Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelets Selectively Regulate the Release of BDNF, But Not That of Its Precursor Protein, proBDNF

Background Brain-derived neurotrophic factor (BDNF) plays a role in synaptic plasticity and neuroprotection. BDNF has well-established pro-survival effects, whereas its precursor protein, proBDNF, induces apoptosis. Thus, it has been suggested that the proBDNF/BDNF ratio could be an indicator of neuronal health. Access to neurons is, understandably, limited. Because of their similarities, platelets have been put forward as a non-invasive biomarker of neuronal health; indeed, they store large quantities of BDNF and can release it into circulation upon activation, similarly to neurons. However, whether platelets also express the precursor proBDNF protein remains unknown. We therefore sought to characterize proBDNF levels in human platelets and plasma. Methods The presence of proBDNF was assessed by immunoblotting, cell fractionation, flow cytometry, and confocal microscopy in washed platelets from 10 healthy volunteers. Platelets from 20 independent healthy volunteers were activated with several classical agonists and the release of BDNF and proBDNF into plasma was quantified by ELISA. Results Platelets expressed detectable levels of proBDNF (21 ± 13 fmol/250 x 106 platelets). ProBDNF expression was mainly localized in the intracellular compartment. The proBDNF to BDNF molar ratio was ~1:5 in platelets and 10:1 in plasma. In stark contrast to the release of BDNF during platelet activation, intraplatelet and plasma concentrations of proBDNF remained stable following stimulation with classical platelet agonists, consistent with non-granular expression. Conclusions Platelets express both the mature and the precursor form of BDNF. Whether the intraplatelet proBDNF to BDNF ratio could be used as a non-invasive biomarker of cognitive health warrants further investigation.
Extracting, Mining and Predicting Users' Interests from Social Media

The abundance of user generated content on social media provides the opportunity to build models that are able to accurately and effectively extract, mine and predict users’ interests with the hopes of enabling more effective user engagement, better quality delivery of appropriate services and higher user satisfaction. While traditional methods for building user profiles relied on AI-based preference elicitation techniques that could have been considered to be intrusive and undesirable by the users, more recent advances are focused on a non-intrusive yet accurate way of determining users’ interests and preferences. In this monograph, we will cover five important subjects related to the mining of user interests from social media: (1) the foundations of social user interest modeling, such as information sources, various types of representation models and temporal features, (2) techniques that have been adopted or proposed for Fattane Zarrinkalam, Stefano Faralli, Guangyuan Piao and Ebrahim Bagheri (2020), “Extracting, Mining and Predicting Users’ Interests from Social Media”, Foundations and Trends © in Information Retrieval: Vol. 14, No. 5, pp 445–617. DOI: 10.1561/1500000078. Full text available at: http://dx.doi. org/10.1561/1500000078
Quantification et modelisation des flux d'azote resultant de l'epandage de lisier

Malgre une disponibilite croissante en lisiers et leur valeur fertilisante souvent elevee, le raisonnement agronomique de l'utilisation de ces effluents est souvent neglige. Des changements de comportement sont cependant aujourd'hui demandes aux agriculteurs, car l'utilisation irraisonnee des lisiers entraine une pollution notable de l'air et des eaux continentales et littorales. Dans ce contexte, l'objectif de ce travail a ete d'elaborer un modele agronomique operationnel permettant d'affiner la prevision de la valeur fertilisante azotee des lisiers, comparativement aux modeles usuels, et de calculer le risque environnemental resultant des epandages. Le modele, nomme stal, comprend deux modules couples volatilisation-biotransformations, et simule la volatilisation, la nitrification, l'organisation et la mineralisation brute de l'azote du lisier. Stal est un modele dynamique semi-mecaniste, dont les parametres et les variables d'entree sont facilement accessibles. Le parametrage du modele repose sur des resultats experimentaux obtenus en conditions de plein champ et au laboratoire, et fondes sur l'utilisation du marquage 1 5nh 4. Nous avons constate l'importance et la variabilite des pertes gazeuses, representant pour des apports en sol nu 30 a 60% de l'azote ammoniacal apporte. L'etude au laboratoire de l'organisation-mineralisation a mis en evidence le role determinant de la fraction soluble de la mo du lisier sur la cinetique de mineralisation du c. Les flux d'organisation et de mineralisation de l'azote sont etroitement correles au flux de mineralisation du c, ce qui justifie une approche simplifiee des relations c-n. Enfin, nous avons montre le role preponderant exerce par le sol sur la cinetique de nitrification. La qualite predictive du modele apparait relativement homogene entre modules, et sa precision satisfaisante. Enfin, l'analyse de sensibilite a permis d'etudier les relations de concurrence exercees par les differents processus vis a vis du compartiment ammoniacal ; elle a aussi permis de calculer les erreurs commises lorsque le modele est renseigne avec moins de precision, et d'en proposer une version operationnelle minimale.
Axonal remodeling of the corticospinal tract during neurological recovery after stroke

