Plastic debris detection along coastal waters using Sentinel-2 satellite data and machine learning techniques.

Few studies have effectively shown how to use satellites that gather optical data to monitor plastic debris in the marine environment. For the first time, floating macro-plastics distinguishable from seaweed are identified in optical data from the European Space Agency's Sentinel-2 satellites. Case studies from three Brazilian areas, selected for suspected macro-plastics in Sentinel-2 data, utilized a unique Floating Debris Index (FDI) for the Sentinel-2 Multi-Spectral Instrument (MSI) to detect surface material patches. Sub-pixel-scale detection revealed macro-plastics mixed with seaweed and sea foam. Using a Machine Learning-based Naive Bayes algorithm, we classified materials and identified macro-plastics, achieving an 87.25 % accuracy in identifying suspected plastics. Temporal analysis tracked plastic debris movement and accumulation. This methodology is scalable and transferable, with potential applications for monitoring marine plastic pollution in other coastal regions globally.

Identification and analysis of alloreactive T lymphocytes from peripheral blood mononuclear cells.

Alloreactive T-cell responses against mismatched MHC or minor histocompatibility antigens may result in deleterious graft-versus-host disease (GVHD) and increased morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, these T-cell responses may be directed against residual tumor cells (the graft-versus-tumor effect, GVT), thus preventing relapse of the disease. Recent findings have shown that CD45RA+ naïve T cells, but not CD45RA- memory T cells are the major contributors to GVHD, thus leading to clinical trials where CD45RA+-depleted, memory-enriched T-cell products are adoptively transferred following allo-HSCT to prevent GVHD and enhance immune reconstitution. However, residual alloreactivity may still be present in the memory T-cell compartment, thus contributing to prevent disease relapse by GVT. Here, we describe a simple cell-based protocol to identify alloreactive naïve and memory T cells by co-culturing T-cell subsets and third-party antigen-presenting cells. The responding cells are identified following dilution of carboxyfluorescein succinimidyl ester (CFSE) and upregulation of the activation marker CD25. These CFSE-diluting cells can be further phenotyped by high-dimensional flow cytometry, or purified with a cell sorter for downstream genomic and functional assays.

High HIV-1 genetic diversity and low prevalence of transmitted drug resistance among treatment-naive people living with HIV in Madagascar.

BACKGROUND AND OBJECTIVES: Data on HIV drug resistance in Madagascar are rare and outdated. In this study, we assessed the prevalence of HIV drug resistance mutations to antiretrovirals (ARVs) and genetic diversity of circulating strains in treatment-naive people living with HIV (PLHIV) in Madagascar. MATERIALS AND METHODS: We amplified the protease (PR), fragments of the Reverse Transcriptase (RT) and Integrase (IN) genes according to the French ANRS protocol. The amplicons were sequenced using next-generation sequencing technology on an Illumina platform (MiSeq). We determined HIV-1 subtypes through phylogenetic analysis using maximum likelihood in PhyML. Resistance interpretation was performed using the Stanford algorithm (version 9.5.1). RESULTS: We included 239 HIV-infected adults and children, sampled between January 2019 and November 2023, with a median age of 30 years and a mean plasma HIV viral load of 6.3 Log copies/mL. We sequenced at least one genomic fragment (PR or RT or IN) of the 239 samples, but 9 were excluded from analysis (mean depth < 10,000×). Phylogenetic analysis of 230 sequences revealed the presence of subtype C (33.91 %), A1 (11.30 %), B (11.30 %), CRF02_AG (9.56 %), subtype G (3.04 %), subtype D (0.43 %), CRF01_AE (0.43 %), and a significant proportion of unique recombinant forms (URFs) (30.30 %). The prevalence of transmitted drug resistance (TDR) was 4.95 % (10/202) among patients aged 15 years and older. When stratified by ARV class, this prevalence was 4.79 % for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.59 % for Nucleoside Reverse Transcriptase inhibitors (NRTIs), and 0.50 % for integrase strand transfer inhibitors (INSTIs). Among children under 15 years old (n = 28), the prevalence of TDR was 14.28 % (4/28), with all mutations conferring resistance to NNRTIs. No mutation conferring resistance to protease inhibitors was found, neither in children nor in adults. CONCLUSION: Our results show a low prevalence of ARV resistance mutations among adult treatment-naive PLHIV in Madagascar. In children under 15 years old, 92 % were infants under two years old, the high resistance rate is likely related to mother-to-child transmission. No resistance mutation to dolutegravir was detected. We also observed high frequencies of subtypes C, B, A1 and a high proportion of URFs, highlighting an ongoing dynamic epidemic.

Cdk8 and Hira mutations trigger X chromosome elimination in naive female hybrid mouse embryonic stem cells.

Mouse embryonic stem cells (ESCs) possess a pluripotent developmental potential and a stable karyotype. An exception is the frequent loss of one X chromosome in female ESCs derived from inbred mice. In contrast, female ESCs from crosses between different Mus musculus subspecies often maintain two X chromosomes and can model X chromosome inactivation. Here we report that combined mutations of Hira and Cdk8 induce rapid loss of one X chromosome in a Mus musculus castaneus hybrid female ESC line that originally maintains two X chromosomes. We show that MEK1 inhibition, which is used for culturing naive pluripotent ESCs is sufficient to induce X chromosome loss. In conventional ESC media, Hira and Cdk8 mutant ESCs maintain both X chromosomes. Induction of X chromosome loss by switching to naive culture media allows us to perform kinetic measurements for calculating the chromosome loss rate. Our analysis shows that X chromosome loss is not explained by selection of XO cells, but likely driven by a process of chromosome elimination. We show that elimination of the X chromosome occurs with a rate of 0.3% per cell per division, which exceeds reported autosomal loss rates by 3 orders of magnitude. We show that chromosomes 8 and 11 are stably maintained. Notably, Xist expression from one of the two X chromosomes rescues X chromosomal instability in ΔHiraΔCdk8 ESCs. Our study defines mutations of Hira and Cdk8 as molecular drivers for X chromosome elimination in naive female ESCs and describes a cell system for elucidating the underlying mechanism.

Identification of multimodal brain imaging biomarkers in first-episode drugs-naive major depressive disorder through a multi-site large-scale MRI consortium data.

BACKGROUND: Major depressive disorder (MDD) is a severe and common mental illness. The first-episode drugs-naive MDD (FEDN-MDD) patients, who have not undergone medication intervention, contribute to understanding the biological basis of MDD. Multimodal Magnetic Resonance Imaging can provide a comprehensive understanding of brain functional and structural abnormalities in MDD. However, most MDD studies use single-modal, small-scale MRI data. And several multimodal studies of MDD are limited to simple linear combinations of functional and structural features. METHODS: We screened a large sample of FEDN-MDD patients and healthy controlsmultimodal MRI data. Extracting the fractional amplitude of low-frequency fluctuations (fALFF) feature from functional magnetic resonance imaging and the gray matter volume (GMV) feature from structural magnetic resonance imaging. The mCCA-jICA method was used to integrate these two modal features to investigate the functional-structural co-variation abnormalities in MDD. To validate the stability of the extracted functional-structural covariant abnormalities features, we apply them to identify FEDN-MDD patients. RESULTS: The results show that compared to healthy controls, FEDN-MDD patients exhibit joint group-discriminative independent component and modality-specific group-discriminative independent component, suggesting functional-structural covariant abnormalities in MDD patients. Using lightGBM classifier, we achieve a classification accuracy of 99.84 %. LIMITATION: We use GMV and fALFF for multimodal fusion shows promise, but requires further validation with other datasets and exploration of additional multimodal features. CONCLUSIONS: This may indicate that multimodal fusion features can effectively explore information between different modalities and can accurately identify FEDN-MDD patients, suggesting their potential as multimodal brain imaging biomarkers for MDD.

Efficacy and safety of treat-and-extend intravitreal brolucizumab in naive and switched patients with macular neovascularization: one-year follow-up study.

BACKGROUND: to analyze, at one year, the efficacy and safety of treat-and-extend (T&E) intravitreal (IV) Brolucizumab in patients affected by macular neovascularization (MNV). Both naïve and previously treated (i.e., switched) patients were included, and the data from the two groups were compared. METHODS: anatomical (i.e., central subfoveal thickness, CST; presence of fluid), functional (i.e., best corrected visual acuity, BCVA) and treatment-related (i.e., number of IV injections within the study period; number of patients reaching a 12-weeks interval between treatments) data from 41 eyes of 41 subjects (20 naïve and 21 switched) were analyzed. Patients were treated with 3 monthly IV injections followed by a T&E regimen based on a disease activity assessment performed at each scheduled IV treatment. RESULTS: significant CST reduction (from 412.1 ± 115.8 to 273.2 ± 61.6; p < 0.05) and BCVA (mean; p) improvement were observed in the naïve group, while in the switched cohort, both parameters were almost stable. In the naïve and switched groups, 55% and 33.5% of patients, respectively, reached a 12-week IV interval at one year, with a mean of 6.55 ± 1 and 7.43 ± 0.68 IV treatments, respectively. One patient with mild anterior uveitis without sequelae was recorded. CONCLUSION: In patients with MNV, IV Brolucizumab injections following a T&E regimen demonstrated great efficacy and a good safety profile, with greater anatomical and functional results in naïve patients. TRIAL REGISTRATION: This study was approved by the Local Ethics Committee (protocol number 155/2020, general registry number n°11486, InterHospital Ethics Committee, San Luigi Gonzaga Hospital, Orbassano, Italy).

Evaluating Faricimab in Treatment-Naive Neovascular Age Related Macular Degeneration: A Retrospective Analysis of Real-World Data.

Purpose: To evaluate the efficiency and safety of Faricimab on treatment-naive neovascular age related macular degeneration (nAMD) in a real world UK clinic. Patients and Methods: This single centre, retrospective note review was conducted on treatment-naive patients with nAMD. The data collected included demographics, best corrected visual acuity (BCVA), central macular thickness (CMT), total retinal fluid (TRF), the presence of intraretinal fluid (IRF) and subretinal fluid (SRF). Results: A total of 66 eyes from 62 patients were analysed. The average age was 77 years (range 36-91) and 54% of patients were female. After the first dose of faricimab, the average BCVA improved by 0.05 LogMAR (+2.5 letters), the average CMT decreased by 65.9µm and 41% of patients were found to be inactive. The follow-up intervals after the third loading dose were divided into 2 subsets of 4 and 8 week extensions. The 4 week extension subset saw a smaller improvement in BCVA (+3 letters) than the 8 week extension (+6 letters) while both had an average decrease in CMT by 86.6 µm. The total retinal fluid decreased by 45% and 70.7%, leaving only 30% and 12.2% residual intraretinal fluid (IRF) and 30% and 24.4% residual subretinal fluid (SRF), respectively. Over a ten-month period, the average number of injections received was 6.6, including 3 initial loading doses. There was only one reported case of an adverse event out of 66 eyes (1/66, 1.5%). Conclusion: Three loading doses of Faricimab appear efficacious and safe for the treatment of nAMD.

What is already known on this topic: Faricimab is recombinant humanised bispecific IgG monoclonal antibody which binds and neutralises both VEGF-A and angiopoietin-2 (VEGFA and ANG2).Clinical trials have reported faricimab dosing intervals of up to Q16W. What this study adds: To offer a glimpse into real-world effectiveness and safety of faricimab beyond the constraints of a randomised controlled study in treatment naïve nAMD patients.Presents results derived from implementing a "Treat and Extend" algorithm with faricimab in nAMD management, showcasing its beneficial impact on the strategic planning and execution of patient care. How this research may affect research, practice or policy: Faricimab should be seen as a viable therapy in treatment-naive patients with nAMD.Employing a shortened loading regimen of three doses presents no discernible detriment to treatment efficacy when compared to the established four-dose schedule.

Success rates and adherence to antiretroviral therapy among treatment-naïve patients in Davao City, Philippines: A ten-year retrospective cohort study.

Background: Antiretroviral therapy (ART) has significantly improved the prognosis and quality of life of HIV/AIDS patients. However, ART success is greatly influenced by patient adherence to the treatment regimens. This study aimed to assess the association between patient adherence to ART and the treatment success rate among antiretroviral-naïve patients in Davao City, Philippines. Methods: This study utilized a 10-year retrospective cohort design, including 517 antiretroviral-naïve patients from an HIV treatment hub in Davao City, the Philippines. Using strict inclusion criteria, 183 antiretroviral-naïve patients were analyzed. Findings: The study found significant associations between the type of ART (p = 0.011) and the timing of ART initiation (p = 0.006) with both patient adherence and the ART success rate. Specifically, patients who achieved sustained viral suppression were predominantly those who initiated ART early, with 71.6 % (n = 131) of them prescribed a regimen consisting of 2 NRTIs and 1 NNRTI. Moreover, 73.8 % of patients demonstrated good adherence (<50 HIV copies/mL). Importantly, patient adherence to ART was strongly correlated with treatment success rate. Interpretation: This study highlights the significance of adherence to antiretroviral therapy (ART) for successful treatment outcomes among antiretroviral-naïve patients living with HIV/AIDS. Early initiation of ART and consistent adherence to treatment regimens are essential for achieving sustained viral suppression and improving treatment effectiveness.

Regulatory T cells modulate monocyte functions in immunocompetent antiretroviral therapy naive HIV-1 infected people.

We previously demonstrated that the overall number of regulatory T (Treg) cells decrease proportionately with helper CD4+ T cells and their frequencies increase in antiretroviral therapy (ART)-naive human immunodeficiency virus type-1 (HIV-1) infected individuals. The question now is whether the discrepancies in Treg cell numbers and frequencies are synonymous to an impairment of their functions. To address this, we purified Treg cells and assessed their ability to modulate autologous monocytes functions. We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC). This activity of Treg cells has been shown to be influenced by immunocompetence including but not limited to helper CD4+ T cell counts, in individuals with HIV-1 infection. Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-ß) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-ß and IL-10 in the suppressive activity of Treg cells.

Long-acting muscarinic antagonist and long-acting ß2-agonist combination for the treatment of maintenance therapy-naïve patients with chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count <300 cells/µL) patients. In randomized controlled trials (RCTs), LAMA/LABA combination therapy improved lung function, St. George's Respiratory Questionnaire (SGRQ) total score, and Transitional Dyspnea Index (TDI) focal score and reduced the use of rescue medications, exacerbation risk, and risk of first clinically important deterioration (CID), compared with LAMA or LABA monotherapy. However, there is limited evidence regarding the efficacy and safety of LAMA/LABA combination therapy versus LAMA or LABA monotherapy in maintenance therapy-naïve patients. This review discusses the rationale for the early initiation of LAMA/LABA combination therapy in maintenance therapy-naïve patients with COPD. In post hoc analyses of pooled data from RCTs, compared with LAMA or LABA monotherapy, LAMA/LABA combination therapy improved lung function and quality of life and reduced COPD symptoms, risk of first moderate/severe exacerbation, risk of first CID, and use of rescue medication, with no new safety signals. In a real-world study, patients initiating LAMA/LABA had significantly reduced risk of COPD-related inpatient admissions and rate of on-treatment COPD-related inpatient admissions over 12 months than those initiating LAMA. Consequently, LAMA/LABA combination therapy could be considered the treatment of choice in maintenance therapy-naïve patients with COPD, as recommended by the GOLD 2024 report.

