The aim of the study was to explore and understand the organizational culture of a workplace in terms of support and well‐being for staff experiencing perimenopausal and menopausal symptoms at work.Issues in Mental Health Nursing, 42, 2021, 541–548). The perimenopause and menopause transition can be a challenging time where many may require symptom management and support . This paper presents a case study research (CSR) approach to examine one healthcare organization.It is widely acknowledged that perimenopause and menopause symptoms are experienced by a large percentage of the female workforce. There is a lack of research into how nurses are supported through menopause  showed a majority female workforce of 81.9% with 40.6% aged between 41 and 55 years old, meaning a third of the organization working through perimenopause and menopause. Survey responses (n = 167) collected biographical and psychometric data on the prevalence of perimenopausal and menopausal symptoms. Seven managers were interviewed highlighting two themes: Access to support and culture of menopause and 13 documents from the organization on menopause were analysed for content. The study design permitted an iterative approach to data collection and providing an in‐depth understanding of the needs and support for those experiencing perimenopause and menopause. The findings help healthcare organizations to understand their workforce and take in to account the larger numbers of female employees particularly nurses with the need to provide person‐centred support mechanisms and an organizational approach for all employees.The case study generated both quantitative and qualitative data using surveys, interviews and documentation. Data from the organization ( It is aThere are many influential authors and researchers who have contributed to the development of CSR. From an epistemology viewpoint, case study researchers must capture the knowledge and experience of the reality of the case and CSR provides a framework for this and the researcher must choose the right methods to investigate. CSR can be defined in a variety of ways but has one guiding principle; to explore an event or phenomenon in depth and in its natural context Yin, . Stake  sees leaAccording to Yin , case stThe selected case should allow the research team access to the group of individuals, the organisation or the processes which will form the chosen unit of analysis for the study. A case could be pre‐selected for the researcher, with decisions being influenced by key stakeholders or because of empirical research leading to the rationale for choice and thereby needing access to a specific site. For example, this case was based on empirical evidence where Cronin et al.  qualitatThis paper therefore reports in a study where CSR was used to explore and understand the organisational culture of one UK healthcare organisation in terms of support and well‐being for staff experiencing perimenopausal and menopausal symptoms at work.3Menopause typically occurs in the midlife period between the ages of 45 and 55 years , 4To understand the prevalence and severity of perimenopausal and menopausal symptoms in employees.To explore factors that may be influencing these symptoms and their severity.To examine how the organisation might help employees whose working lives are impacted by perimenopausal and menopausal symptoms.The study set out to explore and understand the organisational culture of the workplace in terms of support and well‐being for staff experiencing perimenopausal and menopausal in one local organisation aiming to:The goal of CSR is to create an accurate description of the case with data being collected prospectively with the phenomenon under investigation embedded in everyday practice, by taking a snapshot of time (March to June 2022). To ensure the CSR methods were appropriate for this organisation, a service user group established from the UK arm of the primary study .The online survey accessible on a range of mobile devices and computer was based on self‐report, with 75 questions taking approximately 20–25 min to complete. These included demographic and health‐related questions and a range of validated tools that are used widely to measure health and well‐being. There were a range of health and well‐being questions including sleep quality, levels of depression and a rating scale for menopause comparing severity of symptoms and a range of relationship to work‐related variables.Questions around work in the organisation included role, working hours, work status, how long they have worked, shift patterns, flexibility, job satisfaction and level of job stress. There were questions around the work environment, work and job demands, control, support from manager and peers, relationships at work and role. Job performance included questions on presenteeism, absences related to perimenopause or menopause symptoms and leaving work early or arriving late for work. There were questions on turnover intentions: whether reducing hours, intending to leave workforce or the organisation itself.Perimenopause and menopause questions related to the menstrual cycle, description, and duration of symptoms and seeking professional support. Other questions included who menopause symptoms were discussed with; whether receiving support or supporting someone else with menopause. The survey ended asking if employees were felt informed on the topic of menopause, whether they felt equipped to talk about menopause and asked what support would help.6Seven managers were interviewed using a semi‐structured schedule conducted (JA) remotely by zoom minimising the risks associated with face‐to‐face visitation during the post‐pandemic phase. All interviews were transcribed verbatim ranging in duration from 10 to 26 min. The managers were employed across the organisation and length of service ranged from 3 to 32 years with an average of 15.1 years' service.7Thirteen documents were provided from the organisation (SS), published from 2017 to 2021 in a variety of formats and presented in different platforms transportable as electronic files across the organisation.8Quantitative and qualitative data was generated and analysed in this case study. Descriptive and inferential analyses were performed (NA) on quantitative data to understand the sample and scales using the statistical software package SPSS of which the findings are presented elsewhere.n = 7) were entered in NVivo (version 11) and thematically analysed  using the Braun and Clarke framework  of the participants had never smoked. The average height was 158.38 cm and average weight 76.77 kg, giving the average BMI of 30.6 (category obese).The demography of survey employees was 92% female, 8% male with the average employee aged 47.3 years (age range 23–66 years). Working status: 73% full‐time, 26% part‐time and 1% consisted of students and self‐employed and 61%  for past face‐to‐face menopause training events promoting menopause in lunch and learn sessions. There were copies of past presentations (n = 3) to employees and managers given by the same external consultant covering broadly the same topics on menopause physiology, the importance of diet and exercise, sexual health, contraception and availability of HRT. There were some other resources documents from an external human resource and research and development company offering generic workplace resources and recommendations, however not specific to the healthcare environment displayed a corporate feel, using images of women in business attire and largely grey and blue tones. One other resource advocated talking about menopause, and not making assumptions. It used a quote: ‘many women will continue to suffer in silence unless we break the taboo and start talking openly about the menopause at work’.This data included one draft workplace policy and 12 other documents and resources. Of these documents, there were flyers  reported experiencing menopausal symptoms ranging from mild symptoms (38%), moderate (49%), and 13% reported experiencing severe symptoms impacting work and home life. These rates align with those reported nationally in Bazeley et al.  study of‘we have an ageing population and its impact in the workforce is only being recently seen as we have more people working later in life and we have not had to deal with this before’.Of those reporting moderate or severe symptoms, at least 60% had taken time off, left early or been late for work in the preceding 4 weeks, because of their symptoms. Of those with severe symptoms, 64% reported an intention to reduce working hours, 47% intended to leave the workforce, and 44% intended to leave their employing organisation. This organisation seems to be ambivalent of its environment and its effect on employees despite the fact rightly or wrongly assuming those working in a healthcare environment would be more prepared for perimenopause and menopause systems. As one manager put it Through the documentation the organisation has evidence of information sessions, seminars and policy development from various departments across the organisation; however, data from interviews and the employee survey showed variable levels of engagement, and furthermore reflected in employee lack of knowledge of menopausal symptoms. Managing perimenopause and postmenopausal health is an issue for all areas in health care and training for healthcare professionals should include menopausal health in their curriculum (Rees et al., Interestingly, it appears to be quite different from the individual perspective with few employees seeking support, and some managers thought other symptoms may mask menopausal symptoms and felt that employees rather that labelling as menopause would be fearful of what their organisation might say or do, and consequently influencing rates of absentiseem. This study also found that there appeared a misunderstanding around the term presenteeism and what it meant from both managers and employees. Presenteeism or employees working when they are ill or displaying symptoms is an increasing fact driven through a range of issues: obligation of role, stress or financial concerns (NHS England, The interviews with managers shared scope on flexible working depending on employee role. While there was discussion around adjustments and approachability, it was felt that employees might find it difficult to approach managers, occupational health or GPs. Arguably menopause conversations are needed in the workplace to remove these barriers. Beck et al.  survey oSurvey data reported employees feeling uncomfortable discussing menopause with their managers, whereas the interviews illustrated a different narrative with managers perceiving themselves to be approachable. Beck et al.  survey fThe interview data showed if symptoms were reported managers would discuss needs and would make necessary adjustments but felt very few employees came to speak about menopause. Newson  workplacThe culture of menopause needs to change and as it is not going away. Menopause needs to be treated differently, firstly, menopause as an issue for a growing older workforce working longer and secondly menopause is an issue that includes everyone needs to know about. This organisation employed a majority female workforce of 81.9%, higher than the national average with 78% in healthcare settings followed by 70% in education (Devine & Foley, Healthcare environments are known to have significant stress and this study found correlation with high levels of stress and anxiety. Together with added pressures of the covid pandemic, those working in healthcare settings are predisposed to more severe menopausal symptoms. The interviews also saw that managers typically found employees want to continue to work despite their symptoms and therefore there may be some contradiction or just the need to recognise that those suffering menopause symptoms need support in the workplace. This includes learning and talking about their symptoms, learning to track symptoms and getting help or signposting to treat their symptoms Cronin, .Several limitations included the low survey response rate, although this was reported to be in‐line with organisational norms and comparatively higher response rate than Hardy et al.  national12This study provided an in‐depth snapshot of a case, attempting to explore and understand the organisational culture of the workplace in terms of support and well‐being for staff experiencing perimenopausal and menopausal symptoms.CSR provided an in‐depth analysis of this organisation showing a female majority workforce and a third working through perimenopause and menopause. This organisation has a majority female workforce with a third of the organisation working through perimenopause and menopause. Both employees and managers have disclosed and observed a range of issues, the organisation needs a joined‐up approach and the culture of menopause needs to change with good conversation where employees can talk, track and treat their symptoms. All staff need to understand menopause through education for themselves and others; and recognise that this type of organisation can be stressful for employees and may exacerbate symptoms of perimenopause and menopause.CC developed the concept, project design, contributed to analysis and drafted the manuscript. JA was a researcher employed for the duration of the project and conducted qualitative analysis. Statistical analysis was done by NA and contributed the review of the manuscript. The study site co‐ordinator on the project was SS.This project was funded by the University of Essex PVC‐R Fund.None declared.This study received HRA ethical approval [22/HRA/0590].


