Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptome profiling reveals new insights into the roles of neuronal nitric oxide synthase on macrophage polarization towards classically activated phenotype

In response to various stimuli, naïve macrophages usually polarize to M1 (classically activated) or M2 (alternatively activated) cells with distinct biological functions. Neuronal nitric oxide synthase (NOS1) is involved in M1 macrophage polarization at an early stage. Here, we show for the first time that NOS1 is dispensable for M2 macrophage polarization for the first time. Further, differentially expressed genes (DEGs) regulated by NOS1 signaling in M1-polarized macrophages stimulated with lipopolysaccharide (LPS) were characterized by transcriptome analysis of wild-type (WT) and NOS1 knockout mouse macrophages. Thousands of affected genes were detected 2 h post LPS challenge, and this wide-ranging effect became greater with a longer stimulation time (8 h post LPS). NOS1 deficiency caused dysregulated expression of hundreds of LPS-responsive genes. Most DEGs were enriched in biological processes related to transcription and regulation of the immune and inflammatory response. At 2 h post-LPS, the toll-like receptor (TLR) signaling pathway, cytokine–cytokine receptor interaction, and NOD-like receptor signaling pathway were the major pathways affected, whereas the main pathways affected at 8 h post-LPS were Th1 and Th2 cell differentiation, FoxO, and AMPK signaling pathway. Identified DEGs were validated by real-time quantitative PCR and interacted in a complicated signaling pathway network. Collectively, our data show that NOS1 is dispensable for M2 macrophage polarization and reveal novel insights in the role of NOS1 signaling at different stages of M1 macrophage polarization through distinct TLR4 plasma membrane-localized and endosome-internalized signaling pathways.
Molecular Acquisition, Cleaning and Evaluation in R (MACER) - A tool to assemble molecular marker datasets from BOLD and GenBank

Abstract Molecular sequence data is an essential component for many biological fields of study. The strength of these data is in their ability to be centralised and compared across research studies. There are many online repositories for molecular sequence data, some of which are very large accumulations of varying data types like NCBI’s GenBank. Due to the size and the complexity of the data in these repositories, challenges arise in searching for data of interest. While data repositories exist for molecular markers, taxa and other specific research interests, repositories may not contain, or be suitable for, more specific applications. Manually accessing, searching, downloading, accumulating, dereplicating and cleaning data to construct project-specific datasets is time-consuming. In addition, the manual assembly of datasets presents challenges with reproducibility. Here, we present the MACER package to assist researchers in assembling molecular datasets and provide reproducibility in the process.
Central Administration of Hydrogen Sulfide Donor NaHS Reduces Iba1-Positive Cells in the PVN and Attenuates Rodent Angiotensin II Hypertension

Hydrogen sulfide (H2S) is a gaseous signaling molecule with neuromodulatory, anti-inflammatory, and anti-hypertensive effects. Here, we investigate whether chronic intracerebroventricular (ICV) infusion of sodium hydrosulfide (NaHS), an H2S donor, can alleviate angiotensin II (Ang II)–induced hypertension (HTN), improve autonomic function, and impact microglia in the paraventricular nucleus (PVN) of the hypothalamus, a brain region associated with autonomic control of blood pressure (BP) and neuroinflammation in HTN. Chronic delivery of Ang II (200 ng/kg/min, subcutaneous) for 4 weeks produced a typical increase in BP and sympathetic drive and elevated the number of ionized calcium binding adaptor molecule 1–positive (Iba1+) cells in the PVN of male, Sprague–Dawley rats. ICV co-infusion of NaHS (at 30 and/or 60 nmol/h) significantly attenuated these effects of Ang II. Ang II also increased the abundance of cecal Deltaproteobacteria and Desulfovibrionales, among others, which was prevented by ICV NaHS co-infusion at 30 and 60 nmol/h. We observed no differences in circulating H2S between the groups. Our results suggest that central H2S may alleviate rodent HTN independently from circulating H2S via effects on autonomic nervous system and PVN microglia.
Adsorptive removal of antibiotics from water using peanut shells from agricultural waste

