Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma.

Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients with advanced melanoma but is not limited to melanoma patients. Many patients are refractory to TIL-ACT, however, or their cancer becomes resistant.

Insecticide exposure alters flight-dependent gene-expression in honey bees, Apis mellifera.

The increased reports of wild bee declines and annual losses of managed bees pose a significant threat to biodiversity and agricultural productivity. While these losses and declines are likely driven by various factors, the exposure of bees to agrochemicals has raised significant concern due to their ubiquitous use and potential adverse effects. Despite numerous studies suggesting neonicotinoids can negatively affect bees at the behavioral and molecular level, data linking these two factors remains sparse.

Chronic oral toxicity protocol for adult solitary bees (Osmia bicornis L.): Reduced survival under long-term exposure to a "bee-safe" insecticide.

Pollinators are essential for crop productivity. Yet, in agricultural areas, they may be threatened by pesticide exposure. Current pesticide risk assessments predominantly focus on honey bees, with a lack of standardized protocols for solitary bees.

Colony environment and absence of brood enhance tolerance to a neonicotinoid in winter honey bee workers, Apis mellifera.

In eusocial insects, worker longevity is essential to ensure colony survival in brood-free periods. Trade-offs between longevity and other traits may render long-living workers in brood-free periods more susceptible to pesticides compared to short-lived ones. Further, colony environment (e.

Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs.

Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes.

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance to TIL-ACT possibly due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells.

TGF-β specifies T versus T17 cell fates in murine CD4 T cells through c-Maf.

T follicular helper (T) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-β (TGF-β) induces robust expression of T hallmark molecules CXCR5 and Bcl6 in activated mouse CD4 T cells in vitro. TGF-β-induced mouse CXCR5 T cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T cells and provide critical help to B cells.

T helper cells exhibit a dynamic and reversible 3'-UTR landscape.

3' untranslated regions (3' UTRs) are critical elements of messenger RNAs, as they contain binding sites for RNA-binding proteins (RBPs) and microRNAs that affect various aspects of the RNA life cycle including transcript stability and cellular localization. In response to T cell receptor activation, T cells undergo massive expansion during the effector phase of the immune response and dynamically modify their 3' UTRs. Whether this serves to directly regulate the abundance of specific mRNAs or is a secondary effect of proliferation remains unclear.

Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy.

Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody-drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML).

Leveraging microRNAs for cellular therapy.

Owing to Karl Landsteiner's discovery of blood groups, blood transfusions became safe cellular therapies in the early 1900s. Since then, cellular therapy made great advances from transfusions with unmodified cells to today's commercially available chimeric antigen receptor (CAR) T cells requiring complex manufacturing. Modern cellular therapy products can be improved using basic knowledge of cell biology and molecular genetics.

Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy.

Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for T cell immunotherapies. T cells generated with this model resemble tumor-infiltrating exhausted T cells on a phenotypic and transcriptional level.

Forced expression of the non-coding RNA miR-17∼92 restores activation and function in CD28-deficient CD4 T cells.

CD28 provides the prototypical costimulatory signal required for productive T-cell activation. Known molecular consequences of CD28 costimulation are mostly based on studies of protein signaling molecules. The microRNA cluster miR-17∼92 is induced by T cell receptor stimulation and further enhanced by combined CD28 costimulation.

[Emergency Ultrasound Training for and with Medical Students].

Emergency Ultrasound Training for and with Medical Students Practical basic skills in sonography are a mandatory part of Swiss medical schools since 2018. The universities of Basel and Bern teach students the content of the POCUS component "Basic Emergency Sonography" of the SGUM and have developed the e-learning tool "POCUS Emergency Sonography" for this purpose in cooperation. By using this innovative blend- ed learning concept, students acquire basic skills in sonography and can build upon this know-how in their further education.

[Rare Incidental Finding during a Student Ultrasonography Course - A Case Report].

Rare Incidental Finding during a Student Ultrasonography Course - A Case Report During a sonography class in medical school, a large fluid-filled mass was discovered in the center of the lower abdomen in a healthy, asymptomatic female student; an overflow bladder was suspected. Despite various interdisciplinary investigations, the etiology of the cystic formation could not be clarified. Three months after discovery of the incidental finding, the increasingly symptomatic patient was diagnosed with a cystic tumor in the lower abdomen with secondary urinary retention, and surgical cyst excision was performed.

[Revision of the Young Sonographers Basic e-Learning Abdomen Course].

Revision of the Young Sonographers Basic e-Learning Abdomen Course The Young Sonographers e-learning was created in 2017 and contains the theoretical content and the procedure for the practical examination technique of the basic course on abdominal ultrasound. In order to provide an optimal teaching tool for ultrasound training in Switzerland in the future, this e-learning material has now been revised. The feedback from various experts as well as from participants, tutors and examiners served as the basis for the revision.

CRISPR/Cas-based Human T cell Engineering: Basic Research and Clinical Application.

Engineering human T cells for the treatment of cancer, viral infections and autoimmunity has been a long-standing dream of many immunologists and hematologists. Although primary human T cells have been genetically engineered for decades, this process was challenging, time consuming and mostly limited to transgene insertions mediated by viral transduction. The absence of widely accessible tools to efficiently and precisely engineer T cells genetically in a targeted manner limited their applicability as a living drug.

Correlation Between Increased Homing Flight Duration and Altered Gene Expression in the Brain of Honey Bee Foragers After Acute Oral Exposure to Thiacloprid and Thiamethoxam.

Neonicotinoids as thiamethoxam and thiacloprid are suspected to be implicated in the decline of honey bee populations. As nicotinic acetylcholine receptor agonists, they disturb acetylcholine receptor signaling in insects, leading to neurotoxicity and are therefore globally used as insecticides. Several behavioral studies have shown links between neonicotinoid exposure of bees and adverse effects on foraging activity, homing flight performance and reproduction, but the molecular aspects underlying these effects are not well-understood.

Plasmid- or Ribonucleoprotein-Mediated CRISPR/Cas Gene Editing in Primary Murine T Cells.

The CRISPR/Cas technology allows for genome editing in primary T cells. We herein describe the activation of primary murine CD4 or CD8 T cells, followed by electroporation with plasmid or ribonucleoproteins (RNP) for gene modification. Gene edited T cells can subsequently be transferred to host mice for in vivo studies or cultured in vitro for further characterization.

[Peer Teaching in Ultrasound Education - A Narrative Review].

Peer Teaching in Ultrasound Education - A Narrative Review Learning about ultrasound is becoming an increasingly important component of the undergraduate medical curriculum. However, teaching about this is very time-consuming, which is why many universities use peer teaching in ultrasound training. Peer teaching has various advantages that go beyond reducing specialists' teaching time: students may learn more from their peers because their cognitive schemata are more congruent and they are more likely to be open about their learning deficits.

[e-Learning: Basics of Sonography. Development of a Nationwide Entry-Level Module for Ultrasound Training in Switzerland].

e-Learning: Basics of Sonography. Development of a Nationwide Entry-Level Module for Ultrasound Training in Switzerland Teaching the rudiments of the theoretical and practical aspects of sonography is a challenge for many ultrasound course instructors, which is why the use of e-learning has come to the fore. An e-learning programme has already been implemented as part of a SGUM project: the "Fundamentals of Sonography" module.

Under Review: Data Requirements and Method Development of a New Bee Risk Assessment Scheme for Plant Protection Product Registration.

An up-to-date ecotoxicological risk assessment of plant protection products (PPPs) depends on the constant improvement of risk assessment methods and guidelines, and a thorough evaluation of their impacts. Here, we explain how the risk assessment of PPPs with regard to bees and the authorisation of PPPs is conducted in Switzerland. We further report the design and application of a new method to study homing flights of honey bees using the Radio Frequency Identification (RFID) technique.