Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants

ABSTRACT VRC01 is being evaluated in the AMP efficacy trials, the first assessment of a passively administered broadly neutralizing monoclonal antibody (bnAb) for HIV-1 prevention. A key analysis will assess serum VRC01-mediated neutralization as a potential correlate of protection. To prepare for this analysis, we conducted a pilot study where we measured longitudinal VRC01 serum concentrations and serum VRC01-mediated neutralization in 47 and 31 HIV-1 uninfected AMP participants, respectively. We applied four different statistical approaches to predict serum VRC01-mediated neutralization titer against Env-pseudotyped viruses, including breakthrough viruses isolated from AMP placebo recipients who became HIV-1 infected during the trial, using VRC01 serum concentration and neutralization potency (IC50 or IC80) of the VRC01 clinical lot against the same virus. Approaches 3 and 4, which utilized pharmacokinetics/pharmacodynamics joint modeling of concentration and neutralization titer, generally performed the best or comparably to Approaches 1 and 2, which, respectively, utilized only measured and model-predicted concentration. For prediction of ID80 titers against breakthrough viruses, Approaches 1 and 2 rendered comparable performance to Approaches 3 and 4, and could be reasonable approaches to adopt in practice as they entail reduced assay cost and less complicated statistical analysis. Our results may be applied to future studies of other bnAbs and bnAb combinations to maximize resource efficiency in serum neutralization titer measurement.
High Levels of Fine Particulate Matter (PM2.5) Concentrations from Burning Solid Fuels in Rural Households of Butajira, Ethiopia

The use of solid fuel, known to emit pollutants which cause damage to human health, is the primary energy option in Ethiopia. Thus, the aim of this study was to measure the level of household air pollution by using the 24-h mean concentration of fine particulate matter (PM2.5) in 150 randomly recruited households in rural Butajira, Ethiopia. Data relating to household and cooking practices were obtained by conducting face-to-face interviews with the mothers. The 24-h mean (standard deviation) and median PM2.5 concentrations were 410 (220) and 340 µg/m3, respectively. Households using only traditional stoves and those who did not open the door or a window during cooking had a significantly higher mean concentration compared with their counterparts. There is a statistically significant correlation between the mean concentration of PM2.5 and the self-reported cooking duration. The pollution level was up to 16 times higher than the WHO 24-h guideline limit of 25 μg/m3, thus leaving the mothers and children who spend the most time at the domestic hearth at risk of the adverse health effects from solid fuel use in Ethiopia. Thus, effective short- and long-term interventions are urgently needed.
Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Simple Summary Immunotherapy and, in particular, immune checkpoint inhibitors (ICIs), have transformed non-small cell lung cancer treatment options. Although many patients are treated with ICIs, a large number do not respond. Thus, there is a need to identify biomarkers of response. In this study, we evaluated the value of multiple routinely collected variables (from metastatic sites to levels of several conventional peripheral blood parameters) as biomarkers of response to ICIs. Our data indicates that, although several characteristics are associated with response, many present strong interrelations, which should be taken into account when creating compendiums of biomarkers to maximize their predictivity. Finally, we describe a collection of characteristics (LDH levels, sex, and presence or absence of immune related adverse events) that, in our group of patients, had the best predictive value. Abstract Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response. We assembled a retrospective cohort of 262 NSCLC patients treated with ICIs, compiled relevant clinicopathological characteristics, and studied their associations with treatment outcome using Cox proportional-hazards survival models. Additionally, we investigated the interrelations between clinicopathological features and devised a method to create a compendium associated with ICIs response by selecting those that provide non-redundant information. In multivariate analyses, ECOG performance status (hazard ratio (HR) 1.37 (95% CI 1.11 to 1.68), p < 0.005), LDH (HR 1.24 (95% CI 1.03 to 1.48), p = 0.02)) and PD-L1 negativity were associated with decreased progression-free survival (PFS) (HR 1.92 (95% CI 1.03 to 3.58), p = 0.04), whereas presentation of immune-related adverse events (irAEs) (HR 0.35 (95% CI 0.22 to 0.55, p < 0.005) or females (HR 0.52 (95% CI 0.33 to 0.80, p < 0.005) had longer PFS. Additionally, numerous clinicopathological indicators were found to be interrelated. Thus, we searched for features that provide non-redundant information, and found the combination of LDH levels, irAEs, and gender to have a better association with ICIs treatment response (cross-validated c-index = 0.66). We concluded that several clinicopathological features showed prognostic value in our real-world cohort. However, some are interrelated, and compendiums of features should therefore consider these interactions. Joint assessment of LDH, irAEs, and gender may be a good prognostic compendium.
A bright future for the tree shrew in neuroscience research: Summary from the inaugural Tree Shrew Users Meeting

Tree shrews (Tupaia spp.) have been used in neuroscience research since the 1960s due to their evolutionary proximity to primates. The use of and interest in this animal model have recently increased, in part due to the adaptation of modern neuroscience tools in this species. These tools include quantitative behavioral assays, calcium imaging, optogenetics and transgenics. To facilitate the exchange and development of these new technologies and associated research findings, we organized the inaugural “Tree Shrew Users Meeting” which was held online due to the COVID-19 pandemic. Here, we review this meeting and discuss the history of tree shrews as an animal model in neuroscience research and summarize the current themes being investigated using this animal, as well as future directions.
The Many Applications of Engineered Bacteriophages—An Overview

Since their independent discovery by Frederick Twort in 1915 and Felix d’Herelle in 1917, bacteriophages have captured the attention of scientists for more than a century. They are the most abundant organisms on the planet, often outnumbering their bacterial hosts by tenfold in a given environment, and they constitute a vast reservoir of unexplored genetic information. The increased prevalence of antibiotic resistant pathogens has renewed interest in the use of naturally obtained phages to combat bacterial infections, aka phage therapy. The development of tools to modify phages, genetically or chemically, combined with their structural flexibility, cargo capacity, ease of propagation, and overall safety in humans has opened the door to a myriad of applications. This review article will introduce readers to many of the varied and ingenious ways in which researchers are modifying phages to move them well beyond their innate ability to target and kill bacteria.
Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

Simple Summary B-cell malignancies are a heterogenous group of lymphomas and leukemias and are the 6th most common cancer-related cause of death. Apart from several oncogenes and tumor suppressors involved in their pathogenesis, recently the role of non-coding, regulatory sequences has been implied. Enhancers are DNA elements controlling gene expression to ensure proper cell development and function. However, the activity of enhancers can be redirected, setting cells on the path towards cancer. In this review, we discuss different mechanisms through which enhancers are exploited in malignant B cells. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation. Abstract B-cell lymphomas and leukemias derive from B cells at various stages of maturation and are the 6th most common cancer-related cause of death. While the role of several oncogenes and tumor suppressors in the pathogenesis of B-cell neoplasms was established, recent research indicated the involvement of non-coding, regulatory sequences. Enhancers are DNA elements controlling gene expression in a cell type- and developmental stage-specific manner. They ensure proper differentiation and maturation of B cells, resulting in production of high affinity antibodies. However, the activity of enhancers can be redirected, setting B cells on the path towards cancer. In this review we discuss different mechanisms through which enhancers are exploited in malignant B cells, from the well-studied translocations juxtaposing oncogenes to immunoglobulin loci, through enhancer dysregulation by sequence variants and mutations, to enhancer hijacking by viruses. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation.
Double-Negative T-Cell Reaction in a Case of Listeria Meningitis

