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Recommendations Serum ferritin of <12 g/l in children aged < 5 years and <15 g/l in those aged > 5 years is indicative of iron deficiency (1B) Serum ferritin within the laboratory reference range cannot exclude iron deficiency in the context of raised inflammatory markers or a history of acute or chronic disease, so further investigation may be warranted (2B) Iron studies: serum iron, total iron binding capacity (TIBC) and transferrin saturation (TSAT... Serum iron Serum iron measures only the oxidised ferric form bound to transferrin and not the functional iron component of Hb. Recommendation Inspection of a peripheral blood film should be performed in cases of diagnostic uncertainty (2C) Serum ferritin Ferritin represents the main bulk of protein-bound tissue iron storage. Clin Chem. 1991; 37: 484 - 5. 28 Romslo I, Talstad I. Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects. Keywords: iron; anaemia; haemoglobin; ferritin; iron deficiency EN iron anaemia haemoglobin ferritin iron deficiency 523 529 7 01/28/22 20220201 NES 220201 Methodology This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at: https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf. [Extracted from the article]

Background: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web‐based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper‐based handwritten call log. Materials and Methods: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on‐call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e‐consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult. Results: The REDCap web‐based application includes discrete fields for patients' information, requesting physician contact, type of consult, action items for follow‐up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine‐related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001). Conclusion: E‐consult documentation entered into a web‐based application was a user‐friendly, secure clinical information access and effective handoff system as compared to a paper‐based handwritten call log. [ABSTRACT FROM AUTHOR]

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement was developed to provide guidance for inclusion of key methodological components in clinical trial protocols. However, these standards do not include guidance specific to pathology input in clinical trials. This systematic review aims to synthesise existing recommendations specific to pathology practice in clinical trials for implementation in trial protocol design. Articles were identified from database searches and deemed eligible for inclusion if they contained: (1) guidance and/or a checklist, which was (2) pathology‐related, with (3) content relevant to clinical trial protocols or could influence a clinical trial protocol design from a pathology perspective and (4) were published in 1996 or later. The quality of individual papers was assessed using the AGREE‐GRS (Appraisal of Guidelines for REsearch & Evaluation – Global Rating Scale) tool, and the confidence in cumulative evidence was evaluated using the GRADE‐CERQual (Grading of Recommendations Assessment, Development and Evaluation–Confidence in Evidence from Reviews of Qualitative research) approach. Extracted recommendations were synthesised using the best fit framework method, which includes thematic analysis followed by a meta‐aggregative approach to synthesis within the framework. Of the 10 184 records screened and 199 full‐text articles reviewed, only 40 guidance resources met the eligibility criteria for inclusion. Recommendations extracted from 22 guidance documents were generalisable enough for data synthesis. Seven recommendation statements were synthesised as follows: (1) multidisciplinary collaboration in trial design with early involvement of pathologists, particularly with respect to the use of biospecimens and associated biomarker/analytical assays and in the evaluation of pathology‐related parameters; (2) funding and training for personnel undertaking trial work; (3) selection of an accredited laboratory with suitable facilities to undertake scheduled work; (4) quality assurance of pathology‐related parameters; (5) transparent reporting of pathology‐related parameters; (6) policies regarding informatics and tracking biospecimens across trial sites; and (7) informed consent for specimen collection and retention for future research. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), known to be the causative agent of COVID‐19, has led to a worldwide pandemic. At presentation, individual clinical laboratory blood values, such as lymphocyte counts or C‐reactive protein (CRP) levels, may be abnormal and associated with disease severity. However, combinatorial interpretation of these laboratory blood values, in the context of COVID‐19, remains a challenge. Methods: To assess the significance of multiple laboratory blood values in patients with SARS‐CoV‐2 and develop a COVID‐19 predictive equation, we conducted a literature search using PubMed to seek articles that included defined laboratory data points along with clinical disease progression. We identified 9846 papers, selecting primary studies with at least 20 patients for univariate analysis to identify clinical variables predicting nonsevere and severe COVID‐19 cases. Multiple regression analysis was performed on a training set of patient studies to generate severity predictor equations, and subsequently tested on a validation cohort of 151 patients who had a median duration of observation of 14 days. Results: Two COVID‐19 predictive equations were generated: one using four variables (CRP, D‐dimer levels, lymphocyte count, and neutrophil count), and another using three variables (CRP, lymphocyte count, and neutrophil count). In adult and pediatric populations, the predictive equations exhibited high specificity, sensitivity, positive predictive values, and negative predictive values. Conclusion: Using the generated equations, the outcomes of COVID‐19 patients can be predicted using commonly obtained clinical laboratory data. These predictive equations may inform future studies evaluating the long‐term follow‐up of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Computational phenotyping allows for unsupervised discovery of subgroups of patients as well as corresponding co‐occurring medical conditions from electronic health records (EHR). Typically, EHR data contains demographic information, diagnoses and laboratory results. Discovering (novel) phenotypes has the potential to be of prognostic and therapeutic value. Providing medical practitioners with transparent and interpretable results is an important requirement and an essential part for advancing precision medicine. Low‐rank data approximation methods such as matrix (e.g., nonnegative matrix factorization) and tensor decompositions (e.g., CANDECOMP/PARAFAC) have demonstrated that they can provide such transparent and interpretable insights. Recent developments have adapted low‐rank data approximation methods by incorporating different constraints and regularizations that facilitate interpretability further. In addition, they offer solutions for common challenges within EHR data such as high dimensionality, data sparsity and incompleteness. Especially extracting temporal phenotypes from longitudinal EHR has received much attention in recent years. In this paper, we provide a comprehensive review of low‐rank approximation‐based approaches for computational phenotyping. The existing literature is categorized into temporal versus static phenotyping approaches based on matrix versus tensor decompositions. Furthermore, we outline different approaches for the validation of phenotypes, that is, the assessment of clinical significance. This article is categorized under:Algorithmic Development > Structure DiscoveryFundamental Concepts of Data and Knowledge > Explainable AITechnologies > Machine Learning [ABSTRACT FROM AUTHOR]

Reference regions are important in laboratory medicine to interpret the test results of patients, and usually given by tolerance regions. Tolerance regions of p (≥2)$$ p\;\left(\ge 2\right) $$ dimensions are highly desirable when the test results contains p$$ p $$ outcome measures. Nonparametric hyperrectangular tolerance regions are attractive in real problems due to their robustness with respect to the underlying distribution of the measurements and ease of intepretation, and methods to construct them have been recently provided by Young and Mathew [Stat Methods Med Res. 2020;29:3569‐3585]. However, their validity is supported by a simulation study only. In this paper, nonparametric hyperrectangular tolerance regions are constructed by using Tukey's [Ann Math Stat. 1947;18:529‐539; Ann Math Stat. 1948;19:30‐39] elegant results of equivalence blocks. The validity of these new tolerance regions is proven mathematically in [Ann Math Stat. 1947;18:529‐539; Ann Math Stat. 1948;19:30‐39] under the only assumption that the underlying distribution of the measurements is continuous. The methodology is applied to analyze the kidney function problem considered in Young and Mathew [Stat Methods Med Res. 2020;29:3569‐3585]. [ABSTRACT FROM AUTHOR]

