A considerable number of the questions (n = 19) included only a single nutrition-related answer option that was frequently incorrect and served as a distractor. About 0.5% of questions were entirely nutrition related. Despite undeniable barriers, the inclusion of additional nutrition-related examination questions could serve as an incentive to engage students and medical schools in enhancing medical nutrition education. The recently published competence-oriented learning objective catalog in Germany could play a pivotal role in this context, leading to better recognition of nutrition-related topics in medical education.The state of nutrition education in medicine is inadequate, with nutrition-related topics being poorly integrated into lectures. Most medical students receive only a few contact hours of nutrition instruction during their entire time at medical school. Identifying potential barriers that may explain the paucity of nutritional knowledge in medical students is thus of paramount importance. The extent of nutrition coverage in the second part of Germany’s nationwide medical licensing exam is currently unknown. We addressed this issue and assessed nutrition content, as well as students’ scores, in this pivotal test prior to their graduation. We performed a post hoc analysis of six nationwide medical licensing examinations (2018–2020) undertaken by 29,849 medical students and screened 1920 multiple-choice questions for nutrition-related content. Nutrition-related questions accounted for a minority of the questions (2.1%,  Nutrition is one of the cornerstones of a healthy lifestyle . NeverthOne potential strategy to promote healthier eating patterns is nutrition care provided by healthcare professionals . There iThere is now a general consensus that physicians should actively engage in providing nutritional advice  and mustIn the United Kingdom, the latest National Health Service (NHS) Long-Term Plan emphasized that “frontline staff need to feel equipped to talk about nutrition” ; howeverAlthough there is still room for improvement, it is of utmost importance to identify other barriers that may explain the paucity of nutritional knowledge in medical students. Identifying these factors could help to enhance nutrition education and support prospective physicians to play a meaningful role in a much-needed dietary shift towards a more sustainable treatment of chronic diseases .One approach to identifying the potentially mediating factors is to look beyond medical school curriculums. Very few studies have assessed the nutritional knowledge required in students’ final-year exams ,22. HarkComparable data from other countries is scarce but urgently warranted to potentially enhance the nutritional knowledge of medical students. For the very first time, we aimed to assess nutrition coverage in the second part of Germany’s medical licensing exam, a country with numerous medical faculties and a large student body. The main objectives of this study were twofold: (a) to assess nutrition coverage in the second part of Germany’s nationwide medical licensing exam, and (b) to examine how well students scored on the related questions in this pivotal test prior to graduation.Approbationsordnung für Ärzte) in Germany includes a written medical licensing examination for prospective physicians [Erster Abschnitt der Ärztlichen Prüfung) and the second part (termed Zweiter Abschnitt der Ärztlichen Prüfung) [Our study is based on a secondary data analysis of German medical licensing examination questions . The curysicians . This exPrüfung) ,26. The Institut für Medizinische und Pharmazeutische Prüfungsfragen (IMPP)), located in Mainz, Germany [The exams take place twice annually in spring and autumn. One exam contains 320 multiple-choice questions with 5 possible answer options . The adm Germany ,27. All For this study, we analyzed 6 consecutive second-part medical licensing examinations (autumn and spring 2018–2020). Our analysis included 1920 multiple-choice questions in total. In the first step, we identified all multiple-choice questions with at least one nutrition-related answer option. For this, 3 independent reviewers  manually checked all available questions for suitability for inclusion. Each multiple-choice question had five possible answer options. The majority of questions (>90%) followed the so-called “Apos-design”, with 5 answer options (A through E) but only one correct answer. A minority of questions followed the Aneg-design, where 5 answer options exist for which the incorrect has to be identified. Thus, it often occurred that some answers covered nutrition-related aspects while others did not. In such cases, we included the respective questions if there was at least one nutrition-related answer option, irrespective of whether this answer was correct or not. We also categorized the eligible questions according to the number of answer options with nutrition-related content .In the second step, we assigned the questions to one of five pre-defined nutrition-related categories to gain a better understanding of the frequently covered topics in the examined exams. These topics included (1) “causes and treatment of nutrition-related endocrine and metabolic disorders”, (2) “dietary supplements”, (3) “dietary patterns”, (4) “nutrient content and preparation of dietary products”, and (5) “nutritional deficiencies”.Hochschulspezifische Itemanalyse). Moreover, we performed sub-analyses for each of the aforementioned nutrition-related categories. Finally, we stratified the results by gender .In the third step, we contrasted students’ ratings in the selected nutrition-related questions with the average exam rating. For this, we used nationwide statistics provided by the IMPP .We identified 1920 potentially eligible multiple-choice questions that were included in the 2018–2020 German medical licensing examinations. All questions were manually screened by 3 independent reviewers and a total of 1880 questions were excluded for not meeting the pre-specified inclusion criteria. Forty questions remained eligible for the final analysis  .n = 25/40) of questions covered “causes and treatment of nutrition-related endocrine and metabolic disorders”, followed by questions on “dietary supplements” ). The remaining categories each accounted for ≤10% of the total questions.The question classifications based on the pre-defined nutrition-related categories are shown in n = 4 in autumn 2019 and 2020  to n = 11 in spring 2020 .The number of nutrition-related questions per exam is shown in n = 9/40) of the included multiple-choice questions had five nutrition-related answer options. Almost half of those questions (n = 19/40) included only a single nutrition-related answer option. In 50% of cases, these answer options were incorrect . The remaining 30% of questions (n = 12/40) had more than one but less than five possible nutrition-related answers.Only 22.5% (n = 40), great caution is warranted in such comparisons as they are susceptible to bias.In all but one exam (spring 2018), students performed better in the nutrition-related questions compared to the rest of the exam. The average percentage of correct answers to the included nutrition-related question exceeded the 80% threshold in all but two exams (autumn 2020 and spring 2018). The best performance was found in the autumn 2019 exam, where more than 92.5% of students answered the included nutrition-related questions correctly. The worst performance was found in the spring 2018 exam, where less than 65% of students gave correct answers to the included nutrition-related questions. Given the low number of overall questions (We observed a large heterogeneity with regard to the content of the questions. The questions covered a wide array of topics including (but not limited to) vegetarian and vegan diets, ketogenic diets, gluten-free diets, high-fiber diets, high-fat diets, and histamine-free diets. The questions on supplements and nutritional deficiencies covered Vitamin B12 supplementation, iodine supplementation, Vitamin C supplementation, and Vitamin D supplementation. In light of the low number of total questions and the large heterogeneity in the content, we refrained from additional analyses stratified by question category.Finally, we observed that students scored far above average on all questions focusing on “dietary supplements”. On average, students answered these questions correctly in 94.08% of cases. When looking at all nutrition-related questions (2018–2020), this phenomenon was less pronounced. The average percentage of correct answers, in this case, was 81.63%. Notably, this percentage still exceeded the average percentage of correct answers in the remaining exam questions .n = 9), the average percentage of correct answers dropped to 76.78%. An analysis stratified by sex  revealed no substantial intergroup differences.When we analyzed the questions with five nutrition-related answer options only . A substantial number of questions included only a single nutrition-related answer option, which was frequently incorrect and served as a distractor. Less than n = 10 questions were entirely nutrition-related with five nutrition-related answer options. Students scored better on nutrition-related questions compared to the remainder of the exam. Students scored particularly well on questions about dietary supplements. The number of nutrition-related questions did not increase consistently over the investigated 3-year period.Despite the large heterogeneity in the content of the identified questions, we observed several trends worth discussing. Nutrition-related questions accounted for a minority of the total questions  did not allow for valid statistical calculations. Hence, we opted for a descriptive analysis. As discussed earlier, there is a concerning gap between the nutrition competencies required for doctors to provide effective nutrition care and the nutrition education provided in medical schools [The low number of entirely nutrition-related questions  legislative requirements. A comparison with the aforementioned study by Hark et al. thus appears to be more appropriate . The autInternationally, nutrition remains inadequately represented in accreditation and curriculum guidance for medical education at all levels . The facFurthermore, it may be difficult to construct clear and unambiguous questions in this field that are not open to interpretation from a juridical perspective. The field of nutrition is full of controversies as reflected in the recent diverging (or even contradictory) reports concerning the impact of certain food additives, foods, and nutrients on health that are published each year . This man = 9 questions were entirely nutrition-related. When restricting the analysis to these questions, students’ overall scoring was still slightly better compared to the overall exam scoring. This could be interpreted in multiple ways, e.g., as a high interest in nutrition-related topics, profound knowledge in this area, or simply easy-to-answer questions . Again, it must be mentioned that the limited number of questions might adversely affect the validity of our results, and caution is warranted when discussing our results.Students’ high scoring rates in the nutrition-related questions in our study are difficult to interpret, particularly with regard to the fact that only As discussed earlier, the small number of entirely nutrition-related questions shows that this topic only plays a minor role in German licensing exams. Whether this is justified with regard to the potential of medical nutrition education to reduce the health and economic burden of chronic diseases is subject to debate . ChallenNationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0-NKLM) [kompetenzorientierten Gegenstandskatalog Medizin), which was published by the IMPP in December 2020 and is of paramount importance for licensing exam questions [A unique chance to improve nutrition-related education in German medical schools is the new national competency-based catalog of learning objectives for medicine (.0-NKLM) . This cauestions . UpdatedThe latter is an important step forward in the better recognition of nutrition-related topics in medical education in Germany.Previous studies have demonstrated that nutrition education in residency predicts the frequency of residents’ dietary counseling practices . This apThe present analysis has several strengths and weaknesses worth mentioning. As for the strengths, we present the results from a nationally representative and centralized licensing examination in Germany. As opposed to other studies, we did not ask students directly for their personal (subjective) opinion on nutritional education in Germany. Instead of relying on bias-susceptible questionnaires, we analyzed standardized data from a large central database comprising answers from 29,849 students who took the exam in the aforementioned time frame. This concept is probably the biggest strength and innovation of our study, particularly with regard to the high number of screened questions . The manual question screening process conducted by three independent reviewers is an additional strength and reduced the likelihood of missing relevant questions. Additional strengths include the stratified analyses by sex and the comparison to the general exam results.n = 40), which did not allow for a reliable statistical sub-analysis stratified by question category. Adding other exams would have been necessary to increase the number of questions eligible for analysis. Yet, we focused on the “current” state of nutritional education in medicine in Germany, and thus refrained from adding older exam cycles (2017 and older). Despite the modest number of eligible questions, we believe that the present work allows for important insights into the topic under discussion and is—to the best of our knowledge—the first German-based analysis in the literature.However, the present analysis also has limitations worth discussing. The major limitation is probably the modest number of identified nutrition-related questions (We explored the role of nutrition-related questions in the second part of the written medical licensing examination in Germany. Quantitatively, nutrition-related questions played a minor role in all exams and accounted for approximately 2% of the total questions. Approximately 0.5% of the questions were fully nutrition related.Although there are undeniable barriers to including additional nutrition-related questions, this could be an incentive for engaging students and medical schools in enhancing medical nutrition education. As suggested previously, this step should extend beyond counting dedicated teaching hours and mapping nutrition content to a more contextual understanding of the situated learning that occurs for medical students. The new national competency-based catalog of learning objectives for medicine may help to improve nutrition-related education in German medical schools. Attributing a higher value to nutritional education in German medical schools requires a tectonic shift in thinking but will certainly pay off in light of the large potential to reduce the health and economic burden of nutrition-related chronic health conditions.


It is ethical in that “I” am answerable to the other, as a phenomenological reality, in the moment of intersubjectivity.In their article Little, Jordens, and Sayers developed the notion of “discourse communities”—as groups of people who share an ideology and common “language”—with the support of seminal ideas from M.M. Bakhtin. Such communities provide benefits although they may also impose constraints. An ethical community would open to others’ discourse and be committed to critique. Those commitments may counter the limitations of discourse communities. Since their paper was published in 2003, the notion of “discourse communities” has been widely adopted and applied in healthcare and beyond. Their ideas were influential in the founding of an ethics centre in Sydney and contributed to articulating the values which underpin this journal. This commentary notes that an ethical community is fragile in responding to current onslaughts on truth and meaning—potencies inherent in discourse communities. The essay takes Bakhtin’s ideas further to explore intrinsic forces at play in dialogue, language, and art. This leads to discussing the centrality of ethics in Bakhtin’s thought. For him, the essence of discourse is a dialogic exchange which comprises both art and ethics. It is  A.Travelling with the authors in exploring discourse communities;B.Exploring the nature of those communities, as the authors conceive of them, in terms of both the needs and purposes they serve and their constraints on members;C.Considering the extent to which discourse communities may have served the needs and ideals of the authors themselves—which leads into discussing “the possibility of an ethical community”—and what would be required of such a community;D.Discussing the ideologies and values (and fragility) of discourse communities in responding to a current onslaught on truth and meaning; andE.Returning to the Russian theorist—M.M. Bakhtin—from whom the authors drew seminal ideas in support of their approach to discourse communities.This Critical Response to “Discourse communities and the discourse of experience”  along with other professions and members of trade groups such as plumbers and electricians. Discourse communities also include less clearly defined groups such as racists or postmodernists; and followers of a particular religion, members of church groups, family groups, and those with sporting affiliations. Membership within each community is “defined by a particular use of language” (74). Understood in this way, it is apparent that most of us belong to many discourse communities: as family members, members of professional or trade groups, religious followers (or resolute atheists), and aficionados of one or more sporting codes.In the “Discourse communities” paper, the authors developed a notion of The authors observe that each of these communities “draw on the same linguistic resources, the same lexicon and grammar, but construe meanings in different ways” (80). Yet we move between these communities easily and understand the same words as having different meanings within the context of each discourse community. A word—such as “shock”—will be understood among family members and friends differently from the way it is understood by doctors, seismologists, or electricians.There is also a suggestion in this paper, that membership of different discourse communities may shape the way in which we experience events in our lives or at least the way in which we describe those experiences, although they step carefully around the “epistemological status of experience” whilst acknowledging experience is important as “the matrix upon which meaning and values are mounted” .The paper emerged from the authors’ work with cancer survivors and their carers. They observed different discourse communities in that context and differences in the discourse of those communities in speaking of cancer. Cancer patients and their lay-carers spoke of their experience as “victims of circumstance, people to whom things happen” (78) and as being caught in systems “over which they have little control” (78). By contrast Little et al. found that “Administrators, bureaucrats, business people, lawyers and insurance representatives” spoke “as agents of change to the systems in which they work” and of how “they made events into opportunities” (77-78). Doctors and other healthcare workers however, “tell stories which sit somewhere betwixt and between” (78). Whilst they are “clearly agents of change for their patients” and are “involved morally with the extreme experiences of their patients”, they are also “profoundly affected by the vagaries and demands of the administrative and economic systems within which they must work” (78). The proposition that emerges from this analysis is that the “basic division between discourse communities has to be recognized and understood before there can be any prospect of real dialogue between the representatives of different interests in health care” (79).Since this paper was published, the idea of discourse communities has been adopted widely in the literature. There have been numerous citations.Beyond health, the “Discourse communities” paper has been referred to across a wide variety of topics. These include the “troubles” in Ireland . However, there are also risks. As they put it, “Membership … potentially constrains what we should think” (74) or at least constrains what we say we think. The authors refer to this as a colonizing process in which we are obliged to understand and speak in words with fixed meanings and limited usages. In some cases, “discourse communities … can easily slip from benign intent into exploitation” (82) leading vulnerable people, such as those discussed above, to a sense of being “victims of circumstance” (73). This is also reported by patients with Type 2 diabetes . One might assume that Emma-Jane had opportunities to share her experience of cancer with others who had similar experiences—an opportunity which (in the authors’ words) “can be liberating, and even therapeutic” (83). This is an example of a benefit that derives from belonging to a discourse community.Emma-Jane was also uniquely placed to gain from speaking across discourse communities in that her work (with Miles Little and Christopher Jordens) included analysing interviews with cancer patients, clinical carers, and health policymakers. One benefit, from this broader view, is the “possibility of creative dialogue.” One can imagine that participating in their research provided Emma-Jane with the opportunity to understand what “care” meant within those different discourse communities, an understanding not easily gained by fellow members of a cancer survivor discourse community.Humane Medicine, a book which argued for a shift in emphasis from biomedicine to humane medicine . This has been my experience of the Centre also: conversation among colleagues sharing a common interest, conversation of the best kind—about important issues in medicine and healthcare—skilfully facilitated by Miles who invited and encouraged many perspectives within a supportive atmosphere.Professor Little, on retiring as a practising surgeon, set up the Centre for Values, Ethics and the Law in Medicine (VELiM) at the University of Sydney in 1996, as its Director (until 2003). It is apparent that the “Discourse Communities” paper is an expression of his deep commitment to open discourse. He had previously published e Little . The val Jordens . AlthougThese brief glimpses from the authors’ biographies provide some background and understanding of their commitment to the values expressed in the paper, most clearly in the section “The possibility of an ethical community.” An ethical community is presented as a “species of discourse community” which interrogates ideologies including its own. As an interdisciplinary community it would “not be committed to any one model of ethics” but would be committed to “processes of ethical examination using many models.” Its members would be open-minded and dedicated to examining “underlying values that sustain and justify ethical endeavour of all kinds.” It would also be practical in testing “its conclusions by political and social action … in the light of actual happenings and interactions” (82).It is a remarkable achievement that VELiM—recently renamed “Sydney Health Ethics” (SHE)—has been sustained as an ethical community (in just this way) for twenty-five years. All things change however. Recent events threaten to undermine the community as a discrete entity. SHE has lost its formal status as a Centre, and its staff members have been relocated from a separate building and combined with staff of the School of Public Health. Whether or not it survives as an entity, its manifestation and its maintenance for twenty-five years has “spread … its sphere of influence” . Whilst I applaud that as an ideal, it offers no firm foundation for determining a shared reality or even a basis for finding agreement over historical “facts” such as the holocaust or the ransacking of Capitol Hill. Admittedly, this is to raise fraught issues of epistemology and ontology going back to the beginnings of Greek philosophy. It is an issue that is well captured in the debate between Gadamer and Habermas last century  was a Russian philosopher, literary critic, and linguist who wrote voluminously, although much of his writing has been lost. That which has survived has garnered a late following among linguists and literary theorists beyond Russia. The lost material, and publication of his remaining texts, out of their chronological sequence, has however, “led to a partial view of Bakhtin, which obscured the centrality of ethics in his thought” Çalişkan , 2.The Dialogic Imagination . Discourse in the novel is heteroglossic in that the “novel orchestrates … the speech of characters” and many other elements and permits them to “enter the novel.” For Bakhtin, the “fundamental condition, that which makes a novel a novel … is the speaking person and his discourse” . This critique of literary analysis also extends to language itself. “Every concrete utterance of a speaking subject” contains a tension between conforming with normative standards of language (monoglossia) whilst also participating in “speech diversity” (heteroglossia) in that it is individualized . Subjected to these dynamic forces, language is constantly evolving and breaking from the moulds of conventional analysis. It refuses to be confined by rules . This critique is equally applicable to ethics.Little et al. quote from Bakhtin’s essay “Discourse in the novel” which was published in English as one of four essays in In the Introduction I proposed a further journey—to the interior of the terrain that Bakhtin explored—by drawing on his view of ethics and aesthetics in the moment of intersubjectivity.heteroglossia has a primary sense as a feature of any communicative exchange between two (or more) people. The word is a translation of the Russian raznorečie—from raznyĭ  and reč (meaning “word” or “speech”). Any “speech act” or “utterance” is understood by Bakhtin as one side of a dialogue with an other “I.” If one is to relate to another “I” as a subject, not just as an object, then there is an “aesthetic invention” or act of creativity “that occurs between subjects in actual dialogues” . Yet both are also objects to each other. My image of you, and yours of me, are influential and creative in the exchange.For Bakhtin,  Nielsen , 807. Moself is ever in flux: “I occupy a place in once-occurrent Being that is unique and never-repeatable, a place that cannot be taken by anyone else and is impenetrable for anyone else”  in dialogical exchanges. What makes that art profoundly ethical is that “I” am answerable to others in those exchanges, and continue to be answerable across a flux of time. In this sense, Bakhtin’s ideas are revolutionary. In putting them forward, I am emboldened by Little, Jordens, and Sayers’ open-minded commitment to examining many models of ethics. The influence of these authors and the values of the community they founded—along with the values of the Otago Bioethics Centre—are evident in the commitment of the Journal of Bioethical Inquiry to ethics as “dialogue” and to promoting understanding by listening to “diverse voices in a global conversation [across] geographical borders” (Journal of Bioethical InquiryI have previously argued for balancing normative ethics by sensing the aesthetic and by understanding ethics as art Macneill . Bakhin


Non-covalent π-π and dipolar interactions with small aromatic molecules have been widely demonstrated to be a valid option to tune graphene work functions without adding extrinsic scattering centers for charge carriers. In this work, we investigated the interaction between a CVD-graphene monolayer and a thermally evaporated sub-monolayer and the following few-layer thin films of similar perylene diimide derivatives: PDI8-CN2 and PDIF-CN2. The molecular influence on the graphene work function was estimated by XPS and UPS analysis and by investigating the surface potentials via scanning Kelvin probe force microscopy. The perfluorinated decoration and the steric interaction in the early stages of the film growth determined a positive work function shift as high as 0.7 eV in the case of PDIF-CN2, with respect to the value of 4.41 eV for the intrinsic graphene. Our results unambiguously highlight the absence of valence band shifts in the UPS analysis, indicating the prevalence of dipolar interactions between the graphene surface and the organic species enhanced by the presence of the fluorine-enriched moieties. Its hexagonal carbon monolayer structure exhibits a superior electronic quality such that charge carriers can travel ballistically at the micrometer scale with hole and electron mobilities of more than 102 V−1s−1 . Several2 V−1s−1 , electro2 V−1s−1 . Graphen2 V−1s−1 , creatin2 V−1s−1 ,9,10,11.2 V−1s−1 .This framework has given particular attention to its application as a source-drain electrode in organic electronic devices . SeveralF) above (n-type) or below (p-type) the Dirac point (ED ≈ 4.5 eV). The magnitude of the EF shift controls the static excess of holes or electrons without external field-effect gating. This directly impacts the intrinsic conductivity of a graphene sheet and its effective energetic compatibility with an active material in the final device. Graphene is a two-dimensional material sensitive to virtually any intentional and unintentional exposure to external contamination [Given the versatility of graphene when applied as an electrode material, precise control over its doping state is an absolute necessity for tailoring the transport properties and optimizing its integration into a specific device’s architecture. Namely, the doping conditions of graphene are given by the relative position of the Fermi energy  [2) [F shift as being electrostatically mediated by the presence of fluorine (F) atoms [Surface functionalization with polymeric and molecular layers can reliably control graphene’s (Na-NH2) , vanadyl(Na-NH2) , or moleNH2) [2) . On the NH2) [2)  and paraNH2) [2)  have beeNH2) [2) ,32. AnglF) atoms . Despiten-type organic semiconductors [2-C3F7), for the PDIF-CN2 against the alkyl chain-decorated PDIF8-CN2 (C8H17). Both materials share the same electron-withdrawing cyano insertions on the perylene cores. We probed the graphene work function shift and molecule–graphene interaction with PES analysis, supported by an investigation of the surface potential maps retrieved via scanning Kelvin probe force microscopy (SKPFM). This latter technique is based on determining the contact potential difference between a conductive AFM tip and a sample surface with high spatial resolution, unraveling the additional role of the molecular ordering over the total electrostatic interaction at a nanoscopic level.This work will follow this path, investigating in more detail the role of the fluorine-rich molecular end groups over the doping state of the CVD-graphene surfaces. For the scope, we chose two perylene tetracarboxy diimides derivatives (PDI8-CN2 and PDIF-CN2) that have widely been employed as top-performing environmentally stable nductors . The two2(300 nm)/Si multilayered substrates. PDI8-CN2 and PDIF-CN2  were evaporated from powder precursors via organic molecular beam deposition (OMBD) in high vacuum conditions (P ≈ 10−7 mbar). Deposition rates of R = 0.3 nm/min for PDIF-CN2 and R = 0.4 nm/min for PDI8-CN2, respectively, were employed. Before deposition, the graphene substrates were carefully cleaned in an acetone bath and rinsed with ethanol . During the OMBD process, the substrates were kept at 100 °C via an external PID temperature control system. The organic thin film thickness was monitored through a quartz crystal thickness monitor .Samples were fabricated starting from commercial monolayer CVD-graphene  and transferred onto SiOPhotoelectron spectroscopies (PES) were carried out in an ultra-high-vacuum (UHV) system using a VSW HA100 hemispherical electron energy analyzer with a PSP power supply and control  . UV photVcpd) between a sample and a conductive AFM tip when the two are brought into close contact (≈nm) [surfV) through:We inferred the samples’ morphologies and surface potential mappings via non-contact atomic force microscopy (NC-AFM) and amplitude-modulation scanning Kelvin probe force microscopy (AM-SKPFM) using a XE-100 Park Systems  AFM. The SKPFM technique is based on acquiring the contact potential difference (ct (≈nm) ,37,38. T 4.65 eV , the worVAC amplitude of between 1.8 V and 1.9 V.The analysis was carried out in air using an XE-100 Park atomic force microscope respectively equipped with a PPP-NCHR by NanoSensors  for standard NC topographies and NSC14 Cr/Au conductive cantilevers by MikroMash  for the potential mapping via SKPFM. The potential profile signal was demodulated by employing an external Stanford Research System SR830 DSP Lock-in amplifier  using a sinusoidal reference with a frequency of 18 kHz and a t = 1 nm) on the graphene substrate. For both materials . The atomic percentages from the XPS analysis for PDI8-CN2 were C 83.2%, N 8.2%, and O 8.6%, which were in agreement with the theoretical values of 84.0%, 8.0%, and 8.0%, respectively. The C1 core level  deposited on 200 nm SIOPDIF-CN2 showed electronic properties different from those of PDI8-CN2. The atomic percentages were C 60.6%, N 6.4%, O 6.5%, and F 26.5%, in agreement with the theoretical values of 60.6%, 7.2%, 7.2%, and 25.0%, respectively. The C1s core level . As expe2 substrate, while the peak at 533.22 eV was related to the C−O groups [We performed PES analysis on the PDI8-CN2 and PDIF-CN2 thin films deposited on graphene at nominal thicknesses of 2, 4, and 8 nm, and 2, 3, and 10 nm, respectively. The long-range spectra  showed tO groups . AlthougO groups .2 substrate, two additional components related to the imide group in PDI8-CN2, and CO from the graphene substrate. The N1s core levels showed the two known peak structures  energy shifts suggested the presence of band bending, possibly with charge accumulation at the interface, but no new structures due to LUMO orbital filling were present in the HOMO-LUMO gap. The −0.12 eV shift was achieved only at the highest film thickness  in the determination of the energy level alignment at the heterointerface. The low difference between the SKPFM and the UPS values suggests the perfluoroalkyl chains prevent, to a great extent, the intrusion or the adsorption of contaminants [Specifically, the graphene WF moves downwards with respect to the Dirac point up to 5.19 eV when interacting with the PDIF-CN2, i.e., a 0.39 eV difference if compared with the SKPFM analysis performed in air on a bare graphene surface  led to subsequent organic island growth, also with evidence of a de-wetting mechanism at higher coverages. We found the presence of a surface dipole (approximately +0.5 eV), while a weak band-bending (0.1–0.2 eV) occurred at the highest coverage of 10 nm and was likely related to the differently tilted orientations of the molecules.We analyzed the role of two perylenes tetracarboxy diimides derivatives (PDI8-CN2 and PDIF-CN2) in tuning monolayer graphene electronic properties. Using photoelectron spectroscopies and scanning Kelvin probe force microscopy, we investigated the film growth mechanisms, the interface chemical features, and the work function vs. organic film thickness. PDI8-CN2 showed a typical island growth, with molecules tilted on the graphene surface with a mild organic–inorganic interaction, likely modulated by the organic cyano groups. We evidenced the formation of a surface dipole for all film thicknesses, leading to a WF increase of approximately +0.4 eV (at 8 nm) from the pristine graphene and p-type doping conditions. In-vacuum and air analysis techniques led to very similar qualitative results, even if we found a nearly constant quantitative gap between the work function values, likely related to the different working conditions. The stability, diffusion, and possibility to tune the perylenes’ chemical groups make these organic molecules promising for controlling graphene electronic properties, given the possible industrial scale-up and exploiting the OMBD deposition technique compatibility with in-vacuum large-scale production systems. To this aim, we intend to check our systems’ morphologic and electronic properties with time to verify their stability.Our results highlight the role of the perfluoro-alkyl substitution in unambiguously favoring a dipolar graphene–molecule interaction, which significantly tuned the inorganic electronic properties towards


The individual composite endpoints consistently showed a higher incidence in the lower quartiles of L1 SMI (p < 0.001). In multivariable analysis, the lower L1 SMI quartiles independently predicted 3-year all-cause mortality and MACEs , p = 0.007; and OR 12.3 (95% CI 4.99–30.4), p < 0.001). In conclusion, CT-based L1 SMI demonstrated a distinct dose-dependent relationship with future MACEs in CAD patients undergoing percutaneous coronary intervention, thereby enhancing cardiovascular risk stratification.Sarcopenia is as a non-traditional risk factor for atherosclerotic cardiovascular disease. Further investigation is required to elucidate the prognostic significance of computed tomography (CT)-based sarcopenia assessment in coronary artery disease (CAD). We prospectively enrolled 475 patients, who underwent coronary stent implantation and peri-procedural CT scans within one month. Skeletal muscle index (SMI) was assessed cross-sectionally at the first lumbar vertebra (L1) level. The participants were grouped based on sex-specific L1 SMI quartiles. The primary endpoint was all-cause mortality, and the secondary composite endpoint was major adverse cardiovascular events (MACEs) over a 3-year follow-up period. Three-year all-cause mortality and MACE incidence increased significantly in patients in the lower L1 SMI quartiles compared to those of patients in the higher quartiles ( Sarcopenia has gained recognition as a prominent indicator of both frailty and the aging process, often coinciding with functional and metabolic impairments ,2. This Recently, our group demonstrated the prognostic significance of identifying low skeletal muscle mass using CT in patients who underwent successful coronary stent implantation . MoreoveThe study population was prospectively enrolled from the percutaneous coronary intervention (PCI) registry at Korea University Guro Hospital  between January 2004 and April 2014. Data were analyzed retrospectively. The present study was newly conducted as an extended comparative subgroup analysis derived from a previous cohort  to  to 2) ofWe conducted a clinical follow-up for all participants over a duration of up to three years. The primary endpoint in our study was the occurrence of all-cause mortality over 3-year period. The secondary endpoint was 3-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI), and repeat revascularization. Within the definition of mortality, we differentiated between those attributed to cardiovascular and non-cardiovascular causes, which were categorized as cardiac and non-cardiac deaths, respectively. MI was defined as a substantial increase in cardiac biomarkers along with concurrent symptoms or electrocardiogram findings suggestive of coronary ischemia. Repeat revascularization included all cases of clinically driven revascularization, which could involve either coronary artery bypass surgery or PCI and occurred after discharge from the initial procedure. For further clarification, repeat revascularization was specified in relation to the previously treated vessels or lesions. Finally, a landmark analysis at 1-year follow-up was performed to examine the prognostic significance of L1 SMI quartiles over both short- and long-term periods.p-value < 0.05. All analyses were two-tailed. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software version 20.0 .Categorical variables were expressed as frequencies (percentages), and continuous variables were presented as means ± standard deviations or as medians with interquartile ranges. To compare groups across the L1 SMI quartiles, we used Pearson’s chi-square or Fisher’s exact test for categorical variables and one-way analysis of variance or the Kruskal–Wallis test for continuous variables. Pearson’s correlation coefficient was used to examine the correlations between various skeletal muscle measurements. The cumulative incidence rates for the primary and secondary endpoints were examined using the Kaplan–Meier method and compared using the log-rank test. Patients were censored at the time of the initial occurrence of the specific outcome measurement, with survival analysis conducted independently for both the individual outcome and the composite endpoints. Stepwise Cox-proportional hazards regression analysis was performed to assess the prognostic significance of the lower L1 SMI quartiles along with confounding factors. Four models were constructed by incorporating statistically significant or clinically relevant variables with the highest L1 SMI quartile used as the reference group. Statistical significance was defined as a 2/m2 for men and 21.37 ± 2.56, 26.89 ± 1.34, 30.61 ± 0.92, and 35.76 ± 2.87 cm2/m2 for women (both p < 0.001). The lower L1 SMI quartile groups were associated with older age , lower body mass index , and higher burden of atherosclerotic disease for peripheral artery disease . Those with a lower L1 SMI exhibited worse renal and left ventricular systolic function (both p < 0.001), higher levels of inflammatory marker (p = 0.035) and frailty (p = 0.010). The present study enrolled 475 patients who underwent successful coronary stent implantation for CAD with a median follow-up duration of 4.04 (1.25–3.00) years, and 82.3% of the patients completed the clinical visit at 3 years. The median time interval between the index PCI and CT imaging was −2.0 (−10.0–3.0) days, showing no significant difference between the L1 SMI quartile groups. p < 0.001). Notably, both SMA  of the overall study participants. The L3 SMA and L3 SMI measurements showed significantly higher levels with increasing quartiles of L1 SMI (both p = 0.049) and inserted stents (p = 0.043) marginally increased in the lower quartiles compared to those in the higher quartiles of L1 SMI, the overall disease extent, target/culprit lesion complexity, or coronary stent profiles, including the average diameter and total length, did not differ significantly between the L1 SMI quartile groups. The prescription patterns for secondary prevention medications after PCI were mostly consistent, except for higher statin use in the lower L1 SMI quartiles .p < 0.001; p < 0.001), implicating a potential association between non-cardiac medical comorbidities and sarcopenia. p = 0.081). The secondary composite endpoint of 3-year MACE showed a significantly higher incidence in the lower L1 SMI quartiles than in the higher quartiles  and repeat revascularization , also significantly increased in the lower L1 SMI quartiles compared to those in the higher quartiles. Additional stratified analysis based on individual patients’ frailty status showed consistent trends for a higher incidence of 3-year all-cause mortality and MACE  and an 8.45-fold higher risk of MACE , p < 0.001) compared to the risks associated with the highest L1 SMI quartile. These associations remained consistent after adjusting for the constitutional factors of age, sex, and BMI (Model 2) as well as other significant confounding factors observed at index admission (Model 3). On multivariate analysis with full adjustment (Model 4), the L1 SMI quartiles continued to serve as significant predictors of both the primary and secondary endpoints. Specifically, the lowest L1 SMI quartile was associated with a 4.90-fold higher risk of 3-year all-cause mortality , p = 0.007) and a 12.3-fold higher risk of MACE , p < 0.001) compared to the highest L1 SMI quartile. Further details of this stepwise multivariate analysis are provided in The results of the stepwise multivariate analysis are presented in In this prospective all-comer registry study, we used CT-based measurements of L1 SMI and demonstrated a clear association between the future risk of 3-year all-cause mortality and MACE in patients who underwent successful PCI for CAD. Quantitative assessment of skeletal muscle mass using peri-procedural CT revealed a distinct dose–response relationship with future cardiovascular outcomes. This association was particularly pronounced for predicting 3-year all-cause mortality and MACE, underscoring the clinical significance of assessing skeletal muscle mass using L1 SMI. Notably, individuals in the lowest quartile of L1 SMI1 at baseline showed a 4.9-fold and 12.3-fold higher risk of 3-year all-cause mortality and MACE, respectively, than those in the highest quartile. Our stepwise multivariate analysis robustly confirmed the presence of a dose-response association between L1 SMI and 3-year adverse clinical outcomes. Furthermore, landmark analysis at one-year follow-up indicated that L1 SMI has the potential to predict both short- and long-term prognoses. Taken together, CT-based L1 SMI assessment may serve as a compelling quantitative prognostic marker for assessing future cardiovascular risk in CAD patients undergoing PCI.Compared to previously suggested indirect measurement modalities, CT-based skeletal muscle assessment has the key advantage of ensuring precise measurements with a wide range of clinical availability. The measurement of the SMA using CT scans for a specific anatomical region provides an accurate reflection of the muscle mass in a particular area . Traditi2/m2 in males and 25.00 cm2/m2 in females for defining sarcopenia. However, skeletal muscle mass and the diagnostic threshold for defining sarcopenia vary across races, ethnicities, and study populations [Our group recently validated the feasibility of CT-based L1 SMI measurements and demonstrated their prognostic significance in CAD patients undergoing successful PCI for the first time . The CT-ulations ,8,32. AlSarcopenia is a clinical condition with multifactorial causes and associated risk factors. Sarcopenia often coexists with chronic medical conditions, including malignancies, endocrine disorders, chronic kidney diseases, respiratory diseases, autoimmune disorders, and ASCVD ,33. SeveThe current study’s findings suggest that assessing skeletal muscle mass in patients undergoing PCI during the periprocedural period could offer complementary insights along with conventional risk factors. More specifically, the significantly increased risk of non-cardiac mortality implies that sarcopenia is a complex clinical condition frequently associated with various underlying medical comorbidities. Therefore, it may be relevant to conduct a comprehensive assessment of coexisting modifiable medical factors in individuals with sarcopenia to improve overall clinical outcomes. Furthermore, addressing sarcopenia could offer an additional theoretical basis for secondary prevention strategies, including cardiac rehabilitation and non-pharmacological physical intervention in CAD patients. Contemporary guidelines for the management of CAD strongly recommend multidisciplinary cardiovascular rehabilitation as a Class I recommendation based on its favorable impact on overall health ,42. IncrFirst, this study was based on a secondary analysis of non-randomized all-comer registry data. Although we implemented a multiple-stepwise Cox proportional hazards regression analysis, we must acknowledge that residual confounding factors might have influenced the clinical outcomes. Second, measurement of skeletal muscle mass was not the main objective of the CT scans performed in our study. Although our previous study demonstrated that L1 SMI measurements from different CT scan protocols are highly reproducible, future prospective studies should be conducted using a uniform and standardized image acquisition protocol to ensure a more precise and consistent assessment. Additionally, the integration of an artificial intelligence-assisted automated quantification algorithm has the potential to improve the clinical applicability of CT-based skeletal muscle assessments . Third, The skeletal muscle mass, as assessed using L1 SMI, demonstrated a distinct dose-dependent relationship with future adverse clinical outcomes in CAD patients who underwent successful PCI. Integrating CT-based sarcopenia assessment into routine daily clinical practice has the potential to enhance risk stratification and provide valuable prognostic insights for guiding therapeutic decisions in patients with established ASCVD.


A review of patient records showed that significantly more slow-progressing patients were exposed to NSAIDs (p = 0.003). PGE2/PDE4 signaling may be involved in IPF progression. These findings should be further studied.The ECM propagates processes in idiopathic pulmonary fibrosis (IPF), leading to progressive lung scarring. We established an IPF-conditioned matrix (IPF-CM) system as a platform for testing drug candidates. Here, we tested the involvement of a PGE2 and PDE4 inhibitor, Roflumilast, in the IPF-CM system. Primary normal/IPF tissue-derived human lung fibroblasts (N/IPF-HLFs) were cultured on Matrigel and then removed to create the IPF-CM. N-HLFs were exposed to the IPF-CM/N-CM with/without PGE2 (1 nM) and Roflumilast (1 µM) for 24 h. The effect of the IPF-CM on cell phenotype and pro-fibrotic gene expression was tested. In addition, electronic records of 107 patients with up to 15-year follow-up were retrospectively reviewed. Patients were defined as slow/rapid progressors using forced vital capacity (FVC) annual decline. Medication exposure was examined. N-HLFs cultured on IPF-CM were arranged in large aggregates as a result of increased proliferation, migration and differentiation. A PGE2 and Roflumilast combination blocked the large aggregate formation induced by the IPF-CM ( Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia that is characterized by scar tissue formation and excessive extracellular matrix (ECM) deposition, resulting in the loss of lung function ,2. A majThe ECM plays a significant role in fibrosis progression. As reviewed , IPF-ECMCOX-2 expression is regulated via several signals of injury and inflammation . An abnoIn this study, we explored the effect of PGE2 and PDE4 inhibition on the IPF-CM system as further support to previously published evidence for this approach in IPF.p < 0.001) as well as the total number of cells. Recently, we combined the aggregate size and aggregate number values to create a new, more accurate parameter, the average aggregate size, as published in [p < 0.0001 and p < 0.05, respectively, p < 0.05, p < 0.05, The main outcome of the IPF-CM system is large aggregate formation . As prevished in . Here, wp < 0.05, p < 0.05, Pro-fibrotic gene expression was also tested. We found that COL1A, ACTA2, TGFB1 and MMP2, which were not affected by PGE2 alone, were completely inhibited by the addition of PGE2 + Roflumilast  and reviewed their medication intake. Study population included 107 patients diagnosed with IPF; of them, 62 were classified as SP and 45 as RP, as described in the Moreover, during follow-up, pulmonary function tests were significantly better in patients from the SP group, including forced vital capacity (FVC), total lung capacity (TLC), DLCO and 6 min walking test (6MWT) parameters .p = 0.833, p = 0.71, p = 0. 409, p = 0.271, p = 0.003, Most patients with IPF, as with other patients over the age of 60, suffer from various comorbidities and are prescribed several concomitant medications. These include proton pump inhibitors, anticoagulants, statins, antihypertensive drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), etc. . Thus, wThe ECM plays a major role in IPF progression . In thisPGE2 was shown to inhibit fibroblast proliferation, collagen synthesis and the modulation of TGFβ-induced fibroblast to myofibroblast transition ,27,28. MRoflumilast, a long-acting selective inhibitor of PDE4, had a positive effect by reducing aggregate size and cell migration. The Roflumilast + PGE2 combination inhibited the increase in pro-fibrotic gene expression. This is supported by in vitro ,23, as wInterestingly, Roflumilast with PGE2 had a significantly stronger effect than Roflumilast alone. PDE4 inhibitors, such as Roflumilast, prevent the breakdown of cAMP, while TGFβ modulates cAMP by altering the metabolism of PGE2. The effect of PDE4 inhibitors may have been mediated through a cAMP-stimulated protein kinase, and it depended on fibroblast production of PGE2 and TGFβ-induced PGE2 production. From our results, which show a significant effect of PGE2 addition alone, we can carefully assume that PGE2 levels in the culture are not saturated. Thus, by adding PGE2, we somewhat increased the ‘inflammatory’ state of the culture, also affecting TGFβ signaling and mimicking an inflammation that often, but not always, is present in IPF. Cortijo et al.  suggesteAs recently reviewed by Claire Lugnier, PDE4 inhibition has many possible downstream pathways, leading to reduced inflammation, reduced oxidative stress, TNF-α, and cytokine production , which aOur findings require further research, as there may be several mechanisms of action to achieve the reduction in aggregate formation, which was previously shown to be correlated with the pro-fibrotic phenotype of the HLFs. However, although we did not elucidate the exact mechanism, we prove further evidence of the potential benefit of this already approved treatment for another indication. Due to the inclusion criteria, patients with COPD were not included, and thus, no data regarding Roflumilast were available in this cohort.HIF1A is a facilitator of fibrosis, and it has been considered a pro-inflammatory factor  as well Despite its inevitably progressive nature, IPF is characterized by a highly variable disease course, which makes the natural history of the disease largely unpredictable in individual patients . Our stuIn this relatively preliminary analysis, we examined medication exposure to five major groups of concomitant treatments between the SP and RP patients during the follow-up period of up to 15 years. The medications were grouped into major categories, as the population size was limited. Here, we demonstrated that patients classified as RP were less exposed to NSAID treatment during the course of their illness. Other treatment groups did not reach significance, although some trends were observed. It is important to emphasize, however, that drug exposure in our study was not limited to selective COX-2 inhibitors. Naproxen, a classical NSAID, was found to be effective in reducing lung inflammation and preventing collagen accumulation in a murine model of bleomycin-induced pulmonary fibrosis . InteresOur study has several limitations. First of all, it is a retrospective cohort based on electronic databases where medication exposure is based on those purchased by patients. We were also not able to assess the indications for which the medications were prescribed, which may also influence outcome.Secondly, the follow-up period was very diverse among patients, . Hence, based on the inclusion criteria, a significant drug exposure could range from 6 months to several years, resulting in difficulty interpreting the actual influence of drug exposure among various patients. Thirdly, naturally due to the inconsistent nature of NSAID exposure, we had to define a certain cutoff level. However, as discussed above, the timing of exposure to this class of drugs during disease progression could prove important. Since this is an in vitro study, all drawn conclusions should be cautiously considered.IPF fibroblasts modify the ECM differently than normal fibroblasts, thus creating a CM that further propagates the ‘IPF-like’ phenotype of normal fibroblasts. We found that PGE2 and Roflumilast inhibit the pro-fibrotic effects of IPF-CM. Further research is needed in order to establish this as a possible treatment for IPF.2 at 37 °C. Experiments were performed as previously described [4OH, and N-HLFs were added for further culture. PGE2  and Roflumilast  were diluted in DMSO and added an hour prior to the addition of N-HLFs to the culture.Primary HLFs were isolated from IPF tissues and control samples at the time of biopsy, as described ,41. Follescribed . Brieflyhttps://imagej.nih.gov/ij/download.html, accessed on 1 January 2023. Results were normalized to control (N-CM).Cell cultures were inspected utilizing an Olympus IX71 microscope. The aggregate size and number were evaluated utilizing the ImageJ software: RNA was extracted by a RNeasy kit  and converted to cDNA using GeneAmp . Reactions were performed with SYBR Green  according to the manufacturer’s guidelines. Reactions were set to 40 cycles. Primers sequences  (5′-3′): GAPDH: F-CTCTGCTCCTCCTGTTCGAC, R-TTAAAAGCAGCCCTGGTGAC; MMP2: F-CAAGGACCGGTTTATTTGGC, R-ATTCCCTGCGAAGAACACAGC; IL8: F-CTCTTGGCAGCCTTCCTGATTT, R-TGGGGTGGAAAGGTTTGGAGTA; COL1A: F-CGAAGACATCCCACCAATCAC, R-CAGATCACGTCATCGCACAAC; ACTA2: F-TGAGAAGAGTTACGAGTTGCCTGAT, R-GCAGACTCCATCCCGATGAA; TGFB1: F-TTTTGATGTCACCGGAGTTG, R-AACCCGTTGATGTCCACTTG. GAPDH was used as control.4) were placed in 96-well plates and allowed to adhere for 24 h. Wound closure was monitored immediately after scratching and at 24 h. Areas were measured using ImageJ .HLFs  by flow cytometry according to the manufacturer’s instructions. AnnexinV+/PI− cells were considered apoptotic, and AnnexinV+/PI+ cells were considered late apoptotic/necrotic. Total cell death was the sum of both. All results are expressed as the percent of the total cell number.Assessment of apoptosis/necrosis was conducted with AnnexinV-FITC supplemented with PI  and by SPSS . ANOVA was performed to compare differences between multiple cohorts. Paired Student’s


The growth mode is controlled by limitingthe air exposure of the irradiated substrate and the time betweenirradiation and growth. We conducted Raman mapping, Kelvin-probe forcemicroscopy, X-ray photoelectron spectroscopy, and density-functionaltheory modeling studies to investigate the selective growth mechanism.We conclude that the selective growth is explained by the competitionof three effects: EB-induced defects, adsorption of carbon species,and electrostatic interaction. The method here is a critical steptoward the industry-scale fabrication of 2D-materials-based devices.Van der Waals heterostructures (vdWHSs) enable the fabricationof complex electronic devices based on two-dimensional (2D) materials.Ideally, these vdWHSs should be fabricated in a scalable and repeatableway and only in the specific areas of the substrate to lower the numberof technological operations inducing defects and impurities. Here,we present a method of selective fabrication of vdWHSs via chemicalvapor deposition by electron-beam (EB) irradiation. We distinguishtwo growth modes: positive  on graphene and tungsten disulfide (WS For example, stacking different 2D materialsallows the fabrication of non-volatile flash memory,9 light-emitting diodes,10 orgas sensors.11Two-dimensional (2D) materialsstacked in the van der Waals heterostructures(vdWHSs) provide a unique playground for studying fundamental physics.Among the most substantial breakthroughs enabled by 2D materials stacks,one can indicate the discovery of unconventional superconductivityin magic-angle twisted bilayer graphene14 limiting the performance of the created electronic devices. Furthermore,exfoliation cannot be scaled to satisfy the needs of the electronicsindustry; hence, a repeatable and scalable method of fabricating vdWHSsis necessary. Among different synthesis methods, chemical vapor deposition(CVD) has already proved to yield transfer-free heterostructures oftwo or more different 2D materials aligned vertically or laterally.17 Notably, vertically-aligned stacks are preferable for electronicapplications due to the more robust electrical contact between layers.19However, most 2D-baseddevices are fabricated using exfoliatedand transferred 2D materials, which hinders their practical applications.Exfoliation induces defects and contamination in the layers,20 and van der Waals heterostructures.21 Initially, selective growth was enabled by coatingthe substrate with photopolymer and subsequent deposition of seeds23 or modification of the substrate by partial etching.25 However, these methods require photolithographic pretreatment ofthe substrate, which provides little advantage compared to etchinga complete 2D monolayer. More recent approaches include laser etchingof 2D substrates, enabling the growth of vertical26 and lateral27 vdWHSs, or Hefocused-ion-beam-induced defects in graphene serving as controllablenucleation sites.28 Still, these methodsheavily damage the substrate or need an elaborate experimental setup.An interesting approach is proposed by Ryu et al., showing a triboelectric-basedmethod, which, however, significantly limits the shape of the selectivegrowth area.29Ideally, the area of the substrate where the 2D materialsare synthesizedshould be easily controlled, as it limits the number of subsequenttechnological operations, including photopolymer spin-coating andchemical etching, and preserves the pristine surface. To date, selectivegrowth of 2D materials has been achieved for single 2D materials2,we achieved highly selective growth of molybdenum disulfide (MoS2) and tungsten disulfide (WS2) in the irradiatedareas, both by metal–organic and powder-based CVD. The selectivegrowth of MoS2 was also achieved on the WS2 substrate,and we observed graphene self-healing after the subsequent TMDs synthesis.In this work, we presenta selective growth method based on electron-beam(EB) irradiation of 2D substrates. By irradiating a graphene substratewith an electron dose no lower than 5000 μC/cmFurthermore, we are able to block nucleation in the irradiatedareas with 100 nm spatial resolution by limiting the substrate airexposure and time between irradiation and growth. These two growthmodes are referred to as “positive” and “negative,”respectively, in a manner similar to the photoresist types. To investigatethe selective growth model, we conducted Raman mapping, Kelvin-probeforce microscopy (KPFM), X-ray photoelectron spectroscopy (XPS), anddensity-functional theory (DFT) modeling studies. Three competingmechanisms cause the observed effects: mild degradation of the 2Dsubstrate, adsorption of carbon species during EB irradiation andair exposure, and electrostatic influence of the charged substrate.Considering that the presented method allows self-healing of graphene,provides exceptional spatial resolution, and enables control of thepositive and negative growth, it is foreseen to revolutionize theindustrial-scale growth of van der Waals heterostructures for electronics.22.12 . As presented in 30 but practically indistinguishable in secondaryelectrons imaging (S2). Notably, by using EBlithography, it is possible to irradiate large areas with high spatialresolution up to 100 nm .For the selective growth, CVD graphene on sapphire was irradiatedwith electron doses varying between 1000 and 2,000,000 μC/cm2 S1. As pr imaging 1b and S2Figure S4),albeit the spectra confirm the presence of graphene structure, withoutgraphene oxide31 or amorphous carbon.32 The difference in the ratio of D and G peaksintensity between pristine and irradiated regions is clear, as shownin a large Raman spatial mapping . Furthermore, the Raman spatial mapping enabled us to deconvolutestrain and doping in the irradiated areas.33 As presented in n-type.Raman spectra show that graphene is moderatelydegraded, expressedby a more intense D peak S4,albei2.22 and WS2 on the irradiated graphenesubstrates (both CVD and transferred) has been performed mainly ina tube furnace using molybdenum trioxide (MoO3), tungstentrioxide (WO3), and sulfur powders. Still, to prove theversatility of our method, some of the growth processes were conductedin a metal–organic CVD (MOCVD) system with molybdenum hexacarbonyl(Mo(CO)6) and diethyl sulfide (DES) as precursors. Ourexperiments indicated that it is necessary to age the irradiated substratesby exposing them to ambient air for at least 24 h to achieve positivegrowth. The aging process can be enhanced by mild annealing of thesamples on a hot plate set to 70 °C.The selectivegrowth of MoS2 and WS2 is highly selective, as presentedin 2 (2), and the nucleation is higherin the areas irradiated with higher electron dose. Notably, due toa higher number of defects (both impurities and wrinkles), highernucleation is expected on transferred than CVD-grown samples. Furthermore,MoS2 nucleated more readily on irradiated WS2/graphene heterostructure .It proves that besides graphene, also WS2 and probablyother 2D materials can be used as a substrate for selective growthenabled by electron beam irradiation.The positive growthof MoStedin 2 2a nuclea2 on WS2/graphene presented in Figure S6 was achieved not by EB lithography but by an ordinarySEM imagingperformed on a sample that was kept in an SEM chamber at 10–6 mbar for 16 h prior to characterization. One possible explanationis that during the 16 h period, carbon species from the chamber depositedonto the surface, and the imaging electron beam, much less intensethan the typical EB irradiation used throughout the study, was ableto cause the selective growth. Other samples characterized by SEMthat were not kept in the chamber prior to characterization did notexhibit the selective growth effect.Interestingly, the preferential growth of MoS2, WS2 nucleated preferentiallyin the graphene areas irradiated with higher doses  indicated that nucleationstarts directly on the irradiated spots, visible as a matrix of domainsseparated by 200 nm—the distance between irradiation points.Similar results obtained on CVD-grown and transferred graphene indicatethat the supporting material below the 2D substrate (SiO2 or sapphire in our study) does not influence selective growth.Similar to MoSer doses 2b. The mdoses . The interface is atomically sharp,with no contamination visible. The monolayered nature of the synthesizedWS2 is also confirmed by PL measurements (2 photoluminescence (PL) peak on irradiated and pristinegraphene. Thus, the irradiation does not influence the subsequentgrowth of other 2D materials. The uniformity of PL intensity of thesynthesized WS2 is also excellent, as shown in Figure S9. Interestingly, the Raman spectrumof irradiated graphene does not show signs of degradation (as in S10). In addition, atomic forcemicroscopy (AFM) images prove that graphene is not degraded afterthe growth process . The proposedmechanism of self-healing is discussed later.High-resolution transmission electron microscopy (HRTEM) imagesand energy-dispersive X-ray spectroscopy (EDX) confirmed that monolayerWSgraphene S8. The igraphene S8. The i2.32 2LA(M) Raman peak  using a mechanical mask, excluding the impact of the hydrocarbondeposition. As presented in  regions 4c,d. How2 layers. It is explained by the fact that 2D materialsnucleate more readily on the defects, or, more precisely, the danglingbonds—energetically favorable locations that serve as nucleationspots for 2D materials.40 Still, the mechanicaldegradation of the layer cannot explain the self-healing process observedin the positive and negative mechanisms. Thus, we suggest that duringEB