Online platforms allow individuals to connect with others, share experiences, and find communities with similar interests, providing a sense of belonging and reducing feelings of isolation. Numerous previous studies examined the content of online health communities to gain insights into the sentiments surrounding mental health conditions. However, there is a noticeable gap in the research landscape, as no study has specifically concentrated on conducting an in-depth analysis or providing a comprehensive visualization of Bipolar disorder. Therefore, this study aimed to address this gap by examining the Bipolar subreddit online community, where we collected 1,460,447 posts as plain text documents for analysis. By employing LDA topic modeling and sentiment analysis, we found that the Bipolar disorder online community on Reddit discussed various aspects of the condition, including symptoms, mood swings, diagnosis, and medication. Users shared personal experiences, challenges, and coping strategies, seeking support and connection. Discussions related to therapy and medication were prevalent, emphasizing the importance of finding suitable therapists and managing medication side effects. The online community serves as a platform for seeking help, advice, and information, highlighting the role of social support in managing bipolar disorder. This study enhances our understanding of individuals living with bipolar disorder and provides valuable insights and feedback for researchers developing mental health interventions. With the rapid increase in the number of social media users, social media has become a powerful tool for sharing medical information, gathering user feedback, and establishing support networks , such as functioning and social skills. For example, linguistic and phonological features were applied to detect the early stages of BD from Twitter using a supervised machine-learning approach , by examining social media texts, in order to answer the following research questions:RQ1. What are the main topics and discussions related to bipolar disorder within the Bipolar subreddit?RQ2. What sentiments are expressed by users in the Bipolar subreddit when discussing their experiences with bipolar disorder?RQ3. How does the Bipolar subreddit serve as a platform for seeking help, advice, and information related to bipolar disorder?RQ4. What role does social support play in managing bipolar disorder within the Bipolar subreddit?The findings of this study can contribute to a better understanding of individuals living with BD and offer valuable insights and feedback for researchers developing health interventions. Social media analytics can be used to track the impact and reach of health interventions in real time, allowing for the refinement and adaptation of interventions to maximize their effectiveness. Furthermore, the research framework of this study can be applied to the study of other health conditions as well.This study aimed to examine social media discussions within Bipolar subreddit communities. The experiment utilized topic modeling and sentiment analysis to identify hidden topics and observe polarity in social media data, respectively.www.reddit.com). A finite set of two subreddits related to bipolar disorder, including https://www.reddit.com/r/bipolar and https://www.reddit.com/r/bippolar2, was selected for analysis. The subreddit “r/bipolar” community, dedicated to bipolar-related issues, has over 85.5 k members, while the subreddit “r/bipolar2” has 13.5 k members who live with bipolar disorder type 2 and encompass the entire bipolar spectrum.The data used for this study was collected from the Reddit community . Posts consist of the initial textual statements that initiate communication with other users, while comments are replies to these posts, organized in a tree-like structure  content in Reddit. Topic modeling is a probabilistic generative model based on the assumption that documents contain a mixture of topics consisting of the highest probability for each word. This statistical model helps identify abstract topics that occur in collections of documents. A topic represents a cluster of words that frequently appear together. In this study, we utilized Latent Dirichlet Allocation (LDA) for topic analysis, an unsupervised model that automatically clusters words into topics and associates documents with those topics. The underlying assumption is that a text document has a probability distribution over a mixture of “topics,” where each topic is associated with a distribution over words, and each word is drawn from the mixture  for document d.The dirichlet distribution (α) generates the topic distribution (θd) assigns the topic  for word n of document d.The multinomial distribution of the topic (θk) generate the topic distribution .The corresponding topics from the dirichlet distribution  generates the words .The multinomial distribution of topics  resulted in an overlap of topic words across most topics. Consequently, we determined the optimal number of topics to be 30 for the overview topics and to be 20 for the sentiment topics.The LDA algorithm was employed to perform clustering, aiming to identify coherent topics within the dataset. It was observed that a higher coherence score yielded better clustering results. Coherence served as a metric for determining the optimal number of clusters. The coherence scores were calculated using the scikit-learn metric package. We conducted experiments by varying the number of cluster parameters from 5 to 50, with intervals of 5. Among these values, the coherence score was highest when the number of topics (K) was set to 10. However, we conducted a manual inspection of the data. Upon manual inspection, it became evident that the results were most distinct and interpretable when the Finally, we considered the list of top words in the probability distribution for each topic to assign a name to that specific topic. In other words, this interpretative process of labeling LDA topic outputs involves selecting a set of words from each topic's probability distribution that best represents the theme or subject of that topic. These words essentially serve as labels or names for the topics. Therefore, this process entails selecting words from each topic's probability distribution to provide a meaningful name or label that captures its content or theme. Afterward, we measured the agreement among three annotators regarding the labeling of the topics.An essential task in sentiment analysis is to classify the polarity of a given text at the sentence or document level, determining whether the expressed opinion is positive, negative, or neutral. Advanced sentiment classification can also identify emotions such as happiness, sadness, and anger, providing insights into the psychological patterns in text based on the analysis of human verbal behavior  was utilized for automatic sentiment analysis. SentiStrength is specifically designed for analyzing social web texts and predicts the strength of positive and negative sentiment in short texts, even for informal language, by employing a lexical approach. The sentiment analysis captures reactions to events through free texts, offering new insights into human behavior and people's positive or negative attitudes toward an event  to 5 (very strong positive sentiment) and a negative sentiment strength ranging from −1 (no negative sentiment) to −5 (very strong negative sentiment) to each text (zeros are not used). In the presence of multiple sentiment words, the strongest sentiment word is chosen, while in the absence of sentiment words, a neutral sentiment is assumed. Additionally, the software incorporates special rules for handling negations, questions, booster words , emoticons, and various other special cases  and their top 30 words are as follows:Topic 1. Help and advice (0.161): Social media users shared their conditions, asked for help and information, and expressed appreciation.Topic 2. Bipolar disorder (0.158): Discussions about symptoms, mood swings, diagnosis, and medication.Topic 3. Social process (0.139): Patients expressed the need for mental support from their social environment, such as family and friends.Topic 4. Therapy (0.120): Experiences shared regarding medicine, doctors, and psychiatrists.Topic 5. Drugs (0.116): Discussions about medications used for BD and related mental health issues on Reddit, including Lithium, Lamictal, and Wellbutrin.Topic 6. Episode (0.084): Personal accounts of specific periods or conditions experienced by individuals living with BD.Topic 7. Emotion expression (0.059): Patients with BD expressed their feelings about living with the illness, including emotions such as hate, sadness, and crying.Topic 8. Friend (0.054): Frequent mentions of individuals who interacted with patients in social settings.Topic 9. Relaxation (0.047): Techniques shared for relaxation during times of stress and anxiety, such as smoking, drinking, taking drugs, sleeping, eating, and meditation.Topic 10. Drug-side effect (0.045): Discussions about the side effects of drugs used for BD, with weight gain being the most frequently mentioned side effect .By employing topic-based sentiment analysis on social media data, it becomes possible to identify people's moods, related issues, and emotional responses to specific situations. For instance, when discussing a health topic, the mention of a drug name often evokes strong positive or negative sentiments within the conversation. To gauge the emotional intensity within the bipolar disorder (BD) community, we utilized SentiStrength 2.3 for sentiment analysis. This tool adopts a lexical approach that begins with a collection of terms known to have sentiment associations. It then applies a set of rules to predict the sentiment of texts based on the occurrence of these words. After obtaining the results of positive and negative text classification, we integrated these findings into the topic modeling approach to determine the common topics associated with each polarity.The system employed sentiment analysis to determine the sentiment strength in Reddit data, categorizing each text as neutral, positive, or negative. However, for the purposes of this study, we focused solely on reporting the positive and negative sentiment text to observe the experiences related to bipolar disorder. Each text was assigned two numerical values by SentiStrength: a score between 1 and 5 for positive sentiment strength, and a score between −1 and −5 for negative sentiment strength. Additionally, a score of 1 or −1 indicated no sentiment, while a score of 5 or −5 represented a strong sentiment of that type. For example, a social web text with a score of 1–4 would convey weak positive sentiment and strong negative sentiment. The system utilized two scales because a conviction can encompass both positivity and negativity, and the objective was to detect the expressed viewpoint rather than the overall polarity  1−4 Cried [−3] at [0] work [0] ] ]]Wow, fantastic response. Thank you so much for sharing, you encouraged“me!”