Miracle-dz/UniFAR-FTUs huggingface dataset:
Osimertinib or EGFR-TKIs/chemotherapy in patients with EGFR-mutated advanced nonsmall cell lung cancer

Abstract Background: The aim of this meta-analysis is to investigate the impact of Osimertinib on treatment efficacy in advanced nonsmall cell lung cancer (NSCLC). Methods: Trials comparing Osimertinib against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)/chemotherapy in patients with NSCLC with an epidermal growth factor receptor (EGFR) mutation were included, and the pooled data for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Results: Analysis results based on 6 eligible trials showed that Osimertinib significantly improved the overall PFS (hazard ratio [HR] = 0.38, 95% confidence interval [CI] = 0.29–0.50), improved the OS (HR = 0.66, 95% CI = 0.48–0.89), increased the ORR (odds ratio [OR] = 1.76, 95% CI = 1.14–2.72), increased the overall DCR (OR = 1.18, 95% CI = 1.02–1.37), and reduced the grade 3 or greater AEs (relative ratio [RR] = 0.50, 95% CI = 0.33–0.75) in all subgroups except in the ORR in the Exon 19 deletion (Ex19del) and/or L858R subgroup. Compared to patients with Ex19del and/or L858R mutation, patients with the T790M mutation had the benefits of a greater PFS (41.7%), a greater ORR (80.0%), a greater DCR (71.2%), and fewer grade 3 or greater AEs (70.7%) (each P < .05). Race, sex, age, EGFR mutation, and smoking history may significantly predict additional benefits from Osimertinib, but there were no significant differences between subgroups stratified by these clinical characteristics. Conclusions: Osimertinib showed greater treatment benefit for patients with NSCLC with EGFR mutation than EGFR-TKIs/chemotherapy, especially for T790M mutation-positive patients.
Acute downregulation of novel hypothalamic protein sushi repeat-containing protein X-Linked 2 (SRPX2) after experimental traumatic brain injury.

Traumatic brain injury (TBI) causes damage to the hypothalamo-hypophyseal axis, leading to endocrine dysregulation in up to 40% of TBI patients. Hence, there is an urgent need to identify non-invasive biomarkers for TBI-associated hypothalamo-hypophyseal pathology. Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein expressed in both rat and human brain. Our objective was to investigate the effect of acquired brain injury on plasma SRPX2 protein levels and SRPX2 expression in the brain. We induced severe lateral fluid-percussion injury in adult male rats and investigated changes in SRPX2 expression at 2 h, 6 h, 24 h, 48 h, 72 h, 5 d, 7 d, 14 d, 1 month, and 3 months post-injury. The plasma SRPX2 level was assessed by Western blot analysis. Hypothalamic SRPX2-immunoreactive neuronal numbers were estimated from immunostained preparations. At 2 h post-TBI, plasma SRPX2 levels were markedly decreased compared with the naïve group (AUC=1.00, p<0.05). Severe TBI caused a reduction in the number of hypothalamic SRPX2-immunoreactive neurons bilaterally at 2 h post-TBI as compared to naïve group (5032 ± 527 vs 9440 ± 351, p<0.05). At 1 month after severe TBI, however, the brain and plasma SRPX2 levels were comparable between the TBI and naïve groups (p>0.05). Unsupervised hierarchical clustering using SRPX2 expression differentiated animals into injured and uninjured clusters. Our findings indicate that TBI leads to an acute reduction in SRPX2 protein expression and reduced plasma SRPX2 level may serve as a candidate biomarker of hypothalamic injury.
The influence of electrode for electroluminescence devices based on all-inorganic halide perovskite CsPbBr3

