Diagnostic Tool Research Articles

Monitoring of Red Cell Donor Chimerism in Oncohematological Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a definitive therapy for patients with different oncological and hematological diseases. The study of red cell chimerism is a crucial process for diagnosing transplant engraftment and functioning during the post-transplantation period.
 Aim. To assess the effect of immunohematological (АВО and HLA donor–recipient matching) and medical (conditioning regimens) parameters on the onset time of post-transplantation donor chimerism which is determined by RBC antigens.
 Materials & Methods. The study enrolled 54 patients at the Kirov Research Institute of Hematology and Transfusiology in Russia (25 female and 29 male patients) aged 3–60 years (median 32 years). All of them received allo-HSCT in 2013–2021. Acute leukemias were identified in 39 patients, 8 patients were reported to have malignant lymphoproliferative diseases, 3 patients had myeloproliferative neoplasms, and 4 patients were diagnosed with aplastic anemia. RBC antigens of donors and recipients were analyzed by gel hemagglutination using Bio-Rad (USA) reagents and equipment.
 Results. The onset time of donor chimerism depends neither on the degree of HLA donor–recipient matching, nor on conditioning regimen. Donor chimerism in recipients with major ABO-incompatibility occurs significantly later than in patients with minor АВО-incompatibility and ABO-identity.
 Conclusion. Monitoring of post-transplantation donor chimerism is an important diagnostic and prognostic tool to assess donor hematopoietic cell engraftment, hematologic recovery, graft rejection, and relapse of the disease. After allo-HSCT, first donor red cells occur in pairs with major АВО-incompatibility later than in pairs with minor АВО-incompatibility or ABO antigen compatibility. Other immunohematological and medical parameters do not affect the development rate of donor chimerism determined by RBC antigens.

Evaluation of plasma canine C-reactive protein concentrations in dogs with otitis media, healthy dogs and dogs with chronic otitis externa.

Otitis is characterised by inflammation of one or more of the structures of the ear. At present, to confirm or exclude otitis media (OM), it is most often necessary to perform a computed tomography (CT) scan or magnetic resonance imaging. Inflammation is an immune defence response found in many conditions that can be detected and tracked by measuring biological markers of inflammation as the Canine C-reactive protein (CRP). The objective of this study was to determine whether CRP measurement is useful as an adjunctive diagnostic tool in dogs with otitis and whether elevated concentrations correlated with disease severity/presence of OM. Twenty-four client-owned dogs were recruited over 1 year. The dogs were divided into three groups: chronic or recurrent otitis externa (CO), otitis media (OM) and H (healthy). The dogs with otitis underwent a CT scan of the head, measurement of the plasma CRP concentration and evaluation of a 0-3 Otitis Index Score 3 (OTIS3 score). No dog (0%) in group H had an increased CRP value, compared to 20% in the CO group (one of five dogs) and 23% in the OM group (3 of 13 dogs). Plasma CRP concentrations show a statistically significant positive relationship with the OTIS3 score (p = 0.04). Plasma CRP concentration is not reliable as a discriminatory tool in cases of otitis, although there is a trend for elevation in cases with more severe disease. However, a larger study may provide a statistically more reliable correlation between the severity of OM and CRP concentrations.

Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals.

