Three semi-open-ended and three closed-ended academic questions were used to elicit pre-and post-study oral performance data from the participants. Independent-samples t-tests showed that after the intervention, the mobile-supervised group outperformed its control counterpart in a statistically significant manner in terms of Non-repeated L2 word production (NRW), T-unit count (TC), and Mean Length of Run after pruning (MLRP). The intervention group also significantly reduced their dependence on their L1-based speaker compensatory communication strategies (SC-CSs) in QDCDs. These results suggest that the intervention group outperformed the control group in their L2 academic oral performance and their language use tendency moves toward the L2 during QDCD. Based on the findings, we conclude that, even though L1 oral output may temporally enhance the quality of lower-intermediate-level EFL learners’ tasks, it may inhibit their academic oral proficiency development in the long run. Methods for fragmental bilingual oral output analysis are introduced. Pedagogical implications of the findings for MALL are also discussed.This study investigated the effects of mobile-supervised question-driven collaborative dialogues (QDCDs) on reducing lower-intermediate-level English as a foreign language (EFL) participants’ tendency of their first language (L1) use in academic collaborative dialogues and on improving their academic foreign language (L2) oral performance. Throughout a whole semester, one group ( In EFL contexts, where authentic communicative use of English is minimal, communicative pedagogical approaches have been found to be able to improve EFL learners’ oral performance , as theyGiven that it is during the planning and organizing process of learner-centered activities that learners could virtually interact and negotiate with each other in the L2 to facilitate the transformation of L2 declarative knowledge into procedural knowledge, to ensure EFL learners’ L2 use in collaborative dialogues, In studies on L2 oral development, researchers usually collect and analyze monolingual L2 data. Few studies worked on fragmental bilingual data, which are not regarded as an indicator of strong oral proficiency. However, when examining how L2 learners’ oral performance develops from a low level to a higher level, analyzing their broken L2 oral output becomes meaningful. Nevertheless, some of the existent measurements on complexity, accuracy, and fluency  are not Traditionally, researchers, influenced by Since the turn of the century, however, an increasing number of studies have shown that teachers regard the use of an L1 in the L2 classroom as a helpful and constructive tool for linguistic, managerial and social purposes . LearnerFor people who have not personally experienced the challenge of learning English as a foreign language in a context where the language is not used in society, it may not be easy to understand why limiting the use of their L1 in classroom interactions is so critical. As is well known, it is not uncommon to find that many EFL learners, after studying the foreign language for 6–8 years or even longer, are still not able to use English to communicate orally although they could get quite high scores in reading, writing and listening on the TOEFL or the IELTS .However, when foreign language learners shared a common L1 and when their L2 proficiency was low, the L1 tended to dominate in oral interactions in the foreign language classroom . Swain  and so on. Earlier implementation of MALL usually used mobile devices to deliver content, give vocabulary instruction via SMS  or MALL via SMS . Recent via SMS . SherineNotwithstanding the rich application of mobile devices in language learning, MALL tutorial applications, just as Oral proficiency or performance is usually measured by complexity, accuracy, and fluency . A rangeThese criteria are generally more applicable to monolingual data analysis. Some of them are unsuitable for the analysis of L2 learners’ bilingual oral output. For instance, when the standard deviation of the total oral output is high, non-repeated words could describe oral performance more accurately than the measurements of repeated words, or repetitions per 60 s. For instance, if Learner A utters just five L2 words in 60 s without repetition, his repetitions per 60 s would be zero. In contrast, if Learner B uttered 40 L2 words with six repetitions in 60 s, his repetitions per 60 s reach six. Measured by repetitions per 60 s, Learner A outperformed Learner B, it seems. However, as we can see, Learner B, who produced 40 L2 words, was much more productive than Learner A, who only produced five L2 words during the same time span. In this case, Learner B demonstrated higher L2 oral proficiency than Learner A. For the same reason, calculating the total number of T-units could be more accurate than calculating T-unit per 100 syllables .In many previous studies, while examining learners’ oral output quantity, total L2 words were calculated e.g., . HoweverWhile communication strategies (CSs) are usually used to describe strategies used by L2 learners in oral communication, they could be classified into L1-based and L2-based CSs. Learners’ choice between L1-based strategies  and L2-based strategies  may reflect their confidence and tendency in L1/L2 language choice. Therefore, analyzing L1/L2-based CSs has a potential to demonstrate L2 learners’ L1/L2 use tendency and how they use them. However, up to date, there has been no such report. To fill this gap, we intend to study on how mobile supervision would affect L2 learners’ L1/L2 use tendency by analyzing their L1/L2-based CSs preference.Among the various CS taxonomies, some inconsistencies or overlaps exist. For instance, in To analyze L1/L2 use tendency of the intermediate-level EFL learners with low oral proficiency, proper CSs need to be selected, and analysis methods need to be figured out. This study intends to address these issues.Our study aims to investigate how the recording function of mobile phones could be used to supervise L2 learners’ oral output, and how it could affect their L1/L2 use tendency and their academic oral L2 performance. Mobile phones were adopted in this research because it was a handy tool that almost every learner and instructor had at the university where data were collected. In other contexts, people could just as well use other mobile devices with recording functions. We chose the word “supervise” over “monitor,” because in L2 learning research, “monitor” implies the ability to detect errors and correct them . HoweverAs discussions often involve open-ended questions, we renamed QDGD as QDCD, because collaborative dialogues are those used by speakers in problem-solving and knowledge-building , which mTo supervise L2 use during QDCDs, we used the recording functions of the mobile phones to record the participants’ collaborative dialogues. The mobile phone functioned as a supervisor, encouraging maximal L2 use without excluding the L1, as the participants could think in their L1, use bilingual digital dictionaries and even use some oral L1 when they really had trouble to express themselves in the L2. Mobile-supervised QDCDs was designed in accordance with the theory of Transdisciplinarity, which suggests that a successful integration of different disciplines should not result in more complexity and negate the comprehension of the involved parties but instead should make things easier to follow, and thus create a more effective learning environment .Drawing on the existing literature and related discussions above, we formulated two hypotheses regarding the effects of the mobile-supervised QDCDs on the EFL participants’ change in their L1/L2 use tendency by analyzing their L1-based and L2-based SC-CSs, and their academic oral performance in a naturalistic instructional environment:Hypothesis 1: Mobile-supervised QDCDs will reduce the lower-intermediate-level EFL participants’ dependence on their L1-based SC-CSs in academic collaborative dialogues.Hypothesis 2: Mobile-supervised QDCDs will help improve the lower-intermediate-level EFL participants’ academic L2 oral performance.The study was carried out in two classes of college juniors majoring in English. The general framework of the experiment is shown in The participants were a convenience sample of 50 university juniors majoring in English, ranging from 19 to 21 years old, from two different intact classes. They were two parallel classes in the same university, so they generally attended similar courses according to the syllabus. The two classes were randomly assigned to the intervention group or the control group. Before participating in this research, they had received at least 8 years of English education. All of them shared the same L1 (Mandarin Chinese). To make the data comparable, only the recordings of those who participated in both the pre-study recording and post-study recording were analyzed. Among 24 participants in the intervention group, three girls, who were the top students in class, were absent from the pre-study recording but attended the post one and one boy was absent from the post-study recording. Thus, there were 20 valid participants. Although these four participants were excluded from the analysis, the transcript of the three girls’ post-study recording is shown in Up to our knowledge, there has not been a perfect method which may measure oral output accurately. Many studies on oral proficiency, although used the same content in their pre-post tests, and validity was justified, adopted the examiner scoring system. Although the examiners were trained, the subjective features of the evaluation were still unavoidable. A popular oral test practice is to use the same materials to elicit the pretest and posttest oral data e.g., , but MayBefore the study, the pre-study oral data were collected from the intervention group and the control group. The data from the two groups were compared to see whether the participants’ L2 oral performance was at the same level before the intervention. After the performance similarity of the two groups was confirmed, the intervention was administered to the intervention group. After the intervention, the post-study oral data were collected and results were compared to see whether there were any statistically significant differences between the two groups. The detailed processes are as follows:Advanced English Coursebook). The course ran for two academic semesters, each of which lasted 18 weeks, with an average of three classroom hours per week.The intervention was carried out in the Advanced English Course, a comprehensive English course offered in many Chinese universities to junior English majors to enhance their reading, speaking, listening, writing and translating skills. However, the course was traditionally taught with a focus on grammar and vocabulary. In recent years, it has been undergoing reform to restore its original full-skill-practice purpose. Both groups were taught by the same instructor (the first author), using the same textbook , rhetorical devices  and terms about syntactic functions . The L1 was used by both the instructor and participants in classes for vocabulary study, cultural background introduction and academic term illustration. In their last class of the first semester, the pre-study oral data were collected in their classroom, using the pre-study oral elicit questions to elicit the participants’ QDCDs, which were recorded. Before collecting the pre-study oral data, recording was exercised several times in both groups during their QDCD to familiarize them with the process of recording.Throughout the second term, the two groups received the same general teaching processes， except that 1 h each week was devoted to mobile-supervised QDCDs in the intervention group, while the control group went through non-supervised QDCD, discussing the same questions. To obtain authentic recordings of the collaborative dialogues, it is important to ask the participants to keep their mobile phones in recording mode without stopping them until the end of their discussion. After class, the recordings from each group were sent to the instructor through QQ, a popular mobile phone social communication app widely used in China, offering various services including the exchange of audio, video and other types of files between individuals or in groups. Some recordings were sent to the instructor through e-mails or saved directly to the instructor’s lap top through flash drives when the participants preferred. The instructor in this study sometimes brought several mobile phones to record the students’ QDCD, which proved to be quite convenient, because no data transferring is necessary. The steps in using QDCDs in the Advanced English course are illustrated in Given that wrong answers from a group member could trigger and elicit further meaning negotiation and extended discourse, only the quantity of the recorded L2 oral output was generally evaluated, regardless of the correctness of the answers. No detailed evaluation was made and no detailed feedback was given to the participants about the recordings. To help the control group avoid debilitating anxiety in the post-study recording, mobile phone recording was also used with them from time to time, but the participants were told that the recordings would not be evaluated but were merely used for research purposes, and they were asked to go on with their QDCD in the way they usually do during classroom discussions. It turned out that their usual way was, just as we had observed before, to talk about the questions mainly in their L1 and wrote the answers down in the L2. Consequently, the supervising function of the mobile phone was removed. In the last class of the second term, the post-study oral data were collected in their classroom with the post-study oral elicit questions to elicit the participants’ QDCDs, which were recorded. Group members of the pre-study recordings and post-study recordings were kept the same. To guarantee the quality of the recordings, the recording devices used in the pre-and post-study recordings were prepared by the instructor.Before both of the pre-study and post-study oral data elicit recording, the participants from both groups were told that the recordings made in class would be used by the instructor in a research project only and not for evaluation, and their personal information will not be revealed in any form anywhere. By doing so, neither of the groups was put in the examination context, yet they knew that their recordings would be heard by the instructor later. They all expressed consent to this procedure. We did this because, during the experiment, the intervention group’s QDCDs in each class somewhat resembled oral tests because their recordings were evaluated and scored. However, this was not the case for the control group. Thus, if the participants were put in the pre-and the post-testing conditions, the control group might suffer from anxiety and that may affect the reliability of the data. Therefore, the data we collected were the authentic QDCD data in the naturalistic academic instructional environment. At the end of the intervention, as the participants were extremely busy preparing for final examinations, a brief meeting was held by the instructor to collect the general comments and suggestions from the participants orally. The meeting was held in Mandarin Chinese, their L1.As we mentioned in the literature review, to measure L1/L2 use tendency in this research, counting the number of L1 and L2 words was nonapplicable. We decided to resort to the calculation of L1-based CSs and L2-based CSs. As reviewed above, some CSs are used by speakers and some are used by listeners; some are used to solve language problems by manipulating available language knowledge, and we call them compensatory CSs; while others are labeled sociocultural strategies due to their communicative purposes. Given the aims of this study, we intended to promote speaker compensatory communication strategies for measuring the participants’ L1/L2 use tendency.Achievement Communication Strategies (CSs)Independent Achievement.L1-based strategies: code-switching, foreignization, literal translation.L2-based strategies: paraphrasing, word coinage, restructuring, formal reduction .Dependent Achievement.We adopted the SC-CS typology, as reported in Abandonment Communication StrategyMessage abandonment.Direct appeal This typology analyzed L1-based SC-CSs and L2-based SC-CSs. We proposed that any attempt to express an idea, either grammatically correct or incorrect, in an L1 or an L2, be deemed as an adoption of the achievement strategy see . Therefo{I guess that “by hard” may mean that something is not easily gained — difficultly gained, difficultly obtained}, we coded it as using code-switching twice. While for the consistent L1 expressions, each L1 T-unit was calculated as one instance of code-switching, because we think that the L2 learner, after each L1 T-unit utterance, gets a very good chance to switch back to the target language, but he/she gives up the target language and switches back to the L1 again. This could be a good indicator of the learner’s tendency in the choice of the languages in communication. For example, if Student B said: 他知道有这么一条消息。[code-switching1] 知道具体的消息是什么。[code-switching 2] 他就是，他的助手向他报告了德国入侵俄罗斯的这一则新闻。[code-switching3] {He knew there was such a piece of news. He did not know the exact information. That is his assistant reported to him the news about the invasion of Germany into USSR.}, we coded it as using code-switching three times. We can see that, regarding code-switching calculations, Student B (with three instances of code-switching) has a stronger reliance on the L1 than Student A (with two instances of code-switching). This is more reasonable than calculating all three L1 T-units as one instance of code-switching.While calculating SC-CSs, code-switching encompasses switching both at intersentential and intrasentential levels. Each intrasentential code-switching was calculated. If Student A said: 我觉得 “by hard” 应该是来之不易的吧 — difficultly gained, difficultly obtained. {priority}’ in English?” was a direct appeal.We also distinguished direct appeal in SC-CSs from common questions. For example, “What does the sentence mean?” was considered as a common question; while “How to say ‘优越性As we mentioned in the literature review that this study was different from previous studies in that it focused on bilingual data with high standard deviation and low proficiency, and we found that many existent complexity, accuracy and fluency measurements not applicable. As a result, we adopted one index to measure the total number of non-repeated L2 words, one to count the L2 T-units and another one to measure fluency. Space constraints make it impossible for us to describe these in more detail. Complexity, accuracy and fluency development are discussed in another paper.Non-repeated words (NRW). It is calculated by subtracting the repeated L2 words from the total number of L2 words uttered. T-unit count (TC). It refers to the total number of independent clauses or independent clauses with their dependent clauses ( clauses .Mean length of run after pruning (MLRP). It is calculated as an average number of non-repeated L2 syllables produced between two pauses.Considering the features of bilingual data (L1 and L2 mixed), and drawing from the various existing oral proficiency measurements, especially those proposed by Run-on sentences were counted as two T-units and sentence fragments were not calculated . By doinIn this study, fluency was measured by the mean length of run after pruning (MLRP). Each disfluent pause of 0.25 s and longer, each terminating interruption (an interruption causing the termination of the current utterance), each time of code switching, and each time of L1-based direct appeal were calculated as a pause. If a disfluent pause, a terminating interruption, a code switching or an L1-based direct appeal overlapped with each other, they were integrated into one pause when we calculated the MLRP. Long pauses (silence caused by meditation), which lasted for 20 s or longer were pruned. The reading of the texts or the reading of the questions, as well as the talking with the instructor for help were also pruned.The bilingual recordings were manually transcribed by an instructor of English with the assistance of two English-major learners. The transcribing and coding processes are explained in some detail in As we mentioned before, when we designed the pre-post oral data elicit questions, we intended to see how the control group and the intervention group would be different after the intervention in collaborative dialogues when they had the freedom to choose from the L1 and the L2 for oral output, and when they were forced to use the L2. However, preliminary data analysis showed that that the participants’ choices between L1 and L2 seemed to be more ascribed to their level of confidence in the L2 than to the directions given by the instructor. The control group dominantly resorted to the L1 throughout both recordings, while the intervention group mainly used the L1 in the pre-study recording, but predominantly resorted to the L2 throughout the post-study recording see . It seemAfter the pruning, the pre-study recording of Control Group 4 turned out to be the shortest of all the recordings, averaging ~2.5 min for each participant. Taking 2.5 min as an average length of output per person, we extracted the recordings from each group. For instance, there were four participants in Control Group1, so we extracted a 10-min recording with the most L2 expressions. The recordings extracted turned out to be predominantly related to the discussions over the semi-open-ended questions.The bilingual transcriptions of the extracted recordings were coded by two experienced instructors independently for communication strategies and performance indices. Any disagreements were worked out through discussions until the two coders came to 100% agreement. The transcripts were firstly coded for SC-CSs. Then repetitions were replaced by the mark of #. Each pause of 0.25 s and above caused by disfluency and each end of the turn of talking were coded with @. Interruptions from the others which caused the termination of the utterances were also marked with @. All these codes were then checked for consistency by the two of us authors as a way of verifying their accuracy of the two coders’ coding. Then the utterances made by each participant were singled out for further calculation.The following example demonstrates the coded post-study recording excerpt of St22 from the control group. These utterances originally scattered among the utterances made by all the group members. We singled them out and put them together for analysisExcerpt 1St22:Forbear 是什么意思呀? [csw-L1].{What does “forbear” mean?}St22:世界范围里，大家还没有解决这个问题。[csw-L1].{The problem has not been solved worldwide.}St22:看不懂。 [csw-L1].{I cannot understand.}.St22:嗯 [csw-L1]，bitter peace,{yeah.}St22:是不是来之不易的和平呀?[csw-L1] 就是经历 [csw-L1] hard 和{Does it mean the hard-won peace?} {That is after experiencing hard andbitter 以后才得到的和平。[csw-L1] 所以我们要要更加，就是因为为.bitter, people finally got the peace.} {Thus we should be more, should be more.了这种和平要更加注意。[csw-L1].careful (to maintain) this kind of peace.}St22:就是，我觉得是不是经历过战争以后我们才，[csw-L1]就是慢慢的这.{That is, I feel that it may mean that only after we experienced the war, we gradually.种性格就不去再去挑起战争了[csw-L1]。就锻炼了。[csw-L1].form this characteristics of not starting wars.} {That means “annealed.”}St22:disciplined 怎么讲? [csw-L1].{How should we explain “disciplined”?}St22:他知道这个和平夹杂着 [csw-L1] …… 是痛苦的欢乐吗? [csw-L1].{He knew that this peace were mingled with … pain and happiness?}St22:嗯，那个叫什么来着?[csw-L1] 居安思危吧? [csw-L1].{Yeah, what do we call that? Be prepared for danger in times of peace.}St22:就是经历过磨难以后我们才知道在和平时代自己要自律的那种吧?{That is to say through tribulation we learned that we need to develop self-discipline.[csw-L1] 因为这个和平我们知道是来之不易的。[csw-L1].{in peace, because we know the peace was hard-won.}St22:来之不易的怎么说? [csw-L1].{How can we say “来之不易” (hard-won)” in English?}St22:Human rights? 还是ancient heritage? @ [csw-L1].{or}.St22:Hard 不用翻了。[csw-L1] 就是hard。[csw-L1] 就直接写hard，把.{We do not have to translate < It should be paraphrase > “hard.” It is hard. Let us.bitter 翻译一下就行。[csw-L1].{just write down the word “hard,” and translate < It should be paraphrase > “bitter”}.St22:我觉得是ancient heritage. [csw-L1].{I think it is ancient heritage.}.St22:后面还有一个[csw-L1] which. 21页。[csw-L1].{There is still another one after the word “which.” On Page 21.}St22:就先看前面的 [csw-L1].{Let us handle the former one first.}St22:Oh, my God! @.St22:The human rights that the nation had committed to us @ can.not be achieved @. [frd-L2].St22:好下一个。[csw-L1] Next question.是排比吗?[csw-L1].{Ok, the next one.} {Is it parallelism?}Parallel. @ [frd-L2].St22:Repetition. 哦不对。[csw-L1].{Oh, it’s incorrect.}St22:Parallelism and @ alliteration @. [frd-L2].Using three asterisks (***) to represent the L1, we finally retrieved the following L2 utterances of St22’s: Forbear *** bitter peace, *** hard *** bitter *** disciplined *** Human rights? *** ancient heritage? @ Hard *** # bitter *** ancient heritage. *** which. *** Oh, my God! @ The human rights that the nation had committed to us @ cannot be achieved @. *** Next question. ***?Parallel. @ Repetition. *** Parallelism and @ alliteration @.t-test was used for data processing for the two groups.In the above data, words like “Forbear” and “bitter peace” were not regarded as reading from the book, because the speaker integrated them into the idea being conveyed. According to our pause calculation criteria, St22 paused 20 times altogether while she uttered 68 L2 syllables. Therefore, her MLRP was 3.4. It means that, on average, St22 only produced 3.4 syllables each time when she tried to use the L2. She uttered 39 non-repeated L2 words in total, with one T-unit. Every participant’s singled out L2 expressions were calculated with MLRP, TC, NRW, and SC-CSs, and then the t-tests were run. As shown in t-tests on the pre-study recording data demonstrated that, before the intervention, no statistically significant difference was found between the two groups in SC-CSs . Both groups depended largely on L1-based achievement SC-CSs, the mean frequency of which was 32.4 for the intervention group and was 38.58 for the control group. Abandonment and direct appeal strategies were seldom used.As the dependent variables were normally distributed, t = −10.39 and p = 0.000; for the L2-based SC-CSs, t = 6.09 and p = 0.000. The intervention group used significantly fewer L1-based SC-CSs (mean = 1.25) than the control group (mean = 32.88); while it used considerably more L2-based SC-CSs (mean = 13.40) than the control group (mean = 3.12). The abandonment and the direct appeal SC-CSs remained low. Such a result indicates that during the post-study recording, whenever SC-CSs were needed, the intervention group predominantly resorted to L2-based SC-CSs. Interestingly, among all the L2-based strategies, formal reduction was used predominantly in both groups before and after the intervention.However, after the intervention, statistically significant differences between the two groups in the use of the L1-based and the L2-based achievement SC-CSs were identified: For the L1-based SC-CSs, t = 1.031, p = 0.308; for NRW, t = 1.343, p = 0.186; and for TC, t = −0.176, p = 0.861. This suggests that at the beginning of the intervention, the two groups were almost at the same level in terms of their L2 performance. The means of TC for either of the groups were no more than two T-units. Nevertheless, in the post-study recordings, statistically significant differences were observed in the three oral performance indices between the two groups: for MLRP, t = 8.245, p = 0.000; for NRW, t = 3.918, p = 0.001 and for TC, t = 6.418, p = 0.000. The Standard Deviation of NRW in the post-study recordings was exceptionally high (103.11) for the intervention group, though.Hypothesis 2 was explored by drawing upon the data presented in With respect to Hypothesis 1, which stated that mobile-supervised QDCDs will reduce the lower-intermediate-level EFL participants’ dependence on their L1-based SC-CSs in academic collaborative dialogues, the results clearly support this, as the excerpt from two participants randomly selected for illustration purposes here, StA from the intervention group and St26 from the control group, clearly illustrate.Excerpt 1StA (pre-Rd): 就是没区别。indistinguishable 就是没区别是吧?是一样的。.{It means there was no difference. Indistinguishable means no difference, does not it?}它那个，对，它是双重否定，是吧?Lo- @ lo- @ lo-那个词，loti- @ lotis-.{It is, yeah, it is双重否定 < litotes or double negation>, is not it Lo–lo- lo-?} {That word, loti-lotis-}.黑板上写着呢。 然后第三个, 老赵，.{It is written on the blackboard. Then the third one. Old Zhao < addressing her partner>.F. O. @ F. O. 是Foreign Office …{F. O. @ F. O. is Foreign Office}.StA (post-Rd): The teacher has mentioned @ the same revolutionary belief is equal or equality. All men, all men are created equal @ that is endowed by their nature. “At issue” means revolutionary is still not solved. The revolutionary is objective. No. For them the focus is on the “belief” and “globe,” @ so it’s on the whole world not the independence of America. @The “revolutionary belief” means @ people @ all men are created equal…St26 (pre-Rd):我觉得前面的I was awaken 还是没有I get up。.{I guess that the previously mentioned “I was awaken” means I did not get up yet.}.我觉得是。 to the effect which @ which said that @ Germany is @ likely to @ attack.{I feel it was so.}应该是has began to了吧?应该has take actions to @ to他听到了那个，他听到了.{It means “has began to,” does not it? Should “has take actions to to… “He heard that.攻击。意思是别人告诉他了吧?…{He heard about the attack. Does it mean someone told him?}St26 (post-Rd): 祖先，就前面那些。yet 就是but 吧?But the @ revolution.{Forbears refer to the previously mentioned. Does “yet” mean “but”?}这要不要翻?不用翻? But the same revolutionary belief…@ 人生而平等。.{Do we need to translate it? No?} {All men are created equal.}啊!The revolutionary belief, @ such as the @ equality between @ humans @ human.{Oh!}being @ and 还有什么?就是一句话吗?到 global. 嗯，那就这句话，就这 …{What else? Just one sentence? Till “global.” Yeah, then it’s just this sentence, just this}.{Is it?} and “我觉得是” {I think so.}. During the early stage of the intervention, participants from both groups complained that speaking in the L2 required more attention and that interfered with their trains of thought; therefore, they preferred to use L1-based SC-CS. This might indicate that, before the intervention, for both groups, the L2 had not been activated as the language of communication.From Excerpt 2, we see that both participants resorted mainly to the L1-based code-switching strategy in the pre-study recording, but in the post-study recording StA used none of this, while St26 still stuck to it. We also observed that in the pre-study recordings, both participants resorted to the L1-based CSs even when they expressed very simple ideas, such as “是吧?” {I cannot avoid speaking Chinese}”; “快抓紧时间说中文，等会就不能说了 {Let us make full use of the time speaking Chinese as we will not be allowed to do that later}.” In contrast to this, the intervention group predominantly resorted to the L2 even when they were allowed to answer the first three questions bilingually. The intervention group reduced 60% their use of various SC-CSs, which was mainly replaced by successful direct L2 communication. Using the L2 became an initial and autonomous choice for them, suggesting that mobile-supervised QDCDs had unfettered the participants from their L1 dependence. Moreover, their task products (the answers to the questions in English in written format) were just as qualified as those of the control group. However, the control group, although they were provided with the same opportunities for collaborative dialogues, still heavily depended on L1-based SC-CS. As we mentioned before, the participants’ choices between the L1 and the L2 were more ascribed to their level of confidence in the L2 than to the directions given by the instructor. This discovery could explain, at least in part, why many L2 encouraging methods used by L2 instructors were unsuccessful as we mentioned in the literature review. This finding also implies that it is necessary and important to find methods which may effectively force and assist the lower-intermediate-level EFL learners to use the L2, and mobile-supervised QDCD looms to be a good solution.In the post-study recordings, some participants from the control group still said: “我不能避免说中文 Regarding the functions of CSs, quite a number of studies found that CSs would only temporally improve communication, and their overuse would hinder vocabulary and syntax development in learners e.g., . As mobiRegarding the second hypothesis that mobile-supervised QDCDs will help improve the lower-intermediate-level EFL participants’ L2 academic oral performance, our analysis of data gives us evidence in support of this hypothesis in terms of MLRP, NRW and TC.As we can see, although the intervention group made statistically significant progress compared with the control group in MLRP, it has not reached autonomous stage. However, the progress is considerable, because it suggests that, after the intervention, the majority of the participants from the intervention group could get access to their L2 knowledge faster although the process was still slowed down as they still need to refer to declarative knowledge from time to time. This seems to imply that the intervention helped them to progress from the “cognitive” stage into the “associative” stage of language learning.As regards Non-Repeated Words, the intervention group’s performance increased from 51.4 to 149.1 on average, but that of the control group increased from 36.96 to 49.15. Regarding TC, at the beginning of the intervention, both groups’ T-unit production was low. Five participants from the intervention group and seven from the control group produced zero T-units. It can be speculated that, if the participants always resort to fragmental L2 expressions, little progress will be made in their L2 development. After the intervention, the average T-unit production of the intervention group increased to 13.90. This can be viewed as evidence of how mobile-supervised QDCDs helped the EFL participants in syntax development.The standard deviation of the intervention group’s performance in NRW was high in the post-study recording, reaching 103.11. Virtually the standard deviations of the intervention group in MLRP, NRW, and TC were all higher than those of the control group. Although some participants apparently benefitted much more than the others from the mobile-supervised QDCDs, the big participant performance difference did not undermine the conclusion that the intervention was effective in the EFL context where the current research was based. This conclusion is drawn on the fact that all participants from the intervention group benefited from the intervention significantly in one aspect or another see . Who mayAlthough in previous studies scholars have argued for the facilitating functions of the L1 oral output in L2 development, the findings of our study seemed to suggest that, for lower-intermediate-level EFL learners, the quantity of L1 oral output used during learner-learner collaborative dialogues by the leaners might be inversely related to their L2 oral proficiency development in the long run. During the first few weeks of the current intervention, the intervention group lagged behind the control group both in the quantity and quality of their written answers to the questions because the L2 communication caused some difficulties in meaning negotiation. However, before long, they not only caught up with the control group in their written reports but also outperformed them in their L2 oral output. Their constant and sustained use of the L2 facilitated their L2 oral performance without impeding their reading comprehension or problem solution capacity. These results seemed to suggest that lower-intermediate-level EFL learners could successfully accomplish their academic tasks without depending on their L1.According to the data we collected at the end of the intervention in a brief meeting we held with the participants, about 77% of the participants from the control group complained about the waste of time in discussing the questions. St10, for example, from the control group complained that everyone had different ideas about a question and so they had to persuade each other for a long time. As they always talked in their L1, they made no progress in English. Over 80% of the participants from the control group agreed with him. When asked why they did not use English as their L2 in the discussion, they said they doubted their ability to make each other understand in it. In contrast to this, however, over 90% of the participants from the intervention group felt that they had made progress in L2 oral performance because they said that they had benefited from the intervention. StQ, for example, from the intervention group said that his English was poor so he had worried about the possibility to discuss the questions in English. However, it turned out to be fine even though sometimes he, like others in the group, showed a little bit of anxiety when they were not able to express their ideas quickly. Although he felt he only made some progress in oral English, he felt much more confident to use it now.Hence, we see that in the control group, where the L2 was not being used during the collaborative dialogues, the participants experienced some impatience and anxiety because they felt the discussion was time-consuming and their L2 oral performance barely improved. In contrast, the intervention group felt that they were making progress in improving their L2 oral performance despite them having to undergo some kind of stress, or more accurately, a kind of facilitating anxiety that became the driver for their perseverance in achieving success or reaching out for excellence. The progress they made gave them some enjoyment in learning English and in a way fostered their interest in a growth mindset and willingness to communicate in the L2 see .By integrating teacher evaluation of the participants’ L2 oral output process into the evaluation mechanism, mobile-supervised QDCDs also motivated the participants to engage in the L2 collaborative dialogues because it became personally relevant : their tIn our earlier work , the desOur research results seemed to suggest that predominant L2 use during the planning and organizing process of learner-centered activities for lower-intermediate-level EFL learners was quite effective in promoting their L2 academic oral performance; although predominant L1 use helped to enhance the learners’ immediate task completions, it seemed to have negative effects on their oral development in the long run. Such a conclusion was drawn from the research results that the control group which dominantly used the L1 during the experiment made little progress in oral performance at the end of the experiment although they outperformed the intervention group in answering the questions given by the teacher in the first few weeks. For lower-intermediate-level EFL learners, our findings seemed to support This study also investigated whether the limited use of the L1-based SC-CSs would debilitate task accomplishment. Although some researchers cautioned that without the assistance of the L1 the learners may not have been able to accomplish the tasks as effectively , which cDrawing on the above discussions, we suppose that, for lower-intermediate-level, intermediate level and high level L2 leaners, it might be advisable to integrate teacher evaluation of the participants’ L2 oral output during the planning and organizing process of learner-centered activities into the evaluation mechanism, and mobile-supervised QDCD could be facilitating to such operations. Mobile-supervised QDCD are applicable to many different types of student-centered language learning contexts, for instance, task-based instruction (TBI), project-based in struction (PBI), and content-based instruction (CBI).While designing mobile-supervised QDCDs, it might be advisable that instructors observe several issues: Firstly, it might be necessary to find proper schemes to reduce the level of difficulty of the requirements. For instance, in our study, the oral recording evaluation emphasized quantity over quality, and the L1 was still allowed for dictionary consultation and communication assistance. In this case, the less demanding tasks helped the participants to overcome their doubts about their ability to communicate in the L2, and gradually, with the progress they made, their anticipated value of the outcomes of the activities increased, and therefore the participants were further motivated . SecondlAs for oral output evaluation, there has not been a perfect method for measuring oral output accurately. In this study, field-specific question lists were also used to elicit oral output among learners in QDCD. Under the supervision of mobile phones, they seemed to be quite effective. Such questions are associated with the academic realms that the learners are learning, and these topics might also be associated with their future academic evaluation or future career; therefore, the questions become personally relevant to the learners .Our study also showed that fragmental oral output is worth our instructional attention because it helps us understand how L2 learners develop from low level to higher level oral performance. In the current study we suggested the methods of singling out an individual’s utterance from dialogues or group discussions for oral analysis, coding and analyzing bilingual fragmental oral outputs see . HoweverFor the application of mobile-supervised QDCD, mobile recording devices are important. Although MALL usually refers to any language-related learning activities facilitated mainly by smartphones, personal digital assistants, iPods, we would like to take a more generalized concept of MALL. We hold that any mobile devices, such as mobile digital recorders (or recording pens), could be included as far as they are mobile and could facilitate language learning, as Unipus and pigai.org in our context, only provide to L2 learners with oral practice exercises such as reading-aloud practice, monologue or dialogue about daily issues , our research results seem to suggest that it may be advisable to integrate QDCD academic exercises into the MALL platforms for more advanced EFL learners, where learners could record their L2 collaborative dialogues over certain field-specific questions and then upload them for teacher evaluation and feedback. This could largely enrich the realm of topics and enhance authenticity of communication in oral practice for intermediate-and-above level EFL learners.Our research results may also have implications for MALL platform applications. While many current MALL platforms, such as Despite all the attention we gave to potential issues, we still think that a statement on some limitations is in order. Firstly, given the intensity of the study we had a relatively small sample size and the limited range of performance groups. Accordingly, readers need to exercise caution when interpreting the results. Secondly, instead of using the same materials, we designed two lists of field-specific oral data elicit questions associated with two different texts to elicit the pre-study and post-study oral data. Although we controlled the genre difference, participants’ lack of background information, text complexity and the length of the texts, and when compared with the commonly used oral test examiner scoring system, our linguistic analysis approaches  of the participants’ oral output may not be less objective if not more objective; the potential of using such question lists as oral tests still requires further study. Thirdly, interlocutor effects might have influenced the results of the research. In addition, we counted code-switching as pauses because code-switching might have caused interruptions to L2 utterances. When calculating L2 MLRP, we cannot overlook the possible interruptions caused by code-switching. Previous studies on bilingual oral data seldom measured MLR, maybe due to the difficulty in defining pauses. However, MLR is an important indicator of oral proficiency development, and it seems necessary to find proper ways to measure it when dealing with bilingual data. Therefore, the method used in our study requires further exploration. A further limitation is that in our analysis we extracted an average length of 2.5-min oral output per person from each 4-to-6-person group recording, in which most L2 expressions were uttered. The validity of such performance also needs to be verified through more thorough studies in similar contexts. Finally, we did not create the pretest and posttest conditions for the purpose of alleviating the control group from anxiety. Therefore, the data collected in the current research demonstrate the change that occurred among the participants in their authentic classroom academic oral interactions before and after the experiment. Whether the intervention could influence intermediate EFL learners’ overall academic oral proficiency also requires further study.This study was set up to examine whether mobile-supervised QDCDs would help the participants improve their L2 oral performance. Two hypotheses were examined: 1) mobile-supervised QDCDs will reduce the lower-intermediate-level EFL participants’ dependence on their L1-based SC-CSs in academic collaborative dialogues; and 2) mobile-supervised QDCDs will promote the lower-intermediate-level EFL participants’ L2 academic oral performance.Having nothing to say and not using their L2 are two obstacles to lower-intermediate-level EFL learners’ L2 oral proficiency development. By using list of questions to offer scaffolding for collaborative dialogues and by using mobile-device supervision to motivate the participants to speak in their L2, the mobile-supervised QDCDs seemed to be effective in improving the participants’ L2 oral performance. The mobile-supervised QDCDs successfully elicited more oral L2 output from the EFL participants. It provided a reasonably good platform for the EFL participants to negotiate meaning in their L2. As a result, such collaborative dialogues helped them, statistically speaking, reduce their dependence on SC-CSs significantly, especially on those L1-based SC-CSs, and they improved their L2 oral performance in areas such as MLRP, NRW, and TC. These appeared to have helped the L2 participants proceduralize their stored declarative L2 knowledge and move toward automatization in the very process of L2 production. The research result somewhat relieves us from the worries that without L1 oral output, lower-intermediate-level EFL learners may not successfully accomplish their academic tasks.From a pedagogical point of view, our results suggest that it is advisable for teacher evaluation of leaners’ L2 oral output process to be integrated into the evaluation mechanism so as to enhance their motivation in developing their L2 communicative abilities. Hence, they may have implications for the teaching and learning of EFL in other similar contexts. They might be able to shed light on the ongoing debate on whether interactions should be taken as an adjunct to conventional approaches or as an independent self-sufficient pedagogical methodology . FurtherOur findings also point to additional implications: (1) predominant L2 use during the planning and organizing process of learner-centered activities for lower-intermediate-level EFL learners seems to be quite effective in promoting their L2 academic oral performance; (2) question-guided field-specific oral data eliciting questions could be used potentially as an academic oral test format; (3) semi-open-ended questions, compared with open-ended and close-ended questions, tend to elicit more collaborative dialogues in QDCD; (4) fragmental oral output is worth our instructional attention because it helps us understand how L2 learners develop from low level to higher level oral performance; (5) methods in singling out an individual’s utterance from dialogues or group discussions for oral analysis are useful see ; (6) theClearly, many issues related to mobile-supervised QDCDs require further investigation . Given the design of our study and its findings, future studies may need to investigate whether QDCDs would help EFL learners improve oral proficiency in terms of accuracy and complexity in oral expressions and the appropriate ways for their measurement. Future research might also want to include learners of a range of proficiency levels in order to examine the utility of QDCDs as a pedagogical tool for helping learners improve their L2 proficiency. Researchers interested in this line of research might also want to replicate this study in other foreign language teaching and learning contexts.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the School of Foreign Languages Ethics Review Committee at Huazhong Agricultural University, China. Written informed consent to participate in this study was provided by the patient/participants.YC and LZ conceived and designed the study. YC collected and analyzed the data and drafted the manuscript. LZ finalized it for submission as the corresponding author. All authors contributed to the article and approved the submitted version.This work was financially supported by a grant from the Teaching Reform Research Program of Shenzhen Technology University: Studies on Communication Strategies Used by College Students in ESP Classes. It is also part of the follow-up study of “A Study of the Learning Plateau Phenomenon in Oral English Development (project no. 2012ZYTS001)” sponsored by a grant from the Fundamental Research Funds for the Central Universities.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.


Intravenous (IV) fosfomycin is increasingly used globally for treatment of infections due to multidrug-resistant Gram-negative bacteria (GNB). This study aimed to determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function.th dose of fosfomycin and concentrations were measured and modeled by population PK analysis. Monte Carlo simulations were conducted to evaluate the probability of target attainment (PTA) of different dosages using species-specific 1-log10 kill targets . The kidney function adjusted dosing regimens for E. coli are proposed by using the lowest dose that can achieve ≥ 90% PTA at an MIC of 32 (EUCAST breakpoint) and 64 µg/mL. The highest MIC values at which selected doses provide ≥ 90% PTA for K. pneumoniae and P. aeruginosa were also analyzed.Eligible patients were adults ≥ 18 years who were treated with IV fosfomycin 2-4 g every 6-8 hours. Five serial blood samples were collected after the 4V). The parameter estimates were CL of 0.65 ± 0.1 L/h, and V of 12.59 ± 0.8 L. The PTA of simulated dosages for E. coli are shown in Figure 1. For MIC ≤ 32 mcg/mL, a dosage of 12 g/day achieved ≥ 90% PTA for CLCR 90-120 ml/min. For MIC ≤ 64 µg/mL, a dosage of 24 g/day was needed. The proposed kidney function adjusted dosing regimens for E. coli are shown in Table 1. The highest MIC values of K. pneumoniae and P. aeruginosa where these doses provide ≥ 90% PTA were 128 and 256 µg/mL, respectively.A total of 138 plasma samples from 28 patients were included. The model was best described by a 1-compartment model with linear elimination. Significant covariates in final model were creatinine clearance and male sex on clearance (CL), and body weight on volume of distribution (E. coli at EUCAST susceptible breakpoint in patients with normal renal clearance and dose adjustments are needed for patients with renal insufficiency.A dosage of 12 g/day of fosfomycin is required for jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant


Idiopathic Pulmonary Fibrosis (IPF) is an age-associated progressive lung disease with accumulation of scar tissue impairing gas exchange. Previous high-throughput studies elucidated the role of cellular heterogeneity and molecular pathways in advanced disease. However, critical pathogenic pathways occurring in the transition of fibroblasts from normal to profibrotic have been largely overlooked.We used single cell transcriptomics (scRNA-seq) from lungs of healthy controls and IPF patients (lower and upper lobes). We identified fibroblast subclusters, genes and pathways associated with early disease. Immunofluorescence assays validated the role of MOXD1 early in fibrosis.We identified four distinct fibroblast subgroups, including one marking the normal-to-profibrotic state transition. Our results show for the first time that global downregulation of ribosomal proteins and significant upregulation of the majority of copper-binding proteins, including MOXD1, mark the IPF transition. We find no significant differences in gene expression in IPF upper and lower lobe samples, which were selected to have low and high degree of fibrosis, respectively.Early events during IPF onset in fibroblasts include dysregulation of ribosomal and copper-binding proteins. Fibroblasts in early stage IPF may have already acquired a profibrotic phenotype while hallmarks of advanced disease, including fibroblast foci and honeycomb formation, are still not evident. The new transitional fibroblasts we discover could prove very important for studying the role of fibroblast plasticity in disease progression and help develop early diagnosis tools and therapeutic interventions targeting earlier disease states.The online version contains supplementary material available at 10.1186/s12931-023-02419-0. Idiopathic Pulmonary Fibrosis (IPF) is an age-dependent chronic lung disease affecting individuals generally over 60 years old . The mecExtensive research has provided valuable insight into the origin and contribution of fibroblasts and especially myofibroblasts in pulmonary fibrosis , 10. AllHi macrophages with a potential role in lung fibrosis [To study the disease onset and progression, our group has performed scRNA-seq on upper and lower lobes of fresh human explanted IPF lungs and on healthy controls, identifying a subpopulation of proliferating SPP1fibrosis . Here, wfibrosis  and ribofibrosis –17 have Raw scRNA-seq data were derived from our previous publication . BrieflyHarmony, which integrates multiple scRNA seq datasets by projecting cells into a shared embedding in which cells are grouped by cell type, not the specific conditions related to the datasets [scRNA-seq raw count and cell-UMI (Unique Molecular Identifier) count matrix were generated by Cell Ranger . Single-datasets . t-DistrThe fibroblast cells from scRNA-seq data were processed by Seurat and Harmony to identify subclusters of fibroblast cells. Destiny was used for pseudotime analysis of the subclusters . VelocytFresh lung tissue , washed and incubated overnight at 4 °C with 1:300 of anti-MOXD1  antibody. Specific staining was detected with secondary biotinylated horse anti-rabbit antibody  followed by Vectorstain ABC Elite reagent and DAB peroxidase substrate  and counterstained with haematoxylin. Slides were mounted with permount mounting medium  and analyzed in a light microscopy .Briefly, formalin-fixed paraffin-embebbed tissue sections were deparaffinised, rehydrated and subjected to an antigen retrieval step, blocked with 10% Normal Serum  in DAKO diluent  from the lungs of three healthy control  and six IPF  samples (from three donors) was sequenced using next generation single cell sequencing. An important study design includes tissue from three upper lobes  and fibrotic