Patient Samples Research Articles

Nano fuzzy alarming system for blood transfusion requirement detection in cancer using deep learning

Periodic blood transfusion is a need in cancer patients in which the disease process as well as the chemotherapy can disrupt the natural production of blood cells. However, there are concerns about blood transfusion side effects, the cost, and the availability of donated blood. Therefore, predicting the timely requirement for blood transfusion considering patient variability is a need, and here for the first-time deal with this issue in blood cancer using in vivo data. First, a data set of 98 samples of blood cancer patients including 61 features of demographic, clinical, and laboratory data are collected. After performing multivariate analysis and the approval of an expert, effective parameters are derived. Then using a deep recurrent neural network, a system is presented to predict a need for packed red blood cell transfusion. Here, we use a Long Short-Term Memory (LSTM) neural network for modeling and the cross-validation technique with 5 layers for validation of the model along with comparing the result with networking and non-networking machine learning algorithms including bidirectional LSTM, AdaBoost, bagging decision tree based, bagging KNeighbors, and Multi-Layer Perceptron (MLP). Results show the LSTM outperforms the other methods. Then, using the swarm of fuzzy bioinspired nanomachines and the most effective parameters of Hgb, PaO2, and pH, we propose a feasibility study on nano fuzzy alarming system (NFABT) for blood transfusion requirements. Alarming decisions using the Internet of Things (IoT) gateway are delivered to the physician for performing medical actions. Also, NFABT is considered a real-time non-invasive AI-based hemoglobin monitoring and alarming method. Results show the merits of the proposed method.

Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart.

Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic Tlymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication. ICI-mediated myocarditis (ICI-myocarditis) is a growing clinical entity given the widespread use of ICIs, its increased clinical recognition and growing use of combination ICI treatment, a well-documented risk factor for ICI-myocarditis. In this Review, we approach ICI-myocarditis from a basic and mechanistic perspective, synthesizing the recent data from both preclinical models and patient samples. We posit that mechanistic understanding of the fundamental biology of immune-checkpoint molecules may yield new insights into disease processes, which will enable improvement in diagnostic and therapeutic approaches. The syndrome of ICI-myocarditis is novel, and our understanding of immune checkpoints in the heart is in its nascency. Yet, investigations into the pathophysiology will inform better patient risk stratification, improved diagnostics and precision-based therapies for patients.

Understanding Internalized Stigma’s Role in Sex-Specific Suicidal Ideation among Individuals with Bipolar Disorder

Background: The experience of stigma can exert a profound impact on the mental health and well-being of individuals with bipolar disorder (BD). Our study explores which factors of internalized stigma are associated with suicidal ideation and how they differ between the two sexes in a clinical sample of BD patients. Methods: The study follows a cross-sectional study design, employing the Clinical Global Impression for Bipolar Patients (CGI-BP) to evaluate the overall severity of illness and the alteration in patients affected by bipolar disorder, the Internalized Stigma of Mental Illness (ISMI) assessing self-stigma among individuals experiencing mental disorders, and the Columbia Suicide Severity Rating Scale (C-SSRS) identifying and assessing individuals vulnerable to suicide. Descriptive analyses, analysis of variance (ANOVA), and logistic regression analysis were conducted, and 344 BD subjects were recruited. Results: Our ANOVA results revealed a significant association between sex and suicide across ISMI sub-items (p = 0.000). Logistic regression analysis comprised three phases: Discrimination was consistently significant across all phases (p < 0.001), while Alienation and Stereotype emerged as additional predictors of suicide in later phases of the analysis (p < 0.001). Conclusions: Our study contributes to the growing body of literature on internalized stigma, sex, and suicidality among individuals with bipolar disorder. Early intervention programs and prevention strategies are needed.

Impact of linkage level on inferences from big data analyses in health and medical research: an empirical study

BackgroundLinkage errors that occur according to linkage levels can adversely affect the accuracy and reliability of analysis results. This study aimed to identify the differences in results according to personally identifiable information linkage level, sample size, and analysis methods through empirical analysis.MethodsThe difference between the results of linkage in directly identifiable information (DII) and indirectly identifiable information (III) linkage levels was set as III linkage based on name, date of birth, and sex and DII linkage based on resident registration number. The datasets linked at each level were named as databaseIII (DBIII) and databaseDII (DBDII), respectively. Considering the analysis results of the DII-linked dataset as the gold standard, descriptive statistics, group comparison, incidence estimation, treatment effect, and moderation effect analysis results were assessed.ResultsThe linkage rates for DBDII and DBIII were 71.1% and 99.7%, respectively. Regarding descriptive statistics and group comparison analysis, the difference in effect in most cases was “none” to “very little.” With respect to cervical cancer that had a relatively small sample size, analysis of DBIII resulted in an underestimation of the incidence in the control group and an overestimation of the incidence in the treatment group (hazard ratio [HR] = 2.62 [95% confidence interval (CI): 1.63–4.23] in DBIII vs. 1.80 [95% CI: 1.18–2.73] in DBDII). Regarding prostate cancer, there was a conflicting tendency with the treatment effect being over or underestimated according to the surveillance, epidemiology, and end results summary staging (HR = 2.27 [95% CI: 1.91–2.70] in DBIII vs. 1.92 [95% CI: 1.70–2.17] in DBDII for the localized stage; HR = 1.80 [95% CI: 1.37–2.36] in DBIII vs. 2.05 [95% CI: 1.67–2.52] in DBDII for the regional stage).ConclusionsTo prevent distortion of the analyses results in health and medical research, it is important to check that the patient population and sample size by each factor of interest (FOI) are sufficient when different data are linked using DBDII. In cases involving a rare disease or with a small sample size for FOI, there is a high likelihood that a DII linkage is unavoidable.

Exploring a Desirable Quadr-mRNAs Panel for Non-invasive and Ultrasensitive Bladder Cancer Diagnosis: In-silico and Clinical Studies.

Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.

Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis

The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.

Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti's crystalline dystrophy.

Abnormalities in lipid metabolism have been proposed in Bietti's crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study. All participants were genetically confirmed by CYP4V2 gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites. Routine lipids profiles showed elevated plasma levels of triglyceride (P = 0.043) and low-density lipoprotein cholesterol (P = 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6, P = 0.00068) and eicosapentaenoic acid (EPA, 20:5, P = 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4, P < 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (P < 0.0001) between BCD patients and controls. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4. BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease. What is known BCD is a vision-threatening hereditary disease the causative gene of which is CYP4V2. Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies. The detailed pathogenesis remains unclear and controversial. What is new We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls. BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA). Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.

Evaluating associations between patient-to-nurse ratios and mortality, process of care events and vital sign documentation on paediatric wards: a secondary analysis of data from the EPOCH cluster-randomised trial

ObjectiveTo describe the associations between patient-to-nurse staffing ratios and rates of mortality, process of care events and vital sign documentation.DesignSecondary analysis of data from the evaluating processes of care and...

JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma

BackgroundAccurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two.Methods and materialsThe relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis.ResultsImmunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity.ConclusionOur study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy)indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Plasmodium vivax populations in the western Greater Mekong Subregion evaluated using a genetic barcode.

