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Objective To determine whether a multi-feed, loop-dipole combined approach can be used to improve performance of rectangular dielectric resonator antenna (DRA) arrays human brain for MRI at 7 T. Materials and methods Electromagnetic field simulations in a spherical phantom and human voxel model “Duke” were conducted for different rectangular DRA geometries and dielectric constants εr. Three types of RF feed were investigated: loop-only, dipole-only and loop-dipole. Additionally, multi-channel array configurations up to 24-channels were simulated. Results The loop-only coupling scheme provided the highest B1+ and SAR efficiency, while the loop-dipole showed the highest SNR in the center of a spherical phantom for both single- and multi-channel configurations. For Duke, 16-channel arrays outperformed an 8-channel bow-tie array with greater B1+ efficiency (1.48- to 1.54-fold), SAR efficiency (1.03- to 1.23-fold) and SNR (1.63- to 1.78). The multi-feed, loop-dipole combined approach enabled the number of channels increase to 24 with 3 channels per block. Discussion This work provides novel insights into the rectangular DRA design for high field MRI and shows that the loop-only feed should be used instead of the dipole-only in transmit mode to achieve the highest B1+ and SAR efficiency, while the loop-dipole should be the best suited in receive mode to obtain the highest SNR in spherical samples of similar size and electrical properties as the human head.

Purpose In this study, we aimed to measure the apparent diffusion coefficients (ADCs) of major phosphorous metabolites in the human calf muscle at 7 T with a diffusion-weighted (DW)-STEAM sequence. Methods A DW-STEAM sequence with bipolar gradients was implemented at 7 T, and DW MR spectra were acquired in three orthogonal directions in the human calf muscle of six healthy volunteers (TE/TM/TR = 15 ms/750 ms/5 s) at three b-values (0, 800, and 1200 s/mm2). Frequency and phase alignments were applied prior to spectral averaging. Averaged DW MR spectra were analyzed with LCModel, and ADCs of 31P metabolites were estimated. Results Four metabolites (phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and glycerol phosphorylcholine (GPC)) were quantified at all b-values with mean CRLBs below 10%. The ADC values of PCr, ATP, Pi, and GPC were (0.24 ± 0.02, 0.15 ± 0.04, 0.43 ± 0.14, 0.40 ± 0.09) × 10–3 mm2/s, respectively. Conclusion The ADCs of four 31P metabolites were successfully measured in the human calf muscle at 7 T, among which those of ATP, Pi and GPC were reported for the first time in humans. This study paves the way to investigate 31P metabolite diffusion properties in health and disease on the clinical MR scanner.

Mitochondrial β-barrel proteins are essential for the transport of metabolites, ions and proteins. The sorting and assembly machinery (SAM) mediates their folding and membrane insertion. We report the cryo-electron microscopy structure of the yeast SAM complex carrying an early eukaryotic β-barrel folding intermediate. The lateral gate of Sam50 is wide open and pairs with the last β-strand (β-signal) of the substrate-the 19-β-stranded Tom40 precursor-to form a hybrid barrel in the membrane plane. The Tom40 barrel grows and curves, guided by an extended bridge with Sam50. Tom40's first β-segment (β1) penetrates into the nascent barrel, interacting with its inner wall. The Tom40 amino-terminal segment then displaces β1 to promote its pairing with Tom40's last β-strand to complete barrel formation with the assistance of Sam37's dynamic α-protrusion. Our study thus reveals a multipoint guidance mechanism for mitochondrial β-barrel folding.

