Interferon Regulatory Factor 4 dose-dependently controls peripheral Treg cell differentiation and homeostasis by modulating chromatin accessibility in mice.

FoxP3 regulatory T (Treg) cells restrict excessive immune responses and immunopathology as well as reactivity to self or environmental antigens and thus are crucial for peripheral immune tolerance. The transcription factor Interferon Regulatory Factor 4 (IRF4) controls differentiation and function of T cells. In Treg cells, IRF4 is required for peripheral activation and maturation to effector Treg (eTreg) cells with enhanced suppressive function.

Allografts promote skeletal regeneration of periprosthetic femoral bone loss.

Background: Periprosthetic bone loss is a common clinical problem in hip arthroplasty that must be addressed during revision surgery to achieve adequate implant stability. Although bone allografts represent the clinical standard among substitute materials used, evidence of their regenerative potential at the microstructural, cellular, and compositional level is lacking.

Methods: A multiscale imaging approach comprising contact radiography, undecalcified histology, scanning electron microscopy, and nanoindentation was employed on human femoral explants obtained postmortem many years after allograft use during revision surgery.

Biphasic bone loss in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) and a common cause of neurological disabilities in young adults. Although it is known that the peripheral immune landscape is altered in people with MS (pwMS), the impact on other organ systems than the CNS is frequently overlooked. In addition to neurological deficits, pwMS suffer from impaired bone health and increased fracture risk.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma.

Introduction And Objectives: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease.

Materials And Methods: 107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included.

Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) - a multicenter, randomized, controlled, open-label investigator-initiated trial.

Background: Despite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment.

Corrigendum: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease.

[This corrects the article DOI: 10.3389/fimmu.2023.

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease.

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear.

IRF4 is required for migration of CD4 T cells to the intestine but not for Th2 and Th17 cell maintenance.

The transcription factor Interferon Regulatory Factor 4 (IRF4) is central in control of T cell activation and differentiation. Deficiency of IRF4 results in severe immune deficiency and affects maturation and function of most if not all T cell subsets. Here we use mouse infection models for and to analyze the function of IRF4 in T helper (Th) 17 and Th2 cell responses, respectively.

Radial HR-pQCT and Finite Element Analysis in HPP Patients are Superior in Identifying Susceptibility to Fracture-Associated Skeletal Affections Compared to DXA and Laboratory Tests.

Hypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in the ALPL gene grouped by bone manifestations.

Kidney-resident innate-like memory γδ T cells control chronic infection of mice.

γδ T cells are involved in the control of infection, but their importance in protection compared to other T cells is unclear. We used a mouse model of systemic infection associated with high bacterial load and persistence in the kidney. Infection caused fulminant accumulation of γδ T cells in the kidney.

Maintenance versus replacement of medical equipment: a cost-minimization analysis among district hospitals in Nepal.

Background: About half of all medical devices in low- and lower-middle-income countries are currently non-operational because equipment maintenance is lacking. Thus, choosing a cost-efficient equipment maintenance approach has the potential to increase both the quantity and quality of important health services. Between 2010 and 2014 Nepal's Ministry of Health chose two of its development regions to pilot the contracting-out of maintenance services to the private sector.

Investigation of distal femur microarchitecture and factors influencing its deterioration: An ex vivo high-resolution peripheral quantitative computed tomography study.

While fractures of the distal femur are often considered as fragility fractures, detailed knowledge of the bone microarchitecture at this skeletal site is largely unavailable. Initial evaluation of a patient cohort with distal femur fractures showed a markedly increased occurrence in elderly women. The purpose of this study was to determine the extent to which demographic characteristics of distal femur fractures are reflected by general age- and sex-specific variations in local microarchitectural parameters.

Influence of X-rays and gamma-rays on the mechanical performance of human bone factoring out intraindividual bone structure and composition indices.

Doses of irradiation above 25 ​kGy are known to cause irreversible mechanical decay in bone tissue. However, the impact of irradiation doses absorbed in a clinical setting on the mechanical properties of bone remains unclear. In daily clinical practice and research, patients and specimens are exposed to irradiation due to diagnostic imaging tools, with doses ranging from milligray to Gray.

