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  • Open Access Icon
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  • Research Article
  • 10.21423/awlj-v30.a292
Female Faculty Members at Texas Community Colleges: Any Changes Since 2000?
  • Jul 30, 2025
  • Advancing Women in Leadership Journal
  • Dr John Slate + 1 more

In this study, the authors examined the extent to which the number and percentage of female faculty members employed full-time and part-time at Texas community colleges had changed from 2000 to 2006. Both the absolute number and percentage of female faculty members employed full-time and employed part-time had significantly increased over this 7 year time period. Females comprise more than half of the community college faculty members in the State of Texas. Implications of these findings for faculty diversity are discussed.

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  • Research Article
  • Cite Count Icon 1
  • 10.12932/ap-190822-1437
Improving cytokine-induced killer cell expansion using a gas-permeable culture method for clinical-scale production.
  • Jan 1, 2025
  • Asian Pacific journal of allergy and immunology
  • Supannikar Tawinwung + 8 more

Cytokine-induced killer (CIK) cells are a heterogeneous group of immune cells that exert potent MHC-unrestricted cytotoxicity toward various cancer cells in both solid and hematological malignancies. The purposes of this study were to compare the expansion and characteristics of cytokine-induced killer cells between a standard culture method and a gas-permeable culture method and to develop a clinical-scale expansion protocol for cytokine-induced killer cells using a gas-permeable culture method. We compared the absolute cell number, fold change, cell subsets, activation markers, cytokine concentrations, and cytotoxicity toward myeloid leukemia cell lines between cytokine-induced killer cells expanded using two different culture methods. Then, we determined the ability to achieve clinical-scale expansion of cytokine-induced killer cells using the gas-permeable culture method. Cytokine-induced killer cells in the gas-permeable culture method group exhibited significantly better expansion but maintained similar cell subsets, activation markers, and cytotoxicity to those in the standard culture method group. In addition, we successfully manufactured cytokine-induced killer cells for clinical use using the gas-permeable culture method. We also showed the clinical efficacy of allogeneic cytokine-induced killer cells produced by the gas-permeable culture method in a patient with acute myeloid leukemia that relapsed after allogeneic hematopoietic stem cell transplantation. This patient maintained ongoing disease remission for 2 years with minimal side effects after cytokine-induced killer cell infusion. We successfully developed a simple and effective protocol for the ex vivo expansion of cytokine-induced killer cells using the gas-permeable culture method for clinical application.

  • Research Article
  • Cite Count Icon 17
  • 10.2174/0115733998274323231230131843
Number of People with Type 2 Diabetes Mellitus in 2035 and 2050: A Modelling Study in 188 Countries.
  • Jan 1, 2025
  • Current diabetes reviews
  • Wilmer Cristobal Guzman-Vilca + 1 more

Future demographic changes will increase the number of people living with non-communicable diseases. We projected the number of people with type 2 diabetes mellitus (T2DM) in 2035 and 2050 at the global and country levels. We pooled T2DM prevalence estimates from the Global Burden of Disease Study and population estimates from the United Nations for 188 countries. We computed the absolute number of people with T2DM in 2020 and predicted the future number in 2035 and 2050 under four scenarios for the T2DM prevalence: 1) It held constant, 2) It increased by 50%, 3) It decreased by 10%, and 4) It followed 1990-2019 country-specific past trends. The global number of people with T2DM was 445 million in 2020, and it is projected to increase in 2050 to 730 million if prevalence remains unchanged, 1,095 million if prevalence increases by 50%, 657 million if prevalence decreases by 10%, and 1,153 million if prevalence follows country-specific 1990-2019 past trends. Under all scenarios, Sub-Saharan Africa and lowincome countries had the highest relative increase in the number of people with T2DM. The share of people with T2DM aged <60 years is expected to drop from 5 out of 10 in 2020 to 4 out of 10 people in 2050 under all scenarios. There will be a massive growth in the number of people living with T2DM, and low-income countries and countries in Sub-Saharan Africa will be the most affected. Health systems must be strengthened to ensure optimal care for the future population with T2DM.