The introduction of volatile-rich subducting slabs to the mantle may locally generate large redox gradients, affecting phase stability, element partitioning and volatile speciation

Friction stir welding (FSW) is a solid-state joining process with a wide range of applications in the E-mobility, automotive, aerospace and energy industries. However, FSW is subjected to specific challenges including comparatively high process forces and high requirements on the clamping technique as well as tool wear resulting from the tool-workpiece interaction and thermo-mechanical stresses. Geometric-related tool wear can cause premature tool failure, process instabilities or weld seam irregularities. Therefore, tool wear in general, wear limits and tool life are essential factors for the efficient and sustainable implementation of friction stir welding. Against this background, this study analysed areas of significant tool wear on the shoulder and probe as a function of process temperature, weld seam length and weld seam quality. This provided functional correlations for determining limiting conditions on maximum tolerable tool wear. Geometrical deviations of the tool, induced by wear, were detected experimentally at different measuring points on the probe and shoulder and varying weld seam length. The investigations were carried out using a force-controlled robotized welding setup in which AA-6060-T66 sheets with a thickness of 5 mm were joined by weld seams up to 500 m in length. To identify the maximum tolerable tool wear, the weld seam properties were determined by visual and metallographic inspections and by tensile tests at 50-m intervals on the weld seam. It was shown that a 50% reduction in rotational speed (lower temperatures) resulted in less wear and thus in an increase of tool life of up to 150%. In addition, it was shown that the shoulder, like the probe, was also subject to significant wear. These results can be incorporated into FSW maintenance schedules to maximize tool life and minimize scrap rates.

Today, new lithium-ion battery-recycling technologies are under development while a change in the legal requirements for recycling targets is under way. Thus, an evaluation of the performance of these technologies is critical for stakeholders in politics, industry, and research. We evaluate 209 publications and compare three major recycling routes. An important aspect of this review is that we tackle the need for a critical evaluation of these recycling routes by introducing clear terms and creating a structuring scheme. Our evaluation criteria cover three areas: status of development, process performance, and life-cycle environmental impacts. With respect to development status, we provide an analysis of today’s market. A criterion of process performance is recycling efficiency, which today focuses on the mass of the recovered materials. To include the contributions of critical materials, we add a criterion for the efficiency of recovery of materials. Life-cycle assessments provide information on gross impacts, benefit of substituting virgin material and net impact. Present life-cycle assessments focus on waste management rather than on recovery of critical materials. This review contributes to an understanding of these trade-offs and supports discussion as to what is the “best” recycling route when targets conflict. Graphical Abstract There are three possible process sequences for each lithium-ion battery-recycling route. A distinction is made between pre-treatment steps (gray), direct physical treatment steps (green), pyro-metallurgical treatment (orange), and hydro-metallurgical treatment (blue). The figure is based on a figure from Doose et al. (Joule 3:2622–2646, 2019).

Purpose Oral cancer is an underestimated health problem, and its existence and the relevant prevention measures are not sufficiently known by the general population. The project thus aimed to develop, implement and evaluate an oral cancer campaign in Northern Germany, and to increase problem awareness on various levels: draw public attention to the tumour by media coverage increase awareness of early detection opportunities for the target group, and raise awareness of carrying out early detection measures by the professional groups involved. Methods For each level, a campaign concept was developed and documented in terms of content and timing. The identified target group was elderly educationally disadvantaged male citizens ≥ 50 years. The evaluation concept for each level included pre-, post- and process evaluations. Results The campaign was carried out from April 2012 to December 2014. The issue of awareness within the target group was significantly increased. Media coverage showed that regional media adopted the topic of oral cancer and placed it on their published agenda. Furthermore, the continuous involvement of the professional groups over the course of the campaign led to an increased awareness of oral cancer. Conclusion The development of the campaign concept with a comprehensive evaluation showed that the target group was successfully reached. The campaign was adapted to the required target group and specific conditions, and was also designed to be context sensitive. It is, therefore, recommended that the development and implementation of an oral cancer campaign on a national level be discussed.

Purpose The majority of suspected malignant changes in the oral mucosa are detected by dentists in private practice. Statements regarding the effectiveness of visual examination of the oral cavity for early detection are not necessarily transferable between different health care systems. Our clinical-epidemiological and methodological aim was thus to conduct a prospective regional study in dental practices under everyday conditions, assess the frequency and type of oral mucosal changes, and evaluate the dental examination methodology. Methods A prospective observational study was conducted, combining a feasibility study of early detection of oral cancer and its documentation with phase I ‘modelling’ to conceptualize complex interventions in health services research. Dentists in private practice continuously recruited patients over 6 months and used two different sheets for the documentation of suspicious lesions. Statistical analysis involved descriptive statistics and tests for differences (Welch test) or association (Chi-squared test). Results Twenty-five dentists (mean age: 50 years, 24% females) participated in this study. Eleven dentists achieved the overall aim of recruiting 200 patients. Around 4200 patients (mean age: 52 years, 57.5% females) participated. The prevalence of suspicious lesions was 8.5%. Conclusion It became apparent that a study in cooperation with dentists in private practice to generate clinical-epidemiological data on the early detection of oral mucosal lesions under everyday conditions can be carried out successfully. Further studies with a corresponding level of evidence should be carried out to be able to draw conclusions about the effectiveness of the early detection measure under everyday practice conditions.

The European Union (EU) will implement a Carbon Border Adjustment Mechanism (CBAM) to reach its climate mitigation targets while avoiding the relocation of its industries to countries with less stringent climate policies (carbon leakage). The exact implementation and possible future extensions of such an EU CBAM are still being debated. Here we apply a throughflow-based accounting method on detailed trade network data to assess the coverage of different implementation options. Using a stylized comprehensive EU CBAM as benchmark, we then quantify how an EU CBAM may affect the EU’s trade partners by channeling the EU carbon price to other countries. We find that middle- and low-income countries for which the EU is an important export market would be disproportionally impacted even under conservative implementation options. We finally explore different international revenue recycling schemes to make the EU CBAM inclusive toward vulnerable countries and able to foster global climate cooperation.

Rosette-forming glioneuronal tumors (RGNT) are extremely rare mostly benign tumors of the central nervous system, which are often studied for its histological aspects despite relatively small numbers of clinical especially radiological knowledge.Despite the increasing number of publications on different localizations and treatment protocols, the morphologic and temporal development process of this rare tumor entity is not clear. We were able to coincidentally observe the entire course of the tumor growth of a RGNT on subsequent MRI examinations in a typical case with mild clinical symptoms and no other neurological illnesses, thus possible clinical complications were prevented.

Background The coronavirus pandemic led to a lockdown of public life. For universities, this meant suspensions or corresponding adaptations of practical courses. In Germany, Kiel Dental Clinic received special permission to start practical courses under appropriate hygiene conditions. The study aimed at recording the experiences and associated challenges of course implementation under the special regulations from the perspective of students and teachers. Methods Qualitative guided interviews were conducted with students and teachers at Kiel in the summer semester 2020. Students (4th, 6th, 8th, 10th semesters) were recruited and lecturers responsible for conducting the practical courses within the dental clinic’s four departments. Evaluation was carried out by means of qualitative content analysis, whereby deductive procedures were supplemented by inductive ones. Results Thirty-nine students and 19 lecturers took part. The flow of information at the start of the course was welcomed by students and teachers across the board. The lack of or limited adjustment to the scope tended to be assessed positively by students. The majority of both groups suspected there had been no reduction in learning, and learning had been improved due to the smaller group sizes. Regarding the necessary conditions for conducting the course, positive and negative aspects became apparent. Conclusion Students and teachers felt very relief to start the practical courses under special conditions although the implementation was very challenging for both groups. The structural and content-related course adaptations required a high degree of flexibility on the part of students and lecturers alike, but also meant that courses were able to be conducted without serious deficits in learning gains.