Stroke remains the leading cause of long-term disability. Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex. As the only direct descending motor pathway, the corticospinal tract (CST) is the primary pathway to innervate spinal motor neurons, and thus, forms the neuroanatomical basis to control the peripheral muscles for voluntary movements. Here, we review evidence from both experimental animals and stroke patients, regarding CST axonal damage, functional contribution of CST axonal integrity and remodeling to neurological recovery, and therapeutic approaches aimed to enhance CST axonal remodeling after stroke. The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation, which will significantly impact the current clinical needs of subacute and chronic stroke treatment.
Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy

Autophagy is crucial for maintaining cellular homeostasis, and can be activated after ischemic stroke. It also participates in nerve injury and repair. The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy. A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion. One week after surgery, these rats were raised in either a standard environment or an enriched environment for 4 successive weeks. The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats. Enriched environment-induced elevations in autophagic activity were mainly observed in neurons. Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes, enhanced the lysosomal activities of lysosomal-associated membrane protein 1, cathepsin B, and cathepsin D, and reduced the expression of ubiquitin and p62. After 4 weeks of enriched environment treatment, neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated, and infarct volume was significantly reduced. These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke. This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology, China (approval No. 5301002013855) on March 1, 2019.
Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience

Background: Health-care workers (HCWs) are at high risk of acquiring COVID-19. Hydroxychloroquine (HCQ) possesses in vitro antiviral activity and inhibits viral replication of coronavirus in cell cultures. The national task force for COVID-19 in India recommended the use of HCQ prophylaxis against severe acute respiratory syndrome coronavirus 2 infection in HCWs. Methodology: We conducted a retrospective cohort study in a mixed tertiary care facility to find the incidence and clinical profile of COVID-19 in HCWs between April 2020 and June 2020, who were advised preexposure prophylaxis with HCQ, at the start of the pandemic. Details of HCQ usage were collected using an online questionnaire form. The clinical profile, treatment, and outcome of COVID-19-positive HCWs were also studied. Results: We included 604 HCWs, of which 491 (81.2%) had taken adequate HCQ prophylaxis while 113 (18.7%) did not take adequate HCQ, 443 (73.3%) had high-risk COVID-19 exposure, and 32 HCWs (5.1% of the total) were COVID-19 positive. There were 10 COVID-19 cases (2.1%) among HCWs taking HCQ while 22 (19.4%) cases occurred in HCQ not compliant HCWs, with a relative risk of 0.1046 (95% confidence interval: 0.0510–0.2147, P< 0.0001), indicating a reduced risk of COVID-19 among HCWs taking HCQ prophylaxis. Among the noncompliant cases, 14 (43.7%) never took HCQ, 4 (12.5%) took HCQ but had poor compliance, and 4 (12.5%) stopped HCQ prematurely. Most (91.7%) COVID-19-positive HCWs were asymptomatic or had mild symptoms, moderate symptoms were seen in 3 (9.3%), and there were no severe cases or deaths. Conclusions: The use of HCQ as preexposure prophylaxis in HCWs was associated with reduced risk of COVID-19, suggesting its role as an effective chemoprophylactic agent.
Computer Simulation Studies of Ion Channel Gating: Characteristics of the M2 Channel of Influenza-A Virus in a Phospholipid Bilayer

The 25 amino acids long, transmembrane fragment of the Influenza virus M2 protein forms a homotetrameric channel that transports protons across lipid bilayers. It has been postulated that high efficiency and selectivity of this process is due to gating by four histidine residues that occlude the channel lumen in the closed state. Two mechanisms of gating have been postulated. In one mechanism, the proton is "shuttled" through the gate by attaching to the delta nitrogen atom on the extracellular side of the imidazole ring, followed by the release of the proton attached to the epsilon nitrogen atom on the opposite side. In the second mechanism, the four histidines move away from each other due to electrostatic repulsion upon protonation, thus opening the gate sufficiently that a wire of water molecules can penetrate the gate. Then, protons are transported by "hopping" along the wire. In this paper, both mechanisms are evaluated in a series of molecular dynamics simulations by investigating stability of different protonation states of the channel that are involved in these mechanisms. For the shuttle mechanism, these are states with all epsilon protonated histidines, one biprotonated residue or one histidine protonated in the delta position. For the gate opening mechanism, this is the state in which all four histidines are biprotonated. In addition, a state with two biprotonated histidines is considered. For each system, composed of the protein channel embedded in phospholipid bilayer located between two water lamellae, a molecular dynamics trajectory of approximately 1.3 ns (after equilibration) was obtained. It is found that the states involved in the shuttle mechanism are stable during the simulations. Furthermore, the orientations and dynamics of water molecules near the gate are conducive to proton transfers involved in the shuttle. In contract, the fully biprotonated state, implicated in the gate opening mechanism, is not stable and the channel looses its structural integrity. If only two histidines are biprotonated the channel deforms but remains intact with the gate mostly closed. In summary, the results of this study lend support to the shuttle mechanism but not to the gate opening mechanism of proton gating in M2.
Release of Minerals from Dried Hijiki, Sargassum fusiforme (Harvey) Setchell, during Water-Soaking

