Miracle-dz/UniFAR-FTUs huggingface dataset:
PI3k inhibitors (BKM120 and BYL719) as radiosensitizers for head and neck squamous cell carcinoma during radiotherapy

Approximately 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually. Radiation therapy is an important treatment for oral squamous cell carcinoma (OSCC). The survival rate of patients with HNSCC remained low (50%) in decades because of radiation therapy failure caused by the radioresistance of HNSCC cells. This study aimed to identify PI3K inhibitors that can enhance radiosensitivity. Results showed that pan-Phosphoinositide 3-kinases (PI3K) inhibitor BKM120 and class I α-specific PI3K inhibitor BYL719 dose-dependently reduced the growth of OSCC cells but not that of radioresistant OML1-R cells. The combination treatment of BKM120 or BYL719 with radiation showed an enhanced inhibitory effect on OSCC cells and radioresistant OML1-R cells. Furthermore, the enhanced inhibitory effect of the combination treatment was confirmed in patient-derived OSCC cells. The triple combination treatment of mTOR inhibitor AZD2014 and BKM120 or AZD2014 and BYL719 with radiation showed a significantly enhanced inhibitory effect on radioresistant OML1-R cells. These results suggest that the PI3K inhibitors are potential therapeutic agents with radiosensitivity for patients with OSCC.
Does the Time of Onset of Urinary Symptoms Affect Microablative Fractional CO2 Laser Efficacy in Postmenopausal Women?

To evaluate the safety and efficacy of transvaginal fractional microablative CO2 laser therapy (MLT) on urinary symptoms in postmenopausal women with genitourinary syndrome of menopause (GSM) in relation to the timing of their onset; if prior to or after menopause. Secondary, the efficacy of MLT on vulvovaginal atrophy (VVA)‐related symptoms.
Maternal dietary diversity during pregnancy and risk of low birth weight in newborns: a systematic review

Abstract Objective: Maternal nutrition during pregnancy is a key factor influencing birth outcome. Dietary diversity is a proxy for multiple macro- and/or micronutrient sufficiency of an individual’s diet. This systematic review aimed to summarise the findings on the association between maternal dietary diversity during pregnancy and the risk of low birth weight (LBW) in newborns. Design: This is a systematic review study. Setting: Google and the PubMed, Scopus and Google Scholar databases were searched to extract original studies on humans published until June 2020, without date restrictions. There was no limitation regarding geographic region or economic condition of countries. Duplicated and irrelevant studies were screened out and data were obtained through critical analysis. Participants: Articles that examined the association between maternal dietary diversity during pregnancy and the risk of LBW in infants were included. Results: Of the ninety-eight studies retrieved, fifteen articles were included in the final review. All included articles represent low- and middle-income countries. Eighty percentage of the studies (n 12) indicated that low maternal dietary diversity during pregnancy is associated with an increased risk of LBW infants. Three studies that included a small number of LBW infants and did not take into account factors which may bias study results failed to show this association. Conclusion: The results suggest that low maternal dietary diversity during pregnancy may be associated with the risk of LBW, more specifically in developing countries. Dietary diversity might be a valuable predictor of maternal nutrition during pregnancy and the chance of giving birth to a LBW infant.
Total IgE as a Marker for Chronic Spontaneous Urticaria

Objective Immunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed. Methods Publications were searched via PubMed. The search terms used were “chronic urticaria” and “total IgE. ” Studies were screened by titles and abstracts, and 141 were used in the review. Results CSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies. Conclusion The results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.
Delayed sampling of intraoperative parathormone may be unnecessary during parathyroidectomy in kidney-transplanted and dialysis patients

Abstract Introduction: Some authors advise in favor of delayed sampling of intraoperative parathormone testing (ioPTH) during parathyroidectomy in dialysis and kidney-transplanted patients. The aim of the present study was to evaluate the intensity and the role of delayed sampling in the interpretation of ioPTH during parathyroidectomy in dialysis patients (2HPT) and successful kidney-transplanted patients (3HPT) compared to those in single parathyroid adenoma patients (1HPT). Methods: This was a retrospective study of ioPTH profiles in patients with 1HPT, 2HPT, and 3HPT operated on in a single institution. Samples were taken at baseline ioPTH (sampling at the beginning of the operation), ioPTH-10 min (10 minutes after excision of the parathyroid glands), and ioPTH-15 min (15 minutes after excision of the parathyroid glands). The values were compared to baseline. Results: Median percentage values of ioPTH compared to baseline (100%) were as follows: 1HPT, ioPTH-10 min = 20% and ioPTH-15 min = 16%; 2HPT, ioPTH-10 min = 14% and ioPTH-15 min = 12%; 3HPT, ioPTH-10 min = 18% and ioPTH-15 min = 15%. Discussion: The reduction was equally effective at 10 minutes in all groups. In successful cases, ioPTH decreases satisfactorily 10 minutes after parathyroid glands excision in dialysis and transplanted patients, despite significant differences in kidney function. The postponed sampling of ioPTH appears to be unnecessary.
Erdafitinib as a Novel and Advanced Treatment Strategy of Metastatic Urothelial Carcinoma.