Long-acting bronchodilator combination therapy for the treatment of maintenance therapy­naïve patients with chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease (COPD) is a common lung disease that makes it hard to breathe and is a leading cause of death and disability worldwide. This disease tends to worsen lung function from an early stage, especially in people who only have mild or moderate symptoms. To help stop the loss of lung function and maintain the quality of life for patients with COPD, two main types of long-lasting inhaler medications are used: one type focuses on relaxing the muscles around the airways, and the other type helps open the airways making it easier to breathe. Some medications combine these two types of action and are approved for long-term management of COPD. However, there is not much information on the effectiveness and safety of these combination medications in patients who have never taken long-lasting COPD medication before. Current health guidelines suggest starting these combination medications in patients who are likely to see their symptoms get worse quickly, and who do not have a high level of a specific type of white blood cell. In this review, we discuss the evidence for starting these combination treatments early in patients who have never used long-lasting COPD medications before. There is no strong evidence yet that shows starting treatment early benefits patients with newly diagnosed COPD. However, about 30% of patients in clinical trials designed to study the effectiveness of these combination medications, had never received any long-lasting treatment before. After-the-fact analyses of these patients showed that these combination medications could reduce symptoms such as breathlessness, improve lung function, enhance quality of life, lessen the need for emergency medications, and decrease the risk of severe symptom flare-ups. Overall, the evidence supports using these combination inhaler medications as the first choice of treatment for patients with moderate COPD symptoms who have not previously been treated with long-lasting inhalers.

Relationship of PSC to embryos: Extending and refining capture of PSC lines from mammalian embryos.

Pluripotent stem cell lines derived from preimplantation mouse embryos have opened opportunities for the study of early mammalian development and generation of genetically uncompromised material for differentiation into specific cell types. Murine embryonic stem cells are highly versatile and can be engineered and introduced into host embryos, transferred to recipient females, and gestated to investigate gene function at multiple levels as well as developmental mechanisms, including lineage segregation and cell competition. In this review, we summarize the biomedical motivation driving the incremental modification to culture regimes and analyses that have advanced stem cell research to its current state. Ongoing investigation into divergent mechanisms of early developmental processes adopted by other species, such as agriculturally beneficial mammals and birds, will continue to enrich knowledge and inform strategies for future in vitro models.

Radial polarisation patterns identify macular damage: a machine learning approach.

CLINICAL RELEVANCE: Identifying polarisation-modulated patterns may be an effective method for both detecting and monitoring macular damage. BACKGROUND: The aim of this work is to determine the effectiveness of polarisation-modulated patterns in identifying macular damage and foveolar involvement using a methodology that involved feature selection, Naïve Bayes supervised machine learning, cross validation, and use of an interpretable nomogram. METHODS: A cross-sectional study involving 520 eyes was undertaken, encompassing both normal and abnormal cases, including those with age-related macular disease, diabetic retinopathy or epiretinal membrane. Macular damage and foveolar integrity were assessed using optical coherence tomography. Various polarisation-modulated geometrical and optotype patterns were employed, along with traditional methods for visual function measurement, to complete perceptual detection and identification measures. Other variables assessed included age, sex, eye (right, left) and ocular media (normal, pseudophakic, cataract). Redundant variables were removed using a Fast Correlation-Based Filter. The area under the receiver operating characteristic curve and Matthews correlation coefficient were calculated, following 5-fold stratified cross validation, for Naïve Bayes models describing the relationship between the selected predictors of macular damage and foveolar involvement. RESULTS: Only radially structured polarisation-modulated patterns and age emerged as predictors of macular damage and foveolar involvement. All other variables, including traditional logMAR measures of visual acuity, were identified as redundant. Naïve Bayes, utilising the Fast Correlation-Based Filter selected features, provided a good prediction for macular damage and foveolar involvement, with an area under the receiver operating curve exceeding 0.7. Additionally, Matthews correlation coefficient showed a medium size effect for both conditions. CONCLUSIONS: Radially structured polarisation-modulated geometric patterns outperform polarisation-modulated optotypes and standard logMAR acuity measures in predicting macular damage, regardless of foveolar involvement.

Decoding Breast Cancer: Using Radiomics to Non-Invasively Unveil Molecular Subtypes Directly from Mammographic Images.

