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Abstract Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers. We conducted a comprehensive analysis of this patient’s tumor, including Tumor Mutation Burden, Microsatellite Instability, and genetic profiling to explore further putative druggable targets. The tumor exhibited high PD-L1 expression and showed a notable response to immune checkpoint inhibitors when combined with platinum-based radio-chemotherapy. Our findings indicate that checkpoint inhibitors could play a critical role in treating NUT carcinoma, offering new therapeutic avenues and hope for patients with this challenging diagnosis. Whether PD-L1 expression may be a useful predictor of immune checkpoint inhibitor efficacy warrants further research.

Abstract Background Cancer requires interdisciplinary intersectoral care. The Care Coordination Instrument (CCI) captures patients’ perspectives on cancer care coordination. We aimed to translate, adapt, and validate the CCI for Germany (CCI German version). Methods The original English version contains 29 items in three domains, measured on a 4-point Likert scale (strongly disagree to strongly agree). Validation was conducted in three phases (mixed methods): (I) translation; (II) adaptation: pilot testing and revision in an iterative process using semi-structured, cognitive interviews with patients and professionals (physicians specializing in cancer), with interviews transcribed and qualitatively analyzed by inductive coding; and (III) validation: quantitative validation performed online (LimeSurvey), of at least 80 German patients, each with common cancer (breast, prostate) and rare cancer (different entities), with examination of factor structure (factor analysis) and determination of internal consistency (Cronbach's α) as well as potential influencing factors such as gender, education, or migration background (multivariable regression). Results Six patients and six professionals tested the translated instrument for comprehensibility, readability, and acceptability. Two items were consistently problematic for interviewees. A 31-item version (29 items + 2 alternative items) was validated in 192 patients. The alternative items had a higher variance in response behavior and were better understood; therefore, they replaced the two problematic items. However, the three original domains could not be confirmed statistically. Exploratively, a two-factorial structure (with cross-loadings) emerged, which can be interpreted as “communication/information” (16 items) and “need-based navigation” (17 items). Overall, the instrument had a high internal consistency (total score α = 0.931, M = 47.16, SD = 14.25; communication/information α = 0.924, M = 30.14, SD = 8.93; need-based navigation α = 0.868, M = 23.99, SD = 8.37). Significant factors on the care coordination score are treatment location (hospital vs. private practice oncologist M = -9.83 score points, p = 0.011) and gender (women vs. men M = 8.92 score points, p = 0.002). Conclusion The CCI German version is a valid instrument for measuring patients’ perceptions of cancer care coordination. Both domains reflect important aspects of care. The sensitivity of the CCI should be examined in future studies involving different cancer entities.

The BRAF proto-oncogene plays a key role in oncogenesis, promoting growth and survival through various genetic alterations. Most mutations involve the substitution of valine at amino acid position 600 (V600), resulting in a constitutively active protein, known as class I alterations. The most common class I mutation encodes for the BRAFV600E oncoprotein. Therapeutic targeting of BRAFV600E has led to the approval of dabrafenib plus trametinib for solid tumours [excluding colorectal cancer (CRC)] refractory to standard therapies. In gastrointestinal cancers, dabrafenib and trametinib have shown remarkable results in biliary tract cancers (BTC), establishing this combination as a viable second-line option for BRAFV600E-mutant BTC. In CRC, intrinsic epidermal growth factor receptor (EGFR) activation circumvents BRAF inhibition, necessitating the concurrent use of EGFR inhibitors, whose treatment strategy led to the approval of encorafenib plus cetuximab for BRAFV600E CRC.Despite these advances, resistance to BRAF inhibitors is almost universal, often due to extracellular signal-regulated kinase (ERK)-mediated up-regulation of RAF dimers that is able to overcome the inhibition of BRAF monomers. This resistance mechanism has spurred the development of novel RAF inhibitors able to prevent or to inhibit RAF dimers. Additionally, several treatment strategies are currently being investigated, including multi-step vertical mitogen-activated protein kinase (MAPK) inhibition and targeting parallel signalling pathways capable of bypassing MAPK oncogenic inhibition. While noteworthy results have been achieved with BRAFV600E inhibition, further research is needed to optimize BRAF-targeted therapies and address resistance mechanisms. Continued research and innovation are crucial to improving patient outcomes and addressing the complexities of BRAF mutations in human cancers.

