Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment and characterization of a DOT1L inhibitor‐sensitive human acute monocytic leukemia cell line YBT‐5 with a novel KMT2A‐MLLT3 fusion

Immortalized cell lines are useful for deciphering the pathogenesis of acute leukemia and developing novel therapeutic agents against this malignancy. In this study, a new human myeloid leukemia cell line YBT‐5 was established. After more than 1‐year cultivation from the bone marrow of a patient with acute monocytic leukemia, YBT cell line was established. Then a subclone, YBT‐5, was isolated from YBT using single cell sorting. Morphological and cytogenetical characterizations of the YBT‐5 cell line were determined by cytochemical staining, flow cytometry analysis, and karyotype analysis. Molecular features were identified by transcriptomic analysis and reverse transcription–polymerase chain reaction. To establish a tumor model, 5 × 106 YBT‐5 cells were injected subcutaneously in nonobese diabetic/severe combined immune‐deficiency (NOD/SCID) mice. DOT1L has been proposed as a potential therapeutic target for KMT2A‐related leukemia; therefore, to explore the potential application of this new cell line, its sensitivity to a specific DOT1L inhibitor, EPZ004777 was measured ex vivo. The growth of YBT‐5 does not depend on granulocyte‐macrophage colony‐stimulating factor. Cytochemical staining showed that α‐naphthyl acetate esterase staining was positive and partially inhibited by sodium fluoride, while peroxidase staining was negative. Flow cytometry analysis of YBT‐5 cells showed positive myeloid and monocytic markers. Karyotype analysis of YBT‐5 showed 48,XY,+8,+8. The breakpoints between KMT2A exon 10 and exon 11 (KMT2A exon 10/11) and MLLT3 exon 5 and exon 6 (MLLT3 exon 5/6) were identified, which was different from all known breakpoint locations, and a novel fusion transcript KMT2A exon 10/MLLT3 exon 6 was formed. A tumor model was established successfully in NOD/SCID mice. EPZ004777 could inhibit the proliferation and induce the differentiation of YBT‐5 cells. Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A‐associated leukemia.
Improved Electrophoretic Separation to Assist the Monitoring of Bcl-xL Post-Translational Modifications

Bcl-xL is an oncogene of which the survival functions are finely tuned by post-translational modifications (PTM). Within the Bcl-2 family of proteins, Bcl-xL shows unique eligibility to deamidation, a time-related spontaneous reaction. Deamidation is still a largely overlooked PTM due to a lack of easy techniques to monitor Asn→Asp/IsoAsp conversions or Glu→Gln conversions. Being able to detect PTMs is essential to achieve a comprehensive description of all the regulatory mechanisms and functions a protein can carry out. Here, we report a gel composition improving the electrophoretic separation of deamidated forms of Bcl-xL generated either by mutagenesis or by alkaline treatment. Importantly, this new gel formulation proved efficient to provide the long-sought evidence that even doubly-deamidated Bcl-xL remains eligible for regulation by phosphorylation.
High-Throughput MicroRNA Profiles of Permissive Madin-Darby Canine Kidney Cell Line Infected with Influenza B Viruses

Victoria and Yamagata lineages of influenza B viruses are globally circulating in seasonal epidemics. Madin–Darby canine kidney (MDCK) cells are permissive for viral isolation and vaccine manufacture. Nevertheless, the interplay between influenza B viruses and host microRNAs has not been investigated in this cell line. Therefore, the present study aims at high-throughput analysis of canine microRNA profile upon infection of influenza B viruses. Briefly, MDCK cells were infected with Victoria or Yamagata lineage at MOI of 0.01. After being harvested at 6, 12 and 24 h post infection, microRNAs were subjected to high-throughput sequencing based on MiSeq platform (Illumina). The results demonstrated that five microRNAs including cfa-miR-197, cfa-miR-215, cfa-miR361, cfa-miR-1841, and cfa-miR-1842 were overexpressed in both Victoria and Yamagata lineage infections. Interestingly, computational prediction showed that karyopherin alpha 6 (KPNA6) was targeted by cfa-miR-197 and cfa-miR-215. Moreover, the binding sites of both microRNAs were assessed by 3′-UTR reporter assay. The results showed that only cfa-miR-197 could bind to the target sites of KPNA6, leading to suppressing luciferase activity. Additionally, silencing of KPNA6 was confirmed by overexpression of cfa-miR-197. This study provides canine microRNA responses to seasonal influenza B viruses, suggesting that virus-mediated microRNAs might play crucial roles in host gene regulation.
Reply to Friedman and Banich: Right measures for the research question

In their Letter to the Editor, Friedman and Banich (1) suggest we (2) “overstate” the higher suitability of dependent variables (DVs) derived from surveys for individual difference analyses. We appreciate this opportunity for a continued discussion regarding the measurement of self-regulation. However, their critiques (1) do not provide evidence against the higher reliability of survey DVs, which is central to our conclusions. Instead, they levy criticisms addressed in another of our papers (3). For instance, the authors (1) argue that task DVs could provide value for individual difference analyses via latent variables. Indeed, we confirmed latent variables underlying task DVs are more reliable compared to individual task DVs (2, 3 … [↵][1]1To whom correspondence may be addressed. Email: zenkavi{at}stanford.edu. [1]: #xref-corresp-1-1
The Impact of Postnatal Systemic Steroids on the Growth of Preterm Infants: A Multicenter Cohort Study

Postnatal steroids, often used to prevent and treat bronchopulmonary dysplasia, may influence the growth of preterm infants, although data are scarce in the literature. This is a multicenter cohort study including surviving preterm infants <32 weeks at birth (n = 17,621) from the Spanish Neonatal Network SEN1500 database, without major congenital malformations. Linear regression models were adjusted for postnatal steroids, respiratory severity course (invasive mechanical ventilation at 28 days), progression to moderate–severe bronchopulmonary dysplasia (O2 at 36 weeks), length of stay, sex, gestational age and z-scores at birth. A subgroup analysis depending on the timing of administration, ventilation status at 28 days and moderate–severe BPD diagnosis was also performed. Overall, systemic postnatal steroids were not independently associated with poorer weight gain (0.1; 95% CI: −0.05 to 0.2 g/kg/day), linear growth (0; 95% CI: −0.03 to 0.01 cm/week) or head circumference growth (−0.01; 95% CI: −0.02 to 0 cm/week). Patients who received steroids after 28 days or who were not O2 dependent at 36 weeks after having received steroids gained more weight (0.22; 95% CI: 0.04 to 0.4 and 0.2; 95% CI: 0.004 to 0.5 g/kg/day, respectively). Globally, systemic postnatal steroids had no significant adjusted effect on postnatal growth.
Rheological, Thermal, and Degradation Properties of PLA/PPG Blends

The work presented herein focuses on simulating the compounding process via a torque rheometer, as well as the relationship between the melt viscosity and the polymer molecular weight (MW). We aim to predict the plasticization of polylactic acid (PLA) using polypropylene glycol (PPG) with different MWs. The rheological properties of the PLA/PPG composites containing PPG with different MWs were systematically studied by capillary rheometry and torque rheometry. The initial degradation of PLA/PPG composites during melt processing was monitored in real time. The results indicate that PPG can significantly reduce the melt viscosity of PLA/PPG composites, leading to obvious pseudoplastic fluid behavior. The lower the MW of PPG, the lower the viscosity of the PLA/PPG composite. The addition of PPG was favorable for the degradation of PLA during processing, and the degradation degree of the composite materials increased as the MW of PPG was decreased.
Conversion Surgery for Advanced Pancreatic Cancer

While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.
The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression

Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis.
Rapid Characterization and Discovery of Chemical Markers for Discrimination of Xanthii Fructus by Gas Chromatography Coupled to Mass Spectrometry

Xanthii Fructus (XF) is known as a medicinal plant. It has been used as a traditional medicine because of its high biological efficacy. However, there have been few comprehensive studies on the specific chemical composition of the plant and consequently, the information is lacking for the mechanism of the natural product metabolites in humans. In this study, an efficient analytical method to characterize and discriminate two species of Xanthii Fructus (Xanthium canadense Mill. and Xanthium sibiricum Patrin ex Widder) was established. Volatile organic compounds (VOCs), polar metabolites, and fatty acids were classified by integrated sample preparation, which allowed a broad range for the detection of metabolites simultaneously. Gas chromatography-mass spectrometry (GC-MS) followed by a multivariate statistical analysis was employed to characterize the chemical compositions and subsequently to discriminate between the two species. The results demonstrate that the two species possess obviously diverse chemical characteristics of three different classifications, and discriminant analysis was successfully applied to a number of chemical markers that could be used for the discrimination of the two species. Additional quantitative results for the selected chemical markers consistently showed significant differences between the two species.
Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint‐targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan–Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.
Occupational experiences of homelessness: A systematic review and meta-aggregation

Abstract Background: Studies exploring the occupational experiences of homeless persons have grown in the past twenty years, and there is a need to identify, evaluate, and aggregate existing studies to direct future research. Objectives: To capture the scope and quality of literature exploring the occupational experiences of homeless persons in high-income countries, and to aggregate the findings of these studies to inform future research efforts. Method: Using Joanna Briggs Institute (JBI) guidelines, we conducted a systematic review including a critical appraisal, and meta-aggregation of themes in existing qualitative literature. Results: Fifteen studies were included and were of high quality (Mdn = 8/10; IQR = 2). Meta-aggregation resulted in four themes (n = 335 participants) describing the occupational experiences of homeless persons: 1) Restrictions on time use and activity engagement; 2) Activity as a means of belonging; 3) Institutional processes as determining time use; and 4) Transcending the self through doing. Conclusions: Homeless persons in high-income countries face multiple challenges to engaging in meaningful activity, which we argue is a disabling experience. Simultaneously, homeless persons demonstrate resilience by finding ways to engage in activities of meaning, and opportunities to connect with others in the face of multiple barriers. Significance: Implications for research and practice are discussed.
Optimizing efficiency and skill utilization: Analysis of genetic counselors' attitudes regarding delegation in a clinical setting

This study assessed genetic counselors' (GCs) perceptions of delegation as a tool to increase workforce efficiency and help meet the current gap between the number of genetic service providers and the number of patients. GCs were recruited to participate via an online survey that assessed activities (categorized as typical genetic counseling, administrative, or professional development) performed by a clinical genetic counselor. Respondents indicated which activities represent their largest time consumers, their willingness to delegate these activities, and barriers to and perceived outcomes of delegation. Overall, respondents indicated that they spend 25% of their time performing administrative activities that they would largely be willing to delegate; however, respondents were generally unwilling to delegate many typical genetic counseling and professional development activities, citing concerns regarding accuracy and liability, and highlighting the belief that these activities constitute the core role of a genetic counselor. Respondents indicated that delegation of time‐consuming administrative activities would increase access to genetic services and improve job satisfaction. Additionally, differences were identified among clinical specialties regarding which activities were selected as top time consumers, indicating that potential targets of re‐allocation of time or delegation may be variable. This research indicates a need to reduce the number of administrative tasks in which GCs are directly involved to re‐allocate time toward core responsibilities, direct patient care, and professional development, the result of which is more efficient use of the GC skill‐set.
A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease

The mosquito-borne chikungunya virus (CHIKV) has become a major global health problem. Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available. We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines. Here, we report the vaccines’ protective efficacies against CHIKV infection in a lethal A129 mouse model. Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ΔCap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation. These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss. Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ΔCap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested. We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.
Similarity Graph-Based Camera Tracking for Effective 3D Geometry Reconstruction with Mobile RGB-D Camera

In this paper, we present a novel approach for reconstructing 3D geometry from a stream of images captured by a consumer-grade mobile RGB-D sensor. In contrast to previous real-time online approaches that process each incoming image in acquisition order, we show that applying a carefully selected order of (possibly a subset of) frames for pose estimation enables the performance of robust 3D reconstruction while automatically filtering out error-prone images. Our algorithm first organizes the input frames into a weighted graph called the similarity graph. A maximum spanning tree is then found in the graph, and its traversal determines the frames and their processing order. The basic algorithm is then extended by locally repairing the original spanning tree and merging disconnected tree components, if they exist, as much as possible, enhancing the result of 3D reconstruction. The capability of our method to generate a less error-prone stream from an input RGB-D stream may also be effectively combined with more sophisticated state-of-the-art techniques, which further increases their effectiveness in 3D reconstruction.
Effects of soybean oil and dietary copper levels on nutrient digestion, ruminal fermentation, enzyme activity, microflora and microbial protein synthesis in dairy bulls

ABSTRACT The study evaluated the effects of soybean oil (SO) and dietary copper levels on nutrient digestion, ruminal fermentation, enzyme activity, microflora and microbial protein synthesis in dairy bulls. Eight Holstein rumen-cannulated bulls (14 ± 0.2 months of age and 326 ± 8.9 kg of body weight) were allocated into a replicated 4 × 4 Latin square design in a 2 × 2 factorial arrangement with factors being 0 or 40 g/kg dietary dry matter (DM) of SO and 0 or 7.68 mg/kg DM of Cu from copper sulphate (CS). The basal diet contained per kg DM 500 g of corn silage, 500 g of concentrate, 28 g of ether extract (EE) and 7.5 mg of Cu. The SO × CS interaction was significant (p < 0.05) for ruminal propionate proportion and acetate to propionate ratio. Dietary SO addition increased (p < 0.05) intake and total tract digestibility of EE but did not affect average daily gain (ADG) of bulls. Dietary CS addition did not affect nutrient intake but increased (p < 0.05) ADG and total tract digestibility of DM, organic matter, crude protein and neutral detergent fibre. Ruminal pH was not affected by treatments. Dietary SO addition did not affect ruminal total volatile fatty acids (VFA) concentration, decreased (p < 0.05) acetate proportion and ammonia N and increased (p < 0.05) propionate proportion. Dietary CS addition did not affect ammonia N, increased (p < 0.05) total VFA concentration and acetate proportion and decreased (p < 0.05) propionate proportion. Acetate to propionate ratio decreased (p < 0.05) with SO addition and increased (p < 0.05) with CS addition. Dietary SO addition decreased (p < 0.05) activity of carboxymethyl cellulase, cellobiase and xylanase as well as population of fungi, protozoa, methanogens, Ruminococcus albus and R. flavefaciens but increased (p < 0.05) α-amylase activity and population of Prevotella ruminicola and Ruminobacter amylophilus. Dietary CS addition increased (p < 0.05) activity of cellulolytic enzyme and protease as well as population of total bacteria, fungi, protozoa, methanogens, primary cellulolytic and proteolytic bacteria. Microbial protein synthesis was unchanged with SO addition but increased (p < 0.05) with CS addition. The results indicated that the addition of CS promoted nutrient digestion and ruminal fermentation by stimulating microbial growth and enzyme activity but did not relieve the negative effects of SO addition on ruminal fermentation in dairy bulls.