Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of a Cellodextrin Transporter in Aspergillus niger

Aspergillus niger produces a wide spectrum of extracellular polysaccharide hydrolases that hydrolyze cellulose into soluble glucose and cellodextrins. Transporters are essential for sugar uptake, yet it is not clear whether cellodextrin transporters exist in A. niger. Here, one cellulose inducible cellodextrin transporter CtA was identified in A. niger B2. It was found that CtA not only could transport cellobiose, but also cellotriose, cellotetraose, and cellopentaose. The yeast strain YPβG-CtA, expressing cellodextrin transporter CtA and an intracellular β-glucosidase, grew on cellobiose with the cell growth rate of 0.0830 ± 0.0113 h–1 under aerobic condition. Furthermore, the engineered yeast could produce 1.1 g/L ethanol anaerobically on cellobiose in 2 days. The identification of CtA provides evidence that the cellodextrin uptake is a complementary strategy of cellulose utilization in A. niger, and the CtA could be a strong transporter candidate for constructing engineered cellodextrin-utilizing microorganisms.
Broadly Protective Strategies Against Influenza Viruses: Universal Vaccines and Therapeutics

Influenza virus is a respiratory pathogen that can cause disease in humans, with symptoms ranging from mild to life-threatening. The vast majority of influenza virus infections in humans are observed during seasonal epidemics and occasional pandemics. Given the substantial public health burden associated with influenza virus infection, yearly vaccination is recommended for protection against seasonal influenza viruses. Despite vigilant surveillance for new variants and careful selection of seasonal vaccine strains, the efficacy of seasonal vaccines can vary widely from year to year. This often results in lowered protection within the population, regardless of vaccination status. In order to broaden the protection afforded by seasonal influenza vaccines, the National Institute of Allergy and Infectious Diseases (NIAID) has deemed the development of a universal influenza virus vaccine to be a priority in influenza virus vaccine research. This universal vaccine would provide protection against all influenza virus strains, eliminating the need for the yearly reformulations of seasonal influenza vaccines. In addition to universal influenza vaccine efforts, substantial progress has been made in developing novel influenza virus therapeutics that utilize broadly neutralizing antibodies to provide protection against influenza virus infection and to mitigate disease outcomes during infection. In this review, we discuss various approaches toward the goal of improving influenza virus vaccine efficacy through a universal influenza virus vaccine. We also address the novel methods of discovery and utilization of broadly neutralizing antibodies to improve influenza disease outcomes.
Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies

The P/Q-type CaV2.1 channel regulates neurotransmitter release at neuromuscular junctions (NMJ) and many central synapses. CACNA1A encodes the pore-containing α1A subunit of CaV2.1 channels. In humans, de novo CACNA1A mutations result in a wide spectrum of neurological, neuromuscular, and movement disorders, such as familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), as well as a more recently discovered class of more severe disorders, which are characterized by ataxia, hypotonia, cerebellar atrophy, and cognitive/developmental delay. Heterologous expression of CaV2.1 channels has allowed for an understanding of the consequences of CACNA1A missense mutations on channel function. In contrast, a mechanistic understanding of how specific CACNA1A mutations lead in vivo to the resultant phenotypes is lacking. In this review, we present the zebrafish as a model to both study in vivo mechanisms of CACNA1A mutations that result in synaptic and behavioral defects and to screen for effective drug therapies to combat these and other CaV2.1 channelopathies.
Optimizing Computer–Brain Interface Parameters for Non-invasive Brain-to-Brain Interface

A non-invasive, brain-to-brain interface (BBI) requires precision neuromodulation and high temporal resolution as well as portability to increase accessibility. A BBI is a combination of the brain–computer interface (BCI) and the computer–brain interface (CBI). The optimization of BCI parameters has been extensively researched, but CBI has not. Parameters taken from the BCI and CBI literature were used to simulate a two-class medical monitoring BBI system under a wide range of conditions. BBI function was assessed using the information transfer rate (ITR), measured in bits per trial and bits per minute. The BBI ITR was a function of classifier accuracy, window update rate, system latency, stimulation failure rate (SFR), and timeout threshold. The BCI parameters, including window length, update rate, and classifier accuracy, were kept constant to investigate the effects of varying the CBI parameters, including system latency, SFR, and timeout threshold. Based on passively monitoring BCI parameters, a base ITR of 1 bit/trial was used. The optimal latency was found to be 100 ms or less, with a threshold no more than twice its value. With the optimal latency and timeout parameters, the system was able to maintain near-maximum efficiency, even with a 25% SFR. When the CBI and BCI parameters are compared, the CBI’s system latency and timeout threshold should be reflected in the BCI’s update rate. This would maximize the number of trials, even at a high SFR. These findings suggested that a higher number of trials per minute optimizes the ITR of a non-invasive BBI. The delays innate to each BCI protocol and CBI stimulation method must also be accounted for. The high latencies in each are the primary constraints of non-invasive BBI for the foreseeable future.
Clonal Selection of a Novel Deleterious TP53 Somatic Mutation Discovered in ctDNA of a KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumor Resistant to Imatinib