irradiation, a number of various carbon species are deposited onthe surface of graphene. During the subsequent growth of MoS2 or WS2, these carbonaceous adsorbates serve as “repairkits” for the graphene layer, leading to the self-healing mechanism.Furthermore, in the case of positive growth, the graphene surfaceis exposed to ambient air and airborne contamination that can be adsorbedon the defective graphene. For this reason, the observed self-healingis more pronounced in the positive than negative growth. In addition,self-healing is not observed in the case of RIE-processed samples.Therefore, the mechanism of selective growth byEB irradiationis at least partially based on a mechanical degradation of grapheneand WSSupporting Note 1, a clear conclusion cannot be made based only on thermodynamicand kinetic explanations. Still, a hypothesis for the negative growthcause can be based on electrostatic interaction. As presented in SEMand Raman characterization .Nevertheless, the causefor the change from positive to negativegrowth mode is elusive. Despite the supplementary discussion on the2D materials growth mechanism presented in rization 1b,e, gra2 dose than on pristine graphene. However, thetopography of the irradiated regions differs significantly after themild annealing  measurementsof the graphene immediately after EB irradiation and after 66 h agingat 70 °C in ambient air 5a,b. Thennealing 5c,d. AftHigh-resolution X-ray photoemission spectroscopywas conductedon the irradiated aged graphene substrate to further confirm the proposedselective growth mechanism. As shown in ID/IG mapping . The regions with the three highest doses  started to grow in positivegrowth mode, but lower doses were still negative. This suggests thatthere is a competition between defect-mediated and electrostatic-mediatedgrowth.In addition,we observed that one of the growth processes resultedin mixed negative and positive growth, and the positive and negativegrowth regions have different work functions . Thesimulations indicate that the binding energy between graphene andWS2 is increased when vacancies are introduced to graphene.However, this energy is slightly decreased with the introduction ofa negative charge (Table S1). These simulationsalign with the experimental results and indicate that defectivenessand electronic doping of the graphene substrate influence the nucleationof 2D materials.To test the selective growth model further, we conductedsimplifiedDFT studies considering a supercell with graphene and a W42 substrates by EB irradiation.By irradiating 2D substrates with doses between 5000 and 2,000,000μC/cm2, it is possible to achieve selective growthof MoS2 and WS2 by CVD and MOCVD. Notably, ourresults show that the optimal value of irradiation doses is between10,000 and 100,000 μC/cm2. The growth mode can bemanipulated by modifying the time between EB irradiation and growthand air exposure. If both periods are limited, the growth is negative,i.e., nucleation of TMDs is prohibited in the irradiated areas. Inthe other case, growth occurs in the EB-irradiated regions. Furthermore,our method allows for the self-healing of the graphene substrate.The self-healing is explained by the adsorption of carbon speciesduring EB irradiation and exposure to ambient air, which providescarbon atoms necessary to reconstruct the perfect crystal latticeof graphene during the CVD growth at elevated temperatures.In conclusion, we presenteda method allowing selective growthof TMDs on graphene and WSThe selective growth mechanism was investigated with multiple methods,including Raman mapping, KPFM, XPS, and DFT studies. Based on theseresults, we propose that the selective growth mechanism is based ona competition of three effects: mechanical degradation of the 2D substrate,adsorption of carbon species on substrate surfaces, and electrostaticinteraction between the substrate and the precursor molecules. Asthis method is easily applicable via EB lithography and is suitablefor a wide range of 2D materials, we suggest that it can be a criticalstep in simplifying the technological workflows of the productionof 2D-materials-based nanoelectronics.55.12/Si, CVD graphene on sapphire, andCVD WS2 on CVD graphene on sapphire were used as substrates.Graphene transferred onto SiO2/Si was purchased from Graphenea.Polycrystalline CVD graphene was synthesized on 2 in. c-plane sapphire in an experimental close-couple showerhead AIXTRONreactor. The graphene growth was conducted at 1560 °C for 4 minwith methane as a carbon precursor. The detailed graphene growth procedurewas presented elsewhere.44 The WS2 substrate was synthesized on CVD graphene/sapphire according tothe procedure presented in CVD graphenetransferred onto SiO2/Si were irradiated with doses ranging from 1000 to 2,000,000μC/cm2 in an array of different shapes presentedin Figure S1. The electron beam was focusedto 2 nm, and the irradiation was done in 200 × 200 nm steps.For positive growth, the as-irradiated samples were kept in the airat room temperature for at least 24 h, and the best results were achievedby aging the samples on a hot plate at 70 °C for 66 h. For thenegative growth, the substrates were transferred from EB lithographyto the CVD reactor in under 1 h. These samples were vacuum-packedfor transportation, so the total air exposure was limited to approx.10 min. The WS2/graphene substrate for the selective growthof MoS2 was kept in the SEM chamber for 16 h under a vacuumof 10–6 mbar and then investigated using standardparameters described in EB irradiation was conducted in RaitheLine plus EB lithography. Graphene on sapphire and graphene on SiO5.22 and WS2 was conductedin a 2 in. tube furnace at 770 and 900 °C, respectively. As precursors,sublimed sulfur  and MoO3  or WO3  were used with a smalladdition (2–10 mg) of NaCl . The growthswere conducted for 15 min in an Ar atmosphere. The detailed MoS2 and WS2 growth procedures were presented elsewhere.46CVD growth of MoS2 was conducted in a 4 in. tubefurnace using molybdenum hexacarbonyl and diethyl sulfide as precursorsunder a hydrogen and argon atmosphere. The growth was conducted at870 °C for 60 min. The detailed MoS2 growth procedurewas presented elsewhere.47MOCVD growth of MoS5.3The morphology ofthe samples was investigated using a Raith eLine plus scanning electronmicroscope with in-lens and secondary electron detectors. Typically,the samples were characterized with 1 and 10 kV accelerating voltagewith 6.2 mm working distance and 7 μm aperture.A BrukerDimension Icon atomic force microscope allowed investigation of thesamples’ topography in tapping mode using supersharp tips  and surface potential in Kelvin-probe mode using Pt–Ircoated tips with 25 nm nominal radius.Chemical compositionand photoluminescence were measured usinga Renishaw inVia Qontor Raman spectrometer. A 532 nm laser with 12.5mW and ×100 objective was used for these measurements. The Ramanspatial maps were typically measured using 500 and 2000 nm steps.2/graphene interfacehave been investigated with an FEI-Titan 80-300 transmission electronmicroscope operating at 300 kV, equipped with an image corrector.Before sample preparation, needed for TEM purposes, the investigatedmaterial was covered with an amorphous carbon protective layer ofapproximately 5 nm. Subsequently, an FEI-Helios Nanolab 600 FIB wasused to prepare the WS2/graphene/sapphire interface cross-sectionspecimen by a focused ion beam (FIB) equipped with an OmniProbe nanomanipulatorand platinum gas injection system (GIS). The standard polycrystallineplatinum layer was deposited on the specimen to protect the materialfrom damage during FIB lamella cutting out. The elemental compositiondetermination was performed by EDX using an EDAX 30 mm2 Si(Li) detector.The structural properties of the WS–10 mbar. A hemispherical energy analyzer Phoibos 150(SPECS) with a 2D-CCD detector and the DAR 400 X-ray source with MgKα (1253.64 eV) non-monochromatic radiation was used. The XPSspectra were analyzed with the CasaXPS software. The XPS data analysisinvolved Shirley background subtraction and curve-fitting (mixed Gaussian–Lorentzianfunction with 85% of Gaussian for carbon oxides and asymmetric Doniach-Sunjicline shape for graphene).XPS measurements were performed at room temperaturein a UHV MultiprobeP (Scienta-Omicron) system with a base pressure of 5 × 105.450 To study the bindingenergies between the as-grown 9-atom WS2 clusters (W3S6) and graphene layers , we considered 4 × 4 graphene supercells (31–32carbon atoms) with the adsorbed W3S6 clusterat one side . The details ofthe modeling are presented in Supporting Note 2.We performedtheoretical simulations using the DFT method as implemented in theQuantum ESPRESSO v.7.0 software.5.5Using Raith eLineplus EB lithography, followed by a lift-off process, we fabricated5 nm Cr/100 nm Au contacts to the vdWHS layers. The electrical measurementshave been done with National Instruments DAQ USB-6366 and currentpreamplifier DL Instruments 1211. White halogen light provided scatteredillumination.5.62.Before electrical measurements, the devices were treated with surfacecleaning and sensitizing plasma treatment. The plasma was providedby a Diener electronic Zepto plasma cleaner with the gas mixture ofargon and oxygen of equal proportions . The treatment cleaned the surface of the aged sample and enhancedthe effect of photoconductivity observed in WS