Breast cancer is the most commonly diagnosed cancer worldwide. The therapy used and its success depend highly on the histology of the tumor. This study aimed to explore the potential of predicting the molecular subtype of breast cancer using radiomic features extracted from screening digital mammography (DM) images. A retrospective study was performed using the OPTIMAM Mammography Image Database (OMI-DB). Four binary classification tasks were performed: luminal A vs. non-luminal A, luminal B vs. non-luminal B, TNBC vs. non-TNBC, and HER2 vs. non-HER2. Feature selection was carried out by Pearson correlation and LASSO. The support vector machine (SVM) and naive Bayes (NB) ML classifiers were used, and their performance was evaluated with the accuracy and the area under the receiver operating characteristic curve (AUC). A total of 186 patients were included in the study: 58 luminal A, 35 luminal B, 52 TNBC, and 41 HER2. The SVM classifier resulted in AUCs during testing of 0.855 for luminal A, 0.812 for luminal B, 0.789 for TNBC, and 0.755 for HER2, respectively. The NB classifier showed AUCs during testing of 0.714 for luminal A, 0.746 for luminal B, 0.593 for TNBC, and 0.714 for HER2. The SVM classifier outperformed NB with statistical significance for luminal A (p = 0.0268) and TNBC (p = 0.0073). Our study showed the potential of radiomics for non-invasive breast cancer subtype classification.

Comparative real-world outcomes between ustekinumab, infliximab, and adalimumab in bio-naïve and bio-experienced Crohn's disease patients: a retrospective multicenter study.

BACKGROUND: Numerous studies have compared the efficacy of ustekinumab (UST) and anti-TNF agents [infliximab (IFX) or adalimumab(ADA)] in moderate to severe Crohn's disease (CD) patients. This study aims to compare the efficacy of UST, IFX, and ADA while differentiating between bio-naïve and bio-experienced patients, which is an underexplored aspect, particularly in Asia. METHODS: We conducted a retrospective multi-center study from 2012 to 2023, categorizing patients into bio-naïve and bio-experienced groups. We evaluated clinical remission rates after induction therapy and clinical outcomes, including CD-related hospitalization, intestinal resection, and drug discontinuation during maintenance therapy. RESULTS: Among the 214 bio-naïve CD patients, 60 received UST, 108 received IFX, and 46 received ADA. After 1:1 propensity score matching between UST and anti-TNF agents groups, 59 patients were analyzed in each group (45 in the IFX group and 14 in the ADA group). We found no significant differences in clinical remission rates (P = 0.071), CD-related hospitalization (P = 0.800), intestinal resection (P = 0.390), or drug discontinuation (P = 0.052) between the UST, IFX, and ADA groups in bio-naïve CD patients. In bio-experienced CD patients, with 35 in the UST group and 13 in the anti-TNF agents group, the UST group showed a lower risk of drug discontinuation (P = 0.004) than the anti-TNF agents group. CONCLUSIONS: This study suggests that UST, IFX, and ADA are equally effective in bio-naïve CD patients, while in bio-experienced patients, mostly with previous exposure to anti-TNF agents, UST may offer superior drug durability.

Ex Vivo Analysis of the Association of GFP-Expressing L. aethiopica and L. mexicana with Human Peripheral Blood-Derived (PBD) Leukocytes over 24 Hours.

Leishmania parasites are transmitted to mammalian hosts through the bite of sandflies. These parasites can infect phagocytic cells (macrophages, dendritic cells, and neutrophils) and non-phagocytic cells (B cells and fibroblasts). In mice models, the disease development or resolution is linked to T cell responses involving inflammatory cytokines and the activation of macrophages with the M1/M2 phenotype. However, this mechanism does not apply to human infection where a more complex immunological response occurs. The understanding of interactions between immune cells during Leishmania infection in humans is still limited, as current infection models focus on individual cell types or late infection using controlled human infection models (CHIMs). This study investigated the early parasite infection in freshly isolated peripheral blood-derived (PBD) leukocytes over 24 h. Flow cytometer analysis is used in immunophenotyping to identify different subpopulations. The study found that among the L. aethiopicaGFP-associated leukocytes, most cells were neutrophils (55.87% ± 0.09 at 4 h) and monocytes (23.50% ± 0.05% at 24 h). B cells were 12.43% ± 0.10% at 24 h. Additionally, 10-20% of GFP+ leukocytes did not belong to the aforementioned cell types, and further investigation revealed their identity as CD4+ T cells. Data not only confirm previous findings of Leishmania infection with PBD leukocytes and association with B cells but also suggest that CD4+ T cells might influence the early-stage of infection.