The surgical approach and prognosis for invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA) of the lung differ. However, they both manifest as identical ground‐glass nodules (GGNs) in computed tomography images, and no effective method exists to discriminate them.We developed and validated a three‐dimensional (3D) deep transfer learning model to discriminate IAC from MIA based on CT images of GGNs. This model uses a 3D medical image pre‐training model  and a fusion model to build a classification network. Transfer learning was utilized for end‐to‐end predictive modeling of the cohort data of the first center, and the cohort data of the other two centers were used as independent external validation data. This study included 999 lung GGN images of 921 patients pathologically diagnosed with IAC or MIA at three cohort centers.The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). The model had high diagnostic efficacy for the training and validation groups .Our 3D deep transfer learning model provides a noninvasive, low‐cost, rapid, and reproducible method for preoperative prediction of IAC and MIA in lung cancer patients with GGNs. It can help clinicians to choose the optimal surgical strategy and improve the prognosis of patients. This paper reports the development and validation of a three‐dimensional (3D) deep transfer learning model for the discrimination of two ground‐glass nodule (GGN) cancer subtypes, invasive adenocarcinoma (IAC), and minimally invasive adenocarcinoma (MIA), from computed tomography (CT) images. It is the leading cause of cancer‐related deaths worldwide and has the most rapidly increasing prevalence and mortality among human malignancies.Clinical management strategies, surgical approaches, postoperative treatment options, and survival rates vary among different subtypes of adenocarcinoma.In general, preinvasive lesions and MIA are suitable for planned follow‐up or sublobar resection (wedge resection or segmentectomy) to maximize the preservation of healthy lung tissue and thus reduce surgery‐related mortality and morbidity. By contrast, IAC patients must undergo lobectomy and mediastinal lymph node dissection, with reports stating that postoperative adjuvant therapy can improve their survival.Radiomics is an emerging technology that first transforms medical images into extractable high‐dimensional data and then performs feature extraction, dimensionality reduction analysis, and model development. This allows it to effectively overcome the obstacle to quantitative assessment of tumor heterogeneity, and thus it has significant clinical importance.Recently, a novel deep learning (DL) technique has exhibited outstanding performance in many medical image analysis fields.Although a few studies have applied DL to the prediction of pathological subtypes of GGN‐type lung adenocarcinoma, it has predominantly been used to discriminate between invasive adenocarcinoma (MIA/IAC) and preinvasive lesions (AAH/AIS). This study was conducted to develop a 3D DL‐based model for discriminating between the MIA and IAC GGN subtypes. Specifically, we combined a 3D medical image pretrained model with a fusion model via transfer learning and validated the predictive and discriminative performance of the combined DL‐based model for IAC and MIA.22.1In this retrospective study, the CT GGN images of patients who were pathologically diagnosed with IAC or MIA were collected from the picture archiving and communication systems of three cohort centers. The inclusion criteria for patients were as follows: (1) pathological diagnosis of pulmonary IAC or MIA by surgical resection or percutaneous needle biopsy; (2) subjected to thin‐slice CT scans with slice thickness of ≤1 mm; (3) underwent chest high‐resolution CT (HRCT) scans within 1 month before surgery and had GGNs in CT images; and (4) did not receive therapy before HRCT scans. Those with significant respiratory motion artifacts or incomplete clinical information were excluded. The local institutional review board approved this retrospective study and waived the requirement for written informed consent.Multiple nodules existed in some patients, with each nodule possibly of a different pathological type. Therefore, each GGN was analyzed separately in this scenario. A total of 911 patients  met the inclusion criteria and were included, with a total of 999 pulmonary GGNs, of which 387 lesions were located in the left lung (263 in the upper left lobe and 124 in the lower left lobe), and 612 in the right lung . All patients underwent video‐assisted thoracoscopic surgery, 384 patients underwent lobectomy, 615 patients underwent sublobar resection .The 539 GGNs of the first center  were randomly divided into training and internal validation groups in an 8:2 ratio. The 289 GGNs of the second center  and 171 GGNs of the third center  were used as two independent external validation groups. The workflow is depicted in Figure 2.2At each center, all CT scans were breath‐hold scans performed at the end of deep inspiration while the patients were in a supine position with the head advanced. The scan range covered the entire area from the lung apex to the lung base. The following CT scanners were used: Aquilion ONE (Canon), Brilliance (Philips), Force (Siemens), Definition (Siemens), and uCT 510 (United Imaging). The scan parameters for each CT scanner are presented in Table 2.3www.itksnap.org).All cross‐sectional digital imaging and communications in medicine (DICOM) images of pulmonary GGNs were imported into the software ITK‐SNAP  of the image values to meet the input requirements of the model. After the preprocessing step, the CT images and delineated image were stitched on the channel, and an image block of size 32 × 64 × 64 centered on the nodule was truncated to be used as the input to the model. Data augmentation was performed during model training by randomly flipping the image block in the horizontal and vertical directions. The overall research design is illustrated in Figure 00, 500. 2.4In this study, a DL model was constructed using a 3D medical image pretrained model In this study, the ResNet10 network of MedicalNet was used as the backbone of the feature encoder and the output channel of the last fully connected layer of the original network was set to two. To meet the requirement that the input to MedicalNet be a single‐channel input, after the CT images and delineated image were input to the model, the two input channels were converted to a single channel by passing them through two image‐mask module layers, with each layer consisting of a 3D convolutional layer and a Leaky ReLU activation function.The network was initialized using the pre‐training weights of MedicalNet and optimized using the Adam optimizer and focal loss function, with the ratio of the learning rate of the MedicalNet backbone to the learning rate of all other layers set to 0.01:1. An stochastic gradient descent with warm restarts strategy was adopted to adjust the learning rate; specifically, the initial value was set to 0.02, and after n epochs, a hot restart and resetting of the learning rate to its initial value were carried out. This cleared the momentum buffer of the optimizer and created a temporary period of instability so that it could escape from suboptimal local minima.2.5t‐test or rank‐sum test for continuous variables, with p < 0.05 indicating a significant difference. The predictive performance of the model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC).Descriptive statistical analysis was performed using SPSS (version 26.0) for the training and validation groups of each center. The chi‐square test was performed for qualitative variables and 33.1p > 0.05). Conversely, there were significant intergroup differences in age and tumor diameter for each center. The results showed that nodal diameter is an important indicator for the clinical identification of IAC and MIA, and the analysis of the three‐center data revealed that the optimal nodal diameter cutoff value for differentiating the two subtypes is 10.5 mm.The basic characteristics of the patients in the three centers are listed in Table 3.2p < 0.05). The PR curves show that the model had a similar performance for the training set, internal validation set, and external validation set 2, but a significantly lower performance for external validation set 3 (p < 0.05).For the training group, the radiomics‐based DL model achieved an accuracy of 89%, sensitivity of 98%, specificity of 81%, and AUC of 97%; for the internal validation group, it achieved an accuracy of 80%, sensitivity of 82%, specificity of 78%, and AUC of 92%. The ROC and precision–recall (PR) curves are shown in Figure The main metrics of the model for the training, test, and external validation sets and their corresponding 95% confidence intervals were consistent with the ROC and PR curve analysis, that is, the model performance decreased in the order of internal validation set, external validation set 2, and external validation set 3. See Table 4This study demonstrated for the first time the application of a 3D medical image pretrained DL model combined with transfer learning to evaluate the pathological subtype of GGN‐type lung adenocarcinoma. Furthermore, the model exhibited excellent performance for internal and external validation sets, indicating the effectiveness and robustness of the proposed approach.Most early lung adenocarcinomas appear as GGNs on thin‐slice CT images, and with the widespread availability of HRCT and low‐dose screening, the detection rate of pulmonary GGNs is increasing.Multidisciplinary diagnosis and treatment (MDT) is a widely recognized option for providing many benefits to oncology patients through the multidimensional discussion and analysis of the disease, and it has been reported as capable of significantly improving the prognosis of patients.The size of nodules is an important parameter for assessing the invasiveness of GGNs, and the optimal cutoff diameter is beneficial to the assessment of the invasiveness of lung adenocarcinoma.With the advent of the era of big data, the use of radiomics software to extract quantitative tumor features, and the use of artificial intelligence techniques to mine characteristic variables and construct quantitative prediction models provide new directions for developing analysis and decision‐making tools in imaging diagnosis. Chae et al. used artificial neural networks (ANNs) to build a radiomics‐based prediction model to identify preinvasive lesions (AAH/AIS) versus invasive lesions (MIA/IAC) in mGGN‐type lung adenocarcinoma and achieved excellent results (AUC = 98.1%).p < 0.05), which may be attributed to the significant difference between external validation set 2 compared to other validation sets in the diameter of the IAC tumor (cohort 3: 1.29 cm vs. cohort 2: 1.52 cm vs. cohort 1: 1.60 cm). In other words, the significantly shorter diameter of the IAC tumor at the third center led to reduced model performance on validation set 3.Nevertheless, although the model displayed high predictive performance on both internal and external data, there were significant differences in the ROC and PR curves between external validation sets 2 and 3  The progression of AAH into AIS, MIA, and IAC is a dynamic continuous process involving multiple genes, in which AAH and AIS can gradually develop into MIA and IAC.This study had several limitations. First, it was a retrospective study with inherent bias, and thus prospective applications are needed to ascertain the robustness of the present results further. Second, ROIs were all delineated manually, which was time‐consuming and labor‐intensive. Third, although there were two cohort hospitals as external centers to provide data, the data from the three centers were still focused on one racial group, thus the predictive performance of the model in other racial groups remains to be validated.In future research, we will include a larger sample of patients and develop an artificial intelligence‐based tool for the automatic delineation of ROIs so that the model will improve to become more suitable for large samples. Further, a