Advances in research and technology to boost human space exploration proceed at a brisk pace, although a major obstacle remains: the cold and empty outer space. Can we capitalize on the unique properties of specific materials and structures to address this problem? Considered among the best insulating materials available, aerogels have become prime candidates in this field owing to their ultralight weight, large surface area, deformability, excellent fire and corrosion resistance, as well as low thermal conductivity . HoweverNational Science Review, Yu et al. overcome this critical issue by using an innovative approach featuring hybrid 3D aerogels made of chemically bonded 2D inorganic materials, namely graphene and amorphous boron nitride (a-BNGA) [3NH3) is thermally decomposed and polymerized (at 1000°C) on graphene aerogels, leading to the formation of a-BNGA , being the lowest value recorded in vacuum among solid materials to date. Such an exceptional performance is due to the ‘encasing effect’ of amorphous boron nitride over the graphene layer, whose conduction paths are reduced and phonon transport is hindered because of an enhanced scattering at the boron nitride/graphene interface. Finally, the ultralight, superelastic and thermally superinsulating a-BNGAs were tested for possible deep-space applications. The interior environment of a lunar base model wrapped with such a system experiences a longer (10-h) heating–cooling cycle compared with pristine boron nitride, graphene and silica aerogels, demonstrating the superior performance of a-BNGA in suppressing thermal radiation and heat conduction.Writing in (a-BNGA) . They derized at 000°C on 3C2Tx MXene shows extremely low emissivity in the infrared range [The promising results achieved by combining different 2D materials suggest an opportunity for further material engineering to improve the aerogel performance, since hundreds of 2D materials are available and some of them show superior thermal properties . For exaed range  and can This novel strategy represents a great advance in the field, paving the way toward the production of hybrid 3D aerogels made of 2D materials showing superelasticity and ultralow thermal conductivity for a variety of applications, such as extraterrestrial exploration. However, the use of mechanically robust aerogels in industrial applications at elevated temperatures, when elastic polymer foams cannot work, or at extremely low temperatures in the Arctic and Antarctic, is even more promising. Those terrestrial applications may also provide testing opportunities under practical use conditions that will ensure the reliability of aerogels in future space applications.


The advancement of artificial intelligence (AI), as well as machine learning, has led to its application in various industries, including health care. AI chatbots, such as GPT-4, developed by OpenAI, have demonstrated potential in supporting health care professionals by providing medical information, answering examination questions, and assisting in medical education. However, the applicability of GPT-4 in the field of pharmacy remains unexplored.This study aimed to evaluate GPT-4’s ability to answer questions from the Japanese National Examination for Pharmacists (JNEP) and assess its potential as a support tool for pharmacists in their daily practice.The question texts and answer choices from the 107th and 108th JNEP, held in February 2022 and February 2023, were input into GPT-4. As GPT-4 cannot process diagrams, questions that included diagram interpretation were not analyzed and were initially given a score of 0. The correct answer rates were calculated and compared with the passing criteria of each examination to evaluate GPT-4’s performance.For the 107th and 108th JNEP, GPT-4 achieved an accuracy rate of 64.5% (222/344) and 62.9% (217/345), respectively, for all questions. When considering only the questions that GPT-4 could answer, the accuracy rates increased to 78.2% (222/284) and 75.3% (217/287), respectively. The accuracy rates tended to be lower for physics, chemistry, and calculation questions.Although GPT-4 demonstrated the potential to answer questions from the JNEP and support pharmacists’ capabilities, it also showed limitations in handling highly specialized questions, calculation questions, and questions requiring diagram recognition. Further evaluation is necessary to explore its applicability in real-world clinical settings, considering the complexities of patient scenarios and collaboration with health care professionals. By addressing these limitations, GPT-4 could become a more reliable tool for pharmacists in their daily practice. The development of artificial intelligence (AI), as well as machine learning, has led to its application in many industries and fields. AI is increasingly being used in the medical field, for example, to diagnose diseases through diagnostic imaging and to analyze medical records using natural language processing technology -3. More In this study, GPT-4, the latest LLM released as of April 2023, when the study was conducted, was used among the large-scale language models developed by OpenAI. The system is based on the Generative Pretrained Transformer (GPT) architecture and leverages the transformer model. The core concept of GPT-3 was based on a transformer model with 175 billion parameters . AlthougJNEP is held once a year, and the question texts and answers are published by the Japanese Ministry of Health, Labour, and Welfare. JNEP has undergone several changes in format and content, reflecting the evolving role of pharmacists in health care. These changes have resulted in an increased emphasis on practical skills and knowledge, such as applying pharmaceutical knowledge in a clinical context and understanding relevant laws and ethical considerations. The JNEP criteria are revised approximately every 4 years, with the latest change having occurred at the 106th JNEP in 2020. Because GPT-4 used in this study has information until September 2021, the 107th and 108th JNEPs held in February 2022 and February 2023, respectively, were used.Each examination consists of 345 questions, divided into 3 blocks: 90 essential questions, 105 pharmacy theory questions, and 150 practical pharmacy questions. The essential questions are questions that examine the basic knowledge required for pharmacists. The pharmacy theory questions are based on the theoretical knowledge necessary to evaluate and solve common problems encountered in pharmacists’ practice. The practical pharmacy questions are designed to assess basic, practical, and general knowledge for solving common problems in health care and public health. The practical pharmacy questions are often based on practical and clinical cases. Each question is from one of the following 9 areas: physics, chemistry, biology, hygiene, pharmacology, pharmaceutics, pathobiology, regulations, and practice. All questions are in the form of multiple-choice answers; however, each question has 1 or 2 correct answers, and if 2 correct answers are chosen, the answer must be complete to be considered correct. In addition to questions in which the examinee must answer correctly or incorrectly from each field, there are questions in which the examinee must perform calculations based on the conditions of the question as well as questions related to drug therapy in the presented case. The calculation questions require examinees to perform calculations from given conditions, and the results are chosen from a list of answer choices. All questions are written in Japanese. The passing criteria for the 107th JNEP included achieving a minimum of 70% correct answers in essential questions, a minimum of 30% correct answers in each area, a minimum of 217 (62.9%) correct answers overall, and a limit of 2 of the several contraindicated choices. Contraindicated choices, in this context, refer to certain choices within the questions that, if selected, could be ethically incorrect, potentially violate laws, or pose significant risks causing harm to patients and public health. Because information on contraindications was not disclosed by the question authors, it was decided to exclude them from the criteria used for evaluation. The passing criteria for the 108th JNEP included 70% or higher correct answers in essential questions, 30% or higher correct answers in each area, 235 (68.1%) or more correct answers overall, and no more than 2 contraindicated choices. In recent years, the pass rate for JNEP has averaged around 70%, with the pass rates for the 107th and 108th JNEPs standing at 68.0%  and 69.0% , respectively.Question texts and answer choices of the target JNEP were entered into GPT-4, and the selected choices were tabulated as GPT-4’s answers. The question text was input into GPT-4 in Japanese. In the 107th JNEP, there was 1 question for which the answer was undefined, and it was excluded from the list of questions to analyze. During the study, GPT-4 did not allow the input of diagrams as information; therefore, all questions that required reading diagrams to come up with answers were excluded from the answer set. All questions that were not answered were given a score of 0, and the accuracy rate was calculated and compared with the passing criteria. In addition, as a subanalysis, the accuracy rate was calculated by excluding questions that GPT-4 could not answer and then was compared to the passing criteria. Moreover, the accuracy rates were compared according to the question content—whether they were multiple-choice, calculation, or case study questions. For each comparison, the Pearson chi-square test was performed using JMP Pro 16 (SAS Institute Inc).An ethics approval did not apply to this study. It should be noted that the examination questions and answers used in this study were originally produced and copyrighted by the Ministry of Health, Labour, and Welfare of Japan. These materials are publicly available and used for the purpose of academic research in this study. Any copyrights about the exam content belong to the Ministry of Health, Labour, and Welfare of Japan, and this study did not infringe upon these rights.The results of the 107th and 108th JNEPs by GPT-4 are shown in For the 107th JNEP, 284 (82.6%) questions were available for input into GPT-4, of which 222 were answered correctly by GPT-4, for its accuracy rate of 64.5% (222/344). GPT-4 could not answer 60 questions that required reading diagrams to come up with answers. In terms of question type, the accuracy rate for essential questions was 72.2% (65/90), the accuracy rate for the pharmacy theory questions was 48.6% (51/105), and the accuracy rate for the practical pharmacy questions was 71.1% (106/149). The accuracy rates for all questions exceeded the passing criteria. However, only 20% (1/5) of the essential questions in chemistry were answerable, which was below the passing criteria. Only for questions that GPT-4 could answer, its accuracy rate for all questions was 78.2% (222/284), meeting all passing criteria.For the 108th JNEP, 288 (83.5%) questions could be input into GPT-4, of which 217 were answered correctly by GPT-4, for its accuracy rate of 62.9% (217/345). GPT-4 could not answer 57 questions, as it required reading diagrams to come up with answers. In terms of question type, the accuracy rate for essential questions was 72.2% (65/90), the accuracy rate for the pharmacy