Miracle-dz/UniFAR-FTUs huggingface dataset:
BBIQ, a pure TLR7 agonist, is an effective influenza vaccine adjuvant

ABSTRACT Better adjuvants are needed for vaccines against seasonal influenza. TLR7 agonists are potent activators of innate immune responses and thereby may be promising adjuvants. Among the imidazoquinoline compounds, 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ) was reported to be a highly active TLR7 agonist but has remained relatively unexplored because of its commercial unavailability. Indeed, in silico molecular modeling studies predicted that BBIQ had a higher TLR7 docking score and binding free energy than imiquimod, the gold standard TLR7 agonist. To circumvent the availability issue, we developed an improved and higher yield method to synthesize BBIQ. Testing BBIQ on human and mouse TLR7 reporter cell lines confirmed it to be TLR7 specific with significantly higher potency than imiquimod. To test its adjuvant potential, BBIQ or imiquimod were admixed with recombinant influenza hemagglutinin protein and administered to mice as two intramuscular immunizations 2 weeks apart. Serum anti-influenza IgG responses assessed by ELISA 2 weeks after the second immunization confirmed that the mice that received vaccine admixed with BBIQ had significantly higher anti-influenza IgG1 and IgG2c responses than mice immunized with antigen alone or admixed with imiquimod. This confirmed BBIQ to be a TLR7-specific adjuvant able to enhance humoral immune responses.
Gomez–López–Hernández syndrome: A case report with clinical and molecular evaluation and literature review

Gomez–López–Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES‐associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.
Translocation domain of botulinum neurotoxin A subtype 2 potently induces entry into neuronal cells

Botulinum neurotoxin (BoNT) is the causative agent of botulism in humans and animals. Only BoNT serotype A subtype 1 (BoNT/A1) is used clinically because of its high potency and long duration of action. BoNT/A1 and BoNT/A subtype 2 (BoNT/A2) have a high degree of amino acid sequence similarity in the light chain (LC) (96%), whereas their N‐and C‐terminal heavy chain (HN and HC) differ by 13%. The LC acts as a zinc‐dependent endopeptidase, HN as the translocation domain, and HC as the receptor‐binding domain. BoNT/A2 and BoNT/A1 had similar potency in the mouse bioassay, but BoNT/A2 entered faster and more efficiently into neuronal cells. To identify the domains responsible for these characteristics, HN of BoNT/A1 and BoNT/A2 was exchanged to construct chimeric BoNT/A121 and BoNT/A212. After expression in Escherichia coli, chimeric and wild‐type BoNT/As were purified as single‐chain proteins and activated by conversion to disulfide‐linked dichains. The toxicities of recombinant wild‐type and chimeric BoNT/As were similar, but dropped to 60% compared with the values of native BoNT/As. The relative orders of SNAP‐25 cleavage activity in neuronal cells and toxicity differed. BoNT/A121 and recombinant BoNT/A2 have similar SNAP‐25 cleavage activity. BoNT/A2 HN is possibly responsible for the higher potency of BoNT/A2 than BoNT/A1.
Movement in the matrix: Pollination and dispersal processes in a tropical coffee and forest landscape mosaic

Ecological and temporal factors can influence animal foraging patterns and may obscure our understanding of how native and exotic species interact. To understand how such factors affect foraging, the visitation of native and exotic bees and wasps was observed at nectar feeders within Mexican agroforestry systems, while documenting (1) vegetation management (low-shade vs. high-shade coffee), (2) light and floral resource levels and (3) recruiting ability, as measured by the change in visitation between two consecutive experimental days. On day one, Africanized honeybee visitation was significantly greater in low-shade habitats, and native solitary bee abundance was significantly greater in high-shade habitats, while native social bee and solitary wasp visitation were not significantly different between habitat types. After 24 h, Africanized honeybee visitation increased significantly in both habitat types, while native social bee visitation increased significantly only in high-shade coffee. In contrast, native solitary bee and native solitary wasp visitation decreased in both habitat types. Overall, this study reveals that Africanized honeybees exhibit only initial foraging preference for low-shade habitats, while native bees exhibit both initial and delayed recruitment-based foraging preferences for high-shade habitats.
Persistent postural perceptual dizziness is on a spectrum in the general population