Background One relevant strategy to prevent the onset and progression of type 2 diabetes mellitus (T2DM) focuses on increasing physical activity. The use of activity trackers by patients could enable objective measurement of their regular physical activity in daily life and promote physical activity through the use of a tracker-based intervention. This trial aims to answer three research questions: (1) Is the use of activity trackers suitable for longitudinal assessment of physical activity in everyday life? (2) Does the use of a tracker-based intervention lead to sustainable improvements in the physical activity of healthy individuals and in people with T2DM? (3) Does the accompanying digital motivational intervention lead to sustainable improvements in physical activity for participants using the tracker-based device? Methods The planned study is a randomized controlled trial focused on 1642 participants with and without T2DM for 9 months with regard to their physical activity behavior. Subjects allocated to an intervention group will wear an activity tracker. Half of the subjects in the intervention group will also receive an additional digital motivational intervention. Subjects allocated to the control group will not receive any intervention. The primary outcome is the amount of moderate and vigorous physical activity in minutes and the number of steps per week measured continuously with the activity tracker and assessed by questionnaires at four time points. Secondary endpoints are medical parameters measured at the same four time points. The collected data will be analyzed using inferential statistics and explorative data-mining techniques. Discussion The trial uses an interdisciplinary approach with a team including sports psychologists, sports scientists, health scientists, health care professionals, physicians, and computer scientists. It also involves the processing and analysis of large amounts of data collected with activity trackers. These factors represent particular strengths as well as challenges in the study. Trial Registration The trial is registered at the World Health Organization International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS), DRKS00027064. Registered on 11 November 2021.

SummaryBackground Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

Purpose To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer. Methods We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated. Results There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279). Conclusion Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Background In mid-March 2020, the coronavirus pandemic led to a national lockdown in Germany. Face-to-face teaching was cancelled in universities for the 2020 summer semester. Teaching moved online with no prior IT testing and lecturer training. The study analyses experiences of the suspension of face-to-face teaching and the move to digitalised learning for students and lecturers of dentistry at Kiel. Methods In summer 2020, qualitative guided interviews were conducted with students (4th, 6th, 8th, and 10th semesters), and lecturers. Deductive and inductive qualitative content analysis of the results was carried out. Results Thirty-nine students (69% female) and 19 lecturers (32% female) were interviewed. Reactions to the changes in teaching were observed. Feelings ranged from an essentially positive attitude, through insecurity and uncertainty to a failure to fully appreciate the situation. The loss of social contact was lamented. Digitalisation was associated with technological challenges and additional work. However, it also fostered learning independent of time and place, and encouraged autonomy. Negative aspects of digitalisation included a lack of feedback and loss of interaction. Conclusion The introduction of ad hoc digitalisation challenged both students and lecturers alike. Dealing with lockdown and the changes in teaching and studying required significant flexibility.

Background The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate. Results The target gas purification of cyclotron produced [11C]CO2 and subsequent conversion to [11C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[11C]choline and L-S-methyl-[11C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [11C]MeI. After 18 min N-methyl-[11C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[11C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [11C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [11C]CO2 was passed through. After complete release of [11C]CO2 the reaction mixture was quenched with water and guided through a series of ion exchangers (H+, Ag+ and OH−). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [11C]CO2 before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [11C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%. Conclusion Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate.

BackgroundHypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits.MethodsTreatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score.ResultsCompared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V37Gy(bladder) and V36Gy(rectum) from a mean of 7.4cm3and 2.0cm3to (5.9cm3, 6.1cm3, 5.2cm3) as well as to (1.4cm3, 1.4cm3, 1.0cm3), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation.ConclusionTreatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy.