Prevalence of osteoporosis and osteopenia in elderly patients scheduled for total knee arthroplasty.

Introduction: Osteoporosis is a common comorbidity in elderly patients with osteoarthritis (OA) and may increase perioperative complications in orthopedic surgery (e.g., component migration, periprosthetic fractures).

Prevalence of low alkaline phosphatase activity in laboratory assessment: Is hypophosphatasia an underdiagnosed disease?

Background: Tissue-nonspecific alkaline phosphatase (TNSALP) encoded by the ALPL gene is of particular importance for bone mineralization. Mutation in the ALPL gene can lead to persistent low ALP activity resulting in the rare disease Hypophosphatasia (HPP) that is characterized by disturbed bone and dental mineralization. While severe forms are extremely rare with an estimated prevalence of 1/100.

The Bone Microarchitecture Deficit in Patients with Hemophilia Is Influenced by Arthropathy, Hepatitis C Infection, and Physical Activity.

Low bone mineral density (BMD) is common in patients with hemophilia (PWHs). The aim of the present study was to describe BMD and microarchitecture in PWHs in Northern Germany and to determine factors contributing to possible skeletal alterations. Demographic characteristics, BMD and microarchitecture, bone metabolism markers, and orthopaedic joint score (OJS) were assessed during routine check-ups.

The ground beetle tribe Platynini Bonelli, 1810 (Coleoptera, Carabidae) in the southern Levant: dichotomous and interactive identification tools, ecological traits, and distribution.

The carabids of the tribe Platynini from the southern Levant (Egypt: Sinai Peninsula, Israel, Jordan) and adjacent regions of Egypt, Lebanon, Syria, Iraq, and Saudi Arabia are reviewed in terms of species taxonomy, ecological, distributional traits, and conservation biology. In addition to a classical dichotomous identification key to the 14 species of the region, identification tools are made freely available via the Xper3 knowledge database "Platynini, southern Levant". Besides an interactive identification key, a matrix with character states for the species and single access identification keys are available.

Anatomical framework for pre-operative planning of laparoscopic left-sided colorectal surgery: Potential relevance of the distance between the inferior mesenteric artery and inferior mesenteric vein.

Background: The medial-to-lateral approach is favored by most colorectal surgeons for laparoscopic retroperitoneal dissection and mobilisation of the left colon. The peritoneal access window, i.e.

Interferon regulatory factor 4 controls effector functions of CD8 memory T cells.

The transcription factor IRF4 is required for CD8 T cell activation, proliferation, and differentiation to effector cells and thus is essential for robust CD8 T cell responses. The function of IRF4 in memory CD8 T cells yet needs to be explored. To investigate the role of IRF4 for maintaining differentiation state and survival of CD8 memory T cells, we used a mouse model with tamoxifen-inducible knockout to preclude effects due to inefficient memory cell differentiation in absence of IRF4.

Bone microarchitecture in patients with autoimmune hepatitis.

In patients with autoimmune hepatitis (AIH), osteoporosis represents a common extrahepatic complication, which we recently showed by an assessment of areal bone mineral density (aBMD) via dual-energy x-ray absorptiometry (DXA). However, it is well established that bone quality and fracture risk does not solely depend on aBMD, but also on bone microarchitecture. It is currently not known whether AIH patients exhibit a site-specific or compartment-specific deterioration in the skeletal microarchitecture.

Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia.

Hypophosphatasia (HPP) is a hereditary musculoskeletal disorder caused by inactivating variants in the ALPL gene and subsequently reduced serum tissue-nonspecific alkaline phosphatase (TNSALP) activity. This inborn error of metabolism results in decreased bone quality, accumulations of osteoid, and reduced bone mineralization. Increased incidence of fractures and prolonged bone healing are characteristic features for HPP.

Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype.

Background: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown.

Pathogen-induced tissue-resident memory T17 (T17) cells amplify autoimmune kidney disease.

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (T) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown.