Miracle-dz/UniFAR-FTUs huggingface dataset:
Noise Reduction in Cochlear Implant Signal Processing: A Review and Recent Developments

Cochlear implant technology successfully restores hearing function to patients with sensory impairment. Although cochlear implant users generally hear well in quiet, they still find noisy conditions very challenging, hence the need to employ noise reduction algorithms in these systems to enhance the user experience. This paper reviews noise reduction algorithms in cochlear implants. Traditionally, such algorithms have been classified as either single- or multiple-channel, depending on the number of microphones they use. This review retains this general classification in looking at recent papers and extends it to reflect recent interest in machine learning techniques. The review concludes with consideration of promising future areas of research.
Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

Background Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome. Methods In this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0–9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event. Results Poor outcomes were significantly more frequent in the CBS 0–9 group. Plasminogen activity on admission was significantly higher in the CBS 0–9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0–9) could be demonstrated (OR:0.519; 95%CI:0.298–0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated. Conclusions CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.
Verticillium dahliae secreted protein Vd424Y is required for full virulence, targets the nucleus of plant cells, and induces cell death

Abstract Fungal pathogens secrete effector proteins that regulate host immunity and can suppress basal defence mechanisms against colonization in plants. Verticillium dahliae is a widespread and destructive soilborne fungus that can cause vascular wilt disease and reduces plant yields. However, little is currently known about how the effectors secreted by V. dahliae function. In this study, we analysed and identified 34 candidate effectors in the V. dahliae secretome and found that Vd424Y, a glycoside hydrolase family 11 protein, was highly upregulated during the early stages of V. dahliae infection in cotton plants. This protein was located in the nucleus and its deletion compromised the virulence of the fungus. The transient expression of Vd424Y in Nicotiana benthamiana induced BAK1‐ and SOBIR1‐dependent cell death and activated both salicylic acid and jasmonic acid signalling. This enhanced its resistance to the oomycetes Phytophthora capsici in a way that depended on its nuclear localization signal and signal peptides. Our results demonstrate that Vd424Y is an important effector protein targeting the host nucleus to regulate and activate effector‐triggered immunity in plants.
Conjugate Electrospun 3D Gelatin Nanofiber Sponge for Rapid Hemostasis

Developing an excellent hemostatic material with good biocompatibility and high blood absorption capacity for rapid hemostasis of deep non‐compressible hemorrhage remains a significant challenge. Herein, a novel conjugate electrospinning strategy to prepare an ultralight 3D gelatin sponge consisting of continuous interconnected nanofibers. This unique fluffy nanofiber structure endows the sponge with low density, high surface area, compressibility, and ultrastrong liquid absorption capacity. In vitro assessments show the gelatin nanofiber sponge has good cytocompatibility, high cell permeability, and low hemolysis ratio. The rat subcutaneous implantation studies demonstrate good biocompatibility and biodegradability of gelatin nanofiber sponge. Gelatin nanofiber sponge aggregates and activates platelets in large quantities to accelerate the formation of platelet embolism, and simultaneously escalates other extrinsic and intrinsic coagulation pathways, which collectively contribute to its superior hemostatic capacity. In vivo studies on an ear artery injury model and a liver trauma model of rabbits demonstrate that the gelatin nanofiber sponge rapidly induce stable blood clots with least blood loss compared to gelatin nanofiber membrane, medical gauze, and commercial gelatin hemostatic sponge. Hence, the gelatin nanofiber sponge holds great potential as an absorbable hemostatic agent for rapid hemostasis.
Immunocytochemical evaluation of epithelial–mesenchymal transition in epithelial tumors of dogs and cats