This paper proposes an analytical solution for 2D (two‐dimensional) consolidation of unsaturated soil with impeded drainage boundaries by considering the combined effects of self‐weight stress of soil and time‐dependent loading. The governing equation of the 2D consolidation model was first formulated, followed by an analytical solution employing the methods of the Laplace transform technique and separation of variables. The solution is then degraded to validate the correctness against two classical lab tests and existing solutions. Subsequently, the proposed solution is further verified against finite element calculations. The results indicate that the self‐weight stress of soil acts as an additional load applied to the unsaturated soil, the larger the self‐weight stress, the greater the value of initial EPPs (excess pore pressures). Meanwhile, it can be easily found that the larger the value of self‐weight stress, the larger the consolidation settlement. Without accounting for the effect of self‐weight stress, the settlement of the soil will certainly be underestimated and the dissipation characteristics of EPPs will not be accurately captured. It can be also found that the ratio of ka/kw also significantly influenced the consolidation behavior. [ABSTRACT FROM AUTHOR]

This article draws on 2 years' worth of ethnographic observation of team meetings to explore decision‐making in an NHS clinical genomics service. The focus of discussions was on ambiguous genomic results known as VUS or Variants of Uncertain Significance, which may be pathogenic but which also may turn out to be benign. In examining decision‐making around such results, we note how, in contrast to much policy and promotional material in this area, clinicians in these meetings (clinical geneticists and genetic counsellors) place great emphasis on parental phenotypes and whether the parents of a patient share the symptoms and signs of the suspected condition. This information is then combined with the result of genomic tests to decide whether the variant a patient has is responsible for their condition. This article explores the way in which clinicians attempt to flexibly enrol parents into genomic explanations through informal diagnosis of their possible phenotypes and the way in which actually meeting parents allows some clinicians to trump explanations based on documentary or photographic data. The paper sheds light on the way that earlier scholarly understandings of such decisions (around, say dysmorphology) remain relevant and explores claims that laboratory tests overrule clinical decision‐making. [ABSTRACT FROM AUTHOR]

Introduction: An evidence synthesis approach compiling biological/laboratory data is effective in advancing health‐related knowledge. However, this approach is still underused in the oral health field. Methods: This commentary discusses the opportunities and challenges of systematic and scoping reviews of laboratory data in dentistry. Special focus is on the potential of these reviews to elucidate etiological and treatment concepts of oral diseases, such as periodontitis and peri‐implantitis. Results: The following difficulties associated with such studies are discussed: (i) selection of ideal study design, (ii) assessment of "risk of bias" and definition of "certainty of evidence", (iii) evidence assembly and summary, and (iv) the paper review process. Discussion: Despite those challenges, high‐quality reviews integrating laboratory data may generate relevant scientific information and help identify new avenues for future investigations. Experts in different oral health topics should build a process capable of helping researchers assemble and interpret these types of data. [ABSTRACT FROM AUTHOR]

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Human is the host of the Epstein‐Barr virus (EBV) especially in childhood and adolescence. Most of them are asymptomatic infection and self‐limiting. However, for those patients who suffer from immune dysfunction, EBV infection will be life‐threatening. Epstein‐Barr virus‐associated hemophagocytic lymphohistocytosis (EBV‐HLH) is one of the severe effects. The diagnosis and differential diagnosis of EBV‐HLH and other EBV infectious diseases are mentioned in this paper. The molecular biology mechanism and complications of EBV‐HLH are equally briefly presented. It also provides a practical method for the genetic diagnosis of such diseases and the differential diagnosis with other human immunodeficiency diseases for medical scientists in routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Salivary gland tumors are a diverse group of uncommon neoplasms that are rare in pediatric patients. The aim of this study was to evaluate the clinicopathological profile and survival outcomes of pediatric patients affected by salivary gland tumors. Materials and methods: An extensive search was carried out using the MEDLINE/PubMed, EMBASE, Scopus databases, and grey literature. The risk of bias was available in all papers included. Results: A total of 2,830 articles were initially retrieved with 54 remaining for data extraction, resulting in 2,937 cases. This comprised forty‐five case series' and nine cohort studies. These tumors were slightly more prevalent in females (57.4%). The patients' age ranged from 0.3 to 19 years old, with a mean age of 13.3 years. Parotid was the most affected site (81.9%), and 99.2% of cases clinically exhibited a swelling. Presence of pain/tenderness was reported in 13.5% of the cases, with an average duration of 12.6 months for the appearance of symptoms. Most of the reported cases were malignant tumors (75.4%), with mucoepidermoid carcinoma the most common tumor of all tumors (44.8%), followed by pleomorphic adenoma (24.1%). Surgery alone was the leading treatment choice in 74.9% cases, and the 5‐year overall survival rate of patients was 93.1%. Patients with symptoms (P =.001), local recurrence (P <.001), metastasis (P <.001), and those not undergoing surgery or surgery combined with radiotherapy (P <.001) showed lower survival rates. Conclusion: The pediatric patients present a high frequency of malignant salivary neoplasms and a high overall survival rate. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. Aims: To provide guidance for those who are investigating the pathogenesis of RA‐ILD with animal models. Materials and Methods: An analysis of papers from PubMed during 1978‐2020. Results: We outline the present status quo for animal models of RA‐ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. Discussion: There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA‐ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA‐ILD. Conclusion: These established animal models of the disease can significantly progress our understanding of the etiology of RA‐ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio‐markers, and can contribute to the development and implementation of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives: The main purpose of this paper is to measure the efficiency and ranking of medical diagnostic laboratories by applying a network data envelopment analysis (NDEA). Methods: In this study, each medical diagnostic laboratory is considered as a decision‐making unit (DMU), and an NDEA model is utilized to calculate the efficiency of each medical diagnostic laboratory. Therefore, we design a series of four‐stage system composed of three main laboratory processes (the pretest process, the test process, and the posttest process). We also consider sustainability criteria in order to cover social, economic, and environmental problems of health care organizations. Results: The results show that three of the 22 considered laboratories are efficient. Therefore, the NDEA approach can lead to performance scores and ultimately real ranking. Also, the average efficiency scores show that the decrease of the reception unit's efficiency results in a decrease of the efficiency of each laboratory. Therefore, the laboratories can increase the number of patients. Along with the intermediate values of the reception unit and the sampling unit, the efficiency of the reception unit increases, which results in an increase for the overall efficiency of each laboratory. Conclusion: The proposed model can appropriately help the administrators and managers to identify inefficient units in their laboratory and ultimately improve the laboratory performance. [ABSTRACT FROM AUTHOR]

