Miracle-dz/UniFAR-FTUs huggingface dataset:
A systematic literature review and network meta-analysis of first-line treatments for unresectable hepatocellular carcinoma based on data from randomized controlled trials

ABSTRACT Background Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. First-line treatment options for unresectable HCC include sorafenib, lenvatinib, selective internal radiation therapy (SIRT), and transarterial chemoembolization (TACE). The present study reviewed randomized controlled trials (RCTs) of first-line therapies for unresectable HCC in TACE-ineligible patients. Research design and methods A systematic literature review (SLR) was conducted to identify RCTs of first-line treatments for TACE-ineligible patients with unresectable HCC. Data on overall survival (OS) and progression-free survival were extracted and a contrast-based Bayesian network meta-analysis (NMA) was conducted using Markov Chain Monte Carlo techniques. Results The SLR identified three RCTs: two comparing Y-90 resin microspheres with sorafenib, and one comparing sorafenib with lenvatinib. No RCTs were identified comparing other SIRT technologies with any other approved first-line HCC therapies. The NMA showed no significant OS differences between Y-90 resin microspheres and sorafenib (hazard ratio [HR] 0.92, 95% credible interval [CrI]: 0.79–1.08) or lenvatinib (HR: 0.88, 95% CrI: 0.63–1.22). Conclusions An SLR and NMA showed no significant differences between sorafenib, lenvatinib, and Y-90 resin microspheres in treating unresectable HCC. RCT evidence was not available for any other SIRT technologies and an evaluation of their relative efficacy was therefore not possible.
Parasitoid wasp venom vesicles (venosomes) enter Drosophila melanogaster lamellocytes through a flotillin/lipid raft-dependent endocytic pathway

ABSTRACT Venosomes are extracellular vesicles found in the venom of Leptopilina endoparasitoids wasps, which transport and target virulence factors to impair the parasitoid egg encapsulation by the lamellocytes of their Drosophila melanogaster host larva. Using the co-immunolocalization of fluorescent L. boulardi venosomes and one of the putative-transported virulence factors, LbGAP, with known markers of cellular endocytosis, we show that venosomes endocytosis by lamellocytes is not a process dependent on clathrin or macropinocytosis and internalization seems to bypass the early endosomal compartment Rab5. After internalization, LbGAP colocalizes strongly with flotillin-1 and the GPI-anchored protein Atilla/L1 (a lamellocyte surface marker) suggesting that entry occurs via a flotillin/lipid raft-dependent pathway. Once internalized, venosomes reach all intracellular compartments, including late and recycling endosomes, lysosomes, and the endoplasmic reticulum network. Venosomes therefore enter their target cells by a specific mechanism and the virulence factors are widely distributed in the lamellocytes’ compartments to impair their functions.
Pesticide induced up-regulation of esterase and aldehyde dehydrogenase in indigenous Bacillus spp.

Abstract During bacterial growth an increased mRNA level is usually linked with higher rate of metabolism related to biodegradation of an unusual compound. In this study, quantitative gene expression data derived from mRNA level reveal the presence of pesticide degrading genes in 6 bacterial isolates showing biodegradation of cypermethrin (SG2, SG4), sulfosulfuron (SA2, Sulfo3), and fipronil (FA3, FA4). A correlation existed between the level of esterase coding mRNA and mineralization of cypermethrin in SG2 and SG4. Similarly the level of EST coding mRNA increased with biodegradation of fipronil and sulfosulfuron in FA3, FA4, SA2, and Sulfo3. Expression of est gene was observed in all the bacterial strains, but their level of expression was different. Bacterial strains SG4 and Sulfo3 showed higher level of est gene expression as compared to SG2, FA3, FA4, and SA2 and was in the range of approximately 30- to 60-fold, respectively, in comparison to control. Expression of genes for aldehyde dehydrogenase was observed in SG4 and Sulfo3. We report co expression of aldh (1000 bp) and est (∼550 bp) genes at the same time of pesticide induction/biodegradation.
Functional connectivity in default mode network correlates with severity of hypoxemia in obstructive sleep apnea