Objective To examine the idea that symptoms of persistent postural perceptual dizziness (PPPD) are more common than previously assumed and lie on a spectrum in the general population, thus challenging current theories that PPPD is only a consequence of a vestibular insult. Methods We collected 2 common clinical questionnaires of PPPD (Visual Vertigo Analogue Scale [VVAS] and Situational Characteristics Questionnaire [SCQ]) in 4 cohorts: community research volunteers (n = 1941 for VVAS, n = 1,474 for SCQ); paid online participants (n = 190 for VVAS, n = 125 for SCQ); students (n = 204, VVAS only); and patients diagnosed with PPPD (n = 25). Results We found that around 9%, 4%, and 11%, respectively, of the 3 nonclinical cohorts scored above the 25th percentile patient score on 1 PPPD measure (VVAS) and 49% and 54% scored above the 25th percentile patient score on the other measure (SCQ). Scores correlated negatively with age (counter to expectation). As expected, scores correlated with migraine in 2 populations, but this only explained a small part of the variance, suggesting that migraine is not the major factor underlying the spectrum of PPPD symptoms in the general population. Conclusion We found high levels of PPPD symptoms in nonclinical populations, suggesting that PPPD is a spectrum that preexists in the population, rather than only being a consequence of vestibular insult. Atypical visuo-vestibular processing predisposes some individuals to visually induced dizziness, which is then exacerbated should vestibular insult (or more generalized insult) occur.
Two fatty acid‐binding proteins expressed in the intestine interact differently with endocannabinoids

Two different members of the fatty acid‐binding protein (FABP) family are found in enterocyte cells of the gastrointestinal system, namely liver‐type and intestinal fatty acid‐binding proteins (LFABP and IFABP, also called FABP1 and FABP2, respectively). Striking phenotypic differences have been observed in knockout mice for either protein, for example, high fat‐fed IFABP‐null mice remained lean, whereas LFABP‐null mice were obese, correlating with differences in food intake. This finding prompted us to investigate the role each protein plays in directing the specificity of binding to ligands involved in appetite regulation, such as fatty acid ethanolamides and related endocannabinoids. We determined the binding affinities for nine structurally related ligands using a fluorescence competition assay, revealing tighter binding to IFABP than LFABP for all ligands tested. We found that the head group of the ligand had more impact on binding affinity than the alkyl chain, with the strongest binding observed for the carboxyl group, followed by the amide, and then the glycerol ester. These trends were confirmed using two‐dimensional 1H–15N nuclear magnetic resonance (NMR) to monitor chemical shift perturbation of the protein backbone resonances upon titration with ligand. Interestingly, the NMR data revealed that different residues of IFABP were involved in the coordination of endocannabinoids than those implicated for fatty acids, whereas the same residues of LFABP were involved for both classes of ligand. In addition, we identified residues that are uniquely affected by binding of all types of ligand to IFABP, suggesting a rationale for its tighter binding affinity compared with LFABP.
Comparing and synthesizing quantitative distribution models and qualitative vulnerability assessments to project marine species distributions under climate change

Species distribution shifts are a widely reported biological consequence of climate-driven warming across marine ecosystems, creating ecological and social challenges. To meet these challenges and inform management decisions, we need accurate projections of species distributions. Quantitative species distribution models (SDMs) are routinely used to make these projections, while qualitative climate change vulnerability assessments are becoming more common. We constructed SDMs, compared SDM projections to expectations from a qualitative expert climate change vulnerability assessment, and developed a novel approach for combining the two methods to project the distribution and relative biomass of 49 marine species in the Northeast Shelf Large Marine Ecosystem under a “business as usual” climate change scenario. A forecasting experiment using SDMs highlighted their ability to capture relative biomass patterns fairly well (mean Pearson’s correlation coefficient between predicted and observed biomass = 0.24, range = 0–0.6) and pointed to areas needing improvement, including reducing prediction error and better capturing fine-scale spatial variability. SDM projections suggest the region will undergo considerable biological changes, especially in the Gulf of Maine, where commercially-important groundfish and traditional forage species are expected to decline as coastal fish species and warmer-water forage species historically found in the southern New England/Mid-Atlantic Bight area increase. The SDM projections only occasionally aligned with vulnerability assessment expectations, with agreement more common for species with adult mobility and population growth rates that showed low sensitivity to climate change. Although our blended approach tried to build from the strengths of each method, it had no noticeable improvement in predictive ability over SDMs. This work rigorously evaluates the predictive ability of SDMs, quantifies expected species distribution shifts under future climate conditions, and tests a new approach for integrating SDMs and vulnerability assessments to help address the complex challenges arising from climate-driven species distribution shifts.
High throughput direct 3D bioprinting in multiwell plates

Advances in three dimensional (3D) bioprinting have enabled the fabrication of sophisticated 3D tissue scaffolds for biological and medical applications, where high speed, high throughput production in well plates is a critical need. Here, we present an integrated 3D bioprinting platform based on microscale continuous optical printing, capable of high throughput in situ rapid fabrication of complex 3D biomedical samples in multiwell plate formats for subsequent culture and analysis. Our high throughput 3D bioprinter (HT-3DP) was used to showcase constructs of varying spatial geometries of biomimetic significance, tunable mechanical properties, as well as reproducibility. Live hepatocellular carcinoma 3D tissue scaffolds were fabricated in situ in multiwell plates, after which a functional drug response assay against the chemotherapy drug doxorubicin was performed. Dual cell-type populations involving both live hepatocellular carcinoma as well as human umbilical vein endothelial cells were also printed to demonstrate dual-tissue fabrication capability. This work demonstrates a significant advancement in that the production rate of 3D bioprinted tissue scaffolds with controllable spatial architectures and mechanical properties can now be done on a high throughput scale, enabling rapid generation of in vitro 3D tissue models within conventional multiwell cell culture plates for high throughput preclinical drug screening and disease modeling.
Two-Dimensional Layered Metallic VSe2 /SWCNTs/rGO Based Ternary Hybrid Materials for High Performance Energy Storage Applications.

In this work, the ternary hybrid structure VSe2 /SWCNTs/rGO is reported for supercapacitor applications. The ternary composite exhibits a high specific capacitance of 450 F g-1 in a symmetric cell configuration, with maximum energy density of 131.4 Wh kg-1 and power density of 27.49 kW kg-1 . The ternary hybrid also shows a cyclic stability of 91 % after 5000 cycles. Extensive density functional theory (DFT) simulations on the structure as well as on the electronic properties of the binary hybrid structure VSe2 /SWCNTs and the ternary hybrid structure VSe2 /SWCNTs/rGO have been carried out. Due to a synergic effect, there are enhanced density of states near the Fermi level and higher quantum capacitance for the hybrid ternary structure compared to VSe2 /SWCNTs, leading to higher energy and power density for VSe2 /SWCNTs/rGO, supporting our experimental observation. Computed diffusion energy barrier of electrolyte ions (K+ ) predicts that ions move faster in the ternary structure, providing higher charge storage performance.
Calculating air volume fractions from computed tomography images for chronic obstructive pulmonary disease diagnosis

Quantitative evaluation using image biomarkers calculated from threshold-segmented low-attenuation areas on chest computed tomography (CT) images for diagnosing chronic obstructive pulmonary diseases (COPD) has been widely investigated. However, the segmentation results depend on the applied threshold and slice thickness of the CT images because of the partial volume effect (PVE). In this study, the air volume fraction (AV/TV) of lungs was calculated from CT images using a two-compartment model (TCM) for COPD diagnosis. A relative air volume histogram (RAVH) was constructed using the AV/TV values to describe the air content characteristics of lungs. In phantom studies, the TCM accurately calculated total cavity volumes and foam masses with percent errors of less than 8% and ±4%, respectively. In patient studies, the relative volumes of normal and damaged lung tissues and the damaged-to-normal RV ratio were defined and calculated from the RAVHs as image biomarkers, which correctly differentiated COPD patients from controls in 2.5- and 5-mm-thick images with areas under receiver operating characteristic curves of >0.94. The AV/TV calculated using the TCM can prevent the effect of slice thickness, and the image biomarkers calculated from the RAVH are reliable for diagnosing COPD
Night shift work surrounding pregnancy and offspring risk of atopic disease

Background Night shift work surrounding pregnancy may contribute to the risk of developing atopic diseases in offspring due to alterations in the prenatal environment, from stress. Objective To examine the association of maternal night shift work surrounding pregnancy and offspring risk of developing atopic diseases from childhood to adolescence. Methods We examined the association between night shift work before and during pregnancy among 4,044 mothers in the Nurses’ Health Study II (NHSII) and atopic dermatitis, asthma and hay fever risk in 4,813 of their offspring enrolled in the Growing Up Today Study (GUTS). Mothers reported whether GUTS participants had ever been diagnosed with atopic dermatitis, asthma or hay fever in the GUTS Mothers’ questionnaire. Generalized estimating equation regression models were used to estimate multivariable adjusted odds ratios (OR) and 95% confidence intervals (CIs). Results There were no significant associations between pre-conception maternal night shift work and risk of atopic dermatitis, asthma or hay fever in their offspring. Among 545 mothers with information on night shift work during pregnancy, shift work also was not associated with atopic dermatitis, asthma or hay fever in the offspring. Stratified analyses by history of parental atopy and maternal chronotype showed some statistically significant findings, but they were inconsistent and no significant interaction was seen with increasing duration of night shift work. Conclusion In this study, night shift work before and during pregnancy did not increase offspring risk of developing atopic dermatitis, asthma or hay fever.
Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA‐21 in apolipoprotein E‐deficient mice

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4‐positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E‐deficient (Apoe−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L‐NAME in Apoe−/− mice received DMY. Mechanistically, DMY decreases microRNA‐21 (miR‐21) and increases its target gene dimethylarginine dimethylaminohydrolase‐1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR‐21 in Apoe−/− mice or miR‐21 overexpression in cultured HUVECs abrogates those DMY‐mediated protective effects. These data demonstrate that endothelial miR‐21‐inhibited DDAH1‐ADMA‐eNOS‐NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.
Risk Factors for Carriage of Antibiotic-resistant Bacteria in Healthy Children in the Community

Supplemental Digital Content is available in the text. Background: In addition to health care settings, antibiotic resistance has also been increasing in the community. Healthy children represent an important potential reservoir of antibiotic-resistant (AR) bacteria. However, strategies to reduce the spread of AR bacteria often fail to specifically address the factors that promote the carriage of AR bacteria in this population. The objective of this review was to Identify risk factors for carriage of AR bacteria by healthy children. Methods: We did a systematic search of MEDLINE, Embase and PubMed for studies in developed (OECD) countries that assessed risk factors for carriage of AR bacteria in healthy children in the community. We excluded studies done before 1998 and studies of AR Streptococcus pneumoniae carriage in the absence of pneumococcal conjugate vaccination. Results: Of 1234 studies identified, 30 were eligible for inclusion. These studies assessed the impact of 49 risk factors on AR strains of S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli. The majority of these risk factors were assessed in 2 or fewer studies per bacteria. Recent antibiotic consumption was associated with carriage of resistant respiratory bacteria (S. pneumoniae, H. influenzae); however, it was not consistently associated with carriage of AR bacteria in skin or stool (S. aureus and E. coli). For AR S. aureus, transmission within households appeared to have a greater impact than individual antibiotic use. Conclusions: The factors that promote carriage of AR bacteria by healthy children differed between bacterial species. To reduce reservoirs of AR bacteria in the community, it is essential for intervention strategies to target the specific risk factors for different bacteria.
Metagenome-assembled genome distribution and key functionality highlight importance of aerobic metabolism in Svalbard permafrost

ABSTRACT Permafrost underlies a large portion of the land in the Northern Hemisphere. It is proposed to be an extreme habitat and home for cold-adaptive microbial communities. Upon thaw permafrost is predicted to exacerbate increasing global temperature trend, where awakening microbes decompose millennia old carbon stocks. Yet our knowledge on composition, functional potential and variance of permafrost microbiome remains limited. In this study, we conducted a deep comparative metagenomic analysis through a 2 m permafrost core from Svalbard, Norway to determine key permafrost microbiome in this climate sensitive island ecosystem. To do so, we developed comparative metagenomics methods on metagenomic-assembled genomes (MAG). We found that community composition in Svalbard soil horizons shifted markedly with depth: the dominant phylum switched from Acidobacteria and Proteobacteria in top soils (active layer) to Actinobacteria, Bacteroidetes, Chloroflexi and Proteobacteria in permafrost layers. Key metabolic potential propagated through permafrost depths revealed aerobic respiration and soil organic matter decomposition as key metabolic traits. We also found that Svalbard MAGs were enriched in genes involved in regulation of ammonium, sulfur and phosphate. Here, we provide a new perspective on how permafrost microbiome is shaped to acquire resources in competitive and limited resource conditions of deep Svalbard soils.
Sensory focused exercise improves anxiety in Parkinson’s disease: A randomized controlled trial

Anxiety has been implicated as one of the greatest influences on quality of life in Parkinson’s disease (PD). The etiology of anxiety is unclear, although previous work suggests that anxiety may be linked to sensory deficits that cause uncertainty in movement. Thus, the current study examined whether focusing attention on sensory feedback during goal-based exercise has the potential to provide benefits to anxiety in PD. Thirty-five participants with PD were randomized to either a Sensory Attention Focused Exercise (SAFEx) (i.e. internal focus of attention, n = 18) or Sham Exercise control (i.e. external focus of attention, n = 17) and completed 33 one-hour attention-based exercise sessions over 11-weeks. Before and after the program (pre and post), participants completed the Parkinson Anxiety Scale (PAS) questionnaire. The PAS includes three anxiety sections: persistent, episodic, and avoidance. Changes in the total PAS score and within each section of the PAS were subjected to two-factor mixed repeated measures ANCOVA. Significant group by time interactions demonstrated that from pre to post, total PAS scores (p = 0.007) and episodic anxiety scores (p = 0.010) significantly decreased in the SAFEx group only (ΔTotal PAS = -5.2, F(1,27) = 5.41, p = 0.028, ηp2 = 0.17; ΔEpisodic Score = -1.8, F(1,27) = 6.89, p = 0.014, ηp2 = 0.20). In conclusion, focusing attention on sensory feedback while completing goal-based exercises may provide significant benefits to improving anxiety in PD. As such, sensory attention focused exercise may be a critical adjunct therapy for improving anxiety, and ultimately quality of life in people with PD.