Electroluminescence devices based on all-inorganic halide perovskite material with excellent luminescence performance have been studied extensively in recent years. However, the important role for the electrodes of electroluminescence devices is payed few attention by theoretical and experimental studies. Appropriate electrodes can reduce the Schottky barrier height to decrease the energy loss, and prevent the metal impurities from diffusing into the perovskite material to generate deep traps levels, which improves the luminous efficiency and lifetime of devices. In this paper, not only the interface effects between CsPbBr3 and common metal electrode (Ag, Au, Ni, Cu and Pt) are studied by first-principle calculations, but also the diffusion effects of metal electrode atom into the CsPbBr3 layer are also explored by nudged elastic band calculations. The calculated results show the metal Ag is more suitable for the cathode for CsPbBr3 electroluminescence devices, while the metal Pt is more applicable for the anode. Based on the overall consideration about the interface effects and diffusion effects of the CsPbBr3-metal electrode junctions, the essential principle is analyzed. The work provides theoretical guidance for how to select the right electrode for the electroluminescence performance of all-inorganic halide perovskite. The critical factor of Schottky barrier height between the electrode and the light-emitting semiconductor, and transition level generated by metal impurities also provide a valuable reference how to select the suitable electrodes for other electroluminescence devices.
Single‐cell study of neural stem cells derived from human iPSCs reveals distinct progenitor populations with neurogenic and gliogenic potential

We used single‐cell RNA sequencing (seq) on several human induced pluripotent stem (iPS) cell‐derived neural stem cell (NSC) lines and one fetal brain‐derived NSC line to study inherent cell type heterogeneity at proliferating neural stem cell stage and uncovered predisposed presence of neurogenic and gliogenic progenitors. We observed heterogeneity in neurogenic progenitors that differed between the iPS cell‐derived NSC lines and the fetal‐derived NSC line, and we also observed differences in spontaneous differentiation potential for inhibitory and excitatory neurons between the iPS cell‐derived NSC lines and the fetal‐derived NSC line. In addition, using a recently published glia patterning protocol we enriched for gliogenic progenitors and generated glial cells from an iPS cell‐derived NSC line.
Relative contribution of climate and non-climate drivers in determining dynamic rates of boreal birds at the edge of their range

The Adirondack Park in New York State contains a unique and limited distribution of boreal ecosystem types, providing habitat for a number of birds at the southern edge of their range. Species are projected to shift poleward in a warming climate, and the limited boreal forest of the Adirondacks is expected to undergo significant change in response to rising temperatures and changing precipitation patterns. Here we expand upon a previous analysis to examine changes in occupancy patterns for eight species of boreal birds over a decade (2007–2016), and we assess the relative contribution of climate and non-climate drivers in determining colonization and extinction rates. Our analysis identifies patterns of declining occupancy for six of eight species, including some declines which appear to have become more pronounced since a prior analysis. Although non-climate drivers such as wetland area, connectivity, and human footprint continue to influence colonization and extinction rates, we find that for most species, occupancy patterns are best described by climate drivers. We modeled both average and annual temperature and precipitation characteristics and find stronger support for species’ responses to average climate conditions, rather than interannual climate variability. In general, boreal birds appear most likely to colonize sites that have lower levels of precipitation and a high degree of connectivity, and they tend to persist in sites that are warmer in the breeding season and have low and less variable precipitation in the winter. It is likely that these responses reflect interactions between broader habitat conditions and temperature and precipitation variables. Indirect climate influences as mediated through altered species interactions may also be important in this context. Given climate change predictions for both temperature and precipitation, it is likely that habitat structural changes over the long term may alter these relationships in the future.
The SYNTAX score on its way out or … towards artificial intelligence: part I.

Serruys, Patrick W ; Chichareon, Ply ; Modolo, Rodrigo ; Leaman, David M ; Reiber, Johan H C ; Emanuelsson, Håkan ; Di Mario, Carlo ; Pijls, Nico H J ; Morel, Marie-Angèle ; Valgimigli, Marco ; Farooq, Vasim ; van Klaveren, David ; Capodanno, Davide ; Andreini, Daniele ; Bourantas, Christos V ; Davies, Justin ; Banning, Adrian P ; Escaned, Javier ; Piek, Jan J ; Echavarría-Pinto, Mauro ; Taylor, Charles Anthony ; Thomsen, Brian ; Collet, Carlos ; Pompilio, Giulio ; Bartorelli, Antonio L ; Glocker, Ben ; Dressler, Ovidiu ; Stone, Gregg W ; Onuma, Yoshinobu
AP2/ERF Transcription Factors Integrate Age and Wound Signals for Root Regeneration[OPEN]