Obstructive sleep apnea (OSA)‐associated hypoxemia, sleep fragmentation, and cerebral vascular dysfunction are implicated in cognitive dysfunction. Functional connectivity within default mode network (DMN) is a possible mechanism underlying the cognitive impairment. The aim of this study was to investigate the impact of hypoxemia and sleep fragmentation on functional connectivity and on cognitive performance in patients with OSA.
Cholinergic modulation of Up–Down states in the mouse medial entorhinal cortex in vitro

Cholinergic tone is high during wake and rapid eye movement sleep and lower during slow wave sleep (SWS). Nevertheless, the low tone of acetylcholine during SWS modulates sharp wave ripple incidence in the hippocampus and slow wave activity in the neocortex. Linking the hippocampus and neocortex, the medial entorhinal cortex (mEC) regulates the coupling between these structures during SWS, alternating between silent Down states and active Up states, which outlast neocortical ones. Here, we investigated how low physiological concentrations of acetylcholine (ACh; 100–500 nM) modulate Up and Down states in a mEC slice preparation. We find that ACh has a dual effect on mEC activity: it prolongs apparent Up state duration as recorded in individual cells and decreases the total synaptic charge transfer, without affecting the duration of detectable synaptic activity. The overall outcome of ACh application is excitatory and we show that ACh increases Up state incidence via muscarinic receptor activation. The mean firing rate of principal neurons increased in around half of the cells while the other half showed a decrease in firing rate. Using two‐photon calcium imaging of population activity, we found that population‐wide network events are more frequent and rhythmic during ACh and confirmed that ACh modulates cell participation in these network events, consistent with a role for cholinergic modulation in regulating information flow between the hippocampus and neocortex during SWS.
Meta‐analyzing count events over varying durations using the piecewise Poisson model: The case for poststroke seizures

Meta‐analyzing count data can be challenging when follow‐up time varies across studies. Simply pooling aggregate data over time‐periods would result in biased estimates, which may erroneously inform clinical decision‐making. In this study, we exploit the convolution property of the Poisson distribution to develop a likelihood for observed cumulative counts over varying follow‐up periods, where different Poisson distributions are used to represent the data generating processes for the latent counts in pre‐defined successive intervals of follow‐up. We illustrate this approach using an example of poststroke seizures, a case in which risk may change over time, and mimic its survival duration with time‐varying hazard. Data were extracted from observational studies (1997‐2016) reporting poststroke seizures over a maximum of 10 years of follow‐up. Three clinically meaningful follow‐up time intervals were considered: 0 to 7 days, 8 to 365 days, and 1 to 10 years poststroke. External validation was performed using claims data. Results suggest the incidence rate of seizures was 0.0452 (95% confidence interval: 0.0429, 0.0475), 0.0001 (0, 0.016), and 0.0647 (0.0441, 0.0941) for the three time intervals, respectively, indicating that the risk of seizures changes over time poststroke. We found that the model performed well against the incidence rate of seizures among actual retrospective cohort from claims data. The piecewise Poisson model presents a flexible way to meta‐analyze count data over time and mimic survival curves. The results of the piecewise Poisson model are readily interpretable and may spur meaningful clinical action. The method may also be applied to other diseases.
Sleep Medicine Milestones 2.0: designed for our field.

