN2A occurs in approximately 40% of melanomas, resulting in unregulated MDM2-mediated ubiquitination and degradation of p53. Here, we investigated the therapeutic efficacy of over-riding MDM2-mediated degradation of p53 in melanoma with an MDM2 inhibitor that interrupts MDM2 ubiquitination of p53, treating tumor-bearing mice with the MDM2 inhibitor alone or combined with MAPK-targeted therapy. Experimental Design: To characterize the ability of the MDM2 antagonist, KRT-232, to inhibit tumor growth, we established patient-derived xenografts (PDX) from 15 patients with melanoma. Mice were treated with KRT-232 or a combination with BRAF and/or MEK inhibitors. Tumor growth, gene mutation status, as well as protein and protein–phosphoprotein changes, were analyzed. Results: One-hundred percent of the 15 PDX tumors exhibited significant growth inhibition either in response to KRT-232 alone or in combination with BRAF and/or MEK inhibitors. Only BRAFV600WT tumors responded to KRT-232 treatment alone while BRAFV600E/M PDXs exhibited a synergistic response to the combination of KRT-232 and BRAF/MEK inhibitors. Conclusions: KRT-232 is an effective therapy for the treatment of either BRAFWT or PANWT (BRAFWT, NRASWT) TP53WT melanomas. In combination with BRAF and/or MEK inhibitors, KRT-232 may be an effective treatment strategy for BRAFV600-mutant tumors.
Preventive Behaviors Conveyed on YouTube to Mitigate Transmission of COVID-19: Cross-Sectional Study

Background Accurate information and guidance about personal behaviors that can reduce exposure to severe acute respiratory syndrome coronavirus 2 are among the most important elements in mitigating the spread of coronavirus disease 2019 (COVID-19). With over 2 billion users, YouTube is a media channel that millions turn to when seeking information. Objective At the time of this study, there were no published studies investigating the content of YouTube videos related to COVID-19. This study aims to address this gap in the current knowledge. Methods The 100 most widely viewed YouTube videos uploaded throughout the month of January 2020 were reviewed and the content covered was described. Collectively, these videos were viewed over 125 million times. Results Fewer than one-third of the videos covered any of the seven key prevention behaviors listed on the US Centers for Disease Control and Prevention website. Conclusions These results represent an important missed opportunity for disease prevention.
Loss of Endothelial Glycocalyx Hyaluronan Impairs Endothelial Stability and Adaptive Vascular Remodeling after Arterial Ischemia

We recently reported that loss of hyaluronan (HA) from the endothelial glycocalyx leads to loss of vessel stability in specific microcirculatory vascular beds. Here we hypothesized that such derangements in the glycocalyx may also impair the adaptive response to vascular ischemia. Endothelial specific conditional hyaluronan synthase 2-KO (Has2-cKO) mice revealed reduced endothelial HA expression and lower hindlimb perfusion at baseline compared to control mice. After a single ligation of the common femoral artery in these mice, we observed dysregulated angiogenesis in the gastrocnemius muscle which did not restore capillary perfusion. Mechanistically, decreased endothelial binding of the pericyte-derived molecule angiopoietin1 (Ang1) could be observed in the Has2-cKO mouse. In vitro angiogenesis assays with an endothelial cell-pericyte coculture confirmed such disturbed Ang1-TIE2 signaling resulting in excessive angiogenesis upon loss of HA. These data could be of relevance to diabetes patients, where we confirm loss of endothelial HA in the microcirculation of muscle tissue, indicating that this may contribute to the known disturbed adaptation to ischemia in these patients. In summary, loss of endothelial HA results in impaired microvascular perfusion and endothelial stability in ischemic gastrocnemius muscle. Endothelial HA is a potential target to improve angiogenic therapy in diabetic patients with critical limb ischemia.
Extracellular DNA controls expression of Pseudomonas aeruginosa genes involved in nutrient utilization, metal homeostasis, acid pH tolerance, and virulence

Pseudomonas aeruginosa grows in extracellular DNA-enriched biofilms and infection sites. Extracellular DNA (eDNA) is generally considered a structural biofilm polymer required for aggregation and biofilm maturation. In addition, eDNA can sequester divalent metal cations, acidify the growth media, and serve as a nutrient source. Here we determine the transcriptome of planktonic P. aeruginosa grown in the presence of eDNA using RNA-seq. Transcriptome analysis identified 89 induced genes and 76 repressed genes in the presence of eDNA (FDR<0.05), and transcriptional lux fusions were used to confirm eDNA regulation. A large number of eDNA-induced genes appear to be involved in utilizing DNA as a nutrient. Several eDNA-induced genes are also induced by acidic pH 5.5, and growth in the presence of eDNA or acidic pH promoted an acid tolerance response in P. aeruginosa. The cyoABCDE terminal oxidase is induced at pH 5.5 and contributed to the acid tolerance phenotype. Quantitative metal analysis confirmed that DNA binds to diverse metals, which helps explain why many genes involved in a general uptake of metals were controlled by eDNA. Growth in the presence of eDNA also promoted intracellular bacterial survival and influenced virulence and during the acute infection model of fruit flies. The diverse functions of the eDNA-regulated genes underscore the important role of this extracellular polymer in promoting antibiotic resistance, virulence, acid tolerance, and nutrient utilization; phenotypes that contribute to long-term survival.
Phononic and photonic properties of shape-engineered silicon nanoscale pillar arrays

We report the results of Brillouin–Mandelstam spectroscopy and Mueller matrix spectroscopic ellipsometry of the nanoscale ‘pillar with the hat’ periodic silicon structures, revealing intriguing phononic and photonic—phoxonic—properties. It has been theoretically shown that periodic structures with properly tuned dimensions can act simultaneously as phononic and photonic crystals, strongly affecting the light-matter interactions. Acoustic phonon states can be tuned by external boundaries, either as a result of phonon confinement effects in individual nanostructures, or as a result of artificially induced external periodicity, as in the phononic crystals. The shape of the nanoscale pillar array was engineered to ensure the interplay of both effects. The Brillouin–Mandelstam spectroscopy data indicated strong flattening of the acoustic phonon dispersion in the frequency range from 2 GHz to 20 GHz and the phonon wave vector extending to the higher-order Brillouin zones. The specifics of the phonon dispersion dependence on the pillar arrays’ orientation suggest the presence of both periodic modulation and spatial localization effects for the acoustic phonons. The ellipsometry data reveal a distinct scatter pattern of four-fold symmetry due to nanoscale periodicity of the pillar arrays. Our results confirm the dual functionality of the nanostructured shape-engineered structure and indicate a possible new direction for fine-tuning the light–matter interaction in the next generation of photonic, optoelectronic, and phononic devices.
Electromyographic activity in the gluteus medius, gluteus maximus, biceps femoris, vastus lateralis, vastus medialis and rectus femoris during the Monopodal Squat, Forward Lunge and Lateral Step-Up exercises

The Monopodal Squat, Forward Lunge and Lateral Step-Up exercises are commonly performed with one's own body weight for rehabilitation purposes. However, muscle activity evaluated using surface electromyography has never been analyzed among these three exercises. Therefore, the objectives of the present study were to evaluate the amplitude of the EMG activity of the gluteus medius, gluteus maximus, biceps femoris, vastus lateralis, vastus medialis and rectus femoris muscles in participants performing the Lateral Step-Up, Forward Lunge and Monopodal Squat exercises. A total of 20 physically active participants (10 men and 10 women) performed 5 repetitions at 60% (5 repetition maximum) in each of the evaluated exercises. The EMG amplitude was calculated in percentage of the maximum voluntary contraction. The Monopodal Squat exercise showed a higher EMG activity (p ≤ 0.001) in relation to the Lateral Step-Up and Forward Lunge exercises in all of the evaluated muscles (d > 0.6) except for the rectus femoris. The three exercises showed significantly higher EMG activity in all of the muscles that were evaluated in the concentric phase in relation to the eccentric one. In the three evaluated exercises, vastus lateralis and vastus medialis showed the highest EMG activity, followed by gluteus medius and gluteus maximus. The Monopodal Squat, Forward Lunge and Lateral Step-Up exercises not only are recommended for their rehabilitation purposes but also should be recommended for performance objectives and strength improvement in the lower limbs.
Middle ear pathologies in adults within the mining industry: A systematic review

Background Literature suggests that risk factors for middle ear pathologies, such as traumatic injuries and human immunodeficiency virus (HIV), exist in mines. However, studies on hearing health in mines seem to focus primarily on occupational noise-induced hearing loss and ignore middle ear pathologies. As a result, there is little documented evidence on the trends of middle ear pathologies in mine workers. Objectives The aim of this study was to explore and document published evidence reflecting trends in middle ear pathologies in mine workers. Method A systematic literature review of studies that reported middle ear pathologies in mine workers was conducted. Medline, CINAHL, PubMed, PsychInfo and Google Scholar databases were searched for studies in English published between January 1994 and December 2018 and reporting on trends in middle ear pathologies in mine workers. Results Two research studies met the selection criteria and were included for analysis. One research study used tympanometry with 226 Hz probe tone, while another study used interviews to determine the presence of middle ear pathologies. While these studies indicate that middle ear pathologies exist in individuals working in mines, the evidence is limited. Conclusion While current data indicate that individuals working in mines may present with middle ear pathologies of varying severities, the evidence is too small to provide a clear trend of middle ear pathologies in individuals working in mines. Therefore, the current limited data suggest a need for further studies to examine middle ear pathologies in individuals working in mines.
Analysis of Haplotypic Variation and Deletion Polymorphisms Point to Multiple Archaic Introgression Events, Including from Altai Neanderthal Lineage

Although analysis of modern and ancient genomes showed that Neanderthals contributed genetic material to the ancestors of extant human populations, when and where Neanderthals interacted with modern human populations remain exciting. The time, extent, and genomic effect of the introgressions from archaic humans into ancestors of extant human populations remain some of the most exciting venues of population genetics research in the past decade. Several studies have shown population-specific signatures of introgression events from Neanderthals, Denisovans, and potentially other unknown hominin populations in different human groups. Moreover, it was shown that these introgression events may have contributed to phenotypic variation in extant humans, with biomedical and evolutionary consequences. In this study, we present a comprehensive analysis of the unusually divergent haplotypes in the Eurasian genomes and show that they can be traced back to multiple introgression events. In parallel, we document hundreds of deletion polymorphisms shared with Neanderthals. A locus-specific analysis of one such shared deletion suggests the existence of a direct introgression event from the Altai Neanderthal lineage into the ancestors of extant East Asian populations. Overall, our study is in agreement with the emergent notion that various Neanderthal populations contributed to extant human genetic variation in a population-specific manner.