RNA-sequencing and chromatin immunoprecipitation-sequencing identified a subset of APETALA2/ETHYLENE RESPONSE FACTOR transcription factors as integrating age and wound signals during root regeneration. Age and wounding are two major determinants for regeneration. In plants, the root regeneration is triggered by wound-induced auxin biosynthesis. As plants age, the root regenerative capacity gradually decreases. How wounding leads to the auxin burst and how age and wound signals collaboratively regulate root regenerative capacity are poorly understood. Here, we show that the increased levels of three closely-related miR156-targeted Arabidopsis (Arabidopsis thaliana) SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL2, SPL10, and SPL11, suppress root regeneration with age by inhibiting wound-induced auxin biosynthesis. Mechanistically, we find that a subset of APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors including ABSCISIC ACID REPRESSOR1 and ERF109 is rapidly induced by wounding and serves as a proxy for wound signal to induce auxin biosynthesis. In older plants, SPL2/10/11 directly bind to the promoters of AP2/ERFs and attenuates their induction, thereby dampening auxin accumulation at the wound. Our results thus identify AP2/ERFs as a hub for integration of age and wound signal for root regeneration.
Efficacy of ulinastatin for the treatment of patients with severe acute pancreatitis

Abstract Background: The aim of this study is to explore the efficacy and safety of ulinastatin for the treatment of patients with severe acute pancreatitis (SAP). Methods: We will search randomized controlled trials which assess the efficacy and safety of ulinastatin for patients with SAP from the electronic databases of Cochrane Library, MEDILINE, EMBASE, CINAHL, PsycINFO, Scopus, CBM, Wangfang, VIP, and CNKI. All electronic databases will be searched from inception to the present with no limitations of language and publication status. Two researchers will carry out study selection, data extraction, and study quality assessment independently. Another researcher will help to resolve any disagreements between 2 researchers. Results: The outcomes include overall mortality, time of hospital stay, complications of systematic or local infection, multiple organ deficiency syndrome, health related quality of life (as measured as the 36-Item Short Form Health Survey), and adverse events related to nutrition. Conclusion: This study will provide evidence to evaluate the efficacy and safety of ulinastatin in the treatment of patients with SAP. Systematic review registration: PROSPERO CRD42019149566.
Trough Levels of Infliximab at W6 Are Predictive of Remission at W14 in Pediatric Crohn Disease.

OBJECTIVE Infliximab (IFX) is a frequent therapeutic option for Crohn disease (CD) patients. Early detection of responders to IFX is critical for the management of CD in order to avoid long-term exposure to the drug without benefit. This retrospective study aimed at analysing which early parameters recorded during the induction period are able to predict response to IFX during the maintenance period in pediatric CD. PATIENTS AND METHODS Medical records of all CD patients ages from 2 to 18 years who received IFX at a tertiary IBD center were retrospectively analyzed. Children were classified in 3 groups according to their response at week 14 (W14) (1) remission, (2) clinical response or (3), no response. The factors recorded at W0, W2, and W6, which were associated with remission at W14 were analyzed using a logistic regression. RESULTS Among the 111 patients included, 74.8% patients were responders to IFX at W14, including 38.7% in clinical remission and 36% with partial clinical response. Clinical remission at W14 was associated with normal growth (P < 0.01), and normal albuminemia (P = 0.01) at baseline, It was also associated with trough levels to IFX >8.3 μg/ml at week 6 (P < 0.01). CONCLUSION Trough levels to IFX >8.3 μg/ml at week 6 are predictive of remission at W14 for luminal disease.
Prediction of long-term quality of life after severe traumatic brain injury based on variables at hospital admission

ABSTRACT Objectives: Variables collected early after severe traumatic brain injury (sTBI) could predict health-related quality of life (HRQoL). Our aim was to determine the prevalence of patients with a low HRQoL 4 years after sTBI and to develop a prediction model including early variables. Methods: Adult patients with both sTBI [abbreviated injury score of the head region (HAIS) >3] and disease-specific HRQoL assessments using the ‘Quality of Life after Brain Injury’ (QOLIBRI) were included. The outcome was the total score (TS) of QOLIBRI; cutoff for low HRQoL: <60 points. A multivariate logistic regression model and prediction model were performed. Results: One hundred-sixteen patients [median age 50.8 years (IQR 25.9–62.8; 21.6% >65 years)] were included; 68 (58.6%) with HAIS = 4, 48 (41.4%) with HAIS = 5. Median Glasgow Coma Scale (GCS) was 13 (IQR 3–15). Median TS was 77 (IQR 60–88). Low HRQoL was observed in 28 patients (24.1%). Two variables were associated with low HRQoL: GCS <13, working situation other than employed or retired. The prediction model had an AUROC of 0.765; calibration was moderate (Hosmer Lemeshow Chi2 6.82, p = .556). Conclusion: One in four patients had a low HRQoL after 4 years. A lower GCS and working situations were associated with low HRQoL.
A Novel Framework on Abdominal Aortic Aneurysm Analysis Based on Biomedical Simulation Tools

Nowadays, the mortality rate due to cardiovascular diseases is significant due to noticed critical aneurysm cases. Abnormal swelling at the aorta causes Abdominal Aortic Aneurysm (AAA). They are usually saccular, fusiform according to their shape statistics. Hence it’s better to analyze, segment and model them to aid physicians/surgeons in various aspects of nonsurgical and surgical treatments. Morphological study provides approximate dimensions and risk of rupture. The objective of this work is to provide an extensive study on AAA segmentation, modeling and analysis with individual frameworks in sequence using tools like MATrix LABoratory (MATLAB), Materialise's Interactive Medical Image Control System (MIMICS), 3-matic and Finite Element Biomechanics (FEBio). The ultimate goal is to develop a 3D printed aneurysm replica for further evaluation and analysis using Ultimaker Cura Slicer Software. MATLAB is used to segment the Aorta irrespective of intensity/contrast inhomogeneities using Solidity feature. MIMICS software is used for modeling the aneurysms using three types of Axial, Coronal, and Saggital views. 3-matic provides an easy interface to do the dimensional analysis using imported aneurysm morphology. FEBio with PreView, PostView plugins is a nonlinear finite element solver which offers a chance to study it and to predict the future regions of rupture to some extent via Computational Fluid Dynamics (CFD) features. 3D printing of aneurysm offers the flexibility of knowing their epithelial characteristics and hands-on experience. The main merit of this novel and efficient framework is non-invasive studies of Aneurysm Segmentation, Analysis, and Modeling using five tools which addresses the complete study of AAA.
Lateral interactions at functional monolayers

This review gives an overview of the recent literature regarding lateral molecular interactions in monolayers. The first part (Section 3) focuses on systems of self-assembled monolayers on metal surfaces, discussing the covalent and noncovalent interactions of the terminal functionality or between the molecular chains of the molecules. The second part (Section 4) highlights the intermolecular interactions of monolayers on silicon and metal oxide surfaces. The third part (Section 5) presents examples of lateral interactions on receptor surfaces. A focus in all parts is on examples of lateral interactions in monolayers in which electron or energy transfer occurs.
The degree of genetic variation between strains of Dekkera / Brettanomyces yeast isolated from different Australian wineries and regions

