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Additional file 1: Table 1. Summary of assessment tools used as part of comprehensive geriatric assessment.

Licentiatuppsatsen handlar om förskolans utbildning utifrån barns rätt till stöd. Barns möjligheter till relationer, samspel och interaktion med sin omgivning påverkas av de förutsättningar som finns och skapas. Studiens syfte är att undersöka hur förskollärare och rektorer beskriver sin förståelse av förskolans utbildning utifrån barn som anses vara i behov av särskilt stöd. I studien används en hermeneutisk forskningsansats tillsammans med ett systemteoretiskt perspektiv utifrån Bronfenbrenners ekologiska utvecklingsmodell (Bronfenbrenner, 1979, 1994) och bioekologiska modell (Bronfenbrenner & Morris, 2006). Semistrukturerade intervjuer har använts som metod. Totalt har 15 intervjuer genomförts med åtta rektorer och sju förskollärare. Studiens resultat visar att respondenterna anser att de arbetar med barn i behov av särskilt stöd men de har samtidigt svårt att definiera vilka barn som är barn i behov av särskilt stöd. De menar att alla barn, tillfälligt eller långvarigt, kan vara barn i behov av särskilt stöd och att barnen inte behöver ha någon funktionsnedsättning eller diagnos för att behöva stöd. Resultatet visar också att rektorer och förskollärare beskriver flera organisatoriska förutsättningar i arbetet med barn i behov av särskilt stöd. Rektorns ledarskap och hur det specialpedagogiska stödet organiseras i förskolan är exempel på organisatoriska förutsättningar. Pedagogiska strategier handlar till exempel om hur förskollärare arbetar nära barnen för att kunna se vad om händer i barngruppen och för att kunna ge stöd till barnen om det behövs. Den komplexitet som framträder i resultatet på samhälls-, organisations-, grupp- och individnivå skapar både möjligheter och utmaningar att möta alla barn och att utveckla en likvärdig utbildning i förskolan. The aim of the study is to examine how preschool teachers and preschool principals describe their understanding of preschool's education based on children in need of special support. The following research questions are in focus: How do preschool teachers and preschool principals describe children who they consider to be children in need of special support? What organizational conditions in education for children in need of special supports do the preschool teachers and preschool principals describe? What pedagogical strategies in education for children in need of special supports do the preschool teachers and preschool principals describe? The study applies a hermeneutics framework and a system theoretical perspective. Bronfenbrenner's ecological model (Bronfenbrenner, 1979, 1994) and the further developed bioecological model (Bronfenbrenner & Morris, 2006), with its associated PPCT-components (process, person, context, time), are used. Semi-structured interviews have been used as a method. Fifteen interviews have been conducted, eight with preschool principals and seven with preschool teachers. The result shows that the respondents do consider themselves working with children in need of special support, but they explain that it is difficult to identify which children this applies to. They argue that all children can at some point, temporarily or permanently, need special support and the children do not necessarily need a diagnosis in order be in special needs. The result also shows that the preschool principals and the preschool teachers describe several organizational conditions that can be useful in their work with children in need special support. The leadership of the preschool principal and how the support to children in special need is organized are examples of organizational conditions. Other thing they discuss are the preschool staff´s education and competence. Pedagogical strategies are, for example, how preschool teachers describe their job near the children to monitor what happens in the child group and to be able to support the children. The results suggest that there are shortcomings regarding equity, based on the descriptions given by preschools teachers and principals. There are shortcomings in equity regarding educational issues and how the preschools organize and carry out the work with children in need of special support in preschool.

The role of nurses and nursing in CAP inpatient care is unclear, and nurses are at risk of moral distress due to having to deal with complex demands while lacking organizational support. This study aimed to describe nurses’ and assistant nurses’ experiences working in child and adolescent psychiatric inpatient care. Eight nurses and seven assistant nurses working in a child and adolescent ward in Sweden participated in the study. Data were collected in 2019 using semi-structured qualitative interviews and subject to qualitative content analysis. Results describe nurses’ and assistant nurses’ experiences of child and adolescent psychiatric inpatient care in one theme, Constrained nursing, and four categories: Striving to be there for children and parents; Finding a way to manage work; Depending on others; Lacking nursing leadership. Findings suggest that good, person-centred and recovery-oriented nursing practice can exist in CAP inpatient care but remain unrecognized and lacking support due to unclear roles and responsibilities and lack of nursing leadership. This study is reported in accordance with the COREQ guidelines. Validerad;2022;Nivå 2;2022-02-01 (johcin)