(Positive) 4 –1 Wow[2] fantastic[2][+1 Multiple Positive Words] response[0] ] Thank [1] you [0] so [0] much [0] For [0] sharing [0] you [0] encouraged [1] me [0] ] ]]The software assigned a score to each word in the sentence, and a total weighted score was calculated to predict the text's polarity. Each word received a numerical value based on its strength. For instance, the word “cried” was assigned a strongly negative score of −3, while both “wow” and “fantastic” were rated as moderately positive with a score of 2.The results of the sentiment analysis indicate that there are more negative sentiment  than positive sentiment  within the discussions of Reddit-related bipolar disorder communities. Examples of the experimental results are presented in In order to investigate the polarity of emotions surrounding BD in social media discourse, we identified common issues that were publicly discussed within the Reddit-related bipolar community. The texts from the sentiment analysis results were divided into two datasets: positive and negative. These datasets were then subjected to LDA topic modeling to uncover hidden topics within each polarity. We set the number of topics to 20 and specified that each topic should consist of 20 words with the highest probabilities.The LDA results present the content of documents with 20 different topic mixtures and 20 words per topic. For the purpose of this paper, we selected the top five topics to report. We manually assigned labels to these top five topics based on the words associated with each topic.To illustrate the association between terms and document topics, we constructed a co-word map. The positive and negative text post were processed into graphML format to generate word co-occurrences and create a network of co-occurring words. Subsequently, we visualized the graph using Gephi software, adjusting the nodes to highlight those with high betweenness centrality for improved visualization. This allowed us to observe the graphs with key terms (nodes) representing the core concepts within each polarity. The results are presented below:The online community of Reddit users discussing Bipolar disorder covers a variety of topics related to the condition. The top 10 topics predominantly revolve around symptoms, mood swings, diagnosis, and medication. Users openly share their personal experiences with bipolar episodes, including the challenges they face and strategies for coping. They also express their emotions about living with bipolar disorder, seeking solace and connection with others who can relate to their struggles. Therapy is another crucial topic, with users sharing their experiences and interactions with mental health professionals. They discuss different therapeutic approaches, the benefits of therapy in managing bipolar disorder, and provide tips for finding a suitable therapist.Discussions related to medication are common, as users share their experiences with specific medications such as Lithium, Lamictal, and Wellbutrin. They talk about side effects and how certain drugs have helped them manage their condition. Weight gain is often mentioned as a common side effect, and users seek advice and strategies for managing medication-related effects.The findings demonstrate that a large number of social media users use online community platforms to discuss mental health issues. Users have a keen interest in seeking out information related to treatments, engaging in conversations with others to express their thoughts on the efficacy and potential side effects of treatments, participating in discussions within mental health communities to address their queries, and acquiring insights about their medical conditions , the sentiment was assessed using the SentiStrength software. The software analyzed user-generated text from social media, which described situations related to health problems. The results of the sentiment analysis on the Reddit dataset, under the topic of BD indicated a higher frequency of negative polarity compared to positive polarity. This finding suggests that discussions and expressions within the Bipolar Disorder online community on Reddit tended to lean toward a more negative sentiment. It indicates that individuals sharing their experiences, challenges, and emotions related to BD often conveyed negative feelings or perspectives.It is important to note that sentiment analysis provides an automated assessment of sentiment based on textual content, and it may not fully capture the nuances and complexities of individual experiences. Additionally, the analysis is limited to the specific dataset and platform analyzed, and sentiments expressed may vary across different social media platforms and online communities. For instance, using Twitter content analysis to measure attitudes toward mental illness and analyzing mental health based on the positive language of Facebook users provided different insights into online discussions about mental health  as a clinical diagnosis. Within the context of our research, participants on social media platforms may encompass a diverse range of individuals, including those who have received a professional diagnosis of BD, those who self-identify as bipolar, and individuals who are family members of those with BD. Consequently, this gap introduces a potential risk of misattribution when analyzing sentiments and topics related to BD within the context of discussions about BD. It is important to recognize and consider this limitation.Furthermore, in future work, we should consider the potential value of predicting user post-behavior during the presence of mental symptoms and conducting a sentiment comparison between Bipolar Disorder (BD) and other online communities.This study aimed to explore the topics and sentiments discussed in the Bipolar disorder online community on Reddit. The findings revealed that users engaged in discussions related to various aspects of bipolar disorder, including symptoms, mood swings, diagnosis, medication, therapy, social support, and relaxation techniques. They shared their personal experiences, sought advice, and expressed their emotions about living with bipolar disorder. The analysis showed a predominance of negative sentiment expressed in the community, indicating the presence of challenges and struggles associated with the condition. These findings emphasize the importance of addressing the wellbeing of individuals living with bipolar disorder and highlight the need for appropriate treatment and support. The research framework employed in this study can also be applied to gain insights into other health conditions through social media analysis.In summary, the primary objective of the present study is to enhance the understanding of how individuals with BD communicate on social media platforms. While not providing definitive medical insights, our research offers opportunities for further exploration. We intend to investigate unmet information needs and aspects requiring professional attention in future research, guided by the input of clinicians and individuals with BD, ensuring practical relevance.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The data used in this study was collected from Reddit, a social media platform, in accordance with the platform's terms of service and community guidelines. The data collection process strictly adhered to the ethical standards outlined by Reddit, ensuring respect for user privacy, anonymity, and the responsible use of the platform's content. Consequently, we confirm that the collection, analysis, and reuse of social media data were conducted in strict accordance with Reddit's policies and terms of use, as well as all relevant institutional regulations.TT conceived and co-designed the analysis, collected the data, and co-wrote the paper. QX co-designed the analysis and co-wrote the paper. SL co-wrote the paper. All authors contributed to the article and approved the submitted version.


The introduction and wide application of non-invasive prenatal testing (NIPT) has triggered further evolution of routines in the practice of prenatal diagnosis. ‘Routinization’ of prenatal diagnosis however has been associated with hampered informed choice and eugenic attitudes or outcomes. It is viewed, at least in some countries, with great suspicion in both bioethics and public discourse. However, it is a heterogeneous phenomenon that needs to be scrutinized in the wider context of social practices of reproductive genetics. In different countries with their different regulatory frameworks, different patterns of routines emerge that have different ethical implications.This paper discusses an ethics of routines informed by the perspectives of organizational sociology and psychology, where a routine is defined as a repetitive, recognizable pattern of interdependent organizational actions that is carried out by multiple performers. We favour a process approach that debunks the view – which gives way to most of the concerns – that routines are always blindly performed. If this is so, routines are therefore not necessarily incompatible with responsible decision-making. Free and informed decision-making can, as we argue, be a key criterion for the ethical evaluation of testing routines. If free and informed decision-making by each pregnant woman is the objective, routines in prenatal testing may not be ethically problematic, but rather are defensible and helpful. We compare recent experiences of NIPT routines in the context of prenatal screening programmes in Germany, Israel and the Netherlands. Notable variation can be observed between these three countries (i) in the levels of routinization around NIPT, (ii) in the scope of routinization, and (iii) in public attitudes toward routinized prenatal testing.An ethics of routines in the field of prenatal diagnostics should incorporate and work with the necessary distinctions between levels and forms of routines, in order to develop sound criteria for their evaluation. International bioethical literature and well-argued public concerns raised in many countries have suggested that the “routinization” of prenatal testing is ethically problematic, since it could hamper the quality and freedom of informed decision-making in each individual case, and increase social or moral pressure on women to test. Routine testing for Down syndrome or other relatively common conditions tested in NIPT could also add to stigmatization and discrimination of people who live with that condition. However, from a clinical perspective one can argue that prenatal care is inevitably a highly repetitive and hence routinized field of clinical practice and well-considered professional and clinical routines are essential parts of it. It is therefore hard to imagine how non-invasive prenatal testing (NIPT) could avoid being part of routines. It might rather depend on which forms of routines are adopted than whether routines happen to emerge at all.It is well established in the sociological and anthropological literature that amniocentesis, maternal serum screening and diagnostic ultrasound have changed the experience of pregnancy and reconstructed the social meanings of motherhood , 24, 25.Since NIPT works with cell-free foetal DNA, which is present in maternal blood , it is nunconsidered choices, because under a routine pregnant women do not deliberate and might not be aware of the consequences of testing; (b) constrained freedom to choose, since routine testing becomes self-evident (and will thus be used more frequently), and social pressure to take part in prenatal screening might be felt; (c) negative consequences for people with disability: acceptance of children with this condition might decline so that they then become more stigmatized and discriminated against. Hence, problems of adequate information, freedom of choice, and societal consequences are seen. The authors also