Species of Dekkera/Brettanomyces are reported to be responsible for producing 4-ethylphenol (4-EP), 4ethylguaiacol (4-EG) (volatile phenols) and isovaleric acid, potential spoilage compounds in wine (Coulter et al., 2003). In order to devise a strategy to control the development of Dekkera/Brettanomyces spoilage compounds during winemaking, it is important to define factors such as wine environment and yeast strain that influence their formation. The formation of volatile phenols from hydroxycinnamic acids, such as coumaric and ferulic acids, requires the sequential action of two enzyme activities, decarboxylation and reduction. Whereas the decarboxylation reaction can be carried out by a large number of microbes, the reduction activity appears to be restricted to particular genera, one of which is Dekkera/Brettanomyces (Chatonnet et al., 1993; 1995). Studies on the effect of environment on the formation of these spoilage compounds are sparse. Growth of Dekkera/Brettanomyces appears to be favoured by residual sugar and nitrogen in wine, and by higher pH (Coulter et al., 2003). More detailed studies on a single strain have shown that the conversion of p-coumaric acid into 4ethylphenol seems to be efficient when glucose or ethanol are used as sole carbon sources. In the same study, increasing concentrations of ethanol inhibited yeast growth and 4ethylphenol production (Dias et al., 2003). However, only a few studies on a limited number of strains have been carried out, and there is no information concerning the influence of strain variation on volatile phenol production. The purpose of the current study is to define the distribution and level of genetic diversity that exists in Australian wine isolates of Dekkera/Brettanomyces yeast with the long-term goal of understanding the effect of environment and strain on 4-EP, 4-EG and isovaleric acid formation. With this knowledge, controlling, or even taking advantage of, Dekkera/Brettanomyces ‘spoilage’ will be possible.
Buffering of Fixed Length Burst in Optical Burst Switching Networks

Optical burst switching is a hot area of research. OBS can be considered as variant of optical circuit switching. In OBS information is transmitted in form of bunch of packets. However in each burst number of packets may differ in number. Therefore, in OBS first control packet is sent to reserve advance path, thereafter same path is followed by burst. As burst length is not known, therefore contending burst cannot be stored instead deflection routing is used. To alleviate this problem, this paper discusses a method which proves an estimate of burst length for a particular load and assembly time, thus enable the possibility of storing of burst. Mathematical analysis is presented and results are shown using graphs and finally simulation results are presented for the buffering of burst in terms of burst loss probability.
Institutional Demand and Post-earnings-announcement Return

This paper shows that institutional demand in the pre-announcement period negatively predicts post-earnings-announcement return even after controlling for earnings surprise, past returns, and other stock characteristics. This market inefficiency is distinct from the well-known PEAD anomaly and return reversal, and can even overshadow them. The effect is stronger for stocks with smaller market capitalization, higher arbitrage risk, higher transaction costs and lower investor sophistication, consistent with the hypothesis of limits-to-arbitrage. Moreover, institutional investors trade to exploit market inefficiencies after earnings announcements as arbitrageurs. It suggests a dual role of institutional trading in contributing to and correcting mispricing around earnings announcements. JEL Classification: G10, G12, G14, M40
Ecological Character Displacement in Non-Congeneric Frogs

Character displacement is phenotypic divergence driven by competition (ecological character displacement) or reproductive interference (reproductive character displacement). Although previous studies have examined these phenomena separately, recent evidence suggests that reproductive interference can drive both reproductive and ecological character displacement, in that certain traits are related to both competition and reproduction. Thus, to evaluate the effect of competition, the effect of reproductive interference must be excluded. Here, we analysed ecological character displacement between non-congeneric frogs, which show little reproductive interference. Odorrana amamiensis inhabits the Amami and Tokunoshima Islands, Japan, whereas its non-congeneric competitor Babina subaspera inhabits the Amami Island. We tested three of the Schluter (2000) criteria for ecological character displacement: phenotypic changes in O. amamiensis between the two islands, phenotypic change related to prey preference, prey availability between the two islands. We demonstrated that the three criteria in Schluter (2000) were likely to be satisfied, indicating the occurrence of ecological character displacement in non-congeners without reproductive interference. Thus, we conclude that competition is potentially the main driver of this phenotypic divergence, and that non-congeners may be a suitable model for evaluating ecological character displacement in a variety of organisms, as the influence of reproductive interference can be excluded.