Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation.

Replication forks stalled at co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage-religation cycles mediated by MUS81 endonuclease and DNA ligase IV (LIG4), which presumably relieve the topological barrier generated by the transcription-replication conflict (TRC) and facilitate ELL-dependent reactivation of transcription. Here, we report that the restart of R-loop-stalled replication forks via the MUS81-LIG4-ELL pathway requires senataxin (SETX), a helicase that can unwind RNA:DNA hybrids. We found that SETX promotes replication fork progression by preventing R-loop accumulation during S-phase. Interestingly, loss of SETX helicase activity leads to nascent DNA degradation upon induction of R-loop-mediated fork stalling by hydroxyurea. This fork degradation phenotype is independent of replication fork reversal and results from DNA2-mediated resection of MUS81-cleaved replication forks that accumulate due to defective replication restart. Finally, we demonstrate that SETX acts in a common pathway with the DEAD-box helicase DDX17 to suppress R-loop-mediated replication stress in human cells. A possible cooperation between these RNA/DNA helicases in R-loop unwinding at TRC sites is discussed.

Primary bone diffuse large B-cell lymphoma (PB-DLBCL): a distinct extranodal lymphoma of germinal centre origin, with a common EZB-like mutational profile and good prognosis.

AIMS: Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is not recognized as a separate entity by the current classification systems. Here we define and highlight its distinctive clinical presentation, morphology, phenotype, gene expression profile (GEP), and molecular genetics. METHODS: We collected 27 respective cases and investigated their phenotype, performed gDNA panel sequencing covering 172 genes, and carried out fluorescence in situ hybridization to evaluate MYC, BCL2, and BCL6 translocations. We attempted to genetically subclassify cases using the Two-step classifier and performed GEP for cell-of-origin subtyping and in silico comparison to uncover up- and downregulated genes as opposed to other DLBCL. RESULTS: Most cases (n = 22) were germinal centre B-cell-like (GCB) by immunohistochemistry and all by GEP. Additionally, PB-DLBCL had a mutational profile similar to follicular lymphoma and nodal GCB-DLBCL, with the exception of more frequent TP53 and B2M mutations. The GEP of PB-DLBCL was unique, and the frequency of BCL2 rearrangements was lower compared to nodal GCB-DLBCL. The Two-step classifier categorized eight of the cases as EZB, three as ST2, and one as MCD. CONCLUSION: This study comprehensively characterizes PB-DLBCL as a separate entity with distinct clinical and morpho-molecular features. These insights may aid in developing tailored therapeutic strategies and shed light on its pathogenesis.

Association of maternal and paternal personality disorders with risk of mental disorders in children: A nationwide, register-based cohort study of 1,406,965 children.

BACKGROUND: Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. METHODS: We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0-17). RESULTS: The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59-2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94-2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33-2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91-2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15-4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0-35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1-15.3]). CONCLUSION: Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene-environment pathways. More research into these mechanisms and research into preventive interventions is warranted.

"So at least now I know how to deal with things myself, what I can do if it gets really bad again"-experiences with a long-term cross-sectoral advocacy care and case management for severe multiple sclerosis: a qualitative study.

