Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
Vicarious Traumatization and Burnout among Service Providers for Victims of Commercial Sexual Exploitation

ABSTRACT Victims of commercial sexual exploitation (CSE) are in need of multiple community services to aid in their recovery. Service providers are critical to ensuring these victims receive needed treatment. Given the complex trauma of these victims and the necessity of long-term treatment, these service professionals may experience vicarious trauma (VT) and burnout. This qualitative study interviewed 12 professionals who have provided direct services to victims of CSE about their experiences. They had on average about 8 years of experience and three were survivors of CSE. Almost all reported instances of burnout and VT but also had strategies for the prevention of such experiences. Most participants reported experiences of VT and burnout are inevitable when working with this population, but self-care strategies and peer support are essential to combatting these negative experiences. These results can inform agencies that provide services to victims of CSE so as to ensure their staff stay healthy and avoid burnout.
EFFECTS OF SALINITY STRESS ON MEMBRANE STABILITY, CHLOROPHYLL CONTENT AND YIELD COMPONENTS OF WHEAT INOCULATED WITH PLANT GROWTH PROMOTING BACTERIA AND HUMIC ACID

هديكچ فلتخم یاه شور هب ار یعارز هايگ دركلمع هك تسا ناهج كشخ همين و كشخ قطانم رد یعارز تلاوصحم ديلوت عناوم نيرتمهم زا یكي یروش بيرخت بيترت نيمه هب . دهد یم شهاك ار زتنسوتف تهج هايگ هوقلاب یياناوت ،یروش رثا نيتسخن ناونعب گرب حطس شهاك . دهد یم رارق ريثات تحت و سوموه زا لصاح یلآ ديسا كي ناونع هب كيمويه ديسا و ،تشاد دهاوخ لابند هب ار زتنسوتف شهاك ،ميدس هلمجزا یمس ی اهنوي طسوت ليفورلك صوصخ هب مدنگ رد هناد دركلمع ندرب لااب تهج یياذغ رصانع بذج دوبهب و ینومروه تارثا قيرط زا دشر كرحم یاه یرتكاب و یعيبط عبانم رياس یتاقيقحت هناخلگ رد راركت هسرد یفداصت لاماك حرط بلاق رد ليروتكاف تروص هب یشيامزآروظنم نيدب . دوش عقاو رثوم دنناوت یم یروش شنت طيارش رد ،دهاش :)A0( :لماش حطس ود رد كيمويهديسا لماش یشيامزآ یاهراميت .دش ارجا 1389 لاس رد جرك دحاو یملاسا دازآ هاگشناد یزرواشك هدكشناد نازيم هب لااب یروش :)B2( ،رلاوم یليم 75 نازيم هب نيياپ یروش :)B1( ،دهاش :)B0( :لماش حطس هس رد یروش حوطسو ،كيموهديسا فرصم :)A1( اب رذب حيقلت :)C2( ،مورفوپيل موليريپسوزآ یرتكاب ابرذب حيقلت :)C1( ،دهاش )C0( :لماش حطس جنپ رد اه مسيناگراوركيم زا هدافتسا ،رلاوم یليم 150 ،مورفوپيل موليريپسوزآ ،موكورك رتكابوتزا( یاه یرتكاب ابرذب حيقلت :)C4( ،اديتوپ سانومودوس یرتكاب اب رذب حيقلت :)C3( ،موكوركرتكابوتزا یرتكاب شنت لامعا نامز رد كيمويه ديسا فرصم و دشر كرحم یاه یرتكاب اب رذب حيقلت لباقتم رثا داد ناشن جياتن .دوب لولحم تروص هب )اديتوپ سانومودوسپ رتكابوتزا یرتكاب اب رذب حيقلت راميت زا هناد دركلمع نيرتشيب . دوب راد ینعمb و a ليفورلك و هچلبنس دادعت ،كيژولويب دركلمع ،هناد دركلمع رب یروش یرتكاب اب رذب حيقلت راميت زا كيژولويب دركلمع نازيم نيرتشيب ،دمآ تسدب رلاوم یليم 75 یروش شنت لامعا و كيمويه ديسا فرصم مدع و موكورك اب رذب حيقلت راميت زا هتوب رد هچلبنس دادعت نيرتشيب . ديدرگ لصاح رلاوم یليم 75 یروش شنت لامعا و كيمويه ديسا فرصم و اديتوپ سانومودوس bو a ليفورلك نازيم نيرتشيب هكنآ نمض ،دمآ تسدب یروش شنت لامعا مدع و كيمويه ديسا فرصم و لولحم تروص هب دشر كرحم یاه یرتكاب . دمآ تسد هب رلاوم یليم 75یروش شنت لامعا و كيمويه ديسا فرصم و مورفوپيل موليريپسوزآ یرتكاب اب رذب حيقلت راميت زا زين
Pyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa

P. aeruginosa is one of the most common causative agents for ventilator-associated pneumonia and nosocomial bacteremia and is a leading cause of death in patients with cystic fibrosis. Pandrug-resistant strains of P. aeruginosa are increasingly identified in clinical samples and show resistance to virtually all major classes of antibiotics, including aminoglycosides, cephalosporins, and carbapenems. ABSTRACT Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that frequently causes ventilator-associated pneumonia in intensive care units and chronic lung infections in cystic fibrosis patients. The rising prevalence of drug-resistant bacteria demands the exploration of new therapeutic avenues for treating P. aeruginosa infections. Perhaps the most thoroughly explored alternative is to use novel treatments to target pathogen virulence factors, like biofilm or toxin production. Gallium(III) nitrate is one such agent. It has been recognized for its ability to inhibit pathogen growth and biofilm formation in P. aeruginosa by disrupting bacterial iron homeostasis. However, irreversible sequestration by pyoverdine substantially limits its effectiveness. In this report, we show that disrupting pyoverdine production (genetically or chemically) potentiates the efficacy of gallium nitrate. Interestingly, we report that the pyoverdine inhibitor 5-fluorocytosine primarily functions as an antivirulent, even when it indirectly affects bacterial growth in the presence of gallium, and that low selective pressure for resistance occurs. We also demonstrate that the antibiotic tetracycline inhibits pyoverdine at concentrations below those required to prevent bacterial growth, and this activity allows it to synergize with gallium to inhibit bacterial growth and rescue Caenorhabditis elegans during P. aeruginosa pathogenesis. IMPORTANCE P. aeruginosa is one of the most common causative agents for ventilator-associated pneumonia and nosocomial bacteremia and is a leading cause of death in patients with cystic fibrosis. Pandrug-resistant strains of P. aeruginosa are increasingly identified in clinical samples and show resistance to virtually all major classes of antibiotics, including aminoglycosides, cephalosporins, and carbapenems. Gallium(III) nitrate has received considerable attention as an antipseudomonal agent that inhibits P. aeruginosa growth and biofilm formation by disrupting bacterial iron homeostasis. This report demonstrates that biosynthetic inhibitors of pyoverdine, such as 5-fluorocytosine and tetracycline, synergize with gallium nitrate to inhibit P. aeruginosa growth and biofilm formation, rescuing C. elegans hosts during pathogenesis.
Causes of discrepancies between medications listed in the national electronic prescribing system and patients' actual use of medications

Discrepancies between registered prescriptions and patients' actual use of medications are described as frequent and often resulting in adverse medication events. We aimed to assess the extent of and causes behind discrepancies between medications listed in the Danish national prescription system (Shared Medication Record) and patients' actual use of medications. We prospectively reconciled medication for 260 consecutively admitted polypharmacy patients (>50 years and ≥5 prescriptions) at two hospitals in the Capital Region of Denmark. The type of discrepancies were determined and the cause of the discrepancies were evaluated as primarily caused by (1) the patient (i.e., intentional or unintentional non‐adherence) or (2) the health care system (i.e., lack of appropriate update of the SMR by physicians in primary or secondary care). There was a median of 12 [IQR 9–15] medications listed and 3 [IQR 1–5] medication discrepancies per patient (total n = 925). The majority (53%) of discrepancies were caused by the health care system, 32% were caused by the patients, of which 70% were intentional non‐adherence, and 15% had an indeterminable cause. In conclusion, discrepancies between medications listed in the Shared Medication Record and actual use of medications were frequent and were most often caused by clinicians not updating the prescription information.
Molecularly Imprinted Polymer

Using Zn_2,2′_dipyridyl complex as template,4_vinylpyridine as the functional monomer and triallyl isocyanurate as the cross_linking monomer,a zinc(Ⅱ)_complex template polymer was prepared by molecularly imprinting technology.The regulation effect of Zn(Ⅱ)to the selective recognition of polymer was studied.The results showed that the ability of selective recognition for2,2′_dipyridyl by the polymer was distinctly enhanced in certain zinc(Ⅱ)acetate solution through equilibrium_binding experiment.
Composite Kernel of Mutual Learning on Mid-Level Features for Hyperspectral Image Classification

By training different models and averaging their predictions, the performance of the machine-learning algorithm can be improved. The performance optimization of multiple models is supposed to generalize further data well. This requires the knowledge transfer of generalization information between models. In this article, a multiple kernel mutual learning method based on transfer learning of combined mid-level features is proposed for hyperspectral classification. Three-layer homogenous superpixels are computed on the image formed by PCA, which is used for computing mid-level features. The three mid-level features include: 1) the sparse reconstructed feature; 2) combined mean feature; and 3) uniqueness. The sparse reconstruction feature is obtained by a joint sparse representation model under the constraint of three-scale superpixels’ boundaries and regions. The combined mean features are computed with average values of spectra in multilayer superpixels, and the uniqueness is obtained by the superposed manifold ranking values of multilayer superpixels. Next, three kernels of samples in different feature spaces are computed for mutual learning by minimizing the divergence. Then, a combined kernel is constructed to optimize the sample distance measurement and applied by employing SVM training to build classifiers. Experiments are performed on real hyperspectral datasets, and the corresponding results demonstrated that the proposed method can perform significantly better than several state-of-the-art competitive algorithms based on MKL and deep learning.
Alterations in hormonal signals spatially coordinate distinct responses to DNA double-strand breaks in Arabidopsis roots

Plant hormones cytokinin and auxin orchestrate differential DNA damage responses in Arabidopsis roots. Plants have a high ability to cope with changing environments and grow continuously throughout life. However, the mechanisms by which plants strike a balance between stress response and organ growth remain elusive. Here, we found that DNA double-strand breaks enhance the accumulation of cytokinin hormones through the DNA damage signaling pathway in the Arabidopsis root tip. Our data showed that activation of cytokinin signaling suppresses the expression of some of the PIN-FORMED genes that encode efflux carriers of another hormone, auxin, thereby decreasing the auxin signals in the root tip and causing cell cycle arrest at G2 phase and stem cell death. Elevated cytokinin signaling also promotes an early transition from cell division to endoreplication in the basal part of the root apex. We propose that plant hormones spatially coordinate differential DNA damage responses, thereby maintaining genome integrity and minimizing cell death to ensure continuous root growth.
Single-round deoxyribozyme discovery

Abstract Artificial evolution experiments typically use libraries of ∼1015 sequences and require multiple rounds of selection to identify rare variants with a desired activity. Based on the simple structures of some aptamers and nucleic acid enzymes, we hypothesized that functional motifs could be isolated from significantly smaller libraries in a single round of selection followed by high-throughput sequencing. To test this idea, we investigated the catalytic potential of DNA architectures in which twelve or fifteen randomized positions were embedded in a scaffold present in all library members. After incubating in either the presence or absence of lead (which promotes the nonenzymatic cleavage of RNA), library members that cleaved themselves at an RNA linkage were purified by PAGE and characterized by high-throughput sequencing. These selections yielded deoxyribozymes with activities 8- to 30-fold lower than those previously isolated under similar conditions from libraries containing 1014 different sequences, indicating that the disadvantage of using a less diverse pool can be surprisingly small. It was also possible to elucidate the sequence requirements and secondary structures of deoxyribozymes without performing additional experiments. Due to its relative simplicity, we anticipate that this approach will accelerate the discovery of new catalytic DNA and RNA motifs.
Double‐edged effects of tamoxifen‐in‐oil‐gavage on an infectious murine model for multiple sclerosis

Tamoxifen gavage is a commonly used method to induce genetic modifications in cre‐loxP systems. As a selective estrogen receptor modulator (SERM), the compound is known to have immunomodulatory and neuroprotective properties in non‐infectious central nervous system (CNS) disorders. It can even cause complete prevention of lesion development as seen in experimental autoimmune encephalitis (EAE). The effect on infectious brain disorders is scarcely investigated. In this study, susceptible SJL mice were infected intracerebrally with Theiler's murine encephalomyelitis virus (TMEV) and treated three times with a tamoxifen‐in‐oil‐gavage (TOG), resembling an application scheme for genetically modified mice, starting at 0, 18, or 38 days post infection (dpi). All mice developed ‘TMEV‐induced demyelinating disease’ (TMEV‐IDD) resulting in inflammation, axonal loss, and demyelination of the spinal cord. TOG had a positive effect on the numbers of oligodendrocytes and oligodendrocyte progenitor cells, irrespective of the time point of application, whereas late application (starting 38 dpi) was associated with increased demyelination of the spinal cord white matter 85 dpi. Furthermore, TOG had differential effects on the CD4+ and CD8+ T cell infiltration into the CNS, especially a long lasting increase of CD8+ cells was detected in the inflamed spinal cord, depending of the time point of TOG application. Number of TMEV‐positive cells, astrogliosis, astrocyte phenotype, apoptosis, clinical score, and motor function were not measurably affected. These data indicate that tamoxifen gavage has a double‐edged effect on TMEV‐IDD with the promotion of oligodendrocyte differentiation and proliferation, but also increased demyelination, depending on the time point of application. The data of this study suggest that tamoxifen has also partially protective functions in infectious CNS disease. These effects should be considered in experimental studies using the cre‐loxP system, especially in models investigating neuropathologies.
Inhibiting PDE7A Enhances the Protective Effects of Neural Stem Cells on Neurodegeneration and Memory Deficits in Sevoflurane-Exposed Mice

Abstract Sevoflurane is widely used in general anesthesia, especially for children. However, prolonged exposure to sevoflurane is reported to be associated with adverse effects on the development of brain in infant monkey. Neural stem cells (NSCs), with potent proliferation, differentiation, and renewing ability, provide an encouraging tool for basic research and clinical therapies for neurodegenerative diseases. We aim to explore the functional effects of injecting NSCs with phosphodiesterase 7A (PDE7A) knock-down in infant mice exposed to sevoflurane. The effects of PDE7A in NSCs proliferation and differentiation were determined by cell counting kit-8 (CCK-8) assay and differentiation-related gene expression assay, respectively. The effects of NSCs with modified PDE7A on mice’s long-term memory and learning ability were assessed by behavioral assays. Our data demonstrated that depleting PDE7A promoted, whereas forcing PDE7A suppressed the activation of cAMP/cAMP-response element binding protein (CREB) signaling as well as cell proliferation and neuronal differentiation of NSCs. Inhibition of PDE7A in NSCs exhibited profound improved effects on long-term memory and learning ability of mice exposed to sevoflurane. Our results for the first time show that knock-down of PDE7A improves the neurogenesis of NSCs in vitro and in vivo, and is beneficial for alleviating sevoflurane-induced brain damage in infant mice.
Extracranial metastatic solitary fibrous tumor/hemangiopericytoma expressing G‐CSF and its receptor

Although extracranial metastases are a relatively common phenomenon in patients with solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs), factors involved in the mechanism underlying tumor growth and metastasis have not been identified. We report a case of extracranial metastatic SFT/HPC synthesizing granulocyte colony‐stimulating factor (G‐CSF) and G‐CSF receptor (G‐CSFR). A 39‐year‐old man underwent a gross total resection of a well‐circumscribed, dura‐based, extracerebral primary tumor at the right frontal convexity. Neuropathologic evaluation of the tumor revealed an SFT/HPC characterized by staghorn vessels and a patternless architecture of hypercellular tumor cells, which had the eosinophilic cytoplasm and the nucleus immunoreactive for signal transducer and activator of transcription 6. He was treated with postoperative radiotherapy. He complained of fever and abdominal pain with systemic multiple metastatic tumors 10 years after the operation. The leukocyte count was 70,500/μL with 90.7% neutrophils (compared to 7400/μL at 39 years of age), and the serum G‐CSF level was 283.0 pg/mL. Pathological examination of biopsy specimens of the liver and kidney tumors revealed the metastatic SFT/HPC. Immunohistochemically, G‐CSF was localized in both the primary and metastatic SFT/HPC cells, whereas G‐CSFR was localized only in the metastatic SFT/HPC cells. The tumors seemed to have the ability to produce G‐CSF, even when G‐CSF production is not clinically evident, suggesting that G‐CSFR acquisition contributes to tumor growth, malignancy, and metastasis. In addition, there have been no reports showing G‐CSF production in SFT/HPC cases. The influence of G‐CSF is expected to be one of the factors related to SFT/HPC malignancy. Inhibitors of G‐CSF could be a therapeutic agent for tumors that co‐express both G‐CSF and G‐CSFR in an autocrine manner.
In Memoriam: Leslie Altman Rescorla

Leslie Altman Rescorla left us on October 12, 2020. She was born August 15, 1945, in Washington, D.C., to Alberta (Smith) Altman, a specialist in mental health documentaries on the faculty of the Yale School of Medicine, and Oscar Altman, an economist who was Treasurer of the International Monetary Fund. Leslie earned her Bachelor’s degree Phi Beta Kappa and magna cum laude at Harvard, her Master’s degree at the London School of Economics, and her Ph.D. at Yale. She received clinical training at the Yale Child Study Center, Children’s Hospital of Philadelphia, and the Philadelphia Child Guidance Center. Leslie taught at the University of Pennsylvania and then advanced from Assistant Professor to an endowed Professorship at Bryn Mawr College. At Bryn Mawr, Leslie was Chair of the Psychology Department, Director of the Ph.D. Program in Clinical Developmental Psychology, Director of the School Psychology Certification Program, Director of the Thorne Preschool Programs, and Director of the Child Study Institute, where she provided clinical care to children and their families. She supervised 26 Master’s theses and 45 Ph.D. dissertations. Her hundreds of undergraduate, graduate, and postdoctoral students are eternally grateful for her personal support, as well as for the superb training that she provided. Leslie was especially passionate about supporting women in academia, generously mentoring many female academics over the course of her career. She inspired generations of women to follow exciting and diverse pathways. Leslie was married to the late Robert Rescorla, Professor of Psychology at the University of Pennsylvania, with whom she had sons Eric, who is an executive at Mozilla, and Michael, who is Professor of Philosophy at UCLA. She contributed greatly to the development of her grandsons Darwin, Lincoln, Alex, and Nicky, whom she often visited in California. In 2000, Leslie married Thomas Achenbach, Professor of Psychiatry and Psychological Science at the University of Vermont, with whom she shared many fun projects, travels, and adventures. Leslie’s energy was legendary, as she accomplished more in a day than most people do in a week, even while flying frequently to Vermont, California, Europe, and elsewhere around the world. Leslie was also a talented author of sonnets and other poetry for many special occasions.
Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects

Supplemental Digital Content is available in the text. Objective: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). Approach and Results: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobin-related proteins; P≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. Conclusions: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT00715273; NCT00880178; NCT00120289.