Miracle-dz/UniFAR-FTUs huggingface dataset:
A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia. ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. A nonfunctional convalescent-phase response was significantly more common among patients with invasive pneumococcal disease (i.e., bacteremia) than in patients without invasive disease (53%; P = 0.019). Remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). No correlation was found between anticapsular Ig concentrations and OPA titers. Our findings indicate that an episode of pneumococcal infection may act as an immunizing event, leading to an improved antipneumococcal adaptive immune status. However, in some cases, when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations are important for opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia.
Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant’s microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed “settler types”, based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children’s cohorts based on settler types may reveal group effects that might otherwise be masked.
Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and γ-aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.
Carotid Vessel Wall Imaging on CTA

SUMMARY: Vessel wall imaging has been increasingly used to characterize plaque beyond luminal narrowing to identify patients who may be at the highest risk of cerebrovascular ischemia. Although detailed plaque information can be obtained from many imaging modalities, CTA is particularly appealing for carotid plaque imaging due to its relatively low cost, wide availability, operator independence, and ability to discern high-risk features. The present Review Article describes the current understanding of plaque characteristics on CTA by describing commonly encountered plaque features, including calcified and soft plaque, surface irregularities, neovascularization, and inflammation. The goal of this Review Article was to provide a more robust understanding of clinically relevant plaque features detectable on routine CTA of the carotid arteries.
The miR‐143/145 Cluster, a Novel Diagnostic Biomarker in Chondrosarcoma, Acts as a Tumor Suppressor and Directly Inhibits Fascin‐1

Chondrosarcoma is the second most frequent bone sarcoma. Due to the inherent chemotherapy and radiotherapy resistance and absence of known therapeutic targets, clinical management is limited to surgical resection. Consequently, patients with advanced disease face a poor prognosis. Hence, elucidating regulatory networks governing chondrosarcoma pathogenesis is vital for development of effective therapeutic strategies. Here, miRNA and mRNA next generation sequencing of different subtypes of human chondrogenic tumors in combination with in silico bioinformatics tools were performed with the aim to identify key molecular factors. We identified miR‐143/145 cluster levels to inversely correlate with tumor grade. This deregulation was echoed in the miRNA plasma levels of patients and we provided the first evidence that circulating miR‐145 is a potential noninvasive diagnostic biomarker and can be valuable as an indicator to improve the currently challenging diagnosis of cartilaginous bone tumors. Additionally, artificial upregulation of both miRNAs impelled a potent tumor suppressor effect in vitro and in vivo in an orthotopic xenograft mouse model. A combined in silico/sequencing approach revealed FSCN1 as a direct target of miR‐143/145, and its depletion phenotypically resembled miR‐143/145 upregulation in vitro. Last, FSCN1 is a malignancy‐promoting factor associated with aggressive chondrosarcoma progression. Our findings underscore miR‐143/145/FSCN1 as important players in chondrosarcoma and may potentially open new avenues for specific therapeutic intervention options. © 2020 American Society for Bone and Mineral Research.
A first view on the unsuspected intragenus diversity of N‐glycans in Chlorella microalgae

Summary Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health‐promoting food supplements. A mass spectrometry‐based survey of N‐glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N‐glycan structures. Differing numbers of methyl groups, pentoses, deoxyhexoses, and N‐acetylglucosamine culminated in c. 100 different glycan masses. Thirteen clearly discernible glycan‐type groups were identified. Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4‐O‐methyl‐N‐acetylglucosamine), and substitution of the second N‐acetylglucosamine. Analysis of barcode ITS1–5.8S–ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns. This brief prelude to microalgal N‐glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella‐like microalgae, which are notoriously poor in morphological attributes. In light of the almost identical N‐glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
Superficial sarcomas with CIC rearrangement are aggressive neoplasms: A series of eight cases

CIC rearranged sarcomas have significant overlap with Ewing sarcoma, are aggressive, and typically present in deep soft tissue. They most commonly have a t(4;19)(q35;q13) with CIC‐DUX4 fusion. Superficial presentation is rare. We report eight (6F, 2M; median 45‐years‐old, range 14‐65) superficial CIC‐rearranged sarcomas, involving the extremities (n = 4), vulva (n = 2), and trunk (n = 2). The tumors were composed of nodules/sheets of round cells with necrosis and hemorrhage separated by dense hyaline bands. Tumor cells had vesicular chromatin, prominent nucleoli and frequent mitotic figures. One showed pagetoid spread. Targeted next‐generation sequencing was positive for CIC‐DUX4 fusion (6/6); fluorescence in situ hybridization (FISH) was positive for CIC rearrangement (2/3). Eight of eight had evidence of CIC‐DUX4 fusion/rearrangement by molecular techniques. Immunohistochemistry was positive for CD99+ (8/8) and DUX4+ (4/4). FISH for EWSR1 rearrangement was negative (5/5). Of five patients with at least 6 months follow‐up, three of five died of disease, all within 2 years of presentation. One is alive with disease at 48 months. One is disease free at 3 months. Superficial CIC‐rearranged sarcomas should be considered in cases exhibiting features reminiscent of Ewing sarcoma, but with increased pleomorphism and/or geographic necrosis. In contrast to superficial Ewing sarcomas, superficial CIC‐rearranged sarcomas are aggressive.
Interacting Genomic Landscapes of REC8-Cohesin, Chromatin, and Meiotic Recombination in Arabidopsis[CC-BY]

REC8 association with the genome correlates with multiple chromatin states and is required to organize meiotic chromosome architecture and interhomolog recombination. Meiosis recombines genetic variation and influences eukaryote genome evolution. During meiosis, DNA double-strand breaks (DSBs) enter interhomolog repair to yield crossovers and noncrossovers. DSB repair occurs as replicated sister chromatids are connected to a polymerized axis. Cohesin rings containing the REC8 kleisin subunit bind sister chromatids and anchor chromosomes to the axis. Here, we report the genomic landscape of REC8 using chromatin immunoprecipitation sequencing (ChIP-seq) in Arabidopsis (Arabidopsis thaliana). REC8 associates with regions of high nucleosome occupancy in multiple chromatin states, including histone methylation at H3K4 (expressed genes), H3K27 (silent genes), and H3K9 (silent transposons). REC8 enrichment is associated with suppression of meiotic DSBs and crossovers at the chromosome and fine scales. As REC8 enrichment is greatest in transposon-dense heterochromatin, we repeated ChIP-seq in kyp suvh5 suvh6 H3K9me2 mutants. Surprisingly, REC8 enrichment is maintained in kyp suvh5 suvh6 heterochromatin and no defects in centromeric cohesion were observed. REC8 occupancy within genes anti-correlates with transcription and is reduced in COPIA transposons that reactivate expression in kyp suvh5 suvh6. Abnormal axis structures form in rec8 that recruit DSB-associated protein foci and undergo synapsis, which is followed by chromosome fragmentation. Therefore, REC8 occupancy correlates with multiple chromatin states and is required to organize meiotic chromosome architecture and interhomolog recombination.
Plasma Concentration Rise after the Intramuscular Administration of High Dose Medetomidine (0.13 mg/kg) for Semen Collection in Cats

High dose medetomidine 0.13 mg/kg can be used for semen collection in cats with variable results in terms of quantity and quality. Therefore, a variation in terms of distribution and elimination among patients has been hypothesised. The aim of the study was to characterise the pharmacokinetics of medetomidine (0.13 mg/kg) administered intramuscularly (IM) in healthy male cats. Eighteen male cats undergoing castration were included, and medetomidine (0.13 mg/kg) was administered IM. Venous blood samples were collected at 20, 30, 40, 50, 60, 75 and 90 minutes after medetomidine administration. Before orchiectomy, at T20, sperm collection was attempted. Plasma medetomidine concentrations were determined by liquid chromatography/mass spectrometry analysis. Semen collection was successful in 15/18 cats. The medetomidine plasma concentration following the IM administration of a bolus was best described using a non-compartment model. Time of maximum concentration was observed at 40 minutes (range 20–90); maximum concentration was 32.8 ng/mL (range 26.8–51.2). The median apparent clearance was 11.9 mL/kg/minute (range 0.7–43.8). In conclusion, medetomidine administered IM at 0.13 mg/kg reached its peak plasma concentration slowly and with variability among patients. In addition, it was characterised by low total body clearance probably due to the cardiovascular alterations associated with medetomidine administration.
Differences in Gene Expression of Endogenous Opioid Peptide Precursor, Cannabinoid 1 and 2 Receptors and Interleukin Beta in Peripheral Blood Mononuclear Cells of Patients With Refractory Failed Back Surgery Syndrome Treated With Spinal Cord Stimulation: Markers of Therapeutic Outcomes?

The use of spinal cord stimulation for patients with failed back surgery syndrome (FBSS) is very common. In order to better understand the mechanisms of action of spinal cord stimulation (SCS), our aim was to determine potential changes in relative gene and protein expression in the peripheral blood mononuclear cells (PBMCs) of patients as potential biomarkers of disease outcomes and potential new targets for therapy.
Different Effects of Nicotine and N-Stearoyl-ethanolamine on Episodic Memory and Brain Mitochondria of α7 Nicotinic Acetylcholine Receptor Knockout Mice

Nicotinic acetylcholine receptors of α7 subtype (α7 nAChRs) are involved in regulating neuroinflammation and cognitive functions. Correspondingly, α7-/- mice demonstrate pro-inflammatory phenotype and impaired episodic memory. In addition, nAChRs expressed in mitochondria regulate the release of pro-apoptotic factors like cytochrome c. Here we studied whether the cognitive deficiency of α7-/- mice can be cured by oral consumption of either nicotine or N-stearoylethanolamine (NSE), a lipid possessing anti-inflammatory, cannabimimetic and membrane-stabilizing activity. Mice were examined in Novel Object Recognition behavioral test, their blood, brains and brain mitochondria were tested for the levels of interleukin-6, various nAChR subtypes and cytochrome c released by ELISA. The data presented demonstrate that both substances stimulated the raise of interleukin-6 in the blood and improved episodic memory of α7-/- mice. However, NSE improved, while nicotine worsened the brain mitochondria sustainability to apoptogenic stimuli, as shown by either decreased or increased amounts of cytochrome c released. Both nicotine and NSE up-regulated α4β2 nAChRs in the brain; NSE up-regulated, while nicotine down-regulated α9-containing nAChRs in the brain mitochondria. It is concluded that the level of alternative nAChR subtypes in the brain is critically important for memory and mitochondria sustainability in the absence of α7 nAChRs.
Pedagogical Function of Referees in Youth Sport: Assessment of the Quality of Referee–Player Interactions in Youth Soccer

We assume that all institutions and individuals involved in the organization of sport for children and young people should utilize the educational potential of sport. We assessed the quality of referee interactions with children during sports competitions in soccer. Based on the developmental theory and research suggesting that interactions between kids and adults are the primary mechanism of their development and learning, we focused on the quality of the referee–player interactions in terms of (1) emotional support, (2) game organization, and (3) instructional support. Twenty-five soccer referees who refereed matches for children aged 9–12 years were recruited. The Referee Educational Function Assessment Scoring System (REFASS) was used to assess the quality of the referee–player interactions. This tool was developed based on Classroom Assessment Scoring System—Upper Elementary. Regarding the REFASS dimensions, the mean scores for positive climate, Sensitivity, behavior management, content understanding and quality of feedback were in the medium range, while productivity and negative climate in the high range. In the case of the positive climate variable, the lowest mean ratings were recorded compared to other assessed dimensions. The assessments of the quality of referee–player interactions obtained for particular dimensions translated into the ratings for the specified domains. The highest ratings were given to game organization (6.0 ± 0.8; Me = 6.0), whereas the emotional support and instructional support were in the medium range (4.6 ± 1.5; Me = 4.5, and 5.2 ± 1.8; Me = 6.0, respectively). Referees are usually not aware of their pedagogical function and the complexity of their respective responsibilities. They are commonly considered to be ordinary technicians and evaluators of performance in competition. Based on the results, a postulate was formulated that referees should consciously perform a pedagogical function in the youth sport. Therefore, it is necessary to train them in educational methods and techniques appropriate to the age and needs of the child. The referees will then be prepared to take actions to prevent negative behavior of players on the field and to encourage prosocial behavior.
Comparison of endoscopic surgery and Lichtenstein repair for treatment of inguinal hernias

Abstract Background: This study aimed to identify the best procedure for addressing inguinal hernias by comparing results after transabdominal preperitoneal (TAPP), totally extraperitoneal (TEP), and Lichtenstein repairs using a network meta-analysis. Methods: We conducted a systematic search of MEDLINE, Web of Science, the Cochrane Central Library, and ClinicalTrials.gov up to September 1, 2018 for randomized controlled trials (RCTs) comparing the TAPP, TEP, and Lichtenstein procedures. The study outcome were the hernia recurrence, chronic pain, hematoma, seroma, wound infection, operation time, hospital stay, and return-to-work days. Results: Altogether, 31 RCTs were included in the meta-analysis. The results of this network meta-analysis showed there were no significantly differences among the 3 procedures in terms of hernia recurrence, chronic pain, hematoma, seroma, hospital stays. Lichtenstein had a shorter operation time than TAPP+TEP [MD (95%Crl)]: 12 (0.51–25.0) vs 18 (6.11–29.0) minutes, respectively) but was associated with more wound infections than TEP: OR 0.33 (95%Crl 0.090–0.81). Our network meta-analysis suggests that TAPP and TEP require fewer return-to-work days [MD (95%CI)]: − 3.7 (−6.3 to 1.3) vs −4.8 (−7.11 to 2.8) days. Conclusion: Our network meta-analysis showed that there were no differences among the TAPP, TEP, and Lichtenstein procedures in terms of safety or effectiveness for treating inguinal hernias. However, TAPP and TEP could decrease the number of return-to-work days. A further study with more focus on this topic for inguinal hernia is suggested.
Risks and benefits of CTangiography in spontaneous intracerebral hemorrhage

Background Few studies have examined the risk of computed tomography angiography (CTA) during the acute phase of spontaneous intracerebral hemorrhage (ICH), while the benefits of CTA in ICH have been well-documented. The present study investigated both the benefits of identifying spot signs, which are supposed to indicate hematoma enlargement after admission,andrisksofCTAperformedduringtheacutephase of ICH. Methods We retrospectively assessed 323 consecutive patients with spontaneous ICHs admitted to our hospital between April 2009 and March 2012 and who underwent CTA on admission. Results In 80 patients (24.7 %), spot signs were demonstrated on CTA source images. Multivariate analysis revealed two independent factors correlated with presence of the spot sign: age and hematoma volume (p<0.05 each). The presence of spot sign was associated with unfavorable outcomes at discharge and hematoma growth after admission (p<0.05 each). Adverse events related to CTA occurred in 17 patients (5.2 %), including transient renal dysfunction in 16 patients and allergy to contrast medium in one patient. All adverse events completely resolved within 1 week. Conclusions Presence of the spot sign indicated the possibility of hematoma growth and unfavorable outcomes. A small number of adverse events occurred in association with CTA, but without any permanent deficits. Given the potential benefits and risks, we believe that CTA performed at admission in all patients with ICH is beneficial to improve the outcomes.