Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing.

Background Liver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics. Methods This study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data. Results we found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis. Conclusions This study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients.
Photodynamic therapy of drug-resistant human colon adenocarcinoma using verteporfin-loaded TPGS nanoparticles with tumor homing and penetrating peptide functionalization

Photodynamic therapy (PDT) does well in both curing early stage tumors and improving patients’ quality of life. However, the limited selectivity of photosensitizers (PSs) to tumors has become an urgent issue during the application of PDT clinically, which would exhibit a poor therapeutic outcome and induce skin phototoxicity. To solve this problem, PS-loaded D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS, or simply TPGS) nanoparticles with tumor homing and penetrating peptide tLyp-1 decoration (t-NP) were constructed for PDT of tumors in this study. Verteporfin (VP), as an effective PS, was encapsulated in the core of t-NP, and tLyp-1 was functionalized on the surface as a functional ligand to increase vascular permeability and target the tumor cells. These nanoparticles were spherical in shape and exhibited a narrow size distribution of 23.3 ± 0.80 nm, and had a high encapsulation efficiency and loading capacity of hydrophobic VP. Compared with unmodified nanoparticles (NP), t-NP exhibited enhanced cellular uptake in both primary human umbilical vein endothelial cells (HUVECs) and drug-resistant human colon adenocarcinoma cells (HCT15); and t-NP showed higher selectivity to HCT15 tumors in vivo after intravenous administration of the same dose of VP. The anti-tumor experiment in vivo strongly indicated that nanoparticles with tLyp-1 peptide modification can enhance the selectivity of the PS, and improve the PDT effect.
A low‐cost and high‐throughput benchtop cell sorter for isolating white blood cells from whole blood

The ability to isolate and purify white blood cells (WBCs) from mixed ensembles such as blood would benefit autologous cell‐based therapeutics as well as diagnosis of WBC disorders. Current WBCs isolation methods have the limitations of low purity or requiring complex and expensive equipment. In addition, due to the overlap in size distribution between lymphocytes (i.e., a sub‐population of WBCs) and red blood cells (RBCs), it is challenging to achieve isolation of entire WBCs populations. In this work, we developed an inertial microfluidics‐based cell sorter, which enables size‐based, high‐throughput isolation, and enrichment of WBCs from RBC‐lysed whole blood. Using the developed inertial microfluidic chip, the sorting resolution is sharpened within 2 μm, which achieved separation between 3 and 5 μm diameter particles. Thus, with the present cell sorter, a full population of WBCs can be isolated from RBC‐lysed blood samples with recovery ratio of 92%, and merely 5% difference in the composition percentage of the three subpopulations of granulocytes, monocytes, and lymphocytes compared to the original sample. Furthermore, our cell sorter is designed to enable broad application of size‐based inertial cell sorting by supplying a series of microchips with different sorting cutoff size. This strategy allows us to further enrich the lymphocytes population by twofold using another microchip with a cutoff size between 10 and 15 μm. With simplicity and efficiency, our cell sorter provides a powerful platform for isolating and sorting of WBCs and also envisions broad potential sorting applications for other cell types.
Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients.

Background Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to investigate the molecular mechanisms mediating acquired resistance to cisplatin and fluorouracil (CF) combination-based chemotherapy in GC patients. Methods The microarray datasets (GSE14209, GSE30070) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma package in R/Bioconductor. Possible targets of the DEMs were predicted using miRWalk, and the putative miRNA-mRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were then conducted and visualized using the Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape. The prognostic value of hub genes was revealed by Kaplan-Meier Plotter. The causal relationships and interactions between proteins were displayed using DisNor. Finally, similarity analysis was conducted using the Connectivity Map (CMap) profiles to predict a group of small molecules in GC treatment. Results A total of 394 DEGs and 31 DEMs were identified after analysis of pre- and post-treatment samples of clinical responders to CF therapy. TM9SF4, hsa-miR-185-5p, and hsa-miR-145-5p were found to be critical in the miRNA-mRNA regulatory network. The DEGs were found to be mainly enriched in the processes of ribonucleoprotein complex assembly, catalytic activity acting on RNA, mitochondrial matrix, and thermogenesis. The DEMs were predominantly found to be involved in single-stranded RNA binding and endoplasmic reticulum lumen. HDAC5, DDX17, ILF3, and SDHC were identified as hub genes in the PPI network. Of these, HDAC5, DDX17, and ILF3 were found to be closely related to the overall survival of GC patients. DisNor identified the first neighbors of the key genes. Furthermore, CMap profiles predicted a group of small molecules, including several histone deacetylase inhibitors (HDACIs), menadione, and mibefradil, which could serve as promising therapeutic agents to reverse acquired resistance to CF therapy. Conclusions Our findings reveal new targets and alternative therapies to overcome the acquired resistance of GC patients to CF treatment.
Health system interventions to integrate genetic testing in routine oncology services: A systematic review

Background Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology. Methods The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Eligible studies included routine genetic testing for breast and ovarian cancer or uptake after universal tumour screening for colorectal or endometrial cancer. The titles and abstracts were reviewed and the full text articles screened for eligibility. Data extraction was preformed using a designed template and study appraisal was assessed using an adapted Newcastle Ottawa Scale. Extracted data were mapped to Proctor’s et al outcomes and the Consolidated Framework for Implementation Research and qualitatively synthesised. Results Twenty-seven studies, published up to May 2020, met the inclusion criteria. Twenty-five studies ranged from poor (72%), fair to good (28%) quality. Most interventions identified were complex (multiple components) such as; patient or health professional education, interdisciplinary practice and a documentation or system change. Forty-eight percent of studies with complex interventions demonstrated on average a 35% increase in access to genetic counselling and a 15% increase in testing completion. Mapping of study outcomes showed that 70% and 32% of the studies aligned with either the service and client or the implementation level outcome and 96% to the process or inner setting domains of the Consolidated Framework for Implementation Research. Conclusion Existing evidence suggests that complex interventions have a potentially positive effect towards genetic counselling and testing completion rates in oncology services. Studies of sound methodological quality that explore a greater breadth of pre and post implementation outcomes and informed by theory are needed. Such research could inform future service delivery models for the integration of genetics into oncology services.
MITOGEN-ACTIVATED PROTEIN KINASE 4 impacts leaf development, temperature, and stomatal movement in hybrid aspen

Abstract Stomatal movement and density influence plant water use efficiency and thus biomass production. Studies in model plants within controlled environments suggest MITOGEN-ACTIVATED PROTEIN KINASE 4 (MPK4) may be crucial for stomatal regulation. We present functional analysis of MPK4 for hybrid aspen (Populus tremula × tremuloides) grown under natural field conditions for several seasons. We provide evidence of the role of MPK4 in the genetic and environmental regulation of stomatal formation, differentiation, signaling, and function; control of the photosynthetic and thermal status of leaves; and growth and acclimation responses. The long-term acclimation manifested as variations in stomatal density and distribution. Short-term acclimation responses were derived from changes in the stomatal aperture. MPK4 localized in the cytoplasm of guard cells (GCs) was a positive regulator of abscisic acid (ABA)-dependent stomatal closure and nitric oxide metabolism in the ABA-dependent pathways, while to a lesser extent, it was involved in ABA-induced hydrogen peroxide accumulation. MPK4 also affected the stomatal aperture through deregulation of microtubule patterns and cell wall structure and composition, including via pectin methyl-esterification, and extensin levels in the GC wall. Deregulation of leaf anatomy (cell compaction) and stomatal movement, together with increased light energy absorption, resulted in altered leaf temperature, photosynthesis, cell death, and biomass accumulation in mpk4 transgenic plants. Divergence between absorbed energy and assimilated energy is a bottleneck, and MPK4 can participate in the control of energy dissipation (thermal effects). Furthermore, MPK4 can participate in balancing the photosynthetic energy distribution via its effective use in growth or redirection to acclimation/defense responses.
Hijacking of the host cell Golgi by Plasmodium berghei liver stage parasites

ABSTRACT The intracellular lifestyle represents a challenge for the rapidly proliferating liver stage Plasmodium parasite. In order to scavenge host resources, Plasmodium has evolved the ability to target and manipulate host cell organelles. Using dynamic fluorescence-based imaging, we here show an interplay between the pre-erythrocytic stages of Plasmodium berghei and the host cell Golgi during liver stage development. Liver stage schizonts fragment the host cell Golgi into miniaturized stacks, which increases surface interactions with the parasitophorous vacuolar membrane of the parasite. Expression of specific dominant-negative Arf1 and Rab GTPases, which interfere with the host cell Golgi-linked vesicular machinery, results in developmental delay and diminished survival of liver stage parasites. Moreover, functional Rab11a is critical for the ability of the parasites to induce Golgi fragmentation. Altogether, we demonstrate that the structural integrity of the host cell Golgi and Golgi-associated vesicular traffic is important for optimal pre-erythrocytic development of P. berghei. The parasite hijacks the Golgi structure of the hepatocyte to optimize its own intracellular development. This article has an associated First Person interview with the first author of the paper.
A further look at quantitative trait loci for growth and fatness traits in a White Duroc × Erhualian F3 intercross population

