Count Threshold Research Articles

Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma.

Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics. This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study. The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL). Overall, 822 patients were included. CSEs occurred in 760 (93%) patients pre-treatment and 398 (49%) during follow-up. CSE rate (RR[95% CI]) was reduced in follow-up across all tIgE subgroups (<60 [n=173]: 0.31[0.25, 0.37]; 60-<190 [n=176]: 0.30[0.25, 0.36]; 190-<550 [n=170]: 0.26[0.20, 0.33]; ≥550 kU/L [n=155]: 0.28[0.23, 0.35]) and irrespective of atopic status (yes [n=422]: 0.29[0.26, 0.33]; no [n=52]: 0.33[0.23, 0.47]; unknown [n=348]: 0.28[0.24, 0.32]), prior omalizumab use (yes [n=151]: 0.37[0.30, 0.45]; no [n=671]: 0.27[0.24, 0.30]) or eligibility (eligible (n=349): 0.29[0.25, 0.34]; non-eligible [n=191]: 0.32[0.27, 0.38]). Furthermore, the CSE rate was reduced across all tIgE (kU/L) and BEC (cells/µL) combinations (<81/<300 [n=53]: 0.34[0.24, 0.47], <81/≥300 [n=103]: 0.33[0.26, 0.41], ≥81/<300 [n=98]: 0.36[0.28, 0.47], ≥81/≥300 [n=249]: 0.26[0.22, 0.31]). Mepolizumab demonstrates real-world effectiveness in reducing exacerbations in patients with severe asthma and an eosinophilic phenotype, regardless of any overlapping allergic phenotype.

Establishing Minimally Important Difference Thresholds for Lesion Counts in Acne Clinical Studies

Establishing Minimally Important Difference Thresholds for Lesion Counts in Acne Clinical Studies

Improving the arthritis component of the SLEDAI-2K.

To propose a new definition for SLEDAI arthritis informed by imaging. We performed a planned secondary analysis of observational data from a multicentre study evaluating SLE patients with inflammatory joint pain (swelling not required) using various clinical instruments, laboratory tests and ultrasound. For SLEDAI arthritis, assessors (blinded to ultrasound) were asked which of the glossary terms for arthritis in any version of the SLEDAI drove their decision to score for arthritis. These definitions were tested against ultrasound and other clinical variables. ROC-analysis was used to test optimal joint count thresholds. 78/133 patients had arthritis on SLEDAI-2K. In 21/78, clinician-observed swelling was not a reason for scoring (tenderness : 16/21; reported swelling between visits : 4/21; both of these : 1/21). No patient was scored for warmth or erythema alone. 57 (73.1%) of patients were scored for SLEDAI-arthritis due to observed swelling, 90% had abnormal ultrasound (PPV = 90%, 95%CI : 79,94). Of 21 patients with SLEDAI-arthritis without observed swelling, 48% had abnormal ultrasound (PPV : 48%, 95%CI : 31,67). Patients with SLEDAI-arthritis with swelling had higher ESR, Physician MSK-VAS, patient Early Morning Stiffness (EMS)-VAS and IgG compared with other patients. Optimal sensitivity and specificity for ultrasound synovitis was 1 swollen joint using Youden's criteria. Our data suggest that the definition of arthritis in SLEDAI be modified to: "Inflammatory musculoskeletal pain (symmetrical small joint distribution) with one or more clinically swollen joints that is not explained by another arthropathy".

Immunophenotyping for the Assessment of Asymptomatic Lymphocytosis: A Retrospective Analysis and National Survey.

Asymptomatic lymphocytosis poses a common challenge in haematology. Immunophenotyping can establish whether a clonal population is present, but it is expensive and the benefit of diagnosing asymptomatic patients is unproven. This study aimed to establish data to guide the use of immunophenotyping. We analysed the proportion of lymphocytosis in full blood count (FBC) samples across a five-year period within a large UK National Health Service (NHS) trust. Persistent lymphocytosis was present in 0.18% (437/242678) of repeat community samples. Of samples sent for immunophenotyping, 743/784 (95%) with a lymphocyte count > 10 × 109/L had a clonal population, compared to 223/1696 (14%) with a lymphocyte count < 5 × 109/L. We followed up a longitudinal cohort of asymptomatic patients with clonal lymphocytosis to determine how many required treatment. The minority (11/46) of patients needed treatment within 9 years of follow-up. Of patients needing treatment, 10/11 (91%) had a presenting lymphocyte count > 10 × 109/L. In all cases, treatment was initiated when the patient became symptomatic. We propose a lymphocyte count threshold of > 10 × 109/L for referral and immunophenotyping in patients with asymptomatic lymphocytosis. This approach aims to balance safety and cost-effectiveness and reflects uncertainty in the value of diagnosis for asymptomatic patients.

Anti-Mullerian Hormone and Antral Follicle Count Thresholds for Hyper-Response Risk Assessment in IVF: A HERA Consensus Study

ObjectiveTo determine the serum anti-Müllerian-hormone (AMH) and antral follicle count (AFC) thresholds indicating an increased risk of hyper-response to ovarian stimulation (OS) during in-vitro-fertilization (IVF), as defined by the HERA (Hyper-response Risk Assessment) Delphi Consensus. DesignA retrospective multicenter cohort study. SubjectsIncluded were women with normal ovarian reserve markers according to Poseidon’s criteria (AMH≥1.2ng/mL and an AFC≥5) undergoing their first IVF/ICSI cycle with conventional OS (follicle-stimulating-hormone (FSH)≥150IU/day) using the GnRH-antagonist protocol (2015-2017). ExposureHyper-response was defined as ≥15 retrieved oocytes, based on the HERA definition, compared to non-HERA hyper-responders, defined as patients with ovarian reserve markers within the normal range per the POSEIDON criteria and with <15 oocytes retrieved. Main Outcome MeasuresThe primary outcome was the AMH and AFC threshold values, indicating increased risk for a hyper-response, utilizing receiver operator characteristic (ROC) curves. Outcomes were further stratified by patients’ age (<35 and ≥35 years). Multivariable logistic regression explored factors associated with a HERA hyper-response. ResultsIncluded were 4220 patients, of which 2132 (50.5%) were hyper-responders. ROCs revealed the following thresholds for a hyper-response: AMH≥4.38ng/mL (AUC 0.71) and an AFC≥16 (AUC 0.80) for the entire cohort; AMH≥4.95ng/mL (AUC 0.68) and an AFC≥18 (AUC 0.76) for women <35 years (N=3056); and AMH≥4.33ng/mL (AUC 0.77) and an AFC≥15 (AUC 0.86) for women ≥35 years (N=1164). Older women received higher median daily and total FSH doses than younger women. AMH, AFC, female age, daily/total gonadotropin dose, type of gonadotropin, and trigger strategy were significant predictors for hyper-response. ConclusionAMH and AFC values at and above these thresholds warrant increased caution when planning gonadotropin dosing, regimen, and trigger strategies before OS. These thresholds were lower in older women, potentially due to higher FSH dosing in this population.

Maternal thrombocytopenia is not predictive of neonatal thrombocytopenia: a single-center Irish study

BackgroundMaternal thrombocytopenia during pregnancy is common. However, the relationship between maternal and neonatal thrombocytopenia is poorly understood. ObjectivesWe aimed to determine whether an association exists between platelet counts of neonates born to mothers with moderate-to-severe thrombocytopenia (<100 × 109/L) and neonatal platelet counts. MethodsWe identified records from 557 patients with moderate-to-severe thrombocytopenia (maternal platelet count <100 × 109/L) and the 338 associated newborn charts from 2018 to 2022 in a single large maternity center. Pregnant people with a platelet count of <100 × 109/L prior to delivery during present gestation were included. Any thrombocytopenia that occurred outside of pregnancy or in the postpartum period was excluded. A logistic regression was then generated to examine the association between maternal thrombocytopenia and neonatal thrombocytopenia. A receiver operating characteristic (ROC) curve was generated to assess accuracy of (i) lowest maternal platelet count and (ii) trimester of thrombocytopenia onset in predicting neonatal thrombocytopenia. ResultsA total of 550 full blood count assessments were taken in neonates of pregnant people with thrombocytopenia. Sixteen neonates with clinically significant thrombocytopenia (platelet count <100 × 109/L) were identified. A binomial logistic regression was fitted that demonstrated limited association between lowest maternal platelet count and trimester of onset of maternal thrombocytopenia and the development of neonatal thrombocytopenia. An ROC curve was generated to determine the accuracy of maternal platelet count at identifying neonatal thrombocytopenia. The coordinates of the best platelet count threshold for this dataset were then derived from the ROC curve and determined that a threshold of 77.5 × 109/L maternal platelets offered the best accuracy. ConclusionNeonatal full blood count assessment based on maternal platelet counts of <100 × 109/L has a poor diagnostic yield with no statistically significant association in this cohort on logistic regression analysis. A lower threshold of 77.5 × 109/L may be of higher clinical utility and improve laboratory and clinical workflow.

