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PloS One 2024Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and...
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
Topics: Humans; Ghana; Female; Male; Middle Aged; Cross-Sectional Studies; Risk Factors; Adult; Hepatitis C; Prevalence; Hepacivirus; Young Adult; Seroepidemiologic Studies; Adolescent; Hepatitis C Antibodies; Aged; Child
PubMed: 38941280
DOI: 10.1371/journal.pone.0306292 -
Clinical and Experimental Medicine Jun 2024Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for... (Comparative Study)
Comparative Study
Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for advanced hepatocellular carcinoma (HCC) in China. Different efficacy between the two regimens combined with transvascular intervention for unresectable HCC (uHCC) remain unknown. We retrospectively analyzed uHCC patients treated in three centers by simultaneous combination of A+B or S+B with transarterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs) were compared. Totally 188 patients were included, with 92 and 96 administered A+B+TACE-HAIC (ABTH) and S+B+TACE-HAIC (SBTH), respectively. ORRs (62.0 vs. 70.8%, respectively; P = 0.257) and disease control rates (88.0 vs. 93.8%, P = 0.267) were similar between groups by the mRECIST criteria. ABTH showed no survival advantage over SBTH, with median PFS times of 11.7 months and 13.0 months, respectively (HR = 0.81, 95% CI, 0.52-1.26, P = 0.35) and similar OS times (HR = 1.19, 95% CI, 0.32-4.39, P = 0.8). No significant differences were observed in grade 3-4 TRAEs between groups. Either PD-L1 or PD-1 inhibitor plus bevacizumab combined with TACE-HAIC have similarly excellent therapeutic efficacy with manageable adverse events, representing promising treatment options for uHCC.
Topics: Humans; Carcinoma, Hepatocellular; Male; Bevacizumab; Middle Aged; Female; Liver Neoplasms; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Antibodies, Monoclonal, Humanized; Treatment Outcome; Immune Checkpoint Inhibitors; China; Chemoembolization, Therapeutic; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Fluorouracil; Leucovorin
PubMed: 38940944
DOI: 10.1007/s10238-024-01415-y -
Annals of Intensive Care Jun 2024A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early...
Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024.
BACKGROUND
A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.
METHODS
The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).
RESULTS
During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21).
CONCLUSIONS
Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.
PubMed: 38940865
DOI: 10.1186/s13613-024-01319-w -
Alternative Therapies in Health and... Jun 2024This study aims to investigate the correlation between breast cancer and autoimmune thyroid diseases.
OBJECTIVE
This study aims to investigate the correlation between breast cancer and autoimmune thyroid diseases.
METHODS
A cross-sectional observational study enrolled 100 breast cancer patients at Zhongshan Hospital of Xiamen University from March 2020 to October 2021. Patients were categorized into benign and malignant groups based on tumor pathology. Additionally, 100 healthy female participants underwent physical examinations at the hospital's outpatient center during the same period as controls. The incidence of autoimmune thyroid diseases was assessed via B-type ultrasound, thyroxine level examination, and biopsy. Statistical analyses explored the relationship between autoimmune thyroid diseases and breast cancer.
RESULTS
The pathological type of the malignant group was more severe than that of the healthy group. Although the levels of triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4) in the malignant group fell within the normal range, the concentrations of T3 and T4 in the malignant group were significantly lower than those in the benign and healthy groups. Additionally, the levels of FT4 and antibodies (anti-thyroid peroxidase [anti-TPO] and anti-thyroglobulin [anti-TG]) were significantly higher in the malignant group compared to the benign and healthy groups, demonstrating statistical significance (P < .05). Conversely, the concentrations of free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) in the malignant group showed no statistical significance (P > .05). Furthermore, the levels of T3 and T4 did not correlate with the expression of estrogen receptor (ER) and progesterone receptor (PR) in the study group (P > .05). However, both hormone levels were lower in patients with negative HER-2 expression and those with lymph node metastasis (P > .05).
