Miracle-dz/UniFAR-FTUs huggingface dataset:
HCV Pit Stop at the Lipid Droplet: Refuel Lipids and Put on a Lipoprotein Coat before Exit

The replication cycle of the liver-tropic hepatitis C virus (HCV) is tightly connected to the host lipid metabolism, during the virus entry, replication, assembly and egress stages, but also while the virus circulates in the bloodstream. This interplay coins viral particle properties, governs viral cell tropism, and facilitates immune evasion. This review summarizes our knowledge of these interactions focusing on the late steps of the virus replication cycle. It builds on our understanding of the cell biology of lipid droplets and the biosynthesis of liver lipoproteins and attempts to explain how HCV hijacks these organelles and pathways to assemble its lipo-viro-particles. In particular, this review describes (i) the mechanisms of viral protein translocation to and from the lipid droplet surface and the orchestration of an interface between replication and assembly complexes, (ii) the importance of the triglyceride mobilization from the lipid droplets for HCV assembly, (iii) the interplay between HCV and the lipoprotein synthesis pathway including the role played by apolipoproteins in virion assembly, and finally (iv) the consequences of these complex virus–host interactions on the virion composition and its biophysical properties. The wealth of data accumulated in the past years on the role of the lipid metabolism in HCV assembly and its imprint on the virion properties will guide vaccine design efforts and reinforce our understanding of the hepatic lipid metabolism in health and disease.
Dissociation between changes in sprinting performance and Nordic hamstring strength in professional male football players

The aim of the present study was to evaluate the consequence of implementing a Nordic Hamstring exercise (NHE) protocol during the first 15 to 17 weeks of the season to assess the effect on sprinting and NHE strength (NHEs) in professional football players. The study examined 50 healthy male professional football players (age 18.8±0.8yr; height 176.8±6.9cm; weight 71.3±5.7kg) belonging to 3 of the reserve squads of three Spanish La-Liga clubs divided in 2 intervention teams [Nordic-Group1 (NG-1) and Nordic-Group2 (NG-2, extensive experience in NHE)] and 1 team as a control-group (CG). NHEs and linear sprint (T5, T10, T20-m) were evaluated at the beginning of the season and at the end of an intervention period of conditioning and football training, supplemented with a NHE protocol (24 sessions for NG-1 and 22 sessions for NG-2) or without using the NHE at all (CG). Sprint times were substantially improved in all groups (ES from -2.24±0.75 to -0.60±0.37). NHEs was enhanced absolute and relative to body-mass only in NG-1 after the training period (ES from 0.84±0.32 to 0.74±0.26), while in the NG-2 there were only improvements in average NHEs relative to body-mass (ES = 0.39±0.36). The improvements in T20-m were substantially greater in NG-2 vs. NG-1, and there were no differences in sprint performance changes between NG-1 and CG. Changes in sprinting performance and NHEs were unrelated. NHEs was largely correlated with the body-mass of the players. Results indicate that the improvements in sprint are not dependent on the NHEs changes, with no relationships between NHEs and sprint performance, and between sprint changes and changes in NHEs.
Bipotent stem cells support the cyclical regeneration of endometrial epithelium of the murine uterus