An improved understanding of the Plasmodium vivax populations in the Great Mekong Subregion (GMS) is needed to monitor the progress of malaria elimination. This study aimed to use a P. vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics and explore the gene flow among P. vivax parasite populations in the western GMS (China, Myanmar and Thailand). A total of 315 P. vivax patient samples collected in 2011 and 2018 from four regions of the western GMS were genotyped for 42 SNPs using the high-throughput MassARRAY SNP genotyping technology. Population genetic analysis was conducted to estimate the genetic diversity, effective population size, and population structure among the P. vivax populations. Overall, 291 samples were successfully genotyped at 39 SNPs. A significant difference was observed in the proportion of polyclonal infections among the five P. vivax populations (P = 0.0012, Pearson Chi-square test, χ2 = 18.1), with western Myanmar having the highest proportion (96.2%, 50/52) in 2018. Likewise, the average complexity of infection was also highest in western Myanmar (1.31) and lowest in northeast Myanmar (1.01) in 2018. The older samples from western China in 2011 had the highest pairwise nucleotide diversity (π, 0.388 ± 0.046), expected heterozygosity (He, 0.363 ± 0.02), and the largest effective population size. In comparison, in the neighboring northeast Myanmar, the more recent samples in 2018 showed the lowest values (π, 0.224 ± 0.036; He, 0.220 ± 0.026). Furthermore, the 2018 northeast Myanmar parasites showed high and moderate genetic differentiation from other populations with FST values of 0.162-0.252, whereas genetic differentiation among other populations was relatively low (FST ≤ 0.059). Principal component analysis, phylogeny, and STRUCTURE analysis showed that the P. vivax population in northeast Myanmar in 2018 substantially diverged from other populations. Although the 42 SNP barcode is a valuable tool for tracking parasite origins of worldwide parasite populations, a more extended barcode with additional SNPs is needed to distinguish the more related parasite populations in the western GMS.

Emergency Hospital Admissions of Elderly Patients with Dementia: General Characteristics, Outcome, and Areas of Improvement at an Accident and Emergency Department

Aim: Age-related disorders, such as dementia, are relevant for healthcare services and health systems worldwide. The prevalence of dementia across European countries is estimated to exceed 7 %, and may rise over time. Those patients are at increased risk for hospital admission and prolonged hospitalization, and such care increases the cost for the healthcare system. Less is known regarding patients with dementia in Greece that visit the Accident and Emergency departments (A&amp;E) in general hospitals. The present retrospective study aimed to address this issue. Subjects and methods: The sample of patients and the control group were traced in the A&amp;E department of the University Hospital of Ioannina, Northwest Greece. The study sample consisted of 100 patients with dementia, aged &gt; 65 years and 100 matched controls. The median age of patients with dementia was 85 years, for the control group 83 years, and 63 % were females. In most cases the diagnosis had been made by primary care physicians, and in of patients 21 % by neurologists/psychiatrists. Results: In both groups a median of 2 comorbidities was recorded, with hypertension, heart failure and dyslipidaemia being the most common. Fever and falls were the most common reasons for dementia patients visiting the A&amp;E department. Infection was the most common diagnosis in dementia patients, whereas in 17 % of cases no diagnosis was made and no interventions were needed. The probability of admission after an A&amp;E visit was significantly higher for the dementia group, whereas there were no differences regarding length of hospital stay between patients and controls. Conclusions: The results of the study are in line with international research and highlight the need for the establishment of a national register for patients with dementia, that would enable information exchange between primary and tertiary care and would enable proper diagnosis, management and discharge arrangements.

Savižudiškų minčių intensyvumo skalė (SIDAS) ir Savižudiško elgesio klausimynas – patikslintas (SBQ-R): lietuviškų versijų psichometriniai rodikliai

The Suicidal Ideation Attributes Scale (SIDAS) and the Suicidal Behaviors Questionnaire-Revised (SBQ-R) are widely used psychological instruments for assessing people‘s suicidal ideation and suicidal behavior. The aim of this study was to examine the psychometric characteristics of the Lithuanian versions of the SIDAS and SBQ-R. We analysed data collected from four samples: a Lithuanian general population quota sample based on age, gender and place of residence (N = 697, 52.9% women, aged 18–79 years); a sample of students (N = 2013, 72 % women, aged 18–29 years); a clinical sample of suicidal patients (N = 35, 77.1% women, aged 18–59 years); and a test-retest sample of students who completed the instruments twice within a two-week period (N = 54, 70.4% women, aged 18–47 years). The participants answered questions on gender, and age and completed the SIDAS and SBQ-R. The data analysis revealed that the Lithuanian versions of the SIDAS and SBQ-R have good internal consistency, temporal stability, construct, convergent, and criterion validity. The Lithuanian versions of the SIDAS and SBQ-R can be used to measure suicidality in research settings, as well as in clinical work as auxiliary tools.

Bromodomain-containing 4 is a positive regulator of the inflammatory cytokine response in the gut.

Bromodomain-containing protein 4 (BRD4), one of the components of the bromodomain and extraterminal domain (BET) family, is a transcriptional and epigenetic regulator of cellular proliferation and cytokine production. In this study, we assessed whether BRD4 regulates the cytokine response in inflammatory bowel diseases (IBD). BRD4 expression was analyzed in intestinal mucosal samples of patients with ulcerative colitis (UC), patients with Crohn's disease (CD), normal controls (CTRs), and mice with chemically-induced colitis by real-time PCR, Western blotting, and confocal microscopy. Cytokine production was evaluated in lamina propria mononuclear cells (LPMCs) of IBD patients and mucosal tissues of colitic mice treated with BRD4 inhibitors. Finally, we evaluated the effect of JQ1, an inhibitor of the BRD4 signaling pathway, on the course of murine colitis. BRD4 RNA and protein expression was up-regulated in the inflamed mucosa of patients with UC and patients with CD as compared to the uninvolved areas of the same patients and CTRs, and in the inflamed colon of colitic mice. Knockdown of BRD4 with a specific antisense oligonucleotide in IBD LPMCs led to reduced expression of TNF-α, IL-6, IFN-γ, and IL-17A. Administration of JQ1 to colitic mice inhibited the inflammatory cytokine response and attenuated the ongoing colitis. This is the first study showing the up-regulation of BRD4 in IBD and suggesting the role of such a protein in the positive control of the inflammatory cytokine response in the gut.

Suppressing SENP1 inhibits esophageal squamous carcinoma cell growth via SIRT6 SUMOylation.

Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear. Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro. Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion. SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC.

Clinical diagnostic value of targeted next‑generation sequencing for infectious diseases (Review).

As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next‑generation sequencing (mNGS) is increasingly used. This shift underscores the growing need for more cost‑effective and universally accessible sequencing assays to improve patient care and public health. Therefore, targeted NGS (tNGS) is gaining prominence. tNGS involves enrichment of target pathogens in patient samples based on multiplex PCR amplification or probe capture with excellent sensitivity. It is increasingly used in clinical diagnostics due to its practicality and efficiency. The present review compares the principles of different enrichment methods. The high positivity rate of tNGS in the detection of pathogens was found in respiratory samples with specific instances. tNGS maintains high sensitivity (70.8‑95.0%) in samples with low pathogen loads, including blood and cerebrospinal fluid. Furthermore, tNGS is effective in detecting drug‑resistant strains of Mycobacterium tuberculosis, allowing identification of resistance genes and guiding clinical treatment decisions, which is difficult to achieve with mNGS. In the present review, the application of tNGS in clinical settings and its current limitations are assessed. The continued development of tNGS has the potential to refine diagnostic accuracy and treatment efficacy and improving infectious disease management. However, further research to overcome technical challenges such as workflow time and cost is required.

Monocyte infiltration is an independent positive prognostic biomarker in vulvar squamous cell carcinoma

BackgroundVulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment.MethodsA total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan–Meier analyses).ResultsHealthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR−CD11c−CD14+CD68−CD163−CD33−) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001).ConclusionA hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC.

Development and validation study of compact biophotonic platform for detection of serum biomarkers

The application of advances in personalized medicine requires the support of in vitro diagnostic techniques aimed at the accurate, fast, sensitive, and precise determination of selected biomarkers. Herein, a novel optical centrifugal microfluidic device is developed for clinical analysis and point-of-care diagnostics. Based on compact disc technology, the integrated biophotonic system enables multiple immunoassays in miniaturized mode. The disposable microfluidic discs are made in cyclic olefin copolymer (COP), containing arrays of immobilized probes. In the developed approach, up to six patient samples can each be tested simultaneously. A portable instrument (< 2 kg) controls the assay and the high-sensitive reproducible optical detection in transmission mode. Also, the instrument incorporates specific functionalities for personalized telemedicine.The device (analytical method, disc platform, reader, and software) has been validated to diagnose IgE-mediated drug allergies, such as amoxicillin and penicillin G. The total and specific IgE to β-lactam antibiotics were determined in human serum from patients (25 μL). The excellent analytical performances (detection limit 0.24 ng/mL, standard deviation 7-20%) demonstrated that the developed system could have the potential for a broader impact beyond the allergy field, as it applies to other IVD tests.

Biometric description of 34 589 eyes undergoing cataract surgery: sex differences.

To describe gender differences in the biometric parameters of a large sample of patients with cataract. Cataract surgery has evolved from a vision restoration to a refractive procedure, and population-based studies are vital to optimize normative databases and postsurgical outcomes. Miguel Servet University Hospital, Zaragoza, Spain. Retrospective single-center observational study. The study included 34 589 eyes (20 004 patients with cataract). Biometric data were obtained from IOL Master 700 and Pentacam HR. Linear mixed models were used to account for intereye correlation. HofferQST formula was used to calculate the hypothetical distribution of intraocular lens (IOL) power (arbitrary lens; A = 119.2). Most biometric variables showed significant differences between sexes ( P < .0001), such as 0.53 mm shorter eyes found in females, of which 0.16 mm are explained by shorter aqueous depth. Steeper anterior keratometries (∼0.75 diopter [D]) were found in women, to end up in no difference on anterior astigmatism magnitude, but different orientation ( P < .0001). The distribution of IOL power differed between sexes ( P < .001), with the interquartile range shifting 1 D toward more powerful lenses in women and odds ratio (power >26 D) = 2.26, P < .0001 (Fisher). Large sample size studies provide smaller margin of error, higher power, and controlled risk of reporting false (negative or positive) findings. Highly significant differences between sexes in ocular biometry were found; this supports the idea that including sex as a parameter in IOL calculation should be explored and may improve results. In addition, the distribution of IOL powers was provided, which may be useful for manufacturers and hospital stock planning.

Causes of Visual Impairment in a Sample of Adult Iraqi Patients

Purpose: To identify causes of visual impairment in adult patients seeking treatment at teaching hospital in Iraq. Study Design: Descriptive observational. Place and Duration of Study: Ibn Al-Haytham Teaching Eye Hospital (IAHTEH) in Baghdad, Iraq during the year 2023. Methods: This study comprised of 125,804 adults. All the participants had comprehensive history and ocular examination. Mild, moderate and sever visual impairment were defined as from 6/9 to 6/18, 6/24 to 6/36 and 6/60 or below respectively. Results: Among 125,804 patients, the breakdown of conditions was as follows: 60,650 (48%) had cataracts, 37,741 (30%) had refractive errors, 12,071 (10%) had diabetic retinopathy, 8,328 (7%) had glaucoma, and 7,014 (5%) had experienced trauma. Most patients (54%) had severe visual impairment, followed by moderate (29%) and mild (17%) impairment. The majority of cases (45%) were in individuals aged 60 years and older, with 26% in the 40-59 years age group and 29% in the 20-39 years age group. Diabetic retinopathy was most common in the 40-59 years age group, while glaucoma and cataracts were predominantly in those aged 60 and above. Refractive errors and trauma were mainly found in the 20-39 years age group. Females accounted for 63% of patients with reduced vision, whereas males predominated among trauma cases, with 29% of trauma cases involving blunt trauma. Conclusion: Cataract is the most prevalent condition in older patients. Younger adults frequently experience refractive errors and trauma. Females are more likely to have reduced vision, whereas males are more prone to trauma-related vision issues.