The purpose of this study was to investigate the diagnostic value of urine lipoarabinomannan (LAM) detection based on chemiluminescence assay for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in HIV-negative individuals. A total of 215 patients and 37 healthy individuals were included according to inclusion and exclusion criteria, including 173 cases of PTB and 42 cases of EPTB. Sputum smears, sputum culture, TB-RNA, GeneXpert, and urine LAM results were obtained from all patients before treatment. Using the composite reference standard as the reference, the diagnostic performance of these methods for PTB and EPTB was evaluated, and the diagnostic performance and cost-effectiveness of different combinations were analyzed. In PTB, LAM exhibited the highest sensitivity (55.49%), followed by GeneXpert (44.51%). In EPTB, LAM also had the highest sensitivity (40.48%), followed by GeneXpert (33.33%). When combined with one method, LAM combined with GeneXpert showed the highest sensitivity for both PTB (68.79%) and EPTB (61.9%). When combined with two methods, culture, GeneXpert, and LAM showed the highest sensitivity for both PTB (73.99%) and EPTB (69.05%). In terms of cost-effectiveness analysis, the price of LAM was significantly lower than that of GeneXpert ($129.82 vs. $275.79 in PTB and 275.79 vs. 502.33 in EPTB). Among all combinations, the combination of LAM and sputum smear had the lowest cost, with prices of $124.94 for PTB and $263.72 for EPTB. Urine LAM detection based on chemiluminescence assay can be used as an adjunct diagnostic tool for PTB and EPTB in HIV-negative individuals. This facilitates expanding the current application of urine LAM from solely HIV-positive populations to the general population. LAM detection can overcome the limitations of obtaining clinical samples, and its ease of sample acquisition will be beneficial for its broader application in a larger scope. For economically better-off areas, we recommend using a combination of LAM + GeneXpert+culture for higher sensitivity; for economically disadvantaged areas, LAM + smear microscopy combination can provide a quick and accurate diagnosis of tuberculosis at a lower cost.

'Evaluation of beta-2-microglobulin and neuron-specific enolase as prognostic factors in patients over 65 years of age with frailty syndrome hospitalized for acute coronary syndrome'.

The aim of the study is to assess the value of beta-2-microglobulin (B2M) and neuron-specific enolase (NSE) as prognostic factors in the population of patients over 65 years of age with frailty hospitalized due to acute coronary syndrome (ACS). Patients aged ≥65 years with ACS were included. Assessment of frailty was carried out using the FRAIL scale. The measurement of NSE and B2M was carried out three times during hospitalization: (1) at the time of admission, (2) on the second day of hospitalization, (3) on the seventh day of hospitalization, or the day of discharge if it was before the seventh day. The primary endpoint was all-cause mortality, and the secondary endpoint was unscheduled rehospitalization. Of the 127 patients, frailty was identified in 39.3%. Multivariate analysis of variance showed significantly higher levels of NSE ( P = 0.012) and B2M ( P < 0.001) in patients with frailty compared to the nonfrail group and significant changes in marker levels during hospitalization - decreased NSE ( P < 0.001) and increased B2M levels ( P < 0.001). Elevated B2M-1 level was an independent marker of the occurrence of frailty [odds ratio (OR), 1.98 (1.09-4.00); P = 0.044], and the optimal cutoff point for the diagnosis of frailty was 2.85 mg/l [area under the curve (AUC), 0.718 (0.632-0.795)] with sensitivity 52% and specificity 84.4% ( P < 0.001). Elevated NSE-3 level was associated with all-cause mortality, and each 1 ng/ml increase in NSE-3 increased the risk of death by 1.07-fold [OR, 1.07 (1.03-1.10]). Meanwhile, elevated B2M-3 level was associated with unscheduled rehospitalization, and each 1 mg/l increase in B2M-3 increased the risk of unscheduled rehospitalization by 1.21-fold [OR, 1.21 (1.03-1.42)]. The Harrell's C-index for all-cause mortality was higher for NSE-3 [0.820 (95% confidence interval {CI}, 0.706-0.934)] compared to frailty assessed by the FRAIL scale [0.715 (95% CI, 0.580-0.850)], which means that additional NSE-3 assessment may improve the prediction of all-cause mortality. However, Uno's C-Statistic analysis showed that the difference was not statistically significant (Pr>chi-square 0.556). Harrell's C-index for unscheduled rehospitalization was higher for frailty assessed by the FRAIL scale compared to B2M-3. Monitoring NSE and B2M marker levels in patients over 65 years of age with frailty and ACS does not provide additional benefits in terms of prognostic ability compared to tests assessing frailty. B2M, assessed upon hospital admission and monitoring NSE and B2M levels during hospitalization may be considered in the diagnosis of frailty and risk stratification in a group of patients for whom currently available frailty diagnostic tools cannot be used.

A rare case of neglected parasitic zoonosis.

Infections caused due to zoonotic hookworms are rare and are often under reported. Here we report a case of diarrheal disease caused by Ancylostoma ceylanicum, an important emerging zoonotic hookworm. There is limited knowledge about the epidemiology and disease burden of A. ceylanicum infections in Kerala. A 50-year-old male patient presented with complaints of loose stools for past five weeks. The laboratory investigations revealed a high total WBC count and eosinophil count. Diagnostic colonoscopy showed numerous worms which were identified as A. ceylanicum. Timely diagnosis aided in successful treatment of the patient. Improvement in diagnostic tools and awareness enable accurate and early detection of this neglected but emerging pathogen.

Chelator impact: investigating the pharmacokinetic behavior of copper-64 labeled PD-L1 radioligands.

Programmed cell death ligand 1 (PD-L1) plays a critical role in the tumor microenvironment and overexpression in several solid cancers has been reported. This was associated with a downregulation of the local immune response, specifically of T-cells. Immune checkpoint inhibitors showed a potential to break this localized immune paralysis, but only 30% of patients are considered responders. New diagnostic approaches are therefore needed to determine patient eligibility. Small molecule radiotracers targeting PD-L1, may serve as such diagnostic tools, addressing the heterogeneous PD-L1 expression between and within tumor lesions, thus aiding in therapy decisions. Four biphenyl-based small-molecule PD-L1 ligands were synthesized using a convergent synthetic route with a linear sequence of up to eleven steps. As a chelator NODA-GA, CB-TE2A or DiAmSar was used to allow radiolabeling with copper-64 ([64Cu]Cu-14-[64Cu]Cu-16). In addition, a dimeric structure based on DiAmSar was synthesized ([64Cu]Cu-17). All four radioligands exhibited high proteolytic stability (> 95%) up to 48 h post-radiolabeling. Saturation binding yielded moderate affinities toward PD-L1, ranging from 100 to 265nM. Real-time radioligand binding provided more promising KD values around 20nM for [64Cu]Cu-14 and [64Cu]Cu-15. In vivo PET imaging in mice bearing both PC3 PD-L1 overexpressing and PD-L1-mock tumors was performed at 0-2, 4-5 and 24-25h post injection (p.i.). This revealed considerably different pharmacokinetic profiles, depending on the substituted chelator. [64Cu]Cu-14, substituted with NODA-GA, showed renal clearance with low liver uptake, whereas substitution with the cross-bridged cyclam chelator CB-TE2A resulted in a primarily hepatobiliary clearance. Notably, the monomeric DiAmSar radioligand [64Cu]Cu-16 demonstrated a higher liver uptake than [64Cu]Cu-15, but was still renally cleared as evidenced by the lack ofuptake in gall bladder and intestines. The dimeric structure [64Cu]Cu-17 showed extensive accumulation and trapping in the liver but was also cleared via the renal pathway. Of all tracer candidates and across all timepoints, [64Cu]Cu-17 showed the highest accumulation at24h p.i. in the PD-L1-overexpressing tumor of all timepoints and all radiotracers, indicating drastically increased circulation time upon dimerization of two PD-L1 binding motifs. This study shows that chelator choice significantly influences the pharmacokinetic profile of biphenyl-based small molecule PD-L1 radioligands. The NODA-GA-conjugated radioligand [64Cu]Cu-14 exhibited favorable renal clearance; however, the limited uptake in tumors suggests the need for structural modifications to the binding motif for future PD-L1 radiotracers.

Patterns and assessment of spastic hemiplegic gait.

Hemiparetic gait disorders are common in stroke survivors. A circumductory gait is often considered the typical hemiparetic gait. In clinical practice, a wide spectrum of abnormal gait patterns is observed, depending on the severity of weakness and spasticity, and the anatomical distribution of spasticity. Muscle strength is the key determinant of gait disorders in hemiparetic stroke survivors. Spasticity and its associated involuntary activation of synergistic spastic muscles often alter posture of involved joint(s) and subsequently the alignment of hip, knee, and ankle joints, resulting in abnormal gait patterns. Due to combinations of various levels of muscle weakness and spasticity and their interactions with ground reaction force, presentations of gait disorders are variable. From a neuromechanical perspective, a stepwise visual gait analysis approach is proposed to identify primary underlying causes. In this approach, the pelvic and hip joint movement is examined first. The pelvic girdle constitutes three kinematic determinants. Its abnormality determines the body vector and compensatory kinetic chain reactions in the knee and ankle joints. The second step is to assess the ankle and foot complex abnormality. The last step is to examine abnormality of the knee joint. Assessment of muscle strength and spasticity of hip, knee, and ankle/foot joints needs to be performed before these steps. Lidocaine nerve blocks can be a useful diagnostic tool. Recognizing different patterns and identifying the primary causes are critical to developing clinical interventions to improve gait functions.

Measurement of serum hepcidin-25 by latex agglutination in healthy volunteers and patients with hematologic disorders.

Iron is an essential trace metal, vital for various physiologic processes, but excess levels can harm health. Maintaining iron homeostasis is critical, with hepcidin playing a key role. The isoform hepcidin-25 exerts the most significant influence on iron metabolism, making its serum levels a valuable diagnostic tool. However, mass-spectrometry and other conventional measurement methods can be difficult to perform, and some immunoassays lack reliability. In this study, we employed a recently developed latex agglutination method integrated with a readily available automated analyzer to quantify serum hepcidin-25 levels in both volunteers recruited from personnel of our hospital (n = 93) and patients with various hematological disorders (n = 112). Our findings unveiled a robust positive correlation between serum hepcidin-25 and ferritin, as well as C-reactive protein levels, in both volunteers and patients. Among the patients with hematological disorders, there was a noteworthy negative correlation between hepcidin-25 levels and hemoglobin concentrations, as well as reticulocyte counts. Interestingly, the hepcidin-25/ferritin ratio was remarkably low in patients with hemolytic anemia and myelodysplastic syndromes with ring sideroblasts. Our findings suggest that quantifying serum hepcidin-25 and the hepcidin-25/ferritin ratio using this method may be valuable for screening of hematopoietic diseases and other iron metabolism disorders.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Prevalence and Predictive Factors of Panic Disorder among Adults in Saudi Arabia: A Cross-Sectional Study.

Panic disorder (PD) is a severe anxiety disorder characterized by recurrent and unexpected panic attacks that cause intense distress. Despite the high prevalence of panic disorder and its significant impact on life, limited research has been conducted on its prevalence and their associated factors in Saudi Arabia. This study seeks to contribute to the understanding of PD among adults in Saudi Arabia by examining its prevalence and associated factors, using an online survey method. A validated questionnaire-based cross-sectional study was conducted targeting 1276 Saudi adults. Data were collected electronically via Google Forms from the eligible participants. The questionnaire comprised three sections: sociodemographic information, medical history, and a validated diagnostic tool for PD. The prevalence of PD among Saudi adults was 13.1%. Most individuals with PD experienced their first panic attack before the age of 18. Only 38.3% individuals with PD sought medical attention, and approximately one-third of those who sought help did not receive a diagnosis. Multiple logistic regression analysis revealed that significant risk factors for PD included being female; having chronic health problems, a comorbid psychiatric disorder, a high body mass index; and experiencing suicidal ideation (P < 0.05). The highest risk was associated with chronic diseases (adjusted odds ratio = 3.1, 95% confidence interval: 2.1-4.6). This study demonstrates that PD is a prevalent and debilitating mental health condition among Saudi Arabian adults. Non-mental health physicians should be aware of PD, as many cases remain undiagnosed.

Near-Infrared Spectroscopy for Distinguishing Malignancy in Thyroid Nodules.

Thyroid nodules are common clinical entities, with a significant proportion being malignant. Early, accurate, and non-invasive tools to differentiate benign and malignant nodules can optimize patient management and reduce unnecessary surgery. This study aimed to evaluate the efficacy and accuracy of near-infrared spectroscopy (NIRS) in distinguishing benign from malignant thyroid nodules. A diffuse reflectance spectrum for a total of 20 thyroid nodule samples (10 samples as colloid goiter and 10 samples as thyroid cancer), were acquired in the wavelength range from 1000 to 2500 nm. Spectral data from NIRS were analyzed by means of principal component analysis (PCA), quadratic discriminant analysis (QDA), and linear discriminant analysis (LDA) to classify and differentiate thyroid nodule samples. The present study found that NIRS effectively distinguished colloid goiter and thyroid cancer using the first two principal components (PCs), explaining 90% and 10% of the variance, respectively. QDA discrimination plot displayed a clear separation between colloid goiter and thyroid cancer with minimal overlap, aligning with reported 95% accuracy. Additionally, applying LDA to seven PCs from PCA achieved a 100% accuracy rate in classifying colloid goiter and thyroid cancer from near-infrared spectral data. In conclusion, NIRS offers a promising, non-invasive complementing diagnostic tool for differentiating benign from malignant thyroid nodules with high accuracy. Future work should integrate these results into predictive model development, emphasizing external validation, alternative performance metrics, and protecting against potential overfitting translation of a machine learning model to a clinical setting.

Comparison of magnetic resonance elastography and diffusion-weighted imaging for differentiating benign and malignant liver lesions

BackgroundImaging is a crucial diagnostic tool in focal liver lesions (FLLs) diagnosis. Without the need for an intravenous contrast agent, two such MRI methods that can distinguish between benign and malignant FLLs are diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). The purpose of this study was to assess the utility of diffusion-weighted magnetic resonance imaging and magnetic resonance elastography in the identification and differentiation of benign and malignant hepatic focal lesions.MethodsThis cross-sectional study was carried out on ninety patients (with mean age 52 years) with hepatic focal lesions (29 benign and 61 malignant). Both MRE and DWI were performed on the patients. A modified gradient-echo sequence was used for MRE, and respiratory-triggered fat-suppressed single-shot echoplanar DW imaging (b = 0.800) was used for DWI. Maps of the apparent diffusion coefficient (ADC) and stiffness were produced. Regions of interest were placed over the FLLs on stiffness and ADC maps to get FLL ADC values and mean stiffness. Receiver operating curve (ROC) analysis was used to compare the roles of MRE and DWI in the differentiation of benign and malignant FLL.ResultsThe ADC of FLLs and MRE stiffness exhibited strong negative correlation [(r: −0.559; p < 0.001)]. Compared to malignant FLLs, benign FLLs had much higher mean ADC values. However, compared to benign FLLs, malignant FLLs exhibited much greater mean stiffness. FNH has the lowest mean stiffness of all FLLs, at less than 2.22 kPa. Among FLLs, CCAs had the lowest mean ADC values and the highest mean stiffness. The results showed that the MRE and DWI cutoff values were > 4.23 and ≤ 1.43, respectively; the area under the curve (AUC) values were 0.991 and 0.894, and the sensitivity and specificity results were 96.7%, 93.1%, and 85.2%, 89.7%, respectively.ConclusionsMRE was found to be more sensitive method for identifying benign and malignant hepatic focal lesions than DWI.

Detection of lung cancer and stages via breath analysis using a self-made electronic nose device

ABSTRACT Background Breathomics is an emerging area focusing on monitoring and diagnosing pulmonary diseases, especially lung cancer. This research aims to employ metabolomic methods to create a breathprint in human-expelled air to rapidly identify lung cancer and its stages. Research design and methods An electronic nose (e-nose) system with five metal oxide semiconductor (MOS) gas sensors, a microcontroller, and machine learning algorithms was designed and developed for this application. The volunteers in this study include 114 patients with lung cancer and 147 healthy controls to understand the clinical potential of the e-nose system to detect lung cancer and its stages. Results In the training phase, in discriminating lung cancer from controls, the XGBoost classifier model with 10-fold cross-validation gave an accuracy of 91.67%. In the validation phase, the XGBoost classifier model correctly identified 35 out of 42 patients with lung cancer samples and 44 out of 51 healthy control samples providing an overall sensitivity of 83.33% and specificity of 86.27%. Conclusions These results indicate that the exhaled breath VOC analysis method may be developed as a new diagnostic tool for lung cancer detection. The advantages of e-nose based diagnostics, such as an easy and painless method of sampling, and low-cost procedures, will make it an excellent diagnostic method in the future.

Prévalence des troubles psychiatriques en population carcérale française : une revue systématique de la littérature

IntroductionThe prevalence of psychiatric disorders among prisoners remains a major public health issue worldwide. In France, despite the increasing number of persons who are incarcerated (+30% between 1992 and 2002 with a 120% prison overcrowding), and a historical concern about the mental health of persons in detention and its management, no systematic review has been published on this subject. The aim of this article is to present the results of a systematic review of the literature on the prevalence of psychiatric disorders in French prisons. MethodThe reporting of this systematic review conforms to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. We searched the PubMed and Web of Science databases. We used combinations of keywords relating to prison (prison*, jail*, inmate*), to psychiatry (“mental health”, psychiatr*), and to France (France, French). This work was completed with a search through the digital libraries of the École des Hautes Études en Santé Publique (EHESP) and of the Système Universitaire de Documentation (Sudoc) to obtain data from academic works and the gray literature. References cited in studies included in this review were also examined. All references published up to September 2022, written in English or French, presenting the results of original quantitative studies on the prevalence of psychiatric disorders in correctional settings were included. Two researchers independently extracted data from included references according to a pre-established protocol. ResultsAmong 501 records identified, a total of 35 papers based on 24 epidemiological studies met the eligibility criteria for inclusion in this review: 16 were cross-sectional, 7 retrospective and 1 both cross-sectional and retrospective. All papers were published between 1999 and 2022. We found one European study, 5 international studies, 18 regional or local studies. Of these, 21 studies had all-male or mixed gender samples (but when the sample was mixed gender, it was always at least 92% male). Almost half of the studies (n=11) involved a small sample of fewer than 500 persons. Half of the studies involved a sample of recently incarcerated persons: 6 involved a random sample of persons in detention, and 1 involved a sample of people incarcerated for more than 5 years. The last 5 studies focused on persons aged over 50 years and incarcerated for more than one year (n=1), incarcerated for sexual offences (n=2), placed in disciplinary cells (n=1) or in a special wing for radicalized or suspected radicalized individuals (n=1). Nine studies used standardized and validated diagnostic tools. According to the 4 studies involving representative samples and using standardized and validated diagnostic tools, the prevalence of the following psychiatric disorders was: 29.4–44.4% for anxiety disorders, 5–14.2% for PTSD, 28–31.2% for mood disorders, 6.9–17% for psychotic disorders, 32% for personality disorders and 11% for ADHD. ConclusionThis systematic review of the literature highlights the high prevalence of psychiatric disorders in French prisons. The data collected are in line with international studies. The great methodological heterogeneity of the papers included in this review calls for further rigorous research to better understand the rates of mental disorders in French prisons and to explore their determinants.

Dispersion of Beliefs Bounds: Sentimental Recovery

We present a nonparametric method to recover a bound on ex ante dispersion of beliefs (DBB) from asset prices with minimal assumptions. DBB constrains the dispersion among all possible distributions in an economy, consistent with observed prices and subject to a good-deal bound. In model-based economies, DBB effectively tracks belief heterogeneity and serves as a diagnostic tool for evaluating model calibrations. Empirically, DBB relates to common proxies of belief dispersion, offering a real-time, market-implied disagreement measure. Our versatile approach applies to both complete and incomplete markets represented by any asset class. This paper was accepted by Kay Giesecke, finance. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01587 .

Application of LightGBM hybrid model based on TPE algorithm optimization in sleep apnea detection.

Sleep apnoea syndrome (SAS) is a serious sleep disorder and early detection of sleep apnoea not only reduces treatment costs but also saves lives. Conventional polysomnography (PSG) is widely regarded as the gold standard diagnostic tool for sleep apnoea. However, this method is expensive, time-consuming and inherently disruptive to sleep. Recent studies have pointed out that ECG analysis is a simple and effective diagnostic method for sleep apnea, which can effectively provide physicians with an aid to diagnosis and reduce patients' suffering. To this end, in this paper proposes a LightGBM hybrid model based on ECG signals for efficient detection of sleep apnea. Firstly, the improved Isolated Forest algorithm is introduced to remove abnormal data and solve the data sample imbalance problem. Secondly, the parameters of LightGBM algorithm are optimised by the improved TPE (Tree-structured Parzen Estimator) algorithm to determine the best parameter configuration of the model. Finally, the fusion model TPE_OptGBM is used to detect sleep apnoea. In the experimental phase, we validated the model based on the sleep apnoea ECG database provided by Phillips-University of Marburg, Germany. The experimental results show that the model proposed in this paper achieves an accuracy of 95.08%, a precision of 94.80%, a recall of 97.51%, and an F1 value of 96.14%. All of these evaluation indicators are better than the current mainstream models, which is expected to assist the doctor's diagnostic process and provide a better medical experience for patients.

Repeatability of swept-source optical coherence tomography angiography automated macular vessel density.

Optical Coherence Tomography Angiography Ratio Analysis (OCTARA) is capable of visualizing inner and outer retinal vascular plexuses, choriocapillaris, and larger choroidal vasculature in vivo without contrast injection. The aim of this study was to assess the intrasession repeatability of automated vessel density measurements using Triton Swept-Source Optical Coherence Tomography Angiography (OCTA) innovative algorithm OCTARA in retinal and choroidal vasculature. To study population between 65-90 years old with no eye diseases. For each subject measurements were performed four times. The intraclass correlation coefficient and the coefficient of variation were calculated to analyze repeatability of the OCTARA automatically generated vessel density measurements. A total of 35 eyes were included in the study. The intraclass correlation coefficient of the global vessel density in the superficial capillary plexus and the deep capillary plexus were 0.963 and 0.975, respectively, and the coefficient of variation were 5.4% and 4.4%, respectively. The intraclass correlation coefficient of the rest of the global measurements was indicative of good reliability with the exception of the deep choroid layer with an intraclass correlation coefficient of 0.6 indicative of moderate reliability. Our results proved excellent repeatability of automated vessel density measurements in the superficial and deep capillary plexus layers in our cohort using a OCTARA algorithm indicating that it may be a reliable diagnostic tool. It also showed good reliability in choriocapillary and mid choroid layer. These findings may be of value in assessing the significance of differences in capillary density measurements over time and across different settings.

Clinical application of next generation sequencing for Mendelian disease diagnosis in the Iranian population

Next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype–phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond.

Understanding genomic medicine for thoracic aortic disease through the lens of induced pluripotent stem cells.

Thoracic aortic disease (TAD) is often silent until a life-threatening complication occurs. However, genetic information can inform both identification and treatment at an early stage. Indeed, a diagnosis is important for personalised surveillance and intervention plans, as well as cascade screening of family members. Currently, only 20% of heritable TAD patients have a causative mutation identified and, consequently, further advances in genetic coverage are required to define the remaining molecular landscape. The rapid expansion of next generation sequencing technologies is providing a huge resource of genetic data, but a critical issue remains in functionally validating these findings. Induced pluripotent stem cells (iPSCs) are patient-derived, reprogrammed cell lines which allow mechanistic insights, complex modelling of genetic disease and a platform to study aortic genetic variants. This review will address the need for iPSCs as a frontline diagnostic tool to evaluate variants identified by genomic discovery studies and explore their evolving role in biological insight through to drug discovery.

Complement Activation in Nephrotic Glomerular Diseases.

The nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood-urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches.