Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.
The impact of maternal protein restriction during perinatal life on the response to a septic insult in adult rats

Abstract Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.
Cross‐matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting

Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross‐matching, on the assumption that they are immune‐privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra‐articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri‐articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor‐specific antibodies in mismatched recipients compared with recipients receiving matched allogeneic or autologous MSCs. Importantly, in matched allogeneic and autologous recipients, but not mismatched allogeneic recipients, there was increased stromal derived factor‐1 along with increased MSC concentrations in synovial fluid. Until immune recognition of MSCs can be avoided, repeated clinical use of MSCs should be limited to autologous or cross‐matched allogeneic MSCs. When non–cross‐matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed.
Patients’ conceptions of undergoing physiotherapy for persistent low back pain delivered in Finnish primary healthcare by physiotherapists who had participated in brief training in cognitive functional therapy

Abstract Purpose To explore the conceptions of patients with persistent low back pain (LBP) of undergoing physiotherapy delivered in Finnish primary healthcare by physiotherapists who had participated in brief training in Cognitive Functional Therapy (CFT). Methods As part of a feasibility implementation study exploring CFT in management of LBP in the Finnish primary healthcare system, we interviewed nine patients from four geographical areas in Finland after receiving care. We used a phenomenographic approach to explore the variation in their conceptions. Results The analysis revealed four descriptive categories: “hung out to dry,” “stuck,” “making sense and taking control,” and “holistic approach to care and living,” that varied based on six themes. Conclusions Although the participants accepted this approach to care well, there was significant variation in patients’ conceptions. Restricted access to care within the healthcare system and a lack of social support led some of them to feel they had been left alone to suffer with their pain. On the other hand, based on the results of this study, positive experiences of physiotherapy and good collaboration with the physiotherapist, wider social support outside of physiotherapy, a better understanding of the multidimensional nature of pain and the acquisition of self-management skills were reported as positive aspects of undergoing physiotherapy that may be related to positive treatment outcomes. Implications for rehabilitation The participants of this study saw undergoing physiotherapy delivered within biopsychosocial framework as different from their previous physiotherapy experiences and for some the process ended with feeling empty-handed and for others it could be a turning point in their lives. This study encourages the health care providers to create flexible care pathways and ongoing support for more vulnerable individuals so that they don’t feel abandoned by the system. Professionals could also pay attention to building strong therapeutic alliance, help patients understand pain in biopsychosocial framework, take into consideration social support networks of the patients, and support patients toward effective self-management strategies.
Time restricted feeding and mental health: a review of possible mechanisms on affective and cognitive disorders

Abstract In the last decades, a high increase in life expectancy not adequately balanced by an improvement in the quality of life has been observed, leading possibly to an increase in the prevalence of affective and cognitive disorders related to aging, such as depression, cognitive impairment, dementia and Alzheimer’s disease. As mental illnesses have multifactorial aetiologies, many modifiable factors including lifestyle and nutrition play an essential role. Among nutritional factors, intermittent fasting has emerged as an innovative strategy to prevent and treat mental health disorders, sleep disturbances and cognitive impairment. Among all types of intermittent fasting regimens, the time restricted feeding appears to be the most promising protocol as it allows to induce benefits of a total fasting without reducing global calories and nutrients intake. This review summarises the evidence on the effect of time restricted feeding towards brain health, emphasising its role on brain signalling, neurogenesis and synaptic plasticity.
Global impact of tobacco control policies on smokeless tobacco use: a systematic review protocol

Introduction Smokeless tobacco (ST) was consumed by 356 million people globally in 2017. Recent evidence shows that ST consumption is responsible for an estimated 652 494 all-cause deaths across the globe annually. The WHO Framework Convention on Tobacco Control (FCTC) was negotiated in 2003 and ratified in 2005 to implement effective tobacco control measures. While the policy measures enacted through various tobacco control laws have been effective in reducing the incidence and prevalence of smoking, the impact of ST-related policies (within WHO FCTC and beyond) on ST use is under-researched and not collated. Methods and analysis A systematic review will be conducted to collate all available ST-related policies implemented across various countries and assess their impact on ST use. The following databases will be searched: Medline, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Scopus, EconLit, ISI Web of Science, Cochrane Library (CENTRAL), African Index Medicus, LILACS, Scientific Electronic Library Online, Index Medicus for the Eastern Mediterranean Region, Index Medicus for South-East Asia Region, Western Pacific Region Index Medicus and WHO Library Database, as well as Google search engine and country-specific government websites. All ST-related policy documents (FCTC and non-FCTC) will be included. Results will be limited to literature published since 2005 in English and regional languages (Bengali, Hindi and Urdu). Two reviewers will independently employ two-stage screening to determine inclusion. The Effective Public Health Practice Project’s ‘Quality Assessment Tool for Quantitative Studies’ will be used to record ratings of quality and risk of bias among studies selected for inclusion. Data will be extracted using a standardised form. Meta-analysis and narrative synthesis will be used. Ethics and dissemination Permission for ethics exemption of the review was obtained from the Centre for Chronic Disease Control’s Institutional Ethics Committee, India (CCDC_IEC_06_2020; dated 16 April 2020). The results will be disseminated through publications in a peer-reviewed journal and will be presented in national and international conferences. PROSPERO registration number CRD42020191946.
Rheological Characterization of Nitrocellulose Gels