Objectives To set out the second in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis that concerns retrograde intrarenal surgery (RIRS), with the aim of providing a clinical framework for urologists performing RIRS. Materials and Methods After a comprehensive search of RIRS-related literature published between 1 January 1964 and 1 October 2021 from the PubMed database, systematic review and assessment were performed to inform a series of recommendations, which were graded using modified GRADE methodology. Additionally, quality of evidence was classified using a modification of the Oxford Centre for Evidence-Based Medicine Levels of Evidence system. Finally, related comments were provided. Results A total of 36 recommendations were developed and graded that covered the following topics: indications and contraindications; preoperative imaging; preoperative ureteric stenting; preoperative medications; peri-operative antibiotics; management of antithrombotic therapy; anaesthesia; patient positioning; equipment; lithotripsy; exit strategy; and complications. Conclusion The series of recommendations regarding RIRS, along with the related commentary and supporting documentation, offered here should help provide safe and effective performance of RIRS.

Natural antisense transcripts (NATs) constitute a significant group of regulatory, long noncoding RNAs. They are prominently expressed in testis but are also detectable in other organs. NATs are transcribed at low levels and co-expressed with related protein coding sense transcripts. Nowadays NATs are generally considered as regulatory, long noncoding RNAs without closer focus on the inevitable interference between sense and antisense expression. This work describes a cellular system where sense and antisense transcription of a specific locus (

The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGFβ on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.

As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal-like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal-like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air-liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS-CoV-2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs.

Reverse transcription is the first step of most analyses of gene expression, yet the quantitative biases it introduces are largely overlooked. Following a series of purpose-designed systematic experiments we cherry-pick examples of various biases introduced by reverse transcription, and alert the “gene expression community” to the pitfalls and improved practice of this fundamental technique.

The phototrophic bacterium

Patients find forensic psychiatric care inadequate in that they are not treated as individuals and not involved in their own care. The purpose of this study was to describe patients' experiences and perceptions of forensic psychiatric inpatient care. Semi-structured interviews were conducted with 11 inpatients. A qualitative content analysis resulted in a recurring theme, 'I know what I need to recover', and three main categories: 'A need for meaning in a meagre existence', 'A need to be a person in an impersonal context', and 'A need for empowerment in a restricted life'. Participants experienced and perceived forensic care as predominantly monotonous, predetermined, and not adapted to them as individuals, forcing them to fight and adapt to get through it and not lose themselves. Perceived needs were largely ignored or opposed by staff due to the content and structure of care. Findings suggest a need for reflective practices and patient involvement in order to develop and maintain a person-centred and recovery-oriented nursing practice. The study adds to previous research showing the importance of patients in forensic psychiatric inpatient care being listened to and involved in their care. The study is reported in accordance with the COREQ guidelines.

Background Febrile neutropenia is generally recognised as a complication of myelosuppressive chemotherapy. Recombinant human granulocyte colony stimulating factor (G-CSF) is commonly used as a primary or secondary prophylaxis to reduce the degree and duration of neutropenia in patients at risk of developing chemotherapy-induced neutropenic fever and infectious complications. G-CSF is known to decrease mortality and increase the possibility of maintaining adequate chemotherapy dose intensity and density, which is essential in curable malignancies. Common side effects are generally mild. However, potentially fatal adverse events have also been reported. Case presentation Herein, we summarise previously reported and report two new independent cases of G-CSF-induced aortitis, both in patients treated with chemotherapy for breast cancer. The two cases, identified only a few months apart, share several common characteristics including type of cancer, gender, age, chemotherapy, G-CSF treatment regimen, and time span from G-CSF initiation to aortitis manifestation. The two cases were both diagnosed by CT scan and successfully treated with corticosteroids along with discontinuation of G-CSF. Conclusion This case report highlights that although aortitis is a rare adverse event of G-CSF treatment, it should be considered in cases of unexplained fever and/or clinical and laboratory findings that do not respond to antibiotics.

Background: HER2 positive Breast Cancers (BC) have aggressive behavior and poor prognosis. Previously, we have identified miR-342-5p as an upstream regulator of HER2 signaling, as well as inhibitor of HER2 positive BC cell line growth. Objective: Here, we aimed to further investigate the molecular mechanisms behind miR-342-5pinduced HER2 pathway deregulation. Method: Two HER2 amplified breast cancer cell lines were transiently transfected with miR-342-5p mimic or negative control, and gene expression was analyzed by Agilent microarrays. Three clinical datasets with BC patients were used to identify correlations between candidate genes and miR-342- 5p, and associations with survival. Results: Pathway analyses of all deregulated genes revealed a significant suppression of the HER2 downstream pathways ERK/MAPK and SAPK/JNK, whereas the miR-342-5p predicted target genes were enriched for pathways associated with cell motility.Biological functions linked to mitochondrial stability were ranked among the top toxicological functions in both gene lists. Among the most deregulated genes, Cytochrome B5 Reductase 3 (CYB5R3) and Rap Guanine Nucleotide Exchange Factor 6 (RAPGEF6) significantly anticorrelated and correlated, respectively, with miR-342-5p in all three clinical BC datasets. Low CYB5R3 levels and high RAPGEF6 levels were significantly associated with survival, although this was not directly associated with HER2 expression. Conclusion: Our data suggest that miR-342-5p overexpression in HER2 positive BC cell lines elicits broad effects on HER2 downstream signaling, cell motility and mitochondrial stability. Together these effects may render cells less proliferative and more sensitive to cellular stress.

The present work shows that thermal expansion experiments can be used to measure the \(\gamma\)'-solvus temperatures of four Ni-base single-crystal superalloys (SX), one with Re and three Re-free variants. In the case of CMSX-4, experimental results are in good agreement with numerical thermodynamic results obtained using ThermoCalc. For three experimental Re-free alloys, the experimental and calculated results are close. Transmission electron microscopy shows that the chemical compositions of the \(\gamma\)- and the \(\gamma\)'-phases can be reasonably well predicted. We also use resonant ultrasound spectroscopy (RUS) to show how elastic coefficients depend on chemical composition and temperature. The results are discussed in the light of previous results reported in the literature. Areas in need of further work are highlighted.

As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal‐like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal‐like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air‐liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS‐CoV‐2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs., We have developed a protocol to generate airway epithelial basal‐like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways that are capable of supporting SARS‐CoV‐2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways.

Key pointsThe zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding.We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature.Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature.We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation.Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides prominent input to the VTA, although it has not yet been investigated whether this projection regulates feeding. Therefore, we investigated the role of ZI to VTA projection neurons in the regulation of several aspects of feeding behaviour. We determined the effects of (in)activation of ZI to VTA projection neurons on feeding microstructure, food-motivated behaviour under a progressive ratio schedule of reinforcement, locomotor activity and core body temperature. To activate or inactivate ZI neurons projecting to the VTA, we used a combination of canine adenovirus-2 in the VTA, as well as Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox-mediated inactivation of ZI to VTA projection neurons reduced food-motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD-mediated chemogenetic activation of ZI to VTA projection neurons promoted food-motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food-motivated behaviour and meal initiation, without affecting general activity.

In this paper, we propose to model the short-term impact of recommendation revisions on stock price movements in probabilistic framework. Through the Bayesian models, we can consolidate the information of all analysts’ recommendations on stocks and predict the post-recommendation price drifts of the underlying stocks. In addition, typically there are only a small number of recommendation revisions on specific stocks on each day. It implies that other analysts’ views to a specific stock are unobservable. With the advantage of generative models, missing observations in the data of recommendation revisions can be accommodated easily. Secondly, we perform an empirical investigation of the Hong Kong equity market and find that the impact of recommendation revisions on stock prices is significant in the 1-day horizon, but insignificant in the longer time horizon when taking account of the transaction costs. Also, we propose trading strategies derived from the posterior probability of directions of price drifts based on the Bayesian models. In our experiment, during the out-of-sample period (1 Jan, 2019 to 21 Feb, 2020), the trading strategies gain double-digit profit returns after transaction costs.