Multi-Fingerprints Indoor Localization for Variable Spatial Environments: A Naive Bayesian Approach.

Fingerprint-based indoor localization has been a hot research topic. However, the current fingerprint-based indoor localization approaches still rely on a single fingerprint database, where the average level of data at reference points is used as the fingerprint representation. In variable environmental conditions, the variations in signals caused by changes in the environmental states introduce significant deviations between the average level and the actual fingerprint characteristics. This deviation leads to a mismatch between the constructed fingerprint database and the real-world conditions, thereby affecting the effectiveness of fingerprint matching. Meanwhile, the sharp noise interference caused by uncertainties such as personnel movement has a significant interference on the creation of the fingerprint database and fingerprint matching in online stage. Examination of the sampling data after denoising with Robust Principal Component Analysis (RPCA) revealed distinct multi-fingerprint characteristics with clear boundaries at certain access points. Based on these observations, the concept of constructing a fingerprint database using multiple fingerprints is introduced and its feasibility is explored. Additionally, a multi-fingerprint solution based on naive Bayes classification is proposed to accurately represent fingerprint characteristics under different environmental conditions. This method is based on the online stage fingerprints. The corresponding state space is selected using the naive Bayes classifier, enabling the selection of an appropriate fingerprint database for matching. Through simulations and empirical evaluations, the proposed multi-fingerprints construction scheme consistently outperforms the traditional single-fingerprint database in terms of positioning accuracy across all tested localization algorithms.

Treatment Management Challenges in Naïve and Experienced HIV-1-Infected Individuals Carrying the M184V Mutation.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation (RAM) is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of the M184V mutation on the treatment outcomes in people living with HIV (PLWH). Since 3TC remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure (VF). ART guidelines do not recommend the use of drugs impacted by RAMs as they have been confirmed to comprise a risk factor for VF. However, there is evidence that 3TC/FTC can remain active even in the presence of M184V. Given the potential benefits of 3TC in ART combinations, the investigation of M184V remains of high interest to clinicians and researchers, especially in certain regions with limited resources, and especially for its unusual effects. This is a review of the literature on the challenges in treating both naïve and experienced individuals carrying the M184V mutation, including virological failure, virological suppression, and resistance to ART.

A post-hoc pooled analysis to evaluate efficacy and safety of insulin glargine 300 U/mL in insulin-naïve people with type 2 diabetes with/without prior use of glucagon-like peptide-1 receptor agonist therapy.

AIMS: To evaluate treatment advancement with insulin glargine 300 U/mL (Gla-300), with or without prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in type 2 diabetes (T2D). METHODS: Efficacy and safety outcomes of insulin-naïve patients intensifying with Gla-300, with/without prior GLP-1 RA therapy, were evaluated in three analyses (N = 3562): a pooled analysis of seven interventional studies, a subanalysis comparing participants who stopped GLP-1 RA therapy and initiated Gla-300 with those who received add-on Gla-300, and an expanded analysis including two observational studies. RESULTS: Glycaemic outcomes, including HbA1c improvement and fasting plasma glucose, were similar between groups with/without prior GLP-1 RA use. HbA1c least squares mean change from baseline was - 1.7 % and - 1.6 % with and without prior GLP-1 RA, respectively. Glycaemic outcomes were similar between participants who stopped GLP-1 RA therapy when initiating Gla-300 and those who received add-on Gla-300, although more participants receiving add-on Gla-300 achieved HbA1c targets. The expanded analysis yielded similar results. Incidence of hypoglycaemia was low with no clinically relevant weight changes in all analyses. CONCLUSIONS: Treatment advancement with Gla-300 in patients with T2D, with/without prior GLP-1 RA therapy, improved glycaemic outcomes with no relevant impact on weight, while maintaining a low hypoglycaemia risk.

Combined bictegravir, emtricitabine and tenofovir alafenamide for treating people with HIV: a plain language summary of the BICSTaR study up to 1 year.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about an ongoing study called the BICSTaR study.The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test.People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment.Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year. WHAT ARE THE KEY TAKEAWAYS?: Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an 'undetectable viral load' and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly.Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1 year. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects.