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Chimeric antigen receptor (CAR) T cell therapies have demonstrated significant successes in treating cancer. Currently, there are six approved CAR T cell products available on the market that target different malignancies of the B cell lineage. However, to overcome the limitations of CAR T cell therapies, other immune cells are being investigated for CAR-based cell therapies. CAR natural killer (NK) cells can be applied as allogeneic cell therapy, providing an economical, safe, and efficient alternative to autologous CAR T cells. To improve CAR research and future in-patient monitoring of cell therapeutics, a simple, reliable, and versatile CAR detection reagent is crucial. As most existing CARs contain a single-chain variable fragment (scFv) with either a Whitlow or a G4S linker site, linker-specific monoclonal antibodies (mAbs) can detect a broad range of CARs. This study demonstrates that these linker-specific mAbs can detect different CAR NK cells in vitro, spiked in whole blood, and within patient-derived tumor spheroids with high specificity and sensitivity, providing an effective and almost universal alternative for scFv-based CAR detection. Additionally, we confirm that linker-specific antibodies can be used for functional testing and enrichment of CAR NK cells, thereby providing a useful research tool to fast-track the development of novel CAR-based therapies.

Abstract A critical step in the administration of oral vaccines in aquaculture is the effective protection of the vaccine antigens through the delivery route of water to stomach to the mucosal immune system in the gut. Bioactive substances can be incorporated into protective matrices to ensure safe ingestion and controlled release into the posterior digestive tract. Polyethylene glycol and alginate are promising and frequently applied substances in the oral administration of pharmaceutical substances; however, their direct influence on the intestinal tract or inflammatory response is not well investigated in aquaculture fish. In the current study, these two substances were evaluated separately and in combination. They were included in a commercial diet for juvenile rainbow trout (18.7 ± 0.1 g) and applied over 22 days in controlled feeding to determine possible gut alterations and inflammatory responses. Three different sections of the intestine, the anterior pyloric caeca, the mid‐intestine, and the posterior intestine, were histologically examined, and expression of inflammatory genes was measured in each. The inclusion of polyethylene glycol in the diet led to a significant reduction of villus height in the pyloric caeca and thus a significant reduction in active surface area. In the mid‐intestine, alginate inclusion resulted in a significant reduction of the mucus‐secreting goblet cells and a significant increase in villus width. In the posterior intestine, polyethylene glycol inclusion caused a significant increase in number of large vacuoles present; the addition of alginate buffered this effect. The results of the histological evaluation indicated symptoms that are usually evident in intestinal inflammation and can reduce functions of the respective intestinal segments. No significant increases in pro‐inflammatory gene expression tumor necrosis factor‐α, interleukin (IL)‐8, or IL‐1β were present, indicating no severe inflammatory response. Based on the observed histological impairments, negative consequences such as reduced efficiency of an oral vaccine or productivity of aquaculture rearing due to hindered nutrient digestion can be considered unlikely.

Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation. In this study, conducted in three endemic countries of West Africa where yaws remains a significant public health concern (Ghana, Cameroon, and Côte d'Ivoire), we aimed to assess the knowledge, attitudes, and practices related to yaws among community members, community health workers (CHWs), and traditional healers. The study revealed variations in the perception of causes of yaws among community members: the majority or participants in Ghana attributed yaws to germs (60.2%); in Cameroon the most reported form of transmission was contact with or drinking infected water sources (44.6%); and in Côte d'Ivoire both of these answers were also the most prevalent (60.3% germs and 93.% water sources). A substantial proportion of participants in Côte d'Ivoire also associated yaws with witchcraft and divine punishment (44.8%). Only a small proportion of individuals in Ghana and Côte d'Ivoire correctly identified contact with an infected person as a form of transmission (11.9% and 20.7%, respectively) and less than half in Cameroon (42.6%), although more than 98% of all participants reported avoidance behaviours towards yaws infected people due to fear of getting infected. Most participants expressed a preference for seeking care at hospitals (49.2%, 60.6%, 86.2%) or health care professionals including doctors and nurses (58.5%, 41,5% and 17.2%) if they were diagnosed with yaws, although a quarter of participants in Côte d'Ivoire also sought support from traditional healers. The CHWs interviewed were generally well-trained on yaws causes and treatment options, although they often reported low availability of treatment and diagnostic tests for yaws. Our findings underscore the need for community education, awareness campaigns, ongoing CHW training, and improved access to yaws treatment and diagnostic resources. The data also suggest that collaboration with traditional healers, who usually hold a highly esteemed position in the society, such as giving training on yaws causes and transmission or exchanging knowledge on treatment options, could be beneficial in certain regions, particularly in Côte d'Ivoire.

Summary: Animals need to sharpen their behavioral output in order to adapt to a variable environment. Hereby, light is one of the most pivotal environmental signals and thus behavioral plasticity in response to light can be observed in diurnal animals, including humans. Furthermore, light is the main entraining signal of the clock, yet immediate effects of light enhance or overwrite circadian output and thereby mask circadian behavior. In Drosophila, such masking effects are most evident as a lights-on response in two behavioral rhythms – the emergence of the adult insect from the pupa, called eclosion, and the diurnal rhythm of locomotor activity. Here, we show that the immediate effect of light on eclosion depends solely on R8 photoreceptors of the eyes. In contrast, the increase in activity by light at night is triggered by different cells and organs that seem to compensate for the loss of each other, potentially to ensure behavioral plasticity.

Abstract (Deutsch) Der vorliegende Artikel untersucht die sich ergänzenden Aspekte von Künstlicher Intelligenz (KI) und Lernen mit digitalen Medien im Bereich des Fremdsprachenerwerbs. Um eine Betrachtung möglicher Synergien in den Fokus zu rücken werden die jüngsten Fortschritte im digitalen Lernen dargelegt, wobei ein besonderer Schwerpunkt auf die Rolle von KI im Lehr-Lern-Kontext gelegt wird. Vorgestellt wird ebenso eine lehr-lerntheoretische Perspektive, die für die Entwicklungen im Bereich der Digitalisierung geeignet scheint. Darüber hinaus werden mögliche Auswirkungen dieser digitalen Fortschritte im Bildungsbereich auf den Fremdsprachenerwerb betrachtet und die Potentiale für den Fremdsprachenerwerb diskutiert, die sich aus der Kombination von KI und Lernansätzen mit digitalen Medien ergeben. Das Bewusstsein für die Bedeutung dieser Synergie soll geschärft und damit ein Beitrag zur Weiterentwicklung der Forschung im Bereich des Fremdsprachenerwerbs durch technologiegestütztes Lernen geleistet werden. Abstract (English) This article explores the relationship between Artificial Intelligence (AI) and digital media in foreign language acquisition. Recent advances in digital learning are outlined, with a particular emphasis on the role of AI in the teaching-learning context. Moreover, a teaching-learning theory perspective is presented that seems appropriate for developments in the field of digitalization. Additionally, this article considers the potential impact of digital advancements in education on foreign language learning. It also discusses the potential benefits of combining AI and learning approaches with digital media for foreign language learning. The objective is to increase awareness of the significance of this synergy and contribute to the further development of research in the field of technology-supported foreign language learning.

Epidemics of yaws-like cutaneous ulcers are regularly documented in children in the tropics. They occur mainly in poor and remote communities without access to health facilities. The integration of molecular tools into yaws control efforts has made it possible to describe Haemophilus ducreyi (HD) as a major cause of cutaneous ulcers. The objective of this study was to determine the prevalence of HD as cause of cutaneous ulcers, investigate its presence in asymptomatic individuals and identify associated risk factors. A cross-sectional study was conducted in yaws endemic districts of Cameroon. Participants included people presenting yaws-like ulcers and asymptomatic individuals. Swab samples were collected from each participant and tested for HD and Treponema pallidum (TP) using an established qPCR method. Additionally, demographic, habitat, proximity, and hygiene characteristics were collected using a structured questionnaire. A total of 443 individuals participated in the study, including 271 ulcer cases and 172 asymptomatic contacts. The prevalence of HD in ulcers was 30.3% (Confidence Interval (CI) 95% [24.8-35.7]) and the prevalence of asymptomatic HD carriage was 8.6% (CI95% [4.5-12.9]). TP was also detected in our sample among ulcer cases but in lower proportion (5.2% CI95% [2.5-7.8]) compared to HD. The adjusted logistic regression model showed that women were as much at risk of having HD cutaneous ulcer as men regardless of age. Physical proximity to a confirmed ulcer case was the major factor identified favouring HD transmission. HD ulcers were more likely to be present on Bantu individuals compared to Baka as well as HD colonization. These findings highlight HD as the most common cause of cutaneous ulcers in yaws-endemic communities in Cameroon. The exact implications of detecting HD on intact skin are not yet clear. Further studies are needed to understand the significance of this carriage in the spread dynamics of the disease.

Abstract Background Primary hypoadrenocorticism (PH) is rare in cats and knowledge about treatment is sparse. Objective To describe cats with PH with a focus on long‐term treatment. Animals Eleven cats with naturally occurring PH. Methods Descriptive case series with data on signalment, clinicopathological findings, adrenal width, and doses of desoxycorticosterone pivalate (DOCP) and prednisolone during a follow‐up period of >12 months. Results Cats ranged from 2 to 10 years (median 6.5); 6 cats were British Shorthair. Most common signs were reduced general condition and lethargy, anorexia, dehydration, obstipation, weakness, weight loss, and hypothermia. Adrenal glands on ultrasonography were judged small in 6. Eight cats could be followed for 14 to 70 months (median: 28). Two were started on DOCP doses ≥2.2 mg/kg (2.2; 2.5) and 6

Abstract Background Lipase activity and pancreatic lipase immunoreactivity (PLI) have not been compared in dogs hospitalized for acute pancreatitis (AP). Objectives To describe the progression of lipase activity and PLI, and correlations with clinicopathologic features in dogs with AP. Animals Thirty‐nine dogs with AP based on clinical signs and lipase activity >350 U/L (reference interval [RI], 24‐108 U/L). Methods Retrospective study. Lipase activity (LIPC Roche), PLI (SpecPL), and clinical signs were recorded daily. Admission (d1) data (clinical, laboratory, and ultrasound [US] findings), and clinical signs during hospitalization (d2‐d3) were assessed for correlation with lipases. Results Median (range) duration of clinical signs before presentation was 2 days (1‐7 days). Median (range) lipase activity and PLI at d1 were 1070 U/L (range, 357‐1500 U/L) and 1111 μg/L (range, 292‐1500 μg/L). Strong correlation between assays at d1 (rs 0.96; P

BackgroundParticipatory Design (PD), albeit an established approach in User-Centered Design, comes with specific challenges when working with older adults as research participants. Addressing these challenges relates to the reflection and negotiation of the positionalities of the researchers and research participants and includes various acts of giving and receiving help. During the COVID-19 pandemic, facets of positionalities and (mutual) care became particularly evident in qualitative and participatory research settings. ObjectiveThe aim of this paper was to systematically analyze care practices of participatory (design) research, which are to different extents practices of the latter. Using a multiyear PD project with older people that had to take place remotely over many months, we specify different practices of care; how they relate to collaborative work in the design project; and represent foundational practices for sustainable, long-term co-design. Our research questions were “How can digitally-mediated PD work during COVID-19 and can we understand such digital PD as ‘care’?” MethodsOur data comes from the Joint Programming Initiative “More Years, Better Lives” (JPI MYBL), a European Union project that aims to promote digital literacy and technology appropriation among older adults in domestic settings. It targeted the cocreation, by older adults and university researchers, of a mobile demo kit website with cocreated resources, aimed at improving the understanding of use options of digital tools. Through a series of workshops, a range of current IT products was explored by a group of 21 older adults, which served as the basis for joint cocreative work on generating design ideas and prototypes. We reflect on the PD process and examine how the actors enact and manifest care. ResultsThe use of digital technology allowed the participatory project to continue during the COVID-19 pandemic and accentuated the digital skills of older adults and the improvement of digital literacy as part of “care.” We provide empirically based evidence of PD with older adults developing digital literacy and sensitizing concepts, based on the notion of care by Tronto for differentiating aspects and processes of care. The data suggest that it is not enough to focus solely on the technologies and how they are used; it is also necessary to focus on the social structures in which help is available and in which technologies offer opportunities to do care work. ConclusionsWe document that the cocreation of different digital media tools can be used to provide a community with mutual care. Our study demonstrates how research participants effectively enact different forms of care and how such “care” is a necessary basis for a genuinely participatory approach, which became especially meaningful as a form of support during COVID-19. We reflect on how notions of “care” and “caring” that were central to the pandemic response are also central to PD.

Abstract Basal-like breast cancer (BLBC) is a highly aggressive breast cancer subtype frequently associated with poor prognosis. Due to the scarcity of targeted treatment options, conventional cytotoxic chemotherapies frequently remain the standard of care. Unfortunately, their efficacy is limited as BLBC malignancies rapidly develop resistant phenotypes. Using transcriptomic and proteomic approaches in human and murine BLBC cells, we aimed to elucidate the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in these mammary tumors. Specifically, we identified and characterized a novel short isoform of Roundabout Guidance Receptor 3 (ROBO3s), upregulated in BLBC in response to chemotherapy and encoding for a protein variant lacking the transmembrane domain. We established an important role for the ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving resistance of BLBC cells to cytotoxic drugs. By uncovering the conservation of ROBO3s expression across multiple cancer types, as well as its association with reduced BLBC-patient survival, we emphasize its potential as a prognostic marker and identify a novel attractive target for anti-cancer drug development.

Abstract Background Current incidence estimates of SARS-CoV-2 in Germany rely to a large extent on case notifications. However, the large number of mild or asymptomatic infections is likely to result in underestimation. Population-based studies can provide valid estimates of the SARS-CoV-2 incidence and thus support health authorities to monitor the epidemiological situation and to initiate, maintain, strengthen or relax effective countermeasures. Methods This study was conducted in Cologne, Germany. Six-thousand randomly drawn Cologne residents, 18 years of age or older, were contacted by mail in March 2021. Study envelopes contained a kit for self-administered saliva sample and access details to a questionnaire on sociodemographic characteristics, previous positive SARS-CoV-2 RT-qPCR and completed COVID-19 vaccinations. Participants were again invited for a second round in June 2021, while those who declined participation were replaced by additional randomly drawn Cologne residents in order to reach a total of 6000 potential participants again. The saliva samples were sent to the laboratory by mail and tested for SARS-CoV-2 using RT-qPCR. The incidence estimates were adjusted for sensitivity and specificity of the test procedure and compared with the official numbers of new SARS-CoV-2 cases in the adult Cologne population. Results The first surveillance round in March 2021 (response rate: 34.08%, N = 2045) showed a SARS-CoV-2 seven-day incidence of 85 cases per 100,000 adult Cologne residents (95% CI: 9 to 319). In the same period, the officially registered cases were 125 per 100,000. The second surveillance round in June 2021 (response rate: 36.53%, N = 2192) showed a seven-day incidence of 27 per 100,000 adult Cologne residents (95% CI: 1 to 142), while the official figures for newly registered SARS-CoV-2 cases in the same period were 15 per 100,000. Conclusions The incidence estimates do not indicate relevant underestimation of new SARS-CoV-2 infections based on case notification. Regular use of the surveillance method developed here may nevertheless complement the efforts of the health authorities to assess the epidemiological situation. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

The fifth episode of #DefendingTheDefenders, the rule of law podcast by Deutscher Anwaltverein and Verfassungsblog, focuses on Colombia, where the situation for attorneys and human rights defenders is particularly dangerous.