Miracle-dz/UniFAR-FTUs huggingface dataset:
FoxO3a depletion accelerates cutaneous wound healing by regulating epithelial-mesenchymal transition through β-catenin activation

The hysteresis of keratinocyte (KC) re-epithelialization is an important factor resulting in chronic wounds; however, the molecular mechanisms involved in this cellular response remain yet to be completely elucidated. The present study demonstrated the function of transcription factor Forkhead box O3a (FoxO3a) in KC growth and migration functional effects, resulting in restrained KC re-epithelialization during wound healing. In chronic wound tissue samples, the expression of FoxO3a was significantly increased when compared with the acute wound healing group (P<0.01). Overexpressing FoxO3a significantly inhibited, whereas silencing endogenous FoxO3a enhanced, the growth and migration of HaCaT cells in vitro. Further investigation revealed that FoxO3a negatively regulated matrix metalloproteinases 1 and 9, and increased the expression of tissue inhibitor of metalloproteinase 1. In addition, the upregulation of FoxO3a retarded, whereas the downregulation of FoxO3a accelerated, transforming growth factor-β1-induced epithelial-mesenchymal transition in HaCaT cells. Mechanistically, the overexpression of FoxO3a inactivated β-catenin signaling and markedly reduced the levels of nuclear β-catenin. These results reveal a novel mechanism of FoxO3a in regulating KC re-epithelialization, and provide novel targets for the prevention and treatment of chronic wounds.
Stormy water on Mars: The distribution and saturation of atmospheric water during the dusty season

Water reaches Mars' upper atmosphere Mars once hosted abundant water on its surface but subsequently lost most of it to space. Small amounts of water vapor are still present in the atmosphere, which can escape if they reach sufficiently high altitudes. Fedorova et al. used data from the ExoMars Trace Gas Orbiter spacecraft to determine the distribution of water in Mars' atmosphere and investigate how it varies over seasons. Water vapor is sometimes heavily saturated, and its distribution is affected by the planet's large dust storms. Water can efficiently reach the upper atmosphere when Mars is in the warmest part of its orbit, and this behavior may have controlled the overall rate at which Mars lost its water. Science, this issue p. 297 ExoMars Trace Gas Orbiter data show how the distribution of water vapor in the atmosphere of Mars varies with the seasons. The loss of water from Mars to space is thought to result from the transport of water to the upper atmosphere, where it is dissociated to hydrogen and escapes the planet. Recent observations have suggested large, rapid seasonal intrusions of water into the upper atmosphere, boosting the hydrogen abundance. We use the Atmospheric Chemistry Suite on the ExoMars Trace Gas Orbiter to characterize the water distribution by altitude. Water profiles during the 2018–2019 southern spring and summer stormy seasons show that high-altitude water is preferentially supplied close to perihelion, and supersaturation occurs even when clouds are present. This implies that the potential for water to escape from Mars is higher than previously thought.
Anion Effect on Gas Absorption in Imidazolium-Based Ionic Liquids

We performed classical Molecular Dynamics computer simulations to analyze solutions of the gases CO2, N2 and CH4 into four 1-n-butyl-3-methylimidazolium based ionic liquids (1-n-butyl-3-methylimidazolium acetate, 1-n-butyl-3-methylimidazolium prolinate, 1-n-butyl-3-methylimidazolium bromide and 1-n-butyl-3-methylimidazolium tetrafluoroborate). Typical experimental conditions (10 bar gas pressure and room temperature) have been chosen to study mixtures of the ionic liquids with the gases at a single gas molar fraction of 0.25. Structural aspects are discussed to judge the absorption capacities of the ionic liquids. We observed that CO2 coordinates preferentially within the polar domain of the ionic liquids with the bromide and tetrafluoroborate anions presenting the best performances. The other gases, N2 and CH4, remain in the less polar domains of the ionic liquids. Cluster size analysis indicates phase separation for these two gases. Considering both, the absorption tendency and gas separation capacity of the ionic liquids, the anion is desired to be small and possessing multiple coordination sites. In this aspect, the tetrafluoroborate anion accomplished the best results.
Insights from user reviews to improve mental health apps