Significance Disorders of endometrial epithelial regeneration result in severe pathological conditions, including uterine cancer, endometriosis, and infertility. The lack of a detailed understanding of the cellular mechanisms underlying endometrial epithelial regeneration during the mouse estrous cycle or human menstrual cycle hinders the effective treatment of such diseases. Here, I demonstrate that the mouse uterine endometrial epithelium is maintained by a resident tissue stem cell population. These stem cells survive cyclical uterine tissue loss and persistently generate all endometrial epithelial lineages during a female’s reproductive lifespan. Such findings in mice should facilitate the study of human uterine stem cells and regeneration, which will further the understanding of uterine physiology and pathology. The endometrial epithelium of the uterus regenerates periodically. The cellular source of newly regenerated endometrial epithelia during a mouse estrous cycle or a human menstrual cycle is presently unknown. Here, I have used single-cell lineage tracing in the whole mouse uterus to demonstrate that epithelial stem cells exist in the mouse uterus. These uterine epithelial stem cells provide a resident cellular supply that fuels endometrial epithelial regeneration. They are able to survive cyclical uterine tissue loss and persistently generate all endometrial epithelial lineages, including the functionally distinct luminal and glandular epithelia, to maintain uterine cycling. The uterine epithelial stem cell population also supports the regeneration of uterine endometrial epithelium post parturition. The 5-ethynyl-2′-deoxyuridine pulse-chase experiments further reveal that this stem cell population may reside in the intersection zone between luminal and glandular epithelial compartments. This tissue distribution allows these bipotent uterine epithelial stem cells to bidirectionally differentiate to maintain homeostasis and regeneration of mouse endometrial epithelium under physiological conditions. Thus, uterine function over the reproductive lifespan of a mouse relies on stem cell-maintained rhythmic endometrial regeneration.
Sensitivity of Cladosporium caryigenum to Propiconazole and Fenbuconazole.

Monoconidial isolates of the pecan scab fungus, Cladosporium caryigenum, were obtained in 1993 and 1994 from one pecan orchard each in Jeff Davis and Troup counties in Georgia, counties with no previous history of exposure to demethylation-inhibiting (DMI) fungicides. Isolates were grown on potato dextrose agar (PDA) amended with propiconazole or fenbuconazole at 0,0.0001, 0.0005, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1.0, or 5.0 µg ml-1. After 4 to 5 weeks at 25°C, the diameter of each colony was measured. Relative growth was expressed as the colony diameter for each fungicide concentration as a percentage of the diameter on unamended PDA. (ED)50 values for both fungicides in all years and locations were lognormally distributed. Mean (ED)50 values ranged from 0.19 to 0.30 µg ml-1 for fenbuconazole and 0.12 to 0.17 µg ml-1 for propiconazole. There were highly significant positive correlations between sensitivity to propiconazole and sensitivity to fenbuconazole at all locations and years, indicating significant potential for development of cross-resistance to these compounds. A discriminatory concentration of 0.2 µg ml-1 propiconazole was selected for further monitoring of DMI sensitivity. With this discriminatory concentration, a sample size of 50 isolates was estimated to be sufficient to detect a difference of 8.3% in mean relative growth between two populations.
Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate

Oxygen sensing revisited The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way in which hypoxia alters gene expression have focused on oxygen-sensing enzymes that regulate the activity of a transcription factor called hypoxia-inducible factor (see the Perspective by Gallipoli and Huntly). Chakraborty et al. and Batie et al. now show that hypoxia can also affect gene expression through direct effects on chromatin regulators. Certain histone demethylases, such as KDM6A and KDM5A, were found to be direct sensors of oxygen. In cell-culture models, hypoxia diminished the activity of these enzymes and caused changes in the expression of genes that govern cell fate. Science, this issue p. 1217, p. 1222; see also p. 1148 Certain chromatin regulators can directly sense changes in oxygen levels, leading to changes in gene expression. Oxygen sensing is central to metazoan biology and has implications for human disease. Mammalian cells express multiple oxygen-dependent enzymes called 2-oxoglutarate (OG)-dependent dioxygenases (2-OGDDs), but they vary in their oxygen affinities and hence their ability to sense oxygen. The 2-OGDD histone demethylases control histone methylation. Hypoxia increases histone methylation, but whether this reflects direct effects on histone demethylases or indirect effects caused by the hypoxic induction of the HIF (hypoxia-inducible factor) transcription factor or the 2-OG antagonist 2-hydroxyglutarate (2-HG) is unclear. Here, we report that hypoxia promotes histone methylation in a HIF- and 2-HG–independent manner. We found that the H3K27 histone demethylase KDM6A/UTX, but not its paralog KDM6B, is oxygen sensitive. KDM6A loss, like hypoxia, prevented H3K27 demethylation and blocked cellular differentiation. Restoring H3K27 methylation homeostasis in hypoxic cells reversed these effects. Thus, oxygen directly affects chromatin regulators to control cell fate.
Hypoxia induces rapid changes to histone methylation and reprograms chromatin

Oxygen sensing revisited The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way in which hypoxia alters gene expression have focused on oxygen-sensing enzymes that regulate the activity of a transcription factor called hypoxia-inducible factor (see the Perspective by Gallipoli and Huntly). Chakraborty et al. and Batie et al. now show that hypoxia can also affect gene expression through direct effects on chromatin regulators. Certain histone demethylases, such as KDM6A and KDM5A, were found to be direct sensors of oxygen. In cell-culture models, hypoxia diminished the activity of these enzymes and caused changes in the expression of genes that govern cell fate. Science, this issue p. 1217, p. 1222; see also p. 1148 Certain chromatin regulators can directly sense changes in oxygen levels, leading to changes in gene expression. Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor–independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell’s transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition.
Experimental Study on Shear Capacity of Reinforced Concrete Beams with Corroded Longitudinal Reinforcement

In this study, shear tests were conducted to investigate the effects of longitudinal reinforcement corrosion on the shear capacity of reinforced concrete (RC) members with transverse reinforcement. To this end, a total of eight test specimens were fabricated, and the corrosion rates and anchorage details of rebars were set as test variables. In addition, an accelerated corrosion technique was used to introduce corrosion into the longitudinal reinforcement without corroding shear reinforcement. The test results indicated that the capacities of the specimens in which tension reinforcement was not properly anchored at the ends of the members decreased rapidly at high corrosion rates, whereas the capacities of the specimens in which tension reinforcement was properly anchored by hooks were similar to or higher than those of the non-corroded specimens, despite bond loss caused by corrosion.
Extracellular Vesicles as Diagnostics and Therapeutics for Structural Epilepsies

Extracellular vesicles (EVs) are small vesicles involved in intercellular communication. Data is emerging that EVs and their cargo have potential as diagnostic biomarkers and treatments for brain diseases, including traumatic brain injury and epilepsy. Here, we summarize the current knowledge regarding changes in EV numbers and cargo in status epilepticus (SE) and traumatic brain injury (TBI), which are clinically significant etiologies for acquired epileptogenesis in animals and humans. We also review encouraging data, which suggests that EVs secreted by stem cells may serve as recovery-enhancing treatments for SE and TBI. Using Gene Set Enrichment Analysis, we show that brain EV-related transcripts are positively enriched in rodent models of epileptogenesis and epilepsy, and altered in response to anti-seizure drugs. These data suggest that EVs show promise as biomarkers, treatments and drug targets for epilepsy. In parallel to gathering conceptual knowledge, analytics platforms for the isolation and analysis of EV contents need to be further developed.
Physiotherapists’ views, perceived knowledge, and reported use of psychosocial strategies in practice

ABSTRACT Background: Research has addressed the usefulness of psychosocial strategies within physiotherapy, as part of a biopsychosocial model. A lack of current research in Australia concerning the views of physiotherapists, from a range of practice areas, regarding a variety of strategies, suggests the need for broader exploration. Methods: This research employed a cross-sectional survey asking Australian physiotherapists (n = 251) to rate their perceived importance and perceived benefits of psychosocial strategies; perceived positive effects on rehabilitation outcomes and adherence; confidence in applying strategies, and perceived benefits of further training. Data were analyzed using descriptive statistics, Crosstabs with Chi-Squared Tests of Contingencies and Spearman’s Rank-Order Correlations. Results: Physiotherapists reported that having knowledge of such strategies was important and considered them beneficial for practice. Respondents rated highly their perceived knowledge about goal setting and positive reinforcement, both of which were reported as most used in practice. Approximately one quarter of physiotherapists reported using cognitive behavioral therapy and motivational interviewing. Physiotherapists communicated a lack of confidence to apply psychosocial strategies in their practice, and desired further training. Conclusion: Physiotherapists could benefit from tailored instruction regarding psychosocial strategies at a level appropriate to, and within their scope of practice. This could enhance their practice from a biopsychosocial perspective, subsequently improving outcomes for their patients.
Clinical and Serologic Characteristics of Systemic Lupus Erythematosus in the Arab World: A Pooled Analysis of 3,273 Patients.

