Single-cell RNA-sequencing of human spleens reveals an IDO-1 tolerogenic dendritic cell subset in pancreatic cancer patients that is absent in normal individuals.

Local and systemic immunosuppression are prominent features of pancreatic cancer, rendering anti-tumor effector cells inactive and immunotherapeutic approaches ineffective. The spleen, an understudied point of antigen-presentation and T cell priming in humans, holds particular importance in pancreatic cancer due to its proximity to the developing tumor. As main effectors of antigen presentation, dendritic cells display antigens to lymphocytes, thereby bridging the innate and adaptive immune response.

Attosecond chronoscopy of the photoemission near a bandgap of a single-element layered dielectric.

We report on the energy dependence of the photoemission time delay from the single-element layered dielectric HOPG (highly oriented pyrolytic graphite). This system offers the unique opportunity to directly observe the Eisenbud-Wigner-Smith (EWS) time delays related to the bulk electronic band structure without being strongly perturbed by ubiquitous effects of transport, screening, and multiple scattering. We find the experimental streaking time shifts to be sensitive to the modulation of the density of states in the high-energy region ( ≈ 100 eV) of the band structure.

Liposomal Fba and Met6 peptide vaccination protects mice from disseminated candidiasis.

Unlabelled: Epitopes from the cell surface proteins Fba and Met6 are putative vaccine targets for invasive candidiasis. Here, we describe a vaccine approach in which short peptides derived from Fba and Met6 are used in spontaneous nanoliposome antigen particle (SNAP) format. SNAP was enabled by the interaction of cobalt porphyrin phospholipid in liposomes with three histidine residues on the N-terminus of synthetic short peptide immunogens from Fba (F-SNAP), Met6 (M-SNAP), or bivalent Fba and Met6 (FM-SNAP).

Total Synthesis of Dynobactin A.

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate β-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.

Documentation of Disability Status and Accommodation Needs in the Electronic Health Record: A Qualitative Study of Health Care Organizations' Current Practices.

Background: This qualitative study aimed to understand how early adopting health care organizations (HCOs) implement the documentation of patients' disability status and accommodation needs in the electronic health record (EHR).

Methods: The authors conducted qualitative interviews with HCOs that had active or past initiatives to implement systematic collection of disability status in the EHR. The interviews elicited participants' current experiences, desired features of a standard EHR build, and challenges and successes.

Novel Intravenous Immunoglobulin Therapy for the Prevention and Treatment of Candida auris and Candida albicans Disseminated Candidiasis.

Disseminated candidiasis is a life-threatening disease and remains the most common bloodstream infection in hospitalized patients in the United States. Despite the availability of modern antifungal therapy, the crude mortality rate in the last decade has remained unacceptably high. Novel approaches are urgently needed to supplement or replace current antifungal therapies.

Atroposelective Total Synthesis of Darobactin A.

A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne.

Eso-Sponge® for anastomotic leakage after oesophageal resection or perforation: outcomes from a national, prospective multicentre registry.

Background: Anastomotic leakage (AL) after oesophagectomy and oesophageal perforations are associated with significant morbidity and mortality. Minimally invasive endoscopy is often used as first-line treatment, particularly endoluminal vacuum therapy (EVT). The aim was to assess the performance of the first commercially available endoluminal vacuum device (Eso-Sponge®) in the management of AL and perforation of the upper gastrointestinal tract (GIT).

Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa.

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions.

Informed consent in psychotherapy: a survey on attitudes among psychotherapists in Switzerland.

Background: The legal and ethical guidelines of psychological professional associations stipulate that informed consent by patients is an essential prerequisite for psychotherapy. Despite this awareness of the importance of informed consent, there is little empirical evidence on what psychotherapists' attitudes towards informed consent are and how informed consent is implemented in psychotherapeutic practice.

Methods: 155 psychotherapists in Switzerland completed an online survey assessing their attitudes regarding informed consent.

Towards compatibility of EUnetHTA JCA methodology and German HTA: a systematic comparison and recommendations from an industry perspective.

Objective: The transferability of the EU joint clinical assessment (JCA) reports for pharmaceuticals for the German benefit assessment was evaluated by systematically comparing EU JCA and German clinical assessments (CA) based on established assessment elements for HTA and assessing the potential impact of differences on Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) ability to derive the therapeutic added value.

Methods: Identification of all pharmaceuticals undergoing both, EU JCA and German CA between January 2016-June 2020. Qualitative review and data extraction from the assessments, assessment of methodological differences using a hierarchical model.

IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents 3% of all cancer cases and 7% of all cancer deaths in the United States. Late diagnosis and inadequate response to standard chemotherapies contribute to an unfavorable prognosis and an overall 5-year survival rate of less than 10% in PDAC. Despite recent advances in tumor immunology, tumor-induced immunosuppression attenuates the immunotherapy response in PDAC.

Cell-Surface-Specific Monoclonal Antibodies Protect Mice against Invasive Infection.

is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important species.

Synthetic conjugate peptide Fba-Met6 (MP12) induces complement-mediated resistance against disseminated Candida albicans.

The fungal genus Candida includes common commensals of the human mucosal membranes, and the most prevalently isolated species, C. albicans, poses a threat of candidemia and disseminated infection associated with an unacceptably high mortality rate and an immense $4 billion burden (US) yearly. Nevertheless, the demand for a vaccine remains wholly unfulfilled and increasingly pressing.

Importance of strain selection in the generation of heterologous immunity to Glaesserella (Haemophilus) parasuis.

Glaesserella (Haemophilus) parasuis is a part of the microbiota of healthy pigs and also causes the systemic condition called Glässer's disease. G. parasuis is categorized by it capsular polysaccharide into 15 serovars.

Total Synthesis of Tagetitoxin.

The intriguing structure of tagetitoxin (), a long-standing challenge in natural product synthesis, has been the subject of multiple revisions and has been confirmed through total synthesis. The route commences from a renewable furan starting material and features a number of unusual transformations (such as rearrangements, bromocyclization, and P(V)-based phosphate installation) to arrive at the target in 15 steps. As the route was designed to enable access to both enantiomers, the absolute configuration of the natural product could be assigned using a bioassay on (+)- and (-)-.

Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor's arsenal.

Late detection, compromised immune system, and chemotherapy resistance underlie the poor patient prognosis for pancreatic ductal adenocarcinoma (PDAC) patients, making it the 3 leading cause of cancer-related deaths in the United States. Cooperation between the tumor cells and the immune system leads to the immune escape and eventual establishment of the tumor. For more than 20 years, sincere efforts have been made to intercept the tumor-immune crosstalk and identify the probable therapeutic targets for breaking self-tolerance toward tumor antigens.

[Patient reported outcome measures in public reporting : Objectification of quality information via physicians and hospitals].

Patient reported outcome measures (PROM) are considered a good method of measuring the results of treatment outcomes with the aim of improving the functional, cognitive and mental state of patients and the quality of life during and after treatment. The publication of these results serves the patient's interest in finding the best provider for a treatment. The existing interest of many service providers for the integration of electronic PROM into everyday clinical practice is often faced by barriers due to financial, personnel and technical factors.

Generation and Evaluation of a Glaesserella (Haemophilus) parasuis Capsular Mutant.

() is a commensal bacterium of the upper respiratory tract in pigs and also the causative agent of Glässer's disease, which causes significant morbidity and mortality in pigs worldwide. Isolates are characterized into 15 serovars by their capsular polysaccharide, which has shown a correlation with isolate pathogenicity. To investigate the role the capsule plays in virulence and host interaction, a capsule mutant of the serovar 5 strain HS069 was generated (HS069Δcap) through allelic exchange following natural transformation.

Experimental Mouse Models of Disseminated Candida auris Infection.

Disseminated candidiasis is a life-threatening disease and remains the most common bloodstream infection in hospitalized patients in the United States. Despite the availability of modern antifungal therapy, crude mortality in the last decade has remained unacceptably high. In particular, is a multidrug-resistant, health care-associated fungal pathogen and has recently emerged as the first fungal pathogen to cause a global public health threat.

Administration of granulocyte-colony stimulating factor (G-CSF) to pigs results in a longer mean survival time after exposure to Streptococcus suis.

The use of immunomodulators is a promising alternative to the use of antibiotics for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease. Previously we demonstrated a replication-defective adenovirus vector that expresses porcine granulocyte colony-stimulating factor (G-CSF) elicited a sustained neutrophilia, lasting nearly 3 weeks, which may be beneficial to prevent bacterial diseases during times of peak incidence. In a pilot study using the vectored G-CSF with a Caesarian-derived, colostrum-deprived (CDCD) pig model of Streptococcus suis disease, only 1 of 4 pigs given G-CSF developed disease, while 3 of 4 non-treated pigs developed Streptococcal disease.

Design of a mimotope-peptide based double epitope vaccine against disseminated candidiasis.

Hematogenously disseminated candidiasis in humans is the third leading cause of nosocomial bloodstream infections in the US. There is no FDA approved antifungal vaccine or prophylactic/therapeutic antibody for use in humans. We first reported novel synthetic peptide and glycopeptide vaccines against Candida albicans cell surface epitopes that protect mice against disseminated candidiasis.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

Objectives: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave.

Methods: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1.