Mental health applications hold great promise as interventions for addressing common mental issues. Although many people with mental health issues use mobile app interventions, their adherence level remains low. Low engagement affects the effectiveness of mobile interventions. However, there is still a dearth of research to explain the reasons for low engagement. User experience and usability are two factors that determine the adoption and usage of apps. Analyzing user reviews of mobile apps for mental health issues reveals user experience and what features users liked and disliked in the apps and hence informs future app design and refinements. This research aims to analyze user reviews of publicly available mental health applications to uncover their strengths, weaknesses, and gaps, hence revealing why users are likely to cease using these applications. We mined reviews of 106 mental health apps retrieved from Apple’s App Store and Google Play and employed thematic analysis on 13,549 reviews. The review analysis shows that users placed more emphasis on the user interface and the user-friendliness of the app. Users also appreciated apps that present them with a variety of options, functionalities, and content that they can choose. Again, apps that offer adaptive functionalities that allow users to adapt some app features also received high ratings. In contrast, poor usability emerged as the most common reason for abandoning mental health apps. Other pitfalls include lack of a content variety, lack of personalization, lack of customer service and trust, and security and privacy issues.
Pneumonia may be more frequent and have more fatal outcomes with clozapine than with other second‐generation antipsychotics

World Psychiatry 19:1 February 2020 deterrents of parasites. This invites speculations that drug efficacy in the treatment of schizophrenia might be related, in part, to the anti-parasitic effect of the medications. However, currently available drugs against T. gondii infection do not have the potential to ameliorate the symptoms of schizophrenia. Parasitic behavior manipulation is widespread in nature, yet under-researched as a causative factor of disease in humans. This is so because knowledge about parasite-host interaction and other evolutionary aspects germane to medicine still linger to be implemented in curricula at medical schools. Thus, both clinicians and pharmaceutical companies are oblivious to putative mechanisms of parasitic action. However, if action were taken to follow up on the above evolutionary insights, one could see schizophrenia as an ancestral “vestige” from a time when early humans fell prey to large feline predators. Future research into schizophrenia may be advised to study the link between T. gondii infection, clinical symptomatology contributing to social exclusion, and genetic factors involving the major histocompatibility complex and other immunologically relevant genes such as DISC1, some of which have been positively selected during human evolution. It might eventually turn out that there is a chance of causal treatment for schizophrenia realized by the development of new antibiotics against latent toxoplasmosis, rather than (or in addition to) reiterating attempts to ameliorate epiphenomena of the condition.
Relationship between arm span and height among elderly persons in a rural area of Ballabgarh, Haryana

Centre for Community Medicine and *Department of Biostatistics, All India Institute of Medical Sciences, New Delhi. Corresponding author: Dr. Sanjeev Kumar Gupta, Professor of Community Medicine, Centre for Community Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi– 110029, India. Ph. : +91-11-26594218, +91-9868528573, E-mail: sgupta_91@yahoo.co.in Received: 03-12-2012 | Accepted: 11-06-2013 | Published Online: 16-06-2013 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (creativecommons.org/licenses/by/3.0) Conflict of interest: None declared | Source of funding: Nil | DOI: http://dx.doi. org/10.7713/ijms.2013.0025 Abstract
Renal Replacement Knowledge and Preferences for African Americans With Chronic Kidney Disease.

BACKGROUND Renal replacement therapies (RRT) other than in-centre haemodialyses are underutilised by African Americans with end-stage renal disease (ESRD) even though they are associated with reduced costs, morbidity and mortality as well as improved quality of life for patients. OBJECTIVES To understand African American patients' knowledge of RRT options and how patient, provider and system-factors contribute to knowledge and preferences. Participants' interviews were conducted at the University of Chicago Medical Center with African American patients with chronic kidney disease (CKD). The final analysis included 28 interviews; 22 patients had CKD not yet on dialysis or having received a transplant, while 6 had reached ESRD and were receiving treatment for kidney failure. Approach Transcripts were uploaded into NVivo8 for coding. Thematic analysis was used for data interpretation. RESULTS Four themes were identified: (1) limited knowledge of home modalities and deceased donor options, (2) CKD patients gave little thought to choosing RRT options, (3) CKD patients relied on doctors for treatment decisions, and (4) while patients reported knowledge of living kidney donation transplants (LKDT), it did not translate to receiving an LKDT. CONCLUSION African Americans face significant knowledge and access barriers when deciding on their RRT treatment. Even patients with advanced CKD were still in the early stages of RRT selection. Understanding the knowledge gaps and barriers patients face will inform our subsequent intervention to educate and motivate patients to increase CKD self-care and improve communication between patients, their families and their providers about different RRT treatments.
Concordance of Three International Guidelines for Thyroid Nodules Classified by Ultrasonography and Diagnostic Performance of Biopsy Criteria

Objective To investigate the concordance of three international guidelines: the Korean Thyroid Association/Korean Society of Thyroid Radiology, American Thyroid Association, and American College of Radiology for thyroid nodules classified by ultrasonography (US) and the diagnostic performance of simulated size criteria for malignant biopsies. Materials and Methods A total of 2586 thyroid nodules (≥ 1 cm) were collected from two multicenter study datasets. The classifications of the thyroid nodules were based on three different guidelines according to US categories for malignancy risk, and the concordance rate between the different guidelines was calculated for the classified nodules. In addition, the diagnostic performance of criteria related to four different simulated biopsy sizes was evaluated. Results The concordance rate of nodules classified as high- or intermediate-suspicion was high (84.1–100%), but low-suspicion or mildly-suspicious nodules exhibited relatively low concordance (63.8–83.8%) between the three guidelines. The differences in sensitivity, specificity, and accuracy between the guidelines were 0.7–19.8%, 0–40.9%, and 0.1–30.5%, respectively, when the original biopsy criteria were applied. The differences decreased to 0–5.9%, 0–10.9%, and 0.1–8.2%, respectively, when simulated, similar biopsy size criteria were applied. The unnecessary biopsy rate calculated with the original criteria (0–33.8%), decreased with the simulated biopsy size criteria (0–8.7%). Conclusion We found a high concordance between the three guidelines for high- or intermediate-suspicion nodules, and the diagnostic performance of the biopsy criteria was approximately equivalent for each simulated size criterion. The difference in diagnostic performance between the three guidelines is mostly influenced by the various size thresholds for biopsies.
WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia

Tcell acute lymphoblastic leukemias (T-ALL) are aggressive and heterogeneous hematologic tumors resulting from the malignant transformation of T-cell progenitors. The major challenges in the treatment of T-ALL are dose-limiting toxicities of chemotherapeutics and drug resistance. Despite important progress in deciphering the genomic landscape of T-ALL, translation of these findings into effective targeted therapies remains largely unsuccessful. New targeted agents with significant antileukemic efficacy and less toxicity are urgently needed. Here we report that the expression of WEE1, a nuclear tyrosine kinase involved in cell cycle G2-M checkpoint signaling, is significantly elevated in T-ALL. Mechanistically, oncogenic MYC directly binds to the WEE1 promoter and activates its transcription. T-ALL cells particularly rely on the elevated WEE1 for cell viability. Pharmacological inhibition of WEE1 elicits global metabolic reprogramming which results in a marked suppression of aerobic glycolysis in T-ALL cells, leading to an increased dependency on glutaminolysis for cell survival. As such, dual targeting of WEE1 and glutaminase (GLS1) induces synergistic lethality in multiple TALL cell lines and shows great efficacy in T-ALL patient-derived xenografts. These findings provide mechanistic insights into the regulation of WEE1 kinase in T-ALL and suggest an additional vulnerability during WEE1 inhibitor treatments. We also highlight a promising combination strategy of dual inhibition of cell cycle kinase and metabolic enzymes for T-ALL therapeutics.
MCPIP1 overexpression in human neuroblastoma cell lines causes cell‐cycle arrest by G1/S checkpoint block

Monocyte chemoattractant protein‐1‐induced protein 1 (MCPIP1) has a multidomain structure, which assures its pleiotropic activity. The physiological functions of this protein include repression of inflammatory processes and the prevention of immune disorders. The influence of MCPIP1 on the cell cycle of cancer cells has not been sufficiently elucidated. A previous study by our group reported that overexpression of MCPIP1 affects the cell viability, inhibits the activation of the phosphoinositide‐3 kinase/mammalian target of rapamycin signalling pathway, and reduces the stability of the MYCN oncogene in neuroblastoma (NB) cells. Furthermore, a decrease in expression and phosphorylation levels of cyclin‐dependent kinase (CDK) 1, which has a key role in the M phase of the cell cycle, was observed. On the basis of these previous results, the purpose of our present study was to elucidate the influence of MCPIP1 on the cell cycle of NB cells. It was confirmed that ectopic overexpression of MCPIP1 in two human NB cell lines, KELLY and BE(2)‐C, inhibited cell proliferation. Furthermore, flow cytometric analyses and imaging of the cell cycle with a fluorescence ubiquitination cell‐cycle indicator test, demonstrated that overexpression of MCPIP1 causes an accumulation of NB cells in the G1 phase of the cell cycle, while the possibility of an increase in G0 phase due to induction of quiescence or senescence was excluded. Additional assessment of the molecular machinery responsible for the transition between the cell‐cycle phases confirmed that MCPIP1 overexpression reduced the expression of cyclins A2, B1, D1, D3, E1, and E2 and decreased the phosphorylation of CDK2 and CDK4, as well as retinoblastoma protein. In conclusion, the present results indicated a relevant impact of overexpression of MCPIP1 on the cell cycle, namely a block of the G1/S cell‐cycle checkpoint, resulting in arrest of NB cells in the G1 phase.
A rapid and quantitative safranin-based fluorescent microscopy method to evaluate cell wall lignification.

One of the main characteristics of plant cells is the presence of the cell wall located outside the plasma membrane. In particular cells, this wall can be reinforced by lignin, a polyphenolic polymer that plays a central role for vascular plants, conferring hydrophobicity to conducting tissues and mechanical support for upright growth. Lignin has been extensively studied by a range of different techniques including anatomical and morphological analyses using dyes to characterize the polymer localization in situ. With the constant improvement of imaging techniques, it is now possible to revisit old qualitative techniques and adapt them to obtain efficient, highly resolutive, quantitative, fast and safe methodologies. In this study, we revisit and exploit the potential of fluorescent microscopy coupled to safranin-O staining to develop a quantitative approach for lignin content determination. The developed approach is based on ratiometric emission measurements and the development of an ImageJ macro. To demonstrate the interest of our methodology compared to other commonly-used lignin reagents, we showed that safranine-O staining was used to evaluate and compare lignin contents in previously characterized A. thaliana lignin biosynthesis mutants. In addition, the analysis of lignin content and spatial distribution in the Arabidopsis laccase mutant also provided new biological insights into the effects of laccase gene down-regulation in different cell types. Our safranine-O based methodology, also validated for flax, maize and poplar, significantly improves and speed-up anatomical and developmental investigations of lignin, which we hope will contribute to new discoveries in many areas of cell wall plant research.
Environmentally-relevant exposure to diethylhexyl phthalate (DEHP) alters regulation of double-strand break formation and crossover designation leading to germline dysfunction in Caenorhabditis elegans

Exposure to diethylhexyl phthalate (DEHP), the most abundant plasticizer used in the production of polyvinyl-containing plastics, has been associated to adverse reproductive health outcomes in both males and females. While the effects of DEHP on reproductive health have been widely investigated, the molecular mechanisms by which exposure to environmentally-relevant levels of DEHP and its metabolites impact the female germline in the context of a multicellular organism have remained elusive. Using the Caenorhabditis elegans germline as a model for studying reprotoxicity, we show that exposure to environmentally-relevant levels of DEHP and its metabolites results in increased meiotic double-strand breaks (DSBs), altered DSB repair progression, activation of p53/CEP-1-dependent germ cell apoptosis, defects in chromosome remodeling at late prophase I, aberrant chromosome morphology in diakinesis oocytes, increased chromosome non-disjunction and defects during early embryogenesis. Exposure to DEHP results in a subset of nuclei held in a DSB permissive state in mid to late pachytene that exhibit defects in crossover (CO) designation/formation. In addition, these nuclei show reduced Polo-like kinase-1/2 (PLK-1/2)-dependent phosphorylation of SYP-4, a synaptonemal complex (SC) protein. Moreover, DEHP exposure leads to germline-specific change in the expression of prmt-5, which encodes for an arginine methyltransferase, and both increased SC length and altered CO designation levels on the X chromosome. Taken together, our data suggest a model by which impairment of a PLK-1/2-dependent negative feedback loop set in place to shut down meiotic DSBs, together with alterations in chromosome structure, contribute to the formation of an excess number of DSBs and altered CO designation levels, leading to genomic instability.
Biological therapy safety in chronic inflammatory arthropathy patients.

OBJECTIVE The marketing of biological therapies transformed the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. But there is still concern about patient safety and management in daily clinical practice. The aim of this study was to estimate risk factors of the adverse effects in a cohort of Spanish patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS A single institution, descriptive, retrospective, cohort study was developed from January 2009 to December 2016. Patients diagnosed with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis on biological therapies were included. Undesirable events affecting patients during biological therapy, their clinical implications and the use of health resources related to adverse effects were collected. RESULTS Three hundred and sixty-two patients corresponding to 478 biological therapy lines were analysed. It implied 1192 years of monitoring. There were 57 adverse effects per 100 biological patient-years and 4.8 serious adverse effects per 100 biological patient-years. The only significant factor for a likely serious adverse effect was having a Charlson Index ≥10, OR of 6.2 (CI 95%: 3.4-11.1, p<0.001). Around 15 % of patients with adverse effects were admitted to hospital and 25% received attention at the Emergency Department. CONCLUSION Over half of the patients with arthropathies on biological therapy can suffer adverse effect during treatment but only 8.5% of these effects are serious. Special vigilance must be paid to patients with a higher number of comorbidities because they are more likely to experience serious adverse effects.
Inhibitor incidence in an unselected cohort of previously untreated patients with severe hemophilia B: a PedNet study

The incidence of factor IX (FIX) inhibitors in severe hemophilia B (SHB) is not well defined. Frequencies of 3-5% have been reported but most studies to date have been small, including patients with different severities, and without prospective follow up for inhibitor incidence. The study objective was to investigate the inhibitor incidence in patients with SHB followed up for to 500 exposure days (ED), the frequency of allergic reactions, and the relationship with genotypes. Consecutive previously untreated patients (PUP) with SHB enrolled into the PedNet cohort were included. Detailed data was collected for the first 50 ED, followed by the annual collection of the inhibitor status and allergic re-actions. The presence of inhibitors was defined by at least two consecutive positive samples. Additionally, data on FIX gene mutation was collected. One hundred and fifty-four PUP with SHB were included; 75% were followed up until 75 ED, and 43% until 500 ED. Inhibitors developed in 14 patients (seven high-titer). The median number of ED at inhibitor manifestation was 11 (interquartile range [IQR]: 6.5-36.5). The cumulative inhibitor incidence was 9.3% (95% Confidence Interval [CI]: 4.4-14.1) at 75 ED, and 10.2% (95% CI: 5.1-15.3) at 500 ED. Allergic reactions occurred in four (28.6%) inhibitor patients. Missense mutations were most frequent (46.8%) overall but not associated with inhibitors. Nonsense mutations and deletions with large structural changes comprised all mutations among inhibitor patients and were associated with an inhibitor risk of 26.9% and 33.3%, respectively. In an unselected, well-defined cohort of PUP with SHB, the cumulative inhibitor incidence was 10.2% at 500 ED. Nonsense mutations and large deletions were strongly associated with the risk of inhibitor development. The ‘PedNet Registry’ is registered at clinicaltrials.gov; identifier: NCT02979119.