Introduction: Hemolysate in plasma samples from patients may cause misleading results in coagulation assays. Even though modern coagulation instruments often are equipped with modules that can detect hemolysis, icterus, and lipemia (HIL), studies that report the influence of these interferences are still limited. The present paper focuses on the influence of hemolysis on 10 coagulation assays. Methods: Artificial hemolysis was created by freezing/thawing, and the hemolysates generated were added to pools of patient plasma. Pathological and normal levels were pooled separately. These spiked samples were analyzed on a STA R Max 2 instrument. The coagulation assays evaluated utilize clot, chromogenic, or immunoturbidimetric detection. Results: Four of the evaluated assays were not influenced by hemolysis: fibrinogen, von Willebrand factor antigen, activated partial thromboplastin time, and factor VIII. Interestingly, normal and slightly elevated prothrombin time (INR < 2.0) was insensitive to hemolysis, whereas samples with a high INR (≥2.0) exhibited falsely high readings. The assays for antithrombin and fibrin D‐dimer displayed an intermediate sensitivity to hemolysis. The most sensitive assay turned out to be anti‐Xa, followed by protein C and protein S. For the anti‐Xa assay, the results are decreased by 10% already at 0.5 g/L hemoglobin. Conclusion: The present study shows that hemolysis affects several of commonly used coagulation assays. Since the sensitivity for hemolysis is dependent on the brand of the assay as well as the instrument and principle of measurement, it is necessary to evaluate the influence of each specific combination. [ABSTRACT FROM AUTHOR]

Summary: This paper presents the design and real‐time verification of a high‐precision and low‐cost attitude determination and control system (ADCS) for CubeSat based on a micro‐electro‐mechanical (MEMS) gyroscope. The CubeSat new missions require accurate and sophisticated ADCS with attitude drift adjustment. Moreover, designing an effective ADCS for the CubeSat poses a difficult challenge. The satellite comprises of a two‐unit CubeSat, which denotes that the ADCS is designed with small size, tight mass, and energy limitations. The ADCS has been enhanced in the former few years from fairly small resolution of 10 to around 0.6 m. This attitude drift, if not properly compensated, will cause a slow attitude information loss as the error in attitude rises between the actual and estimated. To correct the attitude adrift, the proposed system utilizes a MEMS gyroscope sensor which offers a comparative attitude to the Kalman filter for estimated attitude update. Real‐time verification and validation for the ADCS are performed through Matlab/Simulink environment and lab testing to prove the efficacy of the proposed system. Simulation of the ADCS shows accurate results with error of no more than 1°. [ABSTRACT FROM AUTHOR]

Group testing is an indispensable tool for laboratories when testing high volumes of clinical specimens for infectious diseases. An important decision that needs to be made prior to implementation is determining what group sizes to use. In best practice, an objective function is chosen and then minimized to determine an optimal set of these group sizes, known as the optimal testing configuration (OTC). There are a few options for objective functions, and they differ based on how the expected number of tests, assay characteristics, and testing constraints are taken into account. These varied options have led to a recent controversy in the literature regarding which of two different objective functions is better. In our paper, we examine these objective functions over a number of realistic situations for infectious disease testing. We show that this controversy may be much ado about nothing because the OTCs and corresponding results (eg, number of tests and accuracy) are largely the same for standard testing algorithms in a wide variety of situations. [ABSTRACT FROM AUTHOR]

The International Collaboration on Cancer Reporting (ICCR) is a not‐for‐profit organisation sponsored by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists in association with the Canadian Partnership Against Cancer, the European Society of Pathology, the American Society of Clinical Pathology and the Faculty of Pathology, Royal College of Physicians of Ireland. Its goal is to produce standardised, internationally agreed‐upon, evidence‐based datasets for cancer pathology reporting throughout the world. This paper describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of carcinoma of the urethra in urethrectomy specimens. The dataset is composed of 'required' (mandatory) and 'recommended' (non‐mandatory) elements, which are based on a review of the most recent evidence and supported by explanatory commentary. Fourteen required elements and eight recommended elements were agreed by the international dataset authoring committee to represent the essential/required (core) and recommended (non‐core) information for the reporting of carcinoma of the urethra in urethrectomy specimens. Use of an internationally agreed, structured pathology dataset for reporting carcinoma of the urethra (in urethrectomy specimens) will provide the necessary information for optimal patient management, will facilitate consistent data collection and will provide valuable data for research and international benchmarking. The dataset will be valuable for those countries and institutions that are not in a position to develop their own datasets. [ABSTRACT FROM AUTHOR]

Purpose/research question: Pitting or new bone formation on or around tendon insertions, marginal osteophytes, eburnation, cystic changes, and altered contours have been utilized by some palaeopathologists for recognition of the rotator cuff condition, with the purpose of this paper to evaluate the reliability for diagnosis (sensitivity and specificity) of these criteria as documented in the clinical literature. Materials and methods: The spectrum of medical literature is examined without time limitation, utilizing the phrase "rotator cuff" to assess criteria utilized for diagnosis of a rotator cuff conditions, the reliability of those criteria, and the relationship to symptoms and limitations/disability. Results: None of the skeletal features previously referred to by palaeopathologists have reliable indicators for recognition and may simply be age‐related phenomena. New methodology is described, offering the opportunity for confident diagnosis. Conclusions: There have been no validated evidence‐based criteria applicable for recognizing rotator cuff conditions in skeletons, in the absence of soft tissue structures. Greater tuberosity osteopenia has been noted but not yet evaluated for specificity. Rotator cuff conditions may actually be unrelated to lifestyle but may simply represent the accumulation/culmination of lifetime stresses (aging). The ratio of acromial lateral extension and height provides greater opportunity for confident diagnosis. Given the disconnection between presence or extent of pathology and clinical symptoms and limitations/disability, identification of any of the components utilized in previous consideration of rotator cuff disease diagnosis does not permit extrapolation to confidently hypothesize lifestyle or occupation. Contribution to knowledge/originality/value: Documents a methodology for confident diagnosis of rotator cuff disease and the challenge of confident attribution of skeletal conditions and clinical/lifestyle implications Limitations of this study: Evidence, rather than conjecture/consensus‐based. Suggestions for further research: Population survey utilizing ratio of acromial length extension and height. [ABSTRACT FROM AUTHOR]

Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self‐reported medical history of individuals diagnosed with sarcopenia through a self‐administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi‐deficiency, Yang‐deficiency, Yin‐deficiency, Blood‐stagnation, and Qi‐stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi‐deficiency (in males, OR = 1.126), Yang‐deficiency (OR = 1.062), Phlegm‐dampness (in males, OR = 0.833), and Blood‐stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang‐deficiency and blood‐stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross‐sectional study of older people with higher original Qi‐deficiency, Yin deficiency, Yang‐deficiency, Blood‐stagnation, and Qi‐stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males. [ABSTRACT FROM AUTHOR]

