Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic value of mean platelet volume to plateletcrit ratio in patients with osteosarcoma

Objective The objective of this study was to investigate the prognostic value of preoperative mean platelet volume to plateletcrit (MPV/PCT) ratio in patients with osteosarcoma. Materials and methods The retrospective study included 188 consecutive osteosarcoma patients who experienced neoadjuvant chemotherapy and surgical resection of tumor. The relationships between MPV/PCT and clinicopathological characteristics were analyzed. The Kaplan–Meier analysis and Cox regression proportional hazard model were applied to assess the prognostic value of MPV/PCT ratio. Results MPV/PCT ratio was found to be significantly associated with platelet count, platelet distribution width, and PCT (all P<0.001). Kaplan–Meier analysis showed that high MPV/PCT ratio (≥43.58) was associated with a prolonged disease-free survival (DFS, P=0.035). The multivariate Cox revealed that only good chemotherapy response was an independent predictor of better DFS in the overall population. However, the stratification analysis showed that a high MPV/PCT ratio (≥43.58) was indicated as an independent prognostic factor for a favorable DFS (HR =0.137, 95%CI =0.029–0.644, P=0.012) in the male osteosarcoma patients but not in female patients. Conclusion The high preoperative MPV/PCT ratio may serve as an independent prognostic factor for a favorable prognosis in male osteosarcoma patients. Further studies are needed to confirm the findings.
Complex Patterns of GABAergic Neuronal Deficiency and Type 2 Potassium-Chloride Cotransporter Immaturity in Human Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is a common histopathologic finding in cortical specimens resected for refractory epilepsy. GABAergic neuronal abnormalities and K-Cl cotransporter type 2 (KCC2) immaturity may be contributing factors for FCD-related epilepsy. We examined surgical specimens from 12 cases diagnosed with FCD, and brain tissues without developmental abnormality obtained from 6 autopsy cases. We found that GABAergic neuronal density was abnormal in FCD with 2 distinct patterns. In 7 of 12 (58%) FCD subjects, the GABAergic neuron density in dysplastic regions and in neighboring nondysplastic regions was equally reduced, hence we call this a "broad pattern. " In the remaining cases, GABAergic neuron density was decreased in dysplastic regions but not in the neighboring nondysplastic regions; we designate this "restricted pattern. " The different patterns are not associated with pathologic subtypes of FCD. Intracytoplasmic retention of KCC2 is evident in dysmorphic neurons in the majority of FCD type II subjects (5/7) but not in FCD type I. Our study suggests that (1) "broad" GABAergic deficiency may reflect epileptic vulnerability outside the dysplastic area; and (2) abnormal distribution of KCC2 may contribute to seizure generation in patients with FCD type II but not in type I.
Comparison of analgesia, adverse effects, and quality of life in cancer patients during treatment of procedural pain with intravenous morphine, fentanyl nasal spray, and fentanyl buccal tablets

Aim Comparison of analgesia, adverse effects, and quality of life (QoL) of cancer patients in the treatment of procedural pain induced by nursing procedures with the use of intravenous morphine, fentanyl nasal spray, and fentanyl buccal tablets. Methods In adults with cancer with opioid tolerance and suffering procedural pain, intravenous morphine was used at an inpatient palliative medicine unit (20 patients) and fentanyl by intranasal (15 patients) and buccal routes (nine patients) at home. Five procedural pain episodes were examined: the Mini-Mental State Examination was used to assess cognitive function, the Brief Pain Inventory – short form (BPI-SF) to assess intensity and impact of pain on daily activities, a pain and adverse-effect questionnaire to assess the intensity of pain and adverse effects, and the European Organisation for Research and Treatment of Cancer QLQ-C15-PAL to assess QoL. Results All five procedural pain episodes were completed by 32 patients. Twelve patients stopped treatment due to death or referral to the hospital (four patients in each group), changes in the treatment of background pain (three patients), and intense drowsiness (one patient). Similar beneficial analgesic effects were observed in all patient groups. During fentanyl therapy, a smaller negative effect of pain on patients’ activity, walking, and work (BPI-SF) was observed. Among adverse effects, fewer breaths (10–14 per minute) were observed in 17 patients and slight disturbances of consciousness in seven. For QoL, an improvement in emotional functioning, overall QoL, and fatigue was observed. Patients treated with intranasal and buccal fentanyl had higher physical functioning and were more active. Conclusion In the treatment of procedural pain induced by nursing procedures in cancer patients, intravenous morphine and rapid-onset fentanyl show similarly high analgesic efficacy, with good tolerance of treatment and improvement in QoL.
Pinniped- and Cetacean-Derived ETosis Contributes to Combating Emerging Apicomplexan Parasites (Toxoplasma gondii, Neospora caninum) Circulating in Marine Environments