HIV disease progression among heterosexually-infected individuals before the introduction of universal ART in China: A linear mixed-effects model.

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm3. From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV.

Platelet transfusion in neonatal intensive care units of 22 European countries: a prospective observational study

Platelet transfusions are given to preterm infants with severe thrombocytopenia aiming to prevent haemorrhage. The PlaNeT2/MATISSE trial revealed higher rates of mortality and/or major bleeding in preterm infants receiving prophylactic platelet transfusions at a platelet count threshold of 50×109/L compared to 25×109/L. The extent to which this evidence has been incorporated into clinical practice is unknown, thus we aimed to describe current neonatal platelet transfusion practices in Europe. We performed a prospective observational study in 64 neonatal intensive care units across 22 European countries between September 2022 and August 2023. Outcome measures included observed transfusion prevalence rates (per country and overall, pooled using a random effects Poisson model), expected rates based on patient-mix (per country, estimated using logistic regression), cumulative incidence of receiving a transfusion by day 28 (with death and discharge considered as competing events), transfusion indications, volumes and infusion rates, platelet count triggers and increment, and adverse effects. We included 1143 preterm infants, of whom 71 (6.2%, [71/1143]) collectively received 217 transfusions. Overall observed prevalence rate was 0.3 platelet transfusion days per 100 admission days. By day 28, 8.3% (95% CI: 5.5-11.1) of infants received a transfusion. Most transfusions were indicated for threshold (74.2%, [161/217]). Pre-transfusion platelet counts were above 25×109/L in 33.1% [53/160] of these transfusions. There was significant variability in volume and duration. The restrictive threshold of 25×109/L is being integrated into clinical practice. Research is needed to explore existing variation and generate evidence for various aspects including optimal volumes and infusion rates. Sanquin, EBA, and ESPR.

Prognostic value of a modified pathological staging system for gastric cancer based on the number of retrieved lymph nodes and metastatic lymph node ratio.