Summary During the water‑soaking process to remove arsenic from dried Hijiki at 30℃ some other beneficial elements are also lost. During this process the amounts of calcium iron magnesium and zinc released into water were 49 % 32 % 77 % and 70 % of those originally present respectively. Thus water‑soaking for longer than 30 min at room temperature is recommended to eliminate arsenic from Hijiki but it should be cooked together with other materials such as soybeans carrot etc to supply the lost beneficial elements.
Idiopathic Sudden Sensorineural Hearing Loss in Children: A Systematic Review and Meta-analysis

Objective Idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon in children, and its treatment and outcome are debated. We aimed to critically review evidence in the literature about treatment options and functional outcomes of pediatric ISSNHL. Additionally, we performed a meta-analysis of the results of combined systemic-intratympanic steroid therapy versus solely systemic treatment. Data Sources A search was run in the PubMed, Scopus, and Google Scholar databases. Review Methods Included articles were original ISSNHL case series, written in English, with a population age ranging from 2 to 19 years. Other study types (single case reports, editorials, and reviews) and case series with known etiology of sudden hearing loss were excluded. Descriptive data of patients, treatments, outcomes, and possible prognostic factors were extracted and recorded for every included study. Results Twelve articles (7 cohort and 5 case-control studies) met all the selection criteria. Based on only the studies that provided sufficient data about clinical outcome, the pooled overall recovery rate was 67.91% (95% CI, 58.34%-77.48%). No studies showed a significant difference between systemic steroid and combined systemic-intratympanic steroid. The pooled odds ratio for combined systemic-intratympanic steroid versus systemic steroid alone was 0.90 (95% CI, 0.36-2.27) based on a random effects model, ruling out any significant difference between these treatment options. Conclusions The results of our meta-analysis did not support combination therapy more than systemic steroid alone. Further prospective clinical trials are necessary to establish evidence-based therapies.
A practical guide to enzymology

Provided in this book are guidelines and practical advice for anyone working with enzymes. It offers advice on: how solvents, salts, substrates, and denaturants affect enzyme function and stability; developing a scheme for purifying an enzyme from different kinds of tissue; applying different techniques for fractionating proteins - ammonium sulfate, polyethylene glycol, and organic solvent fractionation - ion exchange, dye ligand, and bio-ligand affinity chromatography; characterizing proteins by determining molecular weight, isoelectric pH, amino acid composition and sequence, ligand binding and enzyme kinetics. Basic guidelines to a procedure and hints for operation of a technique are offered along with many references to the literature which provides additional details and theory. Methods for treating electrophoretic, gel permeation, enzyme kinetic and binding data are treated in detail. Various protein quantitation methods are described and their sensitivities are compared.
Inherited SLP76 deficiency in humans causes severe combined immunodeficiency, neutrophil and platelet defects

SLP76 is a key molecule involved in the T cell signaling pathway; therefore, SLP76 deficiency can lead to a severe type of immunodeficiency. By reporting on a patient with germline mutation in SLP76, deficiency in this gene is linked, for the first time, to a human disease.
Statistical shape model-based planning organ-at-risk volume: application to pancreatic cancer patients

Purpose. To introduce the concept of statistical shape model (SSM)-based planning organ-at-risk volume (sPRV) for pancreatic cancer patients. Methods. A total of 120 pancreatic cancer patients were enrolled in this study. After correcting inter-patient variations in the centroid position of the planning target volume (PTV), four different SSMs were constructed by registering a deformable template model to an individual model for the stomach and duodenum. The sPRV, which focused on the following different components of the inter-patient variations, was then created: Scenario A: shape, rotational angle, volume, and centroid position; Scenario B: shape, rotational angle, and volume; Scenario C: shape and rotational angle; and Scenario D: shape. The conventional PRV (cPRV) was created by adding an isotropic margin R (3–15 mm) to the mean shape model. The corresponding sPRV was created from the SSM until the volume difference between the cPRV and sPRV was less than 1%. Thereafter, we computed the overlapping volume between the PTV and cPRV (OLc) or sPRV (OLs) in each patient. OLs being larger than OLc implies that the local shape variations in the corresponding OAR close to the PTV were large. Therefore, OLs/OLc was calculated in each patient for each R-value, and the median value of OLs/OLc was regarded as a surrogate for plan quality for each R-value. Results. For R = 3 and 5 mm, OLs/OLc exceeded 1 for the stomach and duodenum in all scenarios, with a maximum OLs/OLc of 1.21. This indicates that smaller isotropic margins did not sufficiently account for the local shape changes close to the PTV. Conclusions. Our results indicated that, in contrast to conventional PRV, SSM-based PRVs, which account for local shape changes, would result in better dose sparing for the stomach and duodenum in pancreatic cancer patients.
Multifunctional DNA Nanogels for Aptamer-Based Targeted Delivery and Stimuli-Triggered Release of Cancer Therapeutics.

Targeted, stimulus-responsive DNA nanogels hold considerable promise for cancer therapeutics. To expand their functionality including thermoresponsiveness, here, multifunctional DNA nanogels are developed for potential application toward cancer-targeted delivery and stimuli-responsive release of cancer therapeutics. Three types of functionalized DNA nanobuilding units are formed into DNA nanogels of ≈200 nm via sequence-dependent self-assembly. The sequence-dependent assembly of nanobuilding units is precisely designed for controlled assembly and thermal disassembly at physiological temperatures. The supramolecular structure exhibits multifunctionalities including temperature-induced disassembly, aptamer-mediated cancer cell targeting, and light-triggered temperature increase. The nanogels support co-loading of cancer therapeutics including anti-sense oligonucleotides and doxorubicin along with stimuli-responsive release of loaded drugs through temperature-responsive structural disassembly and pH-responsive deintercalation. The nanogels exhibit efficient aptamer-mediated cancer-specific intracellular delivery and combinational anticancer effects upon light triggering. The developed DNA nanogels, thus, constitute potential noncationic nanovectors for targeted delivery of combinational cancer therapeutics.
Surface Acoustic Wave Sensor for C-Reactive Protein Detection

A surface acoustic wave (SAW) sensor was investigated for its application in C-reactive protein (CRP) detection. Piezoelectric lithium niobate (LiNbO3) substrates were used to study their frequency response characteristics in a SAW sensor with a CRP sensing area. After the fabrication of the SAW sensor, the immobilization process was performed for CRP/anti-CRP interaction. The CRP/anti-CRP interaction can be detected as mass variations in the sensing area. These mass variations may produce changes in the amplitude of sensor response. It was clearly observed that a CRP concentration of 0.1 μg/mL can be detected in the proposed SAW sensor. A good fitting linear relationship between the detected insertion loss (amplitude) and the concentrations of CRP from 0.1 μg/mL to 1 mg/mL was obtained. The detected shifts in the amplitude of insertion loss in SAW sensors for different CRP concentrations may be useful in the diagnosis of risk of cardiovascular diseases.
Does obesity lead to lower rates of clinically meaningful improvement or satisfaction after total hip arthroplasty? A propensity score-matched study

Background: Current literature lacks consensus regarding the impact of obesity on clinical outcomes of total hip arthroplasty (THA). The variability of results may reflect the lack of minimal clinically important difference (MCID) analysis, which helps to standardise the interpretation of patient-reported outcome measures (PROMs). We compared the PROMs, patient satisfaction and survivorship between obese and non-obese patients after THA. Methods: Prospectively collected registry data of 192 obese patients and 192 propensity score-matched controls who underwent primary THA at a single institution were reviewed. Clinical outcomes and satisfaction rates were assessed at 6 months and 2 years. Reoperations for surgical complications and revision rates were analysed. Results: Obese patients had a significantly poorer Oxford Hip Score (OHS) at 6 months and WOMAC-Function at 2 years. However, there was no difference in overall WOMAC, WOMAC-Pain, WOMAC-stiffness, SF-36 mental and physical component summary (PCS). A similar proportion of patients in each group achieved the MCID for OHS, WOMAC and SF-36 PCS. At 2 years, 90.3% of obese patients and 91.7% of controls were satisfied (p = 0.755). At a mean follow-up of 9 years, there were 5 reoperations (2.6%) for surgical complications in the obese group and 1 (0.5%) in the control group; whereas 12 revisions (6.3%) were recorded in the obese group and 3 (1.6%) in the control group (p = 0.021). Conclusions: Despite a higher revision rate, obese patients undergoing THA may experience a similar level of clinical meaningful improvement and satisfaction as their non-obese counterparts. This study provides valuable prognostic information for obese patients and guides preoperative counselling.