Various nitrocellulose, NC, based propellant formulations need to be processed using new and more environmentally friendly solvent combinations on the one hand and using continuous processing methodologies on the other hand. A detailed understanding of the significant changes that take place in the structure and hence the rheological behavior of NC based formulations during manufacture is required to minimize the use of organic solvents and to revert to safer and green solvents. Towards achieving these objectives, experimental methodologies were developed for the first time to enable the accurate characterization and thus fingerprinting of the rheological behavior of NC gels. In these methodologies linear viscoelastic measurements are employed. The concentration of the solvents existing in the gel sample during rheological characterization is concomitantly monitored to allow the documentation of the major source of error associated with the rapid loss of the typical solvents, which generally exhibit relatively high vapor pressures. These measurements have indicated that the source of the NC fibers and the treatment method alter the rheological behavior and can be tracked. The rheological properties of the NC gels can be linked to their manufacturability and such data can be used to pinpoint optimum geometries and processing conditions. The processability of the NC based formulations can also be tailored on the basis of rheological characterization, allowing the manufacturers greater latitude for reducing costs and environmental footprint during manufacture, as well as improving the quality of their NC based energetic formulations.
The Solubility of Nitrogen and Air in Liquids

This review covers the solubility of nitrogen and air in liquids as a function of temperature and pressure. Solubility data for individual systems were critically evaluated. Recommended or tentative values are presented as smoothing equations and/or in tabular form. Trends in homologous series or related solvents are discussed. Data for the n‐alkanes were smoothed with respect to temperature, pressure, and carbon number. Liquids include: water; heavy water; seawater; aqueous salt solutions; mixed solvents; hydrocarbons; organic compounds containing oxygen, halogen, sulfur, nitrogen, or silicon; olive oil; various biological fluids; H2S; SO2; NH3; CO2; nitrogen oxides; and several halogen and boron containing inorganic solvents.
USP22 controls necroptosis by regulating receptor‐interacting protein kinase 3 ubiquitination

Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin‐specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of mono‐ubiquitination from histones H2A and H2B, thereby regulating gene transcription. However, novel roles for USP22 have emerged recently, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in human tumor cell lines. Loss of USP22 expression significantly delays TNFα/Smac mimetic/zVAD.fmk (TBZ)‐induced necroptosis, without affecting TNFα‐mediated NF‐κB activation or extrinsic apoptosis. Ubiquitin remnant profiling identified receptor‐interacting protein kinase 3 (RIPK3) lysines 42, 351, and 518 as novel, USP22‐regulated ubiquitination sites during necroptosis. Importantly, mutation of RIPK3 K518 reduced necroptosis‐associated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of RIPK3 ubiquitination as crucial regulator of necroptotic cell death.
Crystallization of atmospheric sulfate‐nitrate‐ammonium particles

Relative humidity (RH) history and chemical composition determine whether atmospheric particles are liquid or solid. Particle physical state affects many climatic and environmental phenomena such as radiative transfer, visibility, and heterogeneous chemistry. Here we report the crystallization RH (CRH) at 293 K of particles throughout the entire sulfate‐nitrate‐ammonium composition space, and the new laboratory data are expressed as an empirical polynomial. Particles with compositions close to ammonium sulfate crystallize near 30% RH. Such particles are common in the boundary layer, including the eastern USA and East Asia though not Europe. Our measurements show the formation of several solids within the same particle for compositions enriched in nitrate or somewhat acidic, although the CRH is under 30%. The CRH for homogeneous nucleation is 40 to 55% below the deliquescence RH (DRH) for most chemical compositions. Our new results provide essential data for the incorporation of particle physical state in global models of chemistry and climate.
A unifying framework for rare variant association testing in family-based designs, including higher criticism approaches, SKATs, and burden tests

MOTIVATION Analysis of rare variants in family-based studies remains a challenge. Transmission-based approaches provide robustness against population stratification, but the evaluation of the significance of test statistics based on asymptotic theory can be imprecise. In addition, power will depend heavily on the choice of the test statistic and on the underlying genetic architecture of the locus, which will be generally unknown. RESULTS In our proposed framework, we utilize the FBAT haplotype algorithm to obtain the conditional offspring genotype distribution under the null hypothesis given the sufficient statistic. Based on this conditional offspring genotype distribution, the significance of virtually any association test statistic can be evaluated based on simulations or exact computations, without the need for asymptotic approximations. Besides standard linear burden-type statistics, this enables our approach to also evaluate other test statistics such as SKATs, higher criticism approaches, and maximum-single-variant-statistics, where asymptotic theory might be involved or does not provide accurate approximations for rare variant data. Based on the p-values, combined test statistics such as the aggregated Cauchy association test (ACAT) can also be utilized. In simulation studies, we show that our framework outperforms existing approaches for family-based studies in several scenarios. We also applied our methodology to a TOPMed whole-genome sequencing dataset with 897 asthmatic trios from Costa Rica. AVAILABILITY FBAT software is available at https://sites.google. com/view/fbatwebpage. Simulation code is available at https://github.com/julianhecker/FBAT_rare_variant_test_simulations. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection.

