Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Resectable N2 in NSCLC: A Single Center Experience and Review of the SEER Database

Background Non-small cell lung carcinoma (NSCLC) with ipsilateral and/or subcarinal mediastinal lymphatic spread (N2) is a heterogeneous disease. The role of surgical resection in patients with N2 NSCLC remains controversial and no survival-based definition of “resectable N2” exists. The purpose of this study is to evaluate the factors that potentially affect the survival of N2 NSCLC patients who receive surgical resection and to define “resectable N2” based on the survival benefits. Methods Data from the open Surveillance, Epidemiology, and End Results (SEER) database from the National Cancer Institute in the United States were used to construct a nomogram. Patients who received surgery between 2010 and 2015 for N2 NSCLC were included. Independent prognostic factors for survival identified through Cox regression analysis were used to create the nomogram. The C-index, receiver operating characteristics (ROC) analyses, calibration curves, and risk stratification were used to evaluate the nomogram. The nomogram was also validated using data from 222 patients from Peking Union Medical College Hospital (PUMCH). Furthermore, lung cancer–related deaths were compared using competitive risk analysis. Results In total, 4267 patients were included in the SEER cohort. Male gender, old age, high T stage and grade, adenosquamous and squamous cell carcinoma, lower lobe and overlapping lesions, extended lobe or bilobectomy and pneumonectomy, no chemotherapy, radiation before and after surgery, positive number of lymph nodes, and lymph node ratio (LNR) were identified as independent risk factors for higher mortality. The nomogram was created using these parameters. The C-index was 0.665 (95% confidence interval (CI), 0.651-0.679) and 0.722 (95% CI, 0.620-0.824) in the SEER and PUMCH cohorts, respectively. The calibration curves showed satisfactory consistency between the predicted and actual survival status in both the SEER and PUMCH cohorts. Competitive risk analysis confirmed that the variables in the nomogram, except radiation, are risk factors for prognosis. Conclusions “Resectable N2” should be assessed by a multidisciplinary team. The novel nomogram developed in this study may help with clinical decision-making for this patient population.
An Experimental Test of Defenses Against Avian Brood Parasitism in a Recent Host

Theoretical studies predict that hosts of avian brood parasites should evolve defenses against parasitism in a matter of decades. However, opportunities to test these predictions are limited because brood parasites rarely switch to naïve hosts. Here, we capitalize on a recent host switch by the brood-parasitic Pacific Koel (Eudynamys orientalis) in eastern Australia, to investigate how quickly the Red Wattlebird (Anthochaera carunculata), a recent host that has been annexed by the koel within the last 90 years, can learn to recognize and mob adult cuckoos and evolve the ability to eject parasite eggs. Pacific Koel nestlings kill all host young, so there should be strong selection for hosts to evolve defenses. However, low parasitism rates and high egg recognition costs might slow the spread of egg ejection in our study populations, while adult parasite recognition should be able to spread more rapidly, as this defense has been shown to be a learned trait rather than a genetically inherited defense. We tested Red Wattlebirds at two sites where parasitism rate differed. As predicted, we found that the Red Wattlebird showed little or no ability to eject foreign model eggs at either site, whereas two historical hosts showed high levels of egg ejection at both sites. However, Red Wattlebirds responded significantly more aggressively to a koel mount than to mounts of a harmless control and nest predator at the site with the higher parasitism rate and gave significantly more alarm calls overall toward the koel mount. Our results support previous evidence that recognition and mobbing of a brood parasite are learned traits and may be especially beneficial to naïve hosts that have not had enough time or a high enough selection pressure to evolve egg rejection.
Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4th and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52–28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2–56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.
Pupillary Response to Postural Demand in Parkinson’s Disease

Background: Individuals with Parkinson’s disease (PD) may need to spend more mental and physical effort (i.e., cognitive workload) to maintain postural control. Pupillary response reflects cognitive workload during postural control tasks in healthy controls but has not been investigated as a measure of postural demand in PD. Objectives: To compare pupillary response during increased postural demand using vision occlusion and dual tasking between individuals with PD and healthy controls. Methods: Thirty-three individuals with PD and thirty-five healthy controls were recruited. The four conditions lasted 60 s and involved single balance task with eyes open; single balance task with eyes occluded; dual task with eyes open; dual task with eyes occluded. The dual task comprised the Auditory Stroop test. Pupillary response was recorded using an eye tracker. The balance was assessed by using a force plate. Two-way Repeated Measures ANOVA and LSD post-hoc tests were employed to compare pupillary response and Center of Pressure (CoP) displacement across the four conditions and between individuals with PD and healthy controls. Results: Pupillary response was higher in individuals with PD compared to healthy controls (p = 0.009) and increased with more challenging postural conditions in both groups (p < 0.001). The post-hoc analysis demonstrated increased pupillary response in the single balance eyes occluded (p < 0.001), dual task eyes open (p = 0.01), and dual task eyes occluded (p < 0.001) conditions compared to single task eyes open condition. Conclusion: Overall, the PD group had increased pupillary response with increased postural demand compared to the healthy controls. In the future, pupillary response can be a potential tool to understand the neurophysiological underpinnings of falls risk in the PD population.
Detection and Aggregation of Listeria Monocytogenes Using Polyclonal Antibody Gold-Coated Magnetic Nanoshells Surface-Enhanced Raman Spectroscopy Substrates

Magnetic nanoshells with tailored surface chemistry can enhance bacterial detection and separation technologies. This work demonstrated a simple technique to detect, capture, and aggregate bacteria with the aid of end-functionalized polyclonal antibody gold-coated magnetic nanoshells (pAb-Lis-AuMNs) as surface-enhanced Raman spectroscopy (SERS) probes. Listeria monocytogenes were used as the pathogenic bacteria and the pAb-Lis-AuMNs, 300 nm diameter, were used as probes allowing facile magnetic separation and aggregation. An optimized covalent bioconjugation procedure between the magnetic nanoshells and the polyclonal antibody was performed at pH six via a carbodiimide crosslinking reaction. Spectroscopic and morphological characterization techniques confirmed the fabrication of stable pAb-Lis-AuMNs. The resulting pAb-Lis-AuMNs acted as a SERS probe for L. monocytogenes based on the targeted capture via surface binding interactions and magnetically induced aggregation. Label-free SERS measurements were recorded for the minimum detectable amount of L. monocytogenes based on the SERS intensity at the 1388 cm−1 Raman shift. L. monocytogenes concentrations exhibited detection limits in the range of 104–107 CFU ml−1, before and after aggregation. By fitting these concentrations, the limit of detection of this method was ∼103 CFU ml−1. Using a low-intensity magnetic field of 35 G, pAb-Lis-AuMNs aggregated L. monocytogenes as demonstrated with microscopy techniques, including SEM and optical microscopy. Overall, this work presents a label-free SERS probe method comprised of a surface-modified polyclonal antibody sub-micron magnetic nanoshell structures with high sensitivity and magnetic induced separation that could lead to the fabrication of multiple single-step sensors.
Prognostic Factors and Models for Changes in Cognitive Performance After Multi-Domain Cognitive Training in Healthy Older Adults: A Systematic Review

Background: Cognitive Training (CT) may contribute to the maintenance and even enhancement of cognitive functions in healthy older adults. However, the question who benefits most from multi-domain CTs is still highly under-investigated. Objective: The goal is to investigate prognostic factors and models for changes in cognitive test performance in healthy older adults after a multi-domain CT. Methods: The data bases MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched up to July 2019. Studies investigating prognostic factors and/or models on cognitive outcomes (global cognition, memory, attention, executive functions, language, visuo-spatial abilities) after conducting a multi-domain CT in healthy older adults were included. Risk of Bias was assessed using the QUIPS and the PROBAST tool. Results: 23 prognostic factor and model studies were included. Results indicate a high heterogeneity regarding the conducted multi-domain CTs, the investigated prognostic factors, the investigated outcomes, and the used statistical approaches. Age and neuropsychological performance at study entry were the most investigated predictors, yet they show inconsistent results. Conclusion: Data on prognostic factors and models of changes after multi-domain CT are still too rare and inconsistent to draw clear conclusions due to statistical shortcomings and low reporting quality. Approaches for future research are outlined. Registration: https://www.crd. york.ac. uk/prospero/, ID: CRD42020147531
NK Cells and PMN-MDSCs in the Graft From G-CSF Mobilized Haploidentical Donors Display Distinct Gene Expression Profiles From Those of the Non-Mobilized Counterpart

A recent approach of hematopoietic stem cell (HSC) transplantation from haploidentical donors “mobilized” with G-CSF is based on the selective depletion of αβ T and B lymphocytes from the graft. Through this approach, the patient receives both HSC and mature donor-derived effector cells (including NK cells), which exert both anti-leukemia activity and protection against infections. We previously showed that donor HSC mobilization with G-CSF results in accumulation in the graft of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), capable of inhibiting in vitro the anti-leukemia activity of allogeneic NK cells. Here, we performed a detailed gene expression analysis on NK cells and PMN-MDSCs both derived from mobilized graft. Cytotoxicity assays and real time PCR arrays were performed in NK cells. Microarray technology followed by bioinformatics analysis was used for gene expression profiling in PMN-MDSCs. Results indicate that NK cells from the graft have a lower cytolytic activity as compared to those from non-mobilized samples. Further, mobilized PMN-MDSCs displayed a peculiar transcriptional profile distinguishing them from non-mobilized ones. Differential expression of pro-proliferative and immune-modulatory genes was detected in mobilized PMN-MDSCs. These data strengthen the concept that G-CSF-mobilized PMN-MDSCs present in the graft display unique molecular characteristics, in line with the strong inhibitory effect on donor NK cells.
Identification and Validation of SNP-Containing Genes With Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis

Background Gastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer. Methods SNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells. Results From the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients. Conclusion Our results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.
The Molecular Information About Deadwood Bacteriomes Partly Depends on the Targeted Environmental DNA

Microbiome studies mostly rely on total DNA extracts obtained directly from environmental samples. The total DNA consists of both intra- and extracellular DNA, which differ in terms of their ecological interpretation. In the present study, we have investigated for the first time the differences among the three DNA types using microbiome sequencing of Picea abies deadwood logs (Hunter decay classes I, III, and V). While the bacterial compositions of all DNA types were comparable in terms of more abundant organisms and mainly depended on the decay class, we found substantial differences between DNA types with regard to less abundant amplicon sequence variants (ASVs). The analysis of the sequentially extracted intra- and extracellular DNA fraction, respectively, increased the ecological depth of analysis compared to the directly extracted total DNA pool. Both DNA fractions were comparable in proportions and the extracellular DNA appeared to persist in the P. abies deadwood logs, thereby causing its masking effect. Indeed, the extracellular DNA masked the compositional dynamics of intact cells in the total DNA pool. Our results provide evidence that the choice of DNA type for analysis might benefit a study’s answer to its respective ecological question. In the deadwood environment researched here, the differential analysis of the DNA types underlined the relevance of Burkholderiales, Rhizobiales and other taxa for P. abies deadwood decomposition and revealed that the role of Acidobacteriota under this scenario might be underestimated, especially compared to Actinobacteriota.
Laparoscopic vs. Transabdominal Treatment for Overflow Fecal Incontinence Due to Residual Aganglionosis or Transition Zone Pathology in Hirschsprung's Disease Reoperation

Objective: The aim of this study was to describe the details of laparoscopic-assisted reoperative surgery for Hirschsprung's disease (HSCR) with overflow fecal incontinence, and to retrospectively compare laparoscopic-assisted surgery with transabdominal pull-through surgery. Methods: We retrospectively analyzed patients with HSCR with overflow fecal incontinence after the initial surgery in our center between January 2002 and December 2018. Pre-operative, peri-operative, and post-operative data were recorded for statistical analysis. Results: Thirty patients with overflow fecal incontinence after initial megacolon surgery [17 who underwent transanal pull-through (TA-PT) and 13 who underwent laparoscopic-assisted pull-through (LA-PT)] required a secondary surgery [reoperation with LA-PT (LAR-PT) (n = 16) or reoperation with transabdominal pull-through (TR-PT) (n = 14)]. Indications for reoperation were residual aganglionosis (RA) (7/30, 23.3%) or transition zone pathology (TZP) (23/17, 76.7%). Blood loss was significantly decreased in the LAR-PT group (75 ± 29.2 ml) compared to the TR-PT group (190 ± 51.4 ml) (P = 0.001). The length of hospital stay was significantly shorter in the LAR-PT group (10 ± 1.5 days) than that in the TR-PT group (13 ± 2.4 days). No significant differences were found between two groups in surgical methods, defecation function score, or post-operative complications except for wound infection (LAR-PT vs. TR-PT 0 vs. 28.6%, P < 0.05). Conclusions: It is necessary to make a comprehensive analysis of the causes of fecal incontinence after HSCR surgery and make an accurate judgment using appropriate methods. If a reoperation was inevitable for patients with overflow fecal incontinence due to RA or TZP, a comprehensive evaluation prior to the operation is required to maximize the benefit from reoperation. Although laparoscopic reoperation with heart-shaped anastomosis was safe and feasible for patients with failed initial Soave technique, unnecessary reoperation should be avoided as much as possible.
Glutamate and GABA Homeostasis and Neurometabolism in Major Depressive Disorder

Major depressive disorder (MDD) is a leading cause of distress, disability, and suicides. As per the latest WHO report, MDD affects more than 260 million people worldwide. Despite decades of research, the underlying etiology of depression is not fully understood. Glutamate and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters, respectively, in the matured central nervous system. Imbalance in the levels of these neurotransmitters has been implicated in different neurological and psychiatric disorders including MDD. 1H nuclear magnetic resonance (NMR) spectroscopy is a powerful non-invasive method to study neurometabolites homeostasis in vivo. Additionally, 13C-NMR spectroscopy together with an intravenous administration of non-radioactive 13C-labeled glucose or acetate provides a measure of neural functions. In this review, we provide an overview of NMR-based measurements of glutamate and GABA homeostasis, neurometabolic activity, and neurotransmitter cycling in MDD. Finally, we highlight the impact of recent advancements in treatment strategies against a depressive disorder that target glutamate and GABA pathways in the brain.
ARTEMIS: A Novel Mass-Spec Platform for HLA-Restricted Self and Disease-Associated Peptide Discovery

Conventional immunoprecipitation/mass spectroscopy identification of HLA-restricted peptides remains the purview of specializing laboratories, due to the complexity of the methodology, and requires computational post-analysis to assign peptides to individual alleles when using pan-HLA antibodies. We have addressed these limitations with ARTEMIS: a simple, robust, and flexible platform for peptide discovery across ligandomes, optionally including specific proteins-of-interest, that combines novel, secreted HLA-I discovery reagents spanning multiple alleles, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon conventional methods. This platform fills a middle ground between existing techniques: sensitive and adaptable, but easy and affordable enough to be widely employed by general laboratories. We used ARTEMIS to catalog allele-specific ligandomes from HEK293 cells for seven classical HLA alleles and compared results across replicates, against computational predictions, and against high-quality conventional datasets. We also applied ARTEMIS to identify potentially useful, novel HLA-restricted peptide targets from oncovirus oncoproteins and tumor-associated antigens.