BACKGROUND: Persons with severe Multiple Sclerosis (PwsMS) face complex needs and daily limitations that make it challenging to receive optimal care. The implementation and coordination of health care, social services, and support in financial affairs can be particularly time consuming and burdensome for both PwsMS and caregivers. Care and case management (CCM) helps ensure optimal individual care as well as care at a higher-level. The goal of the current qualitative study was to determine the experiences of PwsMS, caregivers and health care specialists (HCSs) with the CCM. METHODS: In the current qualitative sub study, as part of a larger trial, in-depth semi-structured interviews with PwsMS, caregivers and HCSs who had been in contact with the CCM were conducted between 02/2022 and 01/2023. Data was transcribed, pseudonymized, tested for saturation and analyzed using structuring content analysis according to Kuckartz. Sociodemographic and interview characteristics were analyzed descriptively. RESULTS: Thirteen PwsMS, 12 caregivers and 10 HCSs completed interviews. Main categories of CCM functions were derived deductively: (1) gatekeeper function, (2) broker function, (3) advocacy function, (4) outlook on CCM in standard care. Subcategories were then derived inductively from the interview material. 852 segments were coded. Participants appreciated the CCM as a continuous and objective contact person, a person of trust (92 codes), a competent source of information and advice (on MS) (68 codes) and comprehensive cross-insurance support (128 codes), relieving and supporting PwsMS, their caregivers and HCSs (67 codes). CONCLUSIONS: Through the cross-sectoral continuous support in health-related, social, financial and everyday bureaucratic matters, the CCM provides comprehensive and overriding support and relief for PwsMS, caregivers and HCSs. This intervention bears the potential to be fine-tuned and applied to similar complex patient groups. TRIAL REGISTRATION: The study was approved by the Ethics Committee of the University of Cologne (#20-1436), registered at the German Register for Clinical Studies (DRKS00022771) and in accordance with the Declaration of Helsinki.

Digital clinical empathy in a live chat: multiple findings from a formative qualitative study and usability tests.

BACKGROUND: Clinical empathy is considered a crucial element in patient-centered care. The advent of digital technology in healthcare has introduced new dynamics to empathy which needs to be explored in the context of the technology, particularly within the context of written live chats. Given the growing prevalence of written live chats, this study aimed to explore and evaluate techniques of digital clinical empathy within a familial cancer-focused live chat, focusing on how health professionals can (a) understand, (b) communicate, and (c) act upon users' perspectives and emotional states. METHODS: The study utilized a qualitative approach in two research phases. It examined the expected and implemented techniques and effectiveness of digital clinical empathy in a live chat service, involving semi-structured interviews with health professionals (n = 9), focus group discussions with potential users (n = 42), and two rounds of usability tests between health professionals (n = 9) and users (n = 18). Data were examined using qualitative content analysis. RESULTS: Expected techniques of digital clinical empathy, as articulated by both users and health professionals, involve reciprocal engagement, timely responses, genuine authenticity, and a balance between professionalism and informality, all while going beyond immediate queries to facilitate informed decision-making. Usability tests confirm these complexities and introduce new challenges, such as balancing timely, authentic responses with effective, personalized information management and carefully framed referrals. CONCLUSIONS: The study reveals that the digital realm adds layers of complexity to the practice of clinical empathy. It underscores the importance of ongoing adaptation and suggests that future developments could benefit from a hybrid model that integrates the strengths of both AI and human health professionals to meet evolving user needs and maintain high-quality, empathetic healthcare interactions.

CD27 is required for protective lytic EBV antigen-specific CD8+ T-cell expansion.

Primary immunodeficiencies in the costimulatory molecule CD27 and its ligand, CD70, predispose for pathologies of uncontrolled Epstein-Barr virus (EBV) infection in nearly all affected patients. We demonstrate that both depletion of CD27+ cells and antibody blocking of CD27 interaction with CD70 cause uncontrolled EBV infection in mice with reconstituted human immune system components. While overall CD8+ T-cell expansion and composition are unaltered after antibody blocking of CD27, only some EBV-specific CD8+ T-cell responses, exemplified by early lytic EBV antigen BMLF1-specific CD8+ T cells, are inhibited in their proliferation and killing of EBV-transformed B cells. This suggests that CD27 is not required for all CD8+ T-cell expansions and cytotoxicity but is required for a subset of CD8+ T-cell responses that protect us from EBV pathology.

ATG5 promotes eosinopoiesis but inhibits eosinophil effector functions.

Eosinophils are white blood cells that contribute to the regulation of immunity and are involved in the pathogenesis of numerous inflammatory diseases. In contrast to other cells of the immune system, no information is available regarding the role of autophagy in eosinophil differentiation and functions. To study the autophagic pathway in eosinophils, we generated conditional knockout mice in which Atg5 is deleted within the eosinophil lineage only (designated Atg5eoΔ mice). Eosinophilia was provoked by crossbreeding Atg5eoΔ mice with Il5 (IL-5) overexpressing transgenic mice (designated Atg5eoΔIl5tg mice). Deletion of Atg5 in eosinophils resulted in a dramatic reduction in the number of mature eosinophils in blood and an increase of immature eosinophils in the bone marrow. Atg5-knockout eosinophil precursors exhibited reduced proliferation under both in vitro and in vivo conditions but no increased cell death. Moreover, reduced differentiation of eosinophils in the absence of Atg5 was also observed in mouse and human models of chronic eosinophilic leukemia. Atg5-knockout blood eosinophils exhibited augmented levels of degranulation and bacterial killing in vitro. Moreover, in an experimental in vivo model, we observed that Atg5eoΔ mice achieve better clearance of the local and systemic bacterial infection with Citrobacter rodentium. Evidence for increased degranulation of ATG5low-expressing human eosinophils was also obtained in both tissues and blood. Taken together, mouse and human eosinophil hematopoiesis and effector functions are regulated by ATG5, which controls the amplitude of overall antibacterial eosinophil immune responses.

Therapeutic properties of Helicobacter pylori-derived vacuolating cytotoxin A in an animal model of chronic allergic airway disease.

BACKGROUND: It has previously been shown that the Helicobacter pylori (H. pylori)-derived molecule vacuolating cytotoxin A (VacA) could be suitable for the treatment of allergic airway disease. The therapeutic activity of the protein, which acts through modulation of dendritic cells (DC) and regulatory T cells (Tregs), was demonstrated in murine short-term acute models. The aim of this study is to further evaluate the therapeutic potential of VacA by determining the effectiveness of different application routes and the suitability of the protein for treating the chronic phase of allergic airway disease. METHODS: VacA was administered by the intraperitoneal (i.p.), oral (p.o.) or intratracheal (i.t.) routes, and long-term therapeutic effectiveness, allergic airway disease hallmarks, and immune phenotype were analyzed in murine models of acute and chronic allergic airway disease. RESULTS: Administration of VacA via the i.p., p.o or i.t. routes was associated with a reduction in airway inflammation. The i.p. route showed the most consistent effect in reducing airway inflammation and i.p. treatment with VacA was the only treatment that significantly reduced mucus cell hyperplasia. In a murine model of chronic allergic airway disease, both short- and long-term treatment with VacA showed a therapeutic effect, with a reduction in a variety of asthma hallmarks, including bronchoalveolar lavage eosinophilia, lung inflammation and goblet cell metaplasia. Short-term treatment was associated with induction of Tregs, while repetitive long-term administration of VacA influenced immunological memory in the lung. CONCLUSIONS: In addition to showing therapeutic efficacy in short-term models, treatment with VacA also appeared to be effective in suppressing inflammation in a chronic airway disease model. The observation that treatment was effective after administration via several different routes highlights the potential of VacA as a therapeutic agent with different routes of administration in humans.

Food Interactions Observed in a Pharmacokinetic Investigation Comparing Two Marketed Cold Preparations (BNO1016 and ELOM-080) after Administration to Beagle Dogs - A Pilot Study.

Sinupret extract (BNO 1016) and Gelomyrtol forte (ELOM-080) represent the two top-selling cold remedies in Germany nowadays. Whereas BNO 1016 is a typical immediate release coated tablet, ELOM-080 is an enteric-coated soft gelatin capsule. The latter formulation, however, is at risk of pharmacokinetic interactions affecting absorption, especially in cases of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 were administered under fasting and fed conditions. Blood was sampled up to 30 h post-administration and plasma concentrations of the characteristic ingredients of BNO 1016 as well as ELOM-080 analytes were determined. Pharmacokinetic parameters focusing on the rate and extent of absorption were derived. BNO 1016 analytes demonstrated a similar course in both the fasted and fed states. ELOM-080 analytes also showed a similar picture in the fasted state. However, lag times (time from administration to first quantifiable time point in plasma) of up to 2 h post-administration with corresponding time to reach maximum concentration (obtained directly from the measured concentration) values of 3 to 4 h were observed, reflecting a longer gastric residence time. In the fed state, ELOM-080 showed significant pharmacokinetic characteristics, suggesting a clear food effect. A major observation was a double peak phenomenon that could be observed in two of three dogs. Furthermore, lag times of some analytes, up to 3 - 4 h, and corresponding time to reach maximum concentration values, up to 6 - 8 h, occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may also be a significant risk for food effects with ELOM-080 in humans.

"My everyday life has returned to normal"- Experiences of patients and relatives with a palliative day care clinic: a qualitative evaluation study.

PURPOSE: Palliative day care clinics (PDCCs) complement inpatient and home palliative care and provide access to a range of multi-professional services. However, they are not part of standard care in Germany. Yet, international studies show that PDCCs have a positive impact on e.g. quality of life. To evaluate one of the first PDCCs in Germany (Aschaffenburg-Alzenau (PDCC-AA)) by describing the experiences, satisfaction, challenges, wishes of patients and relatives and possible alternatives to treatment in the PDCC. METHODS: Qualitative study using semi-structured telephone interviews. Data was analyzed using qualitative structuring content analysis according to Kuckartz with deductive a priori categories and inductive subcategories. RESULTS: A total of 31 patients and 38 relatives completed telephone interviews. The majority of patients were diagnosed with a cancer or tumor disease. The following four main themes emerged: (1) alternatives to treatment at the PDCC, (2) symptom relief, (3) sense of security, (4) "everyday life framing" (normality of everyday life). Participants valued the medical treatment (especially for pain), psychosocial support given and having direct access to a range of services (e.g., wound care and pleural drainage), while relatives valued being provided respite services. A sense of security, availability of therapies, and devoted time that healthcare providers spent to explain e.g., treatment options were mentioned most positively, as well as confidence in dealing with the illness. As to whether there was an alternative to treatment in the PDCC, some saw further inpatient stays, the emergency room or care by general practitioners as options (although not preferred). Patients expressed concern that they were not treated and informed according to their needs in other care settings. CONCLUSIONS: PDCCs may close a gap between inpatient and home palliative care. Participants mentioned that hospital stays can be delayed or even prevented.

Understanding Trust Determinants in a Live Chat Service on Familial Cancer: Qualitative Triangulation Study With Focus Groups and Interviews in Germany.

BACKGROUND: In dealing with familial cancer risk, seeking web-based health information can be a coping strategy for different stakeholder groups (ie, patients, relatives, and those suspecting an elevated familial cancer risk). In the vast digital landscape marked by a varied quality of web-based information and evolving technologies, trust emerges as a pivotal factor, guiding the process of health information seeking and interacting with digital health services. This trust formation in health information can be conceptualized as context dependent and multidimensional, involving 3 key dimensions: information seeker (trustor), information provider (trustee), and medium or platform (application). Owing to the rapid changes in the digital context, it is critical to understand how seekers form trust in new services, given the interplay among these different dimensions. An example of such a new service is a live chat operated by physicians for the general public with personalized cancer-related information and a focus on familial cancer risk. OBJECTIVE: To gain a comprehensive picture of trust formation in a cancer-related live chat service, this study investigates the 3 dimensions of trust-trustor, trustee, and application-and their respective relevant characteristics based on a model of trust in web-based health information. In addition, the study aims to compare these characteristics across the 3 different stakeholder groups, with the goal to enhance the service's trustworthiness for each group. METHODS: This qualitative study triangulated the different perspectives of medical cancer advisers, advisers from cancer support groups, and members of the public in interviews and focus group discussions to explore the 3 dimensions of trust-trustor, trustee, and application-and their determinants for a new live chat service for familial cancer risk to be implemented at the German Cancer Information Service. RESULTS: The results indicate that experience with familial cancer risk is the key trustor characteristic to using, and trusting information provided by, the live chat service. The live chat might also be particularly valuable for people from minority groups who have unmet needs from physician-patient interactions. Participants highlighted trustee characteristics such as ability, benevolence, integrity, and humanness (ie, not a chatbot) as pivotal in a trustworthy cancer live chat service. Application-related characteristics, including the reputation of the institution, user-centric design, modern technology, and visual appeal, were also deemed essential. Despite the different backgrounds and sociodemographics of the 3 stakeholder groups, many overlaps were found among the 3 trust dimensions and their respective characteristics. CONCLUSIONS: Trust in a live chat for cancer information is formed by different dimensions and characteristics of trust. This study underscores the importance of understanding trust formation in digital health services and suggests potential enhancements for effective, trustworthy interactions in live chat services (eg, by providing biographies of the human medical experts to differentiate them from artificial intelligence chatbots).

Intentions of Patients With Cancer and Their Relatives to Use a Live Chat on Familial Cancer Risk: Results From a Cross-Sectional Web-Based Survey.

BACKGROUND: An important prerequisite for actively engaging in cancer prevention and early detection measures, which is particularly recommended in cases of familial cancer risk, is the acquisition of information. Although a lot of cancer information is available, not all social groups are equally well reached because information needs and communicative accessibility differ. Previous research has shown that a live chat service provided by health professionals could be an appropriate, low-threshold format to meet individual information needs on sensitive health topics such as familial cancer risk. An established German Cancer Information Service is currently developing such a live chat service. As it is only worthwhile if accepted by the target groups, formative evaluation is essential in the course of the chat service's development and implementation. OBJECTIVE: This study aimed to explore the acceptance of a live chat on familial cancer risk by patients with cancer and their relatives (research question [RQ] 1) and examine the explanatory power of factors associated with their intentions to use such a service (RQ2). Guided by the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2), we examined the explanatory power of the following UTAUT2 factors: performance expectancy, effort expectancy, social influence, facilitating conditions, and habit, supplemented by perceived information insufficiency, perceived susceptibility, perceived severity, and cancer diagnosis as additional factors related to information seeking about familial cancer. METHODS: We conducted a cross-sectional survey via a German web-based access panel in March 2022 that was stratified by age, gender, and education (N=1084). The participants are or have been diagnosed with cancer themselves (n=144) or have relatives who are or have been affected (n=990). All constructs were measured with established scales. To answer RQ1, descriptive data (mean values and distribution) were used. For RQ2, a blockwise multiple linear regression analysis was conducted. RESULTS: Overall, 32.7% of participants were (rather) willing, 28.9% were undecided, and 38.4% were (rather) not willing to use a live chat on familial cancer risk in the future. A multiple linear regression analysis explained 47% of the variance. It revealed that performance expectancy, social influence, habit, perceived susceptibility, and perceived severity were positively associated with the intention to use a live chat on familial cancer risk. Effort expectancy, facilitating conditions, information insufficiency, and cancer diagnosis were not related to usage intentions. CONCLUSIONS: A live chat seems promising for providing information on familial cancer risk. When promoting the service, the personal benefits should be addressed in particular. UTAUT2 is an effective theoretical framework for explaining live chat usage intentions and does not need to be extended in the context of familial cancer risk.

Atypical neurocognitive functioning in children and adolescents with obsessive-compulsive disorder (OCD).

Atypical neurocognitive functioning has been found in adult patients with obsessive-compulsive disorder (OCD). However, little work has been done in children and adolescents with OCD. In this study, we investigated neurocognitive functioning in a large and representative sample of newly diagnosed children and adolescents with OCD compared to non-psychiatric controls. Children and adolescents with OCD (n = 119) and non-psychiatric controls (n = 90) underwent psychopathological assessment, intelligence testing, and a neurocognitive test battery spanning cognitive flexibility, planning and decision-making, working memory, fluency, and processing speed. The MANOVA main effect revealed that children and adolescents with OCD performed significantly worse than the control group (p < .001, [Formula: see text] = 0.256). Atypical patient performance was particularly found for indices of cognitive flexibility, decision-making, working memory, and processing speed. We found no evidence of differences in planning or fluency. Moreover, we found no significant associations between neurocognitive performance and OCD symptom severity or comorbidity status. Our results indicate that children and adolescents with OCD show selective atypical neurocognitive functioning. These difficulties do not appear to drive their OCD symptoms. However, they may contribute to lifespan difficulties and interfere with treatment efficacy, an objective of our research currently.

Cultural adaptation of the Integrated Palliative care Outcome Scale for neurological symptoms.

OBJECTIVES: Standardized measures for assessing neurological patients needing palliative care remain scarce. The Integrated Palliative care Outcome Scale for neurological patients in its short form (IPOS Neuro-S8) helps assess and identify patients' symptom burden and needs early but has not yet been validated in German. The aim was to culturally adapt and translate the IPOS Neuro-S8 into the German health-care context and evaluate its face and content validity. METHODS: Cultural adaptation study following the first 6 out of 8 phases of the Palliative care Outcome Scale measures manual: (1) conceptual definition, (2) forward translation to German, (3) backward translation to English, (4) expert review, (5) cognitive debriefing, (6) proofreading. Neurological patients needing palliative care and clinical staff of the Department of Palliative Medicine or Neurology of the University Hospital of Cologne were included. Data were analyzed using thematic content analysis and descriptive statistics. RESULTS: A total of 13 patients and 16 clinical staff participated in this study. The expert review panel (phase 4) consisted of 11 additional members. While patients (n = 9) and clinical staff (n = 11) confirmed that the IPOS Neuro-S8 is an intelligible tool that is well accepted (phase 5), some linguistic and cultural differences were found between the original English and German versions. These mainly concerned the items mouth problems and spasms. SIGNIFICANCE OF RESULTS: The German version of the IPOS Neuro-S8 has demonstrated face and content validity and captures relevant symptoms of neurological patients needing palliative care. Its psychometric properties, including construct and criterion validity, will be investigated next.

Information concerning the application to become an associate professor in the nursing sciences section of the French Conseil national des universités des disciplines de santé (National Council of Universities for Health Disciplines) / Éléments d'informations concernant le dossier de qualification à la fonction de maître de conférences à la section « Sciences infirmières ¼ du Conseil national des universités des disciplines de santé

In 2019, the nursing sciences section of the Conseil national des universités des disciplines de santé was created. One of its missions is to evaluate the applications of candidates wishing to qualify as university professors and associate professors. Qualification authorizes the applicant to apply a competitive examination for the position of university professor or assistant professor at a French university offering a position. The members of the section must assess whether the requirements in terms of research, teaching, and expertise have been met by the candidate so that they can sit the competitive examination. As a result, there are a number of requirements, which it is useful to reiterate in order to enhance the quality of future applications. Only those requirements relating to qualification as a associate professor will be covered here.

En 2019, la section « Sciences infirmières ¼ du Conseil national des universités pour les disciplines de santé a été créée. Parmi ses missions, elle évalue chaque année les dossiers de demande de qualification de maîtres de conférences et de professeurs des universités. La qualification autorise la personne à candidater à un concours de recrutement au poste de maître de conférences ou de professeur des universités dans une université française proposant un poste. Les membres de la section doivent apprécier si les requis en termes de recherches, d'enseignements et d'expertises sont suffisants pour pouvoir présenter le concours. De ce fait, certaines exigences sont attendues, qu'il paraît nécessaire de rappeler pour favoriser un gain en qualité des futurs dossiers de candidature. Seules les exigences relatives à la qualification aux fonctions de maître de conférences seront traitées ici.

IRF4 Expression Is Required for the Immunoregulatory Activity of Conventional Type 2 Dendritic Cells in Settings of Chronic Bacterial Infection and Cancer.

The lamina propria of the gastrointestinal tract and other mucosal surfaces of humans and mice host a network of mononuclear phagocytes that differ in their ontogeny, surface marker and transcription factor expression, and functional specialization. Conventional dendritic cells (DCs) in particular exist as two major subpopulations in both lymphoid and nonlymphoid organs that can be distinguished based on their surface marker and transcription factor expression. In this study, we show in various Th1- and/or Th17-polarized settings of acute and chronic bacterial infection and of tumor growth that the conditional ablation of Irf4 in CD11c+ DCs results in more efficient immune control of Helicobacter pylori, Mycobacterium bovis bacillus Calmette-Guérin, and Citrobacter rodentium and of tumor growth in a syngeneic tumor model. We attribute the phenotype of IRF4ΔDC mice to unrestricted Th1 responses and in particular to IFN-γ- and TNF-α-expressing CD4+ T cells. This activity of IRF4-expressing DCs is linked to a DC-specific immunoregulatory transcriptional program. In contrast, in Th2-polarized settings such as house dust mite-induced allergic airway inflammation, the lack of IRF4 expression in the DC compartment alleviates inflammation and goblet cell metaplasia. The combined data provide evidence for immunoregulatory properties of this versatile DC population in Th1-polarized infection settings.

