Ubiquitous atmospheric production of organic acids mediated by cloud droplets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.

Saturation of Fishbone Instability by Self-Generated Zonal Flows in Tokamak Plasmas.

Gyrokinetic simulations of the fishbone instability in DIII-D tokamak plasmas find that self-generated zonal flows can dominate the nonlinear saturation by preventing coherent structures from persisting or drifting in the energetic particle phase space when the mode frequency down-chirps. Results from the simulation with zonal flows agree quantitatively, for the first time, with experimental measurements of the fishbone saturation amplitude and energetic particle transport. Moreover, the fishbone-induced zonal flows are likely responsible for the formation of an internal transport barrier that was observed after fishbone bursts in this DIII-D experiment. Finally, gyrokinetic simulations of a related ITER baseline scenario show that the fishbone induces insignificant energetic particle redistribution and may enable high performance scenarios in ITER burning plasma experiments.

A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Population-based epidemiological projections of rheumatoid arthritis in Germany until 2040.

OBJECTIVES: Our aim was to conduct a population-based projection to estimate the number of rheumatoid arthritis (RA) cases in Germany until 2040. METHOD: Data obtained from a report published in 2017 (doi:10.20364/VA-17.08) were used for future prediction analysis. The data were originally collected by the German Central Institute for Statutory Health Insurance. We used the illness-death model to estimate future numbers of RA cases, considering nine possible scenarios based on different incidence and mortality rates. RESULTS: In the baseline scenario, the number of women with RA is projected to increase by 417 000 cases and men by 179 000 cases by 2040, compared with 2015. Peak numbers of cases are concentrated in the 70-80-year-old age group, particularly among women. In the most favourable scenario (scenario 2), assuming a decreasing incidence, the total number of RA cases is projected to rise by 284 000 by 2040, reflecting a 38% relative increase from 2015 to 2040. The least favourable scenario (scenario 9), assuming an increasing incidence, projects a significant burden on the healthcare system. The total number of RA cases is expected to rise by 1.16 million by 2040, marking a substantial 158% relative increase from 2015 to 2040. CONCLUSIONS: Our research emphasizes a discernible trend: with an ageing society, improving treatment effectiveness, and declining all-cause mortality, we anticipate a rise in the absolute numbers of RA cases in Germany in the coming years. Our models robustly support this viewpoint, underscoring impending challenges for healthcare systems. Addressing these challenges demands multifaceted interventions.

Experimental and Monte Carlo based dosimetric investigation of a novel 3 mm radiosurgery 3 MV beam using the microSilicon detector.

BACKGROUND: The ZAP-X system is a novel gyroscopic radiosurgical system based on a 3 MV linear accelerator and collimator cones with a diameter between 4 and 25 mm. Advances in imaging modalities to detect small and early-stage pathologies allow for an early and less invasive treatment, where a smaller collimator matching the anatomical target could provide better sparing of surrounding healthy tissue. PURPOSE: A novel 3 mm collimator cone for the ZAP-X was developed. This study aims to investigate the usability of a commercial diode detector (microSilicon) for the dosimetric characterization of this small collimator cone; and to investigate the underlying small field perturbation effects. METHODS: Profile measurements in five depths as well as PDD and output ratio measurements were performed with a microSilicon detector and radiochromic EBT3 films. In addition, comprehensive Monte Carlo simulations were performed to validate the measurement observations and to quantify the perturbation effects of the microSilicon detector in these extremely small field conditions. RESULTS: It is shown that the microSilicon detector enables an accurate dosimetric characterization of the 3 mm beam. The profile parameters, such as the FWHM and 20%-80% penumbra width, agree within 0.1 to 0.2 mm between film and detector measurements. The output ratios agree within the measurement uncertainty between microSilicon detector and films, whereas the comparisons of the PDD results show good agreement with the Monte Carlo simulations. The analysis of the perturbation factors of the microSilicon detector reveals a small field correction factor of approximately 3% for the 3 mm circular beam and a correction factor smaller than 1.5% for field diameters above 3 mm. CONCLUSIONS: It could be shown that the microSilicon detector is well-suitable for the characterization of the new 3 mm circular beam of the ZAP-X system.

[An instrument to assess biopsychosocial pain concepts in adults : Development and evaluation by experts]. / Ein Instrument zur Erfassung biopsychosozialer Schmerzkonzepte von Erwachsenen : Entwicklung und Evaluation durch Expert*innen.

BACKGROUND: The biopsychosocial model is fundamental for the understanding and treatment of chronic pain; however, little research has focused on whether those affected show a biopsychosocial understanding. The multidimensional questionnaire Biopsychosocial Pain Concept Matrix (BiPS matrix) is presented. The conception of the BiPS matrix is based on the biological, psychological and social areas as well as on the common sense model of self-regulation with five dimensions: (1) type of disorder, (2) assumptions on the causes, (3) consequences, (4) duration of the disease and (5) possibilities for control and treatment. OBJECTIVE: The present study aims to examine the content relevance and comprehension of the areas, dimensions and items, including the use of the BiPS matrix with children by interdisciplinary expert ratings. The questionnaire can be perspectively used by treating professionals for diagnostic purposes. METHOD: In an online study 17 experts were questioned. In addition to descriptive statistics, comments were evaluated using qualitative content analysis according to Mayring. RESULTS: All experts rated the assessment of pain concepts with the BiPS matrix as well as the areas and dimensions as very relevant. With respect to the items, suggestions were made mainly regarding the wording of the items and adjustments for children. DISCUSSION: From an expert point of view the BiPS matrix represents a relevant instrument. Further research on the psychometric properties of the BiPS matrix in adults and children is indicated. In addition, the BiPS matrix can also be used to investigate pain concepts of medical and psychotherapeutic professional groups to demonstrate the biopsychosocial understanding of pain and the associated treatment options.

[Update on lupus nephritis]. / Update Lupusnephritis.

In addition to the butterfly rash, lupus nephritis is the most specific manifestation of systemic lupus erythematosus (SLE). The perspective on this organ manifestation has fundamentally changed as well as the manifestation of SLE itself 40 years after the first multicenter clinical study on lupus nephritis. Even if there is a faint glimpse of hope of a cure, there is still the fight against the problem of nonresponders and also the progressive loss of organ function. This update gives an overview of the current importance of lupus nephritis in the context of the whole SLE disease, of the special features and on the options provided by the new diagnostic and therapeutic developments.

Stimulated Amplification of Propagating Spin Waves.

Spin-wave amplification techniques are key to the realization of magnon-based computing concepts. We introduce a novel mechanism to amplify spin waves in magnonic nanostructures. Using the technique of rapid cooling, we create a nonequilibrium state in excess of high-energy magnons and demonstrate the stimulated amplification of an externally seeded, propagating spin wave. Using an extended kinetic model, we qualitatively show that the amplification is mediated by an effective energy flux of high energy magnons into the low energy propagating mode, driven by a nonequilibrium magnon distribution.

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

Ossification of the posterior capitellum: description of a new pathology and its radiological appearance.

BACKGROUND: Boxer elbow and handball goalkeeper elbow are causes of impingement characterized by osteophytes formation at the olecranon and coronoid tip as well as their corresponding fossae. Herein, we present another distinct pathology in these patients: the formation of an exostosis at the posterolateral aspect of the elbow. METHODS: Between April 2016 and May 2020, 12 athletes with boxer elbow and handball goalkeeper elbow (mean age of 22 years) suffering from elbow pain were enrolled in the present study. Plain radiography, magnetic resonance imaging (MRI), and computer tomography (CT) scans were used to evaluate the bone conformation of the posterolateral aspect of the elbow. Assessment and staging of the ossification was performed by two independent fellowship-trained elbow surgeons. RESULTS: Bone marrow edema of the posterior aspect of the elbow at the origin of the anconeus muscle was initially detected in MRI scans. With the progression of the condition, imaging revealed an ossification posterior to the capitellum with bony bridges. In the advanced stage of the disease, the exostoses was unstable as the ossification had no adherence to the posterior capitellum during surgical excision. Plain radiographs are limited in their ability to detect the condition, whereas MRI and CT scans allow to identify a signal enhancement at the posterolateral aspect of the elbow. CONCLUSION: In patients without history of elbow trauma, bony irregularities of the posterior aspect of the capitellum may indicate ossification of the posterolateral aspect of the elbow, most likely caused by repetitive hyperextensions.

BRD4S interacts with viral E2 protein to limit human papillomavirus late transcription.

The E2 protein encoded by human papillomaviruses (HPV) is a sequence-specific DNA-binding protein that recruits viral and cellular proteins. Bromodomain-containing protein 4 (BRD4) is a highly conserved interactor for E2 proteins that has been linked to E2's functions as transcription modulator, activator of viral replication and segregation factor for viral genomes. In addition to BRD4, a short form of BRD4 (BRD4S) is expressed from the BRD4 gene which lacks the C-terminal domain of BRD4. E2 proteins interact with the C-terminal motif (CTM) of BRD4, but a recent study suggested that the phospho-dependent interaction domain (PDID) and the basic interaction domain (BID) in BRD4 also bind to E2. These domains are also present in BRD4S. We now find that HPV31 E2 interacts with the isolated PDID domain in living cells and also with BRD4S which is present in detectable amounts in HPV-positive cell lines and is recruited into HPV31 E1 and E2 induced replication foci. Overexpression and knockdown experiments surprisingly indicate that BRD4S inhibits activities of E2. In line with that, the specific knockdown of BRD4S in the HPV31-positive CIN612-9E cell line induces mainly late viral transcripts. This occurs only in undifferentiated but not differentiated cells in which the productive viral replication cycle is induced. These data suggest that the BRD4S-E2 interaction is important to prevent HPV late gene expression in undifferentiated keratinocytes which may contribute to immune evasion and HPV persistence.ImportanceHuman papillomaviruses (HPV) have coevolved with their host by using cellular factors like bromodomain-containing protein 4 (BRD4) to control viral processes such as genome maintenance, gene expression and replication. We here show that, in addition to the C-terminal motif in BRD4, the phospho-dependent interaction domain in BRD4 interacts with E2 proteins which enable the recruitment of BRD4S, the short isoform of BRD4, to E2. Knock-down and overexpression of BRD4S reveals that BRD4S is a negative regulator of E2 activities. Importantly, the knockdown of BRD4S induces mainly L1 transcripts in undifferentiated CIN612-9E cells, which maintain replicating HPV31 genomes. Our study reveals an inhibitory role of BRD4S on HPV transcription, which may serve as an immune escape mechanism by the suppression of L1 transcripts and thus contribute to the establishment of persistent HPV infections.

Hot Spot Evolution Measured by High-Resolution X-Ray Spectroscopy at the National Ignition Facility.

Evolution of the hot spot plasma conditions was measured using high-resolution x-ray spectroscopy at the National Ignition Facility. The capsules were filled with DD gas with trace levels of Kr and had either a high-density-carbon (HDC) ablator or a tungsten (W)-doped HDC ablator. Time-resolved measurement of the Kr Heß spectra, absolutely calibrated by a simultaneous time-integrated measurement, allows inference of the electron density and temperature through observing Stark broadening and the relative intensities of dielectronic satellites. By matching the calculated hot spot emission using a collisional-radiative code to experimental observations, the hot spot size and areal density are determined. These advanced spectroscopy techniques further reveal the effect of W dopant in the ablator on the hot spot parameters for their improved implosion performance.

Measurement of Dark Ice-Ablator Mix in Inertial Confinement Fusion.

We present measurements of ice-ablator mix at stagnation of inertially confined, cryogenically layered capsule implosions. An ice layer thickness scan with layers significantly thinner than used in ignition experiments enables us to investigate mix near the inner ablator interface. Our experiments reveal for the first time that the majority of atomically mixed ablator material is "dark" mix. It is seeded by the ice-ablator interface instability and located in the relatively cooler, denser region of the fuel assembly surrounding the fusion hot spot. The amount of dark mix is an important quantity as it is thought to affect both fusion fuel compression and burn propagation when it turns into hot mix as the burn wave propagates through the initially colder fuel region surrounding an igniting hot spot. We demonstrate a significant reduction in ice-ablator mix in the hot-spot boundary region when we increase the initial ice layer thickness.

Towards quantum simulations in particle physics and beyond on noisy intermediate-scale quantum devices.

We review two algorithmic advances that bring us closer to reliable quantum simulations of model systems in high-energy physics and beyond on noisy intermediate-scale quantum (NISQ) devices. The first method is the dimensional expressivity analysis of quantum circuits, which allows for constructing minimal but maximally expressive quantum circuits. The second method is an efficient mitigation of readout errors on quantum devices. Both methods can lead to significant improvements in quantum simulations, e.g. when variational quantum eigensolvers are used. This article is part of the theme issue 'Quantum technologies in particle physics'.

Results after arthroscopic treatment of iliopsoas impingement after total hip arthroplasty.

BACKGROUND: A cause of groin pain after total hip arthroplasty (THA) is mechanical irritation or impingement of the iliopsoas tendon. The incidence is about 4%. If conservative therapy fails, an arthroscopic release of the iliopsoas tendon can be performed. The aim of the study was to assess the mid-term clinical outcome after arthroscopic release. We hypothesize that good results can be achieved by a minimally invasive endoscopic procedure. METHODS: Using our in-house database, all patients who received an endoscopic release of the iliopsoas tendon due to mechanical irritation after THA were identified. Inclusion criteria were mechanical irritation of the iliopsoas tendon after cementless THA with minimal acetabular component prominence. Exclusion criteria were marked prominence of the acetabular component and groin pain after THA for any other reason. In these patients, the modified Harris Hip Score (mHHS), the pain level using the numerical analogue scale and the UCLA Activity Score were measured. The mean follow-up period was 7 ± 3.8 (2.6-11.7) years. RESULTS: 25 patients were identified in whom an arthroscopic release of the iliopsoas tendon had been performed since 2007. The data of 20 patients were available at follow-up. The gender ratio was 1:1, the average age at the time of arthroscopy was 59 ± 27.7 (52-78) years. The average interval between THA and arthroscopy was 6.3 ± 4.0 (1.7-15) years. The mHHS showed a significant improvement from preoperative 31.2 ± 9.8 (17.6-47.3) to 82.0 ± 9.8 (46.2-100) points (p = 0.001). The pain level on the NAS decreased significantly from 8.5 ± 1.2 (7-10) to 2.5 ± 1.8 (0-6) points (p = 0.001). The activity level based on the UCLA Activity Score raised from 4.0 ± 2.7 (0-7) to 6.5 ± 1.8 (3-9) (p = 0.09). CONCLUSION: Mechanical irritation and impingement of the iliopsoas tendon is an important diagnosis to be considered in persistent groin pain after total hip arthroplasty. In failure of non-operative treatment, good clinical results can be achieved with arthroscopic release and the pain level can be significantly reduced. LEVEL OF EVIDENCE: IV.

Assessment of acetabular chondral damage and labral pathologies via direct MR arthrography: specialization matters.

AIMS: To compare the diagnostic accuracy of investigators from different specialities (radiologists and orthopaedic surgeons) with varying levels of experience of 1.5 T direct magnetic resonance arthrography (dMRA) against intraoperative findings in patients with femoroacetabular impingement syndrome (FAIS). METHODS: A total of 272 patients were evaluated with dMRA and subsequent hip arthroscopy. The dMRA images were evaluated independently by two non-hip-arthroscopy-trained orthopaedic surgeons, two fellowship-trained musculoskeletal radiologists, and two hip-arthroscopy-trained orthopaedic surgeons. The radiological diagnoses were compared with the intraoperative findings. RESULTS: Hip arthroscopy revealed labral pathologies in 218 (79%) and acetabular chondral lesions in 190 (69%) hips. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for evaluating the acetabular labral pathologies were 79%, 18%, 79%, 18%, and 66% (non-hip-arthroscopy trained orthopaedic surgeons), 83%, 36%, 83%, 36%, and 74% (fellowship-trained musculoskeletal radiologists), and 88%, 53%, 88%, 54% and 81% (hip-arthroscopy trained orthopaedic surgeons). The sensitivity, specificity, PPV, NPV and accuracy of dMRA for assessing the acetabular chondral damage were 81%, 36%, 71%, 50%, and 66% (non-hip-arthroscopy trained orthopaedic surgeons), 84%, 38%, 75%, 52%, and 70% (fellowship-trained musculoskeletal radiologists), and 91%, 51%, 81%, 73%, and 79% (hip-arthroscopy trained orthopaedic surgeons). The hip-arthroscopy trained orthopaedic surgeons displayed the highest percentage of correctly diagnosed labral pathologies and acetabular chondral lesions, which is significantly higher than the other two investigator groups (p < 0.05). CONCLUSION: The accuracy of dMRA on detecting labral pathologies or acetabular chondral lesions depends on the examiner and its level of experience in hip arthroscopy. The highest values are found for the hip-arthroscopy-trained orthopaedic surgeons. LEVEL OF EVIDENCE: Retrospective cohort study; III.

[Further development of regional early care-Many roads lead to Rome : Developmental stages of four established rheumatological early care concepts in different regions of Germany]. / Regionale Frühversorgung weiterentwickeln ­ Viele Wege führen nach Rom : Entwicklungsetappen von 4 etablierten rheumatologischen Frühversorgungskonzepten in verschiedenen Regionen Deutschlands.

In order to shorten the prognostically relevant waiting time until diagnosis and initiation of appropriate treatment in inflammatory rheumatic diseases, rheumatological centers in many regions across Germany have established and continuously developed specific early care concepts. Evaluated models from Altötting·Burghausen, Berlin Buch, Düsseldorf and Heidelberg and their developmental stages as a response to internal and external challenges are presented in this overview. The transparent publication of the developmental steps and the exchange of experiences aim at promoting new early care concepts in other regions and continuing the joint dialogue for improvement of the early detection and quality of care of inflammatory rheumatic diseases in Germany.

[Development of quality standards for patients with rheumatoid arthritis for use in Germany]. / Entwicklung von Qualitätsstandards für die Versorgung von Patient*innen mit rheumatoider Arthritis zur Anwendung in Deutschland.

Despite a qualitatively and structurally good care of patients with rheumatoid arthritis (RA) in Germany, there are still potentially amendable deficits in the quality of care. For this reason, the German Society for Rheumatology (DGRh) has therefore decided to ask a group of experts including various stakeholders to develop quality standards (QS) for the care of patients with RA in order to improve the quality of care. The QS are used to determine and quantitatively measure the quality of care, subject to relevance and feasibility. The recently published NICE and ASAS standards and a systematic literature search were used as the basis for development. A total of 8 QS, now published for the first time, were approved with the intention to measure and further optimize the quality of care for patients with RA in Germany.

[Development of quality standards for patients with axial spondyloarthritis for use in Germany]. / Entwicklung von Qualitätsstandards für Patient*innen mit axialer Spondyloarthritis zum Einsatz in Deutschland.

Quality standards (QS) are measurable constructs designed to quantify gaps in care and subsequently to improve quality of care. The Assessment of SpondyloArthritis International Society (ASAS) recently generated and published international QS for the management of patients with axial spondyloarthritis (axSpA) for the first time. The German Society of Rheumatology (DGRh) then decided to translate, review and possibly adopt these standards by a group of experts from different care settings. Against this background, national QS for the management of patients with axSpA for Germany were developed for the first time. The main focus was on feasibility and practical relevance. Ultimately, nine QS were defined with which the quality of care in Germany can and should be measured and improved.

Orf Virus-Based Therapeutic Vaccine for Treatment of Papillomavirus-Induced Tumors.

Orf virus (ORFV) represents a suitable vector for the generation of efficient, prophylactic antiviral vaccines against different pathogens. The present study investigated for the first time the therapeutic application of ORFV vector-based vaccines against tumors induced by cottontail rabbit papillomavirus (CRPV). ORFV-CRPV recombinants were constructed expressing the early CRPV gene E1, E2, E7, or LE6. In two independent experiments we used in total 23 rabbits which were immunized with a mixture of the four ORFV-CRPV recombinants or empty ORFV vector as a control 5 weeks after the appearance of skin tumors. For the determination of the therapeutic efficacy, the subsequent growth of the tumors was recorded. In the first experiment, we could demonstrate that three immunizations of rabbits with high tumor burden with the combined four ORFV-CRPV recombinants resulted in significant growth retardation of the tumors compared to the control. A second experiment was performed to test the therapeutic effect of 5 doses of the combined vaccine in rabbits with a lower tumor burden than in nonimmunized rabbits. Tumor growth was significantly reduced after immunization, and one vaccinated rabbit even displayed complete tumor regression until the end of the observation period at 26 weeks. Results of delayed-type hypersensitivity (DTH) skin tests suggest the induction of a cellular immune response mediated by the ORFV-CRPV vaccine. The data presented show for the first time a therapeutic potential of the ORFV vector platform and encourage further studies for the development of a therapeutic vaccine against virus-induced tumors.IMPORTANCE Viral vectors are widely used for the development of therapeutic vaccines for the treatment of tumors. In our study we have used Orf virus (ORFV) strain D1701-V for the generation of recombinant vaccines expressing cottontail rabbit papillomavirus (CRPV) early proteins E1, E2, LE6, and E7. The therapeutic efficacy of the ORFV-CRPV vaccines was evaluated in two independent experiments using the outbred CRPV rabbit model. In both experiments the immunization achieved significant suppression of tumor growth. In total, 84.6% of all outbred animals benefited from the ORFV-CRPV vaccination, showing reduction in tumor size and significant tumor growth inhibition, including one animal with complete tumor regression without recurrence.