The standard of care for the first-line treatment of advanced gastrointestinal stromal tumor (GIST) is represented by imatinib, which is given daily at a standard dosage until tumor progression. Resistance to imatinib commonly occurs through the clonal selection of genetic mutations in the tumor DNA, and an increase in imatinib dosage was demonstrated to be efficacious to overcome imatinib resistance. Wild-type GISTs, which do not display KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations, are usually primarily insensitive to imatinib and tend to rapidly relapse in course of treatment. Here we report the case of a 53-year-old male patient with gastric GIST who primarily did not respond to imatinib and that, despite the administration of an increased imatinib dose, led to patient death. By using a deep next-generation sequencing barcode-aware approach, we analyzed a panel of actionable cancer-related genes in the patient cfDNA to investigate somatic changes responsible for imatinib resistance. We identified, in two serial circulating tumor DNA (ctDNA) samples, a sharp increase in the allele frequency of a never described TP53 mutation (c.560-7_560-2delCTCTTAinsT) located in a splice acceptor site and responsible for a protein loss of function. The same TP53 mutation was retrospectively identified in the primary tumor by digital droplet PCR at a subclonal frequency (0.1%). The mutation was detected at a very high allelic frequency (99%) in the metastatic hepatic lesion, suggesting a rapid clonal selection of the mutation during tumor progression. Imatinib plasma concentration at steady state was above the threshold of 760 ng/ml reported in the literature for the minimum efficacious concentration. The de novo TP53 (c.560-7_560-2delCTCTTAinsT) mutation was in silico predicted to be associated with an aberrant RNA splicing and with an aggressive phenotype which might have contributed to a rapid disease spread despite the administration of an increased imatinib dosage. This result underlies the need of a better investigation upon the role of TP53 in the pathogenesis of GISTs and sustains the use of next-generation sequencing (NGS) in cfDNA for the identification of novel genetic markers in wild-type GISTs.
TEOS Modified With Nano-Calcium Oxalate and PDMS to Protect Concrete Based Cultural Heritage Buildings

Cultural Heritage constructions of twentieth century consist largely of mortar and concrete substrates. These concrete structures have suffered different types of decay processes. One of the most widely used consolidants is the Tetraethoxysilane (TEOS), which forms the basis of most existing commercial strengthening agents to protect porous building materials against deterioration. A novel, non-toxic strengthening and protective agent for mortar and concrete substrates was synthesized in a one-pot sol-gel procedure, incorporating in TEOS, Polydimethyl siloxane (PDMS), and nanoparticles of synthesized calcium oxalate (CaOx). PDMS provided hydrophobicity and reduced surface tension that causes cracks on the surface of produced xerogel. The synthesized nanocomposite both in sol and xerogel form was assessed with a variety of analytical techniques (FTIR, XRF, SEM, Optical Microscopy, Dynamic Light Scattering, Thermogravimetric analysis). The excellent physical properties of the produced colloidal solution of the nanocomposite, such as low viscosity and density, allow a penetration up to 2 cm from the surface in the treated cement mortars. This involved improvement of the mechanical and physical properties, such as the dynamic modulus of elasticity and increased water repellency. The treated cement mortars exhibited well-preserved aesthetic surface parameters and significant maintenance of the treatment. Furthermore, no harmful byproducts were identified indicating the nanocomposite compatibility to the siliceous and carbonate nature of the treated cement mortars.
Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells

Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontrollable deviations in the induction of stem cells differentiation, there are few materials that can currently be translated into clinical applications. In addition to the favorable mechanical properties and biocompatibility of IVD materials, maintaining stem cells activity in the local niche and increasing the ability of stem cells to differentiate into nucleus pulposus (NP) and annulus fibrosus (AF) cells are the basis for promoting the application of IVD-regenerating materials in clinical practice. The purpose of this review is to summarize IVD-regenerating materials that focus on stem cells strategies, analyze the properties of these materials that affect the differentiation of stem cells into IVD-like cells, and then present the limitations of currently used disc materials in the field of stem cell therapy and future research perspectives.
Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are used as a treatment for non‐small‐cell lung cancer. There have been some reports of EGFR‐TKIs being associated with vascular adverse events. We found that EGFR‐TKIs decreased the proliferation of HMEC‐1s (immortalized human dermal microvascular endothelial cells) and HMVECs (human dermal microvascular endothelial cells), and also inhibited the phosphorylation of EGFR and ERK. We examined the mRNA expression profile of erlotinib‐treated HMEC‐1s and identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most consistently up‐regulated transcript and protein. IQGAP1 was also overexpressed and co‐localized with endothelial cells in the lesional skin. Notably, increased IQGAP1 expression was associated with decreased transendothelial electrical resistance and increased vascular permeability in vitro. Erlotinib treatment enriched the staining of IQGAP1 and reduced the intensities of α‐catenin at the sites of cell–cell contact. In conclusion, erlotinib induces adherens junction dysfunction by modulating the expression of IQGAP1 in dermal endothelial cells. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Feline Distal Tibial Physeal Fracture Repair Using a Modified Cross-Pin Technique with Four Pins

Abstract Objective The aim of this article was to report the surgical technique and clinical outcome of a modified cross-pin technique for the treatment of distal tibial physeal fractures in cats without postoperative external coaptation. Study Design This study was a retrospective clinical study. Animals A total of 9 cats were presented with fracture of the distal tibial physis. Materials and Methods Medical records from July 2014 to September 2018 were reviewed. In all cases, a second medial and a craniolateral Kirschner wires were added to the traditional cross-pin technique. Information reviewed included orthogonal radiographs pre- and post-surgery and at subsequent re-examinations, subjective assessment of lameness and passive range of motion, veterinary clinical assessment and completion of a functional questionnaire (feline musculoskeletal pain index) at the time of writing this report. Eight owners completed the questionnaire. The mean questionnaire follow-up time was 12.7 months. Results Uncomplicated fracture healing occurred in all patients. Two patients required implant removal due to Kirschner wire migration and protrusion through the skin at 5 and 12 months post-surgery. No other complications were noticed. Eight patients had an excellent outcome, and one patient had a good outcome. Conclusion Distal tibial physeal fractures in cats can be treated successfully with the use of a modified cross-pin technique and without the use of external coaptation. Prognosis should be considered favourable for this type of fracture.
Teenager, Parent, and Clinician Perspectives on the Electronic Health Record

* Abbreviation: EHR — : electronic health record Management of adolescent confidentiality and sensitive services has always posed challenges to medical clinicians. State and federal laws, as well as institutional policies, may dictate what information can or cannot be shared by a clinician with a parent or guardian of an adolescent. Clinicians concerned about diagnosis disclosure via insurance notifications may limit their testing or prescription, refer sensitive services to more specialized reproductive health clinics, or appeal to noninsurance funders to cover sensitive testing and confidential prescriptions. All factors may be burdensome to patients, families, and/or clinicians. With the advent of electronic health records (EHRs), clinicians face additional challenges for preserving adolescent confidentiality.1 Clinicians are frequently in the difficult situation of balancing their patient’s need for confidentiality with creating an accurate and complete medical record that enhances coordination of care with families and other clinicians.2 Current EHR systems are often extremely limited in their ability to ensure confidentiality of items such as medications or problem lists across the many interfaces in which these items could be disclosed (such as after-visit summaries, shared or open notes, problem and medication lists within the portal system). 3 Whereas some institutions have a practice of using confidential note types or confidential encounters for sensitive information, this practice relies on clinicians to consistently document the appropriate information in the appropriate location. Institutions have also used custom-built functionality for excluding specific laboratory values or medications from being shared within the portal, but this is a labor-intensive undertaking that requires … Address correspondence to Jennifer L. Carlson, MD, Division of Adolescent Medicine, School of Medicine, Stanford University, 770 Welch Rd, Suite 100, Palo Alto, CA 94304. E-mail: carlson2{at}stanford.edu
The Preferred Management of a Single-Digit Distal Phalanx Amputation

Abstract Background Replantation of a single digit at the distal phalanx level is not routinely performed since it is technically challenging with questionable cost-effectiveness. The purpose of this study was to analyze international microsurgeons' clinical decisions when faced with this common scenario. Methods A survey of a right-middle finger distal phalanx transverse complete amputation case was conducted via online and paper questionnaires. Microsurgeons around the world were invited to provide their treatment recommendations. In total, 383 microsurgeons replied, and their responses were stratified and analyzed by geographical areas, specialties, microsurgery fellowship training, and clinical experiences. Results Among 383 microsurgeons, 170 (44.3%) chose replantation as their preferred management option, 137 (35.8%) chose revision amputation, 62 (16.2%) chose local flap coverage, 8 (2.1%) chose composite graft, and 6 (1.6%) favored other choices as their reconstruction method for the case study. Microsurgeons from the Asia-Pacific, Middle East/South Asia, and Central/South America regions tend to perform replantation (70.7, 68.8, and 67.4%, respectively) whereas surgeons from North America and Europe showed a lower preference toward replantation (20.5 and 26.8%, respectively p < 0.001). Having completed a microsurgery fellowship increased the attempt rate of replantation by 15.3% (p = 0.004). Clinical experience and the surgeons' specialties did not show statistical significance in clinical decision making. Conclusion From the present study, the geographic preferences and microsurgery fellowship experience influence the method of reconstruction for distal phalanx amputation. Multiple factors are taken into consideration in selecting the most suitable reconstructive method for each case scenario. In addition to the technical challenges of the proposed surgery, the cost of the procedure and the type of facility needed are important variables in the decision making process.
Geo-Social Top-k and Skyline Keyword Queries on Road Networks