Resumo Esta revisão bibliográfica objetivou tecer considerações teóricas sobre a doação de órgãos e tecidos, alternativa terapêutica eficaz no tratamento de diversas doenças e no controle de insuficiências terminais de alguns órgãos e falência de certos tecidos, com potencial de melhorar a qualidade e a perspectiva de vida de pacientes transplantados. Os principais empecilhos à efetivação do procedimento são a recusa da família de possíveis doadores, a falta de conhecimento do processo de doação-transplante e a escassez de políticas de educação continuada de profissionais da saúde que atuam na área, além dos desdobramentos decorrentes do não conhecimento. Para modificar a opinião pública, esse profissional deve atuar como educador, estimulando a população a participar de debates sobre transplantes de órgãos e legislação. É grande o número de pessoas na lista de espera em comparação ao total de doações, apesar da atitude positiva da população mundial sobre doação de órgãos.

This study presents a trilateral test array of new opto-acoustic Underwater Fish Observatories (UFOs) that were operated and tested in Kiel Bight as part of the “UFOTriNet” project. While hydroacoustic and optical techniques have so far been used individually to observe and monitor fish stocks, we present a coupled hybrid system consisting of an optical device intended to scan the near-field as a subsample of a spatially larger medium-to-far-field, scanned by an acoustical device. The optical device consists of two residual light amplifying camera modules able to detect and classify various marine species at a high resolution in the range of at max 4 meters in the study area. To compensate for this spatial limitation, the acoustical component consists of a 2D imaging sonar with a maximum range of 50 m, albeit with a lower resolution. Species affiliation, morphometric characteristics of fish and other marine organisms were stereo-optically detected and classified in the nearfield, blended with acoustical activity in medium to far range, and projected onto the entire insonified area using a hybrid algorithm. Through the synchronous acquisition of multiparametric abiotic and biotic data, UFO allows an automatic, continuous, and non-invasive long-term monitoring of various fish and other marine species and their habitats at regional hotspots. An 86-day multiparametric sample revealing an abrupt shift from a clupeid fish to a gelatinous plankton dominated regime in summer/autumn 2021 in Kiel Fjord is used to demonstrate the potential of UFO for various applications.

PurposeTo develop techniques and establish a workflow using hyperpolarized carbon-13 (13 C) MRI and the pyruvate-to-lactate conversion rate (kPL ) biomarker to guide MR-transrectal ultrasound fusion prostate biopsies.MethodsThe integrated multiparametric MRI (mpMRI) exam consisted of a 1-min hyperpolarized 13 C-pyruvate EPI acquisition added to a conventional prostate mpMRI exam. Maps of kPL values were calculated, uploaded to a picture archiving and communication system and targeting platform, and displayed as color overlays on T2 -weighted anatomic images. Abdominal radiologists identified 13 C research biopsy targets based on the general recommendation of focal lesions with kPL  >0.02(s-1 ), and created a targeting report for each study. Urologists conducted transrectal ultrasound-guided MR fusion biopsies, including the standard 1 H-mpMRI targets as well as 12-14 core systematic biopsies informed by the research 13 C-kPL targets. All biopsy results were included in the final pathology report and calculated toward clinical risk.ResultsThis study demonstrated the safety and technical feasibility of integrating hyperpolarized 13 C metabolic targeting into routine 1 H-mpMRI and transrectal ultrasound fusion biopsy workflows, evaluated via 5 men (median age 71 years, prostate-specific antigen 8.4 ng/mL, Cancer of the Prostate Risk Assessment score 2) on active surveillance undergoing integrated scan and subsequent biopsies. No adverse event was reported. Median turnaround time was less than 3 days from scan to 13 C-kPL targeting, and scan-to-biopsy time was 2 weeks. Median number of 13 C targets was 1 (range: 1-2) per patient, measuring 1.0 cm (range: 0.6-1.9) in diameter, with a median kPL of 0.0319 s-1 (range: 0.0198-0.0410).ConclusionsThis proof-of-concept work demonstrated the safety and feasibility of integrating hyperpolarized 13 C MR biomarkers to the standard mpMRI workflow to guide MR-transrectal ultrasound fusion biopsies.

