Miracle-dz/UniFAR-FTUs huggingface dataset:
Major Aspects of Burkholderia gladioli and Burkholderia cepacia Infections in Children

Background: Burkholderia cepacia complex is an aerobic, non–spore-forming, catalase-positive, nonfermentative, Gram-negative bacterium common in environment. It is a serious pathogen especially for patients with cystic fibrosis (CF). But pathogenicity of Burkholderia is not limited to patients with CF. Herein, we aimed to reveal clinical patterns and outcomes of Burkholderia infections in pediatric patients in our hospital and also antimicrobial susceptibility of the isolated strain. Methods: This retrospective study was conducted in Ankara Hematology Oncology Children’s Training and Research Hospital. Patients with isolates of Burkholderia spp. between January 6, 2013, and January 12, 2018, were included in the study. Results: Burkholderia spp. was isolated from 55 patients. 94.6% of these patients had underlying diseases and had prior hospitalization within a year. Burkholderia gladioli grew in 15 patients’ samples (27.3%); 38 patients grew B. cepacia (69.1%). None of the patients that B. gladioli was isolated was diagnosed as CF;. all had nosocomial infections. B. gladioli seemed to be more susceptible to aminoglycosides, piperacillin-tazobactam, carbapenems and ciprofloxacin than B. cepacia (P = 0.00), whereas B. cepacia seemed to be more susceptible to ceftazidime than B. gladioli (P = 0.032). In addition, B. cepacia was more susceptible to trimethoprim-sulfamethoxazole and levofloxacin than B. gladioli, but this difference was not statistically significant (P = 0.76). Conclusions: The incidence of nosocomial infections caused by Burkholderia spp. is rare especially in pediatric literature. In our study, nosocomial Burkholderia infections occurred mostly in intensive care unit patients. The surveillance of Burkholderia infections is still very important, and the clinicians should be aware of changing epidemiology and increasing resistance of the microorganism. Besides, there are no internationally agreed minimal inhibitory concentration breakpoints and disk-diffusion test thresholds for susceptibility testing for Burkholderia. Thus, the methods which were used for antibiotic susceptibility testing in our center might cause uncertainty about the results and internationally agreed minimal inhibitory concentration breakpoints and disk-diffusion test thresholds for susceptibility testing for Burkholderia is still a gap to fill for the current literature.
Comprehensive evaluation of SPATS2 expression and its prognostic potential in liver cancer

Abstract Spermatogenesis associated serine rich 2 (SPATS2) has been reported to be dysregulated in few types of cancer; however, no reports have investigated SPATS2 in liver cancer. The aim of the present study was to investigate SPATS2 expression in liver cancer and to analyze its association with the prognosis of liver cancer patients. We examined the differential expression of SPATS2 in liver cancer by exploring The Cancer Genome Atlas (TCGA) database. The diagnostic efficiency of SPATS2 was obtained by Receiver Operating Characteristic (ROC) curve. The Chi-Squared test was used to assess clinical relevance. Survival analysis and Cox regression model were used to detect the effect of SPATS2 on the survival of liver cancer patients. Gene Set Enrichment Analysis (GSEA) was used to identify signaling pathways related to SPATS2 expression. SPATS2 is highly expressed in liver cancer (P < 2.2e-16) and has the high diagnostic ability (AUC = 0.964). Survival analysis showed that patients with high SPATS2 expression have an apparently shorter overall survival (OS, P < .0001) and relapse-free survival (RFS, P < .0001). Cox regression analysis showed that high SPATS2 expression might be an independent risk factor for liver cancer (OS, HR = 2.41, P = .000; RFS, HR = 1.90, P < .001). GSEA analysis identified 3 signaling pathways (Mitotic spindle, G2 M checkpoint, E2F targets) that were enriched in the presence of high SPATS2 expression. SPATS2 expression could be a novel diagnostic and prognostic biomarker in liver cancer.
Study on structural atrophy changes and functional connectivity measures in Alzheimer’s disease

Abstract. Alzheimer’s disease (AD) is characterized by the progressive accumulation of neurofibrillary tangles associated with amyloid plaques. We used 80 resting-state functional magnetic resonance imaging and 80 T1 images acquired using MP-RAGE (magnetization-prepared rapid acquisition gradient echo) from Alzheimer’s Disease Neuroimaging Initiative data to detect atrophy changes and functional connectivity patterns of the default mode networks (DMNs). The study subjects were classified into four groups (each with n = 20) based on their Mini-Mental State Examination (MMSE) score as follows: cognitively normal (CN), early mild cognitive impairment, late mild cognitive impairment, and AD. The resting-state functional connectivity of the DMN was examined between the groups using the CONN functional connectivity toolbox. Loss of gray matter in AD was observed. Atrophy measured by the volume of selected subcortical regions, using the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library’s Integrated Registration and Segmentation Tool (FIRST), revealed significant volume loss in AD when compared to CN (p < 0.05). DMNs were selected to assess functional connectivity. The negative connectivity of DMN increased in AD group compared to controls. Graph theory parameters, such as global and local efficiency, betweenness centrality, average path length, and cluster coefficient, were computed. Relatively higher correlation between MMSE and functional metrics (r = 0.364, p = 0.001) was observed as compared to atrophy measures (r = 0.303, p = 0.006). In addition, the receiver operating characteristic analysis showed large area under the curve (AZ) for functional parameters (AZ > 0.9), compared to morphometric changes (AZ < 0.8). In summary, it is observed that the functional connectivity measures may serve a better predictor in comparison to structural atrophy changes. We postulate that functional connectivity measures have the potential to evolve as a marker for the early detection of AD.
Taxane-based or platinum-based combination chemotherapy given concurrently with radiation followed by surgery resulting in high cure rates in esophageal cancer patients

Abstract Background: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. Methods: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. Results: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3–122.0); 81.6 months (95% CI, 55.9–not estimable) for the DF group and 67.7 months (95% CI, 41.6–not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1–61.7) for the entire cohort; 49.5 months (95% CI, 38.6–70.3) for DF and 33.0 months (95% CI, 18.1–70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. Conclusion: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.
The diversity and distribution of endophytes across biomes, plant phylogeny, and host tissues-how far have we come and where do we go from here?

The interiors of plants are colonized by diverse microorganisms that are referred to as endo-phytes. Endophytes have received much attention over the past few decades, yet many basic questions remain unanswered regarding patterns in their biodiversity at local to global scales. To characterize research effort to date, we synthesized results from ~600 published studies. Our survey revealed a global research interest and highlighted several gaps in knowledge. For instance, of the seventeen biomes encompassed by our survey, seven were understudied and together composed only 7% of the studies that we considered. We found that fungal endophyte diversity has been characterized in at least one host from 30% of embryophyte families, while bacterial endophytes have been surveyed in hosts from only 10.5% of families. We complimented our survey with a vote counting procedure to determine endophyte rich-ness patterns among plant tissue types. We found that variation in endophyte assemblages in above-ground tissues varied with host growth habit. Stems were the richest tissue in woody plants, whereas roots were the richest tissue in graminoids. For forbs, we found no consistent differences in relative tissue richness among studies. We propose future directions and guidelines to fill the gaps in knowledge we uncovered and inspire further research. This article is protected by copyright. All rights reserved.
Biomarkers of fitness and welfare in dairy cattle: healthy productivity

Abstract Milk production intensification has led to several unwanted aspects, such as sustainability issues and environmental pollution. Among these, increased milk outputs that have been achieved over the last 70 years have led to several health and pathophysiological conditions in high yielding dairy animals, including metabolic diseases that were uncommon in the past. Increased occurrence of diverse metabolic diseases in cattle and other domestic animals is a key feature of domestication that not only affects the animals' health and productivity, but also may have important and adverse health impacts on human consumers through the elevated use of drugs and antibiotics. These aspects will influence economical and ethical aspects in the near future. Therefore, finding and establishing proper biomarkers for early detection of metabolic diseases is of great interest. In the present review, recent work on the discovery of fitness, stress and welfare biomarkers in dairy cows is presented, focusing in particular on possible biomarkers of energy balance and oxidative stress in plasma and milk, and biomarkers of production-related diseases and decreased fertility.
CloudASM: an ultra-efficient cloud-based pipeline for mapping allele-specific DNA methylation

Summary Methods for quantifying the imbalance in CpG methylation between alleles genome-wide have been described but their algorithmic time complexity is quadratic and their practical use requires painstaking attention to infrastructure choice, implementation, and execution. To solve this problem, we developed CloudASM, a scalable, ultra-efficient, turn-key, portable pipeline on Google Cloud Computing (GCP) that uses a novel pipeline manager and GCP’s serverless enterprise data warehouse. Availability and Implementation CloudASM is freely available in the GitHub repository https://github.com/TyckoLab/CloudASM and a sample dataset and its results are also freely available at https://console.cloud. google.com/storage/browser/cloudasm. Contact emmanuel.dumont@hmh-cdi.org Supplementary information None.
Life lacks meaning without acceptance: Ostracism triggers suicidal thoughts.

Eleven studies (N = 2,254; 2 preregistered) examined whether ostracism would trigger suicidal thoughts and whether perceived meaning in life would account for this effect. The feeling of ostracism was induced via recalling a past experience (Studies 1a, 1c, 2c, and 3b), imagining a future experience (Studies 1d, 1e, and 2b), engaging in an online real-time interaction (Studies 1b and 2d), or receiving bogus personality feedback (Study 3a). Across all 11 studies, ostracism increased suicidal thoughts. Study 1a found that ostracism increased implicit associations of "death" and "me" relative to "life" and "me" on the Implicit Association Test of Suicide (Nock et al., 2010). In Study 1b, ostracized participants showed more suicidal thoughts in imagined stressful situations than did included participants. Studies 1c, 1d, and 1e further showed that ostracism increased explicit suicidal thoughts compared with both inclusion and neutral experiences. Furthermore, we found that perceived meaning in life accounted for ostracism's effect on suicidal thoughts (Studies 2a and 2b), even after controlling for depressive affect (Study 2c). In Study 2d, a preregistered study, we directly compared the contributions of perceived meaning in life and the 4 basic needs and mood proposed in William's (2007, 2009) ostracism framework, and we found that perceived meaning in life had a distinct mediating role in the ostracism-suicidal thinking link. Finally, Studies 3a and 3b found that self-affirmation exercises reduced suicidal thoughts following ostracism. Life lacks meaning without social connection, thereby activating suicidal thoughts. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
-Role of natural compounds in preventing and treating breast cancer.

Breast cancer (BrCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women. Alarming increases in the cases quests for more effective treatment of BrCa. As most chemotherapeutic drugs are associated with drug resistance, cancer relapse, and side effects, scientists are turning to agents with more efficacy, such as natural compounds for treatment and prevention of BrCa. Selected natural compounds, substances derived from living organisms, promote apoptosis and inhibit metastasis, preventing cancer growth. As a result, these compounds have the potential to suppress BrCa progression, thus increasing patient survival rates and decreasing the number of BrCa-related deaths. In this review, we summarize natural compounds that have displayed, anti-cancer effects on BrCa cells in various studies. These natural compounds inhibit the development of BrCa, suppress the growth of cancer cells, and promote cell death. We conclude that natural compounds are efficient, effective and promising agents for treating BrCa other than therapeutic methods.
Successful Introduction of Peritoneal Dialysis in an End-stage Renal Failure Patient with Idiopathic Aplastic Anemia

A 45-year-old man with idiopathic aplastic anemia required renal replacement therapy (RRT) due to end-stage renal disease (ESRD). We succeeded in inserting the peritoneal dialysis (PD) catheter under cover of frequent red blood cell and platelet infusions because of severe pancytopenia. During the one-year period after starting PD using an ultraviolet-ray sterilization device, he developed severe leukopenia but no PD-related peritonitis or exit site/tunnel infection until he died of pneumonia. This case suggests that PD might be a suitable choice as RRT in ESRD patients with aplastic anemia, even in those with severe pancytopenia.
Nitric oxide metabolism in the human placenta during aberrant maternal inflammation

Nitric oxide (NO) is a gasotransmitter with important physiological and pathophysiological roles in pregnancy. There is limited information available about the sources and metabolism of NO and its bioactive metabolites (NOx) in both normal and complicated pregnancies. The present study characterized and quantified endogenous NOx in human and mouse placenta following determination of the stability of exogenous NOx in placental homogenates. NOx have differential stability in placental homogenates. NO and iron nitrosyl species (FeNOs), are relatively unstable in placental homogenates from normal placentas. Exogenous NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. FeNOs were also detected endogenously in mouse and human placenta. NOx levels in placental villous tissue are increased in fetal growth restriction vs. placentas from women with normal pregnancies, particularly in fetal growth restriction associated with pre‐eclampsia. Villitis was not associated, however, with an increase in NOx levels in either normotensive or pre‐eclamptic placentas. The results call for further investigation of FeNOs in normal and complicated pregnancies.
Overview of computational models of hippocampus and related structures: Introduction to the special issue

Extensive computational modeling has focused on the hippocampal formation and associated cortical structures. This overview describes some of the factors that have motivated the strong focus on these structures, including major experimental findings and their impact on computational models. This overview provides a framework for describing the topics addressed by individual articles in this special issue of the journal Hippocampus.
Defects in long‐chain 3‐hydroxy acyl‐CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma

The incidence of both nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) have been increasing at an alarming rate. Little is known about NAFLD without cirrhosis as a risk for HCC. Here we report, for the first time, generation of a mouse model with a defect in long‐chain 3‐hydoxy acyl‐CoA dehydrogenase (LCHAD). The LCHAD exon 15 deletion was embryonic lethal to the homozygous mice whereas heterozygous mice (HT) develop significant hepatic steatosis starting at young age (3 months old) and HCC at older age (>13 months old) without any evidence of fibrosis or cirrhosis. None of the wild‐type (WT) mice developed steatosis and HCC (n = 39), whereas HT‐LCHAD mice (n = 41) showed steatosis and ~20% (8/41) developed liver masses with histological features of HCC. Proteomic analysis of liver tissues from WT‐mice and HT‐mice with no signs of HCC was conducted. Proteins with significant changes in abundance were identified by mass spectrometry. Abundance of 24 proteins was significantly different (p < 0.01) between WT and HT‐LCHAD mice. The proteins found to vary in abundance are associated with different cellular response processes ranging from intermediary metabolism of carbohydrate, protein and lipid to oxidative stress, signal transduction and the process of tumorigenesis. Protein expression pattern of the HT‐LCHAD mouse liver indicates predisposition to HCC and suggests that impaired hepatic mitochondrial fatty acid oxidation plays an important role in the development and progression of HCC. To assess the implication of these studies in human disease, we demonstrated significant downregulation of HADHA transcripts in HCC patients.
Effect modifiers for patient-reported outcomes in operatively and nonoperatively treated patients with adult symptomatic lumbar scoliosis: a combined analysis of randomized and observational cohorts.

OBJECTIVE Adult symptomatic lumbar scoliosis (ASLS) is a common and disabling condition. The ASLS-1 was a multicenter, dual-arm study (with randomized and observational cohorts) examining operative and nonoperative care on health-related quality of life in ASLS. An aim of ASLS-1 was to determine patient and radiographic factors that modify the effect of operative treatment for ASLS. METHODS Patients 40-80 years old with ASLS were enrolled in randomized and observational cohorts at 9 North American centers. Primary outcomes were the differences in mean change from baseline to 2-year follow-up for the SRS-22 subscore (SRS-SS) and the Oswestry Disability Index (ODI). Analyses were performed using an as-treated approach with combined cohorts. Factors examined were prespecified or determined using regression tree analysis. For each potential effect modifier, subgroups were created using clinically relevant cutoffs or via regression trees. Estimates of within-group and between-group change were compared using generalized linear mixed models. An effect modifier was defined as a treatment effect difference greater than the minimal detectable measurement difference for both SRS-SS (0.4) and ODI (7). RESULTS Two hundred eighty-six patients were enrolled and 256 (90%) completed 2-year follow-up; 171 received operative treatment and 115 received nonoperative treatment. Surgery was superior to nonoperative care for all effect subgroups considered, with the exception of those with nearly normal pelvic incidence-lumbar lordosis (PI-LL) match (≤ 11°). Male patients and patients with more (> 11°) PI-LL mismatch at baseline had greater operative treatment effects on both the SRS-SS and ODI compared to nonoperative treatment. No other radiographic subgroups were associated with treatment effects. High BMI, lower socioeconomic status, and poor mental health were not related to worse outcomes. CONCLUSIONS Numerous factors previously related to poor outcomes with surgery, such as low mental health, lower socioeconomic status, and high BMI, were not related to outcomes in ASLS in this exploratory analysis. Those patients with higher PI-LL mismatch did improve more with surgery than those with normal alignment. On average, none of the factors considered were associated with a worse outcome with operative treatment versus nonoperative treatment. These findings may guide future prospective analyses of factors related to outcomes in ASLS care.
Atomistic to continuum model for studying mechanical properties of RNA nanotubes

Abstract With rapid advancements in the emerging field of RNA nanotechnology, its current and potential applications, new important problems arise in our quest to better understand properties of RNA nanocomplexes. In this paper, our focus is on the modeling of RNA nanotubes which are important for many biological processes. These RNA complexes are also important for human beings, with their theurapeutical and biomedical applications discussed vigorously in the literature over the recent years. Here, we develop a continuum model of RNA nanotubes, originally obtained from self assembly of RNA building blocks in the molecular dynamics simulation. Based on the finite element method, we calculate the elastic properties of these nanostructures and provide a relationship between stress and strain induced in the RNA nanotube. We also analyze the variations in the displacement vector along the assembly axis for RNA nanotubes of different sizes. In particular, we show that oscillations in the amplitudes of strains and displacements significantly differ for such RNA nanotubes. These findings are discussed in the context of atomistic simulations and experimental results in this field.