deplore a significant lack of clarity about the meaning of the term ‘routinization’ in the literature [The 2017 report by the British Nuffield Council on Bioethics on ethical issues of NIPT mentions in a nuanced evaluation the establishment of routines as a main concern: “Some women accept screening because it is perceived to be a routine part of prenatal care, and in these cases it might be better described as an instance of conformity rather than active choice” In order to see more clearly what the umbrella term of ‘routinization’ covers, and which ethical questions are the most pertinent to raise about routinization of NIPT, we first consider the state of research on routines in the sociology and psychology of organizations. We need to distinguish between different perspectives on routines and routine decisions , and how they are perceived from these perspectives, in order to see what is problematic and why.We then look more closely at experiences of NIPT routines in the context of prenatal screening programmes in three countries. The different experiences of countries with different policies regarding the introduction of NIPT allow us to see which routines have emerged, how routines  are being negotiated, created and deployed in the public health system to respond to a new technology (NIPT) which has disrupted earlier routines in the procedures of prenatal care. A comparison between Germany, Israel and the Netherlands provides evidence that current practices and discussions diverge in some key respects.Routines in prenatal care do not merely follow an instrumental logic and technological imperatives, but are also shaped by the cultural contexts of views on disability, eugenics, welfare and prevention. These views may lead both to demands for routines as an organizational requirement for efficiency and quality as well as to criticisms of problematic routinization.The introduction of NIPT constitutes the most recent major transformation of prenatal diagnostic practices . But NIPscreening) is perhaps no different in principle from the routinization of previous PND technologies such as biochemical or nuchal translucency screening. The significance of looking at NIPT/NIPS stems from examining the multiple social factors that shape a new and highly acclaimed biomedical technology, and the social impact of this genomic technology on patients and families as it makes the transition from testing into screening while still manifesting uncertainties and conflicts. Because this transition is still in the process of unfolding, with various questions  still being contested, NIPT/NIPS highlights a significant ethical dilemma of prenatal care in post-industrial societies: the routinization of prenatal screening for genetic risks within a normative framework that ought to be based on two ethical values [We focus here on the routinization of NIPT while it makes a transition from a second-tier test offered on a case-by-case basis in high-risk pregnancies, to a first-tier screening offered to all pregnant women, as it is the case in Belgium or the Netherlands , 2, 4. Tl values : (i) frereject such testing must be prepared to give explanations and justifications, whilst testing is the default. “People ask ‘Why not?’ No one asks ‘Why?’” (ibid.). One main bioethical concern has been that routinization represents social pressure to conform to testing, i.e. to comply with unwritten rules of a society. As already mentioned, the Nuffield Council  means a practice without deliberation, or without reflection, which therefore may contain an uninformed, perhaps involuntary decision. Like the concept of ‘medicalization’, which is often used critically, actually to indicate a kind of over-medicalization, the common use of ‘routinization’ also implies, by default, some problematic aspect. Routinization in this sensitive field would mean, as Susan Suter wrote in a classic paper, that “testing has become part of social norms and expectations” , p. 241)Council  does however not seem to us to be fully evident. It would rather depend on the actual content and the form of the routine, i.e. how the procedure is routinely offered, and what kind of decision-making situation this routinely creates for the woman. We argue that routinization of NIPT does not therefore necessarily mean applying NIPT routinely, or even terminating a pregnancy routinely after a positive confirmatory test. Routines might also be preoccupied with creating a good decision-making situation about NIPT for the woman.Giovanni Rubeis et al.  Empirical studies that have examined these concerns have shown that a great majority of women who underwent NIPT reported to have made an informed choice: 77,9%  and in Originally, routines have been regarded as mechanistic and lacking agency, “a fixed response to defined stimuli” March and Simon , quoted Routines cannot be set aside from the people enacting them. In addition to being “repetitive, recognizable patterns of interdependent organizational actions carried out by multiple performers” , p. 95),Hence, routines could support the decision-making process, such as the routine provision of particular information about the implications of NIPT, and routines could also allow sufficient time for reflection. Routinization of NIPT often involves various inter-connected actions whose performance can vary in terms of regularity and social control, such as: (i) the offer of a test, (ii) the testing itself, (iii) the provision of certain types of information about the implications of the test, and (iv) actions taken if the test turns out positive. These routines can be organized in better or more problematic ways, e.g. by not giving the pregnant women enough time to think about the offer or to consult others.As stated before, empirical studies about women’s decision making about prenatal screening report high levels of informed choice, even though more than 20% reported not to have made informed choices , 20. OneThis sheds a different light on routines as well. How are pregnant women referring to ‘routines’ or ‘routinization’ themselves? Routines could also, under certain circumstances, be vessels that provide helpful communicative reassurance because one is not left alone with one’s decisions. They could help to define the situation, to understand and carry the burden of responsibility and hence, as instruments of choice, provide a sense of freedom all pregnant women that NIPS is the most sensitive screening option for traditionally screened aneuploidies ” [As NIPT has a high sensitivity (> 99%) and specificity , from thdromes)” .Although the development, introduction and marketing of NIPT have been commercially driven by various private companies worldwide, first in the US in 2011 , and orilevel(s) of social practice in prenatal diagnostics routines are established? Is it a routine offer of NIPT, together with the necessary information for individual decision-making, or is it a routine that affects the way tests are carried out as screening? 2) What is the scope of emerging PND routines in this country? Are they based on individualized decision-making, restricted to certain clinics or institutions, or through nation-wide programmes? 3) What are the characteristics of public discourse about NIPT and prenatal screening? Which concerns seem to be dominant?We chose three countries that cover a broad spectrum of NIPT implementation: (i) Germany, with its restrictive policy and a high level of moral concern about NIPT in the public discourse, much influenced by the need to break from the history of eugenics in the National Socialist era , (ii) thWe start with Germany, a country that is overall still resistant to NIPS routines, continue with Israel, where offering universal NIPS is still an experiment, and conclude with the Netherlands, where universal NIPS is offered as standard in prenatal care. Our comparison is based on analysis of policy documents concerning NIPS issued in the relevant countries, as well as on the report by Valera Lema et al. .PraenaTest in cooperation with German and Swiss PND centres and university clinics since 2009. In May 2018, six different providers of NIPT operated in the German market, with a variety of options, with NIPT available at prices of approximately EUR 200–550. NIPT was offered mainly to high-risk women upon medical indication and at their own expense, but some health insurance plans have already begun to refund NIPT on a case-by-case basis.NIPT was introduced to the German health care sector and market in 2012 by the German company LifeCodexx AG, which had been developing its Arbeitskreis Frauengesundheit wrote: “the prenatal search for genetic characteristics is not pregnancy screening, but a selective search for unwanted deviations.”From its introduction, NIPT in Germany was accompanied by public controversy concerning market entry, public R&D funding and cost coverage , 8. At tjustified individual cases and after medical consultation.not belong to the generally recommended examinations”Against this backdrop, in September 2019, the Federal Joint Committee  for public health decided that NIPT should be covered, in In the German public discourse on NIPT, the word “routinization” is used negatively to indicate a fear of social pressure, a selective, eugenic attitude and a challenge to individual autonomy. This is illustrated by the wording of the invitation to a public online forum on NIPT, organized by the German Ethics Council on 23 February 2022, which addressed “the fear” that it “could become routine practice”.11not replace existing screening, namely first trimester ultrasound for nuchal translucency and biochemical tests. Although NIPT is currently not part of the Israeli ‘health basket’ , various financial agreements exist between the seven private companies offering NIPT in Israel and Israeli HMOs . These agreements, as well as the specific insurance the woman holds, determine the fraction of the test cost paid by the HMO and the fraction paid by the woman. The overall cost of NIPT is relatively high: around NIS 3000–4000 . A recent unpublished report of the Israeli Ministry of Health on uptake in 2014–2017  showed a high uptake of invasive prenatal tests (11.8% out of Israeli women who gave birth that year), while NIPS was only performed in 4.3%. NIPS uptake did not rise significantly in these years, alongside a very modest decline in invasive procedures. In contrast to the rapid decrease in the rate of invasive testing in the “NIPS era” observed in many other countries, Israeli women seem generally to prefer the more diagnostically accurate and comprehensive chromosomal microarray analysis (CMA) testing, which in Israel is integrated into amniocentesis when medically indicated .There has been no public debate about NIPT/NIPS in Israeli public media. The chairperson of one of Israel’s Down syndrome advocacy organizations has called upon the Israeli government to subsidize NIPT and make it available to all women that “the cost of this test is an outrageous wrongdoing… Since it is a blood test (a short and simple procedure) and since this test could prevent, for those who wish it, bringing into the world a child with special needs, it seems to us extremely important to reduce the costs of the test immediately and make it accessible.”In 2019, for the first time and with the approval of the Ministry of Health, a major Israeli hospital in Tel Aviv started offering NIPS to all pregnant women from week 8 of pregnancy, through the hospital’s Genetics Lab, for a reduced cost of NIS 2600 (approx. EUR 650). Following standard practice in Israel the new service includes pre- and post-test-counselling. This local service may soon pave the way to further routinization in the universal offer of NIPS.In Belgium, Denmark and the Netherlands, NIPS is currently offered to all pregnant women as first-tier screening : 52). Froffer does not imply high uptake in this case. The current uptake of NIPS is about 40–45% of pregnant women, and did not change significantly between 2003 and 2016 [19However, the routinization of the and 2016 .17 Partiand 2016 . NeverthIn the Dutch case , 53, theWhile the situation is still dynamic, Germany, Israel and the Netherlands highlight important axes in the process of routinization, such as the level of routinization ; the scope of routinization ; and the public discourse surrounding the meanings of routinization. A comparison like this shows how national variations exist alongside co-evolution in terms of the stages and goals of the process of routinization  and its mandatory certified licensing and training. In the Netherlands there are also concerns about routinization, but universal routinization of offering screening is predominantly seen as a way to protect individual decision-making by pregnant women. As the Dutch experience shows, routinization of offering NIPT, under appropriate conditions, does not lead to devaluing free and informed decision-making by individuals. But for this to be the case, a routinized offer of a test must be accompanied by other parts of the routines that provide relevant information and support for personal decision-making.Routinization in prenatal diagnostic practice raises ethical questions, but routinization per se cannot be ethically evaluated without greater specification from a sociological and psychological perspective. Some forms of routines can be empowering and endorse agency, while others can hamper free and informed decision-making. It also depends on a positive or negative image of people with Down Syndrome, availability of support and on their inclusion in society. Strict regulation and responsible implementation of NIPT can safeguard quality of care as well as women’s autonomy. However, whether this is the case for all women remains to be shown, as in the Netherlands where the uptake of the NIPT is much lower in socioeconomically disadvantaged neighbourhoods , signallOpen questions remain to be answered by empirical follow-up studies in different countries. Three groups of issues should be emphasized. First, since in most cases prenatal diagnosis does not lead to treatment or prevention other than abortion, it remains to be seen whether, how far and under which contextual conditions the argument that individual informed choice is routinely enabled, can convincingly outweigh concerns about selective reproduction. Thus, the discussion about the inherent complex ethical considerations related to prenatal screening decisions remains pertinent. Second, some aspects of the setting may contribute to the acceptability of NIPT routines to disability advocates. In a non-inclusive societal environment the existence of a routine offer of NIPT, even though it remains strictly on the basis of individual free decision-making, can be perceived as sending a difficult message for those living with the conditions for which tests are offered. And, most importantly, it depends on how children with disabilities are included and supported (instead of discriminated against) in society , 38.Third, pregnant women have different vulnerabilities. Some forms of  autonomy are worth having , other iRoutinization of screening can be seen both as the source of a problem and also its antidote, however dependent on the level and content of routines, which in our view suggests a need to open up the concept of routinization and look for an interdisciplinary definition of its meanings and elements. While an ethical critique on routinization of NIPT is valid, it needs to be complemented by sociological and a psychological perspectives related to evidence on actual informed choice of pregnant women and the broader sociological context of quality and access to care. Our analysis confirms Ruth Horn’s proposition that the ethical acceptability of routines depends on the availability of information and social support to raise a child with a disability . If womeThe discussion about routinization in the field of prenatal diagnostics  should incorporate and work with the necessary distinctions between levels and forms of routines, in order to develop sound criteria for their ethical evaluation. Routinization per se is too blunt a term to be discussed ethically. It needs to be empirically established whether or not routinization affect individual informed decision-making and restrict freedom of choice due to perceived social expectations to act in a certain way. Furthermore, whether or not prenatal screening has a negative impact on people with disability, need to be discussed in light of the inclusiveness (or not) of a society. Routine abortion for conditions like Down syndrome would be considered the ethically most problematic level of routinization, if the termination is not well considered individually but made ‘by the book’. Yet the choice about the child women do or do not want to give birth to reflects parental autonomy as long as it is their choice. Routines that are unavoidably emerging as part of social and health care practice should therefore have built-in checks and balances to ensure that communication is two-way, information is balanced, and choice really is informed and well-considered. Moreover, all these elements should be assessed in the context of wider society as well, and include the interests of people with disabilities.An ethics of routines should not just focus on discussing the normative statements contained in regulations and guidelines. It needs to consider the development of routines in the context of emerging social practices and individual informed choices.


Objectives: We examined the washing evaluation method of the flusher disinfector installed in the medical site by visual evaluation using an ISO test soil and adenosine triphosphate (ATP) measurement. Methods: The test soil shown in ISO15883-5 was applied to the bedpan using 2 methods (N = 10) and was then visually evaluated using a 4-step scale. The ATP value on the surface of the bedpan corresponding to each scale was measured, and the correlation with the visual scale was confirmed. In addition, a visual evaluation was performed using a different flusher disinfector and bedpan (N = 3). Results: In the visual evaluation, when the test soil was applied to the entire surface of the bedpan, it remained in the parts where the water flow was hard to hit. When the test soil was applied to the surface of the bedpan except the lid, no soil remained. The 4-step visual evaluation scale and the logarithm of ATP value showed a positive correlation. In visual evaluations with different flusher disinfector and bedpan combinations, the residual soil patterns tended to be different. Some bedpans showed washing failure related to improper design. Conclusions: Poor cleaning of flusher disinfectors may occur when the amount of water used is insufficient or when the bedpan is significantly contaminated. It is important to carry out flusher disinfector washing evaluation at medical sites to evaluate the function of flusher disinfectors. An appropriate program must be utilized for staff education and appropriate management. Because flusher disinfectors and bedpans differ, flusher disinfector cleaning evaluations should be carried out at all facilities.


The review summarizes the fabrication, microstructures, and sensor applications of highly ordered electrospun nanofibers. In the traditional electrospinning process, electrospun nanofibers usually have disordered or random microstructures due to the chaotic oscillation of the electrospinning jet. Different electrospinning methods can be formed by introducing external forces, such as magnetic, electric, or mechanical forces, and ordered nanofibers can be collected. The microstructures of highly ordered nanofibers can be divided into three categories: uniaxially ordered nanofibers, biaxially ordered nanofibers and ordered scaffolds. The three microstructures are each characterized by being ordered in different dimensions. The regulation and control of the ordered microstructures can promote electrospun nanofibers’ mechanical and dielectric strength, surface area and chemical properties. Highly ordered electrospun nanofibers have more comprehensive applications than disordered nanofibers do in effect transistors, gas sensors, reinforced composite materials and tissue engineering. This review also intensively summarizes the applications of highly ordered nanofibers in the sensor field, such as pressure sensors, humidity sensors, strain sensors, gas sensors, and biosensors. Nanomaterials have at least one dimension at the nanoscale. Nanomaterials consist of zero-dimensional nanoparticles and quantum dots, one-dimensional nanofibers and nanotubes, two-dimensional nanosheets and nanofilms, and a three-dimensional architecture ,2,3. Nan0.8SR0.2TiO3 (BST) nanofiber arrays. The humidity sensor made from this uniaxially ordered fiber array exhibited fast response recovery characteristics at room temperature, which demonstrates the potential application of the sensor in detecting environmental humidity. The biaxially ordered structure has a unique advantage in air filtration. Cheng et al. //[Eu(BA)3phen/PAN] nanofibers, respectively. As seen in 3O4 nanoparticles on the surface. As seen in 3O4/PANI/Eu(BA)3phen/PAN] nanofibers, respectively. As seen in 3O4 nanoparticles are distributed on each nanofiber. As seen in In summary, the conjugate electrospinning method can successfully produce heterogeneous nanofibers. Although the heterogeneous nanofiber yarns are twisted, the nanofiber yarns possess a high degree of alignment and orientation. Additionally, nanofiber yarns have great potential in the field of gas sensors.In addition to improving the collection device, highly ordered nanofibers can be obtained by a modified method of preparing bundles such as using multi-filament yarn. Esrafilzadeh et al. studied the crystallization sequence and mechanical properties of PAN nanofibers by electrospinning and post-processing. To maintain the tension of the nanofibers during post-processing, an improved method of preparing nanofiber bundles, such as by using multi-filament yarn, was used to successfully control the arrangement and linear density of nanofiber bundles. With the increase in the diameter of nanofibers, the orientation of nanofibers improves obviously. Li et al.  preparedElectrospinning technology contains both far-field electrospinning and near-field electrospinning abilities. Near-field electrospinning is also called near-field direct writing technology or electrofluidic printing technology. The near-field direct-write electrospinning process works on the principle that highly ordered nanofibers can be prepared with the aid of precision motion control when the spacing between the collection device and the nozzle is controlled in the range from 0.5 to 5 mm . Mai et Generally, the receptor and the signal transducer form the sensor are indispensable. Both are instrumental in contributing to the ultimate performance of the sensor and in broadening its field of application. There are two major performance indicators for the sensors: detection performance and signal conduction performance. Both are influenced by the performance of the nano additives in the system. The detection performance of the sensor is also referred to as receptor performance. The key performance metrics of highly ordered nanofibers are different for different sensor applications. Generally speaking, the degree of order of a nanofiber affects the electron transfer efficiency and thus determines the sensor’s performance. At the same time, the addition of different materials to the fiber directly affects its electrochemical performance. In some special cases, such as in pressure sensors, the diameter of the fiber also affects the sensitivity of the sensor . An exceMelt electrospinning was reported to produce a thin film made of polyether block amide. A thin film for resistive pressure sensors can be obtained by arranging the spun cylindrical fibers in an orderly manner into a narrow vertical wall. The polystyrene sulfonate 3,4-ethylene dioxythiophenetrodes in the film are coated with poly polystyrene sulfonate. When pressure is applied to the sensor, the contact area between the electrode and the film changes, this change produces a sensitive current response, and a range of pressure changes can be detected .−1 loading sweep rate condition. The sensor still has high sensitivity and repeatability after 2500 measurements. This work demonstrates the potential application of this microstructure in pressure-sensing platforms. The ordered and compressible cylindrical microstructure is expected to be applied to flexible electronic products and wearable devices in the future.In the past decade or so, researchers have made tremendous progress in the sensitivity, response time, and detection limits of pressure sensors. However, piezoelectric pressure sensors with electrospun nanofibers still face some challenges. (1) poor biocompatibility—among the current piezoelectric polymers, polyvinylidene fluoride (PVDF) and its copolymers have the highest piezoelectric performance, but their solvents are all environmentally hazardous; (2) Poor wear resistance—the wear resistance of electrospun nanofiber-based pressure sensors has not been well-focused and -characterized, though it is an important factor affecting the durability of wearable devices; (3) an immature electrospinning technique—the current electrospinning technology is not yet able to mass-produce nanofibers to prepare wearable devices.Fortunately, electrospinning technology has made great progress in the past 20 years. The development of needleless electrospinning has significantly increased spinning material rates and yields. Near-field electrospinning enables the fabrication of neatly aligned fiber bundles and the construction of novel three-dimensional structures. It is expected that with the development of electrospinning technology, a new textile industry can be formed in the future to realize self-powered human health monitoring.Xia et al. used electrospinning combined with electrical fabricated BST nanofiber arrays. As seen in This work has successfully synthesized uniaxially aligned BST nanofiber arrays. Although the response performance of ordered fibers is better than that of disordered fibers, there is no significant change in their recovery performance. Special attention needs to be paid to improving their recovery performance to manufacture more efficient humidity sensors. Because the synthetic-array humidity sensor shows rapid response and recovery at room temperature, the sensor is expected to be used to detect indoor humidity.In addition to testing indoor environmental humidity, humidity sensors have broad application prospects in the production of flexible wearable devices. Zhou et al.  preparedZhu et al.  fabricatIn this work, ordered, porous, piezoelectric electrospun PLLA fibers were fabricated and strain sensors were prepared. The sensor is expected to be applied to the collection of energy generated during the movement of human joints. However, its maximum peak power is only 19.5 nW, which is far from that required for practical applications.Many studies are conducted on preparing nanofibers and making strain sensors using electrospinning. Various materials with high flexibility and electrical properties are used, among which polymeric nanomaterials are the most promising. Electrostatically spun P(VDF-TrFE(Tri fluoroethylene)) nanofiber mats for 3D stress sensors have excellent sensitivity even at 0.1 Pa. Additionally, the aligned electrostatically spun core–shell P(VDF-TrFE) nanofibers are nearly 40 times more sensitive than thin-film PVDF-based stress sensors. PVDF and PVDF copolymer nanofibers produced by electrostatic spinning are expected to be the most promising materials for flexible tactile sensing applications.2/Si, confirming that this receiving board could fabricate highly ordered PVA nanofibers. 2 substrate worked together to form the 3D CuPc films.Wang et al. used an electrospun receiving board with an inclined gap and fabricated highly ordered PVA parallel nanofiber arrays. Then, they evaporated copper phthalocyanine (CuPc) on the PVA parallel nanofiber arrays to obtain a 3D CuPc organic field effect transistor sensor . Figure −13 A. The conductivity (slope) of the CuPc/PVA parallel nanofiber arrays sensor is lower than the conductivity of the single CuPc sensor. The reason for this may be that the CuPc/PVA sensor has thinner sensing films than the single CuPc sensor does under the same conditions. 10 Ω, and those of single CuPc sensors are 7.07 × 109 Ω. The concentration of NO2 is changed from 1 ppm to 25 ppm, and the dotted line in the figure represents the baseline. As can be seen from the figures, the resistance of all sensors changed distinctly when the NO2 concentration was 1 ppm. Nevertheless, the recovery time of a single CuPc sensor is longer than that of a CuPc/PVA parallel nanofiber array sensor. At the same time, the recovery rate of a CuPc/PVA parallel nanofiber array sensor is much better than that of a single CuPc sensor. 2 concentration and its responses. The results indicate that CuPc/PVA parallel nanofiber array sensors can detect the presence or absence of NO2 within a short time. It has a fast response/recovery property.2 is in contact with the surface of the CuPc films, the NO2 molecules are immediately absorbed on the film’s surface. Additionally, then, the NO2 molecules capture free electrons on the surface of 3D CuPc films with highly ordered PVA parallel nanofiber arrays and single CuPc films. Compared with single CuPc films, the 3D structure of CuPc films with highly ordered PVA parallel nanofiber arrays contact more NO2 molecules in various angles and directions. Therefore, the highly ordered PVA parallel nanofiber array sensor has broader concentration detection abilities.2 gas and is expected to expand to the real-time detection of other gases.In this work, highly ordered PVA parallel nanofiber arrays were spun, and sensors were prepared. The sensor can detect 0.3 ppm of NOBased on the environmental pollution caused by various types of gases and people’s requirements for quality of life, the future direction of research on gas sensors can be carried out in terms of the following aspects: (1) the development of gas sensors with excellent selectivity, ultra-high response, low detection limits and fast response times; (2) the combination of electrospinning with post-processing techniques such as chemical deposition or sputtering, which will result in nanomaterials with enhanced catalytic activity and attractive sensing properties; (3) The development of sensors that can provide good gas-sensitive properties at room temperature, as the optimum operating temperature of gas sensors is generally too high, and there is a risk of explosion in explosive environments. Carbon nanotubes have the advantages of large specific surface areas and high electron transfer rates, which make them construct high-power biosensors. Nevertheless, van der Waals forces make carbon nanotubes aggregate easily and generate electrical resistance. Simply incorporating carbon nanotubes into electrodes directly cannot maximize its advantages. A technique was reported to obtain highly ordered carbon nanofibers to maximize their intrinsic conductive and structural properties. In this work, pyrroloquinoline quinone-dependent glucose dehydrogenase highly ordered and disordered CNT nanofibers were prepared and made into electrodes. CV and impedance measurements show that ordered carbon nanotube electrodes perform better than random carbon nanotube electrodes do. This is expected to be valuable for building high-powered biological devices, such as biosensors and biofuel cells.In the future, biosensors made using electrospun fibers may be developed in the following directions: (1) The diversification of functions. Biosensors will combine more functions in one. (2) The achievement of easy portability. Biosensors will be made more wearable and comfortable. (3) The achievement of intelligent and networked devices. Biosensors will connect with more smart devices and collect and analyze data in time.This review overviews the highly ordered electrospun nanofibers in three aspects. Firstly, different electrospinning methods for forming highly ordered nanofibers re summarized. Electrospinning was modified to stabilize the polymer jet by introducing magnetic fields, controllable platforms and needles, and parallel electrodes. The improved collection devices can obtain highly ordered nanofibers. Secondly, different microstructures of highly ordered nanofibers are summarized and compared. Nanofibers are one-dimensional nanomaterials, but they can be arranged to form uniaxially ordered filaments, biaxially crossed and ordered nanofiber webs, and 3D-ordered scaffolds. Finally, different applications of highly ordered nanofibers in the field of sensors are summarized. Different nanofibers have attracted extensive attention because of their high specific surface area and reactive activity. Highly ordered nanofibers have been shown to have superior mechanical and dielectric strength compared to disordered nanofibers, which could expand their applications in the sensor field, such as in pressure sensors, humidity sensors, strain sensors, gas sensors and biosensors. Although many methods have been developed to fabricate highly ordered nanofibers, the preparation process still has some challenges and limitations: (1) Improvement of nanofiber production efficiency. Improvements in electrospinning equipment are needed to facilitate the transition from laboratory to industry. (2) Batch quality assurance. Fiber quality is greatly affected by environmental factors, and the change in temperature and humidity will bring different fiber quality. (3) The reduction of production cost. Including material and labor cost reduction. How to develop cheaper and more efficient production materials? (4) The limitations of characterization methods for nanomaterials. For example, SEM is commonly used to characterize the surface morphology of nanofibers. However, due to the electron beam secondary imaging principle of SEM, the surface morphology is easily incorrectly reflected. (5) The establishment of recognized characterization methods. For example, no recognized characterization method has been established for the strength and modulus of nanofibers.


Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic.Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species,  In antibiotic-free environments, however, resistant bacteria are expected to incur a fitness cost  and to be eventually outcompeted by their susceptible, more fit counterparts. This fitness cost may result from the alteration of an enzyme by mutation, the disruption of a metabolic pathway following gene loss or inactivation, or the additional energy required for the overexpression of a gene or the expression and replication of a new gene acquired through horizontal transfer.Antimicrobial resistance (AMR) increases at an alarming rate worldwide, imposing a considerable burden to health systems and menacing the safety of modern medical procedures . AMR hasThe biology and ecology of AMR emergence differ fundamentally depending on whether AMR results from the mutation of a chromosomal gene  or the acquisition of a transferable AMR gene . AMR mutE. coli, to ease interpretation of the results by avoiding biasing fitness evaluation across multiple host species. Using a multilevel meta-analysis framework, we examined whether the fitness cost of AMR, from a single determinant to an accumulation of many genes or mutations, differs when provided by horizontally transferable genes such as those encoding beta-lactamases, comparable to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance.To fill this knowledge gap, we conducted a comparative meta-analysis of the fitness cost of resistance, with a focus on the transferable nature of AMR determinants. We focused on a single, well-studied species, 2.2.1.E. coli. Several procedures exist to estimate relative fitness, mostly based on competition assays between a resistant strain and its susceptible, isogenic counterpart. We retained three different estimations of relative fitness, briefly described below.This is a systematic review and meta-analysis of the relative fitness of AMR determinants in In the first estimation method described by Remark that this equation does not explicitly take The second estimation method  explicitThe third estimation method  is basedThe three estimators E. coli, assuming a 20 min doubling time) are sufficient to virtually eliminate the resistant variant. Hence, a relative fitness of 0.9 may be considered a very strong fitness cost. For E. coli. Hence, a relative fitness of 0.99 may be considered a moderate fitness cost. The relation for The biological impact of the relative fitness can be illustrated more intuitively by computing the number of generations 2.2.Escherichia coli’ or ‘E. coli’ and ‘antibiotic resistance’ or ‘antimicrobial resistance’ or ‘drug resistance’. Search results were limited to peer-reviewed studies in English available online by the 29th September 2022. No start date was specified.We searched the PubMed database using terms ‘fitness’ and ‘To be included, studies had to report relative fitness findings numerically in the text, in a table or a figure. Relative fitness measurements should meet the following criteria. The relative fitness had to be measured in competition assays in an approximate proportion of 1:1 between a resistant strain (mutant) and a wild-type  strain only differing by the absence of resistance. Studies in which the data were reported in an unstandardized protocol without competition with a control strain were excluded. Studies comparing two resistant strains were also excluded. The competition assays had to be conducted at 37°C in a stable antibiotic free environment. Experiments involving a modification of environmental conditions were excluded. Finally, relative fitness had to be estimated using one of the three methods Of 335 studies matching the search criteria, 127 reported relative fitness values and 46 were included in the final dataset , represe2.3.blaOxa48, when harbored on mobile genetic elements, or AMR mutations and indels in non-transferable genes such as rpoB, referred to as mutated AMR genes. For each acquired AMR gene or mutation, the class, family, and mechanism of action of the targeted antibiotic was identified from the literature ij the intra-study heterogeneity at level 2, δ(3)j the inter-study heterogeneity at level 3, and ε(1)ij the sampling error of strains estimated as the standard deviation of relative fitness.The overall effect size I2 statistic  over 24 h . Relative fitness estimates decreased significantly with the duration of competition assays , the n = 309, 39.5%), or the n = 96, 12.3%). Interestingly, we could not detect a significant impact of the estimation method on the relative fitness . One hundred and thirty strains (16.6%) included both mutated and acquired AMR genes. Strains with only mutated AMR genes were resistant to an average of 2.2 drug families, with a maximum of 5 drug families in a strain carrying AMR mutations in 11 different genes  were acquired and 68 (46.6%) were mutated. One hundred and sixty-three unique mutations were identified among the mutated AMR genes, corresponding to an average of 2.7 mutations per gene . The AMR determinants most commonly studied were nt genes . Strainsnt genes . A meta-The relative fitness did not differ significantly between strains with only mutated AMR genes, only acquired AMR genes, or both . When stTo examine the fitness impact of gene mutation or acquisition on AMR accumulation, we used meta-regression models to quantify the change of relative fitness with each additional mutated or acquired AMR gene ,C. Each 3.3.n = 266), we observed that plasmid size, that averaged to 83 kbp, significantly correlated with a decrease of fitness cost of 0.06% per kbp , with an average relative fitness of 0.928. Strains with IncA/C and IncX plasmids appeared more costly than the other Inc. groups , while IncP plasmids seemed to have a lesser impact on fitness . Using the meta-regression approach on the subset of strains with exactly one AMR plasmid .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1186920/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.


Molecular electronics break-junction experiments are widely used to investigate fundamental physics and chemistry at the nanoscale. Reproducibility in these experiments relies on measuring conductance on thousands of freshly formed molecular junctions, yielding a broad histogram of conductance events. Experiments typically focus on the most probable conductance, while the information content of the conductance histogram has remained unclear. Here we develop a microscopic theory for the conductance histogram by merging the theory of force-spectroscopy with molecular conductance. The procedure yields analytical equations that accurately fit the conductance histogram of a wide range of molecular junctions and augments the information content that can be extracted from them. Our formulation captures contributions to the conductance dispersion due to conductance changes during the mechanical elongation inherent to the experiments. In turn, the histogram shape is determined by the non-equilibrium stochastic features of junction rupture and formation. The microscopic parameters in the theory capture the junction’s electromechanical properties and can be isolated from separate conductance and rupture force (or junction-lifetime) measurements. The predicted behavior can be used to test the range of validity of the theory, understand the conductance histograms, design molecular junction experiments with enhanced resolution and molecular devices with more reproducible conductance properties. Conductance histograms are common setups to study molecular junctions, but the dispersion of the signals makes it difficult to interpret at microscopic level. Here the authors develop a physical model of molecular junctions that connects this observable with molecular properties. In particular, single-molecule conductance measurements have been used to investigate conformational dynamics11, chemical reactions17, quantum interference20, charge transport coherence21 and to develop single-molecule spectroscopies23. Further, they are routinely used to establish structure–transport relations that can guide the design and our ability to understand photovoltaics26, redox catalysis27, energy transport and storage28, photosynthesis29, and biological signaling30. In addition, the platform has been used to construct molecular-based devices such as switches31, transistors35, and diodes37.The study of charge transport across single-molecules is a powerful tool to investigate fundamental physics and chemistry at the nanoscale43. In these experiments  of the junction, its mechanical manipulation, and the ability of the molecule to transport charge. While this view of the origin of the conductance histogram is only capturing one of the possible contributing factors to the conductance dispersion, it allows us to obtain analytic expressions that are useful for fitting, modeling, and interpreting experimental conductance histograms.56 and molecular dynamics simulations of junction formation and evolution57, and efforts to classify molecular conductance events through machine learning59. The main advance is that it provides a useful microscopic picture of junction formation and evolution that recovers the shape of experimental conductance histogram, enables extracting information about the microscopic parameters, and establishes a foundation for generalizations.This study complements and advances previous efforts to model conductance histograms through phenomenological broadening of junction parameters62, we develop a theory of break-junction experiments in which the metal-metal and metal-molecule rupture events, that lead to the formation and breaking of the molecular junction, are modeled as stochastic escapes from one-dimensional wells modulated by mechanical forces. This leads to a range of initial and final gaps between electrodes (electrode gap) that determine the molecular ensemble that is sampled in the experiment. By relating the electrode gap to junction conductance, we isolate an expression for the conductance histogram. The main results of this work are analytical equations  that caTo develop a theory for the conductance histograms, we partition the break-junction experiment Fig.  into sixIn the theory, the conductances that enter into the histograms are those encountered by the junction during (5). The distribution of junction elongations that determine such conductances are given by the distribution of initial nanoscopic gaps in (3) and at rupture in (6). The probability of a given conductance value, thus, depends on the probability that a given electrode gap is visited during (5) and the relation between molecular junction conductance and such electrode gaps.G(ξ)〉 and junction gap ξ. For a given gap, there is a whole thermal ensemble of possible molecular and junction configurations that are accessible and contribute to the conductance. However, since experiments measure a current that is time-averaged over microseconds, these individual contributions are averaged out and cannot be experimentally resolved leading to simpler conductance traces. One coordinate that systematically changes during pulling in timescales slower than the integration time of the current is the electrode gap, ξ. In experiments, the junction is pulled with speeds of nm/s, and thus sub-Ångstrom variations of electrode gap ξ can be experimentally resolved in the conductance measurements44. This effectively leads to a conductance that parametrically depends on the electrode gap, 〈G(ξ)〉.The theory supposes that there is an effective