“Not in the mood”: The fear of being laughed at is better predicted by humor temperament traits than diagnosis in neurodevelopmental conditions

BACKGROUND: Research has shown that autistic individuals seem to be more prone to develop gelotophobia (i.e., the fear of being laughed at) than typically developing individuals. The goals of the present study were to discover whether the high levels of gelotophobia found in autism in previous studies were replicated here, to expand the research to Down syndrome (DS) and Williams syndrome (WS), and to assess the relation between individual differences and social impairments, affective predispositions, and humor temperament. METHODS: Questionnaires were distributed to parents of autistic individuals (N = 48), individuals with DS (N = 139), and individuals with WS (N = 43) aged between 5 and 25 years old. RESULTS: Autistic individuals were shown to frequently experience at least a slight level of gelotophobia (45%), compared to only 6% of individuals with DS and 7% of individuals with WS. Interestingly, humorless temperament traits (i.e., seriousness and bad mood) manifested as the strongest predictors of gelotophobia. This relation even transcended group differences. CONCLUSION: The results confirm that gelotophobia seems to be particularly concerning for autistic individuals, whereas individuals with DS and WS seem to be more protected from developing such a fear. Moreover, it appears that gelotophobia seems to be more linked to high seriousness and irritability than diagnosis

Aging of bone marrow mesenchymal stromal cells: Hematopoiesis disturbances and potential role in the development of hematologic cancers

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression

Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections

Background. Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry. Methods. Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes. Results. The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice. Conclusions. We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation

Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis

Background: Cost‐effective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decision‐making. A concentration–response relationship for ustekinumab at trough is uncertain owing to the contradictory results reported. Objectives: To investigate the relationship between 4‐week postinjection ustekinumab concentrations and clinical response in patients with psoriasis. Methods: Forty‐nine patients with moderate‐to‐severe psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for ≥ 16 weeks were included. Ustekinumab serum concentrations and anti‐ustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI). Results: At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 μg mL−1 (ρ = –0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI ≤ 2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 μg mL−1, P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 μg mL−1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had anti‐ustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively). Conclusions: A concentration–response relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4‐week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization

Protein processing characterized by a gel-free proteomics approach

We describe a method for the specific isolation of representative N-terminal peptides of proteins and their proteolytic fragments. Their isolation is based on a gel-free, peptidecentric proteomics approach using the principle of diagonal chromatography. We will indicate that the introduction of an altered chemical property to internal peptides holding a free α-N-terminus results in altered column retention of these peptides, thereby enabling the isolation and further characterization by mass spectrometry of N-terminal peptides. Besides pointing to changes in protein expression levels when performing such proteome surveys in a differential modus, protease specificity and substrate repertoires can be allocated since both are specified by neo-N-termini generated after a protease cleavage event. As such, our gel-free proteomics technology is widely applicable and amenable for a variety of proteome-driven protease degradomics research

Collagen type XIV is proportionally lower in the lung tissue of patients with IPF

Abnormal deposition of extracellular matrix (ECM) in lung tissue is a characteristic of idiopathic pulmonary fibrosis (IPF). Increased collagen deposition is also accompanied by altered collagen organization. Collagen type XIV, a fibril-associated collagen, supports collagen fibril organization. Its status in IPF has not been described at the protein level yet. In this study, we utilized publicly available datasets for single-cell RNA-sequencing for characterizing collagen type XIV expression at the gene level. For protein level comparison, we applied immunohistochemical staining for collagen type XIV on lung tissue sections from IPF patients and compared it to lung tissue sections from never smoking and ex-smoking donors. Analyzing the relative amounts of collagen type XIV at the whole tissue level, as well as in parenchyma, airway wall and bronchial epithelium, we found consistently lower proportions of collagen type XIV in all lung tissue compartments across IPF samples. Our study suggests proportionally lower collagen type XIV in IPF lung tissues may have implications for the assembly of the ECM fibers potentially contributing to progression of fibrosis.</p

Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy

Background. Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. Methods. We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. Results. We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P = .008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P < .001]). Conclusions. MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patient