theory questions was 55.2% (58/105), and the accuracy rate for the practical pharmacy questions was 62.7% (94/150). The accuracy rates for all questions and for the essential questions in physics and chemistry were below the passing criteria. Only for questions that GPT-4 could answer, its accuracy rate for all questions was 75.3% (217/288), meeting all passing criteria. Therefore, the accuracy rate for the questions that could be input into GPT-4 for the 107th and 108th JNEP met the passing criteria.P<.001), fields (P<.001), and whether or not the question was a calculation question (P=.003).This result was also obtained from GPT-4’s accuracy rate in the JNEP, specifically for questions that GPT-4 could answer .The results of inputting the 107th and 108th JNEP questions into GPT-4 showed that GPT-4 failed to meet some passing criteria. However, only for questions that GPT-4 could answer, its accuracy rate met all the passing criteria. In the past, LLMs have demonstrated the ability to answer several professional examinations at a passing level. For example, ChatGPT has been reported to be capable of answering questions of the law school and business management course examinations  and the Although GPT-4 is not specifically trained or specialized in any particular field of study, it has demonstrated a certain level of ability to respond to questions in each of these areas. However, the accuracy rate varied depending on the field of questions. When limited to questions that GPT-4 could answer, accuracy rates tended to be higher for biology and pharmacology questions and lower for physics and chemistry. Nisar et al  reportedIn this survey, there were not only simple correct or incorrect questions about events but also many questions in which a case was presented and the question was about pharmacotherapy for the case. The accuracy rate of the case questions that GPT-4 could answer was 74.8%, which was as high as the percentage for all questions except for the case questions. This indicates that GPT-4 could be used by pharmacists to support their pharmacotherapy practice in clinical settings. However, in discussing the limitations of GPT-4 in real-world pharmacy practice, several factors should be considered. Although GPT-4 demonstrated strong performance on standardized exam questions, its effectiveness in handling diverse clinical scenarios and patient-specific factors may be limited. This is primarily due to the challenge of processing a wide range of patient information that extends beyond the scope of exam questions. In real-world clinical settings, patient data include detailed medical history, medication history, laboratory data, and allergy information, which change with time. It is unclear whether GPT-4 can accurately process such diverse information. Another important consideration is the lack of communication skills with other health care professionals. In real clinical practice, pharmacists collaborate and exchange information with various members of the health care team. However, GPT-4 cannot mimic this collaborative communication with other professionals. It was reported that ChatGPT lacks thoughtful reasoning like humans  and cannIt is important to note that the accuracy rate of GPT-4 was not 100%, and caution is needed regarding ethical issues related to the input of patients’ personal information . It is rIn addition, the accuracy rate for questions for which the participants were required to perform calculations under the indicated conditions was low (42.9%). In some cases, the results were incorrect due to the omission of values with different units, and in other cases, the results were correct; however, GPT-4 made a mistake in selecting the option with the closest value. In a previous report , it has In conclusion, GPT-4 showed that some passing criteria were not met in terms of the accuracy rate for all JNEP questions, but the accuracy rates for the questions that GPT-4 could answer met all of the passing criteria. Nevertheless, recognizing the limitations of the current GPT-4 model is crucial, particularly in terms of its performance in answering highly specialized questions, calculation questions, and questions requiring diagram recognition. Furthermore, exploring the practical applicability of GPT-4 in real-world clinical settings is essential by evaluating its performance on more detailed work data sets . By addressing these limitations and validating its performance in a broader range of tasks, GPT-4 could become a more reliable and effective tool for pharmacists in their day-to-day practice.


Transposable elements, such as Long INterspersed Elements (LINEs), are DNA sequences that can replicate within genomes. LINEs replicate using an RNA intermediate followed by reverse transcription and are typically a few kilobases in length. LINE activity creates genomic structural variants in human populations and leads to somatic alterations in cancer genomes. Long-read RNA sequencing technologies, including Oxford Nanopore and PacBio, can directly sequence relatively long transcripts, thus providing the opportunity to examine full-length LINE transcripts. This study focuses on the development of a new bioinformatics pipeline for the identification and quantification of active, full-length LINE transcripts in diverse human tissues and cell lines. In our pipeline, we utilized RepeatMasker to identify LINE-1 (L1) transcripts from long-read transcriptome data and incorporated several criteria, such as transcript start position, divergence, and length, to remove likely false positives. Comparisons between cancerous and normal cell lines, as well as human tissue samples, revealed elevated expression levels of young LINEs in cancer, particularly at intact L1 loci. By employing bioinformatics methodologies on long-read transcriptome data, this study demonstrates the landscape of L1 expression in tissues and cell lines. Transposable elements (TEs) are mobile DNA sequences that can move from one part of the genome to another and generate genomic diversity. Barbara McClintock’s discovery of TEs in the 1940s ,3,4. In Among different types of TEs, the Long INterspersed Elements (LINEs) contribute to approximately 17% of the human genome and replicate using an RNA intermediate followed by reverse transcription, known as the “copy and paste” mechanism . In the LINEs have been present in the human genome for millions of years, accumulating mutations, rendering most inactive. While the majority of the older and mutated L1 elements have lost their ability to retrotranspose, younger and less divergent L1 elements with fully intact ORFs and polyadenylation signals retain the necessary machinery for retrotransposition and pose a greater risk for genetic instability ,25,26,27Conventional short-read sequencing techniques have severe limitations when studying TEs. In particular, TEs are highly repetitive in the genome and make it challenging to map the short reads to a particular TE when a short read matches to multiple TEs in the genome . AlthougIn this study, we implemented a novel bioinformatics approach to assess the transcription of active L1 elements across multiple cell lines and somatic tissues. Our strategy involved utilizing RepeatMasker  to diffeThe number of samples and the sequencing platforms used in each dataset are detailed in In addition to the GTEx tissue and cell line samples, several long-read RNA sequencing cell line datasets from both ONT and PacBio platforms were included in the study. The ONT sequenced datasets included the following cell lines: Universal Human Reference (UHR), HepG2, Human Embryonic Kidney 293T (HEK293T), HCT116, MCF7, A549, HeLa, and Acute Myeloid Leukemia (AML). The UHR dataset consisted of ten human cell lines derived from various human tissues, including liver, testis, mammary gland, cervix, brain, skin, liposarcoma, macrophage, T-lymphoblast, and B-lymphocyte (BioProject Accession Number: PRJNA639366) . Datasethttps://downloads.pacbcloud.com/public/dataset/UHR_IsoSeq/) [The PacBio sequenced datasets included the following cell lines: UHR (Accessed on 2 June 2023 and available online at IsoSeq/) , HepG2 (IsoSeq/) . The norIsoSeq/) . Supplemhttps://github.com/WGLab/LINE-Expression-LRS. For raw datasets that were in the FAST5 format, FAST5 files were basecalled using Guppy6 [minimap2 -ax map-ont “L1_reference.fasta” “input_reads.fasta” > “LINE_input_reads.fasta”) to obtain reads that have at least one mapping to a LINE element. The resulting FASTA file was analyzed with RepeatMasker (version 4.1.5 released March 2023) [RepeatMasker -pa 6 -dir “output_directory” -nolow -norna -species human -no_is -a -u -xsmall -xm “LINE_input_reads.fasta”). Using the RepeatMasker output, sequences containing L1 elements that were identified as less than 10% diverged from the consensus sequence, as determined by the “div” column, were selected for the downstream analysis.An overview of the analysis pipeline employed in this study to characterize the expression of young L1 elements is presented in g Guppy6  to generg Guppy6  of the hg Guppy6  (minimapch 2023)  for LINEminimap2 -ax splice --junc-bed reference_splice_junctions.bed -uf --secondary=no -k14 -t 8 hg38_reference.fasta input_reads.fasta -o aligned_reads.sam). The generated SAM file was then converted to a BAM file using samtools view, after which the BAM file was sorted according to genomic location and indexed. LongReadSum (v1.3.0) [python LongReadSum bam -i sample_input.bam) and the following statistics are presented in Reads containing L1 elements with less than 10% divergence were then mapped to the hg38 reference genome using Minimap2 with splice-aware parameters. A reference junction BED file (GENCODE.v40 ) was use(v1.3.0)  was usedHomo sapiens) was generated from the GRCh38 assembly, where the consensus sequence for different subfamilies and details about the existence of ORFs are reported [bedtools intersect [bedtools intersect -a “reference_regions.bed” -b “GENCODE.v43.annotation_exons.bed” -v > “reference_no_exons.bed”). As a result, three distinct reference files were obtained: active L1 elements (FLI-L1s) (115 regions), inactive L1 elements (FLnI-L1s) , and L1 elements intact only in ORF2 (ORF2-L1s) (97 regions). The purpose of this filtering was to ensure that each reference file contained specific and non-overlapping regions for subsequent L1 analysis. Each resulting reference file  was used to determine the coverage of the different types of L1 elements within the samples. Reads where less than 90% of the read was mapped to the L1 regions were removed . By retaining reads with at least 90% mapped to the L1 loci, we ensured the retention of reads primarily aligned within the L1 regions of interest. Once the number of mapped reads for each locus was determined, reference L1 loci with fewer than two mapped reads were also excluded. For reads mapped to the remaining L1 loci, the start positions of the reads within each L1 region were compared. L1 loci with variable read starting positions that were more than 100 bps from the most common read start position were removed. Finally, the overall most common start positions of the reads within an L1 region were compared with the L1 region’s start position. An L1 loci was excluded if the most common read start position was more than 1.5 kb away from the reference L1 start position. This filtering approach further improved the accuracy and reliability of L1 analysis by filtering out potential false positives from possible technical biases due to library preparation, polymerase chain reaction (PCR) amplification biases, sequencing errors, and mapping errors.The L1Base2 (v2) database for the human genome . This resulted in a bedgraph, which has varying read count intervals of the coverage values across the L1 loci. Then, the bedtools map function [bedtools map -a reference_L1.bed -b coverage. bg -c 4 -o mean -null 0 > mean_coverage.txt). Here, the bedtools map function calculated the mean number of RNA sequencing reads that intersected with the coordinates of the L1 loci from the L1Base2 reference. To determine the general expression level of these L1 loci, the calculated coverage values were normalized by the total number of reads in the sample to account for variations from the multiple datasets with varying total number of reads. A weighted average L1 expression value was then computed across all L1 loci in each of the reference L1Base2 categories: active, inactive, and intact only in ORF2, for each sample. This weighted average involved assigning weights based on the length of the reference L1 element with its corresponding expression value, scaled in millions, as displayed in Equation (1), where i takes the L1 reference category, “active”, “inactive”, and “intact only in ORF2” to represent the different categories.Following the read filter portion of the artifact-based filtering step, the filtered BAM files were processed through the function  (bedtoolfunction  was usedSubfamily names of L1 elements longer than 4.5 kb in length from the UCSC Genome Browser (hg38) RepeatMasker Track, namely L1HS and L1PA2, were used to determine the L1 subfamily breakdown in the active, full-length L1 loci. Manual review using the Integrative Genomic Viewer (IGV)  was perfThe current study developed a bioinformatics pipeline leveraging long-read sequencing technologies to investigate the transcription patterns of L1s in human tissue and cell line samples. The degree to which L1 elements contribute to human genome function varies depending on several factors, including the tissue-specific regulation, the expression level of L1s, and the specific genomic locations of their transcription and subsequent insertions. Building upon previous work in L1 biology, we used long-read RNA sequencing datasets from ONT and PacBio to examine tissue-specific expression patterns of L1 elements.Among the datasets used in this study , 88 tissAn overview of the analysis pipeline is presented in We further examined the distribution of the human tissue subtypes in brain and heart B and obsThere are several caveats to the analysis: first, because existing long-read RNA-seq library and sequencing protocols are geared towards typical transcripts (~1.5 kb length on average), they may not be optimal for the analysis of L1 elements (~6 kb length) as only part of the L1 transcript sequences may be present in the data. Second, we used a relatively stringent bioinformatics protocol and removed a portion of the candidate L1 transcripts from the final analysis to focus on the most reliable subset of reads arising from L1 elements in the analysis. Third, the “less than 10% diverged” was a relatively arbitrary threshold to focus our analysis to recently diverged elements, but the ~3% sequencing error rate of ONT  and theNext, we extended our analysis to include a variety of cell lines. Cell lines sequenced by PacBio are shown in To further confirm that our results reflect authentic L1 transcription, we manually evaluated L1 expression levels and patterns at the identified L1 regions using the Integrative Genomics Viewer (IGV) . We examVarious alignment patterns were observed, including almost full coverage, reads concentrated at the 5′ or 3′ ends, and reads distributed throughout the middle of the region. In addition to the ESCC samples, the UHR dataset sequenced using PacBio exhibited high coverage values in a few active L1 regions. Over the identified regions, the supporting reads revealed a consistent pattern of aligning towards the 5′ end, as displayed in Our analysis also examined the L1 expression patterns in human tissues, where the brain samples had the highest level of L1 expression. Analyzing the IGV plots from the brain sample provided evidence that suggested the expression of active L1 elements . SupplemIn our analysis we noticed a wide variety of alignment patterns within the L1 regions, including consistently uniform expression of L1 loci at the 5′ end. The partial L1 coverage alignment pattern suggested that full-length coverage was limited to certain portions of the L1 regions, or that only a partial portion of full-length transcripts were sequenced due to technical limitations such as RNA degradation or lower efficiency of reverse transcription for longer RNAs during the sequencing library construction. The results further emphasized that the lack of concordance in profiling L1 elements remained, even after implementing a rigorous filtering strategy to exclude low abundance reads that could have potentially introduced artifacts or were prone to mapping errors. The assumption that the expression at the 5′ end of L1 transcripts can be considered as an estimate for autonomous transcription was influenced by previous studies and by the observed imbalance between 5′ truncated copies and those fuller-length copies, which aligns with findings from prior research . Given aOne important aspect of our analysis was the utilization of data from both PacBio and ONT long-read sequencing technologies. Given the highly repetitive nature of L1 elements, the sequence similarity of different subfamilies, and the accumulation of mutations through time, longer reads from both technologies helped to assign the reads more accurately to their proper positions during genome mapping. However, it is important to note that ONT sequencing is known for its higher levels of basecalling error (compared to the PacBio HiFi protocol), which can impact mapping accuracy . AlthougUsing the data from both ONT and PacBio platforms also allowed us to examine the sequencing statistics  and asseOur study provides insights into the expression patterns and characteristics of L1 elements in human tissue and cell line samples, specifically focusing on L1s that diverged less than 10%. We observed low expression levels of full-length L1s in normal tissues, except for the brain, while variable expression was found in cell lines, with higher levels observed in tumor cell lines. As one of our future research directions, we plan to examine L1 elements in putamen samples from Parkinson’s disease patients and compare these with L1 expression in normal putamen samples. This is motivated by our observation of substantial coverage of active L1 regions in the putamen, which is implicated in the pathology of Parkinson’s disease. The prominent expression of the active L1HS subfamily supports its potential role in transpositional mutagenesis in the context of disease ,61,62. T


The aim of this study was to determine the acceptability and psychometric properties of the Hypo-METRICS  application (app): a novel tool designed to assess the direct impact of symptomatic and asymptomatic hypoglycemia on daily functioning in people with insulin-treated diabetes.s>±0.3) and divergent (rs<±0.3) validity.100 adults with type 1 diabetes mellitus  or insulin-treated type 2 diabetes mellitus  completed three daily ‘check-ins’  via the Hypo-METRICs app across 10 weeks, to respond to 29 unique questions about their subjective daily functioning. Questions addressed sleep quality, energy level, mood, affect, cognitive functioning, fear of hypoglycemia and hyperglycemia, social functioning, and work/productivity. Completion rates, structural validity, internal consistency, and test-retest reliability were explored. App responses were correlated with validated person-reported outcome measures to investigate convergent (rs≥0.7). Convergent and divergent validity were demonstrated for most scales.Participants’ mean±SD age was 54±16 years, diabetes duration was 23±13 years, and most recent HbA1c was 56.6±9.8 mmol/mol. Participants submitted mean±SD 191±16 out of 210 possible ‘check-ins’ (91%). Structural validity was confirmed with multi-level confirmatory factor analysis showing good model fit on the adjusted model . Scales had satisfactory internal consistency , and high test-retest reliability (rHigh completion rates and satisfactory psychometric properties demonstrated that the Hypo-METRICS app is acceptable to adults with T1DM and T2DM, and a reliable and valid tool to explore the daily impact of hypoglycemia. Hypoglycemia remains a daily threat for most people with type 1 diabetes (T1DM) or insulin-treated type 2 diabetes (T2DM). Hypoglycemia impacts on many areas of daily life including sleep duration and quality, mood, cognition, and productivity, and can in extreme cases lead to coma or even death . Both thPrevious studies on the impact of hypoglycemia have important limitations. These include recall bias for retrospective measures , low ecoTo investigate whether broad use of the Hypo-METRICS app in research and practice is indicated, this study investigates the app’s acceptability (completion rates) and psychometric characteristics . These investigations are essential instrument validation steps, that are required before we can address the Hypo-METRICS study key objectives  in futuHypo-METRICS is part of the EU IMI2-funded Hypo-RESOLVE (Hypoglycemia–Redefining SOLutions for better liVEs) project ,13, acroa priori and consists of the first 100 participants to complete the Hypo-METRICS study. This sample size was based on guidelines suggesting an item-to-participant ratio of 1:10 [Eligible participants were aged 18–85 years, had experienced at least one self-reported hypoglycemic episode in the past 3 months, and were willing to complete the app three times per day and wear a blinded CGM for 10 weeks. Informed written consent was obtained from all participants. Participants from the following three groups were recruited: a) T1DM with intact awareness of hypoglycemia (Gold Score <4 ), b) T1D of 1:10  for evalThe app consists of seven modules with 29 unique questions see , most ofs>±0.3) were expected to evidence convergent validity, and low or no correlations (rs<±0.3) were expected for divergent validity.Validated PROMs were included for the purpose of validating the Hypo-METRICS app. Two of these were also completed via the app platform on a weekly basis, while the remaining were completed via Qualtrics  at baseline and end of study see . PROMs wAt the start of the study, age, gender, employment status, education, medical history, previous episodes of hypoglycemia, HbA1c and method of glucose monitoring, were recorded by the study site personnel and entered into an electronic database .s) were applied. Between-person variance was examined using the Intraclass Correlation Coefficient (ICC) [s>0.7 considered to indicate satisfactory internal consistency [Statistical analyses were conducted with R Studio . Descripnt (ICC)  and day-nt (ICC) . To examnt (ICC) ,31. Itemnt (ICC) . Internasistency . Questio1c was 56.6±9.8mmol/mol. For T1DM and T2DM respectively, 22% and 17% had impaired awareness of hypoglycemia (Gold score ≥4), 13% and 8% had moderate-severe anxiety, and 13% and 17% had moderate-severe depression as determined by the GAD-7 and PHQ-9.The first 100 participants who completed the Hypo-METRICS study included 64 adults with T1DM and 36 adults with T2DM, from the United Kingdom (57%) or the Netherlands (43%). How well did you get along with other people today?”), was skipped marginally more frequently (0.9%) than other questions. Questions in the work and productivity section were frequently skipped (range: 36–47%). Inspection of histograms revealed floor effects as indicated by more than 15% (range: 15–28%) of responses on the lowest score for the four negatively phrased questions .Participants completed 191±16 of 210 possible check-ins, a completion rate of 91%. Slight differences in completion between the morning, afternoon and evening check-ins were observed with completion rates of 90%, 89% and 94%, respectively. When a check-in was submitted, all questions (except the work/productivity questions) were completed more than 99% of the time . One ques = 0.20–0.81) and multicollinearity was absent (determinant range 0.000922–0.0134 across the three check-ins). Kaiser-Meyer-Olkin values ranged from 0.76–0.93 across all questions suggesting good factorability.Based on kurtosis values and histograms, data were considered non-normally distributed. The ICC ranged from 0.15 to 0.85 and all but two questions (both relating to sleep) included at least one participant with zero variability across the study period (RMSSD = 0) . ExploriApplying the five-step approach by Huang  to the m1c’ and ‘Diabetes duration’ (included solely for expected low correlations). However, many of the correlations in the remaining dark grey boxes in s>±0.3 . The validated weekly work-productivity questionnaire  were found across all two-questions and single-question scales . For conaire see , showed This study examined the acceptability and psychometric properties of an innovative smartphone app (Hypo-METRICS): results of the present study support its use as an innovative research tool to determine the impact of hypoglycemia on daily functioning among adults with T1DM or T2DM using insulin. Average completion rates were high and the percentage of skipped questions low. The Hypo-METRICS scales had satisfactory model fit , high test-retest reliability and satisfactory convergent and divergent validity. Overall, these findings indicate that the novel Hypo-METRICS app is both valid and reliable for assessing the impact of hypoglycemia on daily functioning in research, with high ecological validity and low recall bias.How many hours did you miss from activities other than work today for ANY reason” does not require the participant to have a paid job to respond to, and the high skip rate could suggest that participants found the question difficult to respond to, difficult to understand, irrelevant, or poorly explained.The high completion rates suggest that the Hypo-METRICS app is an acceptable instrument for assessments of daily functioning by people with T1DM and insulin-treated T2DM, up to three times per day, seven days per week for up to 10 weeks. All three check-ins were similarly acceptable, which may be attributed to the broad/flexible timeframes and that participants could select a convenient time for app completion. The low percentage of skipped questions (for the non-work-related questions) indicates that questions were generally applicable for most participants. The non-work-related question that was skipped the most was the ‘Social functioning’ question, which could be explained by the context of the COVID-19 pandemic . The high percentage of work and productivity questions skipped was expected, as participants were instructed to skip these if they did not have paid employment or if it did not concern a workday. However, the question “How irritable do you feel right now?”). Alternative explanations could be that the questions were not capable of capturing variability in the construct in this group of participants, or that variability only occurs within days and not between days. The floor effects are not considered problematic, since it is not desirable, or possible, to reach lower scores than ‘not at all’, and most participants had variable responses to these questions over time. The low variability for some questions may also indicate ‘automatic’ or ‘habitual’ responding’, wherein participants select the same responses when presented with the same questions in the same order multiple times [At a question-level, the ICC values show that most questions, in particular those focused on worries about hypoglycemia and hyperglycemia, have greater variability between than within individuals. Further, RMSSD values show that for some participants and some questions (particularly negatively-worded and work-related questions), there was no day-to-day variability in responses across the 70-day study period. This may suggest stability in the construct or in sample characteristics  and is supported by the floor effects on negatively-worded questions  at the between-person level, but not at the within-person level for ‘Negative affect’  and ‘Cognitive functioning’ (evening check-in). Internal consistency is highly dependent on number of questions in the scale , and sims = 0.76  to rs>0.9 (for the ‘Fear of hypoglycemia’ and ‘Fear of hyperglycemia’ single questions). These findings suggest reasonable consistency, across a few weeks, in the average scores on the measured constructs.EMA methods allow an exploration of the variation in outcomes from timepoint to timepoint. Expecting perfect test-retest reliability (correlations) between assessments contradicts the general assumption of the method . Howevers up to -0.70). However, it is important to note that no collinearity was present, suggesting that the app is not a redundant measure. Further, EMA offers advantages over retrospective questionnaires: it captures variation in the outcomes over time, and it allows assessment of the direct impact of events  on the outcomes. All app scales correlated highly with several PROMs, which was expected as previous studies have shown associations between symptoms of anxiety and depression [The correlations between the app scales and validated PROMs overall showed satisfactory convergent validity. The majority of the hypothesized highest correlations  and lowest correlations  were confirmed, although some of the hypothesized lowest correlations ” PROM) were higher than anticipated. Correlations between app scales (aggregated over periods of 1–4 weeks) and validated PROMs were, in some cases, high . Additional work is needed to determine the acceptability and psychometric properties of these questions. Similarly, this study should be replicated in independent samples with diverse characteristics . Further research is also needed to fully understand respondents’ completion patterns, including potential predictors of completion. Qualitative research would enable a subjective evaluation of the app completion, including the perceived value and/or burden of using the app across many weeks and ways to improve user experience. Qualitative research would further allow for additional investigation of the content validity  of the app questions. Future versions of the app could be automated and include conversational agents that, by combining CGM data with daily functioning data from the app, could deliver daily guidance on how to optimize treatment plans and/or improve quality of life.Overall, these findings show that the Hypo-METRICS app is an acceptable, valid, and reliable tool for research to advance knowledge of how hypoglycemia impacts on daily functioning. In addition to its potential in research, the app may have utility in clinical practice to enhance personalized treatment and care for people with diabetes.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.


This study evaluated the use of two large language models (LLMs), ChatGPT and Google Bard, in anatomy education. The models were asked to answer questions, generate multiple-choice questions, and write articles on anatomy topics. The results showed that the models were able to perform these tasks with varying degrees of accuracy. ChatGPT and Google Bard did not differ significantly in terms of answering questions. Both models were able to generate multiple-choice questions with a high degree of accuracy. However, the performance of the models in article writing was not yet at a sufficient level. The study also found that the use of LLMs in medical education requires caution. This is because LLMs are still under development and they can sometimes generate inaccurate or misleading information. It is important to carefully evaluate the output of LLMs before using them in educational settings. Overall, the study found that LLMs have the potential to be valuable tools for anatomy education. However, more research is needed to improve the accuracy of the models and to better understand how they can be used effectively in educational settings. The development of large language models (LLMs) is a major advance in artificial intelligence (AI) and natural language processing (NLP). LLMs have the capacity to process and understand natural language data with extraordinary skill and are already used in a variety of applications such as chatbots, machine translation, and question-answering -3. Some Data collectionhttps://chat.openai.com/) and Google Bard (https://bard.google.com/) chat boards. Then for the first stage, ChatGPT and Google Bard platforms were requested to answer the last five years of the Medical Specialty Exam (MSE) questions. MSE is the main specialization exam for medicine in Türkiye and is held twice a year by The Measuring, Selection and Placement Center . The anatomy sections of the MSE were about 14 questions (2021-2 MSE questions were given as an example in Appendix 1). As it could not be reached, the first exam in 2023 and the two exams in 2022 could not be evaluated. In order to evaluate whether the language option affects the success of the chat boards, the questions were also translated into English through them. After the translation process was done by the chat boards, it was checked by two anatomists . The questions that were found to be wrong or insufficient were corrected by the evaluators and asked on the chat boards. Two questions in ChatGPT and one question in Google Bard were corrected due to syntax and grammar errors. Since the software cannot evaluate visual content, all questions except those with visual content were asked. A total of 131 questions were asked on the chat boards for each user. The users were ChatGPT Turkish 1, ChatGPT Turkish 2, ChatGPT English, Google Bard Turkish 1, Google Bard Turkish 2, and Google Bard English. The accuracy of the answers was assessed according to the existing literature. The correct answers to Turkish and English questions were compared. A second user was created in both apps to assess whether the responses to the questions were systematic or whether the apps taught random answers. When these answers were compared, it was also observed whether asking the same questions resulted in more accurate answers in the second answer, thanks to machine learning. The accuracy rate of the answers given by the first and second users created in the same chat board was evaluated by comparing them with each other. In the next step, the question-answer capabilities of the software were evaluated. ChatGPT and Google Bard were asked to create and answer MSE-level multiple-choice anatomy questions. Almost all of them were correctly constructed. We asked about 100 questions for 40 different topics and only four of them were wrong. These 40 topics were identified by two anatomists. In order not to expand the boundaries of the article too much, instead of 40 topics, three random topics were sampled in the article. Then, the level was adjusted by giving the commands "make the question harder" or "recreate this question" for those who did not have the appropriate content. The MSE level emerged with the experience of two anatomists studying the exam questions of the last 10 years. The accuracy of the questions and answers at all stages was evaluated according to the current literature. And, finally, the software was asked to describe its ability to write academic papers. The validity of the anatomical information in the paper was checked, and the evaluation of whether it was detailed enough as a scientific article was done by the two different anatomists.In order to evaluate the usability of the applications in anatomy education, three stages were first defined. In the first stage, the answers of the applications to the anatomy exam questions would be evaluated. In the second stage, their ability to form questions and in the last stage to write scientific articles would be evaluated. For these processes to be applied sequentially, user accounts were first created for both ChatGPT (The free version of the LLMs’ was used (ChatGPT 3.5 and Google Bard). All the data were collected from ChatGPT and Google Bard.Statistical analysisAll data were analyzed by using the IBM SPSS  version 22.0 package. The data were expressed as numbers and percentages. For the analysis of results, two simple t-tests were used for parametric variables, while the Mann-Whitney U test was used for non-parametric variables. Kruskal Wallis test was used to evaluate the differences between all groups. The significance level was set at p < 0.05.Answering questionsThe scores obtained after asking questions to the applications are shown in Figure Question generatingAt this stage, the software was tasked with preparing three sample questions about facial nerve, peritoneum, and diencephalon anatomy which were selected by the two anatomists. The questions and answers created by the ChatGPT are shown in Figure The answer to the third question generated by ChatGPT was wrong .The questions and answers created by the Google Bard are shown in Figure All the answers to the questions generated by ChatGPT were correct .Article writingThe models were asked to write an academic paper on the anatomy of the facial nerve. The article written by ChatGPT is shown in Figure And, the article written by Google Bard is shown in Figure Although artificial intelligence applications are widely used in the field of medicine, there is not enough evaluation in the field of anatomy and anatomy education yet. Mogali used ChatGPT in the fields of asking questions, engaging like a tutor, and writing assessment items, and as a result, states that although his contribution to students and teachers in type education is not yet at a sufficient level, it has a potential for development . SimilarSimilar to these studies, we observed that ChatGPT and Google Bard, which we evaluated in terms of generating questions, responding to questions, and writing scientific articles in our study, have a significant potential for improvement in anatomy education for medical students and medical teachers in the future.In addition, when we compared ChatGPT and Google Bard models, we found that there was no difference in problem-solving skills in anatomy. Both chat boards correctly answered about half of the anatomy questions asked. We used ChatGPT-3.5 in our study. Moshirfar et al., on the other hand, used the fourth version of the ChatGPT in their study and found that the fourth version was more successful in answering the questions . The sucLLMs are evolving every day. Therefore, more studies are needed to fully explore its capabilities in the future -20. HoweWhen we evaluated the generating questions, we found that both ChatGPT and Google Bard were quite good. Even though ChatGPT generated one incorrect question, these two chat boards can be used to make exam questions of different difficulty and can save teachers time. In fact, Google Bard can be considered a little better in this regard, because while preparing a question, it also suggests different alternative questions. In terms of creating a scientific article, we saw that both chat boards article writing ability was less detailed, without references, and at a basic level, compared to previously written scientific articles on the subject. ChatGPT has created an article that is more in line with academic norms on this subject, with its general article structure and information divided into subheadings such as embryological development, clinical importance, surgical issues, future directions, and conclusion sections.The model has the potential to become a more reliable and valuable tool for anatomy education and exam preparation by improving the ability to understand anatomy-related concepts and generate appropriate questions and distractors for different difficulties.There were differences in LLM performance, but no significant difference was observed between ChatGPT and Google Bard in terms of answering questions. The question generating of these models was satisfied. It can be useful for exam preparation in educational aspects. The performance of the applications in article writing was not yet at a sufficient level. While LLMs show promise as valuable tools for medical education, their use requires caution, given the complex algorithms and their limitations in dealing with potential inaccuracies. This study highlights the need for continuous improvement and validation of LLMs for reliable healthcare practices. Further research is needed to increase the accuracy of the models and to better understand how they can be used effectively in educational settings.


This study aims to translate and cross-culturally adapt the standard version of the World Endometriosis Research Foundation (WERF) EPHect Endometriosis Patient Questionnaire (EPQ) into Danish and to ensure equivalence of a Danish electronic version.The translation, cultural adaption, and electronic migration followed recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Critical Path Institute. Ten women with endometriosis were enrolled for cognitive debriefing of the paper version (pEPQ) after translation and back translation. The questionnaire was then migrated into an electronic version (eEPQ) and subsequently tested for usability and measurement equivalence by five women with endometriosis.Cross-cultural alterations were needed for medical terms, response options for ethnicity, the educational system, and measurement units. Thirteen questions were altered after back translation, while 21 underwent minor changes after cognitive debriefing. After testing the eEPQ, 13 questions were altered. Questions tested for measurement equivalence across the two modes of administration were found comparable. The median time-to-complete the pEPQ and eEPQ was 62 min (range: 29–110) and 63 min (range: 31–88), respectively. General comments included the questionnaire being relevant but long and repetitive.We find the the Danish pEPQ and eEPQ similar and comparable to the original English instrument. However, attention must be drawn to questions regarding measurement units, ethnicity, and educational systems before cross-country comparison. The Danish pEPQ and eEPQ are suitable for obtaining subjective data on women with endometriosis. Endometriosis is an estrogen-dependent chronic inflammatory disease, affecting 10% of women primarily during their reproductive years . These sIn 2013, the World Endometriosis Research Foundation (WERF) created an international collaboration to develop the Endometriosis Phenome and Biobanking Harmonization Project (EPHect) –7.The purpose of EPHect is to enable large-scale, cross-centre, epidemiologically robust research into the causes of endometriosis, novel diagnostic methods, and better treatments. This is facilitated through the development of tools for detailed clinical and personal phenotyping (phenome) data to be collected from women with endometriosis and controls, as well as standard operating procedures (SOPs) for biological samples with respect to collection, transport, processing, and long-term storage . The WERThe EPQ is a self-administered questionnaire designed to capture anamnesis and phenotypic variations, including symptoms and health status of those with and without endometriosis. It is designed for research and should not be implemented in its full length as a clinical tool, since it is not suitable for making immediate clinical decisions. The EPQ is available in a minimum (EPQ-M) and a standard (EPQ-S) version. In the EPQ-M, sections on symptoms or characteristics during the participants' life course are omitted. Otherwise, the two versions are identical .A self-administered questionnaire can measure non-quantifiable subjective information such as perception of symptoms, health, or treatment effects without interpretation by an interviewer . The useCombining data from non-equivalent questionnaires will result in invalid research data and measurement bias , 15. ThiThis study aimed to translate and cross-culturally adapt the English paper version of the EPQ-S into Danish and to develop an electronic version while ensuring comparability between the paper and electronic mode of administration.The translation, cultural adaption, and electronic migration of the EPQ-S, followed the Good Practice Reports from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Best Practice Recommendations from the Critical Path Institute , 24–26. The EPQ incorporates the McGill Pain Questionnaire and the Pain Catastrophizing Scale. These are already translated and validated into Danish and were omitted from the translation process , 30.We invited women diagnosed with endometriosis by either ultrasound, laparoscopy, or histology to complete the pEPQ and the eEPQ. The women were recruited through the Danish Endometriosis Patients Association or the Endometriosis Clinic at Rigshospitalet, Copenhagen University Hospital. Participants had to be fluent in Danish. All women provided prior verbal and written informed consent.All the translators were native Danish speakers, were fluent in English, and knew the purpose and set-up of the questionnaire. They were asked to keep the translation simple and as close to the original English version as possible .Two multidisciplinary teams completed an independent translation each (T1 and T2). Representatives from each group discussed any discrepancies. Non-resolvable disagreements were settled by contacting experts in endometriosis . One initial forward translation was agreed upon (T3).An independent professional translator, with English as his native language and fluent in Danish, performed the back translation (BT3). The professional translator was not given any prior information on the concept of the questionnaire.Representatives from both groups (T1 and T2) compared the back translation (BT3) to the original English EPQ. Discrepancies were evaluated and by consensus, questions were either preserved, rephrased, or back translated a second time. Questions, where the representatives debated the interpretation by a layperson, were categorized as “critical”. These questions had to be evaluated by each participant during cognitive debriefing. A medical doctor with English as his native language and fluent in Danish conducted a second back translation of relevant questions. Consensus on a preliminary version (T4) for cognitive debriefing was obtained.Ten women were recruited by age, ensuring at least two in each of the following age groups: 18–29, 30–39, 40–49, and 50–60 years. All participants were asked to complete the T4 version without involving the interviewer. Participants were asked to mark phrases, figures, or questions they found inappropriate, unclear, or difficult to understand or answer. The interviewer noted time-to-complete.www.randomresult.com. Any discrepancies between the participant´s and the intervieweŕs interpretation of a translated question led it to be rephrased in collaboration to achieve the same semantics as in the original EPQ. Extensive notes and quotes were saved for future verification. Representatives from the translation groups evaluated all comments and categorized these as either: Type 1: comments that led to rephrasing, Type 2: comments relevant for a possible second revision of the original questionnaire, and Type 3: comments not relevant for rephrasing or a second revision. These categories were based on whether the comments would improve the understanding without changing the concept of a question. Disagreements were resolved by contacting the other translators, experts in endometriosis, or the first author of the original publication  their marked questions, 2) the “critical questions”, and 3) 5–8 randomly selected questions. The random questions were drawn using the website: The first author of the original EPQ  providedIn general, the format of the original paper questionnaire was kept in the electronic version, and necessary design changes were kept as close to the paper version as possible. The extent of design changes for each question was categorized as either minor, moderate, or substantial. According to these categories it has previously been recommended which tests are required to ensure comparability across modes of administration , 24.usability test was performed by asking participants to complete the eEPQ while being observed. Special attention was given to their navigation of the instrument and whether layout alterations were carried out as intended. If they experienced difficulties or doubts during completion, the interviewer was informed, and notes were taken. It was ensured that all sections in the questionnaire were answered by at least one participant. Time-to-complete was registered.Five women were recruited to test the eEPQ. The cognitive debriefing, the participants provided an overall assessment of the questionnaire and elaborated upon any difficulties noted during completion. Equivalence testing was performed by having the participants answer the paper version of questions that previously had been categorized as being moderately or substantially altered during electronic migration.During The study was approved by the Danish Data Protection Agency (P-2021-513) and was exempted from ethical approval by the Regional Ethical Committee for the Capital Region .IBM SPSS Statistics 25.0.0.2  was used for the statistical analysis. Outlier ranges were evaluated using the “1,5*interquartile-range” rule. The Intraclass Correlation Coefficient (ICC) was calculated to evaluate the correlation between the ratio and ordinal scale data from the two modes of administration.The timeline is illustrated in Cross-cultural adaptation difficulties were encountered regarding medical terms, commercial product names, ethnic origin, and the definition of pregnancy loss according to gestational age. The Danish translation of these questions was kept equal in concept to the original questionnaire. Response options on ethnic origin/race, major ancestry, the educational system, and measurement units  had to be changed to fit Danish standards. These questions are therefore not comparable across language versions .Discrepancies between the original English EPQ and BT3 resulted in 18 questions being re-evaluated. Three of these were back translated a second time. In total, 13 out of the 18 questions were altered to ensure semantic equivalence.During harmonization, eight questions were categorized as “critical” .Baseline characteristics and group distributions are presented in The median time-to-complete was 62 min (range: 29–110), as illustrated in Overall, the questionnaire was reported to be easy to read and understand (50%). However, the questionnaire was described as lengthy and time-consuming (80%), but only one participant found it too long (10%). Difficulties relating to either recall or details required were described (60%), as were a feeling of repetitiveness (40%). A lack of questions relating to pain outside the pelvic area was highlighted (40%), including discomfort in the upper abdomen, the back, and pain due to sacral nerve involvement. One woman felt questions relating to the physical and psychological side effects of medical treatment and multiple surgeries should have been included.The participants marked 35 different questions while answering, and 50 different questions were drawn randomly. After cognitive debriefing of the marked, random, and “critical questions”, a total of 21 questions were altered based on comments categorized as Type 1 . A totalAfter the electronic migration, two tables and the Numeric Rating Scale were categorized as moderately modified and assigned for equivalence testing . The desusability, all participants navigated the questionnaire without problems, and only minor changes were required. The median time-to-complete was 63 min (range: 31–88), and no sections were omitted  across the two modes of administration (P = .026) across the two modes. A table featuring nominal data showed no difference across the two modes of administration.When testing the eEPQ's  omitted . During ructions . The pare tested . They festration . The tabThis study is the first to translate and cross-cultural adapt the WERF EPHect EPQ into Danish. It describes the electronic migration of the questionnaire, and present patient-reported recommendations on how the questionnaire could be improved in a potential second edition.With its detailed appendices, this study's decision-making process is relevant for international investigators in the field of translating and validating questionnaires; examples which were previously missing in the literature.Cross-culturally adapting the questionnaire into Danish necessitated four questions to be modified in a way that compromised the possibility of direct cross-country comparison. These questions concerned heritage, measurement units, and educational level. Using terminology common to the Danish layperson should make replying easier, less confusing, and more accurate. Results from the Danish versions can easily be converted back to the corresponding English equivalent, and thus, cross-country data can be combined.The Danish pEPQ and eEPQ were validated step by step, and each stage revealed inaccuracies that led to alterations. This illustrates the importance of a stringent methodology as was applied in this study. We recommend that none of the steps incorporated in our process should be omitted when translating, cross-culturally adapting, and electronically migrating the EPQ into other languages. However, we acknowledge that the process described in this study is time- and resource-demanding. Investigators considering to simplify or omitting any of the steps should critically evaluate the consequences in advance . We encoThe length of the questionnaire made it impossible to evaluate all the questions with each participant during cognitive debriefing. Instead, it was necessary to incorporate adaptations by introducing random questions to reveal any potentially hidden misconceptions that may otherwise have been missed. None of the randomly drawn questions led to alterations that were not otherwise identified during cognitive debriefing. We, therefore, consider the risk of potential hidden misconceptions to be minimal. However, since some of the randomly drawn questions led to comments relevant for a second revision of the original EPQ, we still find this part of the process important.During the electronic migration, the extent of design changes for each question was not always easy to categorize. As a precaution, all questions/tables that were suspected to be moderately modified were assigned to an equivalence test . This apDue to the incorporated skip functions, it was expected that the eEPQ would take less time to complete. Surprisingly, time-to-complete did not seem to differ between the paper and the electronic version. This could be due to unintentional selection bias, since all women testing the eEPQ were <50 years old and reported a higher educational level. However, assuming both factors serve as a proxy for increased computer skills, these would be expected to reduce time-to-complete for the electronic version, which they did not. A more likely explanation could be the observed differences in the number of pregnancies between the two groups. Participants answering the electronic version reported a higher number of pregnancies and parities . For eacCompared to the previously published papers, describing their translation and cross-cultural adaptation of the WERF EPHect EPQ in depth, we find our method equivalent , 20. ThiComparing the time-to-complete reported by previous published translation and validation studies of the EPQ, our study reports the highest time-to-complete , 20. A pAll studies that published comments evaluating the questionnaire reported it being long and/or repetitive , 20, 22.Women without endometriosis were not included in our study. Since the questionnaire was not designed as a construct-specific tool, i.e., to capture change over time or to compare specific case and control groups , we did During equivalence testing, participants were not randomly assigned to respond to the paper or electronic version first. This may have influenced their response regarding their preferred administration mode .A considerable strength of this study was the inclusion of women with endometriosis of differing ages during cognitive debriefing of the pEPQ. It increased the variability of the participants' history with endometriosis, as well as the diversity in their approach to the questionnaire's semantics and concept . We findThe results of this study show that the Danish paper and electronic EPQ are equivalent and comparable to the original English instrument. However, special awareness is required regarding the non-equally translated questions due to cross-cultural differences. For future translations of the EPQ, we recommend that the questionnaire should be thoroughly evaluated by several translators, experts in endometriosis, and those with lived experience of endometriosis. This regards the development of both a paper and/or an electronic version of the EPQ. We recommend that patients should be informed about the purpose and length of the questionnaire to minimize any frustrations related to the time spent answering the questionnaire.


These small modifications let us explore the relationship between the ligand design and the structure of the extended metallosupramolecular architecture. The magnetic properties of the Cu(II) helicates were explored by Electron Paramagnetic Resonance (EPR) spectroscopy and Direct Current (DC) magnetic susceptibility measurements.The study of the inherent factors that influence the isolation of one type of metallosupramolecular architecture over another is one of the main objectives in the field of Metallosupramolecular Chemistry. In this work, we report two new neutral copper(II) helicates, [Cu The search for new routes to obtain new metallosupramolecular architectures and the study of their potential applications is a field of great interest in Metallosupramolecular Chemistry. The knowledge of the different factors that influence the self-assembly process is essential to control the obtainment of a specific type of compound, so it is necessary to deepen our understanding by designing new systems. Among all factors, the ligand design directly influences the structure of the final metallosupramolecular architecture and thus its properties and applications .The term “helicate” was introduced by Jean-Marie Lehn in 1987 to describe a class of copper(I) compounds exhibiting a helicoidal architecture with similar characteristics to the DNA double helix . A helicTo obtain helicoidal architectures, the precursor ligands should contain two or more binding domains separated by a flexible spacer to allow helical coiling, but also it should be rigid enough to prevent multiple binding domains coordinating to the same metal ion, giving rise to mononuclear species ,5,6. MorCurrently, the research on metal helicates is mainly directed towards the search of their potential applications ,11,12,13Schiff base ligands have been extensively used in Coordination Chemistry ,18,19 anWith this precedent in mind, in an attempt to explore the relationship between the ligand design, the extended helical structure and the magnetic properties, we approach the obtainment of helicates combining Schiff base ligands, copper(II) ions and an electrochemical methodology. Herein, we report two novel copper(II) helicates derived from two Schiff base ligands substituted with t-butyl groups and their crystal structures. We studied their magnetic properties by EPR spectroscopy and DC magnetic susceptibility.2L1 and H2L2, In the present work, we approach the obtainment of extended helicates using dianiline-derived Schiff base ligands. It should be highlighted that the long and semi-flexible dianiline-type spacers have been widely used by Hannon and co-workers, proving to be an effective unit for obtaining a wide variety of helicoidal architectures using different metal ions ,23,24. F2L1 and H2L2 are potentially dianionic with two bidentate [NO] domains separated by a semi-flexible aromatic spacer, factors that should favor the isolation of helical-type complexes. The main objective is to find out whether the position of the tert-butyl group influences the final discrete and extended architecture and the magnetic properties of the final compounds. The ligands H2L1 and H2L2 were fully characterized by melting point determination, elemental analysis, infrared spectroscopy, mass spectrometry and 1H NMR spectroscopy techniques . The resulting brown solid complexes were characterized by melting point determination, elemental analysis, infrared spectroscopy, X-ray diffraction and mass spectrometry .2(L1|2)2], with the ligands being coordinated to the copper centers in their dianionic form [L1|2]2−. The infrared spectra of both complexes exhibit a slight shift of the characteristic bands of the ligand skeletons to lower wavenumbers due to the coordination of the metal ions. More in detail, a variation in the ν(C=N) band is observed, indicating that the ligand is bound to the metal via the imine nitrogen atoms. In addition, the increase in intensity and the shift of the vibration band (C-O) suggest the coordination of the copper(II) ions through the phenolic oxygen atoms of the ligand. Similarly, it is observed that both vibrational bands, ν(C-HAr) and ν(CH2), increase in intensity due to the effect of the coordination. The formation of the copper(II) complexes derived from the Schiff base ligands H2L1 and H2L2 was also confirmed by MALDI-TOF (+) mass spectrometry 2] and [Cu2(L2)2]·CH3CN complexes allowed us to achieve good-quality crystals for X-ray diffraction studies. The crystal structures of the complexes ([Cu2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN are depicted in Slow evaporation of the mother liquors from the synthesis of [Cu1|2]2− that cross each other when coordinating the two Cu(II) ions  ions . The ligII) ions .2(L1)2]·4CH3CN and 11.87 Å for [Cu2(L2)2]·CH3CN) are in the order of those found for other Cu(II) helicates with dianiline-type spacers and do not deserve further comments ·4CH3CN; 3.92 Å and 3.86 Å for [Cu2(L2)2]·CH3CN, Each helicate molecule displays eight aromatic rings, which makes possible the establishment of aromatic π-π or CH···π stacking interactions. Thus, both copper(II) helicates display weak π-π interactions between the aromatic rings of the two aniline spacers that contribute to the stabilization of the helicoidal structure (distance between centroids: 3.890 Å for [Cu2(L1)2]·4CH3CN (2(L1)2]·4CH3CN (3.79 Å) cell  cell .2(L2)2]·CH3CN involves one of the phenyl rings of the spacer, with the benzene of a linker domain (centroid–centroid distance 3.79 Å) being an important difference compared to the [Cu2(L1)2]·4CH3CN helicate 2]·CH3CN, which incorporates the tert-butyl groups adjacent to the phenolic groups, establishes hydrogen bond interactions between the CH3 of the tert-butyl groups and the phenolic oxygen atoms  helicate [Cuen atoms  31]..2(L2)2]·It is remarkable to mention that in the case of the two helicates described in this work the distance between the Cu(II) ions of the closest stacked helicates  is notably smaller than the distance between the two metal atoms within the molecule, in the same way as the copper(II) helicate reported by us in 2003  and the 2(L1)2]·4CH3CN helicate (~5.6 Å) (2(L2)2]·CH3CN helicate, which incorporates the tert-butyl substituent in the ortho position (~7.1 Å)  , which e(~7.1 Å) .2L1 and H2L2 are suitable to obtain extended helicate structures through weak intermolecular interactions. In addition, the position of the bulky t-butyl groups influences the microarchitecture of the extended structure, as demonstrated by the shorter intermolecular Cu---Cu distance displayed when the ligand exhibits the tert-butyl groups far away from the binding sites (para position).All this information confirms that the highly aromatic Schiff base ligands HIt is well known that in coordination compounds metal ions can interact with each other when the distance between them is small . Additio2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN helicates were studied by DC magnetic susceptibility and EPR spectroscopy.Thus, taking into account the above background, the magnetic properties of the crystalline samples of both copper(II) ·4CH3CN helicate. This behavior is similar to that previously observed by us for a network assembled from Cu(II) helicates [MT decreases slightly when increasing temperature in [Cu2(L2)2]·CH3CN.The temperature dependence of the magnetic susceptibility, χ, is shown in elicates . On the 2+ ions will result in a μ = 3.54 μB/Cu, and hence χMT ≈ 3.5 emu K mol−1 for a lattice with two Cu sites. In the tetrahedral d9 configuration, the unpaired electron can occupy the dxz or dyz orbitals, so that the complex acquires an orbital angular momentum. The observed increase in χMT in [Cu2(L1)2]·4CH3CN suggests a substantial orbital contribution from a partially distorted octahedral configuration (attributed to acetonitrile coordination), whose orbital occupation changes with temperature. Considering the total orbital contribution to the magnetic moment in Cu2+ species, shown in 2(L2)2]·CH3CN shows the typical EPR spectrum for an axial complex of Cu2+ (S = 1/2) with g//(≈2.26) > gx⊥(≈2.08). These values are in the range reported for copper tetracoordinated by two oxygen and two nitrogen atoms [N2O2] [The differences in the local coordination of copper in both complexes is further demonstrated by the differences observed in the EPR spectra of Cus [N2O2] ,36. The 2(L1)2]·4CH3CN shows a more complex spectrum, consistent with a distorted structure, which could justify a larger and temperature-dependent orbital contribution to χMT, discussed before. The contribution from two copper sites cannot be discarded, and a complete elucidation of the EPR spectrum of this helicate requires further investigation.On the other hand, +; 1H-NMR ): 12.98 , 8.92 , 7.91 ; 7.47 , 7.37 ; 6.89 ; 4.08 , 1.32 .H2L2: 0.5 g (2.5 mmol) of 4,4′-methylenedianiline and 0.88 mL (5.0 mmol) of 3-tert-butyl-2-hydroxybenzaldehyde were dissolved in absolute ethanol (50 mL). Then, a catalytic amount of p-toluensulfonic acid was added and the reaction mixture was heated under reflux with magnetic stirring for 4 h, using a Dean–Stark manifold to remove water and promote ligand formation. The resulting solution was concentrated to half volume and cooled, resulting in the formation of a yellow precipitate. This solid was filtered and dried in air. Yield: 1.02 g (78%); m.p.: 105–110 °C; elemental analysis: % theoretical (C35H38N2O2) C, 81.0; N, 5.4; H, 7.4; experimental C, 80.8; N, 5.4; H, 7.2; IR (cm−1) ν: 3437 vw (O-H); 2955 s (C-H); 1616 vs. (C=N); 1277 m (C-O); 745 s (CH2); ESI+ (m/z): 519.30 [H2L2 + H]+; 1H-NMR ): 14.01 , 8.90 , 7.44–7.37 ; 6.89 ; 4.09 , 1.44 .H2(L1)2] helicate.The neutral copper(II) helicates were obtained by electrochemical synthesis using acetonitrile as solvent, applying a current intensity of 10 mA and potential values in the interval of 10–15 V. As an example, we describe below the electrochemical synthesis of the : Brown solid. Yield: 0.068 g (61%); m.p.: >300 °C; Ef = 0.6 mol·F−1; elemental analysis: % theoretical (C70H72N4O4Cu2) C, 72.5; N, 4.8; H, 6.2; experimental C, 70.9; N, 4.8; H, 6.2; IR (cm−1) ν: 3397 br (O-H); 2954 m (C-H); 1618 vs. (C=N); 1255 m (C-O); 833 s (CH2); MALDI-TOF (m/z): 1159.42 [Cu2(L1)2 + H]+. By slow evaporation of the mother liquor from the synthesis, brown crystals suitable for X-ray diffraction studies were obtained ([Cu2(L1)2]·4CH3CN).[Cu2(L2)2]·CH3CN: Brown solid. Yield: 0.079 g (68%); m.p.: >300 °C; Ef = 0.5 mol·F−1; elemental analysis: % theoretical (C72H75N5O4Cu2) C, 72.0; N, 5.8; H, 6.3; experimental C, 71.5; N, 5.3; H, 6.2; IR (cm−1) ν: 2953 m (C-H); 1611 s (C=N); 1246 w (C-O); 750 s (CH2); MALDI-TOF (m/z): 1159.42 [Cu2(L2)2 + H]+. By slow evaporation of the mother liquor from the synthesis, brown crystals suitable for X-ray diffraction studies were obtained ([Cu2(L2)2]·CH3CN).[Cu2(L1)2]·4CH3CN) and ([Cu2(L2)2]·CH3CN) were collected at 100 K on a Bruker D8 VENTURE diffractometer equipped with a CCD detector, using an MoK (α) graphite monochromator (λ = 0.71073 Å). The data were treated with APPEX3v2018.7-2 software for both compounds.Crystallographic data for both copper(II) dihelicates ([Cu2(L1)2]·4CH3CN and [Cu2(L1)2]·CH3CN dihelicates.In all cases, an absorption correction (SADABS)  was appl2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN were recorded at different temperatures using a Bruker EMX spectrometer operating at 9.5 GHz (X-Band).EPR spectra of both copper(II) helicates ·4CH3CN and [Cu2(L1)2]·CH3CN confirm their helicoidal dinuclear nature. These structures are extended through the establishment of weak π-π or CH···π stacking interactions, with the intermolecular metal distance being smaller than the distance between the metal ions within the molecule, especially in the case of [Cu2(L1)2]·4CH3CN with the external tert-butyl groups located far away from the binding domains, thus confirming the influence of the bulky group location. This structural fact also influences the magnetic properties of the helicates in terms of local environments of the Cu(II) ions, but this finding will require further studies.Two novel Cu(II) neutral dinuclear helicates were isolated using an electrochemical methodology and precursor Schiff base ligands functionalized with bulky tert-butyl groups in ortho and para positions. The discrete crystal structures of both copper(II) compounds [Cu


The fabrication of composite materials is an effective way to improve the performance of a single material and expand its application range. In recent years, graphene-based materials/polymer composite aerogels have become a hot research field for preparing high-performance composites due to their special synergistic effects in mechanical and functional properties. In this paper, the preparation methods, structures, interactions, properties, and applications of graphene-based materials/polymer composite aerogels are discussed, and their development trend is projected. This paper aims to arouse extensive research interests in multidisciplinary fields and provide guidance for the rational design of advanced aerogel materials, which could then encourage efforts to use these new kinds of advanced materials in basic research and commercial applications. Benefitting from its ultralow density, ultrahigh porosity, specific surface area, excellent mass transfer property, and ultralow thermal conductivity, the aerogel shows great promise in numerous fields, such as high adsorption , thermalD network1000 °C) ,16,17,181000 °C) ,21,22. H1000 °C) ,24. Simi1000 °C) ,26.In recent years, graphene-based materials/polymer composite aerogels have been extensively studied. As shown in In order to better understand the composition of graphene-based materials/polymer composite aerogels, Polymer foams are mainly prepared using polymer foaming or gel-drying methods. Polymer foaming methods are divided into three types according to the foaming method: physical, mechanical, and chemical. In physical foaming, low-boiling-point (BP) liquid and polymer are blended and then foamed through pressuring and heating . In addiThe impregnation method includes two steps. First, the 3D network skeleton is prepared in advance, and then, the composite is immersed into the 3D skeleton under vacuum or hydrophobic action. The composite material is obtained after curing.As shown in As shown in The impregnation method is simple, and the structures of the composite aerogels are related to the impregnation times and impregnation concentration.The liquid blending methods have various compositing methods and strong inclusiveness, which are the most studied composite methods in the field of graphene-based materials/polymer composite aerogels at present.In this method, after mixing, reducing, and drying, the polymers and graphene-based materials solutions immediately form graphene-based materials/polymer composite aerogels ,68,69,70In this method, polymer monomers and graphene or GO are polymerized to obtain graphene-based materials/polymer composite aerogels ,76,77. F−3), highly compressible (>90%), and water-adhesive graphene/NRL hybrid aerogel  foaming technology to obtain a graphene/polymer composite aerogel [2 foaming process. The melt-blending method has strict requirements for the processing temperature and is not easy to scale up.At present, there are few studies on the preparation of graphene-based materials/polymer composite aerogels by melt blending. This method first melts the polymer and graphene to obtain a liquated composite, and then uses injection foaming technology or supercritical carbon dioxide  at a current density of 0.5 A g−1 (The conductivity of graphene can reach (6000 S/cm), which makes it possible to prepare composite materials with excellent electrochemical properties. However, the serious restacking of the 2D graphene layer during the manufacturing process leads to lower conductivity. The 3D graphene-based materials aerogel with interconnected network and abundant porous structure can effectively prevent the accumulation of 2D graphene layers, showing good and stable electrochemical performance. For conductive polymers such as polyaniline ,116, PPy.5 A g−1 b. The si−2). Upon irradiation (1 sun), the surface temperature of GA/NRL−0.5 rapidly increased to 108.8 °C within 50 s, which is much higher than that of GA (88.5 °C). The enhanced solar–thermal conversion property of GA/NRL-0.5 resulted from the broad optical absorption of the RGO skeleton and the light scattering from the numerous papillae. Furthermore, nanowrinkles extended the optical path within the aerogel and captured a significant amount of light. Natural rubber particles among the RGO sheets could effectively reduce the heat dissipation between graphene networks.Graphene aerogels can be used in thermal insulation due to their low density and high porosity. The components and pore structures of graphene-based materials composite aerogels are important to thermal insulation. 2/g. In this work, polydopamine (PD) was utilized as an interlayer to bind GO and (PEI) brushes. The uniform and well-controlled coating of an ultrathin PD layer on GO not only enhanced the hydrophilicity of GO sheets, but also provided abundant active sites for further grafting of PEI. The adsorption capacity of the RGO, PD/RGO, PEI/RGO, and PEI-PD/RGO aerogels to Pb2+ were first researched as shown in 2+. This indicated that the synergistic effect between PEI and RGO greatly improved the adsorption performance. 2+, Cd2+, Pb2+, and Hg2+ on PEI/RGO aerogel and PEI–PD/RGO aerogel and commercialized active carbon. The capacities of PEI-PD/RGO aerogel for Cu2+, Cd2+, Pb2+, and Hg2+ are 38, 32, 95, and 113 mg/g, respectively. Graphene/polymer composite aerogels also show the gas-absorption ability. Hsan et al. [2 gas. As shown in 2 adsorption that was recorded on the surface of the aerogels was 11.35 mg g−1 (0.257 mmol g−1) as the pressure was increased to 1 bar. Generally, organic solvents or dyes adsorbed in graphene composite aerogels require external forces to achieve desorption, such as extrusion or heating evaporation. In recent years, researchers have invented new methods to achieve the adsorption and desorption of adsorbates under external stimuli . For example, Zhu et al. [Graphene aerogels can be used as adsorption materials because of their high specific surface areas, high porosities, and hydrophobicity. Combining them with functional polymers can further improve the adsorption capacity and efficiency ,131,132.n et al.  demonstru et al.  preparedmin) value of −14 dB when the absorber thickness and frequency are 5 mm and 9.81 GHz, respectively. Its effective bandwidth (RL < −10 dB) was 3.73 GHz (8.16–11.89 GHz). After being combined with RGO and PI1/2, the RLmin value of the PI-GP1/2 foam could decrease to −20.15 dB at 8.16 GHz when the thickness is 5 mm. The RLmin value at 18.0 GHz of PI-GP1/2-RGO with a thickness of 2 mm was −24.86 dB, and the effective bandwidth was improved to 3.97 GHz (14.03–18 GHz). Comparison with PI-GP1/2 and pure RGO foams, the obvious enhancement in absorption capacity and bandwidth can be attributed to the successful construction of the three-level impedance gradient in the foam. In addition, graphene/polymer composite aerogels can be applied in sound absorption [Graphene-based materials/polymer composite aerogels rely on multiple reflections between pore structures to achieve attenuation of incident electromagnetic waves or by controlling the impedance gradient of the material skeleton, which can make a big difference in absorbing materials. As an example, Pu et al.  exactly sorption . Pang etsorption  reportedGraphene-based materials/polymer composite aerogels have attracted increasing amounts of attention in recent years. In this paper, the research progress of graphene-based materials/polymer composite aerogels is systematically reviewed, including the preparation methods, structures, interactions, properties, and applications.From the perspective of preparation methods, the impregnation methods are simple and easy to scale up. These methods may be the most likely way to achieve industrial mass production. However, these methods have a limited range of structural variation and material properties. At present, the liquid phase blending methods are commonly used because these methods can easily extend to many types of polymers and the prepared composite aerogels show several different 3D networks and properties. Therefore, more and more advanced composite aerogels with unique properties could be prepared using these methods. In terms of structures and interaction, the structures of graphene-based materials/polymer composite aerogels prepared using the impregnation method are often a multi-layer structure with a layer of graphene or polymer coating over a 3D network skeleton. In the liquid phase blending methods, the graphene-based materials solutions are more uniformly compounded with the polymers than in the other methods. In the structure of composite aerogels, polymers often act as a bridge to reduce the stacking of graphene sheets. Different kinds of composite structures and interactions can be achieved using the liquid phase blending methods.First, in terms of properties and applications, the introduction of polymers more effectively improves the mechanical properties of materials than pure graphene aerogels do, and they show superior results in sensor applications. Second, in terms of electrical properties and applications, most polymers are nonconductive. The addition of graphene aerogels can endow them with excellent electrical properties. At the same time, graphene aerogels can play a synergistic role with conductive polymers and show significant application effects in supercapacitors, electromagnetic shielding, and compressible batteries. Third, in terms of thermal properties and applications, graphene aerogel itself has thermal insulation and photothermal properties. The addition of some polymers can improve these properties. Thus, graphene-based materials/polymer composite aerogels can be applied in demanding fields. In addition, since graphene has excellent thermal conductivity, it can be used as a filler to prepare graphene-based materials/polymer composite aerogels with high thermal conductivity, and the composite aerogels show application prospects in thermal management. Fourth, in terms of adsorption performance and application, graphene aerogels can be compounded with functional polymers, and have shown more excellent results in oil absorption, dye and gas adsorption, heavy metal ion adsorption and intelligent adsorption and desorption. Finally, graphene-based materials/polymer composite aerogels also show the performance and great application prospects in advanced functions, such as microwave absorption and sound absorption. Ultimately, for many mechanical and functional properties, graphene-based materials/polymers composites can offer better performance than a single aerogel or foam due to their synergistic effects.In summary, the future research direction of graphene-based materials/polymer composite aerogels will be directed toward the precise design and large-scale preparation of composite materials with multidimensional properties and better performance.