Blood pressure measurement is important in monitoring hypertension. However, blood pressure does not provide much information about renal condition in treated hypertension. This study aimed to evaluate renal oxygenation in hypertensive patients using T2* mapping. Subgroup analysis explored whether R2* values can guide adjustments in antihypertensive treatment. A total of 140 consecutive subjects were recruited: 87 hypertensive subjects and 53 normotensive subjects. Hypertensive subjects were classified into non-medication (non-med), angiotensin II receptor blocker (ARB), and non-ARB-treated groups. Each group was divided into good and poor control subgroups based on blood pressure at enrollment. T2* mapping was utilized to assess renal cortical and medullary R2* values. After a 2-year follow-up, subjects were categorized into stable and unstable based on the need for treatment modifications. The unstable subgroup had higher medullary R2* values than the stable subgroup in all followed patients (p < 0.05). Additionally, the unstable merged non-med with ARB subgroup had higher medullary R2* values overall (p < 0.05) and within the good control subgroup (p < 0.05). Patients with stable hypertension, especially those with good control managed through lifestyle modifications or ARBs, exhibited lower renal medullary R2* values, suggesting higher renal oxygenation.

US and MRI-guided therapeutic US (TUS) can aid in the treatment of prostate, liver, and pancreatic cancer, as well as uterine fibroids and osseous metastases, and understanding the selection and optimization of treatment strategies is essential to furthering TUS advances and innovations.

As precision oncology has become a major part of the treatment landscape in oncology, liquid biopsies have developed as a particularly powerful tool as it surmounts several limitations of traditional tissue biopsies. These biopsies involve most commonly the isolation of circulating extracellular nucleic acids, including cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), as well as circulating tumor cells (CTCs), typically from blood.The clinical applications of liquid biopsies are diverse, encompassing the initial diagnosis and cancer detection, the application as a tool for prognostication in early and advanced tumor settings, the identification of potentially actionable alterations, the monitoring of response and resistance under systemic therapy and the detection of resistance mechanisms, the differentiation of distinct immune checkpoint blockade response patterns through serial samples, the prediction of immune checkpoint blockade responses based on initial liquid biopsy characteristics and the assessment of tumor heterogeneity. Moreover, molecular relapse monitoring in early-stage cancers and the personalization of adjuvant or additive therapy via MRD have become a major field of research in recent years.Compared to tissue biopsies, liquid biopsies are less invasive and can be collected serially, offering real-time molecular insights. Furthermore, liquid biopsies may allow for a more holistic evaluation of a patient's disease, as they assess material from all tumor sites and can theoretically reflect tumor heterogeneity. Furthermore, quicker turnaround-time also constitutes an advantage of liquid biopsies. Disadvantages or hurdles include the challenge of detecting low amounts of tumor deposits in peripheral blood or other fluids and the potential of different amounts tumor-shedding from different metastatic sites, as well as potentially false-positive from clonal hematopoietic mutations of indeterminate potential (CHIP) mutations. The clinical utility of liquid biopsies still must be validated in most settings and further research has to be done. Clinal trials including alternate bodily fluids and leveraging AI-technology are expected to revolutionize the field of liquid biopsies.

Abstract In this study, we present a screening method based on molecular absorption spectrometry to study PFAS uptake and fate in plants. To evaluate the suitability of this method we analyzed plant extracts with molecular absorption spectrometry (MAS) as well as liquid chromatography–tandem mass spectrometry (LC–MS/MS) for mass balance studies (w(F)). French bean plants (Phaseolus vulgaris) were grown on soil spiked using eight PFAS substances that vary in chain length and functional group composition. Specifically, these include three short-chained (C4–C5), five long-chained (C7–C10) carboxylic acids, one sulfonic acid and one sulfonic amide moieties. To investigate substance-specific PFAS uptake systematically, PFAS were spiked as single substance spike. Additionally, we studied one mixture of the investigated substances in equal proportions regarding w(F) and four PFAS mixtures of unknown composition. After 6 weeks, the plants were separated into four compartments. We analyzed the four compartments as well as the soil for extractable organically bound fluorine (EOF) by high resolution-continuum source-graphite furnace-molecular absorption spectrometry (HR-CS-GFMAS) as well as for sum of ten target-PFAS by LC–MS/MS. All three short-chained PFAS perfluorobutanoic acid (PFBA), perfluorobutanoic sulfonic acid (PFBS) and perfluoropentanoic acid (PFPeA) were determined in high concentrations mainly in the fruits of the investigated plants while long-chained PFAS perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were mainly determined in roots. PFBS was determined in remarkably high concentrations in leaves compartment by both quantification methods. Overall, comprehensive results of single substance spikes were in good agreement for both methods except for a few cases. Hence, two phenomena were identified: for mixed PFAS spikes of unknown composition huge differences between EOF and sum of target PFAS were observed with systematically higher EOF values. Overall, both methods indicate comparable results with MS being more reliable for known PFAS contamination and MAS being more valuable to identify PFAS exposure of unknown composition. Graphical Abstract