Risk factors for survival after lung transplantation in cystic fibrosis: impact of colonization with multidrug-resistant strains of Pseudomonas aeruginosa.

Background: Lung transplantation is the ultimate treatment option for patients with advanced cystic fibrosis. Chronic colonization of these recipients with multidrug-resistant (MDR) pathogens may constitute a risk factor for an adverse outcome. We sought to analyze whether colonization with MDR pathogens, as outlined in the German classification of multiresistant Gram-negative bacteria (MRGN), was associated with the success of lung transplantation.

The effect of caregiver opinion leaders to increase demand for evidence-based practices for youth anxiety: A cluster randomized controlled trial.

Background: Dissemination initiatives have the potential to increase consumer knowledge of and engagement with evidence-based treatments (e.g., cognitive behavioral therapy [CBT]).

Pain Reduction in Patellofemoral Knee Patients During 3-Month Intervention with Biomechanical and Sensorimotor Foot Orthoses: A Randomized Controlled Clinical Study.

Patellofemoral pain (PFP) significantly affects patients' daily activities and consequently reduces their quality of life. Custom-made foot orthoses (FOs) are a common method of medical treatment that positively influences biomechanical factors such as the kinematics of the lower extremity and reduces pain perception in patients. However, there is a gap in research regarding the influence of different FO treatments on knee pain.

Mechanism of sensor kinase CitA transmembrane signaling.

Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA.

Mechanisms of increased pain discrimination by contingent reinforcement: a perceptual decision-making and instrumental learning account.

Recent evidence highlights that monetary rewards can increase the precision at which healthy human volunteers can detect small changes in the intensity of thermal noxious stimuli, contradicting the idea that rewards exert a broad inhibiting influence on pain perception. This effect was stronger with contingent rewards compared with noncontingent rewards, suggesting a successful learning process. In the present study, we implemented a model comparison approach that aimed to improve our understanding of the mechanisms that underlie thermal noxious discrimination in humans.

Screening for transcriptomic associations with Swine Inflammation and Necrosis Syndrome.

Background: The recently identified swine inflammation and necrosis syndrome (SINS) affects tail, ears, teats, coronary bands, claws and heels of affected individuals. The primarily endogenous syndrome is based on vasculitis, thrombosis, and intimal proliferation, involving defence cells, interleukins, chemokines, and acute phase proteins and accompanied by alterations in clinical chemistry, metabolome, and liver transcriptome. The complexity of metabolic alterations and the influence of the boar led to hypothesize a polygenic architecture of SINS.

Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

Enhancing NK cell-mediated tumor killing of B7-H6 cells with bispecific antibodies targeting allosteric sites of NKp30.

In this work, we report the discovery and engineering of allosteric variable domains of the heavy chain (VHHs) derived from camelid immunization targeting NKp30, an activating receptor on natural killer (NK) cells. The aim was to enhance NK cell-mediated killing capacities by identifying VHHs that do not compete with the natural ligand of NKp30:B7-H6, thereby maximizing the recognition of B7-H6 tumor cells. By relying on the DuoBody technology, bispecific therapeutic antibodies were engineered, creating a panel of bispecific antibodies against NKp30xEGFR (cetuximab moiety) or NKp30xHER2 (trastuzumab moiety), called natural killer cell engagers (NKCEs).

Microcephaly protein ANKLE2 promotes Zika virus replication.

Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural protein 4A (NS4A) and host microcephaly protein ankyrin repeat and LEM domain-containing 2 (ANKLE2).

Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.

Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels.

What dimensions of school climate promote adaptive functioning in adolescents with ADHD? A prospective longitudinal study.

Background: The study of ADHD has predominantly focused on individual-level risk-factors, and less is known about contextual factors that promote adaptive functioning.

Aims: The present study is the first to evaluate the longitudinal association between five dimensions of school climate (academic expectations, student engagement, disciplinary structure, respect for students, willingness to seek help) and student outcomes, and whether ADHD symptom severity moderates those associations.

Methods And Procedures: Participants included 274 adolescents (45 % female) who completed assessments in 8th (T1) and 10th (T2) grades.

Cognitive Disengagement Syndrome and Autism Traits are Empirically Distinct from each Other and from Other Psychopathology Dimensions.

Recently, an association between cognitive disengagement syndrome (CDS), formerly sluggish cognitive tempo, and autism has been documented, but it is not known if the association is due to overlapping autism and CDS traits or if CDS is empirically distinct from autism. Mothers rated 2,209 children 4-17 years (1,177 with autism, 725 with ADHD-Combined type, and 307 with ADHD-Inattentive type) on the Pediatric Behavior Scale. Factor analysis of the Pediatric Behavior Scale items indicated that CDS and autism traits are empirically distinct from each other without cross-loading and are distinct from eight other factors (attention deficit, impulsivity, hyperactivity, oppositional behavior, irritability/anger, conduct problems, depression, and anxiety).

Spatial Signatures of Electron Correlation in Least-Squares Tensor Hypercontraction.

Least-squares tensor hypercontraction (LS-THC) has received some attention in recent years as an approach to reduce the significant computational costs of wave function-based methods in quantum chemistry. However, previous work has demonstrated that LS-THC factorization performs disproportionately worse in the description of wave function components (e.g.

Evaluating provider report of fidelity to contingency management in opioid treatment programs.

Introduction: With growing adoption of contingency management (CM) in addiction treatment programs, ensuring intervention fidelity over time is essential for improving patient outcomes. Nonetheless, ensuring an intervention is delivered as intended can be time- and resource-intensive for organizations. Finding ways to monitor fidelity without unduly burdening health systems is critical.

Field study on the suitability of oral fluid samples for monitoring of Lawsonia intracellularis and Brachyspira hyodysenteriae by multiplex qPCR under field conditions.

Background: Monitoring or surveillance of infectious diseases is crucial in terms of herd health management of livestock. Investigations of oral fluids have become an animal friendly routine strategy to monitor respiratory pathogens in pigs. Less is known about the suitability of oral fluids for the detection of enteric pathogens in swine.

Innate Immune Response Against Batai Virus, Bunyamwera Virus, and Their Reassortants.

(OBVs) represent a diverse group of RNA viruses, encompassing a progressively increasing number of arboviruses that cause disease in both humans and livestock. Yet, studies investigating these viruses remain scarce despite the critical importance of such knowledge for assessing their zoonotic potential. In this study, we conducted an evaluation of the early immune response against the understudied Batai virus (BATV), as well as the influence of reassortment with the Bunyamwera virus (BUNV) on this response.

Rapid Development of Modified Vaccinia Virus Ankara (MVA)-Based Vaccine Candidates Against Marburg Virus Suitable for Clinical Use in Humans.

Background/objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics.

Minimizing Long-Term Toxicities for Patients with Primary Mediastinal B-Cell Lymphoma Undergoing Modern Radiotherapy: Results from a Monocentric Biophysical Risk Evaluation.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of aggressive B-cell lymphoma with a predominant onset in young patients. The minimization of potential (late) side effects is of cardinal interest for these patients. An anticipation of the individual risk profile is desirable to counsel the patient on the putative impact of radiotherapy (RT).

Laparoscopic Endometriosis Surgery in Patients with Infertility: Identifying Surgical and Non-Surgical Variables Affecting Postoperative Pregnancy. Long-term Follow-up in a University Endometriosis Center.

Background: Endometriosis is a disease which affects the quality of life and fertility of many young women. Choosing the right time for surgery is important for the outcome of patients. We evaluated the surgical variables affecting postoperative pregnancy rates.

MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity.

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.

A minority of Th1 and Tfh effector cells express survival genes shared by memory cell progeny that require IL-7 or TCR signaling to persist.

It is not clear how CD4 memory T cells are formed from a much larger pool of earlier effector cells. We found that transient systemic bacterial infection rapidly generates several antigen-specific T helper (Th)1 and T follicular helper (Tfh) cell populations with different tissue residence behaviors. Although most cells of all varieties had transcriptomes indicative of cell stress and death at the peak of the response, some had already acquired a memory cell signature characterized by expression of genes involved in cell survival.

Insights into the Pathogenesis of Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unclear etiology. Numerous theories of its underlying pathogenesis have been proposed, including external triggers, neutrophilic dysfunction, complement activation, and autoimmunity, as well as a possible component of underlying genetic susceptibility. This review seeks to synthesize current understanding of the pathogenesis of PG and integrate interactions between the multitude of implicated host immune pathways to guide and inform future directions into the treatment of PG.