Epithelial–mesenchymal transition (EMT) plays a crucial role in metastasis of epithelial tumors; however, it is challenging to detect EMT by cytology. In the present study, EMT was visualized by fluorescence-immunocytochemistry (FICC). Air-dried smears from epithelial tumors of dogs (n=22) and cats (n=9) were stained using mouse monoclonal anti-E-cadherin and rabbit monoclonal anti‐vimentin antibodies. Enzymatic immunohistochemistry (IHC) revealed that 51.6% (8/22 in dogs, 8/9 in cats) of the cases showed EMT. In dogs, FICC could detect EMT in 62.5% (5/8) of those cases. In cats, FICC could detect EMT in 100% (8/8) of the cases. In conclusion, the present FICC method could successfully detect EMT using conventional air-dried cytology smear slides.
Tranexamic acid in intracerebral hemorrhage: a meta-analysis

Abstract Background: Tranexamic acid(TA) is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Tranexamic acid might be beneficial for intracerebral hemorrhage(ICH). However, whether TA can treatment of intracerebral hemorrhage is still controversial. Objective Evidence-based medicine was used to evaluate the efficacy and safety of tranexamic acid in patients with intracerebral hemorrhage. Methods Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to October 2020 for randomized controlled trials (RCTs), cohort studies, and retrospective case series . The Jadad scale and RevMan software version 5.3 were used for literature quality assessment and meta-analysis. Results In total, 4 randomized controlled trials and 1 retrospective case series with 2808 participants were included in the meta-analysis. Compared with control intervention in intracerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (odds ratio (OR) =0.81; 95% confidence interval(CI)=0.68 to 0.99; p = 0.04) and Modified Rankin Scale score (MRS) at 90 days at 0–3 (OR = 1.20; 95% CI = 1.00 to 1.43; p = 0.05), mortality by day 90 (OR= 1.03; 95% CI= 0.85–1.25; p = 0.77) and major thromboembolic events (OR= 1.14; 95% CI= 0.73–1.77; p = 0.58). Conclusions Treatment with tranexamic acid could reduce hematoma expansion in intracerebral hemorrhage, and the treatment was safe with no increase in thromboembolic complications. But showed no notable impact on good functional outcomes and mortality.
Gene Therapy for Sickle Cell Disease - Moving from the Bench to the Bedside.

Gene therapy as a potential cure for sickle cell disease (SCD) has long been pursued given that this hemoglobin disorder results from a single point mutation. Advances in genomic sequencing, increased understanding of hemoglobin regulation and discoveries of molecular tools for genome modification of hematopoietic stem cells have made gene therapy for SCD possible. Gene addition strategies using gene transfer vectors have been optimized over the last few decades to enable expression of normal or anti-sickling globins as strategies to ameliorate SCD. Many hurdles had to be addressed prior to clinical translation including collection of sufficient stem cells for gene-modification, increasing expression of transferred genes to a therapeutic level and conditioning patients in a safe manner that enabled adequate engraftment of gene-modified cells. The discovery of genome editors that make precise modifications has further advanced the safety and efficacy of gene therapy and a rapid movement to clinical trial has undoubtedly been supported by lessons learned from optimizing gene addition strategies. Current gene therapies being tested in clinical trial require significant infrastructure and expertise given the needs to harvest cells from and administer chemotherapy to patients who often have significant organ dysfunction and that gene-modification takes place ex vivo in specialized facilities. For these therapies to realize their full potential they would need to be portable, safe and efficient making an in-vivo based approach attractive. Additionally, adequate resources for SCD screening and access to standardized care are critically important for gene therapy to be a viable treatment option for SCD.
Association of Combination of Conformation-Specific KIT Inhibitors With Clinical Benefit in Patients With Refractory Gastrointestinal Stromal Tumors: A Phase 1b/2a Nonrandomized Clinical Trial.

Importance Many cancer subtypes, including KIT-mutant gastrointestinal stromal tumors (GISTs), are driven by activating mutations in tyrosine kinases and may initially respond to kinase inhibitors but frequently relapse owing to outgrowth of heterogeneous subclones with resistance mutations. KIT inhibitors commonly used to treat GIST (eg, imatinib and sunitinib) are inactive-state (type II) inhibitors. Objective To assess whether combining a type II KIT inhibitor with a conformation-complementary, active-state (type I) KIT inhibitor is associated with broad mutation coverage and global disease control. Design, Setting, and Participants A highly selective type I inhibitor of KIT, PLX9486, was tested in a 2-part phase 1b/2a trial. Part 1 (dose escalation) evaluated PLX9486 monotherapy in patients with solid tumors. Part 2e (extension) evaluated PLX9486-sunitinib combination in patients with GIST. Patients were enrolled from March 2015 through February 2019; data analysis was performed from May 2020 through July 2020. Interventions Participants received 250, 350, 500, and 1000 mg of PLX9486 alone (part 1) or 500 and 1000 mg of PLX9486 together with 25 or 37.5 mg of sunitinib (part 2e) continuously in 28-day dosing cycles until disease progression, treatment discontinuation, or withdrawal. Main Outcomes and Measures Pharmacokinetics, safety, and tumor responses were assessed. Clinical efficacy end points (progression-free survival and clinical benefit rate) were supplemented with longitudinal monitoring of KIT mutations in circulating tumor DNA. Results A total of 39 PLX9486-naive patients (median age, 57 years [range, 39-79 years]; 22 men [56.4%]; 35 [89.7%] with refractory GIST) were enrolled in the dose escalation and extension parts. The recommended phase 2 dose of PLX9486 was 1000 mg daily. At this dose, PLX9486 could be safely combined with 25 or 37.5 mg daily of sunitinib continuously. Patients with GIST who received PLX9486 at a dose of 500 mg or less, at the recommended phase 2 dose, and with sunitinib had median (95% CI) progression-free survivals of 1.74 (1.54-1.84), 5.75 (0.99-11.0), and 12.1 (1.34-NA) months and clinical benefit rates (95% CI) of 14% (0%-58%), 50% (21%-79%), and 80% (52%-96%), respectively. Conclusions and Relevance In this phase 1b/2a nonrandomized clinical trial, type I and type II KIT inhibitors PLX9486 and sunitinib were safely coadministered at the recommended dose of both single agents in patients with refractory GIST. Results suggest that cotargeting 2 complementary conformational states of the same kinase was associated with clinical benefit with an acceptable safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT02401815.
The alternative RelB NF-κB subunit is a novel critical player in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid malignancy affecting adults. NF-kB transcription factor family is activated by two main pathways, the canonical and the alternative NF-kB activation pathways with different functions. The alternative NF-kB pathway leads to the activation of the transcriptionally active RelB NF-kB subunit. Alternative NF-kB activation status and its role in DLBCL pathogenesis remain undefined. Here, we reveal a frequent activation of RelB in a large cohort of DLBCL patients and cell lines, independently of their ABC or GCB subtypes. RelB activity defines a new subset of DLBCL patients with a peculiar gene expression profile and mutational pattern. Importantly, RelB activation does not correlate with the MCD genetic subtype, enriched for ABC tumors carrying MYD88L265P and CD79B mutations that cooperatively activate canonical NF-kB, thus indicating that current genetic tools to evaluate NF-kB activity in DLBCL do not provide information on the alternative NF-kB activation. Further, the newly defined RelB-positive subgroup of DLBCL patients exhibits a dismal outcome following immunochemotherapy. Functional studies revealed that RelB confers DLBCL cell resistance to DNA-damage induced apoptosis in response to doxorubicin, a genotoxic agent used in front-line treatment for DLBCL. We also show that RelB positivity is associated with high expression of cIAP2. Altogether, RelB activation can be used to refine the prognostic stratification of DLBCL and may contribute to subvert the therapeutic DNA damage response in a segment of DLBCL patients.
Advocacy of targeting protease‐activated receptors in severe coronavirus disease 2019

Identifying drug targets mitigating vascular dysfunction, thrombo‐inflammation and thromboembolic complications in COVID‐19 is essential. COVID‐19 coagulopathy differs from sepsis coagulopathy. Factors that drive severe lung pathology and coagulation abnormalities in COVID‐19 are not understood. Protein–protein interaction studies indicate that the tagged viral bait protein ORF9c directly interacts with PAR2, which modulates host cell IFN and inflammatory cytokines. In addition to direct interaction of SARS‐CoV‐2 viral protein with PARs, we speculate that activation of PAR by proteases plays a role in COVID‐19‐induced hyperinflammation. In COVID‐19‐associated coagulopathy elevated levels of activated coagulation proteases may cleave PARs in association with TMPRSS2. PARs activation enhances the release of cytokines, chemokines and tissue factor expression to propagate IFN‐dependent inflammation, leukocyte‐endothelial interaction, vascular permeability and coagulation responses. This hypothesis, corroborated by in vitro findings and emerging clinical evidence, will focus targeted studies of PAR1/2 blockers as adjuvant drugs against cytokine release syndrome and COVID‐19‐associated coagulopathy.
Artificial Diets With Different Protein Levels for Rearing Spodoptera frugiperda (Lepidoptera: Noctuidae)

Abstract Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera: Noctuidae) is a pest of great economic importance which can feed on more than 300 plant species. As it is polyphagous, its host plants may have variable physical and chemical constitutions. This may influence larval development, as protein and carbohydrate levels are important factors for adequate biological development. The aim of this study was to evaluate insect developmental parameters as well as to compare the food consumption of S. frugiperda larvae reared using diets with different protein levels under laboratory conditions. Three artificial diet formulations were used: one typically used for routine laboratory rearing, based on bean, wheat germ and brewer’s yeast (D1); one containing half the original amount of protein (D2), and the other with twice the original amount of protein (D3). The relative consumption rate (RCR), relative growth rate (RGR), and efficiency of conversion of ingested food (ECI) for S. frugiperda fourth instar larvae varied among diets. The protein present in the diet influenced the duration of larval and pupal periods and pupal weight, but did not affect larval survival, fecundity and longevity of adults. The different protein levels in the diets did not negatively influence population growth, so these three diet variations can be used for mass rearing in the laboratory. However, the influence of these diets on successive generations of the insect remains untested.
Potential precursor compounds for chlorohydrocarbons detected in Gale Crater, Mars, by the SAM instrument suite on the Curiosity Rover

The detection of chlorinated organic compounds in near‐surface sedimentary rocks by the Sample Analysis at Mars (SAM) instrument suite aboard the Mars Science Laboratory Curiosity rover represents an important step toward characterizing habitable environments on Mars. However, this discovery also raises questions about the identity and source of their precursor compounds and the processes by which they become chlorinated. Here we present the results of analog experiments, conducted under conditions similar to SAM gas chromatography‐mass spectrometry analyses, in which we pyrolyzed potential precursor compounds in the presence of various Cl salts and Fe oxides that have been identified in Martian sediments. While chloromethanes could not be unambiguously identified, 1,2‐dichloropropane (1,2‐DCP), which is one of the chlorinated compounds identified in SAM data, is formed from the chlorination of aliphatic precursors. Additionally, propanol produced more 1,2‐DCP than nonfunctionalized aliphatics such as propane or hexanes. Chlorinated benzenes ranging from chlorobenzene to hexachlorobenzene were identified in experiments with benzene carboxylic acids but not with benzene or toluene. Lastly, the distribution of chlorinated benzenes depended on both the substrate species and the nature and concentration of the Cl salt. Ca and Mg perchlorate, both of which release O2 in addition to Cl2 and HCl upon pyrolysis, formed less chlorobenzene relative to the sum of all chlorinated benzenes than in experiments with ferric chloride. FeCl3, a Lewis acid, catalyzes chlorination but does not aid combustion. Accordingly, both the precursor chemistry and sample mineralogy exert important controls on the distribution of chlorinated organics.
Strategies for climate change adaptation: lessons learnt from long-term planning in the Netherlands and Bangladesh

ABSTRACT This paper evaluates long-term climate change adaptation strategies in the Netherlands and Bangladesh using the Organisation for Economic Co-operation and Development’s (OECD) Principles of Good Water Governance. Deltas face complex challenges, and adequate long-term planning is essential for these regions. However, experience with these long-term planning efforts and linkages with theoretical frameworks on water-related policy and strategy development remain limited. Both countries politically approved significant investment portfolios for a durable adaptive strategy. This paper highlights the similarities and differences in the resulting strategies. Using the learning assessment methodology, we propose to add risk-based approaches and long-term strategic perspectives as additional OECD Principles in the conclusion.
Skeletal muscle thermogenesis enables aquatic life in the smallest marine mammal

Keeping warm when small Several mammal species live in cold-water environments, enabled by adaptations such as blubber and large size. A notable exception to this rule is the sea otter, a species that is orders of magnitude smaller and skinnier than the others. It is known that the sea otter's unusually thick fur helps, but Wright et al. show that they are also internally warmed by thermogenic leak from skeletal muscle, a process that elevates their metabolic rate three times above that expected for their size. This mechanism is present even in infants with immature muscles, providing these animals with internal warmth from birth. Science, abf4557, this issue p. 223 Thermogenesis is a primary regulator of sea otter muscle metabolism, allowing them to inhabit cold water. Basal metabolic rate generally scales with body mass in mammals, and variation from predicted levels indicates adaptive metabolic remodeling. As a thermogenic adaptation for living in cool water, sea otters have a basal metabolic rate approximately three times that of the predicted rate; however, the tissue-level source of this hypermetabolism is unknown. Because skeletal muscle is a major determinant of whole-body metabolism, we characterized respiratory capacity and thermogenic leak in sea otter muscle. Compared with that of previously sampled mammals, thermogenic muscle leak capacity was elevated and could account for sea otter hypermetabolism. Muscle respiratory capacity was modestly elevated and reached adult levels in neonates. Premature metabolic development and high leak rate indicate that sea otter muscle metabolism is regulated by thermogenic demand and is the source of basal hypermetabolism.
Use of Amlodipine in Psittacine Birds: 5 Cases (2010–2018)

Abstract: Amlodipine is a calcium channel blocker shown to be effective in lowering blood pressure with minimal adverse effects in mammals. To provide a retrospective evaluation of amlodipine use in psittacine birds, medical records were reviewed for all avian patients prescribed amlodipine for treatment for the presumptive diagnosis of hypertension, based on clinical signs and indirect blood pressure measurements. Five birds were treated with amlodipine between 2010 and 2018. The median age was 33 years (range, 22–37 years) and 3/5 birds presented for ataxia or seizures. The median indirect systolic blood pressure at diagnosis was 243 mm Hg (range, 200–275 mm Hg). In 3/5 birds, amlodipine was the only drug prescribed, whereas, in 2/5 birds, enalapril was also prescribed in addition to amlodipine. In addition to the prescription of enalapril, blood pressure measurements were obtained indirectly, which are variables to be considered in this report. The initial median dose of amlodipine prescribed was 0.4 mg/kg (range, 0.1–0.4 mg/kg) PO q24h. In 3/5 birds, amlodipine administration was increased either in dose or frequency. Median follow-up time was 25 months (range, 2–55 months) after the initiation of amlodipine treatment. Owners in all 5 cases reported improvement of clinical signs by a median time of 2 months (range, 1–15 months). Three of 5 birds (60%) demonstrated a decreasing trend in blood pressure during the first 6 months after treatment with amlodipine was started (average, ≥20% decrease). Prospective, controlled studies are needed to investigate the efficacy of amlodipine in psittacine birds.