The prognosis for gastric cancer (GC) remains grim, underscoring the importance of accurate staging and treatment. Given the potential benefits of using lymph node ratio (LNR) for improved prognostication and treatment planning, it is critical to incorporate examined lymph nodes (ELN) count in an integrated GC staging system. Patients data from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 was utilized as training set. The Mantel-Cox survival test was used to calculate chi-square values for 40 LNR segments with a 0.025 interval, defining a novel LNR-based N (rN) classification based on the cutoff points. A revised AJCC (rAJCC) staging system was established by replacing the 8th AJCC N staging with a rN classification. The relationship between the ELN count and prognosis or positive lymph node detection was conducted by using multivariable models. The series of the odds ratios and hazard ratios were fitted with a locally weighted scatterplot smoothing (LOWESS) smoother, and the structural break points were determined by Chow test to clarify an optimal minimum ELN count. The integrated GC staging system incorporated both rAJCC system and the ideal ELN count. Discriminatory ability and prognostic homogeneity of the rAJCC and integrated staging system was compared with AJCC staging system in the SEER validation set (2016-2017), the Cancer Genome Atlas Program (TCGA) database, and the Third Affiliated Hospital of Sun Yat-sen University database. The current study found that LNR and ELN count are both significantly associated with the prognosis of GC patients (HR = 0.98, p < 0.001 and HR = 2.51, p < 0.001). Four peaks of the chi-square value were identified as LNR cut-off points at 0.025, 0.175, 0.45 and 0.6 to define a novel rN stage. In comparison to the 8th AJCC staging system, the rAJCC staging system demonstrated significant prognostic advantages and discriminatory ability in the training set (5-Y OS AUC: 71.7 vs. 73.0; AIC: 57,290.7 vs. 57,054.9). The superiority of the rAJCC staging system was confirmed in all validation sets. Using a LOWESS smoother and Chow test, a threshold ELN count of 30 was determined to maximum improvement in the prognosis of node-negative patients without downgrading due to potential metastasis, while also maximizing the detection efficiency of at least one involved lymph node. The integrated staging system, combining the refined rAJCC classification with an optimized ELN count threshold, has demonstrated superior discriminatory performance compared to the standalone rAJCC or the traditional AJCC system. The development of a novel GC staging system, which integrated the LNR-based N classification and the minimum ELN count, has exhibited superior prognostic accuracy, holding promise as a valuable asset in the clinical management of GC. However, it is crucial to recognize the limitations from the retrospective database, which should be addressed in subsequent analyses.

Characterization of fine geographic scale population genetics in sugar kelp (Saccharina latissima) using genome-wide markers

BackgroundKelps are not only ecologically important, being primary producers and habitat forming species, they also hold substantial economic potential. Expansion of the kelp cultivation industry raises the interest for genetic improvement of kelp for cultivation, as well as concerns about genetic introgression from cultivated to wild populations. Thus, increased understanding of population genetics in natural kelp populations is crucial. Genotyping-by-sequencing (GBS) is a powerful tool for studying population genetics. Here, using Saccharina latissima (sugar kelp) as our study species, we characterize the population genetics at a fine geographic scale, while also investigating the influence of marker type (biallelic SNPs versus multi-allelic short read-backed haplotypes) and minor allele count (MAC) thresholds on estimated population genetic metrics.ResultsWe examined 150 sporophytes from 10 locations within a small area in Mid-Norway. Employing GBS, we detected 20,710 bi-allelic SNPs and 42,264 haplotype alleles at 20,297 high quality GBS loci. We used both marker types as well as two MAC filtering thresholds (3 and 15) in the analyses. Overall, higher genetic diversity, more outbreeding and stronger substructure was estimated using haplotypes compared to SNPs, and with MAC 15 compared to MAC 3. The population displayed high genetic diversity (HE ranging from 0.18–0.37) and significant outbreeding (FIS ≤ − 0.076). Construction of a genomic relationship matrix, however, revealed a few close relatives within sampling locations. The connectivity between sampling locations was high (FST ≤ 0.09), but subtle, yet significant, genetic substructure was detected, even between sampling locations separated by less than 2 km. Isolation-by-distance was significant and explained 15% of the genetic variation, while incorporation of predicted currents in an “isolation-by-oceanography” model explained a larger proportion (~ 27%).ConclusionThe studied population is diverse, significantly outbred and exhibits high connectivity, partly due to local currents. The use of genome-wide markers combined with permutation testing provides high statistical power to detect subtle population substructure and inbreeding or outbreeding. Short haplotypes extracted from GBS data and removal of rare alleles enhances the resolution. Careful consideration of marker type and filtering thresholds is crucial when comparing independent studies, as they profoundly influence numerical estimates of population genetic metrics.

A Novel Directed Seed-Based Connectivity Analysis Toolbox Applied to Human and Marmoset Resting-State FMRI.

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the language-network that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis.

Malignant Neoplasm of the Meninges: A 20-Year Retrospective Study to Assess Trends and Disparities in Place of Death.

The site of death is a crucial factor associated with the tumor's progression and complications arising from it; therefore, analyzing nationwide patterns in place of death is essential. The present paper aims to evaluate the disparities in place of death for malignant neoplasm of the meninges using the CDC-WONDER (Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research) database over 22 years (1999-2020). CDC-WONDER data from 1999 to 2020 were analyzed to investigate mortality trends related to malignant neoplasm of the meninges. Data selection ensured inclusivity of all races, with confidentiality and death count thresholds considered. Demographics encompassed Census Regions, all genders, races, and 10-year age groups, along with a five-year forecast. MicrosoftExcel (Microsoft Corporation, Redmond, Washington) and R Software (R Foundation, Boston, Massachusetts) were used for data processing and statistical analysis, with visualization through ARIMA modeling. Cumulative home and hospice deaths were analyzed based on overall age, gender, race, and region, demonstrating that home and hospice deaths increased overall, particularly in the 65-74 and 75-84 age groups, and more so in females. White individuals showed increasing trends, while Black or African American individuals remained stable. Regionally, the South had the highest increase, while the Northeast remained stagnant. There is a concerning upward trend in home or hospice deaths among individuals with malignant neoplasm of the meninges, particularly within the 65-84 age group, in females, among White individuals, and in the Southern region. More comprehensive data is needed, and further research must be conducted to understand the underlying causes for the rise in these demographics and to improve healthcare facilities.

The prognostic effect of blast count in TP53 mutant myeloid neoplasms –the Minnesota experience

In 2022, the World Health Organization (WHO) and International Consensus Classification (ICC) recognized TP53 as an entity-defining alteration in myeloid neoplasms, yet with differing criteria that could lead to discrepant diagnoses and affect clinical trial eligibility. We studied 67 patients with TP53 mutant myeloid neoplasms, reclassifying them using both criteria. While most cases fulfill the criteria for TP53 mutant defined entities, most discrepancies were found in cases with ≥20% blasts. Patients were stratified into three groups based on blast count (<10%, 10–19%, and ≥20%) which revealed comparable clinicopathologic features, genetic characteristics, and outcomes. Notably, patients with ≥10% blasts had shorter overall survival compared to those with <10% blasts (8.1 vs. 12.4 months; p = 0.03). This study is among the few to examine TP53 mutant myeloid neoplasms as a single entity and suggests that the 10% blast count threshold could serve as a gateway to a more harmonized classification for these patients.

Optimizing central venous access devices insertion in thrombocytopenic patients: Balancing efficacy and safety.

Recently, the rising incidence of trauma, cancer, and critical illnesses has led to a growing necessity for Central Venous Access Devices (CVADs). Inserting CVADs in thrombocytopenic patients is still challenging. This study tries to shed light on the safety and associated risks of CVADs insertion in this high-risk group, with the ultimate goal of informing clinical practice and aiding in decision-making processes. This study was conducted as prospective cohort study from September 2020 to September 2023 in Mazandaran University of Medical Sciences, Iran. Individuals aged 18-80 years with a platelet count of less than 50,000/dL included and those designated for subcutaneous port procedures or on anticoagulant and antiplatelet therapy, excluded. Ultrasound-guided CVAD insertion using the Seldinger technique and SIC/FIC strategies performed for participants. Incidence of hemorrhagic complications post-CVAD insertion, requirement for blood product transfusions to amend platelet counts, frequency of non-bleeding complications, and complications related to blood product transfusions monitored. The study comprised 137 participants, 54% of whom were men, with an average age of 46.90 ± 15.70 years. No significant correlation was found between the site of CVAD placement (jugular vs femoral) and the incidence of major or minor bleeding. Femoral catheters were associated with a higher rate of infection. No complications related to transfusion of blood products or mortality seen, indicating that CVAD implantation can be safely performed in patients with thrombocytopenia or coagulation disorders. CVAD insertion in thrombocytopenic patients, even with platelet counts below 10 × 109/L, is safe and associated with minimal complications when performed under ultrasound guidance by experienced surgeons. This finding supports the use of a lower platelet count threshold for CVAD insertion than currently recommended in guidelines, potentially reducing the need for platelet transfusions prior to CVAD placement.

Event-responsive scanning transmission electron microscopy.

An ever-present limitation of transmission electron microscopy is the damage caused by high-energy electrons interacting with any sample. By reconsidering the fundamentals of imaging, we demonstrate an event-responsive approach to electron microscopy that delivers more information about the sample for a given beam current. Measuring the time to achieve an electron count threshold rather than waiting a predefined constant time improves the information obtained per electron. The microscope was made to respond to these events by blanking the beam, thus reducing the overall dose required. This approach automatically apportions dose to achieve a given signal-to-noise ratio in each pixel, eliminating excess dose that is associated with diminishing returns of information. We demonstrate the wide applicability of our approach to beam-sensitive materials by imaging biological tissue and zeolite.

Identifying risk factors for anal cancer in people with HIV in Spain: a multicentre retrospective cohort study nested in the PISCIS cohort

People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. Among 14 238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100 000 person-years (95% CI 59·4-87·6) and median follow-up of 9·5 years (IQR 4·4-15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per μL (IR 105·0 person-years, 95% CI 82·0-132·5) and lowest among those with counts of more than 350 cells per μL (2·9 person-years, 0·1-16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1-211·7) among those with a CD4 count of less than 200 cells per μL, 37·6 person-years (16·2-74·1) among those with a count of 200-350 cells per μL, and 4·8 person-years (0·1-26·9) among those with a count of more than 350 cells per μL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per μL (IR 4·8 person-years, 95% CI 0·1-26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per μL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per μL (adjusted IR ratio 0·03, 95% CI 0·00-0·25; p=0·0010) or 200-350 cells per μL (0·30, 0·17-0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7-206·9; p=0·0010) and people with HIV aged 45-59 years of 21·6 (3·0-156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9-137·5; p<0·0001). A nadir CD4 count threshold below 350 cells per μL, particularly less than 200 cells per μL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. Catalan Health Department, Generalitat de Catalunya.

Fully Automatic Quantitative Measurement of Equilibrium Radionuclide Angiocardiography Using a Convolutional Neural Network.

The aim of this study was to generate deep learning-based regions of interest (ROIs) from equilibrium radionuclide angiography datasets for left ventricular ejection fraction (LVEF) measurement. Manually drawn ROIs (mROIs) on end-systolic and end-diastolic images were extracted from reports in a Picture Archiving and Communications System. To reduce observer variability, preprocessed ROIs (pROIs) were delineated using a 41% threshold of the maximal pixel counts of the extracted mROIs and were labeled as ground-truth. Background ROIs were automatically created using an algorithm to identify areas with minimum counts within specified probability areas around the end-systolic ROI. A 2-dimensional U-Net convolutional neural network architecture was trained to generate deep learning-based ROIs (dlROIs) from pROIs. The model's performance was evaluated using Lin's concordance correlation coefficient (CCC). Bland-Altman plots were used to assess bias and 95% limits of agreement. A total of 41,462 scans (19,309 patients) were included. Strong concordance was found between LVEF measurements from dlROIs and pROIs (CCC = 85.6%; 95% confidence interval, 85.4%-85.9%), and between LVEF measurements from dlROIs and mROIs (CCC = 86.1%; 95% confidence interval, 85.8%-86.3%). In the Bland-Altman analysis, the mean differences and 95% limits of agreement of the LVEF measurements were -0.6% and -6.6% to 5.3%, respectively, for dlROIs and pROIs, and -0.4% and -6.3% to 5.4% for dlROIs and mROIs, respectively. In 37,537 scans (91%), the absolute LVEF difference between dlROIs and mROIs was <5%. Our 2-dimensional U-Net convolutional neural network architecture showed excellent performance in generating LV ROIs from equilibrium radionuclide angiography scans. It may enhance the convenience and reproducibility of LVEF measurements.

CD34+ cell yield among healthy donors: Large-scale model development and validation.

Successful engraftment in hematopoietic stem cell transplantation necessitates the collection of an adequate dose of CD34+ cells. Thus, the precise estimation of CD34+ cells harvested via apheresis is critical. Current CD34+ cell yield prediction models have limited reproducibility. This study aims to develop a more reliable and universally applicable model by utilizing a large dataset, enhancing yield predictions, optimizing the collection process, and improving clinical outcomes. A secondary analysis was conducted using the Center for International Blood and Marrow Transplant Research database, involving data from over 17 000 healthy donors who underwent filgrastim-mobilized hematopoietic progenitor cell apheresis. Linear regression, gradient boosting regressor, and logistic regression classification models were employed to predict CD34+ cell yield. Key predictors identified include pre-apheresis CD34+ cell count, weight, age, sex, and blood volume processed. The linear regression model achieved a coefficient of determination (R2) value of 0.66 and a correlation coefficient (r) of 0.81. The gradient boosting regressor model demonstrated marginally improved results with an R2 value of 0.67 and an r value of 0.82. The logistic regression classification model achieved a predictive accuracy of 96% at the 200 × 106 CD34+ cell count threshold. At thresholds of 400, 600, 800, and 1000 × 106 CD34+ cell count, the accuracies were 88%, 83%, 83%, and 88%, respectively. The model demonstrated a high area under the receiver operator curve scores ranging from 0.90 to 0.93. This study introduces advanced predictive models for estimating CD34+ cell yield, with the logistic regression classification model demonstrating remarkable accuracy and practical utility.

Comparison of MYOCYTER and MUSCLEMOTION in the analysis of Induced Pluripotent Stem Cell Derived Cardiomyocyte Contractility

Patient-specific induced pluripotent stem cells (iPSCs) differentiated into cardiomyocytes (CMs) offer tremendous opportunities for cardiac disease modeling and advancements in precision medicine. There is a need for technologies that allow noninvasive and precise measurements of CM function, such as contractility, to increase throughput for drug screening and testing efforts. Hypoplastic Left Heart Syndrome (HLHS) is a rare and complex congenital heart defect characterized by hypoplasia of the left ventricle, proximal aorta, as well as stenosis or atresia of the mitral and/or aortic valves. Previously it was demonstrated that iPSC-CMs from an HLHS patient with a genetic variant in the alpha myosin heavy chain ( MYH6 gene) exhibited an impaired cardiomyocyte phenotype (dysmorphic sarcomere structure, compensatory expression of MYH7, and altered contractility). Gene editing using CRISPR/Cas9 rescued the phenotype, demonstrating the utility of MYH6 iPSC-CMs as a useful disease model for HLHS. Critical parameters of CM function include contraction and relaxation, assessing systolic and diastolic dysfunction, respectively, in iPSC-CMs. The aim of this study is to compare features from two open-source macros for ImageJ: MYOCYTER and MUSCLEMOTION. MYOCYTER improves upon previous plugins available by allowing for users to select parameters. Both methods allow measurement of movement from high-speed movies. MYOCYTER enables the user to select an optimal threshold, size, and cell count to minimize disturbances such as cellular fragments, background noise, and floating bubbles, to maximize precision during analysis. MUSCLEMOTION allows rapid and easy measurement of movement from high- speed videos and can measure and compare relative or absolute parameters. This study will determine whether a systolic or diastolic dysfunction phenotype is observed under different magnification settings and evaluate the effect of dosing with pharmaceutical compounds. Finally, benefits and drawbacks of both macros will be investigated. Children's Research Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Parity and Somatic Cell Count Threshold on Udder Morphology, Milkability Traits, and Milk Quality in Canarian Goats.

The effects of parity and somatic cell count in milk (SCC) threshold on the udder morphology, milkability traits, and milk composition was evaluated in 41 Canarian goats in mid-lactation. The animals were divided according to parity (1st, 2nd, and 3rd), and a SCC threshold of 2000 × 103 cells/mL in milk was set to evaluate the effect of this factor on the different measured parameters. Results showed that primiparous goats had the udder smaller and less distended than multiparous goats, but no differences were detected on milk flow parameters. Furthermore, SCC and total bacterial count (TBC) tended to be higher when the parity increased. On the other hand, goats with SCC ≤ 2000 × 103 had higher cistern-floor distance (CF) and lower TBC values compared with those goats with a count above the predetermined threshold. The results suggest that a reduction in SCC can be achieved by a selection of udder morphological traits. Moreover, milk flow parameters do not seem to be a tool to determine the udder health status in Canarian goats, but long-term studies are needed to verify it.