clinical risk model for lung cancer will be developed to facilitate the development of personalized clinical treatment plans.This study demonstrated that by jointly using a model pretrained on 3D medical images and transfer learning, it is possible to discriminate between IAC and MIA effectively, although both manifest as pulmonary GGNs. The results verify that the approach can provide a noninvasive, low‐cost, and reproducible method for preoperative prediction in a clinical setting.chunlong fu: Conceptualization (lead); data curation (lead); formal analysis (lead); investigation (lead); methodology ; software ; validation (lead); writing – original draft (lead). zebin yang: Data curation (lead); formal analysis ; investigation ; methodology ; resources ; validation (lead); writing – original draft . ping li: Data curation ; formal analysis ; methodology ; software ; validation ; writing – original draft . kangfei shan: Data curation ; formal analysis ; investigation ; resources ; software ; validation . meikang wu: Data curation ; formal analysis ; investigation ; software ; validation . jieping xu: Data curation ; investigation ; methodology ; software ; validation ; visualization . chijun ma: Data curation ; formal analysis ; investigation ; software ; visualization . fanghong luo: Data curation ; formal analysis ; investigation ; validation ; visualization . long zhou: Conceptualization (lead); formal analysis ; investigation ; methodology (lead); project administration ; software ; supervision ; validation ; visualization ; writing – original draft (lead); writing – review and editing (lead). Ji‐Hong Sun: Conceptualization ; funding acquisition ; project administration ; resources (lead); supervision (lead); writing – review and editing (lead). fenhua zhao: Conceptualization ; funding acquisition (lead); project administration (lead); resources (lead); supervision (lead); writing – review and editing (lead).This study was supported by Jinhua Science and Technology Bureau (2022–3‐015).The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.The study was approved by institutional ethics board of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  and Affiliated Dongyang Hospital of Wenzhou Medical University,   and individual consent for this retrospective analysis was waived.


To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC).The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co‐expression network analysis was used to construct co‐expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features.p < 0.01). A total of 3527 differentially expressed RNAs were screened from RNA sequencing data of 20 cases. original_glrlm_RunVariance showed significant positive correlation with most long noncoding RNAs.Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (OSCC cervical LNM is related to the salivary hair bump signaling pathway and biological process. Original_glrlm_RunVariance correlated with LNM and most differentially expressed long noncoding RNAs. It is the 15th most common malignant tumor in terms of incidence, with more than 480,000 new cases and approximately 220,000 global deaths each yearMolecular characterization of tumor tissue by genomics and proteomics is achieved by obtaining tissue specimens through invasive surgery. However, specimens have an inherent selection bias during the biopsy process and cannot accurately display the entire lesion.The ideal biomarker is noninvasive, predictive, high spatiotemporal resolution, and inexpensive. With tissue and blood compared with liquid‐derived biomarkers, imaging genomics combines radiographic phenotypes and genome data; it analyzes the relevance of genetic mutations and diagnoses radiographic features in intermediate phenotypes to explore disease pathogenesis. These markers can be used to predict treatment response and the likelihood of early metastasis and to personalize treatment decisions.This study was aimed to analyze the correlation between imaging and gene expression in patients with cervical LNM from OSCC. Firstly, the tumor‐based multi‐region analysis included multiple quantitative imaging features, the Minimum Redundancy Maximum Relevance(mRMR) and Least absolute shrinkage and selection operator (LASSO) were used to further screen the optimal radiomics features. Weighted Gene Co‐expression Network Analysis (WGCNA) was performed to capture the gene expression patterns of lymph node metastasis in patients with OSCC. It also screened the association between LNM radiomic features and gene modules, explored imaging biomarkers and pathways of LNM, and aimed to predict the development of LNM in patients with OSCC.22.1www.itksnap.org) was used to determine and delineate the region of interest (ROI) at the edge of the primary tumor on CT images. The PyRadiomics library from python was used to extract radiomic features from the delineated ROI. Finally, mRMR and LASSO were used to further select the optimal radiomic features  ≥1.0 was analyzed using an Agilent 2100 Bioanalyzer. Following digestion with deoxyribonuclease I, a Ribo‐Zero TM kit was used for removing the rRNA from the total RNA, and the messenger RNA (mRNA), long noncoding RNA (lncRNA), and circular RNA were purified. The mRNA was broken into 140–160 nt fragments using a fragmentation buffer, and the secondary structure was denatured and hybridized with primers. A strand of circular deoxyribonucleic acid was synthesized using six‐base random primers by polymerase chain reaction (PCR). Double‐stranded circular deoxyribonucleic acid was synthesized from deoxyuridine triphosphate, and the ends were repaired using a Thermomixer Comfort apparatus by adding adenine bases to the 3′‐end. Following PCR amplification, an Agilent 2100 Bioanalyzer was used for detecting the range of the inserted fragments in the library. An ABI StepOnePlus Real‐Time PCR System (TaqMan Probe) was used to measure the quantitative concentration of the library. The library was denatured into single strands by the addition of sodium hydroxide, and hybridized with the connector on a Flow Cell. Bridge PCR amplification was performed on a cBot system; sequencing was finally performed on a DNBSEQ platform. The low‐quality reads containing adapter sequences and reads with >10% N  were removed. The gene expression profile data were then obtained by quality control of the raw sequencing data using FastQC software.2.3p < 0.05 and |log2FoldChange| > 1. The VennDiagram package (version 1.6.20) in R (version 4.0.1) was used to depict the differentially expressed genes in the 20 OSCC samples and the Cancer Genome Atlas (TCGA) database. The differentially expressed genes that were common between the two groups were subsequently extracted.DESeq software was used for analyzing differential gene expression patterns in the expression profile data; the screening threshold was as follows: 2.4The differential gene expression data were normalized to transcript per million values to ensure comparability of the gene expression profiles among the samples. The optimal act law coefficient β value was determined based on the pickSoftThreshold function in the WGCNA package (version 1.69).The gene expression similarity matrix was converted into a network, constructed based on the adjacency matrix. The degree of dissimilarity between the genes was subsequently calculated and converted into a topological matrix. The topological overlap matrix was used to describe the level of association between the genes, and the hierarchical clustering method was used to obtain a gene clustering tree. The modules were split with the dynamic clipping tree algorithm and the minimum number of genes in each module was set to 30. The modules with similar expression were merged using the parameters TOMType = “unsigned” and MergeCutHeight = 0.25, and the network was finally constructed.p values were indicative of more significant correlation. The labeledHeatmap function was used to visualize the model and the above correlation matrix.The module eigengene (ME) was calculated by principal component analysis of the gene expression matrix of the entire module. The Pearson correlation coefficient between the ME and radiomic features was then calculated for determining the relationship between the modules and radiomic features. Smaller 2.5http://metascape.org/) was used for online analysis of the shared differentially expressed genes identified from the sequencing data and TCGA database for the 20 OSCC samples in this study. Bar charts depicting the results of gene functional pathway enrichment were also prepared using Metascape. The genes that demonstrated significant correlation with the radiomic features were extracted. The genes were annotated by Gene Ontology (GO) analysis, into biological process (GO_BP), molecular function (GO_MF), and cellular component (GO_CC) categories. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for classification and annotation of the genes. The results of KEGG functional enrichment were depicted using bubble charts.Metascape  and Cytoscape (version 3.7.2), respectively.33.1A total of 480 radiomic features were extracted from 140 patients with OSCC. The mRMR algorithm was used to further screen 171 features for LASSO analysis Figure . LASSO r3.2The transcriptome sequencing RNA‐seq data of the 20 patients in the experimental group revealed a total of 3527 differentially expressed RNAs (DERNAs) between LNM and non‐LNM; 2157 genes were upregulated while 1370 were downregulated Figure . Gene we3.3WGCNA is used to simplify complex gene expression data into several functional modules by measuring the co‐expression relationship between gene expression correlation coefficients and radiomic features; the modules with biological significance can be identified by combining the phenotypic information. The optimal act law coefficient β value was determined to be 26; this indicates that the network was scale‐free Figure .The modules with similar expression were merged and a total of 13 gene modules were finally constructed Figure . The larp < 0.001). The correlation between the purple gene module and the square_firstorder_Median feature was second only to that with square_firstorder_Median . The exponential_firstorder_RootMeanSquared feature also showed correlation with the purple gene module . The turquoise and purple gene modules were screened for subsequent analysis.The heat map of correlation between gene modules and radiomic features Figure  showed t3.4The turquoise gene modules were mainly enriched in the “taste transduction” signaling pathway of the KEGG database Figure  and the 3.5p < 0.05) between most genes and the two image features, square_glrlm_ShortRunHighGrayLevelEmphasis and original_glrlm_RunVariance  to establish correlations between gene expression data and radiomic features.Although studies performed over the past few decades have elucidated some of the mechanisms underlying OSCC progression, most studies have focused on protein‐coding genes, with few studies based on noncoding RNA. Protein‐coding genes comprise only 2% of the human genome, and most transcripts are noncoding RNA, including lncRNAs, which exceed 200 nt in length and do not have protein‐coding ability. Studies have shown that genomic regions that cannot encode proteins play an important role in regulating cellular physiological processes and disease progression; these regions are usually transcribed as lncRNA.Many genomic and clinical biomarkers identified from various types of cancer have been included in TCGA; these correlate with corresponding images in the Cancer Imaging Archive database.The main limitations of current imaging genomics models include the lack of reproducibility and stability.In summary, with the development of precision medicine, image genomics has become a bridge between the tumor phenotype and genotype. From the perspective of cancer management, the role of imaging genomics is expected to expand across all stages, including tumor diagnosis, treatment response prediction, and risk monitoring. Imaging genomics not only provides more accurate prediction results, but also more effective treatment options. The use of imaging biomarkers to reflect gene expression analysis of solid tumors provides a rapid and reproducible noninvasive evaluation modality for more accurate diagnosis and prediction through detailed analysis of images. Further studies are needed to explore the association between radiomic features and key genes; this will allow researchers to determine whether new biomarkers can predict diagnosis, metastasis, or treatment response in independent patient populations. It will also improve the accuracy of prognostication and help develop the best treatment plan, thereby contributing to personalized precision therapy.5CT imaging of cervical lymph node metastasis in OSCC is closely related to RNA sequencing. Based on RNA‐seq data analysis from OSCC patients, the findings from this study suggest that the “salivary secretion” signaling pathway and biological process may be related to the development of LNM in OSCC. Correlation analysis of radiomic features and key genes extracted from enhanced CT showed the “original_glrlm_RunVariance” feature to be related to metastasis; it also showed significant positive correlation with most differentially expressed lncRNAs. This forms a basis for the future search of gene imaging substitutes and the interpretation of radiomic features at the gene level.Nenghao Jin: Data curation (lead); writing – original draft (lead). Bo Qiao: Data curation ; investigation . Min Zhao: Methodology ; software (lead). Liangbo Li: Data curation . Liang Zhu: Data curation . Xiaoyi Zang: Data curation . Bin Gu: Funding acquisition (lead); writing – review and editing . Haizhong Zhang: Software ; writing – review and editing .This work were supported by Beijing Natural Science Foundation(Number: Z200001) and the National Key R&D Program of China (No. 2020YFC2008900).