The present work contributes to a better understanding of the basic assumptions and principles behind the design of Ni-based single crystal superalloys (SXs). For this purpose, we cast and heat-treat four SXs and compare their creep performances: ERBO/1 (with Re) and three ERBO/15 variants (no Re but increased levels of Ti, Mo and W). We show that Re can be replaced by other elements without losing creep strength. To come to this conclusion one has to consider both, alloy composition and microstructure. We analyze the mechanical, microstructural and chemical results (creep rates, γʼ-volume fractions, average γʼ-particle sizes, average γ-channel widths and the chemistry of γ- and γʼ-phases) obtained for ERBO/15 and its two leaner variants (less Mo: ERBO/15-Mo and less W: ERBO/15-W). ERBO/15-Mo and ERBO/15-W show higher creep rates than ERBO/15, because they exhibit lower Mo and W concentrations in the γ-channels. This results in higher diffusion rates, accelerated rafting and faster dislocation climb at γ/γʼ-interfaces.

IntroductionThe radiographic appearance of Covid-19 infection is fairly unique – characterized by bilateral symmetrical ground-glass consolidation without pleural effusion – and has been reported on both chest CT and chest radiographs (CXRs). Based on the hypothesis that this uniqueness can be used to reliably diagnose Covid-19 on CXRs, we performed a study to assess and optimize the ability of COVID-Net, an open-source deep learning model published by the University of Waterloo, to detect Covid-19 on local CXRs. ObjectiveTo optimize and validate COVID-Net for the prediction of Covid-19 in CXRs of Malaysian patients Methods[Refer to Poster]. Results[Refer to Poster]. ConclusionThe published (unoptimized) COVID-Net model has mediocre performance which improved tremendously after optimization. This suggests the model is robust but requires optimization with local CXRs before consideration for clinical use. Class activation maps do not reflect disease distribution. Further work is required for model explainability.

Hop (Humulus lupulus) has been used in Scandinavia since at least the ninth century AD, as documented through archaeological findings and written, historical records. The written records are mainly focused on the use of cone-shaped flowers for beer brewing and medical purposes, but there are also records, for example, from the famous Swedish botanist Carl von Linne, who mentions the use of hop fibres for textile production. However, until now no experimental investigations have been published on the use of hop fibres in cultural heritage objects. A major reason for this has been the lack of a suitable characterization method. Hop is a bast fibre, just as flax and hemp and bast fibres cannot be distinguished from each other by simple optical inspection. Recently a new identification method for hop fibres was published by the authors of this article. Here we apply the new method in an investigation of two Swedish cultural heritage objects: (i) a woman’s garment from the nineteenth century, which was labelled as having an upper section made from coarse linen and a bottom section made of hemp and hop and (ii) a textile fragment from an eighteenth-century textile sample book, which was labelled as being made from hop. We show that the woman’s garment is made with hop and hemp fibres and the textile fragment from the textile sample book is made with hop. Our work provides the first direct proof that hop fibres were used for textiles in the past.

Children and adolescents with cerebral palsy often have impaired hand function. This makes it difficult for them to deal with everyday activities. The aim of the study was to explore the experiences of children and adolescents with unilateral spastic cerebral palsy when it comes to learning and dealing with activities requiring bimanual use.Ten participants, attending mainstream schools, with unilateral spastic cerebral palsy (10-18 years, MACS-level I-III) took part in semi-structured interviews. Qualitative analysis with verbatim transcripts were analysed using a Grounded Theory approach.The learning of bimanual activities was described as a process taking place in interaction with the dynamics of everyday situations. Five categories describing the participants experiences emerged: "Reaching a point where you want to learn", "Awareness and acceptance of your own abilities", "Dealing with the boundaries of the disability", "Dealing with the impact of people around you" and "Strategies for learning". A multi-dimensional theory was derived, summarising how the participants learned bimanual activities in daily life.Children and adolescents with unilateral spastic cerebral palsy express that the process of learning bimanual activities can only take place when it fits in with life as it unfolds. Thus, they have to adapt to a changing context and their own developing skills.Implications for RehabilitationThis study support a person-centred perspective in the process of learning bimanual activities.Interventions need to be tailored to life situations and embedding in child's and adolescents everyday lives.The therapist must be compliant with the child's and adolescents desire for learning.