Leukocytes play a major role in combating infections either by phagocytosis, release of antimicrobial granules, or extracellular trap (ET) formation. ET formation is preceded by a certain leukocyte cell death form, known as ETosis, an evolutionarily conserved mechanism of the innate immune system also observed in marine mammals. Besides several biomolecules and microbial stimuli, marine mammal ETosis is also trigged by various terrestrial protozoa and metazoa, considered nowadays as neozoan parasites, which are circulating in oceans worldwide and causing critical emerging marine diseases. Recent studies demonstrated that pinniped- and cetacean-derived polymorphonuclear neutrophils (PMNs) and monocytes are able to form different phenotypes of ET structures composed of nuclear DNA, histones, and cytoplasmic peptides/proteases against terrestrial apicomplexan parasites, e.g., Toxoplasma gondii and Neospora caninum. Detailed molecular analyses and functional studies proved that marine mammal PMNs and monocytes cast ETs in a similar way as terrestrial mammals, entrapping and immobilizing T. gondii and N. caninum tachyzoites. Pinniped- and cetacean leukocytes induce vital and suicidal ETosis, with highly reliant actions of nicotinamide adenine dinucleotide phosphate oxidase (NOX), generation of reactive oxygen species (ROS), and combined mechanisms of myeloperoxidase (MPO), neutrophil elastase (NE), and DNA citrullination via peptidylarginine deiminase IV (PAD4). This scoping review intends to summarize the knowledge on emerging protozoans in the marine environment and secondly to review limited data about ETosis mechanisms in marine mammalian species.
Two new norneolignans from Callicarpa kwangtungensis

Abstract Two new norneolignans, (7S,8R)-3-methoxy-3′,4,9-trihydroxy-4′,7-epoxy-8,3′-neolignane-1′-carboxylic acid (1) and (7R,8R)-3-methoxyl-4,9-dihydroxy-3′:7,4′:8-diepoxyneolignan-1′-carboxylic acid methyl ester (2) were isolated from Callicarpa kwangtungensis, together with ten known compounds, genistin (3), daidzin (4), silybin A (5), isosilybin A (6), isosilybin B (7), p-hydroxybenzaldehyde (8), syringic acid (9), lanceolatin A (10), icariside C5 (11), and (3S,6E,10R)-10-β-D-glucopyranosyloxy-3,11-dihydroxy-3,7,11-trimethyldodeca-1,6-diene (12). Compounds 1 and 2 were evaluated for their effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide induced RAW264.7 cells. Compounds 1 and 2 exhibited inhibitory activity with IC50 values of 31.45 ± 0.38 and 40.72 ± 0.54 μM, respectively.
A Fog Computing Solution for Context-Based Privacy Leakage Detection for Android Healthcare Devices

Intelligent medical service system integrates wireless internet of things (WIoT), including medical sensors, wireless communications, and middleware techniques, so as to collect and analyze patients’ data to examine their physical conditions by many personal health devices (PHDs) in real time. However, large amount of malicious codes on the Android system can compromise consumers’ privacy, and further threat the hospital management or even the patients’ health. Furthermore, this sensor-rich system keeps generating large amounts of data and saturates the middleware system. To address these challenges, we propose a fog computing security and privacy protection solution. Specifically, first, we design the security and privacy protection framework based on the fog computing to improve tele-health and tele-medicine infrastructure. Then, we propose a context-based privacy leakage detection method based on the combination of dynamic and static information. Experimental results show that the proposed method can achieve higher detection accuracy and lower energy consumption compared with other state-of-art methods.
Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation

Abstract Disrupted mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation are often associated with macrophage pyroptosis. It remains unclear how these forms of mitochondrial dysfunction relate to inflammasome activation and gasdermin-D (Gsdmd) cleavage, two central steps of the pyroptotic process. Here, we also found MMP collapse and ROS generation induced by Nlrp3 inflammasome activation as previous studies reported. The elimination of ROS alleviated the cleavage of Gsdmd, suggesting that Gsdmd cleavage occurs downstream of ROS release. Consistent with this result, hydrogen peroxide treatment augmented the cleavage of Gsdmd by caspase-1. Indeed, four amino acid residues of Gsdmd were oxidized under oxidative stress in macrophages. The efficiency of Gsdmd cleavage by inflammatory caspase-1 was dramatically reduced when oxidative modification was blocked by mutation of these amino acid residues. These results demonstrate that Gsdmd oxidation serves as a de novo mechanism by which mitochondrial ROS promote Nlrp3 inflammasome-dependent pyroptotic cell death.
TRPV1 channel contributes to remifentanil-induced postoperative hyperalgesia via regulation of NMDA receptor trafficking in dorsal root ganglion

Background Remifentanil is widely used in general anesthesia due to its reliability and rapid onset. However, remifentanil-induced postoperative hyperalgesia might be a challenge nowadays. Accumulating evidence suggests that the transient receptor potential vanilloid 1 (TRPV1) was involved in the development of neuropathic pain and hyperalgesia. However, the contribution of TRPV1 in modulating remifentanil-induced postoperative hyperalgesia is still unknown. The aim of this study is the contribution of TRPV1 to the surface expression of N-methyl-d-aspartate (NMDA) receptors in remifentanil-induced postoperative hyperalgesia. Methods The hot plate test and the Von Frey test were performed to evaluate thermal and mechanical hyperalgesia. Capsazepine (CPZ) was administrated intrathecally to confirm our results. TRPV1, NMDA receptors, CaMKII (calcium/calmodulin-dependent kinase II), and protein kinase C (PKC) in the dorsal root ganglion (DRG) were detected by Western blotting. Immunofluorescence assay was applied to analyze the distribution of TRPV1 and the relationship between TRPV1 and NMDA receptor subunit 1 (NR1). Results Remifentanil-induced both thermal and mechanical postoperative hyperalgesia. Here, we found the membrane trafficking of NR1, possibly due to the activation of TRPV1 in DRG neurons after remifentanil infusion. Furthermore, intrathecal injection of CPZ was able to relieve remifentanil-induced postoperative hyperalgesia according to a behavioral test and CPZ confirmed that TRPV1 is involved in NR1 trafficking. In addition, CaMKII/PKC but not protein kinase A (PKA) contributed to remifentanil-induced postoperative hyperalgesia. Conclusion Our study demonstrates that TRPV1 receptors are involved in remifentanil-induced postoperative hyperalgesia. TRPV1 contributes to the persistence of remifentanil-induced postoperative hyperalgesia through the trafficking of NMDA receptors via the activation of CaMKII-PKC signaling pathways in DRG neurons.
The fungal ribonuclease-like effector protein CSEP0064/BEC1054 represses plant immunity and interferes with degradation of host ribosomal RNA

The biotrophic fungal pathogen Blumeria graminis causes the powdery mildew disease of cereals and grasses. We present the first crystal structure of a B. graminis effector of pathogenicity (CSEP0064/BEC1054), demonstrating it has a ribonuclease (RNase)-like fold. This effector is part of a group of RNase-like proteins (termed RALPHs) which comprise the largest set of secreted effector candidates within the B. graminis genomes. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in both monocotyledonous and dicotyledonous plants. CSEP0064/BEC1054 interacts in planta with the pathogenesis-related protein PR10. The effector protein associates with total RNA and weakly with DNA. Methyl jasmonate (MeJA) levels modulate susceptibility to aniline-induced host RNA fragmentation. In planta expression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins (RIPs) that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.
Safety and efficacy assessment of transarterial chemoembolization using drug-eluting beads in patients with hepatocellular carcinoma and arterioportal shunt: a single-center experience

Objective To evaluate the feasibility and safety of transarterial chemoembolization with drug-eluting beads (DEB-TACE) in patients with hepatocellular carcinoma (HCC) and arterioportal shunts (APSs). Materials and methods Fifty-eight patients with unresectable HCC and APSs who were treated with DEB-TACE (n=26) or polyvinyl alcohol (PVA) plus TACE (PVA-TACE, n=32) were included in this retrospective study. The tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors. Toxicity was graded by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) and compared between the two groups. Survival curves were calculated by the Kaplan–Meier method and compared by the log-rank test between the two groups. The influence of potential prognostic factors on survival in the DEB-TACE group was analyzed via a multivariate Cox regression model. Results The disease control rate was better in the DEB-TACE group than in the PVA-TACE group. The median survival times were 346 and 274 days in the DEB-TACE group and PVA-TACE group, respectively. There was no significant difference in survival rates between the two groups (P=0.081). Patients treated with DEB-TACE were significantly less likely to have fever (P=0.048) or a low-grade (grade 1–2) increase in transaminases (P=0.046) than the patients treated with PVA-TACE. The potential predictive prognostic factors in the DEB-TACE group were tumor response, APS grading, and serum bilirubin. Conclusion DEB-TACE may be feasible and safe in HCC patients with APS. Survival in the DEB-TACE group was associated with tumor response, APS grading, and serum bilirubin levels.
miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity

The interdependence of selective cues during development of regulatory T cells (Treg cells) in the thymus and their suppressive function remains incompletely understood. Here, we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-181a-1 and miR-181b-1 (miR-181a/b-1) during late T-cell development with very high levels of expression during thymocyte selection, followed by massive down-regulation in the periphery. Loss of miR-181a/b-1 resulted in inefficient de novo generation of Treg cells in the thymus but simultaneously permitted homeostatic expansion in the periphery in the absence of competition. Modulation of T-cell receptor (TCR) signal strength in vivo indicated that miR-181a/b-1 controlled Treg-cell formation via establishing adequate signaling thresholds. Unexpectedly, miR-181a/b-1–deficient Treg cells displayed elevated suppressive capacity in vivo, in line with elevated levels of cytotoxic T-lymphocyte–associated 4 (CTLA-4) protein, but not mRNA, in thymic and peripheral Treg cells. Therefore, we propose that intrathymic miR-181a/b-1 controls development of Treg cells and imposes a developmental legacy on their peripheral function.
Fine-Grained Complexity Theory (Tutorial)

Suppose the fastest algorithm that we can design for some problem runs in time O(n^2). However, we want to solve the problem on big data inputs, for which quadratic time is impractically slow. We can keep searching for a faster algorithm, but maybe none exists. Is there any reasoning that provides evidence against significantly faster algorithms, and thus allows us to stop searching? In other words, is there an analogue of NP-hardness for polynomial-time problems? In this tutorial, we will give an introduction to fine-grained complexity theory, which allows to rule out faster algorithms by proving conditional lower bounds via fine-grained reductions from certain key conjectures. We will define these terms and show exemplary lower bounds.
Gold quantum dots impair the tumorigenic potential of glioma stem-like cells via β-catenin downregulation in vitro

Background Over the past several decades, the incidence of solid cancers has rapidly increased worldwide. Successful removal of tumor-initiating cells within tumors is essential in the field of cancer therapeutics to improve patient disease-free survival rates. The biocompatible multivarient-sized gold nanoparticles (MVS-GNPs) from quantum dots (QDs, <10 nm) to nanosized (up to 50 nm) particles have vast applications in various biomedical areas including cancer treatment. The role of MVS-GNPs for inhibition of tumorigenic potential and stemness of glioma was investigated in this study. Methods Herein, MVS-GNPs synthesized and characterized by means of X-ray diffraction pattern (XRD) and transmission electron microscopy (TEM) techniques. Afterwards, interaction of these GNPs with glioma stem-cell like cells along with cancer cells were evaluated by MTT, cell motility, self-renewal assays and biostatistics was also applied. Results Among these GNPs, G-QDs contributed to reduce metastatic events and spheroid cell growth, potentially blocking the self-renewal ability of these cells. This study also uncovers the previously unknown role of the inhibition of CTNNB1 signaling as a novel candidate to decrease the tumorigenesis of glioma spheroids and subsequent spheroid growth. The accurate and precise biostatistics results were obtained at quantify level. Conclusion In summary, G-QDs may exhibit possible contribution on suppressing the growth of tumor-initiating cells. These data reveal a unique therapeutic approach for the elimination of residual resistant stem-like cells during cancer treatment.
Hemorrhagic extrahepatic recurrence of hepatocellular carcinoma: A case report