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  • Cite Count Icon 6
  • 10.1080/14760584.2023.2299401
Modeling undetected poliovirus circulation following the 2022 outbreak in the United States
  • Dec 31, 2024
  • Expert Review of Vaccines
  • Dominika A Kalkowska + 8 more

ABSTRACT Background New York State (NYS) reported a polio case (June 2022) and outbreak of imported type 2 circulating vaccine-derived poliovirus (cVDPV2) (last positive wastewater detection in February 2023), for which uncertainty remains about potential ongoing undetected transmission. Research Design and Methods Extending a prior deterministic model, we apply an established stochastic modeling approach to characterize the confidence about no circulation (CNC) of cVDPV2 as a function of time since the last detected signal of transmission (i.e. poliovirus positive acute flaccid myelitis case or wastewater sample). Results With the surveillance coverage for the NYS population majority and its focus on outbreak counties, modeling suggests a high CNC (95%) within 3–10 months of the last positive surveillance signal, depending on surveillance sensitivity and population mixing patterns. Uncertainty about surveillance sensitivity implies longer durations required to achieve higher CNC. Conclusions In populations that maintain high overall immunization coverage with inactivated poliovirus vaccine (IPV), rare polio cases may occur in un(der)-vaccinated individuals. Modeling demonstrates the unlikeliness of type 2 outbreaks reestablishing endemic transmission or resulting in large absolute numbers of paralytic cases. Achieving and maintaining high immunization coverage with IPV remains the most effective measure to prevent outbreaks and shorten the duration of imported poliovirus transmission.

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  • Cite Count Icon 6
  • 10.1136/jnnp-2023-332927
Does sex influence the natural history of idiopathic adult-onset dystonia?
  • Jul 15, 2024
  • Journal of Neurology, Neurosurgery & Psychiatry
  • Vittorio Velucci + 52 more

BackgroundSeveral earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias...

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  • Preprint Article
  • Cite Count Icon 4
  • 10.1101/2023.09.14.557527
CircHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.
  • Jun 3, 2024
  • bioRxiv : the preprint server for biology
  • Trine Line Hauge Okholm + 13 more

Circular RNAs (circRNAs) represent a class of widespread endogenous RNAs that regulate gene expression and thereby influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Specifically, we use temporal depletion of circHIPK3 or specific RNA binding proteins (RBPs) and identify several perturbed genes by RNA sequencing analyses. Using expression-coupled motif analyses of mRNA expression data from various knockdown experiments, we identify an 11-mer motif within circHIPK3, which is also enriched in genes that become downregulated upon circHIPK3 depletion. By mining eCLIP datasets, we find that the 11-mer motif constitutes a strong binding site for IGF2BP2 and validate this circHIPK3-IGF2BP2 interaction experimentally using RNA-immunoprecipitation and competition assays in bladder cancer cell lines. Our results suggest that circHIPK3 and IGF2BP2 mRNA targets compete for binding. Since the identified 11-mer motif found in circHIPK3 is enriched in upregulated genes following IGF2BP2 knockdown, and since IGF2BP2 depletion conversely globally antagonizes the effect of circHIPK3 knockdown on target genes, our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2- STAT3 mRNA binding and thereby STAT3 mRNA levels. However, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Finally, we show that circHIPK3 expression correlates with overall survival of patients with bladder cancer. Our results are consistent with a model where relatively few cellular circHIPK3 molecules function as inducers of IGF2BP2 condensation thereby regulating STAT3 and other key factors for cell proliferation and potentially cancer progression.

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  • Cite Count Icon 45
  • 10.1136/bjo-2022-323162
Descemet’s membrane endothelial keratoplasty is the predominant keratoplasty procedure in Germany since 2016: a report of the DOG-section cornea and its keratoplasty registry
  • May 1, 2024
  • British Journal of Ophthalmology
  • Elias Flockerzi + 3 more

Background/aimsThis retrospective multicentric panel study provides absolute numbers, types of and indications for corneal transplantation in Germany from 2011 to 2021 and sets them into the international context.MethodsA questionnaire was...

  • Research Article
  • 10.1136/bjo-2022-322829
Progression, reliability, predicting parameters and sample size calculations for quantitative fundus autofluorescence measures in ABCA4-related retinopathy
  • May 1, 2024
  • British Journal of Ophthalmology
  • Philipp L Müller + 3 more

Background/aimsTo investigate the progression of quantitative autofluorescence (qAF) measures and the potential as clinical trial endpoint in ABCA4-related retinopathy.MethodsIn this longitudinal monocentre study, 64 patients with ABCA4-related retinopathy (age (mean±SD),...

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  • Cite Count Icon 13
  • 10.1186/s12889-024-18316-0
The burden of Cardiovascular diseases in Jordan: a longitudinal analysis from the global burden of disease study, 1990–2019
  • Mar 21, 2024
  • BMC Public Health
  • Yazan A Al-Ajlouni + 7 more

BackgroundCardiovascular Disease (CVD) is the leading cause of mortality worldwide. While countries in the Arab world continue to lack public health data and be severely understudied in health research, previous research has shown that compared to 1990, CVDs had a higher burden of disease in the Arab World in 2010. Jordan, a middle-income Arab country, is profiled with unique attributes such as a dual-sector healthcare system, political stability, and its role as a haven for refugees and migrants. These distinctive factors emphasize Jordan’s suitability as a case study. This investigation aims to quantify CVD burden in Jordan and identify risk factors, contributing to a broader understanding of health challenges in the Arab region and beyond.MethodsThe Global Burden of Disease (GBD) dataset was used to estimate prevalence, death, and disability-adjusted life-years (DALYs) as age-standardized rates from 1990 to 2019. We calculated percentage change for nine specific CVDs and reported trends by gender and age groups. Additionally, data on twelve a priori selected behavioral, clinical, and environmental risk factors attributing to overall age-standardized CVDs DALY were reported per 100,00 population.ResultsIn 2019, the age-standardized CVD prevalence, death, and DALYs rates in Jordan were 7980 (95% uncertainty interval [UI] 7629, 8360), 248 (95% UI 211, 288), and 4647 (95% UI 4028, 5388), respectively. Despite an increase in the absolute number of mortality and prevalence, between 1990 and 2019, the age-standardized prevalence, death, and DALYs rates all decreased by 5.5%, 45.1%, and 46.7%, respectively. In 2019, the leading risk factors contributing to overall age-standardized CVDs DALY per 100,000 population were high systolic blood pressure, high BMI, dietary risks, and high LDL cholesterol.ConclusionDespite decreasing burden rate of CVDs in Jordan between 1990 and 2019, CVDs remain the leading cause of mortality in Jordan, with an increase in the total number of prevalence and mortality. Overall, this contributes to increased healthcare costs. Further research is required to quantify the burden of CVDs and understand it better. Intervention measures and policies tailored to specific CVDs should be designed to reduce the burden of CVDs in Jordan.

  • Research Article
  • 10.1111/imm.13782
Id1 expression in CD4 T cells promotes differentiation and function of follicular helper T cells and upregulation of related functional molecules.
  • Mar 19, 2024
  • Immunology
  • Chen Liu + 9 more

Although the roles of E proteins and inhibitors of DNA-binding (Id) in T follicular helper (TFH) and T follicular regulatory (TFR) cells have been previously reported, direct models demonstrating the impact of multiple E protein members have been lacking. To suppress all E proteins including E2A, HEB and E2-2, we overexpressed Id1 in CD4 cells using a CD4-Id1 mouse model, to observe any changes in TFH and TFR cell differentiation. Our objective was to gain better understanding of the roles that E proteins and Id molecules play in the differentiation of TFH and TFR cells. The CD4-Id1 transgenic (TG) mice that we constructed overexpressed Id1 in CD4 cells, inhibiting E protein function. Our results showed an increase in the proportion and absolute numbers of Treg, TFH and TFR cells in the spleen of TG mice. Additionally, the expression of surface characterisation molecules PD-1 and ICOS was significantly upregulated in TFH and TFR cells. The study also revealed a downregulation of the marginal zone B cell precursor and an increase in the activation and secretion of IgG1 in spleen B cells. Furthermore, the peripheral TFH cells of TG mice enhanced the function of assisting B cells. RNA sequencing results indicated that a variety of TFH-related functional molecules were upregulated in TFH cells of Id1 TG mice. In conclusion, E proteins play a crucial role in regulating TFH/TFR cell differentiation and function and suppressing E protein activity promotes germinal centre humoral immunity, which has important implications for immune regulation and treating related diseases.

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  • Cite Count Icon 11
  • 10.3389/fnut.2024.1366553
Global disease burden linked to diet high in red meat and colorectal cancer from 1990 to 2019 and its prediction up to 2030.
  • Mar 14, 2024
  • Frontiers in Nutrition
  • Xuesong Yang + 6 more

Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

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  • Cite Count Icon 1
  • 10.4103/ijo.ijo_2716_23
Clinicodemographic profile of orbital exenteration in a tertiary eye care center - A 20-year experience.
  • Mar 8, 2024
  • Indian journal of ophthalmology
  • Rachna Meel + 7 more

This study aimed to determine the clinical indications for orbital exenteration, demographic profile of these patients, and clinicopathologic correlations in the current times and to compare these results with previous published data. It was a retrospective study. All exenterations performed at a tertiary eye care center over a period of 20 years (from January 2001 to June 2020) were retrospectively evaluated. Patient records were reviewed to obtain demographic data, presenting symptoms and their duration, laterality, and clinical and histopathologic diagnosis. A total of 352 cases (males:females = 222:130) who underwent exenteration were identified. Patients age ranged from 11 months to 87 years (mean: 43.86 years, median: 50 years). The most common indication for exenteration was found to be eyelid malignancy in 54.36%, followed by retinoblastoma in 18.75% and primary orbital tumors in 14.49%. Out of 156 cases of eyelid malignancies requiring exenteration, squamous cell carcinoma (SCC) was the most common histologic subtype ( n = 94, 60.26%), followed by sebaceous gland carcinoma ( n = 40, 25.64%) and basal cell carcinoma ( n = 20, 12.82%). The most common primary orbital tumors requiring exenteration were adenocystic carcinoma of the lacrimal gland in adults and rhabdomyosarcoma in the pediatric age group. Benign conditions requiring exenteration included fulminant fungal orbital infections and lymphangioma among others. The number of exenterations performed have significantly increased in terms of absolute numbers. However, the ratio of exenteration to other tumor-related surgeries, mainly excision biopsy, has reduced compared to that reported from a previous study. The most common indication in our study remains eyelid malignancy followed by intraocular malignancy. However, SCC has emerged as the most common tumor histologic subtype requiring exenterations.

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  • Cite Count Icon 5
  • 10.1038/s41598-024-56150-x
Progress in site-specific cancer mortality in Canada over the last 70 years
  • Mar 7, 2024
  • Scientific Reports
  • Matthew T Warkentin + 6 more

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.

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  • Cite Count Icon 37
  • 10.3390/cells13050451
Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.
  • Mar 5, 2024
  • Cells
  • Andreia Maia + 7 more

Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited in vivo persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies include optimizing NK cell expansion methods and improving NK cell antitumor responses by cytokine stimulation and genetic manipulations. Using K562 cells expressing membrane IL-15 or IL-21 with or without additional activating ligands like 4-1BBL allows "massive" NK cell expansion and makes multiple cell dosing and "off-the-shelf" efforts feasible. Further improvements in NK cell function can be reached by inducing memory-like NK cells, developing chimeric antigen receptor (CAR)-NK cells, or isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like NK cells demonstrate higher in vivo persistence and cytotoxicity, with early clinical trials demonstrating safety and promising efficacy. Recent trials using CAR-NK cells have also demonstrated a lack of any major toxicity, including cytokine release syndrome, and, yet, promising clinical activity. Recent data support that the presence of TIL-NK cells is associated with improved overall patient survival in different types of solid tumors such as head and neck, colorectal, breast, and gastric carcinomas, among the most significant. In conclusion, this review presents insights into the diverse strategies available for NK cell expansion, including the roles played by various cytokines, feeder cells, and culture material in influencing the activation phenotype, telomere length, and cytotoxic potential of expanded NK cells. Notably, genetically modified K562 cells have demonstrated significant efficacy in promoting NK cell expansion. Furthermore, culturing NK cells with IL-2 and IL-15 has been shown to improve expansion rates, while the presence of IL-12 and IL-21 has been linked to enhanced cytotoxic function. Overall, this review provides an overview of NK cell expansion methodologies, highlighting the current landscape of clinical trials and the key advancements to enhance NK-cell-based adoptive cell therapy.

  • Research Article
  • 10.1111/odi.14916
Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial.
  • Mar 4, 2024
  • Oral diseases
  • Behrouz Arefnia + 5 more

To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[18F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT). Eighty-five patients with peripheral artery disease and severe periodontitis-randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)-underwent nuclear imaging at baseline and at 3 months. Clinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean 'standardized uptake values' (SUVmax, SUVmean) and 'target-to-background ratios' (TBRmax, TBRmean). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group. 2-[18F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.

  • Research Article
  • 10.1158/1538-7445.ovarian23-a076
Abstract A076: T-cell exhaustion is an independent predictive biomarker of clinical outcome in high grade serous ovarian cancer regardless of homologous recombination deficiency status
  • Mar 4, 2024
  • Cancer Research
  • Anna Salvioni + 11 more

Abstract Epithelial ovarian cancer is the most lethal gynecologic malignancy, with 5-year survival rates of 46%. High grade serous carcinoma (HGSC) is the most frequent subtype of epithelial ovarian cancer. Approximately 50% of cases are homologous recombination deficient (HRD). Whereas maintenance treatment by PARP inhibitors has significantly improved the prognosis of patients with HRD tumors, clinical outcome in this malignancy is still poor. Despite the immunogenic nature of HGSC, in which T-cell infiltration correlates to improved clinical outcome following surgery and chemotherapy, the disease exhibits low response rates to immune checkpoint blockade (ICB) monotherapy in advanced line settings. We have previously identified epithelial malignancies including HGSC, CD4 and CD8 populations of tumor-infiltrating and antigen-specific T cells that display features of terminal exhaustion. These populations were key players in the response to anti-PD-1 in patients with epithelial tumors. Here, we set out to characterize tumor-infiltrating T cells in a cohort of 80 HGSC patients treated at our institution from whom we collected tumor samples prior to therapy in which HRD status was assessed. We used multiplex immunofluorescence of FFPE tumor samples to assess infiltration by CD4 and CD8 T cells and multiparametric flow cytometry of frozen viable cell suspensions to assess CD4 and CD8 T-cell exhaustion. The link between biological parameters and clinical outcome was assessed by univariable and multivariable analyses. Assessment of the T-cell infiltrate by immunofluorescence showed no difference in the absolute numbers, per tumor or stroma mm2, of CD8 or CD4 T cells between HRD and homologous recombination proficient (HRP) tumors. Instead, analysis of exhausted CD8 and CD4 T cells showed an increased frequency of terminally exhausted PD-1HighTIM-3+ CD8 T cells in HRD tumors. This population, which expresses the ectonucleotidase CD39, was significantly correlated to the presence of T regulatory cells (Treg), which agreed with previous studies showing comigration of effector and regulatory T cells in ovarian cancer. In addition, terminally exhausted CD4 T cells, expressing the immune checkpoints PD-1 and TIM-3 as well as CD39, were enriched in HRD tumors. Among HRD tumors, no difference was observed between the exhaustion profile in tumors presenting deleterious BRCA1/2 mutations compared to those with other mutations in the homologous recombination pathway. Univariable analyses showed exhaustion parameters to be significant predictors of progression-free survival (PFS). The frequencies of exhausted CD4 and CD8 T cells stood out as predictors of PFS in multivariable analyses. Altogether, these results provide the first evidence of a link between T-cell exhaustion and HRD status and reveal T-cell exhaustion as an independent predictor of disease outcome. They also underline the major role played by the antitumor immune response in HGSC and warrant the development of combination immunotherapies despite the lack of response to ICB monotherapy. Citation Format: Anna Salvioni, Mathilde Del, Marie Michelas, Pierre Vuattoux, Clara-Maria Scarlata, Carlos Martinez-Gomez, Nathalie Van Acker, François-Xavier Frenois, Guillaume Bataillon, Jean-Pierre Delord, Alejandra Martinez, Maha Ayyoub. T-cell exhaustion is an independent predictive biomarker of clinical outcome in high grade serous ovarian cancer regardless of homologous recombination deficiency status [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A076.

  • Research Article
  • Cite Count Icon 65
  • 10.1001/jamaneurol.2024.0190
Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019
  • Mar 4, 2024
  • JAMA neurology
  • Daniela Renedo + 51 more

Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. In this study, no particular exposure was specifically targeted. The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

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  • 10.47360/1995-4484-2024-90-97
Main circulating CD8&lt;sup&gt;+&lt;/sup&gt; T cell subsets in patients with systemic lupus erythematosus
  • Mar 1, 2024
  • Rheumatology Science and Practice
  • S S Benevolenskaya + 14 more

Relevance. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and sustained production of autoantibodies.The aim of the study – to compare composition of peripheral blood cytotoxic CD8+ T lymphocytes (Tc) subsets and assess the clinical significance of them in systemic lupus erythematosus. Materials and methods. A total of 35 SLE patients and 49 healthy volunteers were included in the study. Phenotyping of peripheral blood T cell subpopulations was carried out by means of flow cytometry. T lymphocytes were determined using CD3+, CD4+, CD8+ antibodies. Tc were identified by using CD45RA and CD62L antibodies. Also the expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5) on Tc cells was assessed and the main Tc subpopulations were determined: Type 1 (Tc1), type 2 (Tc2), type 17 (Tc17), type 17/1 (Tc17.1), type 17/22 (Tc17.22) cytotoxic cells and T follicular cytotoxic cells (Tfc).Results. The absolute and relative number of Tc was significantly higher in the group of patients with SLE compared with the control group. Additionally, there was a significant decrease in the relative number of Tc1, Tc 17.1 and Tfc1 and a significant increase in the relative number of Tc2, Tfc 17 and Tfc17.1 within the SLE group when compared to the control group. There were significant positive correlationfor Tc1 and levels of C3 and C4 complement components (r=0.404, p&lt;0.05).Conclusions. The absolute and relative number of peripheral blood Tc subsets is altered in SLE patients compared with the control group. It was found that patients with SLE contained increased number of Tc2 cells, which seems to be associated with markers of disease activity. These results demonstrate a prominent pathological role of Tc2 in SLE. While Tc1, Tc17, Tc17.1, Tfc subsets probably have regulatory functions

  • Open Access Icon
  • Research Article
  • Cite Count Icon 3
  • 10.1089/neur.2023.0102
Exploiting Natural Language Processing to Unveil Topics and Trends of Traumatic Brain Injury Research.
  • Mar 1, 2024
  • Neurotrauma Reports
  • Mert Karabacak + 5 more

Traumatic brain injury (TBI) has evolved from a topic of relative obscurity to one of widespread scientific and lay interest. The scope and focus of TBI research have shifted, and research trends have changed in response to public and scientific interest. This study has two primary goals: first, to identify the predominant themes in TBI research; and second, to delineate "hot" and "cold" areas of interest by evaluating the current popularity or decline of these topics. Hot topics may be dwarfed in absolute numbers by other, larger TBI research areas but are rapidly gaining interest. Likewise, cold topics may present opportunities for researchers to revisit unanswered questions. We utilized BERTopic, an advanced natural language processing (NLP)-based technique, to analyze TBI research articles published since 1990. This approach facilitated the identification of key topics by extracting sets of distinctive keywords representative of each article's core themes. Using these topics' probabilities, we trained linear regression models to detect trends over time, recognizing topics that were gaining (hot) or losing (cold) relevance. Additionally, we conducted a specific analysis focusing on the trends observed in TBI research in the current decade (the 2020s). Our topic modeling analysis categorized 42,422 articles into 27 distinct topics. The 10 most frequently occurring topics were: "Rehabilitation," "Molecular Mechanisms of TBI," "Concussion," "Repetitive Head Impacts," "Surgical Interventions," "Biomarkers," "Intracranial Pressure," "Posttraumatic Neurodegeneration," "Chronic Traumatic Encephalopathy," and "Blast Induced TBI," while our trend analysis indicated that the hottest topics of the current decade were "Genomics," "Sex Hormones," and "Diffusion Tensor Imaging," while the cooling topics were "Posttraumatic Sleep," "Sensory Functions," and "Hyperosmolar Therapies." This study highlights the dynamic nature of TBI research and underscores the shifting emphasis within the field. The findings from our analysis can aid in the identification of emerging topics of interest and areas where there is little new research reported. By utilizing NLP to effectively synthesize and analyze an extensive collection of TBI-related scholarly literature, we demonstrate the potential of machine learning techniques in understanding and guiding future research prospects. This approach sets the stage for similar analyses in other medical disciplines, offering profound insights and opportunities for further exploration.

  • Research Article
  • 10.5414/cp204450
Hoarding of insulin and oral antidiabetics in the first phase oftheCOVID-19 pandemic: Regulatory actions taken to avoid shortage.
  • Mar 1, 2024
  • International journal of clinical pharmacology and therapeutics
  • Björn Zethelius + 4 more

To report on hoarding of prescribed medicines, with focus on insulins, in the early phase of the COVID-19 pandemic and on regulatory actions taken to avoid shortage. The National Prescribed Drug Register which utilizes the Anatomic Therapeutic Chemical (ATC) Classification System and covers the total Swedish population was used. We calculated the number of packages of insulins (ATC code A10A), oral anti-diabetics (A10B), and all medicines across all ATC codes combined (A-S) dispensed per week in 2019 and 2020. Correspondingly, the number of packages of glucose test strips dispensed was calculated using the data source Concise held by the Swedish eHealth Agency. Prompt increases in numbers of dispensed packages were observed in March, peaking at week 11/2020. The absolute numbers of packages dispensed in week 11/2019 and week 11/2020 were: insulin, 49,694 and 95,767, an increase by +92.7%; oral antidiabetics, 55,478 and 82,684, +47.1%; glucose test strips, 18,119 and 23,476, +29:6%; and all medicines across all ATC codes combined, 1,988,456 and 2,659,421, +33.7%. Voluntary restriction of dispensing and a rapid change to applicable regulation were implemented within 2 weeks. A steep decline occurred, which became more pronounced after temporary regulation came in force from April 1, then leveling out during the following months. A signal of insulin hoarding was detected early in the COVID-19 pandemic. A temporary regulation, reducing dispensing to a maximum supply of 3 months was rapidly implemented. A shortage of vitally important prescribed medicines was avoided.

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