CONCLUSION
Autoimmune thyroid disease correlates with breast cancer occurrence. Thyroid hormone and autoantibody levels aid clinical monitoring and prognosis. Positive anti-TG and anti-TPO expressions, along with T3, T4, and FT4 alterations, impact patients.
PubMed: 38940788
DOI: No ID Found -
Microbiology Spectrum Jun 2024We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We report the discovery of monoclonal antibodies...
We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We report the discovery of monoclonal antibodies (mAbs) binding to type 3 fimbrial proteins, including MrkA. We found that anti-MrkA mAbs were cross-reactive to a diverse panel of clinical isolates, representing different O-serotypes. mAbs binding to MrkA have previously been described and have been shown to provide prophylactic protection, although only modest protection when dosed therapeutically in a murine lung infection model. Here, we used a combination of binding and opsonophagocytic killing studies using a high-content imaging platform to provide a possible explanation for the modest therapeutic efficacy reported in that model. Our work shows that expression of type 3 fimbriae in culture is not homogenous within a bacterial population. Instead, sub-populations of bacteria that do, and do not, express type 3 fimbriae exist. In a high-content opsonophagocytic killing assay, we showed that MrkA-targeting antibodies initially promote killing by macrophages; however, over time, this effect is diminished. We hypothesize the reason for this is that bacteria not expressing MrkA can evade opsonophagocytosis. Our data support the fact that MrkA is a conserved, immunodominant protein that is antibody accessible on the surface of and suggest that additional studies should evaluate the potential of using anti-MrkA antibodies in different stages of infection (different sites in the body) as well as against biofilms in the body during infection and associated with medical devices.IMPORTANCEThere is an unmet, urgent need for the development of novel antimicrobial therapies for the treatment of infections. We describe the use of phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We discovered monoclonal antibodies (mAbs) binding to the type 3 fimbrial protein MrkA. The anti-MrkA mAbs were found to be highly cross-reactive, binding to all strains tested from a diverse panel of clinical isolates, and were active in an opsonophagocytic killing assay at pM concentrations. MrkA is important for biofilm formation; thus, our data support further exploration of the use of anti-MrkA antibodies for preventing and/or controlling in biofilms and during infection.
PubMed: 38940542
DOI: 10.1128/spectrum.00400-24 -
Bioinformatics (Oxford, England) Jun 2024Mutations are the crucial driving force for biological evolution as they can disrupt protein stability and protein-protein interactions which have notable impacts on...
MOTIVATION
Mutations are the crucial driving force for biological evolution as they can disrupt protein stability and protein-protein interactions which have notable impacts on protein structure, function, and expression. However, existing computational methods for protein mutation effects prediction are generally limited to single point mutations with global dependencies, and do not systematically take into account the local and global synergistic epistasis inherent in multiple point mutations.
RESULTS
To this end, we propose a novel spatial and sequential message passing neural network, named DDAffinity, to predict the changes in binding affinity caused by multiple point mutations based on protein 3D structures. Specifically, instead of being on the whole protein, we perform message passing on the k-nearest neighbor residue graphs to extract pocket features of the protein 3D structures. Furthermore, to learn global topological features, a two-step additive Gaussian noising strategy during training is applied to blur out local details of protein geometry. We evaluate DDAffinity on benchmark datasets and external validation datasets. Overall, the predictive performance of DDAffinity is significantly improved compared with state-of-the-art baselines on multiple point mutations, including end-to-end and pre-training based methods. The ablation studies indicate the reasonable design of all components of DDAffinity. In addition, applications in nonredundant blind testing, predicting mutation effects of SARS-CoV-2 RBD variants, and optimizing human antibody against SARS-CoV-2 illustrate the effectiveness of DDAffinity.
AVAILABILITY AND IMPLEMENTATION
DDAffinity is available at https://github.com/ak422/DDAffinity.
Topics: Point Mutation; SARS-CoV-2; Computational Biology; Protein Conformation; Humans; Neural Networks, Computer; Protein Binding; COVID-19; Proteins; Algorithms
PubMed: 38940145
DOI: 10.1093/bioinformatics/btae232 -
Journal of Integrative Neuroscience Jun 2024The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica...
OBJECTIVES
The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS.
METHODS
C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test.
RESULTS
We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field.
CONCLUSIONS
We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.
Topics: Animals; Neuromyelitis Optica; Mice, Inbred C57BL; Immunoglobulin G; Aquaporin 4; Female; Humans; Mice; Disease Models, Animal; Microglia; Autoantibodies; Astrocytes; Glial Fibrillary Acidic Protein; Central Nervous System
PubMed: 38940087
DOI: 10.31083/j.jin2306119 -
Frontiers in Bioscience (Landmark... Jun 2024Alzheimer's disease is characterized by extracellular beta-amyloid plaques, intraneuronal tau neurofibrillary tangles and excessive neurodegeneration. The mechanisms of...
BACKGROUND
Alzheimer's disease is characterized by extracellular beta-amyloid plaques, intraneuronal tau neurofibrillary tangles and excessive neurodegeneration. The mechanisms of neuron degeneration and the potential of these neurons to form new nerve fibers for compensation remain elusive. The present study aimed to evaluate the impact of beta-amyloid and tau on new formations of nerve fibers from mouse organotypic brain slices connected to collagen-based microcontact prints.
METHODS
Organotypic brain slices of postnatal day 8-10 wild-type mice were connected to established collagen-based microcontact prints loaded with polyornithine to enhance nerve fiber outgrowth. Human beta-amyloid(42) or P301S mutated aggregated tau was co-loaded to the prints. Nerve fibers were immunohistochemically stained with neurofilament antibodies. The physiological activity of outgrown neurites was tested with neurotracer MiniRuby, voltage-sensitive dye FluoVolt, and calcium-sensitive dye Rhod-4.
RESULTS
Immunohistochemical staining revealed newly formed nerve fibers extending along the prints derived from the brain slices. While collagen-only microcontact prints stimulated nerve fiber growth, those loaded with polyornithine significantly enhanced nerve fiber outgrowth. Beta-amyloid(42) significantly increased the neurofilament-positive nerve fibers, while tau had only a weak effect. MiniRuby crystals, retrogradely transported along these newly formed nerve fibers, reached the hippocampus, while FluoVolt and Rhod-4 monitored electrical activity in newly formed nerve fibers.
CONCLUSIONS
Our data provide evidence that intact nerve fibers can form along collagen-based microcontact prints from mouse brain slices. The Alzheimer's peptide beta-amyloid(42) stimulates this growth, hinting at a neuroprotective function when physiologically active. This "brain-on-chip" model may offer a platform for screening bioactive factors or testing drug effects on nerve fiber growth.
Topics: Animals; Amyloid beta-Peptides; Mice; Nerve Fibers; Brain; tau Proteins; Humans; Immunohistochemistry; Peptide Fragments; Alzheimer Disease; Mice, Inbred C57BL
PubMed: 38940051
DOI: 10.31083/j.fbl2906232 -
Frontiers in Bioscience (Landmark... Jun 2024The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens... (Review)
Review
The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.
Topics: Multiple Myeloma; Antibodies, Bispecific; Humans; Immunotherapy; Antigens, Neoplasm; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological
PubMed: 38940040
DOI: 10.31083/j.fbl2906216 -
Euro Surveillance : Bulletin Europeen... Jun 2024BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA...
A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.
BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.
Topics: Humans; SARS-CoV-2; COVID-19; Seroconversion; Longitudinal Studies; Germany; Antibodies, Viral; Middle Aged; Adult; Male; Antibodies, Neutralizing; Female; COVID-19 Vaccines; Aged; Reinfection; Seroepidemiologic Studies; Adolescent; Young Adult; Child; Child, Preschool; Aged, 80 and over; Vaccination
PubMed: 38940003
DOI: 10.2807/1560-7917.ES.2024.29.26.2300659