Analyzing the regulatory framework gaps for gas distribution networks with decreasing natural gas demand in Germany.

German energy system studies, investigating the energy transition pathways to the set climate targets, depict a significant decrease in gas demand. This leads to a discussion about the long-term need of gas distribution networks. The discussion intensified with the war in Ukraine and the subsequent energy price crisis.

Inpatient burden of respiratory syncytial virus (RSV) in Switzerland, 2003 to 2021: an analysis of administrative data.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalisations in infants (age < 1 year) and young children. Little is known on RSV epidemiology and related inpatient healthcare resource use (HCRU) in Switzerland.AimTo explore RSV-related hospitalisations, inpatient HCRU and medical costs in all age groups, and risk factors for infant hospitalisations in Switzerland.

Preferences of healthcare providers in Switzerland for attributes of pediatric hexavalent vaccines: a discrete-choice experiment.

Objective: To understand the preferences of healthcare providers (HCPs) in Switzerland for pediatric hexavalent vaccine attributes.

Methods: A discrete-choice experiment included a series of choices between 2 hypothetical pediatric hexavalent vaccines with varying attributes: device type (including preparation time and risk of dosage errors), proportion of infants seroprotected against type b (Hib) at 11-12 months (pre-booster), packaging size, years on the market, and the thermostability at room temperature. Odds ratios (ORs) and conditional relative attribute importance (CRAI) were calculated using random-parameters logit.

Burden of seasonal influenza in the Swiss adult population during the 2016/2017-2018/2019 influenza seasons.

Background: Evidence on the burden of seasonal influenza in Switzerland is scarce, yet it is critical for the design of effective prevention and control measures. The objective of this study was to assess influenza-related resource utilization, health care expenditures and quality-adjusted life-years (QALYs) lost in Switzerland across the 2016/2017-2018/2019 influenza seasons.

Methods: We retrospectively analyzed multiple real-world data sources to calculate epidemiological and health outcomes, QALYs lost, and direct medical costs due to influenza in the Swiss adult population.

Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.

Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected.

T cell receptor and IL-2 signaling strength control memory CD8 T cell functional fitness via chromatin remodeling.

Cognate antigen signal controls CD8 T cell priming, expansion size and effector versus memory cell fates, but it is not known if and how it modulates the functional features of memory CD8 T cells. Here we show that the strength of T cell receptor (TCR) signaling controls the requirement for interleukin-2 (IL-2) signals to form a pool of memory CD8 T cells that competitively re-expand upon secondary antigen encounter. Combining strong TCR and intact IL-2 signaling during priming synergistically induces genome-wide chromatin accessibility in regions targeting a wide breadth of biological processes, consistent with greater T cell functional fitness.

Cervicovaginal Tissue Residence Confers a Distinct Differentiation Program upon Memory CD8 T Cells.

Tissue-resident memory CD8 T cells (CD8 T) are critical for maintaining barrier immunity. CD8 T have been mainly studied in the skin, lung and gut, with recent studies suggesting that the signals that control tissue residence and phenotype are highly tissue dependent. We examined the T cell compartment in healthy human cervicovaginal tissue (CVT) and found that most CD8 T cells were granzyme B and TCF-1 To address if this phenotype is driven by CVT tissue residence, we used a mouse model to control for environmental factors.

PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells.

Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing T cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts the activation, survival, and memory formation of T cells. We find that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15.

Revealing non-crystalline polymer superstructures within electrospun fibers through solvent-induced phase rearrangements.

The design of nanofibers for biomedical applications requires a deep understanding of the fiber formation process and the resulting internal structure. In this regard, non-crystalline, mesomorphic structures play a central role in the processing of many polymers as precursors in the formation of crystalline superstructures (e.g.

Attenuation of chronic antiviral T-cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts.

Lymphoid T-zone fibroblastic reticular cells (FRCs) actively promote T-cell trafficking, homeostasis, and expansion but can also attenuate excessive T-cell responses via inducible nitric oxide (NO) and constitutive prostanoid release. It remains unclear how these FRC-derived mediators dampen T-cell responses and whether this occurs in vivo. Here, we confirm that murine lymph node (LN) FRCs produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion.