Objectives This study aims to describe the clinical and immunological characteristics of systemic lupus erythematosus in the Arab world. Materials and methods We searched PubMed and Google Scholar for observational studies describing the clinical and serologic features of systemic lupus erythematosus in adult patients in the Arab world. We used the search terms "lupus in Arabs" and the names of individual Arab countries. Twenty-two articles from 11 countries including 3,273 patients (349 males, 2,924 females; mean age 28.9 years) met the inclusion criteria and were analyzed. Studies that reported on either clinical or serologic data in adult patients were included. Results The mean age at disease onset was 28.9 years. The female to male ratio was 8.34:1. The most common clinical manifestations were arthralgia/arthritis (81.1%), anemia (55.6%), fatigue (53.4%), malar rash (53.1%) and renal manifestations (50.4%). Antinuclear antibodies were present in 97.2%, anti-double stranded deoxyribonucleic acid in 74.1%, anti-Ro/Sjögren syndrome A in 50.5%, anti-ribonucleoprotein in 43.5%, anti-Smith in 40.7% and anti-La/Sjögren syndrome B in 29.2%. The mortality rate was 7.6%. The frequency of various clinical and immunological manifestations varied between different regions. Conclusion Systemic lupus erythematosus displays several different clinical and serologic characteristics, both among different Arab populations and in comparison to other ethnic groups.
Superior Canal Dehiscence Syndrome: Relating Clinical Findings With Vestibular Neural Responses From a Guinea Pig Model.

HYPOTHESIS In superior canal dehiscence (SCD), fluid displacement of the endolymph activates type I vestibular hair cells in the crista of the affected canal and thus irregular superior canal (SC) neurons in Scarpa's ganglion, which provides the neurophysiological basis for the clinical presentation of SCD. BACKGROUND Patients with SCD display sound- and vibration-induced vertigo/nystagmus and increased amplitudes of vestibular evoked myogenic potentials. METHODS Extracellular recordings from n = 25 primary vestibular neurons of 16 female guinea pigs were analyzed. We recorded from the same vestibular neuron before, during and after creating the dehiscence and after closing the dehiscence. Neurobiotin labeling was employed in n = 11 neurons. RESULTS After SCD, previously unresponsive irregular SC neurons displayed a stimulus-locked increase in discharge during application of air-conducted sound (ACS) or bone-conducted vibration (BCV) for a broad range of frequencies (ACS: 200-4000 Hz; BCV: 500-1500 Hz). This typical response was only observed for irregular SC neurons (n = 19), but not regular SC neurons, or irregular/regular horizontal canal neurons (n = 2 each), and was abolished after closing the dehiscence. Eleven irregular SC neurons responsive to ACS and/or BCV were traced back to calyx synapses in the central crista of the affected superior canal by neurobiotin labeling. CONCLUSIONS Stimulus-locked activation of irregular SC neurons by ACS and BCV is the neurophysiological basis for sound- and vibration-induced vertigo/nystagmus and increased VEMP amplitudes in SCD. The results of the present study help to improve vestibular diagnostics in patients with suspected SCD.
How Reliable Is CT Scan in Staging Right Colon Cancer?