None The Accreditation Council for Graduate Medical Education (ACGME) published the first sleep medicine milestones in 2015. However, these milestones were the same among all internal medicine fellowship programs; they were not specific to the specialty. Based on stakeholder feedback, the ACGME called for the creation of specialty-specific milestones. Herein, we outline the history of ACGME reporting milestones, identification of knowledge, skills, and attitudes that define the practice of sleep medicine, and creation of the supplemental guide and sleep medicine-specific milestones (Sleep Medicine Milestones 2.0) to assess developmental progression during fellowship training.
Ion microprobe–measured stable isotope evidence for ammonite habitat and life mode during early ontogeny

Abstract. Ammonites have disparate adult morphologies indicative of diverse ecological niches, but ammonite hatchlings are small (~1mm diameter), which raises questions about the similarity of egg incubation and hatchling life mode in ammonites. Modern Nautilus is sometimes used as a model organism for understanding ammonites, but despite their outward similarities, the groups are only distantly related. Trends in ammonite diversity and extinction vulnerability in the fossil record contrast starkly with those of nautilids, and embryonic shells from Late Cretaceous ammonites are two orders of magnitude smaller than nautilid embryonic shells. To investigate possible environmental changes experienced by ammonite hatchlings, we used secondary ion mass spectrometry to analyze the oxygen and carbon isotope composition of the embryonic shells and early postembryonic whorls of five juveniles of Hoploscaphites comprimus obtained from a single concretion in the Fox Hills Formation of South Dakota. Co-occurring bivalves and diagenetic calcite were also analyzed to provide a benthic baseline for comparison. The oxygen isotope ratios of embryonic shells are more like those of benthic bivalves, suggesting that ammonite eggs were laid on the bottom. Ammonite shell immediately after hatching has more negative δ18O, suggesting movement to more shallow water that is potentially warmer and/or fresher. After approximately one whorl of postembryonic growth, the values of δ18O become more positive in three of the five individuals, suggesting that these animals transitioned to a more demersal mode of life. Two other individuals transition to even lower δ18O values that could suggest movement to nearshore brackish water. These data suggest that ammonites, like many modern coleoids, may have spawned at different times of the year. Because scaphites were one of the short-term Cretaceous–Paleogene extinction survivors, it is possible that this characteristic allowed them to develop a broader geographic range and, consequently, a greater resistance to extinction.
Sequential metastasis to the liver and pancreas 4 years after gestational trophoblastic neoplasia: a case report

This case report describes a 43-year-old female initially diagnosed with gestational trophoblastic neoplasia that then experienced metastasis to the liver and then subsequently to the pancreas nearly 4 years after the primary diagnosis. After resection of the body and tail of the pancreas, the postoperative histopathological examination confirmed a placental site trophoblastic tumour that had developed after several cycles of chemotherapy for the original primary tumour and the liver metastases. This type of sequential recurrence of gestational trophoblastic neoplasia in the primary site or metastatic sites, such as the liver or pancreas, can be cured by a comprehensive treatment strategy involving surgery and/or salvage chemotherapy and continuous follow-up over a long period, especially for patients with a high-risk status.
Microbial carbon source utilization in rice rhizosphere and non‐rhizosphere soils in a 34‐year fertilized paddy field