The rapid growth of GPS-enabled mobile devices has popularized many location-based applications. Spatial keyword search which finds objects of interest by considering both spatial locations and textual descriptions has become very useful in these applications. The recent integration of social data with spatial keyword search opens a new service horizon for users. Few previous studies have proposed methods to combine spatial keyword queries with social data in Euclidean space. However, most real-world applications constrain the distance between query location and data objects by a road network, where distance between two points is defined by the shortest connecting path. This paper proposes geo-social top-k keyword queries and geo-social skyline keyword queries on road networks. Both queries enrich traditional spatial keyword query semantics by incorporating social relevance component. We formalize the proposed query types and appropriate indexing frameworks and algorithms to efficiently process them. The effectiveness and efficiency of the proposed approaches are evaluated using real datasets.
Axial changes in wood functional traits have limited net effects on stem biomass increment in European beech (Fagus sylvatica)

Abstract During the growing season, trees allocate photoassimilates to increase their aboveground woody biomass in the stem (ABIstem). This ‘carbon allocation’ to structural growth is a dynamic process influenced by internal and external (e.g., climatic) drivers. While radial variability in wood formation and its resulting structure have been intensively studied, their variability along tree stems and subsequent impacts on ABIstem remain poorly understood. We collected wood cores from mature trees within a fixed plot in a well-studied temperate Fagus sylvatica L. forest. For a subset of trees, we performed regular interval sampling along the stem to elucidate axial variability in ring width (RW) and wood density (ρ), and the resulting effects on tree- and plot-level ABIstem. Moreover, we measured wood anatomical traits to understand the anatomical basis of ρ and the coupling between changes in RW and ρ during drought. We found no significant axial variability in ρ because an increase in the vessel-to-fiber ratio with smaller RW compensated for vessel tapering towards the apex. By contrast, temporal variability in RW varied significantly along the stem axis, depending on the growing conditions. Drought caused a more severe growth decrease, and wetter summers caused a disproportionate growth increase at the stem base compared with the top. Discarding this axial variability resulted in a significant overestimation of tree-level ABIstem in wetter and cooler summers, but this bias was reduced to ~2% when scaling ABIstem to the plot level. These results suggest that F. sylvatica prioritizes structural carbon sinks close to the canopy when conditions are unfavorable. The different axial variability in RW and ρ thereby indicates some independence of the processes that drive volume growth and wood structure along the stem. This refines our knowledge of carbon allocation dynamics in temperate diffuse-porous species and contributes to reducing uncertainties in determining forest carbon fixation.
Trafficking of siRNA precursors by the dsRBD protein Blanks in Drosophila

Abstract RNA interference targets aberrant transcripts with cognate small interfering RNAs, which derive from double-stranded RNA precursors. Several functional screens have identified Drosophila blanks/lump (CG10630) as a facilitator of RNAi, yet its molecular function has remained unknown. The protein carries two dsRNA binding domains (dsRBD) and blanks mutant males have a spermatogenesis defect. We demonstrate that blanks selectively boosts RNAi triggered by dsRNA of nuclear origin. Blanks binds dsRNA via its second dsRBD in vitro, shuttles between nucleus and cytoplasm and the abundance of siRNAs arising at many sites of convergent transcription is reduced in blanks mutants. Since features of nascent RNAs - such as introns and transcription beyond the polyA site – contribute to the small RNA pool, we propose that Blanks binds dsRNA formed by cognate nascent RNAs in the nucleus and fosters its export to the cytoplasm for dicing. We refer to the resulting small RNAs as blanks exported siRNAs (bepsiRNAs). While bepsiRNAs were fully dependent on RNA binding to the second dsRBD of blanks in transgenic flies, male fertility was not. This is consistent with a previous report that linked fertility to the first dsRBD of Blanks. The role of blanks in spermatogenesis appears thus unrelated to its role in dsRNA export.