Summary: The paper presents a micromechanical approach to describe the failure of low‐permeability brittle rocks as a multiscale fracturing process based on a poroelastic microcrack‐damage model. Failure is formulated deep down at the fine pore scale as a material degradation phenomenon driven by microcrack growth that also impacts upon hydromechanical properties. A set of damage tensors describes the effect of dual‐scale porosities (nanopores and microcracks) on both the hydraulic and poroelastic rock properties. Essentially, the multiscale model reconstructs the coupling effect of hydromechanical forces at the continuum level from the ground up through the upscaling of multiphase interactions at the fundamental structural level of the material. As a result, many macroscopic characteristics emerge naturally such as friction angle, fracture properties, and most importantly, Biot's coefficient taking on a tensorial form that is generally anisotropic. The model is validated within the framework of finite elements to illustrate various baseline constitutive features such as the effect of microcrack growth on the nonlinear stress‐strain response and the induced anisotropy in the context of lab experimental tests and boundary value problems. Heterogeneities of the rock samples were incorporated by choosing material properties to be stochastic following Weibull and lognormal distributions. Numerical results appropriately replicated typical experimental observations where fracture localization and propagation are shown to be a multiscale phenomenon emerging from microcrack growth and coalescence at the microscale, with concomitant enhancement in fluid conductivity. [ABSTRACT FROM AUTHOR]

Despite the growth of research in universities on point-of-care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field--the processes intended to evaluate operation and performance under realistic conditions--are more complicated than they might seem. Two case studies illustrate this process: the development of a paper-based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource-limited environments. [ABSTRACT FROM AUTHOR]

Background Communication failures between clinicians and dermatopathologists are prevalent. Our primary objective was to characterize the concerns and challenges of dermatopathologists posed by incomplete or inaccurate clinical information in the skin biopsy requisition form. Methods An explanatory sequential, mixed-methods study design comprised of a survey sent to 1103 members of the American Society of Dermatopathology ( ASDP), followed by two focus group sessions. Results A total of 54% (598/1103) of dermatopathologists completed the questionnaire. Most dermatopathologists (80%; 436/548) viewed their roles to be providers of histopathological diagnosis and a report that is clinically meaningful. Paper or electronic requisition forms were the most common communication method (85%; 458/541) and were associated with the highest rates of dissatisfaction in 36% (193/537) of respondents. Inadequacy of specimens emerged as an important factor influencing judgment of the quality of provided clinical information. 44.7% (261/584) of dermatopathologists spent 30 minutes or more on average every day searching for relevant clinical information to assist with their histopathologic interpretation. Conclusion ASDP dermatopathologists expressed significant dissatisfaction with the quality of clinical information in the requisition form and the time spent gathering information necessary for accurate, timely and clinically meaningful diagnosis. These findings have implications for the quality, safety and efficiency of dermatologic care. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal eosinophilic sclerosing fibroplasia (GESF) in cats presents as mass(es) associated with the gastrointestinal tract, mesentery, and abdominal lymph nodes. Hypothesis/Objectives: To report the clinicopathological findings, treatment, and outcome of cats with GESF. Animals: Sixty client‐owned cats diagnosed with GESF. Methods: Retrospective review of medical records of cats with histopathologically confirmed GESF. Results: The median age was 5.4 years (interquartile range [IQR], 3.3‐8.9.); 30% were Domestic Shorthairs and 12% were Domestic Longhair cats, with the most prevalent pedigree breeds being Ragdolls (25%), Exotic Shorthair (10%) and Persian (8%) cats. The median duration of clinical signs was 90 days (IQR, 17.5‐247.0); the most common clinical signs were weight loss (60%), hyporexia/anorexia (55%), chronic vomiting (37%), lethargy (35%) and chronic diarrhea (27%). Masses were located in the small intestine (32%), stomach (27%), ileocolic junction (15%), colon (10%), lymph node (8%) and mesentery (8%) and 15% of cats had >1 mass. Eosinophilia was present in 50% and hypoalbuminemia in 28% of cats. The mass was removed surgically in 37% of cases. Most cats (98%) were treated with corticosteroids. Survival was not statistically different between cats treated with surgical resection and cats treated with medical therapy alone, 88% of the cats were still alive at the time of writing. Conclusions and Clinical Importance: GESF is an important differential diagnosis for abdominal masses in cats, and has a much better prognosis than previously reported. [ABSTRACT FROM AUTHOR]

An increasing number of manuscripts related to digital and computational pathology are being submitted to The Journal of Pathology: Clinical Research as part of the continuous evolution from digital imaging and algorithm‐based digital pathology to computational pathology and artificial intelligence. However, despite these technological advances, tissue analysis still relies heavily on pathologists' annotations. There are three crucial elements to the pathologist's role during annotation tasks: granularity, time constraints, and responsibility for the interpretation of computational results. Granularity involves detailed annotations, including case level, regional, and cellular features; and integration of attributions from different sources. Time constraints due to pathologist shortages have led to the development of techniques to expedite annotation tasks from cell‐level attributions up to so‐called unsupervised learning. The impact of pathologists may seem diminished, but their role is crucial in providing ground truth and connecting pathological knowledge generation with computational advancements. Measures to display results back to pathologists and reflections about correctly applied diagnostic criteria are mandatory to maintain fidelity during human–machine interactions. Collaboration and iterative processes, such as human‐in‐the‐loop machine learning are key for continuous improvement, ensuring the pathologist's involvement in evaluating computational results and closing the loop for clinical applicability. The journal is interested particularly in the clinical diagnostic application of computational pathology and invites submissions that address the issues raised in this editorial. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia. Methods: We used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features. Results: There were lower levels of tau pathology (β = 1.86–2.96, p < 0.001) across all tau antibodies in the co‐pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha‐synucleinopathy, higher alpha‐synuclein was associated with greater early tau (AT8 β = 1.37, p < 0.001; MC1 β = 1.2, p < 0.001) but not mature tau (TauC3 p = 0.18), whereas mature tau was associated with beta‐amyloid (β = 0.21, p = 0.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies. Interpretation: Mature tau may be more closely related to beta‐amyloidosis than alpha‐synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy‐Alzheimer's pathology. [ABSTRACT FROM AUTHOR]

Background: Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi‐quadrant fibro‐osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro‐osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified. Methods: In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole‐exome sequencing. Results: Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento‐osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene. Conclusion: Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants. [ABSTRACT FROM AUTHOR]