tissue from three lower lobes   contained mainly cells from the healthy control donors (80% of the control FBs were in Cluster-1) as well as a smaller percentage of the IPF_UP and IPF_LOW cells (24% and 14% respectively). Cluster-2, a much smaller cluster , included cells from each sample origin. Cluster-3  contained mainly IPF_UP and IPF_LOW (56% and 64% respectively). Only 1% of the healthy control FBs classified as Cluster-3. Cluster-4  contained a slightly higher percentage of the IPF_UP and IPF_LOW (12% and 13% respectively) than the healthy control fibroblasts (6%). The breakdown of each cluster to sample types is summarized in Fig. Since fibroblasts in Cluster-1 came predominantly from control samples we consider this to represent the “normal state”; while those in Cluster-3, which came almost exclusively form IPF_UP and IPF_LOW, represent the “disease state”. Cluster-1, Cluster-2 and Cluster-4 had distinct expression profiles, but they were all present in healthy and IPF lungs , while cluster 2 was predominately composed of adventitial fibroblasts (SFRP2+PI16+SERPINF1+)  of Wnt signaling  have been previously shown to increase in lung fibrosis . In addition, we calculated a ribosome biogenesis score based on 267 other genes associated with this process (Gene Ontology Browser). Again, C2G2 showed a significant decrease for this score . Both these observations .To validate this finding, we used a second publicly available scRNA-seq dataset , that haTo identify early IPF biomarkers specific to fibroblasts, we examined the Cluster-3 top upregulated genes that also showed low expression in the rest of the cell types Fig. . The fivImmunofluorescence and immunohistochemistry staining of human lung tissues Fig. D. ImmunoVelocity analysis of fibroblasts using their spliced Fig. E, left aMOXD1 is a copper-binding protein and copper itself has been implicated in pulmonary fibrosis . BlockhuFibroblasts have been previously studied for their role in fibrosis in general and lung fibrosis in particular . ResearcOur results show that the majority of IPF lung fibroblasts have a distinct molecular phenotype, since they form a distinct cluster. Interestingly, fibroblasts from the upper and lower lobes have similar molecular profiles, which is consistent with the hypothesis that gene expression changes in fibroblasts happen at an early disease stage. The observed early shift in gene expression in IPF fibroblasts, especially in extracellular matrix associated genes , agrees with computationally deconvoluted bulk RNA gene expression signatures . These mOur results indicate that underlying cell state differences  influence the differentiation of fibroblasts to myofibroblasts. One of the top differentially expressed genes in the IPF fibroblasts (Cluster-3) is MOXD1, a copper-binding enzyme, which has not been previously studied in IPF. MOXD1 shows a tight association with the ER membrane and is not secreted . CurrentWe find that MOXD1 upregulation in fibrotic cells is part of the more general upregulation of copper binding enzymes, including Lysyl Oxidase Like 1 (LOXL1) and Secreted Protein Acidic and Cystein Rich (SPARC), which have been studied for their pro-fibrotic role in multiple organs , 40. TheDepending on their localization , approximately 15% to 25% of fibroblasts from IPF samples retain a transcriptional profile that resembles that of normal control lung fibroblasts. However, they form a subgroup which indicates that their “normal” phenotype is influenced by the disease environment. Another 25% of IPF fibroblasts along with 15% of control fibroblasts seems to be in “perturbed” states that are characterized by increased expression of ECM genes. It is reasonable to assume that these states may represent normal wound healing processes occurring in both control and IPF lungs. In the case of IPF lungs, these processes would eventually run uncontrolled resulting in severe fibrosis .One particular group of cells (Cluster-2) seem to capture this transition. It shows two distinct cell sub-populations with tendency towards opposing states. One subgroup shows a tendency to revert to a normal state while the other seems to be transitioning towards a profibrotic state. A closer examination of the profibrotic sub-population reveals a downregulation of almost all ribosomal proteins and dysfunctional ribosomal biosynthesis; and upregulation of the majority of copper-binding genes. We validate these findings in a similar cohort from a previous study . PosttraImpairment of ribosomal biogenesis not only could have an impact on the ribosomes’ cellular housekeeping role in protein synthesis but could also affect cell cycle and proliferation , 50. RibIn summary, we examine the events that take place in fibroblasts when cells transition from healthy state to disease. We demonstrate that, at the single cell level, changes in the transcriptome of fibroblasts appear early in the relatively unaffected upper lobes of the IPF lungs. We also identify two focal points (steady states) towards where the normal and the fibrotic cells coalesce. More importantly, we discover a point of transition between these two states, which is characterized by a significant decrease in ribosomal protein genes and a significant increase in copper-binding proteins. We examine the second most upregulated copper-binding protein, MOXD1, and find it to be fibroblast- and IPF-specific. Furthermore, we find that MOXD1 is also expressed at early stages of IPF suggesting that it can be used as an early biomarker of fibroblast pulmonary fibrosis.Increasing evidence supports the idea that IPF fibroblasts have acquired resistance to apoptosis  and haveAt present, a major limitation of this study is the lack of available biomarkers for these transitioning fibroblasts. Future studies can reveal how senescence and alteration of ribosomal protein and copper-binding pathways may affect the switch of fibroblasts from the normal steady state to a profibrotic state. Furthermore, in-depth studies of these fibroblasts may provide a useful diagnostic tool for early detection of IPF and possibly a therapeutic window before extensive tissue damage occurs.Additional file 1. Supplemental Data.Additional file 2. Supplementary Figures.


SCJ = 4.7 mA/cm2, OCV = 0.19 V, and fill factor = 59.73% are found under AM1.5G, exhibiting maximum efficiency of 6.5% (1 sun). The EQE of the cell is well above 60%. This work reports the influence of different substrate thickness, work function, and N-type doping on the efficiency and characteristics of graphene-based Schottky solar cells.Comparative studies of the 2D numerical modelling and simulation of graphene-based gallium arsenide and silicon Schottky junction solar cell are studied using TCAD tools. The performance of photovoltaic cells was examined while taking parameters, such as substrate thickness, relationship between transmittance and work function of graphene, and n-type doing concentration of substrate semiconduction. The area with the highest efficiency for photogenerated carriers was found to be located near the interface region under light illumination. The significant enhancement of power conversion efficiency was shown in the cell with a thicker carrier absorption Si substrate layer, larger graphene work function, and average doping in a silicon substrate. Thus, for improved cell structure, the maximum  Due to graphene’s unique structure and characteristics, a single atomic layer has attracted significant attention, such as high mobility, low resistivity, and band gap . GraphenThe proposed graphene structure is shown in The graphene GaAs and silicon junction solar cell are numerically simulated in this work using standard TCAD tools. It uses a typical method for materials such as amorphous, including state model of continuous density, auger recombination mechanisms, and Schottky, to solve continuity, Poisson, and current density equations. The dependence of these optical parameters with the photon energy has been included, taking into account the thickness of the substrate, work function of graphene, doping level, and their impact on cell efficiency.2/Vs of carrier mobility [Due to the fact that graphene is a novel material, it is not yet included in the SILVACO Atlas material library. As a result, in order to develop a reliable and exact model of the graphene film, the initial definition of the layer used 4H-SiC as the base material, which was then modified to give the metallic material properties and match experimental sheet resistance values . First, mobility , graphenmobility .2 window, and the graphene layer. Here, an oxide window was used to coat the silicon substrate with a 10 nm thick layer of graphene. With the use of TCAD, including the optical intensity, as shown in B* is effective Richardson constant, k is Boltzmann’s constant, and T absolute temperature.Most studies show that the heterojunction device for this structure is fabricated from a transferred chemical vapour deposition graphene layer on silicon in order to avoid expensive deposition methods and complicated processing ,22. In eGE = energy gap semiconductor.Additionally,y is the ray for the provided relative distance, α is the computed absorption coefficient for every combination value of , λ is wavelength, h is Planck’s constant, c is the speed of light, and η0 is the internal quantum efficiency, denoting the carrier number produced per photon per pair. It can be seen from In order to mimic the global terrestrial sunshine, the modelled device was illuminated with AM1.5G solar spectrum, which is taken into account by LUMINIOUS 3D for modelling sunlight in SILVACO Atlas . The ligSCI and OCV to establish how well a solar cell works because they affect how much power it can produce.It is crucial to utilize SCI and OCV utilisation at maximum power is measured via the fill factor. The efficiency can be expressed using FF as:These are the performance metrics that we employed in our research for evaluating solar cells.The Si crystal substrate is illuminated with an orientation <100>. For photogenerated carrier intensity, graphene functions as a transparent electrode. The difference between the work functions was built using a Schottky junction. We computed the I-V curves and external quantum efficiency (EQE), as illustrated in χ and graphene Gф is related to the barrier height Bф, as discussed in Bф, which will make the built-in potential biV increase according to the equation, biV = Bф − nV, where nV is the distance between Ec and Ef in silicon. Consequently, an enhanced graphene work function results in an increase in biV that corresponds to the upper limit of ocV. As shown in biV increases monotonically along with the FF and power conversion efficiency. This result is inconsistent with Y.F. Li’s group’s experimental findings [The difference between silicon findings .OCV and SCI increase for doping concentrations below 3 × 1015 cm−3. When the doping concentration exceeds 3 × 1015 cm−3, the cell’s performance is radically different. The mechanism for electron emission could be the origin of this phenomenon. The emissions of a carrier from silicon to graphene are dominated by the tunnelling emission process rather than the thermionic emission mechanism. As a result, there is a slight decrease in the open-circuit voltage. Second, a high doping level reduces the photogeneration carriers’ lifetime, particularly for light that has a long wavelength. These losses in the carrier collection result in a reduction in SCI. Thirdly, as indicated in 16 cm−3 doping level has the largest fill factor, despite having a lower power conversion efficiency than the other two doping concentrations. Therefore, the optimal efficiency is found at a moderate doping level of 3 × 1015 cm−3.The ability of silicon’s N-type doping to raise the photogeneration carrier intensity and energy level of Fermi is well recognised. Due to the larger barrier height compared to a substrate made of pure silicon, both In order to improve the design, it is also necessary to identify different performance parameters. A solar cell I-V curve with varying substrate thicknesses is depicted in SCJ using the measured EQE.F(λ) = intensity spectrum of AM1.5G sunlight, and q is electron charge. It is found that EQE is well above 60%, which is an indication of an effective cell structure. The absorption and transmission co-efficient of the cell is depicted in FF but lower efficiency. For GaAs, under low illumination, the majority of the carriers created in the region reside relatively near to the interface. When compared to graphene’s lower transmittance and greater work function regarding cell performance, the work function is effective for increasing the cell performance. GaAs with moderate n-type doping has a significant increase in power conversion efficiency; however, this form of device is significantly more sensitive to open-circuit voltage than short-circuit current. Therefore, Si has maximum conversion efficiency in terms of thicker absorption, larger graphene work function, and average doping in semiconductor substrates. As a result, it can be concluded from this work that graphene can function as a semi-transparent charge collector electrode and Schottky junction with a thermionic emission phenomenon for improved efficiency in SBSC solar cells.Silvaco ATLAS software was used to model graphene-based GaAs solar cells and graphene-on-Si Schottky junction solar cells in a unique way for photovoltaic applications. Numerical simulation in two dimensions was used to analyze the output performance. Additionally, we thoroughly examined the performance vs. various graphene work functions, substrate thicknesses, and N-type doping concentrations. The findings demonstrate that greater graphene work function, adequate absorption thickness, and mild silicon doping are superior for increasing the power conversion efficiency. Further analysis revealed that the anode’s vicinity experienced the development of the highest potential, which leads to improved charge collection and an improvement in the solar cell’s overall performance. It is possible to research, design, and construct various structures of graphene-based solar cells using this remarkable optimization technique and data. The conversion of the emission electron mechanism from the thermionic mechanism to the tunnelling emission mechanism is due to the implementation of high-level doping, resulting in maximum


Sarcoidosis is an inflammatory disorder in which patients frequently develop ocular manifestations that precede systemic involvement, sometimes it even presents as an ocular isolated form of the disease. The purpose of this study is to report the ocular and systemic manifestations of sarcoidosis in a series of Mexican patients, as there is a low incidence of the disease in this population.A retrospective case series of patients with positive classification criteria for sarcoidosis who attended Asociacion Para Evitar la Ceguera en Mexico, IAP between 2011 and 2022. Descriptive statistics were used to report the clinical, laboratory, and imaging findings and treatment. Numerical results were presented using median values and first and third quartiles for distribution.Fourteen patients were included in this study, 10 of them had definite ocular sarcoidosis (biopsy-proven), 4 had presumed ocular sarcoidosis. The median age of onset was 52 , with a predominance of female patients (71.4%). Ten patients (71.4%) debuted with ocular manifestations. The most common forms of ocular involvement were bilateral anterior uveitis (50%) and panuveitis (28.6%). Median follow-up was 24 (13–49) months.Sarcoidosis is a rare, underdiagnosed condition in Mexico and ocular involvement can be an early manifestation of the disease. Ophthalmologists should be alert to the signs of ocular sarcoidosis and collaborate with a multidisciplinary team to screen for systemic involvement if suspicion is high. Sarcoidosis is an inflammatory disorder of unknown cause, characterized by systemic inflammation and the formation of noncaseating epithelioid cell granulomas, which can affect practically every organ . It’s inDespite this, sarcoidosis in Latin America is rare, and the information on its prevalence, risk, and morbidity in Hispanic patients is limited –7. ThereThere is a wide spectrum of systemic manifestations of sarcoidosis that encompass many specialties in medicine. Lungs are the most affected organ in the disease  . AlthougThe second most affected organ in patients with sarcoidosis is the eye. Up to 30–50% of patients with systemic sarcoidosis will show eye involvement, or it can only be confined to the eye. The two main ocular manifestations are keratoconjunctivitis sicca and uveitis. Regarding ocular inflammation, anterior uveitis and panuveitis are the most common form of presentation, although the disease can affect any section of the eye –20.Ocular manifestations are often bilateral. These include orbital and adnexal non-specific manifestations, such as keratoconjunctivitis sicca (dry eye), dacryocystitis, conjunctival granulomas, and less commonly diffuse orbital inflammation, ocular nerve palsy, and scleral granulomas .Specific ocular manifestations support clinical diagnosis and help differentiate sarcoid uveitis from other types of inflammation. These are often accompanied by a sudden onset of pain or loss of visual acuity and include anterior segment signs such as mutton fat keratic precipitates (granulomatous uveitis) iris nodules either at the pupillary margin (Koeppe) or in the stroma (Busacca), Berlin nodules (trabecular meshwork nodules) and anterior tent-shaped synechiae at the iridocorneal angle. There are also intermediate and posterior inflammatory manifestations like snowbanking and snowball vitreous opacities, candle wax vascular shedding , microaneurysms, and optic disc nodules (granulomas). These manifestations guide the diagnosis of ocular sarcoidosis , 21, 23.Other manifestations include specific syndromes that have ocular and systemic manifestations, which help diagnose sarcoidosis without the need for a confirmatory biopsy, and include Heerfordt–Waldenström syndrome (uveoparotid fever), a combination of facial palsy, parotid gland enlargement, uveitis, and low/grade fever, and Löfgren syndrome, a combination of fever, BHL, erythema nodosum with migratory arthritis including or without ankle .The aim of this study is to report the ocular manifestations, systemic involvement, management, and outcome of sarcoidosis in a Mexican ophthalmology clinic.Medical charts, and records from patients who arrived at the Inflammatory Eye Disease Clinic from 2011 to 2022, in Association Para Evitar la Ceguera en México were retrieved and classified using the revised International Criteria for the Diagnosis of Ocular Sarcoidosis (IWOS) and the Standardization of Uveitis Nomenclature (SUN) classification criteria for ocular sarcoidosis , 24. PatFurthermore, the clinical evolution of each patient was classified using the SUN nomenclature of clinical status which includes inactive (grade 0 cells on anterior chamber), worsening activity , improved activity , remission (inactive disease for > 3 months after discontinuation of treatment) .A rheumatologist performed a systemic evaluation with laboratory and imaging studies. Systemic involvement findings were collected using the updated World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) tool . DiagnosLaboratory studies included angiotensin-converting enzyme (ACE), which is an enzyme produced by epithelioid cells derived from activated macrophages (characteristic of sarcoidosis) and lysozyme (LYS) is an enzyme produced by giant epithelioid cells, that reflects the presence of granulomas. Both were considered high when they exceeded > 120% of the laboratory reference value, blood serum calcium, and lymphocyte count values were collected retrospectively when available. Hypercalcemia was defined as serum calcium > 10.2 mequ/L and lymphopenia as < 1000 lymphocytes. Also, infectious diseases were ruled out, including syphilis, with a negative venereal disease research laboratory (VDRL) test and FTA-ABS, and tuberculosis with the tuberculin test (PPD) and/or IGRA test . If a paPulmonary involvement was defined as the presence of micronodules, atelectasis, hilar lymphadenopathies, or parenchymal changes without predisposing factors. The amount of involvement was categorized using the Scadding test for chest X-rays . Chest cConfirmation was achieved with the presence of non-caseating granulomas, Schawman, or asteroid bodies in a tissue biopsy or a classic specific form of sarcoidosis, such as Heerfordt´s or Lofgren´s syndromes , 21.Results were analyzed using the IBM Statistical Package for the Social Sciences (SPSS) 25.0. Descriptive statistics were used to report the clinical, laboratory, and imaging data. Numerical results were presented using median values and first and third quartiles for distribution.The study was approved by the Institutional Review Board (IRB) of our hospital and adhered to the tenets of the Declaration of Helsinki.Fourteen patients with a clinical and/or histological diagnosis of sarcoidosis were identified. The median age was 52 years , and 71.4% (n = 10) were female. The median follow-up was 24 (13–49) months. Two patients had tattoos and one had a history of smoking. Ten (71.4%) patients were defined as a biopsy-proven definite diagnosis of ocular sarcoidosis , and pulmonary manifestations  Tables  and 3.ACE serum levels were available in 10 (71.1%) patients, 6 (60%) had increased levels, with a median concentration of 70.5  UI/l. Lysozyme was available in 8 patients (57.1%), showing high levels in 5 cases 62.5%) with a median of 3.81  mg/L. PPD was available for 13 patients; one had a positive result, so tuberculosis was discarded by clinical picture, negative IGRA, and a positive skin lesion biopsy for sarcoidosis ., 21.2, 2Ocular manifestations, although diverse, can be crucial in the suspicion and diagnosis of systemic sarcoidosis. In our experience, every patient that starts as an isolated form of ocular inflammation later resulted in systemic sarcoidosis. Therefore, ophthalmologists should be attentive to the manifestations of ocular sarcoidosis, and screen for systemic involvement, along with a multidisciplinary team, when suspicion is high.


All calculations were benchmarked against graphene. We showed that depending on the initial vertical height of a nucleobase above the Ti3C2 surface, two interaction mechanisms are possible, namely, physisorption and chemisorption. For graphene, DNA nucleobases always physisorbed onto the graphene surface irrespective of the initial vertical height of the nucleobase above the graphene sheet. The PBE+vdW binding energies for graphene are high (0.55–0.74 eV) and follow the order G > A > T > C, with adsorption heights in the range of 3.16–3.22 Å, indicating strong physisorption. For Ti3C2, the PBE+vdW binding energies are relatively weaker (0.16–0.20 eV) and follow the order A > G = T > C, with adsorption heights in the range of 5.51–5.60 Å, indicating weak physisorption. The binding energies for chemisorption follow the order G > A > T > C, which is the same order for physisorption. The binding energy values (5.3–7.5 eV) indicate very strong chemisorption (∼40 times larger than the physisorption binding energies). Furthermore, our band structure and electronic transport analysis showed that for physisorption, there is neither significant variation in the band structure nor modulation in the transmission function and device density of states. The relatively weak physisorption and strong chemisorption show that Ti3C2 might not be capable of identifying DNA nucleobases using the physisorption method.We investigated the interaction of DNA nucleobases  with single-layer Ti I.2),2),π–π interaction, which produces strong physisorption of the nucleobases.2 membranes are polar, direct bandgap semiconductors and have been shown to have better ability in detecting the individual nucleobases in terms of a higher signal-to-noise ratio and have lower tendency of nucleobases to stick to its surface.2 membranes can suffer degradation over time when repeatedly exposed to high electric fields. Recently, 2D MXenes have emerged as promising alternative materials for DNA nucleobase detection. MXenes have the general formula Mn+1XnTx, where M is a transition metal , X is carbon or nitrogen, Tx represents different functional groups  on the MXene surface, and n can take values between 1 and 3.3C2 MXene nanopores by Yadev et al.et al.2C(OH)2 MXene nanopores combining density functional theory (DFT) and the non-equilibrium Green’s function (NEGF) method by Prasongkit et al.et al.2NS2 MXene nanochannel device.The interaction of DNA nucleobases with atomically thin two-dimensional (2D) materials has garnered significant interest in the field of materials science because of its importance in single-molecule detection and DNA sequencing. Indeed, a great number of theoretical and experimental studies have been performed to investigate the viability of various 2D materials for DNA sequencing, such as graphene,3C2 MXene using the Van der Waals (vdW)-corrected DFT and NEGF technique. The binding energy of nucleobases on the Ti3C2 sheet was benchmarked against graphene. We find that for graphene, the DNA nucleobases physisorbed strongly on the graphene sheet irrespective of the initial vertical height between the nucleobase and the graphene surface. For the Ti3C2 sheet, two interaction mechanisms were observed. Depending on the initial vertical height of DNA bases above the Ti3C2 sheet, the final equilibrium geometry showed that nucleobases interact with the Ti3C2 sheet either via physisorption (relatively weak compared to graphene) or chemisorption. Furthermore, our band structure and electronic transport analysis showed that for physisorption, there is neither significant variation in the band structure nor modulation in the transmission function and the device density of states (DDOS). The relatively weak physisorption and strong chemisorption show that Ti3C2 might not be capable of identifying DNA nucleobases using the physisorption method.So far, most of the studies for DNA sequencing using 2D MXenes have been based on the nanoporeII.3C2 MXene and graphene) and the DNA nucleobases. For the nucleobases, each nucleobase was placed in a large simulation box of a dimension of 15 × 15 × 30 Å3 to avoid spurious interaction between the nucleobase and its periodic image. For graphene and Ti3C2, the unit cells were first optimized; then using the optimized coordinates, a 5 × 5 supercell was created, which is large enough for adsorption studies of nucleobases.3C2, a vacuum of 30 Å was used to avoid interlayer interactions. For adsorption studies, each nucleobase was placed approximately above the center of the 5 × 5 supercells for Ti3C2 and graphene. All relaxation calculations were performed using DFT. For DFT studies, we modeled the exchange-correlation potential within the generalized gradient approximation (GGA) using the Perdew–Burke–Ernzerhof (PBE) functional.We performed relaxation calculations separately for the 2D membranes (TiIII.A.Eg) of the nucleobases A (adenine), G (Guanine), C (Cytosine), and T (Thymine) was calculated as the difference between the LOMO  and HOMO . The energy gap  of a DNA base was determined using the following equation:Esub+base is total energy for the combined system (Ti3C2 or graphene substrate + base), Esub is the total energy of the substrate (Ti3C2 or graphene), and Ebase is the total energy of the nucleobase.The adsorption of DNA nucleobases was carried out by placing the bases above the graphene or TiFor graphene, optimization calculations were performed in the AB stacking configuration, as shown in 3C2 surface was performed for two adsorption sites, that is, the hollow and bridge configurations, as shown in 3C2, and the titanium atom on the third layer appears at the center of the ring. In the carbon-centered (bridge) configuration, the hexagonal ring on the DNA base is placed above the titanium-carbon bond so that the carbon atom in the second layer appears at the center of the hexagonal ring on the DNA nucleobase. Relaxation calculations were performed for the two different configurations, and the relative energies were obtained for each nucleobase. After comparing the relative energies for the two configurations, it was determined that the carbon-centered configuration was slightly energetically favorable than the titanium-centered configuration (the difference in energy is less than 1 meV).The adsorption of DNA nucleobases on the Ti3C2 .Unlike graphene, where the DNA nucleobases only physisorbed onto the graphene sheet, we found that two interaction mechanisms are possible for Ti3C2 see . Dependi1.3C2. 3C2, the PBE+vdW binding energies are relatively weaker (0.16–0.20 eV) and follow the order A > G = T > C, with adsorption heights in the range of 5.51–5.60 Å, indicating weak physisorption. The small binding energies for nucleobases on the Ti3C2 surface suggest minimal sticking of bases on the Ti3C2 surface compared to that on graphene.3C2.3C2 substrates with DNA bases is shown in 3C2 upon physisorption of DNA nucleobases are negligible. This correlates with the weak physisorption of nucleobases on Ti3C2 compared to graphene.The band structure of the graphene and Ti2.3C2, namely, physisorption and chemisorption. 3C2 surface. For chemisorption, A and G chemisorbed with the nucleobases parallel to the surface of Ti3C2. For T and C, the bases chemisorbed at a tilted angle. The binding energies for chemisorption are shown in 3C2 and increase the error rates for identification of nucleobases.As already discussed in Sec. 3C2 substrate with DNA bases chemisorbed are shown in 3C2 produces a negligible change in the band structure , forming a device structure. In addition to pristine Ti3C2 , four other device configurations (given by the physisorption or chemisorption interaction mechanisms) are examined: Ti3C2+A, Ti3C2+G, Ti3C2+T, Ti3C2+C . To that end, the optimized structures are attached to the Ti3C2 electrodes, as illustrated in medium basis sets of local numerical orbitals.The electronic transport properties of TiEF, which is set to zero). The transmission is influenced by both electrodes and the electronic structure of a system . However, the DDOS is associated with the system attached to them. Hence, a zero transmission at a certain energy may not refer to a zero DDOS at that energy. For all device structures, the transmission shown in EF. The nonzero transmission at this specific energy suggests a finite zero-bias conductance. As shown in 3C2+T for which it is slightly lower (0.77). The chemisorption interaction brings about non-identical transmissions at both EF and other energies, as illustrated in 3C2+T device drops to 0.51, becoming well below that of other devices. The appreciable transmission in the vicinity of EF suggests that Ti3C2+ base structures can be employed to develop functional conducting devices. The alteration of transmission with dramatic increments at particular energies is evident. As there is more than one transmission channel in the system, the transmission coefficient can be higher than 1.00. The salient transmission peaks (resonances) shown in The transmission coefficient and DDOS spectra of each device for both physisorption and chemisorption interaction mechanisms are illustrated in 3C2+ base systems are chiefly determined by well-defined and suppressed DDOS peaks. As the states around EF are crucial in electronic transport, the prominent DDOS peaks right below and above it play a significant role in the electronic nature of Ti3C2+ base devices. EF, a sharp peak representing the Ti3C2+C device above EF is obvious [EF for both Ti3C2+A and Ti3C2+G devices [EF.The available electronic states of the system linked to the electrodes can be revealed with the help of the DDOS, which is shown in  obvious . Dependi devices . BesidesIV.3C2 MXene and graphene using vdW-corrected DFT and NEGF methods. We showed that depending on the initial vertical height of a nucleobase above the Ti3C2 surface, two interaction mechanisms are possible, namely, physisorption and chemisorption. For graphene, DNA nucleobases always physisorbed onto the graphene surface irrespective of the initial vertical height of the nucleobase above the graphene sheet. The PBE+vdW binding energies for graphene are high (0.55–0.74 eV) and follow the order G > A > T > C, with adsorption heights in the range of 3.16–3.22 Å, indicating strong physisorption. For Ti3C2, the PBE+vdW binding energies are relatively weaker (0.16–0.20 eV) and follow the order A > G = T > C, with adsorption heights in the range of 5.51–5.60 Å, indicating weak physisorption. The binding energies for chemisorption follow the order G > A > T > C, which is the same order for the binding energies for physisorption. The binding energy values (5.3–7.5 eV) indicate very strong chemisorption. The chemisorbed binding energies are ∼40 times larger than the physisorbed binding energies. Furthermore, our band structure and electronic transport analysis showed that for physisorption, there is neither significant variation in the band structure nor modulation in the transmission function and the device density of states (DDOS). The relatively weak physisorption and strong chemisorption show that Ti3C2 might not be capable of identifying DNA nucleobases using the physisorption method.In summary, we have investigated the interaction of DNA nucleobases with single-layer Ti