GeneTrail 3: advanced high-throughput enrichment analysis.

We present GeneTrail 3, a major extension of our web service GeneTrail that offers rich functionality for the identification, analysis, and visualization of deregulated biological processes. Our web service provides a comprehensive collection of biological processes and signaling pathways for 12 model organisms that can be analyzed with a powerful framework for enrichment and network analysis of transcriptomic, miRNomic, proteomic, and genomic data sets. Moreover, GeneTrail offers novel workflows for the analysis of epigenetic marks, time series experiments, and single cell data. We demonstrate the capabilities of our web service in two case-studies, which highlight that GeneTrail is well equipped for uncovering complex molecular mechanisms. GeneTrail is freely accessible at: http://genetrail.bioinf.uni-sb.de.

"The education is a mirror of where palliative care stands in Israel today": An exploration of palliative care undergraduate education at medical schools in Israel.

OBJECTIVE: Israel serves as a case study for understanding the importance of undergraduate palliative care (PC) education in implementing, developing, and enabling access to palliative care services. This article presents the findings collected from the five medical schools. METHOD: This qualitative study supported by a survey explores and describes the state of undergraduate PC education at medical schools in Israel. The survey included questions on voluntary and mandatory courses, allocation of different course models, teaching methods, time frame, content, institutions involved, and examinations. Semi-structured interviews with teaching faculty were conducted at the same locations. RESULTS: Eleven expert interviews and five surveys demonstrate that PC is taught as a mandatory subject at only two out of the five Israeli universities. To enhance PC in Israel, it needs to become a mandatory subject for all undergraduate medical students. To teach communication, cultural safety, and other basic competencies, new interactive teaching forms need to be developed and adapted. In this regard, nationwide cooperation is proposed. An exchange between medical schools and university clinics is seen as beneficial. The new generation of students is open to PC philosophy and multidimensional care provision but resources to support their growth as professionals and people remain limited. SIGNIFICANCE OF RESULTS: This study underlines the importance of teaching in PC at medical schools. Undergraduate education is a central measure of PC status and should be used as such worldwide. The improvement of the teaching situation would automatically lead to a better practical implementation for the benefit of people. Medical schools should cooperate, as the formation of expertise exchange across medical schools would automatically lead to better PC education.

Nurturing Socioculturally and Medically Appropriate Palliative Care Delivery: Lessons Learned by Israeli Medical Faculty.

Israel is one of the few countries worldwide with a national policy and defined standards of palliative care (PC); its culture is highly diverse and more traditionally oriented in comparison with Western countries. This study describes the current state of PC in Israel through examination of: (1) its current status, self-image and structural factors; (2) its relation to cultural and political characteristics; and (3) the chances, goals and obstacles of advancing PC in Israel. Face-to-face interviews were conducted at all five public medical faculties in Israel from November 2017 to February 2018. The following findings are reported: (1) definition of palliative care, (2) multidisciplinary approach, (3) special role of nurses, (4) personal perceptions of death, (5) understanding the role of medicine, (6) specialty palliative medicine, (7) religious, spiritual and cultural aspects, (8) political and economic aspects, (9) obstacles and weaknesses, and (10) prospects and goals of palliative care. Participants perceive PC as an integrative healthcare service that should be available to all patients, including children and their families, at any stage of illness. They internalize that PC principles apply regardless of ethnic, cultural, and religious background. Utilizing nurses' leadership, enhancing multidisciplinary teamwork, and person-centered approach, supports better PC to more people.