Drug induced kidney injury (DIKI) is a common reason for compound attrition in drug development pipelines with proximal tubule epithelial cells (PTECs) most commonly associated with DIKI. Here, we investigated freshly isolated human (hPTECs) as an in vitro model for assessing renal tubular toxicity. The freshly isolated hPTECs were first characterized to confirm gene expression of important renal transporters involved in drug handling which was further corroborated by confirming the functional activity of organic cation transporter 2 and organic anion transporter 1 by using transporter specific inhibitors. Additionally, functionality of megalin/cubilin endocytic receptors was also confirmed. A training set of 36 compounds was used to test the ability of the model to classify them using six different endpoints which included three biomarkers (Kidney Injury Molecule-1, Neutrophil gelatinase-associated lipocalin, and Clusterin) and three non-specific injury endpoints (ATP depletion, LDH leakage, and barrier permeability via transepithelial electrical resistance) in a dose-dependent manner across two independent kidney donors. In general, biomarkers showed higher predictivity than non-specific endpoints, with Clusterin showing the highest predictivity (Sensitivity/Specificity - 65.0/93.8 %). By using the thresholds generated from the training set, nine candidate internal Takeda compounds were screened where PTEC toxicity was identified as one of the findings in preclinical animal studies. The model correctly classified four of six true positives and two of three true negatives, showing validation of the in vitro model for detection of tubular toxicants. This work thus shows the potential application of freshly isolated primary hPTECs using translational biomarkers in assessment of tubular toxicity within the drug discovery pipeline.

A review of pharmacokinetic and metabolism studies show that triclopyr is well absorbed from the oral route in numerous species (≥80%), primarily as parent compound. Absorption is quite rapid in rats, dogs and human volunteers. Plasma or blood clearance is also rapid (t1/2 3–9 h), except for dog (12–96 h). Systemic exposure is not dose-proportional: in the rat above 20 mg/kg (dietary) or between 3 and 60 mg/kg (gavage), or in dogs above 5 mg/kg, with systemic exposure in human more comparable to rat than dog. Triclopyr is highly bound to protein in rat, dog and human plasma (≥97% at or below 7 μg/mL), indicating that species differences in systemic exposure are not due to differences in the free fraction of this test material in plasma. An in vitro flux study in renal proximal tubule cells showed that net renal transport of triclopyr is in the direction of secretion in rat and human donors, while reabsorption predominated in the dog, possibly via organic anion transporters such as OAT1/3. These results fit well into the framework of utilizing metabolism and toxicokinetics across species and exposure levels to allow for toxicity testing in the most relevant species as well as at proper dose levels.

In the present work, three Ni-based single-crystal superalloys (SXs) were investigated, a Re-containing alloy ERBO/1 (CMSX-4 type) and two Re-free SXs referred to as ERBO/15 and ERBO/15-W, which differ in W content. The microstructural evolution of the three alloys during heat treatment and their creep behavior is investigated. When one applies one heat treatment to all three alloys, one obtains different γ/γ′-microstructures. Subjecting these three alloys to creep in the high-temperature low-stress creep regime, ERBO/15 outperforms ERBO/1. In order to separate the effects of alloy chemistry and microstructure, the kinetics of the microstructural evolution of the three alloys was measured. The results were used to establish similar microstructures in all three alloys. Comparing ERBO/15 with ERBO/15-W, it was found that in ERBO/15-W particles grow faster during the first precipitation heat treatment and that ERBO/15-W creeps significantly faster. At constant microstructures, ERBO/15 and ERBO/1 show similar creep behavior. In the high-temperature and low-stress creep regime, ERBO/15 shows lower minimum creep rates but ERBO/1 features a slower increase of creep rate in the tertiary creep regime. It was also found that in the high-temperature low-stress creep regime, ERBO/1 shows a double minimum creep behavior when particles are small.

Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-β1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel-Pfkfb3 axis has potential for therapeutic applications in fibrotic disease. ispartof: NATURE METABOLISM vol:2 issue:11 ispartof: location:Germany status: published