BACKGROUND The observation of inferior oncologic outcomes after surgery for proximal colon cancers has led to the investigation of alternative treatment strategies, including surgical procedures and neoadjuvant systemic chemotherapy in selective patients. OBJECTIVE The purpose of this study was to determine the accuracy of CT staging in proximal colon cancer in detecting unfavorable pathologic features that may aid in the selection of ideal candidates with unfavorable pathologic features for alternative treatment strategies, including extended lymph node dissection and/or neoadjuvant chemotherapy. DESIGN This was a retrospective consecutive series. SETTINGS Trained abdominal radiologists from 2 centers performed a blinded review of CT scans obtained to locally stage proximal colon cancer according to previously defined prognostic groups, including T1 to T2, T3 to T4, N+, and extramural venous invasion positive. CT findings were compared with histopathologic results as a reference standard. Unfavorable pathologic findings included pT3/4, pN+, or pre-extramural venous invasion positive. PATIENTS Consecutive patients undergoing right colectomy in 2 institutions between 2011 and 2016 were retrospectively reviewed from a prospectively collected database. MAIN OUTCOME MEASURES T status, nodal status, and extramural venous invasion status comparing CT with final histologic findings were measured. RESULTS Of 150 CT scans reviewed, CT failed to identify primary cancer in 19.3%. Overall accuracy of CT to identify unfavorable pathologic features was 63% with sensitivity, specificity, positive predictive value, and negative predictive value of 63% (95% CI, 54%-71%), 63% (95% CI, 46%-81%), 87% (95% CI, 80%-94%) and 30% (95% CI, 18%-41%). Only cT3/4 (55% vs 45%; p = 0.001) and cN+ (42% vs 58%; p = 0.02) were significantly associated with correct identification of unfavorable features at final pathology. CT scans overstaged and understaged cT in 23.7% and 48.3% and cN in 28.7% and 53.0% of cases. LIMITATIONS The study was limited by its retrospective design, relatively small sample size, and heterogeneity of CT images performed in different institutions with variable equipment and technical details. CONCLUSIONS Accuracy of CT scan for identification of pT3/4, pN+, or pre-extramural venous invasion positivity was insufficient to allow for proper identification of patients at high risk for local recurrence and/or in whom to consider alternative treatment strategies. Locoregional overstaging and understaging resulted in inappropriate treatment strategies in <48%. See Video Abstract at http://links.lww. com/DCR/A935.
Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer

Cells establish and sustain structural and functional integrity of the genome to support cellular identity and prevent malignant transformation. In this review, we present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization (HCO) that are perturbed in breast cancer onset and progression. Implications for dysfunctions that occur in hormone regulation, cell cycle control, and mitotic bookmarking in breast cancer are considered, with an emphasis on epithelial‐to‐mesenchymal transition and cancer stem cell activities. The architectural organization of regulatory machinery is addressed within the contexts of translating cancer‐compromised genomic organization to advances in breast cancer risk assessment, diagnosis, prognosis, and identification of novel therapeutic targets with high specificity and minimal off target effects.
Variations of the plantar tarsometatarsal ligaments

This study investigated the morphological variations of the plantar tarsometatarsal ligaments of the foot by classifying them based on their ligamentous components. Fifty embalmed feet from 27 adult Korean cadavers were used. The plantar tarsometatarsal ligaments comprised nine components (medial cuneiform‐first metatarsal, pCn1‐M1; medial cuneiform‐second metatarsal, pCn1‐M2; medial cuneiform‐second and third metatarsals, pCn1‐M2,3; median cuneiform‐second metatarsal, pCn2‐M2; lateral cuneiform‐third metatarsal, pCn3‐M3; lateral cuneiform‐fourth metatarsal, pCn3‐M4; lateral cuneiform‐third and fourth metatarsals, pCn3‐M3,4; cuboid‐fourth metatarsal, pCb‐M4; and cuboid‐fifth metatarsal, pCb‐M5). pCn1‐M2 was newly observed in the present study. The number of the bands composing the ligament was one in the pCn1‐M2, pCn2‐M2, pCn3‐M3, and pCn3‐M4 components, and one or two in the pCn1‐M1, pCn1‐M2,3, pCn3‐M3,4, pCb‐M4, and pCb‐M5 components. The plantar tarsometatarsal ligaments were classified into five types based on the combination of their components. The pCn1‐M1, pCn1‐M2,3, and pCn2‐M2 components were consistently observed in types I–IV (88%), along with pCn3‐M3,4 in type I, pCn3‐M4 and pCb‐M5 in type II, and pCn3‐M3 in type IV. In type V (12%), the pCn1‐M1 and pCb‐M5 components were consistently present. Improved comprehension of the variations in plantar tarsometatarsal ligament anatomy is expected to help diagnose diverse injuries to this region, better understand the structural pathomechanism of the injuries, and contribute to successful treatment. Clin. Anat. 32:699–705, 2019. © 2019 Wiley Periodicals, Inc.