Urothelial carcinoma has become the ninth most common malignancy in the world. Since 1980s, diverse studies and treatment methods came out with their possible effects along with certain limitations. Initially, platinum chemotherapy was considered as first line treatment of the disease. Although it was proved to be effective in the beginning yet most number of cases reported the reoccurrence of the disease. Furthermore, aberrant ligand-dependent and constitutive ligandindependent fibroblast growth factor receptor (FGFR) signalling has been reported in large number of solid tumours including urothelial carcinoma that became the basis for FGFR inhibition for the treatment of the disease. Erdafitinib is a pan-FGFR inhibitor that was recently approved in the USA for the treatment of locally advanced or metastatic FGFR3 or FGFR2 urothelial carcinoma. The drug is also being investigated as a treatment for other cancers including cholangiocarcinoma, liver cancer, non-small cell lung cancer, prostate cancer, lymphoma cancer and oesophageal cancer. This article summarizes the various treatments evolved for bladder cancer till now, brief description of biology of FGFR inhibition, clinical pharmacology and various clinical trials of erdafitinib.
American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2021 Version.

Lawrence J. Hirsch,* Michael W.K. Fong,† Markus Leitinger,‡ Suzette M. LaRoche,§ Sandor Beniczky,k Nicholas S. Abend,¶ Jong Woo Lee,# Courtney J. Wusthoff,** Cecil D. Hahn,†† M. Brandon Westover,‡‡ Elizabeth E. Gerard,§§ Susan T. Herman,kk Hiba Arif Haider,§ Gamaleldin Osman,¶¶ Andres Rodriguez-Ruiz,§ Carolina B. Maciel,## Emily J. Gilmore,* Andres Fernandez,*** Eric S. Rosenthal,††† Jan Claassen,‡‡‡ Aatif M. Husain,§§§ Ji Yeoun Yoo,kkk Elson L. So,¶¶¶ Peter W. Kaplan,### Marc R. Nuwer,**** Michel van Putten,†††† Raoul Sutter,‡‡‡‡ Frank W. Drislane,§§§§ Eugen Trinka,‡ and Nicolas Gaspardkkkk
Reactive oxygen species during heart regeneration in zebrafish: Lessons for future clinical therapies

In humans, myocardial infarction (MI) is associated with irreversible damage to heart tissue, resulting in increased morbidity and mortality in patients. By comparison, the zebrafish (Danio rerio) is capable of repairing damaged and injured hearts by activating a full regenerative response. By studying model organisms that can regenerate loss heart tissue following injury, such as the zebrafish, a greater insight will be gained into the molecular pathways that can induce and sustain a regenerative response following injury. There is hope that such information may lead to new treatments or therapies aimed at stimulating a better regenerative response in humans that have suffered heart attacks. Recent findings in zebrafish have highlighted an important role for sustained elevated levels of Reactive Oxygen Species (ROS), including hydrogen peroxide (H2O2) in the promotion of a regenerative response. Given that elevated levels of H2O2 can be harmful, simply elevating ROS levels directly may not be easy or practical to translate clinically. An alternative approach would be to identify the critical downstream targets of ROS in the promotion of heart regeneration, and then target these clinically using drugs. One such family of potential downstream targets of ROS during heart regeneration are the family of protein tyrosine phosphatases (PTPs), which are known to be exquisitely sensitive to redox regulation and whose inhibition have been linked to the promotion of heart regeneration in zebrafish. In this review, we present an overview of the zebrafish as a model organism for studying cardiac regeneration, including the molecular mechanisms by which cardiac regeneration occurs in response to injury. We then present recent findings linking elevated ROS levels to heart regeneration and their potential downstream targets, the PTPs, including protein tyrosine phosphatase 1B (PTP1B) and the dual specificity phosphatase 6 (DUSP6) in the promotion of heart regeneration.
Assessment of optic nerve vascularity in healthy eyes using superb microvascular imaging: a preliminary study

Background Changes in optic nerve vascularity are observed in many diseases. Superb microvascular imaging (SMI) has the potential to become the method of choice for detecting microvasculature in the optic nerves. Purpose To evaluate optic nerve vascularity in healthy individuals through power Doppler sonography (PDUS) and SMI. Material and Methods Twenty-seven healthy patients with 54 eyes were prospectively evaluated. The duration of the examination for optic nerve vascularity lasted until the posterior ciliary artery blood supply was observed in PDUS and SMI. The visibility of vascularity, as well as the ratio of the vascular structures to the optic nerves (vascular index [VI]), was evaluated. Results Fifty-four eyes were evaluated from a total of 27 patients (mean age = 49.0 ± 19.42 years). The VI value for the right optic nerve was 29.58 ± 4.00 while for the left optic nerve, it was 31.21 ± 3.52. Vascularity was clearly observed in both eyes (n = 54) in all 27 cases in the evaluation performed with the SMI technique. However, with the power Doppler examination, vascular flow was not observed in 14 right eyes and in 10 left eyes within the specified timeframe. Conclusion The results indicate that imaging of vascular structures can be done faster and better with SMI than PDUS examination. The normal VI values may provide important information about the blood supply of the optic nerve, which is of relevance in orbital pathologies and many systemic conditions.
The potassium status of some pacific island soils

Abstract The potassium (K) status of 22 soil samples from 12 pedons originating in 6 Pacific Island countries has been investigated by several techniques. The total K contents of the soils studied were found to be low to very low. Use of various methods available for measuring exchangeable cations in soils showed exchangeable K to be dependent on factors such as ionic strength and displacement cation of the extracting solution. The proportions of non‐exchangeable K that are plant available were found to be very low for most soils. Data obtained from quantity/intensity measurements suggest that the soils would be responsive to added K.
Steady‐State and Transient Behavior of Organic Electrochemical Transistors

In recent years, organic electrochemical transistors (OECTs) have emerged as attractive devices for a variety of applications, particularly in the area of sensing. While the electrical characteristics of OECTs are analogous to those of conventional organic field effect transistors, appropriate models for OECTs have not yet been developed. In particular, little is known about the transient characteristics of OECTs, which are determined by a complex interplay between ionic and electronic motion. In this paper a simple model is presented that reproduces the steady‐state and transient response of OECTs by considering these devices in terms of an ionic and an electronic circuit. A simple analytical expression is derived that can be used to fit steady‐state OECT characteristics. For the transient regime, comparison with experimental data allowed an estimation of the hole mobility in poly(3,4‐ethylenedioxythiophene) doped with poly(styrene sulfonate). This work paves the way for rational optimization of OECTs.
Tembusu Virus Entering the Central Nervous System Caused Nonsuppurative Encephalitis without Disrupting the Blood-Brain Barrier

TMUV disease has caused huge losses to the poultry industry in Asia and is potentially harmful to public health. Neurological symptoms and their sequelae are the main characteristics of this disease. ABSTRACT Tembusu virus (TMUV) is an emerging and reemerging zoonotic pathogen that has adversely affected the poultry industry in recent years. TMUV disease is characterized by nonsuppurative encephalitis in ducklings. The duckling infection model was established to study the mechanism of TMUV crossing the blood-brain barrier (BBB) into the central nervous system (CNS). Here, we showed that no obvious clinical symptoms and enhancement of BBB permeability occurred at the early stage of infection (∼3 to 5 days postinfection [dpi]), while virus particles were simultaneously observed by transmission electron microscopy in the brain, inducing the accumulation of inflammatory cytokines. Neurological symptoms and disruption of the BBB appeared at the intermediate stage of infection (∼7 to 9 dpi). It was confirmed that TMUV could survive and propagate in brain microvascular endothelial cells (BMECs) but did not affect the permeability of the BBB in vivo and in vitro at an early date. In conclusion, TMUV enters the CNS, then causes encephalitis, and finally destroys the BBB, which may be due to the direct effect of TMUV on BMECs and the subsequent response of the “inflammatory storm. ” IMPORTANCE TMUV disease has caused huge losses to the poultry industry in Asia and is potentially harmful to public health. Neurological symptoms and their sequelae are the main characteristics of this disease. However, the mechanism of how this virus enters the brain and causes encephalitis is unclear. In this study, we confirmed that the virus entered the CNS and then massively destroyed the BBB, and the BBB damage was closely associated with the subsequent outbreak of inflammation. TMUV may enter the CNS through the transcellular and “Trojan horse” pathways. These findings can fill the knowledge gap in the pathogenesis of TMUV-infected poultry and be of benefit for the treatment of TMUV disease. In addition, TMUV is a representative for the study of the infection of avian flavivirus. Therefore, our studies have significance both for the understanding of the full scope of the mechanisms of TMUV and other flavivirus infections and, conceivably, for therapeutics.
Preparation of solid dispersion systems for enhanced dissolution of poorly water soluble diacerein: In-vitro evaluation, optimization and physiologically based pharmacokinetic modeling

Diacerein (DCN), a BCS II compound, suffers from poor aqueous solubility and limited bioavailability. Solid dispersion systems (SD) of DCN were prepared by solvent evaporation, using hydrophilic polymers. In-vitro dissolution studies were performed and dissolution parameters were evaluated. I-Optimal factorial design was employed to study the effect of formulation variables (drug:polymer ratio and polymer type) on the measured responses including; drug content (DC) (%), dissolution efficiency at 15 min (DE (15 min)%) and 60 min (DE (60 min)%) and mean dissolution time (MDT) (min). The optimized SD was selected, prepared and evaluated, allowing 10.83 and 3.42 fold increase in DE (15 min)%, DE (60 min)%, respectively and 6.07 decrease in MDT, compared to plain drug. DSC, XRD analysis and SEM micrographs confirmed complete amorphization of DCN within the optimized SD. Physiologically based pharmacokinetic (PBPK) modeling was employed to predict PK parameters of DCN in middle aged healthy adults and geriatrics. Simcyp® software established in-vivo plasma concentration time curves of the optimized SD, compared to plain DCN. Relative bioavailability of the optimized SD compared to plain drug was 229.52% and 262.02% in healthy adults and geriatrics, respectively. Our study reports the utility of PBPK modeling for formulation development of BCS II APIs, via predicting their oral bio-performance.
Desmethyl butenolides are optimal ligands for karrikin receptor proteins.

Strigolactones and karrikins are butenolide molecules that regulate plant growth. They are perceived via the α/β-hydrolase DWARF14 (D14) and its homologue KARRIKIN INSENSITIVE2 (KAI2), respectively. Plant-derived strigolactones have a butenolide ring with a methyl group that is essential for bioactivity. By contrast, karrikins are abiotic in origin, and the butenolide methyl group is non-essential. KAI2 is probably a receptor for an endogenous butenolide, but the identity of this compound remains unknown. Here we characterise the specificity of KAI2 towards differing butenolide ligands using genetic and biochemical approaches. We find that KAI2 proteins from multiple species are most sensitive to desmethyl butenolides that lack a methyl group. Desmethyl-GR24 and desmethyl-CN-debranone are active via KAI2 but not D14. They are more potent KAI2 agonists than their methyl-substituted reference compounds both in vitro and in plants. The preference of KAI2 for desmethyl butenolides is conserved in Selaginella moellendorffii and Marchantia polymorpha, suggesting that it is an ancient trait in land plant evolution. Our findings provide insight into the mechanistic basis for differential ligand perception by KAI2 and D14, and support the view that the endogenous substrates for KAI2 and D14 have distinct chemical structures and biosynthetic origins.
Transcranial magnetic stimulation and depression.

Major depressive disorder (MDD) is one of the most common mental illnesses in the US occurring in approximately 7% of the population. Treatment of MDD traditionally includes psychotherapy, medications, or a combination of the two. However, not all patients respond to these methods of treatment, and some are unable to tolerate the many adverse reactions of antidepressant medications. As a result, behavioral health specialists, such as psychiatric mental health nurse practitioners (PMHNPs) or psychiatrists, are forced to formulate alternative treatment strategies including transcranial magnetic stimulation (TMS). This article will discuss the implications of TMS, including its mechanism of action, targeted patient population, safety, effi cacy, and recommendations for practice. TMS is a nonpharmacologic intervention treatment using neuromodulation to target depressive symptoms in adults with MDD. Unlike electroconvulsive therapy, this form of neuromodulation is noninvasive and nonconvulsive, and treatments are administered while the patient is awake and alert, which means there are no sedatives or other medications given to the patient during treatment. TMS applies rapid bursts of magnetic energy to the superfi cial layers of the cerebral cortex. These magnetic pulses are delivered through a coil placed over the forehead at the area of the dorsolateral prefrontal cortex (DLPFC), which travel unimpeded through the skull and into the brain. Decreased activity in the DLPFC is linked with MDD, and therefore, TMS therapy is used to indirectly induce electrical currents in this area. DLPFC stimulation triggers the neurons to start fi ring and release neurotransmitters at the synapse. These neurotransmit-
Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures

Abstract Excessive activation of mTOR in microglia impairs CNS homeostasis and causes severe epilepsy. Autophagy constitutes an important part of mTOR signaling. The contribution of microglial autophagy to CNS homeostasis and epilepsy remains to be determined. Here, we report that ATG7KO mice deficient for autophagy in microglia display a marked increase of myelination markers, a higher density of mature oligodendrocytes (ODCs), and altered lengths of the nodes of Ranvier. Moreover, we found that deficiency of microglial autophagy (ATG7KO) leads to increased seizure susceptibility in three seizure models (pilocarpine, kainic acid, and amygdala kindling). We demonstrated that ATG7KO mice develop severe generalized seizures and display nearly 100% mortality to convulsions induced by pilocarpine and kainic acid. In the amygdala kindling model, we observed significant facilitation of contralateral propagation of seizures, a process underlying the development of generalized seizures. Taken together, our results reveal impaired microglial autophagy as a novel mechanism underlying altered homeostasis of ODCs and increased susceptibility to severe and fatal generalized seizures.