Carbon (C) is playing an important role in regulating soil nutrient cycling, maintaining soil fertility and crop yield, but there is still need to further study on how C source utilization characteristic respond to soil physical and chemical properties change with different fertilizer treatments under a double‐cropping rice (Oryza sativa L.) field in southern China. Therefore, the effects of 34‐year long‐term fertilizer regime on C source utilization characteristic in rice rhizosphere and non‐rhizosphere soils under a double‐cropping rice field in southern China were studied by using 18O–H2O method in the present paper. The field experiments were included four fertilizer treatments: mineral fertilizer alone (MF), rice straw and mineral fertilizer (RF), 30% organic manure and 70% mineral fertilizer (OM), and without fertilizer input as control (CK). The results showed that microbial biomass C content, basal respiration of soil microorganism and microbial growth rate in rice rhizosphere and non‐rhizosphere soils with OM and RF treatments were significantly higher (p < .05) than that of CK treatment. The microbial C utilization efficiency (CUE) in rhizosphere soil with MF and CK treatments were significantly higher (p < .05) than that of OM treatment, but there was no significantly difference (p > .05) in microbial CUE in non‐rhizosphere soil between MF, RF, OM, and CK treatments. In the different parts of soil, the microbial biomass C content and basal respiration of soil microorganism in rhizosphere soil were higher than that of non‐rhizosphere soil, but the microbial growth rate and microbial CUE in non‐rhizosphere soil were higher than that of rhizosphere soil. Compared with CK and MF treatments, the metabolic capacity of soil microorganism to exogenic C source with RF and OM treatments were significantly higher (p < .05) than that of MF and CK treatments. The largest type of exogenic C source used by soil microorganism was carboxylic acids, followed by amino acid and carbohydrate, and complex compounds was the smallest. In the different parts of soil, the metabolic capacity of soil microorganism to the types of exogenic C source in non‐rhizosphere soil was higher than that of rhizosphere soil. The redundancy analysis results indicated that there had obvious difference in utilization characteristic of soil microorganism to exogenic C source among different fertilizer treatments. In conclusion, this results indicated that characteristic of soil C source utilization were significantly changed under different long‐term fertilizer condition.
The Relationship between Flipped Classrooms and Academic Achievement Motivation of the Students of Higher Educational Studies

The current research paper aims to design a Flipped Classroom Model (FCM) and measure its effectiveness in promoting the academic achievement motivation of the students of higher educational studies at King Abdulaziz University. The study sample consisted of (56) students enrolled in the Higher Education Studies Program at King Abdulaziz University. Aquasi-experimental design used two groups: an experimental group which used a proposed Flipped Classroom Model, and a control group which used traditional classrooms. Furthermore, an academic achievement motivation measure has been developed. The implementation results have revealed that Flipped Classrooms (FCs) are more effective in promoting the academic achievement motivation of the experimental group than the control group of the traditional classrooms. [Abdulellah Abdullah Mohammad Alsulaimani. The Relationship between Flipped Classrooms and Academic Achievement Motivation of the Students of Higher Educational Studies. Life Sci J 2019;16(5):86-93]. ISSN: 1097-8135 (Print) / ISSN: 2372-613X (Online). http://www.lifesciencesite. com. 12. doi:10.7537/marslsj160519.12.
Hydroxypropyl Cellulose Adhesives for Transfer Printing of Carbon Nanotubes and Metallic Nanostructures.

Transfer printing is one of the key nanofabrication techniques for the large-scale manufacturing of complex device architectures. It provides a cost-effective and high-throughput route for the integration of independently processed materials into spatially tailored architectures. Furthermore, this method enables the fabrication of flexible and curvilinear devices, paving the way for the fabrication of a new generation of technologies for optics, electronics, and biomedicine. In this work, hydroxypropyl cellulose (HPC) membranes are used as water soluble adhesives for transfer printing processes with improved performance and versatility compared to conventional silicone alternatives. The high-water solubility and excellent mechanical properties of HPC facilitate transfer printing with high yield for both metal and carbon nanotubes (CNTs) inks. In the case of metal inks, crack-free stripping of silver films and the simple fabrication of Moiré Plasmonic architectures of different geometries are demonstrated. Furthermore, HPC membranes are used to transfer print carbon nanotube films with different thicknesses and up to 77% transparency in the visible and near infrared region with potential applications as transparent conductive substrates. Finally, the use of prepatterned HPC membranes enables nanoscale patterning of CNT with feature resolution down to 1 µm.
Biomarker-based outcome prediction in prostate adenocarcinoma depends on the TMPRSS2-ERG status