The recurrence of hepatocellular carcinoma (HCC) can mainly be divided into two phases or types: the intrahepatic recurrence (IHR) and the extrahepatic recurrence (EHR). Generally speaking, the EHR is usually referenced as being the less common of the two types or categories. In a post-hemihepatectomy patient with routine surveillance at 6 months, it was noted that the patient appeared to have an elevated alpha-fetoprotein, and also complained of vague lower abdominal pain. The accompanying computed tomography scan revealed a 6 cm-sized heterogeneous mass located at the pelvis region. Next, during a laparotomy for resection, the tumor was found to be bleeding from the omental deposition. In conclusion, a high index of suspicion and early surgical intervention can help in detecting possible bleeding extrahepatic recurrence in the background of a patient with history of HCC.
Variability in Sensitivity to Metalaxyl in vitro, Pathogenicity, and Control of Pythium spp. on Sugar Beet.

Pythium ultimum var. sporangiiferum (76 isolates) and P. aphanidermatum (21 isolates) cultured from diseased sugar beet seedlings in Minnesota and North Dakota were tested for sensitivity to metalaxyl, pathogenicity on sugar beet, and disease control by metalaxyl seed treatment. Sensitivity to metalaxyl (effective concentration causing 50% growth inhibition [EC50]) was determined by linear growth on corn meal agar amended with 0, 0.01, 0.1, 1, 10, and 100 μg a.i. metalaxyl ml-1 after 48 h in the dark at 21 ± 1°C. Variation among isolates was significant (P = 0.05) within and between species, and EC50 values averaged 0.16 (range: 0.05 to 1.30 μg ml-1) for P. ultimum var. sporangiiferum and 2.06 (range: 1.19 to 3.12 μg ml-1) for P. aphanidermatum. In pathogenicity tests on sugar beet, most isolates of P. ultimum var. sporangiiferum (72 of 76) and all of P. aphanidermatum significantly (P = 0.05) decreased final stands compared to the noninoculated control. There was no correlation between aggressiveness in the absence of metalaxyl and in vitro sensitivity to metalaxyl. When Pythium-infested soil was planted with seed treated with metalaxyl at the standard (0.625 g a.i. kg-1) or half rate, some isolates that were least sensitive to metalaxyl in vitro resulted in a significant (P = 0.05) reduction in disease control. These results may explain, at least in part, why producers do not attain expected stands when they plant metalaxyl-treated sugar beet seed.
Eustachian tube balloon dilation in treatment of equalization problems of freediving spearfishermen.

BACKGROUND Eustachian tube balloon dilation is a minimally invasive surgical procedure used to treat Eustachian tube dysfunction which is not responsive to conventional therapies. METHODS In this cohort intervention series we report the results of balloon dilation in treating refractory equalization problems in 20 freediving spearfishermen; in 19 cases the problem was unilateral and in one case bilateral. All the patients had already received medical and insufflation therapy and four patients had also had nasal surgery. None of these treatments or procedures had achieved improvement. We used a 20 mm x 3 mm disposable balloon catheter inserted through a 70-degree guide catheter and inflated up to 12 ATM three times at three different depths of insertion within the Eustachian tube. Every inflation lasted 120 seconds. RESULTS Fifteen out of 20 patients improved. Ten patients reported a complete resolution of equalization problems, five showed improvement with persistence of a slight equalization delay on the treated side. Five patients did not report any improvement. Two complications occurred: subcutaneous emphysema of the parotid region in one case; and a mild high frequency (4-8 KHz) sensorineural hearing loss in another patient. CONCLUSION Balloon dilation of the Eustachian tube is an effective therapy in the treatment of equalization problems with a good success rate.
Impact of body mass index on short‐term and long‐term survival in prevalent hemodialysis patients

Introduction: Numerous studies showed that higher body mass index (BMI) is associated with better survival in hemodialysis (HD) patients. Most of them evaluated short‐term mortality. It has been suggested that presence of inflammation may be a key modifier of relationship between BMI and mortality in incident HD patients. We examined whether presence of inflammation modifies the association between BMI and mortality in both short‐term and long‐term follow‐up in a large group of prevalent HD patients.