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The studies involving human participants were reviewed and approved by Ethics Office of Chinese PLA General Hospital(Number: S2022‐203‐01). And the consent to participate in the study have been obtained from participants. Author confirm that all the experiments on the use of human tissue samples confirm that all experiment were performed in accordance with the Declaration of Helsinki's guidelines and regulations. The study was approved and the participants gave their informed consent.Not applicable.Supplementary Figure 1 Venndiagram of the common differential genes in RNA‐seq and TCGA databases of 20 OSCC patients, blue circles are the differential genes between LNM and non‐LNM groups of OSCC patients in TCGA database, yellow circles are the differential genes obtained by RNA‐seq analysis of pathological samples of 20 OSCC patients in experimental group. A total of 41 genes were differentially expressed in both datasets.Supplementary Figure 2 Enrichment analysis of common differential gene pathways showed that genes were mainly enriched in the GO: 0031424 (Keratinization) pathwaySupplementary Figure 3 Selection of parameters for network construction. A. The β values are presented on the x‐axis and the R2 values  are presented on the y‐axis; B. The x‐axis represents the β values and the y‐axis represents the average adjacency coefficient under different β values.Supplementary Figure 4 Enrichment bubble diagram: Enrichment bubble diagram of Turquoise gene module based on GO_CC (A) and GO_MF (B); Purple module gene based on GO_CC (C) and GO_MF (D).Supplementary Table 1 Information of 140 patients with oral squamous cell carcinomaSupplementary Table 2 The correlation of OSCC clinical‐pathological variablesSupplementary Table 3 13 color genes Number of genes contained in the color moduleClick here for additional data file.


The tissue within the cluster containing the most abnormal region was compared with the resection volume using the dice score. The proposed abnormality cluster overlapped with the resection in 71% of ILAE 1 patients. Conversely, an overlap only occurred in 15% of ILAE 2+ patients. This effect discriminated outcome groups well (AUC = 0.82). Our novel approach identifies clusters of spatially similar tissue with high abnormality. This is clinically valuable, providing (a) a data‐driven framework to validate current hypotheses of the epileptogenic zone localization or (b) to guide further investigation.Successful epilepsy surgery depends on localizing and resecting cerebral abnormalities and networks that generate seizures. Abnormalities, however, may be widely distributed across multiple discontiguous areas. We propose spatially constrained clusters as candidate areas for further investigation and potential resection. We quantified the spatial overlap between the abnormality cluster and subsequent resection, hypothesizing a greater overlap in seizure‐free patients. Thirty‐four individuals with refractory focal epilepsy underwent pre‐surgical resting‐state interictal magnetoencephalography (MEG) recording. Fourteen individuals were totally seizure‐free (ILAE 1) after surgery and 20 continued to have some seizures post‐operatively (ILAE 2+). Band power abnormality maps were derived using controls as a baseline. Patient abnormalities were spatially clustered using the  Surgical success relies on the accurate delineation and resection of the epileptogenic zone (EZ), an area of tissue needed to generate seizures.One approach to develop quantitative markers of the EZ involves neurophysiological abnormality mapping.We developed a framework to account for neurophysiology abnormalities and their spatial proximity. We use clustering techniques to group areas that are both highly abnormal and spatially similar. We hypothesized a greater overlap between the abnormal cluster and subsequent resection in patients who were seizure‐free after surgery. Second, we hypothesize that identifying clusters of abnormality has clinical value to assist the localization of the EZ.22.1z‐score across frequencies. A complete description of data acquisition, pre‐processing, and abnormality mapping has been outlined previously.Resting‐state MEG recordings were acquired for 34 refractory neocortical patients and 70 healthy controls using a 275‐channel whole head CTF MEG scanner. Individual subject T1‐weighted MRI was performed using a 3T GE Signa HDx scanner. Fourteen patients were entirely seizure‐free (ILAE 1) 1 year post‐operatively.2.2k‐means clustering to account for the spatial similarity of regions when proposing tissue for resection. K‐means is an unsupervised clustering technique that assigns observations into K clusters, minimizing the intra‐cluster sum of squared distances. Four features were selected to cluster the data. The first three correspond to the standard space x, y, and z coordinates of each neocortical region of interest (ROI) centroid. The fourth feature corresponds to the band power abnormality within each ROI. All four features were mean‐centered and scaled by the standard deviation to minimize the bias when computing measures of cluster distance. Once partitioned into K clusters, the cluster containing the most abnormal neocortical region was chosen for further investigation. Finally, we constrained the cluster to a single hemisphere by retaining only regions in the most common hemisphere. Regions were constrained to a single hemisphere to better reflect focal resections, which would not span multiple hemispheres. These methods provide a data‐driven approach to propose a spatially constrained cluster, which can be considered for resection or further investigation. Note that this approach means that different patients can have different‐sized clusters, which conforms to the clinical practice of different patients with different resection sizes.We used K), we varied the number of strongest cortical abnormalities (N) used to identify the clusters of abnormality. The optimal parameter set was chosen using a leave‐one‐out procedure. The parameter pair that maximized the separability of surgical outcome groups in the remaining 33 patients was chosen as the optimal for the hold‐out patient. The top N abnormalities were chosen over a set z‐score threshold as the magnitudes of abnormalities in patients have been shown to relate to the duration of epilepsyK, 2‐4, were selected based on visual inspection of patient scree‐plots and the N strongest abnormalities were thresholded between 30 and 70 as this range provides a good balance between sensitivity and specificity.In addition to the number of clusters . The DSC, defined in Equation 3K) based on the results of the leave‐one‐out procedure.Using pre‐operative interictal MEG band power abnormality maps we sought to propose plausible areas of high abnormality that could contain the EZ while accounting for the spatial proximity of neocortical regions. Two clustering parameters were tuned for each patient using a leave‐one‐out approach which maximizes the separability of surgical outcome groups in the remaining patients. The optimal clustering parameters were identical for all patients and were identified as the top 50 strongest neocortical abnormalities (N), partitioning into three clusters . Individuals with overlap between the abnormality cluster and actual resection were 14 times more likely to be seizure‐free post‐operatively at 12 months . Similar results were found for other measures of overlap (see Appendix Expanding the analysis to the full cohort Figure  it is ev4In this study, we introduced a novel framework to identify spatially proximal abnormality clusters. We demonstrated that abnormality clusters overlap with the subsequent resection in almost all seizure‐free patients. In contrast, most patients who were not seizure‐free had resections that were completely discordant with the abnormality cluster. We suggest that abnormality clusters could be clinically useful to assist in the delineation of the cortex to be resected or investigated further to cure drug‐resistant focal epilepsy.k‐means clustering, demonstrating that simple clustering techniques could be applied to current markers of epileptogenic tissue in order to suggest realistic data‐driven areas of tissue for resection.Our current study could complement the existing literature that develops markers of the EZ using structuralIt has been established that the resection of epileptogenic tissue is associated with seizure freedom post‐surgically.One limitation of our current clustering framework is the added constraint that abnormalities should reside in a single hemisphere. Although the constraint of single hemisphere clusters better reflects a focal resection, it is conceivable that the strongest abnormalities could span both hemispheres. As such by constraining abnormalities to a single hemisphere we are discarding potentially valuable information that may alter clinical decision making. Future studies could investigate whether intracranial EEG implantation is associated with MEG band power abnormalities and determine if the cluster of strongest abnormalities provides complementary information to guide electrode implantation in seemingly healthy tissue across both hemispheres.The accurate delineation and resection of the EZ have been shown to be associated with surgical success. We introduce a fully data‐driven clustering technique to spatially constrain markers of the EZ into plausible clusters of abnormality. Our approach could be clinically valuable, offering a data‐driven cluster of tissue believed to contain the EZ. This can be used for validation against the current candidate tissue for resection, or to guide further investigation.Thomas W. Owen, Yujiang Wang, and Peter N. Taylor contributed to the conception and design of the study. Thomas W. Owen, Vytene Janiukstyte, Gerard R. Hall, Jonathan J. Horsley, Andrew McEvoy, Anna Miserocchi, Jane de Tisi, John S. Duncan, Fergus Rugg‐Gunn, Yujiang Wang, and Peter N. Taylor, contributed to the acquisition and analysis of data. Thomas W. Owen and Peter N. Taylor contributed to the drafting of the text and preparing the figures.No relevant conflicts of interest are reported. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.Appendix S1Click here for additional data file.