one-to-one relation between measured conductance 〈G(ξ)〉 accounts for many of these changes, but it cannot capture physical situations in which multimodal conductance features are accessible at a given electrode gap. When there is no interconversion between these modes, multimodality can be simply accounted for through independent one-to-one 〈G(ξ)〉 relations. The proposed theory can also be generalized to the more complex case where different long-lived conformers are accessible at a given ξ and interconvert during the pulling process. For definiteness, we focus on a one-to-one relation for 〈G(ξ)〉 and discuss its generalization in the outlook.We note that, even in the presence of time-averaging, the experiments can discriminate molecular conformations that are mechanically stabilized, or that survive for times longer than the current integration time, such as changes in the binding configuration or transitions between stable molecular conformations . The one-to-one assumption for 〈L and not ξ 〉 at their rupture point. In ref. 44 we showed computationally that even in ideal experiments (with reproducible electrode shape and binding configuration) this will lead to a dispersion of 〈G(L)〉 curves as the elongation in which the junction ruptures varies between experiments. However, as shown in ref. 44, if the conductance trajectories are plotted with respect to the electrode gap they collapse into a single curve, justifying the one-to-one relation 〈G(ξ)〉 in the theory.The experimentally controllable variable is the overall length of the junction t ξ Fig. . These q65 as needed, for instance, in the description of the force-spectroscopy of protein unfolding. To map this into conductance, which is the main observable, we first develop a model for the mechanical driving of the molecular junction that maps the distribution of rupture forces into a distribution of electrode gaps at junction formation and rupture. Then, based on the parametric relation between the average conductance and electrode gap 〈G(ξ)〉, we connect the distribution of initial and final junction elongations to a distribution of conductances. This results in a general equation for the conductance histogram. We further specialize the model to the case in which the conductance depends exponentially on ξ which is then used to fit representative experiments and analyze the theory. For clarity in presentation, Table To describe the nonequilibrium stochastic features inherent to the junction formation and rupture, we take advantage of the theory of rupture-force statistics developed in biophysics to describe mechanically modulated transitions between two statesξeq at zero force (F = 0). The transition state between the ruptured and unruptured state, represented by the barrier top, is located a distance χ‡ away from the well bottom, and has a F = 0. The unruptured state corresponds to the unbounded portion of the FEP (ξ > ξeq + χ‡).The rupture of the metal–metal contact and of the molecular junction (processes (3) and (6)) can be understood as a free energy barrier-crossing event in the presence of an external force from an unruptured state to a ruptured state. Specifically, the thermodynamic state of the  junction is represented by a one-dimensional FEP along the pulling coordinate see Fig. . The unrF > 0) reduce the activation barrier making it more probable for the junction to rupture. We assume a brittle system where ξeq and the distance to the transition state (χ‡) do not change with force as shown in Fig. 60, the force-dependent rupture rate follows Bell’s formula65:k0 is the spontaneous rupture rate at F = 0, β is the inverse temperature and where the force F(t), as represented in Fig. 65 for a soft spring constant κ by considering that the FEP is distorted in the presence of forces as S(t) follows a first-order rate equation of the form pF(F)—i.e., the force required to mechanically break the junction—is (see Ref. 61 for details):The application of an external force modifies the FEP, modulating the junction rupture rates. For example, positive forces  experiments, the rupture force of a metal-metalBreak-junction experiments involve two junction rupture events during the mechanical pulling: the rupture of the metal-metal contact to create the gap in which the molecule is initially placed Fig. a and theκsurf. The top spring  is then given by 1/κf = 1/κsurf + 1/κcant.As represented in Fig. L > 0 until its rupture at ΔL = ΔLf. At this point the electrodes return to their mechanical equilibrium leaving a gap ΔLf = ξ0, where we have assumed that there is no plastic deformation of the gold electrodes, i.e., changes in the electrode geometry due to the mechanical manipulation78. Such events change the equilibrium length of the electrodes but leave the analysis intact. Further extensions of the model that allow directly estimating the free energy barrier79 and transitions from brittle to ductile regimes can be captured by adding an additional parameter to the free energy profile, as proposed in ref. 60.The junction is elongated Δξ0 gaps. Specifically, a rupture force Ff = κfΔLf = κfξ0 leads to a p0(ξ0), can be calculated from the probability density function of rupture forces pF(F), as p0(ξ0) = κfpF(F = κfξ0). Then, from Eq.  is determined by the probability density function of rupture forces of the molecular junction. As proposed in Fig. Fr = κrΔLr, where κr is the overall spring constant and ΔL the overall elongation, can be written in terms of the gap between electrodes Δξ as Fr = κξΔξ = κξ(ξr − ξeq), where κξ is the molecular effective spring constant and ξeq is the electrode gap at which the molecular junction is in mechanical equilibrium (F = 0). This yields an expression for the probability density function of electrode gaps at rupture given byp0(ξ0) and pr(ξr) probability density functions for a model system with the set of example parameters shown in Table 74. As discussed below, the resulting rupture force and conductance histograms obtained from these parameters are within the range of values that are typically measured in experiments.Similarly, the probability density function of molecular junction gaps at rupture (mentclass2pt{minimp0(ξ0)) and final (pr(ξr)) molecular elongations during pulling determines the probability of visiting a particular molecular junction gap, ξ, during the break-junction experiment. To extract this quantity, we assume that for a given trajectory all ξ are equally probable between a given initial and rupture points, in agreement with the constant pulling speed in these experiments and the harmonic picture for the mechanical deformation. The probability of visiting a particular electrode gap during pulling corresponds to the product of the probabilities that the junction has been formed already (P0(ξ)) and has not been ruptured (1 − Pr(ξ)) at ξ. Therefore, the probability of sampling an electrode gap ξ is∞, ∞) range to account for the pushing and pulling of the junction. Figure P(ξ) and its contributions from the probabilities of junction formation and rupture (dashed lines) calculated with Eq.  to the probability density of measuring a time-averaged log-transmission N is a normalization constant. Equation . We now specialize our considerations to the case in which the average transmission T = T0eγξ exponentially increases (γ > 0) or decreases (γ < 0) with the electrode gap. In this case,ξ with slope determined by γ. Here, the base transmission T0 is defined as the extrapolated transmission at ξ → 0. This functional dependence was observed in detailed atomistic simulations of alkane-based junctions44. As discussed below, this specific g(ξ) enables the development of a tractable theory and captures the conductance histograms of a wide class of molecules. Other possible forms can be developed to capture additional features of the conductance histograms.Computing a conductance histogram using Eq.  requiresc1,2 and c3,4 are characteristic coefficients due to the molecular-junction formation and rupture, respectively, given bySubstituting Eq.  in Eq.  results mentclass2pt{minimc1 and c2 (Eqs. (c3 and c4 (Eqs. (c1–c4 on the conductance histogram.Equation  providesc2 (Eqs.  and 10)c1 and c2c4 (Eqs.  and 12)c1 and c2T0, γ, and γ and the base transmission T0 are the quantities that define the intrinsic transport properties of the molecule. Figure γ. Specifically, small values of ∣γ∣ correspond to molecular junctions whose conductance is not very sensitive to changes in elongation, resulting in narrow histograms. In the figure, we have covered a wide range of values of γ to exemplify this effect; actual experiments might show less dramatic changes. Nevertheless, the chemical design of molecules with small ∣γ∣ is the key to creating molecular junctions with reproducible conductance features.Equation  enables ξ visited once the junction is formed, P(ξ), is asymmetric with a tail toward smaller ξ . Figure γ < 0, decreasing the loading rate results in the conductance histogram shifting toward higher conductance values. This is because when the junction is elongated slowly, statistically, it breaks at shorter elongations. For γ > 0, decreasing The loading rate, 83. Under the experimentally realistic conditions of Table The exponential (or any other monotonic) relation between the electrode gap and conductance will result in histograms that depend on the loading rate. This dependency has not been experimentally observed yet in the few characterizations that have been conductedn-(SMe)-Au molecules (CnSMe), (d)–(f) complex aromatic systems (A1 and A2), (g)–(i) supramolecular complexes composed of metallofullerenes and (j)–(l) radical containing molecules of varying length and charge. Overall, Fig. To demonstrate that Eq.  is usefu56 based on Gaussian broadening of energy levels and molecule-metal couplings. While both show good agreement . This class of molecular junctions leads to bimodal conductance distributions, corresponding to two stable binding configurations of the thiol anchor group on the Au electrode surface (top and bridge configurations)44. We show that the experimental histogram can be fitted to Equation  can alsod by Eq. . From thentclass1pt{minimaFigures 84. For completeness, we have included fits using Eq.  are known. Fitting the rupture-force histogram of both the metal-metal and molecular junction to Eq. (k0) and the distance to the transition state (χ‡) in each case. Fitting the conductance histogram to Eq. , the molecular base transmission (ξeq). This set of parameters completely defines the electro-mechanical model.To interpret the conductance histograms it is desirable to extract all microscopic parameters that define the entclass1pt{minimam to Eq.  to extramentclasspt{minimaTo demonstrate this procedure and test its numerical robustness, we generated synthetic rupture force and conductance histograms consistent with the parameters in Table k0 and χ‡85, instead of performing separate force measurements.Another possible strategy is to measure junction lifetimes to extract In conclusion, we developed a rigorous microscopic theory of conductance histograms in molecular electronics by merging the theory of force-spectroscopy with molecular conductance. As a result, we obtained a general and analytical expression (Eq. ) for the44.This theory is based on a physical picture in which the mechanical manipulation of the molecular junction determines the width of the histogram, and the stochastic nature of junction rupture and formation determines its shape. This picture emerged from a recent theory-experiment analysis of the contributing factors