Overdiagnosis refers to diagnosis that does not benefit patients because the diagnosed condition is not a harmful disease in those individuals. Overdiagnosis has been identified as a problem in cancer screening, diseases such as chronic kidney disease and diabetes, and a range of mental illnesses including depression and attention deficit hyperactivity disorder. In this paper, we describe overdiagnosis, investigate reasons why it occurs, and propose two different types. Misclassification overdiagnosis arises because the diagnostic threshold for the disease in question has been set at a level where many people without harmful disease are nonetheless diagnosed. We illustrate misclassification overdiagnosis using the example of chronic kidney disease. Misclassification occurs in diseases diagnosed using biomarkers or based on patient reported phenomena. Maldetection overdiagnosis arises because, at the time the diagnosis is made and despite the presence of a 'gold standard' diagnostic test, it is not possible to discriminate between harmful and non-harmful cases of the index disease. We illustrate maldetection overdiagnosis using the example of thyroid cancer. While there is some overlap between misclassification and maldetection overdiagnosis, this conceptual analysis helps to clarify the phenomenon of overdiagnosis and is a necessary first step in developing strategies to address the problem. [ABSTRACT FROM AUTHOR]

Analysis of the volatile part of the metabolome (volatile organic compounds, VOC) present in the gas phase of excreted materials is a promising new screening tool for several cancers, including colorectal cancer ( CRC). The VOC signature can reflect health status, like a 'fingerprint', and can be modified in several diseases. Technical difficulties still limit the widespread use of VOC analysis in the clinical setting, but this approach has already been applied successfully in the diagnosis of CRC. The present study reviews the available data on VOC present in the headspace (the gaseous constituents of a closed space above a liquid or solid) of blood, urine, faeces and breath as a potential screening tool for CRC. A systematic electronic literature search was conducted in PubMed, Scirus and Google using the following keywords: Metabolomic, Volatile Organic Compounds ( VOC), Electronic-nose and Colorectal Cancer. Only articles published in English between 2000 and 2015 were selected and these were independently checked by two of the authors. Ten papers describing the reliability of VOC analysis in breath and faeces, blood and urine were selected; all indicated good reliability in detecting CRC. The use of different substrates and different analytical platforms has led to the identification of different patterns of VOC. The reliability of a metabolomic approach as a noninvasive biomarker for use in CRC screening is supported by this review despite several limitations due to the number of patients included in each study, the different analytical platforms and biological materials used and different VOC identified. [ABSTRACT FROM AUTHOR]

Gout is a common inflammatory arthropathy in adults, with the prevalence increasing in males of older age. It occurs when monosodium urate (MSU) crystals are deposited in joints and connective tissue causing inflammation. The gold standard for the diagnosis of gout is the demonstration of negatively birefringent, needle-shaped MSU crystals through synovial fluid aspiration. However, this is an invasive technique and may not always be conclusive or feasible. Imaging techniques have been developed to aid in diagnosis of gout non-invasively. Radiography has a low utility in the early diagnosis of gout and demonstrates erosions in late stages. Ultrasound (US) has a high overall sensitivity in diagnosing gout with the 'double contour' sign having a high specificity. Magnetic resonance imaging is good at detecting tophi, bone marrow oedema and erosions, but has a limited role in diagnosis because of its high cost and limited availability. Conventional computed tomography (CT) has no role in the routine diagnosis of gout before development of erosions and tophi. A newer technology, dual-energy CT (DECT) has been shown to be able to detect MSU crystals burden with high accuracy. It has a higher specificity and lower sensitivity that US in gout diagnosis. However, because of radiation exposure and cost, it has a better utility in diagnosing clinically suspected gout complicated by other concurrent rheumatologic conditions or if radiography, US and synovial aspiration are inconclusive or not feasible. This paper will review the clinico-pathologic and imaging features of gouty arthropathy. [ABSTRACT FROM AUTHOR]

Objective: Despite low patient numbers, rural emergency departments have a similar diversity of case presentations as urban tertiary hospitals, with the need to manage high‐acuity cases with limited resources. There are no consistent descriptions of the resources available to rural emergency departments internationally, limiting the capacity to compare clinical protocols and standards of care across similarly resourced units. This review aimed to describe the range of human, physical and specialist resources described in rural emergency departments in developed countries and propose a typology for use internationally. Design and setting: A systematic literature search was performed for journal articles between 2000 and 2019 describing the staffing, access to radiology and laboratory investigations, and hospital inpatient specialists. Results: Considerable diversity in defining rurality and in resource access was found within and between Australia, New Zealand, Canada and USA. Discussion: A typology was developed to account for (a) emergency department staff on‐floor, (b) emergency department staff on‐call, (c) physical resources and (d) access to a specialist surgical service. This provides a valuable tool for relevant stakeholders to effectively communicate rural emergency department resources within a country and internationally. Conclusion: The proposed five‐tiered typology draws together international literature regarding rural emergency department services. Although further research is required to test this tool, the formation of this common language allows a base for effective communication between governments, training providers and policy‐makers who are seeking to improve health systems and health outcomes. [ABSTRACT FROM AUTHOR]

This paper presents a mathematical model for better understanding of the functionality of a newly-proposed Malignant Hyperthermia (MH) diagnosis device. MH is a rare life-threatening condition that is usually triggered by exposure to certain drugs such as a volatile anesthetic agent, neuromuscular blocking agent, or succinylcholine. It is highly recommended to have this condition diagnosed immediately after its common symptoms appear. However, it is often only when the patient has had a severe or fatal reaction to anesthetic that a diagnosis is finally made. Due to this, many deaths have been reported before a patient has been diagnosed with this condition. Further for the diagnosis, the patients are subject to an expensive clinical diagnostic procedure and it is also necessary to continuously monitor the condition. In this study, a micro-total analysis system for MH diagnosis through the assessment of the end-tidal CO2 concentration level that can also aid point-of-care testing is presented. Various model parameters of the system are considered and their effects on the behaviour of the system are assessed. The results presented in this study are based on the proposed mathematical model for the new MH diagnosis device and can be used to evaluate the device's functionality and performance prior to its manufacture. [ABSTRACT FROM AUTHOR]

Introduction Practice guidelines provide helpful support for clinical laboratories. Our goal was to assemble an inventory of publically listed guidelines on hematology laboratory topics, to create a resource for laboratories and for assessing gaps in practice-focused guidelines. Methods PubMed and website searches were conducted to assemble an inventory of hematology laboratory-focused guidelines. Exclusions included annual, technical, or collaborative study reports, clinically focused guidelines, position papers, nomenclature, and calibration documents. Results Sixty-eight guidelines were identified on hematology laboratory practice topics from 12 organizations, some as joint guidelines. The median year of publication was 2010 and 15% were >10 years old. Coagulation topics had the largest numbers of guidelines, whereas some areas of practice had few guidelines. A minority of guidelines showed evidence of periodic updates, as some organizations did not remove or identify outdated guidelines. Conclusions This inventory of current practice guidelines will encourage awareness and uptake of guideline recommendations by the worldwide hematology laboratory community, with the International Society for Laboratory Hematology facilitating ongoing updates. There is a need to encourage best guideline development practices, to ensure that hematology laboratory community has current, high-quality, and evidence-based practice guidelines that cover the full scope of hematology laboratory practice. [ABSTRACT FROM AUTHOR]

Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the C andida spp., C ryptococcus spp., P neumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of P neumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement). [ABSTRACT FROM AUTHOR]

We performed laboratory tests and field surveys to evaluate the performance of a low‐cost 3‐component seismometer, consisting of three passive electromagnetic spring‐mass sensors, whose 4.5 Hz natural frequency is extended down to 0.5 Hz thanks to hyper damping. Both lab and field datasets show that the −3 dB band of the seismometer ranges approximately from 0.7 to 39 Hz, in agreement with the nominal specifications. Median magnitude frequency response curves obtained from processing field data indicate that lower corner of the −3 dB band could be extended down to 0.55 Hz and the nominal sensitivity may be overestimated. Lab results confirm the non‐linear behavior of the passive spring‐mass sensor expected for high‐level input signals (a few to tens of mm/s) and field data confirm relative timing accuracy is ±10 ms (1 sample). We found that absolute timing of data collected with USB GPS antennas can be affected by lag as large as +0.5 s. By testing two identical units, we noticed that there could be differences around 0.5 dB (i.e., about 6%) between the components of the same unit as well as between the same component of the two units. Considering shallow passive seismic applications and mainly focusing on unstable slope monitoring, our findings show that the tested seismometer is able to identify resonance frequencies of unstable rock pillars and to generate interferograms that can be processed to estimate subsurface velocity variations. Plain Language Summary: This study describes some tests that we did to evaluate a seismometer that is cheaper than similar products on the market. A seismometer is able to sense and collect seismic waves and can be used for several applications including global seismology and hydrocarbon exploration. In our work, we consider passive seismic applications, that is, we focus on seismic waves generated by non‐controlled sources (aka seismic noise). Either the seismic sources are natural or man‐made, a valuable seismometer should allow to record weak signals in a wide frequency band, especially at relatively low frequency (<5 Hz). The results of our tests show that the cheap seismometer can record frequencies down to approximately 0.5 Hz, while, to keep costs low, the highest frequency is limited to about 40 Hz. Field tests show that the seismometers can retrieve information from seismic noise as weak as a few micrometers per second, while lab test with higher inputs shows that the response of the seismometer is dependent upon the input velocity. Overall, we found that the nominal specifications of the seismometers are met, thus the tested unit is a valuable tool for shallow passive‐seismic applications with relatively‐low‐frequency, low‐amplitude signals, and a limited budget. Key Points: A low‐cost 3‐component seismometer has been tested for passive shallow applicationsThe seismometer has non‐linear response for high‐amplitude (mm/s) excitation signalsLab and field tests confirm the −3 dB band ranges from 0.7 to 39 Hz and an offset of about 0.5 s was found in the filed data whose timing was provided by a USB GPS antenna [ABSTRACT FROM AUTHOR]

This letter has been written in response to the paper by Decaussin‐Petrucci et al. published in Cytopathology, Volume 28, issue 6 ('Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy'). Indeterminate FNAB results (Bethesda 3) can be controversial in regards to treatment. In their article, Decaussin‐Petrucci et al. demonstrated that molecular tests can be routinely performed and are strong predictors of malignancy. In our letter we comment on this hypothesis from the clinicians' perspective. [ABSTRACT FROM AUTHOR]

Introduction: Laboratory quality assurance (QA) includes internal quality control (IQC), external quality assurance (EQA) and quality improvement (QI). EQA identifies quality deviations and training needs. D‐dimers are breakdown products of thrombus and results guide various clinical decisions. Methods: The National Health Laboratory Service (NHLS) in South Africa performs the pathology tests for more than 80% of the population. The NHLS Quality Assurance Department distributed 301 questionnaires to laboratories enquiring about D‐dimer testing. Two levels of STAGO® and Siemens® commercial D‐dimer assay control material were distributed for analysis and returned results analysed. Results: A total of 64 (21.2%) completed questionnaires were returned and 26 (40.6%) laboratories were performing D‐dimers with 25 (97%) subscribing to an EQA scheme. All laboratories reported results in D‐dimer units with a negative result cut‐off of ≤0.25 mg/L but various testing platforms were in use. All returned interpretations of analyses on the blinded control material were correct. The results were also within the respective reference ranges of the controls apart from three outliers. One laboratory obtained a result on STAGO® pathological control that was above the cut‐off of the control reference range but the reason for this error could not be identified. Another obtained results on the STAGO® and on the Siemens® normal controls that were both below the cut‐off of the control reference range due to transcription errors. Conclusion: The study demonstrated the feasibility of a local EQA scheme for D‐dimers based on commercial control material that could mitigate against the cost of international EQA scheme participation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 5-year-old boy with a history of a painful scalp lesion diagnosed as kerion celsi caused by Trichophyton tonsurans. Topics discussed include brief background of kerion celsi, result of the physical examination done on the patient, and mainstay treatment for kerion celsi.

Summary: Background: There is limited evidence regarding the treatment and outcomes of larval cyathostominosis. Objectives: To describe the presentation, treatment and outcomes of horses with larval cyathostominosis in two equine hospitals. Study design: Retrospective, multicentred cohort study. Methods: Clinical records were reviewed (2009–2020). Inclusion criteria included a diagnosis of larval cyathostominosis (determined by faecal assessment and/or post‐mortem examination). Data were assessed for normality. Descriptive analysis was performed for frequency results and central tendencies. Statistical analysis between survivors and nonsurvivors was determined by Chi‐square/Fisher's exact test for categorical variables, and Student's t‐test/Mann–Whitney for continuous variables. Results: Of 38 cases, 21 (55%) were nonsurvivors (3/38 dead on arrival). Nonsurvivors died by 2.9 days ± 2.4. Tachycardia (mean 61 beats/min ± 14), leucocytosis (mean 17.1 × 109/L ± 9.1), neutrophilia (mean 14.1 × 109/L ± 8.5), hypoalbuminaemia (mean 21.6 g/L ± 6.0), hyperfibrinogenaemia (mean 7.4 g/L ± 2.6) and elevated serum amyloid A (SAA) (median 315.0 mg/L, interquartile range [IQR] 117.0–1460.0) were consistent findings. Faecal shedding of Salmonella spp. occurred in four cases. The mean last recorded albumin was 18.6 g/L ± 4.5 and total protein (TP) 52.3 g/L ± 13.6. Crystalloids were administered in 25/35, synthetic colloids in 5/35 and plasma in 17/35 cases. Anthelmintic treatment was administered in 25/35 cases, of which 22 also received corticosteroids. Recumbency prior to admission (p = 0.037) and administration of isotonic fluid therapy (p = 0.027) were associated with nonsurvival. From peripheral blood analysis, lower TP (p = 0.006) and higher SAA (p = 0.050) concentrations at admission as well as lower last recorded TP (p = 0.002) and lower last recorded albumin concentrations (p = 0.028) were associated with nonsurvival. Main limitations: Results may not be applicable to other populations. Conclusions: Referred cases of larval cyathostominosis have a low survival rate. Several variables are associated with reduced survival: history of recumbency, isotonic fluid therapy, elevated SAA at admission, low TP at admission, low last recorded TP and low last recorded albumin. [ABSTRACT FROM AUTHOR]

This guidance document has been prepared on behalf of the International Council for Standardisation in Hematology. The aim of the document is to provide guidance and recommendations on the measurement of factor VIII (FVIII) and factor IX (FIX) inhibitors. After an introduction on the clinical background and relevance of factor VIII and factor IX inhibitor testing, the following aspects of laboratory testing are included: screening for inhibitors, assay principle, sample requirements, testing requirements and interpretation, quality assurance, interferences and recent developments. This guidance document focusses on recommendations for a standardised procedure for the laboratory measurement of FVIII and FIX type I inhibitors. The recommendations are based on published data in peer‐reviewed literature and expert opinion. [ABSTRACT FROM AUTHOR]

Introduction: Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease without "gold standard" for the diagnosis, long non‐coding RNA (lncRNAs) can participate in regulating gene expression through various mechanisms and may play a role in immune intolerance in ITP. Several previous studies have confirmed that lncRNA lncDC and THRIL are involved in the development of autoimmune diseases. This study investigates the relationship between expression levels of two plasma lncRNAs (lncDC and THRIL) and clinical characteristics of adult primary ITP patients, ascertain their potential applications as diagnostic markers of ITP. Methods: We recruited 102 subjects, including 41 ITP patients, 41 healthy controls (HCs) and 20 patients under myelosuppression phase after chemotherapy (MS). qRT‐PCR was used to detect the expression of two lncRNAs in the peripheral blood plasma of the three groups. Receiver operating characteristic (ROC) curves were used to test the diagnostic efficacy of lncDC and THRIL in ITP. Results: The expression level of lncDC was downregulated in ITP patients compared with HCs (p =. 012) and MS (p =.035), whereas THRIL was significantly upregulated (p =.0005, p <. 0001). We further revealed that lncDC has a high sensitivity (78. 05%), while THRIL has a high specificity (97. 56%). The area under the curve (AUC) (0.869, 95% CI: 0.795–0.943, p <.0001) of the ROC curve for this combination increased significantly. Conclusions: THRIL and lncDC expression levels were changed in adult ITP patients. The lncRNAs lncDC and THRIL can serve as potential diagnostic markers for adult primary ITP. [ABSTRACT FROM AUTHOR]

Key content: Tuberculosis (TB) is an important global cause of maternal and neonatal morbidity and mortality.With increasing migration, cases of tuberculosis in pregnancy or the puerperium are increasing in resource‐rich nations with advanced health care systems.Diagnosis may be delayed given the overlap of some of the symptoms with that of pregnancy.Timely diagnosis is essential to initiate appropriate treatment and prevent maternal and neonatal morbidity and mortality. Learning objectives: To understand the relevant global and UK epidemiology of the disease, including recent goals set by the World Health Organization and the UK.To review the pathophysiology of pulmonary and extrapulmonary TB, and of latent and active TB.To learn how to identify high‐risk women for antenatal assessment and gain an awareness of the screening tests available for latent TB.To gain awareness of the clinical symptoms, diagnosis and therapeutic management of active tuberculosis, including management of any drug resistance.To understand management of the neonate within high‐risk groups and where the mothers have diagnosed latent or active TB. Ethical issues: Pregnant women with TB should be fully counselled about the benefits, risks, and alternate options of management.Should healthcare professionals with high risk of acquiring TB infection be exempt from managing TB infection?Management of TB in HIV‐positive women provides additional challenges.Breastfeeding issues around seropositive mothers should be considered. [ABSTRACT FROM AUTHOR]

Objectives: To explore clinicopathological features of peripheral odontogenic fibromas in dogs and risk factors for their diagnosis. Materials and Methods: Data of cases with a histopathological diagnosis of peripheral odontogenic fibromas were obtained from a UK‐based diagnostic laboratory and retrospectively reviewed. Prevalence amongst all biopsy submissions was assessed using binomial tests and Clopper–Pearson intervals. Age at diagnosis was assessed using t‐test for independent samples. Lesion location, sex, and neuter status were assessed using χ2 and post hoc binomial tests. Breed odds ratios were calculated using univariable logistic regression modelling. Results: The prevalence of peripheral odontogenic fibromas amongst all biopsy submissions was 2.8% (1001 of 35,328, 95% confidence interval [CI]: 2.7 to 3.0). The mean (sd) age was 8.1 (±2.7) years. The most affected quadrant was the rostral maxilla (40.1%). The ratio of maxillary to mandibular lesions was 1.3:1 (95% CI: 1.1 to 1.5), and for cases of multiple peripheral odontogenic fibromas the ratio of maxillary to mandibular lesions was 2.4:1 (95% CI: 1.1 to 5.6). Males had 1.2 times the odds of suffering of peripheral odontogenic fibromas compared to females (odds ratio [OR]: 1.2, 95% CI: 1.1 to 1.4). Neutering was associated with an increased risk of diagnosis (OR: 1.6, 95% CI: 1.3 to 1.9). Breeds with increased odds of peripheral odontogenic fibromas compared to crossbreed dogs included boxers (OR: 3.78, 95% CI: 2.80 to 5.09), border terriers (OR: 3.21, 95% CI: 2.10 to 4.91) and Basset Hounds (OR: 3.18, 95% CI: 1.58 to 6.44). Breeds with increased odds of multiple simultaneous peripheral odontogenic fibromas compared to crossbreed dogs included: Boxers (OR: 12.02, 95% CI: 7.13 to 20.24), border terriers (OR: 5.05, 95% CI: 2.32 to 11.43) and Staffordshire Bull terriers (OR: 2.42, 95% CI: 1.33 to 4.41). Clinical Significance: Knowledge of clinicopathological features and at‐risk breeds for peripheral odontogenic fibroma development can assist clinicians with making a diagnosis. The identification of risk factors provides targets for future research investigating peripheral odontogenic fibroma pathogenesis. [ABSTRACT FROM AUTHOR]

Background: P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co‐test for detecting high‐grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high‐throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. Methods: P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A‐knockout) standards. Since 2018, 24 100‐women (HPV‐positive/‐negative, Pap‐normal/‐abnormal) have been enrolled nationwide for two‐tier validation work. In cross‐sectional studies, age‐ and viral genotype‐dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut‐offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2‐year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV‐positive Pap‐normal, Pap‐abnormal biopsy‐negative and biopsy‐confirmed LSIL. Results: P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A‐positive ratio was 13.9 ± 1.8% among HPV‐negative NILM women and peaked at the ages of 40–49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV‐negative: 17.7 ± 5.0–21.4 ± 7.2%; HPV‐positive: 18.0 ± 5.2–20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV‐combined double‐cut‐off‐ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co‐test. The p16INK4A‐abnormal situation was an independent HSIL+ risk factor for 2‐year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3–7.2). Conclusions: FCM‐based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk‐stratification‐based interventions. [ABSTRACT FROM AUTHOR]

Policy PointsChild lead poisoning is associated with socioeconomic inequity and perpetuates health inequality.Methods for testing and detection of child lead poisoning are ill suited to the current demographics and characteristics of the problem.A three‐pronged revision of current testing approaches is suggested.Employing the suggested revisions can immediately increase our national capacity for equitable, inclusive testing and detection. Child lead poisoning, the longest‐standing child public health epidemic in US history, is associated with socioeconomic inequity and perpetuates health inequality. Removing lead from children's environments ("primary prevention") is and must remain the definitive solution for ending child lead poisoning. Until that goal can be realized, protecting children's health necessarily depends on the adequacy of our methods for testing and detection. Current methods for testing and detection, however, are no longer suited to the demographics and magnitude of the problem. We discuss the potential deployment and feasibility of a three‐pronged revision of current practices including: 1) acceptance of capillary samples for final determination of lead poisoning, with electronic documentation of "clean" collection methods submitted by workers who complete simple Centers for Disease Control and Prevention–endorsed online training and certification for capillary sample collection; 2) new guidance specifying the analysis of capillary samples by inductively coupled plasma mass spectrometry or graphite furnace atomic absorption spectrometry with documented limit of detection ≤0.2 μg/dL; and 3) adaptive "census tract–specific" universal testing and monitoring guidance for children from birth to 10 years of age. These testing modifications can bring child blood lead level (BLL) testing into homes and communities, immediately increasing our national capacity for inclusive and equitable detection and monitoring of dangerous lower‐range BLLs in US children. [ABSTRACT FROM AUTHOR]

Background: It is estimated that 1%–5% of children in the United States are affected by prenatal alcohol exposure while only a small percentage are so identified in clinical practice. One explanation for this discrepancy may be the way in which diagnostic criteria are operationalized. Methods: To evaluate the extent to which three commonly used systems for the diagnosis of Fetal Alcohol Spectrum Disorder (FASD) consistently identified children in a community sample, data from the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (COFASP) study were re‐analyzed. In the data set, there were 2325 children with variables necessary to allow diagnosis by three systems commonly used in North America. These systems were (1) that used by COFASP, which is a revised modification of the Institute of Medicine's recommendations, (2) the 4‐Digit Code, and (3) the most recent Canadian Guidelines. To determine the degree of association among these classifications, the Fleiss Multirater Kappa measure of agreement was applied. Results: Among these three systems, 408 children were classified as FASD, 208 by the CoFASP system, 319 by the 4‐Digit Code, and 28 by the Canadian Guidelines. Agreement among the findings from the three systems varied from slight to fair. Conclusions: These results indicate a lack of consistency in these approaches to FASD diagnosis. Discrepancies result from differences in specifying the criteria used to define the diagnosis, including growth, physical features, neurobehavior, and alcohol‐use thresholds. The question of their relative accuracy cannot be resolved without reference to a measure of validity that does not currently exist, and this suggests the need for a more empirically based diagnostic schema. [ABSTRACT FROM AUTHOR]

Objectives: The latest version of the National Comprehensive Cancer Network recommends neoadjuvant therapy followed by surgical treatment or radical chemoradiotherapy for patients with cT3N0M0. Neoadjuvant therapy can improve the prognosis of patients with locally advanced esophageal cancer. Therefore, the evaluation or prediction of T stage is particularly important because the treatment could differently affect the prognosis. Here, we establish a model to predict the T stage of patients with T2‐3N0M0 to help choose the best treatment strategy. Methods: From 1637 patents with esophageal cancer, we enrolled 48 patients and performed least absolute shrinkage and selection operator regression to screen for independent factors influencing pathological T stage. We, then, trained the decision tree to obtain the decision tree diagram and divided the T stages obtained by different methods into two categories, T2 and T3, for survival analysis. Results: A total of 21 and 27 cases were predicted to be T2 and T3, respectively, under ultrasonic gastroscopy, 19 and 29 under magnetic resonance imaging, and 22 and 26 under pathological examination. Multivariate logistic regression analysis revealed that the muscularis propria thickness (MPT) (p = 0.0097) and the muscularis propria + mucosa thickness (MPMT) in the largest tumor cross‐section (p = 0.0239) were independent influencing factors. We plotted a decision tree diagram with these two factors. MPT in the largest tumor cross‐section >1.3 mm could be judged as pT3; if ≤1.3 mm, MPMT should be considered a thickness ≥1.7 mm could be judged as pT2 (otherwise pT3). Corresponding survival analysis was performed according to the T stage under different examination modalities. Conclusion: MPT in the largest tumor cross‐section and MPMT in the largest tumor cross‐section are independent predicting factors of pathological T stage. [ABSTRACT FROM AUTHOR]

Aims: Bronchiolar adenoma (BA) is a novel entity in the 2021 WHO classification of lung tumours. The expression profile of mucin core proteins in BAs is not clear. The aim of this study was to clarify the expression profiles of mucins and to validate the clinicopathologic and molecular features of BAs. Methods and results: We examined the clinicopathological, immunohistochemical, and molecular features of 20 BAs. Our cohort comprised 10 proximal and 10 distal BAs. Only seven of 18 patients (39%) were accurately diagnosed with BA at the time of intraoperative consultation. The frequent genetic alterations were BRAF V600E (35%) and KRAS (30%) mutations, which were mutually exclusive. The expression of MUC1, MUC4, and MUC5B was observed in all cases and that of MUC5AC and MUC6 was observed in nine (45%) and five (25%) cases, respectively. MUC4 was diffusely expressed in 18 cases. In contrast, MUC1, MUC5AC, MUC5B, and MUC6 displayed a patchy expression pattern. These expression patterns were similar to that of bronchiolar epithelium in normal lung tissue. In addition, overexpression of MUC1 and MUC4 on the entire cell surface was not observed in any of the BAs, suggesting their benign nature. Conclusion: BA commonly exhibits diffuse MUC4 and patchy MUC1 and MUC5B expression. Its unique expression pattern is probably attributed to mucin expression specific to the bronchiolar epithelium. These results confirm the clinicopathologic and molecular characteristics of BA, including the difficulty in intraoperative frozen section diagnosis and the broad morphologic spectrum of BA derived from the bronchiolar epithelium. [ABSTRACT FROM AUTHOR]