Randomized trials indicate that electronic or app-based assessment of patient-reported outcomes may improve outcomes in cancer patients. To analyze if an app-based follow-up would be accepted by elderly cancer patients, we conducted a single-center prospective feasibility study (NCT03196050). Cancer patients (≥60 years) without concurrent uncontrolled severe medical conditions and a Karnofsky performance status (KPS) ≥70 were eligible if they were able to use the smartphone app. The primary endpoint was compliance over 1 year, calculated as patient-specific and study date-specific response rate to questions sent as push notifications; in this interim analysis, we report on 4‑month data. Secondary outcomes included a comparison of a subjective health status item (SPHS) with the physician-rated KPS. Out of 225 patients screened, 54 patients agreed to participate and 29 activated the app and participated in the study. The mean age was 66 years (61–78). The individual compliance rate averaged at 58.3% (standard deviation SD = 35%). Daily compliance was 53.3% on average (SD = 10.8%) and declined over time. The average percentage of patients who sent answers at least weekly was 75.0% (SD = 14.8%) and declined from 100% in week 1 to 53.8% in week 17 post-enrollment. Secondary outcomes indicated that questionnaires such as the EORTC-QLQ-C30 are accepted via app and that there is a significant moderate correlation between the SPHS and KPS scores (r = 0.566; p

CINSARC (Complexity INdex in SARComas) is a prognostic signature for soft tissue sarcoma that determines the risk for recurrence and may serve to guide the decision for adjuvant chemotherapy. The aim of this study was to compare the CINSARC signature of pre- and posttreatment biopsies of sarcoma patients treated within a phase I trial evaluating preoperative sunitinib and irradiation.We retrieved 14 pairs of formalin-fixed paraffin-embedded blocks from pretreatment biopsies and posttreatment resection specimens and performed expression profiling of the 67 CINSARC signature genes.In 5/14 patients, both probes were unsuitable for expression analysis because there was no (vital) tissue left in biopsies or resection specimens. Comparing the CINSARC risk classification before and after treatment in the remaining patients, 2/9 shifted from a high- to a low-risk classification for metastatic disease after preoperative treatment with radiation therapy plus sunitinib and 7/9 pairs of pre- and posttreatment biopsies revealed identical results.Concurrent radiation therapy and sunitinib leads to diverging results of prognostic gene array testing in a relevant proportion of sarcoma patients. These changes may reflect tumor heterogeneity, local treatment effects, or prognostic changes of the disease. Caution is advised in the selection of samples and interpretation of test results.HINTERGRUND: CINSARC (Complexity INdex in SARComas) ist eine prognostische Signatur für Weichgewebesarkome, die zur Abschätzung des Metastasierungsrisikos eingesetzt wird und deren Ergebnis die Entscheidung über eine adjuvante Chemotherapie unterstützen kann. Ziel dieser Studie war es, zu untersuchen, inwieweit eine präoperative Therapie mit Bestrahlung und Sunitinib Einfluss auf das CINSARC-Ergebnis hat.In 14 korrespondierenden Paaren von formalinfixierten und paraffineingebetteten Tumorproben (prätherapeutische Biopsie und posttherapeutisches Resektat) erfolgte die Expressionsanalyse der 67 CINSARC-Signaturgene.Bei 5/14 Probenpaaren war ein Vergleich der CINSARC-Signatur nicht möglich, da nach diagnostischer Aufarbeitung bzw. durch Therapieansprechen kein (vitales) Gewebe in den Biopsien oder Resektaten vorhanden war. In 2/9 Patienten verschob sich das Untersuchungsergebnis von einem hohen zu einem niedrigen Metastasierungsrisiko. In 7/9 Probenpaaren blieb die Risikoeinschätzung identisch.Die präoperative Therapie mit Bestrahlung und Sunitinib kann zu abweichenden Ergebnissen prognostischer Gensignaturen führen. Diese Unterschiede können auf Therapieeffekte oder Tumorheterogenität zurückgeführt werden und sollte bei der Probenauswahl und Testinterpretation von prognostischen Signaturen berücksichtigt werden.

The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins1–4. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex5–9 at 3.8-A resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes1–3. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer. The high-resolution cryo-electron microscopy structure of the yeast translocase of the outer mitochondrial membrane reveals key features of mitochondrial protein import that are conserved in all eukaryotes.

Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease. Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in “intermediate”-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed. The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an “intermediate” risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety. For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.