to the conductance histogram that showed that this factor alone could account for the width of conductance events encountered in experimentsγ determines the conductance width and should be a main parameter to investigate in future works that aim to improve the experimental resolution of conductance measurements. The predictions of Eq. (Equation  can be us of Eq.  can be us of Eq.  providesWe further provided a viable experimental strategy to extract all the microscopic parameters that define the mechanical and conductance properties in the proposed model. For this, it is necessary to complement the conductance histograms with rupture-force or lifetime histograms for the molecular and metal-metal junctions. Such experiments are needed to test the range of applicability of the theory and interpret the conductance histogram in terms of the microscopic parameters defined by the proposed model.59. Further, the theory can be generalized to multi-modal processes in which there is interconversion between different junction configurations that can coexist at a given elongation. This physical situation can be represented through multiple wells in the free energy surface in the presence of force.The theory is based on a single well in the free energy surface for the molecular junction. This unimodal contribution to the overall conductance histogram can be isolated using machine-learning clustering of experimental dataOverall, the developments in this paper open the possibility to extract physical information from the conductance histograms characterizing the electro-mechanical microscopic properties of molecular junctions, to design meaningful strategies to tune the conductance histogram, and to help bridge the gap between atomistic simulations and molecular junction experiments.All fittings were done using the non-linear least squares method, as implemented in the scipy.optimize.curve_fit python package. Example scripts are provided in the Further information on research design is available in the Supplementary InformationPeer Review FileReporting Summary


Perovskite solar cells (PSCs) have great potential for future application. However, the commercialization of PSCs is limited by the prohibitively expensive and doped hole-transport materials (HTMs). In this regard, small molecular dopant-free HTMs are promising alternatives because of their low cost and high efficiency. However, these HTMs still have a lot of space for making further progress in both efficiency and stability. This review firstly provides outlining analyses about the important roles of molecular orientation when further enhancements in device efficiency and stability are concerned. Then, currently studied strategies to control molecular orientation in small molecular HTMs are presented. Finally, we propose an outlook aiming to obtain optimized molecular orientation in a cost-effective way. The B site is mainly Pb2+, and the X site is a halide ion . To fabricate a PSC, the perovskite layer is usually sandwiched between an electron-transport layer (ETL) and a hole-transport layer (HTL), constituting a n–i–p device , obtaining a power conversion efficiency (PCE) of 3.81% and 3.13%, respectively pyrrole (DBTP) moiety as core unit, while methoxy-substituted diphenylamine (DPA) in the spiro-OMeTAD was retained . The two2Pc . Thereby, enhanced short-circuit current density (JSC) and FF were obtained for CuMe2Pc based device . As a result, the unencapsulated CuMe2Pc device retained 95% of initial PCE after being stored under conditions with temperature of 25 °C and relative humidity (RH) of 50% for 2000 h. Under the same conditions, the PCE retention for the CuPc device was 76%. The face-on orientation was retained upon varying the central metal to Pd, Zn or metal free . A. A2Pc  and hexamethyl-mono-n-butyl-substituted ZnPc (Me6Bu-ZnPc) as HTMs for PSCs [6Bu-ZnPc and Me6Bu-ZnPc are soluble in organic solvent, and the latter can form stronger π-π stacking with face-on orientation. Moreover, the perovskite layer stacked with Me6Bu-ZnPc HTL showed a blue-shifted photoluminescence (PL) peak due to decreased spontaneous nonradiative recombination from trap states. This indicates that there is a certain interaction between Me6Bu-ZnPc and the perovskite layer, which passivates the defects on the perovskite surface. The same group also explored the effects of alkyl length in soluble tetra-alkyl substitued Cu(II) phthalocyanines [−3, 1.26 × 10−3 and 8.77 × 10−4 cm2 V−1 s−1. However, their PCEs were still lower than the doped spiro-OMeTAD mainly due to the lower VOC .Pristine CuPc has poor solubility in common organic solvents due to the strong intermolecular π-π interactions. To obtain solution-processable phthalocyanine HTMs, substitution groups with sufficient steric hindrance are introduced to the phthalocyanine ring to weaken the π-π interactions. However, weakened intermolecular interactions do not guarantee a face-on molecular orientation. For example, tetra-tert-butyl substituted CuPc is a commercialized Pc derivative with reasonable solubility in organic solvent, but it forms edge-on stacking on the perovskite layer . In 2019for PSCs . Both H6cyanines ,102. It cyanines . As showower VOC b. It is −3 cm2 V−1 s−1) and PCE (20.56%) than the SM1 HTM (4.71 × 10−4 cm2 V−1 s−1 and 15.37%)  d.Porphyrins (Pors) are analogues to Pcs in regard to the molecular structure. Meanwhile, Pors are thermally and photochemically stable. Therefore, Por-based HTMs also draw wide attention in the field of PSCs . Lee et −5 cm2 V−1 s−1 for BDT-TPA to 8.40 × 10−4 cm2 V−1 s−1 (BDT-TPA-F) and 2.05 × 10−3 cm2 V−1 s−1 (BDT-DPA-F). The hole mobility of BDT-DPA-F is comparable to the doped spiro-OMeTAD (3.43 × 10−3 cm2 V−1 s−1) in efficient PSCs. Encouragingly, the dopant-free BDT-TPA-F-based device exhibited a PCE of 23.12% 2 as the template, the number of fluorine atoms on the A unit varied from 0 (0F) to 1 (1F), 2 (2F), 3 (3F) and 4 (4F). Upon fluorination, consistent with the results of BDT-based HTMs, the hole mobilities of DTS(BTTh2)2-based molecules were significantly increased owing to the enhanced crystallinity. Especially, 2F and 4F displayed maximum mobilities of 0.22 and 0.06 cm2 V−1 s−1, respectively. However, fluorination did not transfer the edge-on orientation to the face-on orientation.Fluorination was also adopted for benzothiadiazole (BDT)-based small molecules as shown in f 23.12% b and T80at 85 °C c,d. In c−1, much lower than that of spiro-OMeTAD and PTAA.Introduction of intramolecular non-covalent interaction is an effective way to improve the coplanarity of the backbone and thereby the intermolecular π-π stacking without extra synthetic ring-fusion steps. Based on the above concept, Yang et al. synthesized a molecule coded as BTORCNA, in which an intramolecular S···O interaction can be formed between adjacent thiophene units . In the −4 cm2 V−1 s−1. The PSC based on KR321 achieved a PCE of 19%, which was identical to the doped spiro-OMeTAD. Upon replacing the malononitrile acceptor with 1,3-indandione, N-ethyl rhodanine, and dicyanovinylene N-ethyl rhodamine  to perovskite [x, FTO, and perovskite substrates [3 perovskite surface via scanning tunneling microscopy (STM) [3 surface, which is consistent with the DFT calculation result. However, molecules were edge-on oriented in CuPc aggregates. The authors proposed that the above results were due to the fact that the CuPc-MAPbI3 interaction is weaker than the intermolecular interactions.Molecular orientation could also be influenced by properties of the substrate. For example, different molecular orientations were observed for Pcs when the substrate was changed from F-doped SnOrovskite ,96. Shibbstrates . The resbstrates . In 2021py (STM) . It was VOC  as HTM in p-i-n PSCs, and the effect of substrate temperature during thermal evaporation was studied . As showVOC c. Meanwhu et al. . In thisBased on the above reports, it can be seen that external factors play a significant role in determining molecular orientation, but related reports are few. According to the research in organic solar cells, processing methods and solution composition may also influence molecular orientation . UndoubtThis review summarizes the influences and impacting factors of molecular orientation in small molecular dopant-free HTMs. Compared to the edge-on orientation, face-on orientation is more beneficial for hole extraction, hole transport, and interface energy level alignment. Meanwhile, both enhanced photo stability and mechanical stability can be expected for face-on orientation compared to edge-on orientation. Therefore, face-on orientation is more desirable for efficient and stable PSCs. Molecular orientation in HTL is the result of multi-factorial conjunction. While further research ise deserved to reveal the underlying mechanisms of synergism, the significant role of molecular structure, thermal treatment, and substrate properties have been demonstrated.From the viewpoint of molecular design, the relative strength between molecule–molecule interactions and molecule–substrate interactions should be taken into consideration when the face-on orientation is pursued. Generally, the relatively stronger molecule–substrate interaction versus the molecule–molecule interaction is beneficial for face-on orientation. On the one hand, intermolecular interactions can be weakened by increasing the intermolecular steric hindrance. On the other hand, molecule–substrate interactions can be enhanced by introducing atoms  and/or groups  with a passivation effect to form extra interactions with perovskite. Although it was demonstrated to be effective in several cases, molecular engineering should be conducted under deliberative design. This is because both molecule–molecule interactions and molecule–substrate interactions can be simultaneously changed upon variation in the molecular structure. For example, a too large steric hindrance is unfavorable for both molecule–molecule interactions and molecule–substrate interactions. As a result, the pursued molecular orientation may not be obtained. Moreover, the true economic competitiveness of a new HTM depends both on its efficiency and synthetic cost. Hence, synthetic steps and purification procedures of the targeted molecule should be simplified as much as possible.Alternatively, face-on orientation can be obtained via interface engineering according to the factor that molecular orientation is sensitive to the surface properties of substrates. Substrate modification has been demonstrated to be an effective strategy to modulate molecular orientation in the field of organic solar cells . FurtherConsidering the fact that most efficient dopant-free HTMs contain large π-conjugations, it is straightforward to introduce π-conjugated interfacial materials as templates that can induce face-on orientation via strong π-π interactions with HTMs. For example, the templating effects of graphene materials have been demonstrated for different molecules, such as pentacene, DNTT, and copper phthalocyanine ,118,119.


Dr. Pereira-Sanchez will discuss how the climate change emergency apeals psychiatrists and demands both personal and organized responses. Such responses are in the domains of awareness, research, education, and action. Dr. Pereira-Sanchez will present specific examples from his collaborative work at the World Network of Psychiatric Trainees, where a global forum about the topic for trainees was organized, and the World Psychiatric Association, where he assists the coordination of a Tri-Sectional initiative on the topic.None Declared