Abstract Genetic analysis of porcine growth and fatness traits is beneficial to the swine industry and provides a reference to understand human obesity. Here, we obtained 29 growth and fatness traits for 473 individuals from a White Duroc × Erhualian F3 intercross population. Basic statistical analyses showed that: (1) Positive correlations between different-stage body weights were detected, the shorter the time interval the stronger the correlation. (2) Strong correlations existed in the paired fatness traits. (3) With the growth of age, the correlation between fatness and body weight was increasing. All pigs were genotyped by Illumina 50 K SNP chips and their whole-genome genotypes were imputed referred to 109 re-sequencing data. We performed common and imputation-based GWASs for these traits. Two genome-wide significant loci on swine chromosome (SSC) 4 and 7 were repeatedly detected. The strongest association (P = 3.24 × 10−19) was detected at 31.96 Mb on SSC7 for leaf fat weight. On this locus, seven major haplotypes were identified, of which two were novel and had an increasing-fatness effect. In the imputation-based GWAS, three new loci were identified. Our findings provide further insights into and enhance our understanding of genetic mechanism of porcine growth and fat deposition.
A Chromosome-Level Genome Assembly of Ephestia elutella (Hübner, 1796) (Lepidoptera: Pyralidae)

Abstract The moth Ephestia elutella (Hübner), is a storage pest that feeds on tobacco, cacao beans, cereals, dried fruits, and nuts. We generated a chromosome-level genome assembly containing 576.94 Mb using Nanopore long reads (approximately 130×) and Hi-C data (approximately 134×). The final assembly contained 804 scaffolds, with an N50 length of 19.00 Mb, and 94.96% (547.89 Mb) of the assembly was anchored into 31 pseudochromosomes. We masked 58.12% (335.32 Mb) of the genome as repetitive elements, identified 727 noncoding RNAs, and predicted 15,637 protein-coding genes. Gene family evolution and functional enrichment analyses revealed significantly expanded gene families primarily involved in digestion, detoxification, and chemosensation. Strong chromosomal syntenic relationships were also observed among E. elutella, silkworm, and tobacco cutworm. This study could provide a valuable genomic basis for better understanding the biology of E. elutella.
Sleep Insufficiency and Baseline Preseason Concussion-Like Symptom Reporting in Youth Athletes

Supplemental Digital Content is Available in the Text. Objective: To examine the association between insufficient sleep and baseline symptom reporting in healthy student athletes. Design: Cross-sectional cohort study. Setting: Preseason testing for student athletes. Participants: Student athletes (n = 19 529) aged 13 to 19 years who completed the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), including the number of hours slept the night before, and denied having developmental/health conditions, a concussion in the past 6 months, and a previous history of 2 or more concussions. Independent Variables: Total hours of sleep the night before testing (grouped by ≤5, 5.5-6.5, 7-8.5, and ≥9 hours), gender, and concussion history. Main Outcome Measures: Symptom burden on the Post-Concussion Symptom Scale (modified to exclude sleep-related items), cognitive composite scores, and prevalence of athletes who reported a symptom burden resembling the International Classification of Diseases, 10th Revision (ICD-10) diagnosis of postconcussional syndrome (PCS). Results: Fewer hours of sleep, gender (ie, girls), and 1 previous concussion (vs 0) were each significantly associated with higher total symptom scores in a multivariable model (F = 142.01, P < 0.001, R2 = 0.04). When a gender-by-sleep interaction term was included, the relationship between sleep and symptoms was stronger for girls compared with boys. In healthy athletes who slept ≤5 hours, 46% of girls and 31% of boys met the criteria for ICD-10 PCS compared with 16% of girls and 11% of boys who slept ≥9 hours. Sleep duration was not meaningfully associated with neurocognitive performance. Conclusions: Insufficient sleep the night before testing is an important factor to consider when interpreting symptom reporting, especially for girls. It will be helpful for clinicians to take this into account when interpreting both baseline and postinjury symptom reporting.
Effect of bronchoalveolar lavage on the clinical efficacy, inflammatory factors, and immune function in the treatment of refractory pneumonia in children