Empathy is a core skill essential to patient‐centred care. Yet a decline in empathy throughout undergraduate medical education is well recognised. The mainstay of existing teaching approaches to foster medical students' empathic ability has largely focused on the cognitive domain of empathy within the context of communication skills learning. However, there is growing evidence for educational initiatives that better evoke students' affective emotional responses.A student‐led educational initiative was created to enhance medical students' understanding of empathy through undertaking different experiential approaches. Eight medical students were invited to participate in an empathy workshop that involved two experiential approaches: personal simulation, and patient narrative, selected given their expected focus on the affective domain.A subsequent focus group discussion explored students' reactions, learning, and intended future change in practice. Discussions were coded and analysed for descriptive themes. Both initiatives were reported to generate students' empathic responses. Personal simulation evoked more affective domains whilst patient narratives additionally created cognitive empathic insight into the impact of the patient's condition. Students also reported intended changes to their future consulting practices.Although this is a small‐scale exploration of medical students' experiences of empathy‐related teaching initiatives, it offers insight into how each initiative could target different aspects of empathy. Data support the use of even brief experiential teaching to improve medical students' empathy during their undergraduate training. We provide recommendations for clinical educators who are considering designing similar initiatives within their undergraduate medical curricula. Effective communication relies on a patient‐centred approach, to enable shared decision‐making. Empathy is a core skill in patient‐centred consultations in which the clinician must try to ‘enter the patient's world, to see the illness through the patient's eyes’.Riess defines empathy as a ‘complex capability enabling individuals to understand and feel the emotional states of others, resulting in compassionate behaviour’.The cognitive domain of empathy has conventionally been seen as a target for intervention, as it is considered a skill and therefore amenable to modification.Questions, therefore, remain about how best to inculcate empathy among medical students. A systematic review of 18 papers identified several interventions that were evaluated for effectiveness in developing students' empathy.We … designed an educational innovation … exploring medical students' experiences and perspectives of undertaking two different affective‐focused empathy interventions.2This was a single‐site educational initiative among third‐year medical students conducted as a student‐led project.  Students were invited to participate in a voluntary 2‐h workshop focusing on schizophrenia, with the opportunity to experience two different types of initiatives, personal simulation and patient narratives. These were selected given their anticipated focus on the affective domain.Students were invited to participate in a voluntary 2‐h workshop focusing on schizophrenia.Eight students  consented to participate via email and re‐consented at the start of the workshop. They were split randomly into two groups of four; half of the group initially participated in a personal simulation session and the other half in the patient narrative session. They then swapped sessions.The personal simulation session required participants to listen individually to a recorded auditory hallucination for 15 min. The recording used intrusive, negative thoughts that were created by a mental health professional for authenticity. This approach has previously been shown to enhance learners' empathy.Our institution's ethics tool confirmed that this study did not need formal ethics approval though attention was paid throughout to ethical matters. Participation was voluntary and informed consent was obtained for both workshop participation and the use of focus group data within publications, per the Declaration of Helsinki.3All eight participants attended a 1‐h focus group discussion to explore students' experiences and perspectives of each experience, moderated by GM.Focus group discussions were recorded, transcribed and then thematically analysed by the lead author through in‐depth coding to derive descriptive themes.4This innovative educational session explored medical students' experiences of two different empathy‐focused teaching interventions. Whilst both generated students' empathic responses, personal simulation appeared to evoke more affective domains whilst patient narratives additionally created cognitive empathic insight into the patient's lived experience. Our students also commented that this workshop expanded their understanding beyond that of the specific clinical condition covered in the session suggesting the transferability of learning across clinical contexts. Though we acknowledge that students' reported change in future practice was self‐anticipated based on their immediate reflections, others have reported that even brief targeted interventions can have lasting effects on students' ability to display empathy.Whilst both generated students' empathic responses, personal simulation appeared to evoke more affective domains whilst patient narratives additionally created cognitive empathic insight into the patient's lived experience.Our school is currently making revisions to our Year 1 and Year 2 stage of the programme with a planned increase in experiential learning opportunities. In light of this evaluation, we are now incorporating community‐based IPE empathy focussed teaching utilising lessons learnt from this work supplemented by in‐practice early clinical practice. This evaluation has also identified onward questions for future larger‐scale research to identify the best ways to integrate empathy teaching into undergraduate medical curricula. Although we recruited students from the start of their clinical phase, based on findings that empathic decline is most pronounced at this point,Although we recognise the small‐scale exploratory nature of this work, the results still provide a useful foundation from which to make onward recommendations for clinical educators considering delivering similar interventions. These are summarised in Table This approach offers transferability to other health professions education programmes.The authors have no conflict of interest to disclose.Standards of the Declaration of Helsinki were maintained; all data were collected anonymously, and consent for the workshop was gained through email and then again at the start of the workshop to participate in the workshop. Written consent was then obtained again for publication of the data in a journal.


Malignant airway obstruction is a life‐threatening condition that can cause suffocation and recurrent infections due to lung atelectasis. Adenoid cystic carcinoma is a rare and slow‐growing tumour of low‐grade malignancy. We report the case of a 69‐year‐old female who presented with severe chest pain, orthopnea, and a 1‐month history of progressively worsening difficulty in breathing. Emergent rigid bronchoscopy revealed a polypoid tumour originating in the proximal end of the left main bronchus that was obstructing the left main bronchus. Debulking of the tumour using rigid bronchoscopy was performed to restore ventilation to collapsed lung and obtain histopathological examination. Histological analysis revealed a diagnosis of adenoid cystic carcinoma. The patient underwent radical sleeve resection of the left main bronchus without sacrificing lung parenchyma via left posterolateral thoracotomy. No postoperative complications or disease recurrence was found at the 5‐year follow‐up. This case emphasizes the pivotal role of rigid bronchoscopic intervention in malignant central airway obstruction. This paper should be of interest to a broad readership, particularly those in the field of thoracic surgery, because we describe the case of a 69‐year‐old female who was referred to our hospital after presenting with orthopnea, severe chest pain, and progressively worsening difficulty in breathing for 1 month. Radical sleeve resection of the left main bronchus was performed without sacrificing lung parenchyma via left posterolateral thoracotomy. At 5‐year follow‐up, no operative complications or disease recurrence were noted. Adenoid cystic carcinoma (ACC) of the lung is a very rare malignant tumour and is reported to account for less than 0.04%–0.2% of lung tumours.A 69‐year‐old female non‐smoker was referred to our institute with severe chest pain, orthopnea, and a 1‐month history of progressively worsening difficulty in breathing. Chest x‐ray showed complete atelectasis of the left lung and severe deviation of the mediastinum to the left Figure . FlexiblLeft posterolateral thoracotomy was performed through the fourth intercostal space, followed by sleeve resection of the LMB with primary end‐to‐end anastomosis. The length of the resected bronchus was 3 cm. After division of Bottalo's ligament, the aortic arch was retracted upward and the left pulmonary artery was retracted downward with traction tape to obtain better exposure Figure . IntraopACCs are slow‐growing and known to run a progressive clinical course. They are prone to both late local recurrence and distant metastases.Atelectasis prevented definitive evaluation of the extent of the tumour at the distal side prior to debulking of the tumour. However, following observation of the distal extent of the tumour after the initial treatment, we considered that radical resection could be performed without sacrificing lung parenchyma.The cornerstone of treatment of ACCs is complete surgical resection because unsatisfactory results have been reported for alternative treatments such as chemotherapy and radiotherapy.Debulking of tumour under rigid bronchoscopy is a rapid, effective, and safe method of relieving and recanalizing central airway obstruction.In conclusion, emergent rigid bronchoscopic tumour debulking is a key step in the treatment of patients with malignant airway obstruction as it enables diagnostic confirmation and staging when considering surgery, and also provides significant palliative relief even in the case of unresectable lesions.Makoto Takahama drafted manuscript and have read and approved the final version of the manuscript.None declared.This case report was approved by the Osaka City General Hospital Institutional Review Board and the patient provided written informed consent for the use of these data.Written informed consent obtained from the patient for the publication of this manuscript and associated images.


It builds upon many important relevant observations pertinent to brain aging, originating from Professor Love’s group, over several decades. The potential role(s) of amyloid-β—since its discovery by Glenner and Wong in 19842—in the pathogenesis of dementia is not without controversy.3 Nevertheless, the accumulation and presence of phospho-tau, amyloid-β and neuritic plaques are three reliable histologic markers that support the autopsy diagnosis of Alzheimer’s disease.4 However, removing amyloid-β from the brain does not consistently lead to significant improvement of cognitive decline,5 the reasons for which may be extremely complex and multifactorial—including the likelihood that neurodegeneration is well under way prior to amyloid-β deposition within the brain. This study examines how blood pressure may mediate some aspects of its deposition.An important and informative study from the Bristol group6 Although elements of Alzheimer’s disease neuropathologic change can be produced  in animal models, the constellation of neurocognitive impairment and histopathologic abnormalities (which are believed to contribute to said neurologic disability) occur only in the human brain and result in the synaptic loss characteristic of this form of dementia. Studies based upon autopsies are limited by the fact that the brain specimen can be examined at only one point in time—though in rare instances an opportunity has presented itself to look at autopsy brains when a biopsy has previously been done on the deceased subject.7 The brain biopsies done on a small number of the subjects in the Di Patre et al. paper were studied by electron microscopy, yielding interesting observations on the microvasculature though, by definition, the ‘n’ of samples examined was small.8 A morphometric analysis of these same brain biopsies showed evidence of compromise and ‘leakiness’ of the blood–brain barrier (BBB),9 which this study seems to support. A more recent quantitative immunohistochemical study10 has shown BBB abnormalities in Alzheimer’s disease subjects with varying degrees of cerebral amyloid angiopathy (CAA), especially CAA type 1 in which both capillaries and larger vessels are involved.The investigation, which uses human autopsy specimens as a starting point, provides a powerful reminder that Alzheimer’s disease is a distinctly human disease—from both clinical and neuropathologic perspectives.12 It is somewhat surprising that no mention is made of the presence or frequency of brain microbleeds—or any evidence of haemorrhage whatsoever—among the specimens examined . The ‘infarcts/ischemic lesions’ described  were probably all (or predominantly) lacunar or microinfarcts rather than larger cystic infarcts. Only half of each brain was examined by histopathology, and accepting the fact that ischaemic brain lesions may be asymmetrical between the cerebral hemispheres , this may have impacted on interpretation of the data in this relatively small group within the larger study.The present investigation was based upon both immunohistochemical and biochemical  examination of brain samples from subjects with different types or ‘categories’ of dementia, based upon both antemortem clinical examination and neuropathologic study of necropsy brain tissue from affected subjects. Indirect measures suggestive of antemortem brain hypoxia and ischaemia and BBB dysfunction were assessed. Details of the race/ethnicity of the patients whose brains were examined are not provided and might have been of interest, given that the UK represents a culturally and ethnically diverse society. Although it is not specifically indicated in the ‘Materials and Methods’, one assumes that a component of Lewy body disease was excluded from all cases by alpha-synuclein immunohistochemistry on selected tissue blocks. As the authors indicate, their smallest study group comprised those with vascular dementia, and relatively little ‘granularity’ is provided on the neuropathologic findings in those subjects; morphologic substrates of vascular dementia are known to be extremely heterogeneous.1 the blood pressure measurements may have been as few as four over several years, at least in the Alzheimer’s disease and vascular dementia patient groups. Because the study specimens were obtained from a ‘brain bank’ resource, there is no indication that complete autopsies were frequently, or ever, performed on the subjects, so data on generally accepted classic autopsy evidence of hypertension  is not available to provide supporting evidence of longstanding high blood pressure. Seminal studies by Lammie et al.14 indeed suggest that ‘hypertensive microvascular small vessel disease’ may, in many cases, be associated with factors other than high blood pressure in ∼30% of patients.As the authors acknowledge, a weakness of their study is the reliance (for clinicopathologic correlations) on accurate antemortem blood pressure readings. In the time frame during which the subjects were examined clinically, blood pressure assessments probably evolved from manual to more accurate digital measurements. Per Table 1 in their article,This detailed clinicopathologic investigation represents an excellent step in trying to understand the complex interaction between blood pressure regulation and both normal and pathologic brain aging.


Josa (Anyphaenidae). Our micro‐computed tomography data of cryofixed mating pairs show that the primary locking occurs through elements of the copulatory organ itself and that the femoral apophysis does not contact the female genitalia, but hooks to a projection of the copulatory bulb, representing a newly documented self‐bracing mechanism for entelegyne spiders. Additionally, we show that the femoral self‐bracing apophysis is rather uniform within the genus Josa. This is in contrast to the male genital structures that interact with the female, indicating that the male genital structures of Josa are subject to different selective regimes.Spiders evolved a distinctive sperm transfer system, with the male copulatory organs located on the tarsus of the pedipalps. In entelegyne spiders, these organs are usually very complex and consist of various sclerites that not only allow the transfer of the sperm themselves but also provide a mechanical interlock between the male and female genitalia. This interlocking can also involve elements that are not part of the copulatory organ such as the retrolateral tibial apophysis (RTA)—a characteristic of the most diverse group of spiders (RTA clade). The RTA is frequently used for primary locking i.e., the first mechanical engagement between male and female genitalia. Despite its functional importance, some diverse spider lineages have lost the RTA, but evolved an apophysis on the femur instead. It can be hypothesized that this femoral apophysis is a functional surrogate of the RTA during primary locking or possibly serves another function, such as self‐bracing, which involves mechanical interaction between male genital structures themselves to stabilize the inserted pedipalp. We tested these hypotheses using ghost spiders of the genus  The genitalia of spiders are known for their complex interactions during mating. In addition to the elements of the copulatory organs themselves, other structures may be involved in the copulatory process. Here, we reveal the function of a conspicuous femoral apophysis that demonstrates a new self‐bracing mechanism for entelegyne spiders. Beyond this fundamental function, the strong selective pressures on copulatory structures, particularly sexual selection, have led to an enormous diversity of forms and functions   using micro‐computed tomography (micro‐CT) of cryofixed mating pairs, and provide a detailed account of female and male genitalia using optical and scanning electron microscopy.Numerous representatives of Amaurobiodinae (Anyphaenidae) have also undergone losses or reductions of the RTA  were collected in November 2021 in Calilegua National Park, Jujuy, Argentina. After collection, the juvenile specimens were taken to the Museo Argentino de Ciencias Naturales (MACN) and reared to maturity. During this period the spiders were kept in plastic Petri dishes under controlled conditions  and fed twice a week with fruit flies (Drosophila melanogaster) or houseflies (Musca domestica) depending on their size.Juvenile specimens of 2.2For the cryofixation of mating pairs, a virgin adult female was placed and maintained individually in a plastic tube of 4 cm long and 1 cm in diameter. The base of the tube was previously sectioned, and a cotton plug was placed instead. This was done to allow flowing of liquid nitrogen through the tube, as any accumulation of liquid nitrogen during cryofixation can lead to the destruction of the spiders (liquid nitrogen boils violently once poured into the tube). After an acclimatization period of 30 min, a virgin adult male was introduced into the tube. If the spiders engaged in copulation, the tube was carefully placed vertically into a holder and the lid was removed and replaced by a funnel. A small amount of liquid nitrogen (−195.8°C) was then poured into the funnel at the moment a pedipalp insertion occurred. If copulation did not occur within an hour, the pair was recovered from the tube. Successive trials were made after washing the tube with 96% ethanol. After cryofixation, the pair was transferred immediately to cold 80% ethanol (−18°C) and stored at −18°C for 3 weeks. After this period, the spiders were dehydrated in a graded series of ethanol (96%–100%), exchanging the alcohol for a higher grade every one week . For morphological description, the female and male genitalia of Josa sp. were dissected and visualized using scanning electron microscopy (SEM). The SEM samples were dehydrated with a graded series of ethanol , then critical point dried and sputter‐coated with gold–palladium. Images were taken in high vacuum in a FEI XL30 TMP (Thermo Fisher Scientific Inc.). The voucher numbers of the cryofixed specimens used for these analyses are included in the corresponding figure legends.The cryofixed mating pairs were examined with X‐ray microscopy. For this, the already dehydrated pairs were stained in a 1% iodine solution for 12 h and then washed in 100% ethanol  shows relative uniformity in the femoral apophysis and high variability in the shapes of the embolus, median apophysis, paramedian apophysis and conductor   have a basal femoral protuberance that comes into contact with the copulatory bulb in artificially expanded pedipalps , and the denticles probably increase the friction between the femoral apophysis and the receiving projection. Thus, it can be hypothesized that hard genital structures with denticles, which are widespread in taxonomic literature  of many Thomisidae braces against the tegulum during the expansion of the copulatory bulb , a similar VTA interacts with the conductor , which also have two self‐bracing mechanisms , and not on the femoral apophysis, a structure that is used for the structural stability of the pedipalp and is relatively uniform, compared with the remarkable variability of the genital elements that contact the female. It has been shown that sexual traits have higher rates of change than ecological or somatic traits ; formal analysis (lead); investigation (lead); methodology ; writing – original draft (lead); writing – review and editing . Luis N. Piacentini: Conceptualization (supporting); formal analysis (supporting); investigation (supporting); supervision ; writing – original draft (supporting); writing – review and editing . Shou‐Wang Lin: Formal analysis (supporting); investigation ; methodology ; visualization ; writing – review and editing (supporting). Leonel A. Martínez: Formal analysis (supporting); investigation (supporting); writing – review and editing (supporting). Martin J. Ramírez: Conceptualization (lead); project administration ; resources ; supervision ; writing – original draft ; writing – review and editing . Peter Michalik: Conceptualization ; methodology ; project administration ; resources (lead); software (lead); supervision ; writing – original draft ; writing – review and editing .The authors declare no conflict of interest.Figure S1Click here for additional data file.Figure S2Click here for additional data file.Appendix S1Click here for additional data file.


A 79‐year‐old woman with a history of invasive lobular breast cancer presented with a lesion that was endoscopically and histopathologically consistent with poorly differentiated early gastric adenocarcinoma. Endoscopic submucosal dissection was performed, and histopathological examination using additional immunohistochemistry determined that the lesion was metastatic breast cancer. Even if a lesion suspicious of gastric cancer is found on endoscopy in a patient with a history of breast cancer, the possibility of metastasis should be considered and clinicians should inform the pathologists of the possibility. A 79‐year‐old woman with a history of invasive lobular breast cancer presented with a lesion that was endoscopically and histopathologically consistent with poorly differentiated early gastric adenocarcinoma. Endoscopic submucosal dissection was performed, and histopathological examination using additional immunohistochemistry determined that the lesion was metastatic breast cancer. Even if a lesion suspicious of gastric cancer is found on endoscopy in a patient with a history of breast cancer, the possibility of metastasis should be considered and clinicians should inform the pathologists of the possibility. The most common sites of breast cancer metastasis are the skeleton, lungs, and liver, and the incidence of metastasis to the stomach has been estimated at 2%–18%.A 79‐year‐old woman presented with epigastric discomfort during a follow‐up. She had previously undergone partial mastectomy for left invasive lobular breast cancer , followed by a 5‐year adjuvant hormonal therapy with toremifene. Subsequently, she underwent five surgeries for local recurrences . Esophagogastroduodenoscopy revealed a 7‐mm reddish depressed solitary lesion in the greater curvature of the upper gastric body of the stomach Fig. . MagnifyOur endoscopic diagnosis of early gastric cancer was based on a magnifying endoscopy simple diagnostic algorithm for early gastric cancer (MESDA‐G).In this case, both endoscopic and histopathological findings of the lesion closely resembled poorly differentiated early gastric adenocarcinoma. Since it is difficult to distinguish between primary gastric cancer and gastric metastasis of breast cancer using hematoxylin–eosin staining alone, detailed immunohistochemistry is essential for diagnosis.Informed consent was obtained from the patient to publish these images.Supplementary Figure 1.  Poorly differentiated and signet ring cell carcinoma infiltrated the submucosa with lymphovascular invasion (hematoxylin–eosin stain). (d) The tumor cells were positive for GATA binding protein 3. (e) The tumor cells were positive for Gross Cystic Disease Fluid Protein 15.Click here for additional data file.


Dipodomys spectabilis) in the southwestern United States. We found evidence of two decoupled processes that may be driving population dynamics in opposing directions over distinct time frames. Specifically, increasing mean surface temperature corresponded to increased individual fitness, where fitness is defined as the number of offspring produced by a single individual. This result contrasts with our findings for population size, where increasing surface temperature led to decreased numbers of active mounds. These relationships between surface temperature and (i) individual fitness and (ii) population size would not have been identified in the absence of remotely sensed data, indicating that such information can be used to test existing hypotheses and generate new ecological predictions regarding fitness at multiple spatial scales and degrees of sampling effort. To our knowledge, this study is the first to directly link remotely sensed environmental data to individual fitness in a nearly exhaustively sampled population, opening a new avenue for incorporating remote sensing data into eco‐evolutionary studies.The increasing availability of satellite imagery has supported a rapid expansion in forward‐looking studies seeking to track and predict how climate change will influence wild population dynamics. However, these data can also be used in retrospect to provide additional context for historical data in the absence of contemporaneous environmental measurements. We used 167 Landsat‐5 Thematic Mapper (TM) images spanning 13 years to identify environmental drivers of fitness and population size in a well‐characterized population of banner‐tailed kangaroo rats ( Dipodomys spectabilis) population. Specifically, we were able to identify apparently decoupled effects of surface temperature on individual fitness and population size. To our knowledge, this study is the first to directly link remotely sensed environmental data to individual fitness measures, opening a new avenue for incorporating remote sensing data into eco‐evolutionary studies.We leveraged publicly available remote sensing data to provide new context for detailed historic demographic data from a banner‐tailed kangaroo rat ( However, developing this understanding can require information about ecosystems and land cover at scales and sampling frequencies that are impractical to collect from field efforts alone. Beginning with the launch of the Landsat 1 satellite in July 1972, the National Aeronautics and Space Administration/U.S. Geological Survey Landsat Program has consistently provided medium spatial resolution satellite imagery of Earth's surface, with free and open access since 2008  has been the subject of myriad studies, including investigations of mate choice patterns, genetic adaptation to arid environments, philopatry and dispersal, and many other eco‐evolutionary dynamics  images to obtain surface temperature data and three other descriptive indices via the Tasseled Cap Transformation  , such as apparent survival  Figure . Annual Banner‐tailed kangaroo rats rely on these plant communities for food, caching seeds in large mounds (1–3 m in diameter) constructed for food storage, reproduction and protection from predators and harsh environmental conditions Edelman, . Each mo2.2Our banner‐tailed kangaroo rat demographic data was collected from a population monitored by Waser et al. from 1990 through 2007  and additive offset (−0.2) specified in the Landsat 4–7 Collection 2 Level 2 Science Product Guide  covering the study site . Using the known coordinates for 188 mounds, we overlaid the meter‐based locations for all mounds onto the raster and manually assigned the mounds lacking GPS coordinates to cells in the raster. In total, we assigned 214 mounds to raster cells Figure .We also obtained precipitation totals and minimum, mean, and maximum temperatures from the Parameter‐elevation Regressions on Independent Slopes Model (PRISM) at 4‐km resolution  and, for females producing at least one offspring, how many of those offspring survived to age one . We used the capture data to assign each female to a primary mound location within each year. For each female, we summarized remote sensing values by considering the cell containing her mound location and the eight adjacent cells. Given that each cell is 30 m across, the maximum distance from the center of an individual's home range in the raster to the edge is 63 m. Most banner‐tailed kangaroo rats disperse <50 m over their lifetime , meaning that their raster‐defined home range likely contains both their natal and reproductive environments . We compared the final Poisson and negative binomial regressions using a likelihood ratio test, checked the dispersion parameter for each model, and calculated generalized variance inflation factor (GVIF) values for final models with >1 predictor variable retained using the gvif function in the glmtoolbox R package to quantify the contribution of collinearity on uncertainty in each model  as a random variable for both number of offspring and number of offspring surviving. These models were built using the 2.4.2We used the capture data to determine the number of adult females alive in each year as well as the total number of offspring produced. From these data, we calculated the average number of offspring produced per female and average number of offspring surviving to age 1 per female. To define the set of cells to be analyzed within each year, we began by identifying active mounds  within each year. We defined the total set of active cells as all cells containing an active mound plus the eight cells adjacent to each active cell. For each year, we calculated landscape‐level means for each remote sensing index and the PRISM variables as we did for the individual data  and again applied a 6‐month lag Figure .p < .05). Because neither model met the homoskedasticity assumption, we permuted the y‐values and calculated model coefficients 1000 times per model to generate permuted p‐values.We conducted a series of linear regressions to identify relationships between macrohabitat conditions and population‐level fitness by testing each combination of a single environmental predictor variable and response variable separately. Two summer rainy season variables (wetness and brightness) were found to be significant predictors for average number of offspring surviving to age 1  and again permuted the y‐values and calculated model coefficients 1000 times to generate p‐values.Again using capture data, we calculated the number of mounds with resident individuals within each year. We assumed that if a mound was occupied, an experienced surveyor of the site could reasonably identify occupied mounds as active based on signs left by residents . We applied the same predictor variables and statistical approaches as for the population fitness data, using annual and summer and winter rainy season means from July in year t − 1 on population size in year t, we repeated our statistical approach using (i) absolute change in population size from year t − 1 to year t and (ii) proportional change in population size from year t − 1 to year t as response variables .To confirm that number of active mounds is a reasonable proxy for population size, we constructed linear models to relate number of active mounds to number of adult females and census population size using the capture data. We also tested for relationships between both number of active mounds and number of adult females and fitness rates  to determine whether fitness rates could be the result of density‐dependent population processes. Finally, to account for the effect of population size in year 3r = .89; Figure We analyzed 167 Landsat 5 TM scenes spanning 13 years (July 1993–June 2005), calculating surface temperature (°C) and scaled and centered Tasseled Cap greenness, wetness, and brightness indices for each. For surface temperature, patterns matched expectations with maximum temperatures observed during June/July and minima during December/January and with little variation across cells analyzed at each time point as indicated by small standard deviations around mean values Figure . For TasFor individual fitness, we found that mean annual brightness and surface temperature for the area immediately surrounding a female's home location had positive effects on number of offspring produced Table . With reIncluding female ID as a random effect did not affect the results for number of offspring with respect to the identity or significance of retained predictor variables when compared to the negative binomial models that only included fixed effects , indicating that these two indices likely capture distinct soil characteristics, but we cannot explicitly define those characteristics without ground‐truthed data.For two variables—Tasseled Cap brightness and wetness—our results matched our expectations that were based on previously published relationships between kangaroo rat demographic measures and environmental conditions. In each individual‐level model where brightness was retained as a significant predictor and at the population level, brightness positively affected fitness. This is consistent with previous studies that explicitly tested the relationship between habitat openness  and kangaroo rat abundance  will require pairing with ground‐truthed data from the site to confirm, our results and conservative interpretations were consistent with previous findings from our focal population and other systems. The contrasting results for surface temperature across sampling scales demonstrate that, while conducting relatively lower effort mound surveys likely captures demographic trends well enough to identify abiotic determinants of population size, the additional resolution provided by linking parents and offspring via genetic sampling allows for the detection of counterintuitive relationships that could influence long‐term population stability.Avril M. Harder: Conceptualization ; data curation (lead); formal analysis (lead); methodology (lead); visualization (lead); writing – original draft (lead); writing – review and editing . Mekala Sundaram: Methodology ; writing – review and editing . Lana L. Narine: Methodology ; writing – review and editing . Janna R. Willoughby: Conceptualization ; writing – review and editing .


To the Editor,We would like to share the experiences we have recently had while conducting online qualitative studies. We believe people have contacted members of our research teams, offering to participate in interviews for a health study, who were not the people they initially purported to be. We reimburse participants to cover time and expenses for their involvement in research, with varying views on the complex issue of incentivization.(1)Suspect participants sometimes cited recruitment sites that were not used by the study(2)More than one suspect participant gave the same social media platform as their source for learning about the study, despite the use of multiple platforms for recruitment in a study(3)Participants responded quickly, sometimes within minutes, of recruitment advertisements being posted on social media, and some of these posted multiple follow‐up emails in quick succession(4)Emails from multiple suspect participants had similar configurations and frequently came from the same email platform(5)Blank subject lines in emails expressing interest in the study (as well as emails that were only a sentence or two long) were common, with some potential participants copying text from recruitment ads verbatim(6)In some cases, a single participant was suspected of slightly changing their story and sociodemographics to complete multiple interviews, which could be difficult to detect quickly, especially where more than one researcher was conducting interviews (7)Researchers noted matches between participants' voices, stories and limitations in accounts of the health condition under investigation, as well as similar sociodemographic profiles(8)Concerns about timing and methods of payment were a priority for the participant(9)There were requests for payment via PayPal or in the form of vouchers, and a reticence to share bank details for bankers' automated clearing system (BACS) payments, citing concerns around confidentiality(10)Researcher requests for details of participants' professional backgrounds resulted in participants verbatim copying a profession from the examples listed in the recruitment advertisement(11)‘Health professional’ participants declined to give their work  email for verification purposes, claiming concerns around anonymity (12)Requests for an institutional email address to authenticate participants' profession before payment resulted in no further communication from those participants(13)Suspect participants who were interviewed via video links chose to keep their cameras off, citing a range of reasons, for example, shyness(14)Preference was expressed for online interviews  over telephone interviews, and there was a reticence to disclose a telephone contact number(15)Interview questions elicited vague answers, and participants seemed distracted or otherwise occupied during interviewsNevertheless, three recent online qualitative studies in which we recruited healthcare professionals, and a further two online studies  aroused suspicion amongst our research teams regarding the authenticity of some potential participants. It took research teams varying amounts of time to piece together evidence of the inauthenticity in participants/interviews, especially in cases where participants gave apparently plausible accounts and/or were difficult to understand. On reflection, the following indicators suggested to us that these may have been ‘imposter’ participants:This phenomenon is not something we, as a group of researchers, had come across pre‐COVID. We wondered if it might be related to the accelerated move to online research methods necessitated by the pandemic,Importantly, this is not a new problem; Hydock(1)Considering closing recruitment from the social media source singled out by suspect participants(2)Participants sending subsequent suspect requests to participate politely advised that recruitment had closed for their particular sociodemographic(3)Checking email configurations and formats of all new participation requests for patterns(4)Being up‐to‐date with information security as well as means for identifying phishing (and accessing training available) in researchers' organizations(5)Checking names on professional registers to authenticate professional participants(6)Considering BACS payments for reimbursement, as opposed to vouchers(7)Where participants give similar or odd stories, researchers review these particular accounts(8)Where multiple study team members are carrying out qualitative interviews, it is helpful for interviewers to meet and regularly review accounts in the data, thus ensuring any potential issue is identified as quickly as possible(9)Removal of the suspect interview data from the studyHow can we better mitigate against fraud? For studies involving NHS staff, researchers took the approach of asking potential participants to verify their identities via NHS email, while allowing conversations about the study to happen via personal emails. They also concluded that it is better to prioritize online video platforms, with the camera switched on, than use the telephone for interviews where possible, whilst being aware that telephone options are still important for accessibility for many participants. Others among us asked that participants turn their video on at least for a preinterview chat, or at the start of the interview, to discourage imposter participants. Further steps taken by researchers to deal with potential imposters included:1.During recruitment, how could I verify that the participants meet the inclusion criteria? How confident can I be in this information?2.During data collection, was the participant hesitant or flustered when asked probing questions for additional detail?3.Did I document impressions of honesty in my reflexive journal?4.Did the participant's answers make sense, and were they detailed enough about the topic being researched?Lawlor et al.Jones et al.In conclusion, recruiting participants online and conducting virtual interviews are likely to become increasingly popular practices for qualitative researchers. All qualitative researchers using online methods should consider and prepare a protocol for dealing with potential imposter participants in their qualitative studies. And at a time when even recent internet‐mediated research ethics guidelines are yet to get to grips with the problem,Should we consider any other factors? For example, if you become aware that a participant is being dishonest during an interview, how do you handle this in real time? What kinds of safety risks might a researcher be opening themselves up to from an imposter participant? We would welcome discussion amongst readers of HEX on the issue of imposter participants in qualitative research.Damien Ridge: Co‐ordination of letter drafting; conceptualization; contribution of content; review and editing; and approval of the final manuscript. Laurna Bullock: Conceptualization; review and editing; and approval of the final manuscript. Hilary Causer and Samantha Hider: Conceptualization; contribution of content; review and editing; and approval of the final manuscript.   Tom Kingstone: Conceptualization; contribution of content; supported drafting of the letter; review and editing; and approval of the final manuscript. Lauren Gray: Review and editing; and approval of the final manuscript. Ruth Riley, Tamsin Fisher and Victoria Silverwood: Conceptualisation; review and approval of the final manuscript. Nina Smyth: Contribution of content; conceptualization; supported drafting of the letter; review and editing; and approval of the final manuscript. Johanna Spiers: Contribution of content; review and editing; copy editing and approval of the final manuscript.   Jane Southam: Review and approval of the final manuscript.Health Expectations.The authors of this letter work closely with Professor Carolyn Chew‐Graham, who is Editor in Chief of There are no ethical requirements for this letter/opinion piece.


Bacterial cellulose (BC) is a natural and renewable nanomaterial characterized by a unique three‐dimensional structure that endows it with excellent mechanical properties and high water‐holding capability. BC is a very pure, crystalline and biocompatible polymer. Moreover, BC can be modified to improve its innate features and to provide it with tailored properties or new functionalities which could be applicable in many areas. Due to these outstanding proprieties, BC is receiving a great deal of attention in both academic and industrial fields. Here, we highlight various recent studies and reviews that discuss the molecular aspects of BC biosynthesis and its regulation and summarize the most common commercial applications of BC in the biomedical and textile areas. There is great expectation that BC will be developed to its full potential, and become a modifiable material of choice depending on the demands of the different areas of use.Pandoravirus genus) that incorporate cellulose into their tegument , soil bacteria (Burkholderia and Pseudomonas), plant pathogens (Agrobacterium and Dickeya), plant symbionts (Rhizobium and Azotobacter), animal pathogens  and highly metabolically versatile soil bacteria  can be produced by any of the carbon sources, although with different energy balances  polymerization of glucose units and production of β‐1,4‐glucan chains, (ii) extracellular transport and (iii) crystallization of cellulose  compared to the wild‐type strain , high polymerization degree, high water content of up to 99% and moldability ; writing – original draft ; writing – review and editing . Daniel Pacheco‐Sánchez: Conceptualization ; writing – original draft ; writing – review and editing .The authors declare no conflict of interest.