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint.

Enhancing sensory experiences for very preterm infants in the NICU: an integrative review.

Objective: Very preterm infants hospitalized in the neonatal intensive care unit (NICU) experience alterations in sensory experiences. Defining types, timing and frequency of sensory-based interventions that optimize outcomes can inform environmental modifications. The objective of this study was to conduct an integrative review on sensory-based interventions used with very preterm infants in the NICU to improve infant and parent outcomes.

A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire.

Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown.

Role of proapoptotic BH3-only proteins in Listeria monocytogenes infection.

The ability of pathogens to influence host cell survival is a crucial virulence factor. Listeria monocytogenes (Lm) infection is known to be associated with severe apoptosis of hepatocytes and spleen cells. This impairs host defense mechanisms and thereby facilitates the spread of intracellular pathogens.

Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner.

Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment.

Virtual patients in continuing medical education and residency training: a pilot project for acceptance analysis in the framework of a residency revision course in pediatrics.

Aim: Virtual patients (VPs) are a one-of-a-kind e-learning resource, fostering clinical reasoning skills through clinical case examples. The combination with face-to-face teaching is important for their successful integration, which is referred to as "blended learning". So far little is known about the use of VPs in the field of continuing medical education and residency training.

Assessment of Autism Symptoms During the Neonatal Period: Is There Early Evidence of Autism Risk?

Objective: To define neonatal social characteristics related to autism risk.

Method: Sixty-two preterm infants underwent neonatal neurobehavioral testing. At age 2 yr, participants were assessed with the Modified Checklist for Autism in Toddlers and Bayley Scales of Infant and Toddler Development, 3rd edition.

Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.

Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 differentiation at both high and low doses of antigen.

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control.

Semantically- and Phonologically-Related Primes Improve Name Retrieval in Young and Older Adults.

Word and name retrieval failures increase with age, and this study investigated how priming impacts young and older adults' ability to produce proper names. The transmission deficit hypothesis predicts facilitation from related prime names, whereas the blocking and inhibition deficit hypotheses predict interference from related names, especially for older adults. On half of our experimental trials, we exposed participants to a prime name that is phonologically- and semantically-related to a target name.

Molecular insights for optimizing T cell receptor specificity against cancer.

Cytotoxic CD8 T cells mediate immunity to pathogens and they are able to eliminate malignant cells. Immunity to viruses and bacteria primarily involves CD8 T cells bearing high affinity T cell receptors (TCRs), which are specific to pathogen-derived (non-self) antigens. Given the thorough elimination of high affinity self/tumor-antigen reactive T cells by central and peripheral tolerance mechanisms, anti-cancer immunity mostly depends on TCRs with intermediate-to-low affinity for self-antigens.

RAGE-mediated interstitial fibrosis in neonatal obstructive nephropathy is independent of NF-κB activation.

Urinary tract obstruction during nephron development causes tubular apoptosis, tubular atrophy, and interstitial fibrosis. Leukocyte recruitment is critical in the development of obstructive nephropathy leading to interstitial inflammation and renal fibrosis. RAGE, the receptor of advanced glycation end products, is implicated in chronic inflammation and has been recently identified as a novel receptor for the β2-integrin Mac-1, cooperating with ICAM-1 and thereby directly mediating leukocyte recruitment in vivo.

Searching for interference effects in learning new face-name associations.

In three experiments we attempted to increase interference using experimental manipulations in a face-name learning paradigm. All experiments included young and older adult participants because ageing is associated with increases in both susceptibility to interference and difficulty in learning face-name associations. None of the experiments produced interference for either age group: The inclusion of confusable (i.

Leukocytes induce epithelial to mesenchymal transition after unilateral ureteral obstruction in neonatal mice.

Urinary tract obstruction during renal development leads to tubular apoptosis, tubular atrophy, and interstitial fibrosis. Epithelial to mesenchymal transition (EMT) has been proposed as a key mechanism of myofibroblast accumulation in renal fibrosis. We studied the interplay of leukocyte infiltration, tubular apoptosis, and EMT in renal fibrosis induced by unilateral ureteral obstruction (UUO) in neonatal mice.