Background Prostate adenocarcinoma (PCa) with/without the TMPRSS2-ERG (T2E)-fusion represent distinct molecular subtypes. Objective To investigate gene-signatures associated with metastasis in T2E-positive and -negative PCa, and to identify and validate subtype-specific prognostic biomarkers. Design, setting and participants Gene expression and clinicopathological data of two discovery PCa cohorts (total n=783) were separately analyzed regarding the T2E-status. Selected subtype-specific biomarkers were validated in two additional cohorts (total n=405). Outcome measurements and statistical analysis From both discovery cohorts, we generated two gene lists ranked by their differential intratumoral expression in patients with/without metastases stratified by T2E-status, which were subjected to gene set enrichment and leading-edge analyses. The resulting top 20 gene-signatures of both gene lists associated with metastasis were analyzed for overlaps between T2E-positive and -negative cases. Genes shared by several functional gene-signatures were tested for their association with event-free survival using the Kaplan-Meier method in a validation cohort. Immunohistochemistry was performed in another validation cohort. Results and limitations Metastatic T2E-positive and -negative PCa are characterized by different gene-signatures. Five genes (ASPN, BGN, COL1A1, RRM2 and TYMS) were identified whose high expression was significantly associated with worse outcome exclusively in T2E-negative PCa. This was validated in an independent cohort for all genes and additionally for RRM2 by immunohistochemistry in a separate validation cohort. No prognostic biomarkers were identified exclusively for T2E-positive tumors. Conclusions Our study demonstrates that the prognostic value of biomarkers critically depends on the molecular subtype, i.e. the T2E-status, which should be considered when screening for and applying novel prognostic biomarkers for outcome prediction in PCa. Patient summary Outcome prediction for PCa is complex. The results of this study highlight that the validity of prognostic biomarkers depends on the molecular subtype, specifically the presence/absence of T2E. The reported new subtype-specific biomarkers exemplify that biomarker-based outcome prediction in PCa should consider the T2E-status.
Hematological Findings in Patients with Acute Peripheral Facial Palsy.

OBJECTIVES This study aimed at evaluating the clinical significance of hematological findings in patients with acute peripheral facial palsy. MATERIALS AND METHODS For this retrospective case series review, 84 patients who visited our university hospital and were diagnosed with Bell's palsy (BP) or Ramsay Hunt syndrome (RHS) between March 2017 and March 2019 were enrolled. We documented their epidemiological details, final diagnoses, House-Brackmann (HB) palsy grades, and pretreatment and day 7 post-hospitalization complete blood counts. The outcome was considered favorable if the HB grade at weeks 10-16 was I or II. We analyzed the hematological findings in terms of diagnosis and the final treatment outcomes. RESULTS A higher pretreatment neutrophil-to-lymphocyte ratio (NLR) and neutrophil count and a lower day-7 lymphocyte count were observed in patients with RHS with unfavorable outcomes. In such patients, moderate positive correlations were observed between the pretreatment white blood cell, neutrophil, and basophil counts; the NLR and basophil-to-lymphocyte ratio; and the initial HB grade. Only the latter was a significant risk factor for a poor treatment outcome. In patients with BP, both the initial HB grade and the pretreatment eosinophil count were included in a regression model predicting prognosis. CONCLUSION Inflammation plays an important role in RHS pathogenesis. Initial RHS severity and the response to corticosteroids may determine the final treatment outcome. However, inflammatory markers do not predict all BP outcomes; BP may be etiologically heterogeneous.
A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells

Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin–Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells.
Cell therapy during machine perfusion

There has been increasing use of organs from extended criteria or donation after circulatory death donors to meet the demands of the transplant waiting list. Over the past decade, there has been considerable progress in technologies to preserve organs prior to transplantation to improve the function of these marginal organs. This has led to the development of normothermic machine perfusion, whereby an organ is perfused with warmed, oxygenated blood and nutrients to resume normal physiological function in an isolated ex‐vivo platform. With this advance in preservation comes significant opportunities to recondition, repair and regenerate organs prior to transplantation using cellular therapies. This review aims to discuss the possibilities of machine perfusion technology; highlighting the potential for organ‐directed reconditioning and the future avenues for investigation in this field.