Background Refractory pneumonia is a special type of pneumonia in children. This study aimed to analyze the effect of bronchoalveolar lavage (BAL) on the clinical efficacy, inflammatory factors, and immune function in the treatment of pediatric refractory pneumonia. Methods A total of 196 children with refractory pneumonia admitted to our hospital from January 2017 to January 2020 were enrolled and allocated to a study group (n=99) and a control group (n=97). The study group was treated with BAL treatment plus conventional treatment, and the control group was treated with conventional treatment. The clinical efficacy, time of fever regression, time of cough relief, and length of hospital stay were compared between groups. Changes in inflammatory factors, immune function, pulmonary ventilation function, and complications were analyzed. The levels of inflammatory factors in BAL fluid were compared. Results The times of fever remission, cough relief, and hospital stay of the study group was shorter than those of the control group, and the total clinical effective rate of the study group was higher. At any time after treatment, the levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) in the study group were lower than the control group. After 3-day of treatment, IL-6, CRP and TNF-α in BAL fluid in the study group were significantly decreased compared with before treatment. Immunoglobulin A (IgA) and immunoglobulin G (IgG) levels in the study group were higher than those in the control group at any time after treatment, and immunoglobulin M (IgM) levels were lower than in the control group. The levels of oxygenation index (OI), lung dynamic compliance (Cdyn), and work of breathing (WOB) in the study group were higher than those in the control group at any time after treatment. Conclusions BAL treatment can effectively relieve the inflammatory response, improve immune function and lung ventilation function in children with refractory pneumonia. The clinical effect is remarkable and worthy of promotion.
Presentation of EGFR mutations in 162 family probands with multiple primary lung cancer

Background The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. However, information regarding the etiology of MPLC and responsiveness to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is rare. The present study aims to describe the mutation signatures of EGFR in MPLC. Methods Polymerase chain reaction (PCR) and Sanger sequencing were used to screen EGFR mutations in 162 family probands comprising 366 tumor lesions and 162 paired noncancerous adjacent tissues (NATs). Sequencing data from 3,243 sporadic lung adenocarcinoma (LUAD) samples were analyzed as a control. Results Candidate germline mutations were observed in exons 19 (3, 1.85%), 20 (8, 4.94%) and 21 (5, 3.10%), with a total frequency of 9.88% in NATs (16/162). There were 63 probands harboring somatic mutations (63/162, 38.89%), 9 patients harbored the consistency mutations among lesions, and 8 patients carried 2 or more mutations. The overall rate of EGFR somatic mutations was lower in the MPLC probands, but those of exon 19 p.747-752del, 20 p.V769indelsVASV and 20 p.D770indelsDSVD were significantly higher in MPLC probands than in patients with sporadic LUAD. Conclusions There exists unique EGFR mutation signatures in a large cohort of MPLC probands, which might provide objective evidence of the etiology and effectiveness of clinical TKI treatment of high-risk MPLC patients.
A computer-controlled, high-speed, repetitive gas chromatography system

The system was designed for the automated analysis of vapor samples at parts-permillion and parts-per-billion concentrations. Retention times typically were a few seconds, and complete analysis cycle times were in the 10-20 s range. A gas-cooled and electrically heated metal capillary tube that was used as a cryofocusing inlet system produced injection bandwidths in the 5-10 ms range. A vacuum pump-operated backflushing technique rapidly removed high boiling point compounds and conditioned the column for subsequent injections
Social Prescribing Nomenclature, Occupational Therapy and the Theory of Institutional Work: Creating, Maintaining and Disrupting Medical Dominance

Abstract Social prescribing is a process of helping people to access non-medical activities and services which address health and wellbeing needs. The process is frequently (although not exclusively) initiated by primary health care professionals and often involves prescribing activities or initiatives provided by community and voluntary organizations. To occupational therapy, the links between activity, social-connectedness and health are clearly not new, although there are emerging international examples of social prescribing initiatives, and examples of newly developed roles, processes and funding opportunities, all of which are creating momentum behind the agenda. In this commentary, we draw upon the theory of Institutional Work to examine how the language of “prescription,” and the purposive action of policy-makers and practitioners, is shaping thinking and action in relation to activity and health. Arguably, this language has helped to translate the recommendation of activity to meet a range of health needs in to an accessible and implementable concept. However, it has also potentially contributed to positioning the concept within a medical model of health, upholding medical dominance, and leaving occupational therapy on the margins of the debate.