Gamma delta T-cells are commonly found in response to Listeria monocytogenes infection in mice, whereas this same immunological response has only been reported a few times in vivo in humans. Moreover, gamma delta T-cell response in cerebral spinal fluid samples in conjunction with Listeria meningitis has never been described in medical literature to date. Thus, we describe a 64-year-old male who presented with altered mental status, fever, and neck stiffness. After lumbar puncture revealed elevated glucose, protein, lactate dehydrogenase, and white blood cell count, further cytologic analysis was indicated. The CSF showed a markedly hypercellular sample with a lymphocytic pleocytosis, including some enlarged forms with irregular nuclear contours, and rare macrophage containing intracytoplasmic bacteria. Lymphocyte immunophenotyping was performed via flow cytometric analysis, which ultimately revealed a prominent CD4/CD8 negative T-cell population, suggestive of a gamma delta T-cell population. Thus, an initial suspicion of malignancy was considered but was ruled out due to the absence of mass lesion on imaging and overall features including heterogenous lymphocyte morphology. Shortly after, gram stain and cultures were obtained revealing Listeria monocytogenes. Unfortunately, the patient rapidly succumbed to disease following the diagnosis of Listeria meningitis. Studies suggest that gamma delta T-cells are activated by the protein components of Listeria and thus have been found to be an important mediator of resistance to Listeria infection. Studies have also discovered that the level of activation for these T-cells appears to be tissue specific and dose dependent, with most cases occurring within visceral organs. Hence, we herein present the first case of gamma delta T-cell activation due to Listeria monocytogenes within the cerebral spinal fluid of a human patient.
Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Loaded with Carboplatin Enhance Cytotoxicity on Human Cancer Cell Lines

Cancer is a major global public health problem and conventional chemotherapy has several adverse effects and deficiencies. As a valuable option for chemotherapy, nanomedicine requires novel agents to increase the effects of antineoplastic drugs in multiple cancer models. Since its discovery, carbon nanotubes (CNTs) are intensively investigated for their use as carriers in drug delivery applications. This study shows the development of a nanovector generated with commercial carbon nanotubes (cCNTs) that were oxidized (oxCNTs) and chemically functionalized with hyaluronic acid (HA) and loaded with carboplatin (CPT). The nanovector, oxCNTs–HA–CPT, was used as a treatment against HeLa and MDA–MB-231 human tumor cell lines. The potential antineoplastic impact of the fabricated nanovector was evaluated in human cervical adenocarcinoma (HeLa) and mammary adenocarcinoma (MDA-MB-231). The oxCNTs–HA–CPT nanovector demonstrate to have a specific antitumor effect in vitro. The functionalization with HA allows that nanovector bio–directed towards tumor cells, while the toxicity effect is attributed mainly to CPT in a dose-dependent manner.
Depressive symptoms among people with HIV/AIDS in Northwest Ethiopia: comparative study

Objectives The objective of this study was to compare depressive symptoms among people with HIV/AIDS and the general population sample. We also assessed the factors associated with depressive symptoms. Design A comparative cross-sectional study was conducted. Settings Antiretroviral therapy clinics in three primary healthcare facilities and semi-urban area in Northwest Ethiopia. Participants A total of 1115 participants (558 people with HIV/AIDS and 557 comparison group) aged 18 years and above were recruited. A total of 1026 participants (530 people with HIV/AIDS and 496 comparison group) completed the interview. We excluded people with known HIV-positive status from the comparison group. Outcome measure Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms. The proportion of depressive symptoms was compared between samples of the general population and people with HIV/AIDS using χ2 statistics. Multivariable logistic regression analysis was done to examine the associated factors. Results The overall prevalence of depressive symptoms was 13.3% (11.2%–15.4%). The prevalence was significantly higher in people with HIV/AIDS compared with the community sample (16.6% vs 12.3%), p=0.001. The difference was also significant in the multivariable logistic regression (OR 1.7). For the overall sample, depressive symptoms were significantly associated with older age, being single, divorced/widowed marital status, and poor social support. Conclusions Depressive symptoms were higher in people with HIV/AIDS compared with the general population. It is necessary to include mental healthcare and screening for depression in routine HIV/AIDS care.
Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis

Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.
Identification of the Impurities in Bopu Powder® and Sangrovit® by LC-MS Combined with a Screening Method

Bopu powder® and Sangrovit® were developed from Macleaya cordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.
ErbB4 mediates amyloid β‐induced neurotoxicity through JNK/tau pathway activation: Implications for Alzheimer's disease

Accumulation of amyloid β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). We previously showed that ErbB4 in parvalbumin (PV)‐positive interneurons was associated with Aβ‐induced cognitive deficits; however, the underlying mechanism remains undetermined. Here we found that specific deletion of ErbB4 in PV neurons significantly attenuated oligomeric Aβ‐induced neuronal toxicity and inhibited Aβ‐induced decreases of PSD95 and synaptophysin. Moreover, specific ablation of ErbB4 in PV neurons altered activity‐related protein c‐Fos and decreased hippocampal PV neurons, especially in the dentate gyrus (DG) of hAPP‐J20 mice. Furthermore, c‐Jun N‐terminal kinase (JNK), a protein downstream of ErbB4, was activated by Aβ but not ErbB4's ligand neuregulin 1 (NRG1) β1, suggesting different downstream pathways for Aβ and NRG1β1. JNK phosphorylation was inhibited by the ErbB4 inhibitor AG1478 and by pretreatment with NRG1β1. More importantly, siRNA knockdown of ErbB4 decreased JNK phosphorylation and expression, tau phosphorylation at Ser396 and Thr 205, and Bax expression. Therefore, ErbB4 might mediate Aβ‐induced neuropathology through the JNK/tau pathway and represent a potential therapeutic target in patients with AD.
Longitudinal Associations Between Neighborhood Park and Open Space Access and Children's Accelerometer-Assessed Measured Physical Activity: The Evidence From the MATCH Study.

BACKGROUND Cross-sectional studies have shown positive associations between neighborhood park access and children's physical activity (PA); however, research that examines the relationship longitudinally is lacking. This study investigates how neighborhood park access affects the longitudinal trajectory of PA in 192 children across 3 years. METHODS Accelerometer-assessed PA data of children (N = 202) were collected across 6 semi-annual waves (7 d each) between 2014 and 2018. Geographical information systems was used to measure neighborhood park access (ie, coverage, density, and proximity) at baseline. Mixed-effects models examined the associations of park access with children's baseline and trajectory of moderate to vigorous PA (MVPA) minutes across 3 years and whether the associations differed by sex or weekends versus weekdays. RESULTS Higher neighborhood park density, coverage, and proximity were positively associated with children's baseline MVPA minutes per day. Longitudinally, higher park coverage was associated with smaller decreases in children's MVPA minutes per day, but only during weekends. Park density and proximity were not associated with change in MVPA minutes per day. The above associations did not differ by sex. CONCLUSIONS Having access to more neighborhood parklands protected against age-related declines in children's PA. These findings suggest that neighborhood park coverage should be considered by urban planners when evaluating the health impacts of their policies.
A Comparison of Miniature Lattice Structures Produced by Material Extrusion and Vat Photopolymerization Additive Manufacturing

In this paper, we study the capabilities of two additive manufacturing technologies for the production of lattice structures, namely material extrusion and vat photopolymerization additive manufacturing. A set of polymer lattice structures with diverse unit cell types were built using these additive manufacturing methods and tested under compression. Lattice structures built using material extrusion had lower accuracy and a lower relative density caused by the air gaps between layers, but had higher elastic moduli and larger energy absorption capacities, as a consequence of both the thicker struts and the relatively larger strength of the feedstock material. Additionally, the deformation process in lattices was analyzed using sequential photographs taken during the compression tests, evidencing larger differences according to the manufacturing process and unit-cell type. Both additive manufacturing methods produced miniature lattice structures with similar mechanical properties, but vat polymerization should be the preferred option when high geometrical accuracy is required. Nevertheless, as the solid material determines the compressive response of the lattice structure, the broader availability of feedstock materials gives an advantage to material extrusion in applications requiring stiffer structures or with higher energy absorption capabilities.
In Situ Characterization of Polycaprolactone Fiber Response to Quasi-Static Tensile Loading in Scanning Electron Microscopy

Microstructural responses to the mechanical load of polymers used in tissue engineering is notably important for qualification at in vivo testing, although insufficiently studied, especially regarding promising polycaprolactone (PCL). For further investigations, electrospun PCL scaffolds with different degrees of fiber alignment were produced, using two discrete relative drum collector velocities. Development and preparation of an adjusted sample geometry enabled in situ tensile testing in scanning electron microscopy. By analyzing the microstructure and the use of selected tracking techniques, it was possible to visualize and quantify fiber/fiber area displacements as well as local fractures of single PCL fibers, considering quasi-static tensile load and fiber alignment. The possibility of displacement determination using in situ scanning electron microscopy techniques for testing fibrous PCL scaffolds was introduced and quantified.
PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival

Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.