The residues of sulfonamides in the environment have received widespread attention because of their potential hazards. In this study, the potential of peanut shells for antibiotic removal from aqueous solutions was investigated for four antibiotics (sulfamerazine, sulfamethazine, sulfathiazole, and sulfamethoxazole). The properties of the peanut shells were characterized using Brunauer–Emmett–Teller method, X-ray photoelectron spectroscopy, scanning electron microscopy and Fourier-transform infrared spectroscopy analyses, and the results of the analyses showed that the significant properties of peanut shells were mainly attributed to the antibiotics' adsorption process. A batch adsorption experiment was conducted to study the effect of dosage, concentration, and water factors (Fe3+, Mn2+, and Ca2+) on antibiotic adsorption. Adsorption kinetics and isotherms were also studied. The kinetic data showed that a pseudo-second order kinetic model fitted the experimental data, the adsorption isotherm experimental data fitted the Henry linear adsorption model well, and methanol was found to be an effective eluent for desorption of the antibiotics. The results indicate that peanut shells are a promising material for the removal of antibiotics from contaminated water, when present at low initial concentrations.
Factors affecting uptake of the levonorgestrel-releasing intrauterine device: A mixed-method study of social franchise clients in Nigeria

Background Despite the positive characteristics of the levonorgestrel-releasing intrauterine device (IUD)–a long-acting, highly effective contraceptive with important non-contraceptive attributes–the method has not been widely available in low- and middle-income countries. This study of hormonal IUD, copper IUD, implant and injectable users in Nigeria compares their characteristics, reasons for method choice, and experiences obtaining their method. Methods We conducted a phone survey with 888 women who received a hormonal IUD, copper IUD, contraceptive implant or injectable from 40 social franchise clinics across 18 states in Nigeria. We analyzed survey data descriptively by method and assessed factors associated with hormonal IUD use through multivariate logistic regression models. Follow-up in-depth interviews conducted with 32 women were analyzed thematically. Results There were few differences by method used in the socio-demographic profiles and contraceptive history of participants. Among users choosing a long-acting, reversible method, the top reasons for method choice included perceptions that the method was “right for my body,” long duration, recommended by provider, recommended by friends/family, few or manageable side effects, and high effectiveness. Among hormonal IUD users, 17% mentioned reduced bleeding (inclusive of lighter, shorter, or no period), and 16% mentioned treatment of heavy or painful periods. Qualitative data supported these findings. Among survey respondents, between 25% and 33% said they would have chosen no method if the method they received had not been available. Both quantitative and qualitative data indicated that partner support can affect contraceptive use, with in-depth interviews revealing that women typically needed partner permission to use contraception, but men were less influential in method choice. Conclusions Expanding access to the hormonal IUD as part of a full method mix provides an opportunity to expand contraceptive choice for women in Nigeria. Findings are timely as the government is poised to introduce the method on a wider scale.
Multiple vector-borne pathogens of domestic animals in Egypt

Vector Borne Diseases (VBDs) are considered emerging and re-emerging diseases that represent a global burden. The aim of this study was to explore and characterize vector-borne pathogens in different domestic animal hosts in Egypt. A total of 557 blood samples were collected from different animals using a convenience sampling strategy (203 dogs, 149 camels, 88 cattle, 26 buffaloes, 58 sheep and 33 goats). All samples were tested for multiple pathogens using quantitative PCR and standard PCR coupled with sequencing. We identified Theileria annulata and Babesia bigemina in cattle (15.9 and 1.1%, respectively), T. ovis in sheep and buffaloes (8.6 and 7.7%, respectively) and Ba. canis in dogs (0.5%) as well as Anaplasma marginale in cattle, sheep and camels (20.4, 3.4 and 0.7%, respectively) and Coxiella burnetii in sheep and goats (1.7 and 3%; respectively). New genotypes of An. centrale, An. ovis, An. platys-like and Borrelia theileri were found in cattle (1.1,3.4, 3.4 and 3.4%, respectively), An. platys-like in buffaloes (7.7%), An. marginale, An. ovis, An. platys-like and Bo. theileri in sheep (3.4, 1.7, 1.7 and 3.4%, respectively), An. platys, An. platys-like and Setaria digitata in camels (0.7, 5.4 and 0.7%, respectively) and Rickettsia africae-like, An. platys, Dirofilaria repens and Acanthocheilonema reconditum in dogs (1.5, 3.4, 1 and 0.5%, respectively). Co-infections were found in cattle, sheep and dogs (5.7, 1.7, 0.5%, respectively). For the first time, we have demonstrated the presence of several vector-borne zoonoses in the blood of domestic animals in Egypt. Dogs and ruminants seem to play a significant role in the epidemiological cycle of VBDs.
A simple and practical method to determine peroxide values in edible oils via infrared quartz cuvette-based Fourier transform infrared spectroscopy

A rapid and simple method was developed to determine the peroxide values (PVs) of edible oils by Fourier transform infrared (FTIR) spectroscopy. The spectra of edible oils were obtained using an infrared quartz cuvette (IQC) with a thickness of 10 mm as a spectral accessory. PV calibration was developed using partial least squares (PLS) and validated using the standard method of American oil chemists' society. The results showed that the spectral range of O–H from 3763 cm−1 to 3260 cm−1 was optimal for PLS PV calibration. The correlation coefficients of the blind samples and determined stability were close to 1, and the root mean square error of calibration and validation was low. These findings indicate that the IQC-based FTIR method is more feasible and accurate than the traditional method.
A deep learning based approach identifies regions more relevant than resting‐state networks to the prediction of general intelligence from resting‐state fMRI

Prediction of cognitive ability latent factors such as general intelligence from neuroimaging has elucidated questions pertaining to their neural origins. However, predicting general intelligence from functional connectivity limit hypotheses to that specific domain, being agnostic to time‐distributed features and dynamics. We used an ensemble of recurrent neural networks to circumvent this limitation, bypassing feature extraction, to predict general intelligence from resting‐state functional magnetic resonance imaging regional signals of a large sample (n = 873) of Human Connectome Project adult subjects. Ablating common resting‐state networks (RSNs) and measuring degradation in performance, we show that model reliance can be mostly explained by network size. Using our approach based on the temporal variance of saliencies, that is, gradients of outputs with regards to inputs, we identify a candidate set of networks that more reliably affect performance in the prediction of general intelligence than similarly sized RSNs. Our approach allows us to further test the effect of local alterations on data and the expected changes in derived metrics such as functional connectivity and instantaneous innovations.
Nitric oxide synthase inhibition in healthy adults reduces regional and total cerebral macrovascular blood flow and microvascular perfusion

The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region‐specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L‐NMMA, administered in a randomized, single‐blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L‐NMMA (or volume‐matched saline) was infused intravenously for 5 min prior to imaging. L‐NMMA reduced CBF (L‐NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5–7%) in anterior and posterior cerebral circulations, due in part to the reduced cross‐sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L‐NMMA (L‐NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7–11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults.
Evidence for constancy in the modularity of trunk muscle activity preceding reaching: Implications for the role of preparatory postural activity.

Postural muscle activity precedes voluntary movements of the upper limbs. The traditional view of this activity is that it anticipates perturbations to balance caused by the movement of a limb. However, findings from reach-based paradigms have shown that postural adjustments can initiate center of mass displacement for mobility, rather than minimize its displacement for stability. Within this context, altering reaching distance beyond the base of support would place increasing constraints on equilibrium during stance. If the underlying composition of anticipatory postural activity is linked to stability, coordination between muscles (i.e., motor modules) may evolve differently as equilibrium constraints increase. We analyzed the composition of motor modules in functional trunk muscles as participants performed multi-directional reaching movements to targets within and beyond arm's length. Bilateral trunk and reaching arm muscle activity were recorded. Despite different trunk requirements necessary for successful movement, and the changing biomechanical (i.e. postural) constraints that accompany alterations in reach distance, Non-negative Matrix Factorization identified functional motor modules derived from preparatory trunk muscle activity that shared common features. Relative similarity in modular weightings (i.e., composition) and spatial activation profiles that reflect movement goals across tasks necessitating differing levels of trunk involvement provides evidence that preparatory postural adjustments are linked to the same task priorities (i.e. movement generation rather than stability).
Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging

Supplemental Digital Content is available in the text. Background and Purpose: Computed tomography perfusion imaging allows estimation of tissue status in patients with acute ischemic stroke. We aimed to improve prediction of the final infarct and individual infarct growth rates using a deep learning approach. Methods: We trained a deep neural network to predict the final infarct volume in patients with acute stroke presenting with large vessel occlusions based on the native computed tomography perfusion images, time to reperfusion and reperfusion status in a derivation cohort (MR CLEAN trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands]). The model was internally validated in a 5-fold cross-validation and externally in an independent dataset (CRISP study [CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project]). We calculated the mean absolute difference between the predictions of the deep learning model and the final infarct volume versus the mean absolute difference between computed tomography perfusion imaging processing by RAPID software (iSchemaView, Menlo Park, CA) and the final infarct volume. Next, we determined infarct growth rates for every patient. Results: We included 127 patients from the MR CLEAN (derivation) and 101 patients of the CRISP study (validation). The deep learning model improved final infarct volume prediction compared with the RAPID software in both the derivation, mean absolute difference 34.5 versus 52.4 mL, and validation cohort, 41.2 versus 52.4 mL (P<0.01). We obtained individual infarct growth rates enabling the estimation of final infarct volume based on time and grade of reperfusion. Conclusions: We validated a deep learning-based method which improved final infarct volume estimations compared with classic computed tomography perfusion imaging processing. In addition, the deep learning model predicted individual infarct growth rates which could enable the introduction of tissue clocks during the management of acute stroke.
SARS-CoV-2 Supply Shortages and Tuberculosis Diagnostics: Current Issues Requiring Immediate Solutions

The SARS-CoV-2 pandemic has strained manufacturing capacity worldwide, resulting in significant shortages of laboratory supplies both directly and indirectly. Such shortages include probe-based kits for detection of the Mycobacterium tuberculosis complex from positive liquid broth cultures. ABSTRACT The SARS-CoV-2 pandemic has strained manufacturing capacity worldwide, resulting in significant shortages of laboratory supplies both directly and indirectly. Such shortages include probe-based kits for detection of the Mycobacterium tuberculosis complex from positive liquid broth cultures. These shortages and possible loss of this particular assay have consequences for laboratory testing algorithms and public health in the United States. As there are no FDA-approved, commercially available options that currently exist which could immediately fill this gap, laboratories must identify alternatives and plan for modifying current testing algorithms to accommodate this change.
A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation

Long‐term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L‐CsA‐i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double‐blind, placebo‐controlled, multi‐center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L‐CsA‐i or placebo in addition to triple‐drug immunosuppression. L‐CsA‐i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS‐free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2‐year actuarial difference in BOS‐free survival of 14.1% in favor of L‐CsA‐i in the overall study population, the primary endpoint was not met (p = .243). The pre‐defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L‐CsA‐i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L‐CsA‐i in lung transplant recipients.
Effects of Disease Threat and Attitude Similarity on Willingness to Help: The Mediating Role of Disgust

The current research tested the hypothesis that an increase in perceived disease vulnerability would create more feelings of disgust and a reduced willingness to help persons with dissimilar attitudes. To test these hypotheses, two studies were performed. In the first study, 173 university undergraduates indicated their willingness to help a target person who held similar or dissimilar attitudes. Then the participants’ feelings of disgust about helping, and perceived vulnerability to disease were measured. In the second study, 127 university undergraduates read materials designed to make a disease threat or a non-disease threat salient then indicated their willingness to help a target person with similar or dissimilar attitudes. As predicted a concern about disease and attitude similarity interacted to influence willingness to help and this effect was mediated by feelings of disgust.
Nitrate‐rich beetroot juice ingestion reduces skeletal muscle O2 uptake and blood flow during exercise in sedentary men

Dietary nitrate supplementation has been shown to reduce pulmonary O2 uptake during submaximal exercise and enhance exercise performance. However, the effects of nitrate supplementation on local metabolic and haemodynamic regulation in contracting human skeletal muscle remain unclear. To address this, eight healthy young male sedentary subjects were assigned in a randomized, double‐blind, crossover design to receive nitrate‐rich beetroot juice (NO3, 9 mmol) and placebo (PLA) 2.5 h prior to the completion of a double‐step knee‐extensor exercise protocol that included a transition from unloaded to moderate‐intensity exercise (MOD) followed immediately by a transition to intense exercise (HIGH). Compared with PLA, NO3 increased plasma levels of nitrate and nitrite. During MOD, leg V̇O2 and leg blood flow (LBF) were reduced to a similar extent (∼9%–15%) in NO3. During HIGH, leg V̇O2 was reduced by ∼6%–10% and LBF by ∼5%–9% (did not reach significance) in NO3. Leg V̇O2 kinetics was markedly faster in the transition from passive to MOD compared with the transition from MOD to HIGH both in NO3 and PLA with no difference between PLA and NO3. In NO3, a reduction in nitrate and nitrite concentration was detected between arterial and venous samples. No difference in the time to exhaustion was observed between conditions. In conclusion, elevation of plasma nitrate and nitrate reduces leg skeletal muscle V̇O2 and blood flow during exercise. However, nitrate supplementation does not enhance muscle V̇O2 kinetics during exercise, nor does it improve time to exhaustion when exercising with a small muscle mass.