RATIONALE Rhinovirus C (RV-C) can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. OBJECTIVES To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. METHODS Longitudinal data from the Childhood Origins of ASThma (COAST) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for rhinovirus A (RV-A) and RV-C (3 types each) were determined using a novel polymerase chain reaction-based assay. We pooled data from 14 study cohorts in the United States, Finland, and Australia and used mixed-effects logistic regression to identify factors related to the proportion of RV-C versus RV-A detection. MEASUREMENTS AND MAIN RESULTS In COAST, RV-A and RV-C infections were similarly common in infancy, while RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (p<0.001, chi-square) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5%-27%) at age 2 years, but by age 16, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A, p<0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (p<0.0001), CDHR3 genotype (p<0.05), and wheezing illnesses (p<0.05). Furthermore, certain RV types (e.g., C2, C11, A78, A12) were consistently more virulent and prevalent over time. DISCUSSION Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.
The value of including families in the treatment of anorexia nervosa

Abstract The aim of this paper is to consider family and wider carer involvement in the treatment of anorexia nervosa, and how this can be used to add value to services. We discuss widely adopted interventions involving the family that have been manualised and studied in trials that have outcome measures that are of relevance to illness costs. The therapeutic targets of these interventions range from a focus on feeding to the wellbeing of the whole family. The theoretical models that underpin interventions involving the family/wider carers include both intra and interpersonal processes, with the exception of family‐based therapy, which in its original form holds an agnostic stance towards aetiology. Although formal evaluation of the cost effectiveness of these interventions is minimal, there is evidence that involving the family can reduce bed use and improve the wellbeing of both patients and family members. Moreover, for the most part, these interventions are acceptable to patients and carers. Finally, we consider how these approaches can be disseminated and scaled up more widely into services.
Catalytic Wet Oxidation of Phenol Using Regeneration of Pt/Al2O3

Removal of phenol by wet air oxidation was conducted with 1 wt% Pt/Al2O3 catalyst in a batch reactor and in a continuous flow fluidized bed reactor with air lift tube operated at 423 K and 1.4 MPa. After 60 min in the batch reactor with initial phenol concentration of 1000 mg/l, almost complete conversion into CO2 and H2O was achieved. Pt/Al2O3 catalyst deactivation was observed during the wet oxidation reaction. TEM, EDX, XPS and TPO analyses showed the deactivation was caused by formation and deposition of carbonaceous materials on the catalyst surface. TEM of the deactivated Pt/Al2O3 showed formation of filamentous materials, which linked Pt particles, and some Pt particles were completely encapsulated by deposited material. XPS analysis showed that the carbonaceous materials on the catalyst consisted of four different morphologies (C1, C2, C3, C4). As the wet oxidation proceeded, the C1 peak increased gradually with reaction time, whereas the C2 and C3 peaks passed through maxima. At around the C2 and C3 peak maxima, the C4 peak began to appear and increased continuously up to 10 h reaction. This result indicates that at least two carbonaceous materials of C2 and C3 were transformed morphologically into C4 material. The broad profiles of CO2 formation from the TPO experiment implied that at least two types of carbon deposits were oxidized at different temperatures, one type on Pt particles, the other type on Al2O3. The carbonaceous deposit was formed on Pt particles and migrated continuously onto the support. The continuous flow fluidized bed reactor showed very stable wet oxidation performances in the presence of the air lift tube. The air lift tube was important in continuously regenerating the deactivated catalyst. The accumulated carbon deposits were reduced drastically by the action of the air lift tube.
One‐pot synthesis of 6‐aminohexanoic acid from cyclohexane using mixed‐species cultures

6‐Aminohexanoic acid (6AHA) is a vital polymer building block for Nylon 6 production and an FDA‐approved orphan drug. However, its production from cyclohexane is associated with several challenges, including low conversion and yield, and severe environmental issues. We aimed at overcoming these challenges by developing a bioprocess for 6AHA synthesis. A mixed‐species approach turned out to be most promising. Thereby, Pseudomonas taiwanensis VLB120 strains harbouring an upstream cascade converting cyclohexane to either є‐caprolactone (є‐CL) or 6‐hydroxyhexanoic acid (6HA) were combined with Escherichia coli JM101 strains containing the corresponding downstream cascade for the further conversion to 6AHA. ε‐CL was found to be a better ‘shuttle molecule’ than 6HA enabling higher 6AHA formation rates and yields. Mixed‐species reaction performance with 4 g l‐1 biomass, 10 mM cyclohexane, and an air‐to‐aqueous phase ratio of 23 combined with a repetitive oxygen feeding strategy led to complete substrate conversion with 86% 6AHA yield and an initial specific 6AHA formation rate of 7.7 ± 0.1 U gCDW‐1. The same cascade enabled 49% 7‐aminoheptanoic acid yield from cycloheptane. This combination of rationally engineered strains allowed direct 6AHA production from cyclohexane in one pot with high conversion and yield under environmentally benign conditions.